Phytoplasmas are insect-vectored bacteria that cause disease in a wide range of plant species. The increasing availability of molecular DNA analyses, expertise and additional methods in recent years has led to a proliferation of discoveries of phytoplasma-plant host associations and in the numbers of taxonomic groupings for phytoplasmas. The widespread use of common names based on the diseases with which they are associated, as well as separate phenetic and taxonomic systems for classifying phytoplasmas based on variation at the 16S rRNA-encoding gene, complicates interpretation of the literature. We explore this issue and related trends through a focus on Australian pathosystems, providing the first comprehensive compilation of information for this continent, covering the phytoplasmas, host plants, vectors and diseases. Of the 33 16Sr groups reported internationally, only groups I, II, III, X, XI and XII have been recorded in Australia and this highlights the need for ongoing biosecurity measures to prevent the introduction of additional pathogen groups. Many of the phytoplasmas reported in Australia have not been sufficiently well studied to assign them to 16Sr groups so it is likely that unrecognized groups and sub-groups are present. Wide host plant ranges are apparent among well studied phytoplasmas, with multiple crop and non-crop species infected by some. Disease management is further complicated by the fact that putative vectors have been identified for few phytoplasmas, especially in Australia. Despite rapid progress in recent years using molecular approaches, phytoplasmas remain the least well studied group of plant pathogens, making them a "crouching tiger" disease threat.
Background: (-)-alpha-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-alpha-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-alpha-bisabolol plays a key role in the development of its sustainable production from renewable feedstock. Results: Here, we created an Escherichia coli strain producing (-)-alpha-bisabolol at high titer and developed an in situ extraction method of (-)-alpha-bisabolol, using natural vegetable oils. We expressed a recently identified (-)-alpha-bisabolol synthase isolated from German chamomile (Matricaria recutita) (titer: 3 mg/L), converted the acetyl-CoA to mevalonate, using the biosynthetic mevalonate pathway (12.8 mg/L), and overexpressed farnesyl diphosphate synthase to efficiently supply the (-)-alpha-bisabolol precursor farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway and farnesyl diphosphate synthase enabled a dramatic increase in (-)-alpha-bisabolol production in the shake flask culture (80 mg/L) and 5 L bioreactor culture (342 mg/L) of engineered E. coli harboring (-)-alpha-bisabolol synthase. Fed-batch fermentation using a 50 L fermenter was conducted after optimizing culture conditions, resulting in efficient (-)-alpha-bisabolol production with a titer of 9.1 g/L. Moreover, a green, downstream extraction process using vegetable oils was developed for in situ extraction of (-)-alpha-bisabolol during fermentation and showed high yield recovery (>98%). Conclusions: The engineered E. coli strains and economically viable extraction process developed in this study will serve as promising platforms for further development of microbial production of (-)-alpha-bisabolol at large scale.
A universal feature of the replication of positive-strand RNA viruses is the association with intracellular membranes. Carnation Italian ringspot virus (CIRV) replication in plants occurs in vesicles derived from the mitochondrial outer membrane. The product encoded by CIRV ORF1, p36, is required for targeting the virus replication complex to the outer mitochondrial membrane both in plant and yeast cells. Here the yeast Saccharomyces cerevisiae was used as a model host to study the effect of CIRV p36 on cell survival and death. It was shown that p36 does not promote cell death, but decreases cell growth rate. In addition, p36 changed the nature of acetic acid-induced cell death in yeast by increasing the number of cells dying by necrosis with concomitant decrease of the number of cells dying by programmed cell death, as judged by measurements of phosphatidylserine externalization. The tight association of p36 to membranes was not affected by acetic acid treatment, thus confirming the peculiar and independent interaction of CIRV p36 with mitochondria in yeast. This work proved yeast as an invaluable model organism to study both the mitochondrial determinants of the type of cell death in response to stress and the molecular pathogenesis of (+)RNA viruses. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative agents associated with the development of cholangiocarcinoma in employees working in printing plant in Osaka, Japan. However, few reports have demonstrated an association between these agents and cholangiocarcinoma in rodent carcinogenicity studies. Moreover, the combined effects of these compounds have not been fully elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2-DCP and DCM, alone or combined, in the livers of gpt delta rats. Six-week-old male F344 gpt delta rats were treated with 1,2-DCP, DCM or 1,2-DCP+DCM by oral administration for 4weeks at the dose (200mgkg(-1) body weight 1,2-DCP and 500mgkg(-1) body weight DCM) used in the carcinogenesis study performed by the National Toxicology Program. In vivo mutagenicity was analyzed by gpt mutation/Spi(-) assays in the livers of rats. In addition, gene and protein expression of CYP2E1 and GSTT1, the major enzymes responsible for the genotoxic effects of 1,2-DCP and DCM, were analyzed by quantitative polymerase chain reaction and western blotting. Gpt and Spi(-) mutation frequencies were not increased by 1,2-DCP and/or DCM in any group. Additionally, there were no significant changes in the gene and protein expression of CYP2E1 and GSTT1 in any group. These results indicated that 1,2-DCP, DCM and 1,2-DCP+DCM had no significant impact on mutagenicity in the livers of gpt delta rats under our experimental conditions. Copyright (c) 2016 John Wiley & Sons, Ltd.
This paper presents the simulation results of a linear, fully integrated, two-stage digitally programmable 130 nm CMOS power amplifier (PA) operating at 2.4 GHz. Its power stage is composed of a set of amplifying cells which can be enabled or disabled independently by a digital control circuit. All seven operational modes are univocal in terms of 1 dB output compression point (OCP1dB), saturated output power (P-SAT) and power gain at 2.4 GHz. The lowest power mode achieves an 8.1 dBm P-SAT, a 13.5 dB power gain and consumes 171 mW DC power (P-DC) at an OCP1dB of 6 dBm, whereas the highest power mode reaches an 18.9 dBm P-SAT and a 21.1 dB power gain and consumes 415 mW P-DC at an OCP1dB of 18.2 dBm.
The glycogen branching enzyme (EC 2.4.1.18), which catalyses the formation of alpha-1,6-glycosidic branch points in glycogen structure, is often used to enhance the nutritional value and quality of food and beverages. In order to be applicable in industries, enzymes that are stable and active at high temperature are much desired. Using genome mining, the nucleotide sequence of the branching enzyme gene (glgB) was extracted from the Geobacillus mahadia Geo-05 genome sequence provided by the Malaysia Genome Institute. The size of the gene is 2013 bp, and the theoretical molecular weight of the protein is 78.43 kDa. The gene sequence was then used to predict the thermostability, function and the three dimensional structure of the enzyme. The gene was cloned and overexpressed in E. coli to verify the predicted result experimentally. The purified enzyme was used to study the effect of temperature and pH on enzyme activity and stability, and the inhibitory effect by metal ion on enzyme activity. This thermostable glycogen branching enzyme was found to be most active at 55 degrees C, and the half-life at 60 degrees C and 70 degrees C was 24 h and 5 h, respectively. From this research, a thermostable glycogen branching enzyme was successfully isolated from Geobacillus mahadia Geo-05 by genome mining together with molecular biology technique.
The microbial populations in the activated sludge of two Polish wastewater treatment plants (WWTPs) were identified and quantified using Illumina sequencing of 16S ribosomal RNA amplicons over a 2-year period. Their dynamics over time were compared to Danish WWTPs (data collected in previous studies by Center for Microbial Communities, Aalborg University). The bacterial communities in Polish and Danish WWTPs were similar to each other, but the microbial diversity in Polish WWTPs was lower. The dominant genera in Polish WWTPs were more abundant than in Danish WWTPs; 30 of them constituted more than half the of activated sludge community. Polish WWTPs showed a higher abundance of bacteria involved in nitrogen and chemical oxygen demand removal (Proteobacteria and Bacteroidetes), while polyphosphate-acculumating bacteria were the dominant bacterial group in Danish plants. The microbial community structures in the examined Polish WWTPs were relatively similar to each other and showed strong seasonal variations which are not normally observed in Danish WWTPs.
Background: Broad-range 16S rRNA PCR can be used for the detection and identification of bacteria from clinical specimens in patients for whom there is a high suspicion of infection and cultures are negative. The aims of this study were (1) to compare 16S rRNA PCR results with microbiolog ical culture results, (2) to assess the utility of 16S rRNA PCR with regard to antimicrobial therapy, and (3) to compare the yield of 16S rRNA PCR for different types of clinical specimen and to perform a cost analysis of the test. Methods: A retrospective study was performed on different clinical specimens which had 16S performed over 3 years (2012-2015). Standard microbiological cultures were performed on appropriate media, as per the laboratory protocol. Patient clinical and microbiological data were obtained from the electronic medical records and laboratory information system, respectively. 16S rRNA PCR was performed in a reference laboratory using a validated method for amplification and sequencing. The outcomes assessed were the performance of 16S rRNA PCR, change of antimicrobials (rationalization, cessation, or addition), and duration of therapy. Concordance of 16S rRNA PCR with bacterial cultures was also determined for tissue specimens. Results: Thirty-two patients were included in the study, for whom an equal number of specimens (n = 32) were sent for 16S rRNA PCR. 16S rRNA PCR could identify an organism in 10 of 32 cases (31.2%), of which seven were culture-positive and three were culture-negative. The sensitivity was 58% (confidence interval (CI) 28.59-83.5%) and specificity was 85% (CI 61.13-96%), with a positive predictive value of 70% (CI 35.3-91.9%) and negative predictive value of 77.2% (CI 54.17-91.3%). Antimicrobial therapy was rationalized after 16S rRNA PCR results in five patients (15.6%) and was ceased in four based on negative results (12.5%). Overall the 16S rRNA PCR result had an impact on antimicrobial therapy in 28% of patients (9/32). The highest concordance of 16S rRNA PCR with bacterial culture was found for heart valve tissue (80%), followed by joint fluid/tissue (50%). Conclusions: Despite the low diagnostic yield, results of 16S rRNA PCR can still have a significant impact on patient management due to rationalization or cessation of the antimicrobial therapy. The yield of 16S rRNA PCR was highest for heart valves. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Brinjal little leaf (BLL) is a widespread disease of phytoplasma etiology in India that induces severe economic losses. Surveys were conducted in eight brinjalgrowing states of India during July 2014 to September 2015 and eighteen BLL samples showing little leaf, phyllody and witches' broom symptoms were collected for phytoplasma identification. Presence of phytoplasmas was confirmed in all the eighteen BLL samples using polymerase chain reaction with phytoplasma-specific primer pairs (P1/P6, R16F2n/R16R2). Pair wise sequence comparison and phylogenetic relationship of 16S rRNA gene sequences of BLL phytoplasma strains confirmed that sixteen out of eighteen BLL strains belonged to clover proliferation phytoplasma (16SrVI) group and two BLL strains (GKP-A and GKP-B) from Gorakhpur, Uttar Pradesh, were classified under 16SrII group. Further virtual RFLP analysis of 16S rDNA sequences allowed finer classification of BLL strains into 16SrII-D and 16SrVI-D subgroups. BLL phytoplasma strains belonging to 16SrVI-D subgroup were found as the most widespread phytoplasma strains associated with BLL disease in India. 16SrVI-D subgroup phytoplasma association with two symptomatic weed species viz. Cannabis sativa subsp. sativa at Noida, Uttar Pradesh and Portulaca oleracea at IARI fields, New Delhi was also confirmed by nested PCR assays with similar set of phytoplasma-specific primers, pairwise 16S rDNA sequence comparison, phylogeny and virtual RFLP analysis. Out of five identified leafhopper species from BLL-infected fields at Noida, Uttar Pradesh and Delhi, only Hishimonas phycitis was identified as carrier and natural vector of 16SrVI-D subgroup of phytoplasmas by nested PCR assays, sequence comparison, phylogeny, virtual RFLP analysis and transmission assays.
Surveys for the Cote d'Ivoire lethal yellowing (CILY) phytoplasma were conducted in eight severely CILY-affected villages of Grand-Lahou in 2015. Leaves, inflorescences and trunk borings were collected from coconut palms showing CILY symptoms and from symptomless trees. Total DNA was extracted from these samples and tested by nested polymerase chain reaction/RFLP and sequence analysis of the 16S rRNA, ribosomal protein (rp) and the translocation protein (secA) genes. The CILY phytoplasma was detected in 82.9% of the symptom-bearing palms collected from all the surveyed villages and from all the plant parts. Trunk borings were recommended as the most suitable plant tissue type for sampling. Results indicate that the CILY phytoplasma may have a westward spread to other coconut-growing areas of Grand-Lahou. CILY phytoplasma strains infecting coconut palms in the western region of Grand-Lahou exhibited unique single nucleotide polymorphisms on the rp sequence compared to the strains from the eastern region. Moreover, single nucleotide polymorphisms on the SecA sequence distinguished the CILY phytoplasma from the Cape St. Paul Wilt Disease phytoplasma in Ghana, and the Lethal Yellowing phytoplasma in Mozambique.
Advances in sequencing technologies continue to provide unprecedented opportunities to characterize microbial communities. For example, the Pacific Biosciences Single Molecule Real-Time (SMRT) platform has emerged as a unique approach harnessing DNA polymerase activity to sequence template molecules, enabling long reads at low costs. With the aim to simultaneously classify and enumerate in situ microbial populations, we developed a quantitative SMRT (qSMRT) approach that involves the addition of exogenous standards to quantify ribosomal amplicons derived from environmental samples. The V7-9 regions of 18S SSU rDNA were targeted and quantified from protistan community samples collected in the Ross Sea during the Austral summer of 2011. We used three standards of different length and optimized conditions to obtain accurate quantitative retrieval across the range of expected amplicon sizes, a necessary criterion for analyzing taxonomically diverse 18S rDNA molecules from natural environments. The ability to concurrently identify and quantify microorganisms in their natural environment makes qSMRT a powerful, rapid and cost-effective approach for defining ecosystem diversity and function. (C) 2017 Elsevier B.V. All rights reserved.
1A6/DRIM is a nucleolar protein with a nucleolar targeting sequence in its 3'-terminus. Bioinformatic analysis indicated that human 1A6/ DRIM shares 23% identity and 43% similarity with yeast Utp20, which has been reported as a component of U3 snoRNA protein complex and has been implicated in 18S rRNA processing. In the present study, we found, by utilizing RT-PCR with RNA extracted from anti-1A6/DRIM inummoprecipitates and Northern blotting, that 1A6/DRIM is associated with U3 snoRNA. Pulse-chase labeling assays showed that silencing of 1A6/DRIM expression in HeLa cells resulted in a delayed 18S rRNA processing. Furthermore, immunoprecipitations revealed that 1A6/DRIM was also associated with fibrillarin, another U3 RNP component in HeLa cells. These results indicate that 1A6/DRIM is involved in 18S rRNA processing and is the bona fide mammalian Utp20. (c) 2007 Elsevier B.V. All rights reserved.
Aims: 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic condition associated with an increased risk of developing schizophrenia. Previous studies have shown that negative symptoms represent the most specific clinical characteristic of psychosis in 22q11.2DS and are strongly associated with outcome. However, the psychological mechanisms associated with these symptoms in this population are poorly understood. In accordance with recent conceptualizations in the field of schizophrenia, the present study aims at investigating whether negative symptoms are associated with the presence of negative performance beliefs and cognitive deficits. Methods: Thirty-five participants with 22q11.2DS and 24 typically developing individuals aged between 11 and 24 years were included in the study. Self-reported schizotypal symptoms (cognitive-perceptual, paranoid, negative and disorganization symptoms) and dysfunctional beliefs (negative performance beliefs and need for approval) were assessed. Measures of processing speed, verbal memory, working memory, executive functioning and face recognition-were also extracted from a broad cognitive evaluation protocol. Results: Adolescents with 22q11.2DS reported significantly higher score on the negative dimension of the Schizotypal Personality Questionnaire than controls, even when controlling for the influence of anxiety/depression and intellectual functioning. Negative and paranoid symptoms were associated with the severity of negative performance beliefs and lower face recognition abilities. Mediation analyses revealed that negative performance beliefs significantly mediated the association between face recognition and negative/paranoid symptoms. Conclusions: These findings suggest that negative performance beliefs and basic social cognitive mechanisms are associated with negative and paranoid symptoms in individuals with 22q11.2DS. Implications for intervention are discussed in this article.
Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. Results: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. Conclusions: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS.
Through the comprehensive analysis of the genomic DNA sequence of human chromosome 22, we identified a novel gene of 702 kb encoding a big protein of 2481 amino acid residues, and named it as TPRBK (TPR containing big gene cloned at Keio). A novel protein TPRBK possesses 25 units of the TPR motif, which has been known to associate with a diverse range of biological functions. Orthologous genes of human TPRBK were found widely in animal species, from insecta to mammal, but not found in plants, fungi and nematoda. Northern blotting and RT-PCR analyses revealed that TPRBK gene is expressed ubiquitously in the human and mouse fetal tissues and various cell lines of human, monkey and mouse. lmmunofluorescent staining of the synchronized monkey COS-7 cells with several relevant antibodies indicated that TPRBK changes its subcellular localization during the cell cycle: at interphase TPRBK locates on the centrosomes, during mitosis it translocates from spindle poles to mitotic spindles then to spindle midzone, and through a period of cytokinesis it stays on the midbody. Co-immunoprecipitation assay and immunofluorescent staining with adequate antibodies revealed that TPRBK binds to Aurora B. and those proteins together translocate throughout mitosis and cytokinesis. Treatments of cells with two drugs (Blebbistatin and Y-27632), that are known to inhibit the contractility of actin-myosin, disturbed the proper intracellular localization of TPRBK. Moreover, the knockdown of TPRBK expression by small interfering RNA (siRNA) suppressed the bundling of spindle midzone microtubules and disrupted the midbody formation, arresting the cells at G(2) + M phase. These observations indicated that a novel big protein TPRBK is essential for the formation and integrity of the midbody, hence we postulated that TPRBK plays a critical role in the progress of mitosis and cytokinesis during mammalian cell cycle. (C) 2012 Elsevier B.V. All rights reserved.
Graphene and other two-dimensional materials have received considerable attention regarding their potential applications in nano-electronics. Here, we report top-gate nonvolatile memory field-effect transistors (FETs) with different layers of MoSe2 nanosheets channel gated by ferroelectric film. The conventional gate dielectric of FETs was replaced by a ferroelectric thin film that provides a ferroelectric polarization electric field, and therefore defined as an Fe-FET where the poly (vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) was used as the gate dielectric. Among the devices with MoSe2 channels of different thicknesses, the device with a single layer of MoSe2 exhibited a large hysteresis of electronic transport with an over 10(5) write/erase ratio, and displayed excellent retention and endurance performance. The possible mechanism of the device's good properties was qualitatively analyzed using band theory. Additionally, a comprehensive study comparing the memory properties of MoSe2 channels of different thicknesses is presented. Increasing the numbers of MoSe2 layers was found to cause a reduced memory window. However, MoSe2 thickness of 5 nm yielded a write/erase ratio of more than 10(3). The results indicate that, based on a Fe-FET structure, the combination of two-dimensional semiconductors and organic ferroelectric gate dielectrics shows good promise for future applications in nonvolatile ferroelectric memory.
Relationships between the abundance of potential geosmin- and 2-methylisoborneol-producing (2-MIB) cyanobacteria and bacteria, and concentrations of the two taste and odour compounds (T&Os) were examined in a 7 day incubation of natural water from the surface and bottom of three reservoirs in southeast Queensland, Australia. Only a single known T&O-producing cyanobacterium (Geitlerinema spp.) was detected by microscopy at low density, and only in one reservoir. Densities of potential T&O-producing Streptomyces (determined by quantitative polymerase chain reaction (qPCR) assay) were highest in the bottom water and varied from 0.7 x 10(3) to 775 x 10(3) cells L-1. Geosmin ranged from 6 to 59 ng L-1 (with the highest concentrations in the bottom water), while 2-MIB varied from 6 to 47 ng L-1 (with the highest concentration in surface water). Concentrations of both compounds declined during the incubation under both light and dark conditions. Presence of the geosmin synthase gene, geoA, in cyanobacteria and Streptomyces was examined by different PCR approaches. Cloning of PCR products from amplification of geoA showed a high similarity to geoA in cyanobacteria, but not to streptomycetes. Our results demonstrate that more research on the ecology and molecular biology of T&O producers is required to better understand the dynamics of T&Os and to monitor emerging T&O episodes.
We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both sexes), but resolved within 30 min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d. Immunohistochemical staining indicated alpha(2u)-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500 mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500 mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.
The mu-opioid receptor (MOR) plays a mandatory role in the action of most opioid drugs, such as morphine, fentanyl, and heroin. it has been revealed that a deficiency in the MOR gene (Oprm 1) or a difference in the 3' noncoding region of the gene markedly affects the sensitivity of mice to opioids. As the 3' noncoding region of the human OPRM1 gene had not yet been characterized, in the present study we conducted 3'-rapid amplification of cDNA ends (3'RACE)-PCR and identified the 3' end of the human MOR-1 mRNA, the most abundant transcript among OPRM1 gene transcripts. The poly(A) signal was located at 13612-13617 nucleotides downstream from the stop codon in the OPRM1 gene. Reverse transcription PCR analyses showed that the region from the stop codon to the poly(A) signal was transcribed. In the 3' UTR, we identified 33 AU-rich regions and more than 300 putative transcription factor-binding sites. Furthermore, we compared the 3' noncoding regions of the human and mouse OPRM1/Oprm1] genes and found apparent homology. In Northern blotting with mouse brain mRNAs, a same-size band was detected by a probe for the MOR-1 coding region and by a probe for a mouse genome region corresponding to the human MOR-1 3'UTR. Since 3'UTRs affect gene expression, the present characterization of the 3' noncoding region in the human OPRM1 gene should lead to a better understanding of the mechanisms underlying OPRM1 gene regulation and individual differences in sensitivity to opioids. Published by Elsevier B.V.
An integrated electronic-photonic phase-locked loop (PLL) modulates the frequency of a tunable laser for use in frequency-modulated continuous-wave (FMCW) lidar 3D imaging. The proposed lidar can perform 180k range measurements per second. The rms depth precision is 8 mu m at distances of +/- 5 cm from the range baseline. The range window is 1.4 m, with a precision of 4.2 mm at the edges of the window. Optical circuitry, including input light couplers, waveguides, and photodiodes, is realized on a 3 mm x 3 mm silicon-photonic chip. The 0.18-mu m CMOS ASIC of the same area comprises the frontend transimpedance amplifier, analog electro-optical PLL, and digital control circuitry consuming 1.7 mA from a 1.8 V supply and 14.1 mA from a 5-V supply. The latter includes 12.5-mA bias current for the distributed Bragg reflector section of the tunable laser. The two chips are integrated using through-silicon-vias implemented in the silicon-photonic chip.
3D printing has shown promise for neural regeneration by providing customized nerve scaffolds to structurally support and bridge the defect gap as well as deliver cells or various bioactive substances. Low-level light therapy (LLLT) exhibits positive effects on rehabiliation of degenerative nerves and neural disorders. With this in mind, we postulate that 3D printed neural scaffold coupling with LLLT will generate a new strategy to repair neural degeneration. To achieve this goal, we applied red laser light to stimualte neural stem cells on 3D printed scaffolds and investigated the subsequent cell response with respect to cell proliferation and differentiation. Here we show that cell prolifeartion rate and intracellular reactive oxgen species synthesis were significantly increased after 15 s laser stimulation follwed by 1 d culture. Over culturing time of 14 d in vitro, the laser stimulation promoted neuronal differentiation of neural stem cells, while the glial differentiation was suppressed based on results of both immunocytochemistry studies and real-time quantitative reverse transcription polymerase chain reaction testing. These findings suggest that integration of 3D printing and LLLT might provide a powerful methodology for neural tissue engineering.
With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.
3-mercaptopyruvate sulfurtransferase (3-MST) was a novel hydrogen sulfide (H2S)-synthesizing enzyme that may be involved in cyanide degradation and in thiosulfate biosynthesis. Over recent years, considerable attention has been focused on the biochemistry and molecular biology of H2S-synthesizing enzyme. In contrast, there have been few concerted attempts to investigate the changes in the expression of the H2S-synthesizing enzymes with disease states. To investigate the changes of 3-MST after traumatic brain injury (TBI) and its possible role, mice TBI model was established by controlled cortical impact system, and the expression and cellular localization of 3-MST after TBI was investigated in the present study. Western blot analysis revealed that 3-MST was present in normal mice brain cortex. It gradually increased, reached a peak on the first day after TBI, and then reached a valley on the third day. Importantly, 3-MST was colocalized with neuron. In addition, Western blot detection showed that the first day post injury was also the autophagic peak indicated by the elevated expression of LC3. Importantly, immunohistochemistry analysis revealed that injury-induced expression of 3-MST was partly colabeled by LC3. However, there was no colocalization of 3-MST with propidium iodide (cell death marker) and LC3 positive cells were partly colocalized with propidium iodide. These data suggested that 3-MST was mainly located in living neurons and may be implicated in the autophagy of neuron and involved in the pathophysiology of brain after TBI.
Oxidative stress is closely involved in neurodegenerative diseases. The present study aimed to examine the effect of anti-oxidant DHM (dihydromyricetin) on 3NP (3-nitropropionic acid) -induced behavioral deficits of experimental rats and striatal histopathological injury by using behavioral, imaging, biochemistry, histochemistry and molecular biology technologies. The experimental results showed that both motor dysfunctions and learning and memory impairments induced by 3NP were significantly reduced after DHM treatment. 3NP-induced striatal metabolic abnormality was also remarkably improved by DHM treatment, showed as the increased glucose metabolism in PET/CT scan, decreased MDA (malondialdehyde) and increased SOD (superoxide dismutase) activity in enzyme histochemical staining. In addition, the cell apoptosis was evidently detected in the striatum of the 3NP group, while in the 3NP + DHM group, the number of apoptotic cells was remarkably reduced. 3NP treatment obviously induced down-regulation of Bcl-2, and up-regulations of Bax and Cleaved Caspase-3, while these changes were significantly reversed by DHM treatment. The present results suggested that DHM showed its protective effect by anti-oxidant and anti-apoptosis mechanisms.
The 45 degrees beam splitting mirror plays a vital role on image quality in the Holographic system, in order to study the influence of environment temperature variation on the 45 degrees beam splitting mirror in the Holographic system, finite element analysis method is used to simulate the anti-three through seven mirror deformation at 27 degrees C, 28 degrees C and 29 degrees C temperature in theory. A new real-time monitoring and displaying photoelectric system for ambient temperature and beam splitting mirror distortion detection is designed to provide real-time temperature change and deformation detection, which is made up of laser speckle interferometer, chip temperature sensor, two-operational amplifier, MCU and LED indicator. And the out-plane displacement value measured in the experiment under the condition of temperature correspondingly are 406nm, 420nm and 427 nm. Finally, the relation equation of temperature and mirror deformation is established by the method of exponential equation fitting, which will provide preliminary theoretical and experimental reference for further research.
A thermotolerant bacterium Paenibacillus thiaminolyticus with an ability to produce extracellular -mannanase was isolated from a soil sample. Bacterium produced 45U/mL -mannanase at 50 degrees C. The culture conditions for high-level production of -mannanase were optimized. Optimized MS medium [wheat bran 2% (w/v), ammonium sulfate 0.3% (w/v), yeast extract, and peptone (0.025% each) pH 6.5] was inoculated with 2% of 16H old culture. The culture was incubated at 50 degrees C for 48H resulting in 24-folds higher -mannanase production (1,100 +/- 50U/mL). Optimum pH and temperature for enzyme activity of the crude enzyme was 6.0 and 60 degrees C, respectively. The enzyme demonstrated 65% relative enzyme activity at 37 degrees C. The hydrolytic activity of the crude enzymatic preparation was assessed on various agro residues. Thin-layer chromatographic analysis showed that the enzyme activity to saccharify heteromannans resulted in production of a mixture of manno-oligosaccharides (MOS) and enzyme exhibited classic endo-activity. To evaluate the possible prebiotic potential of the MOS thus obtained, initial screening for their ability to support the growth of probiotics was carried out by the pure culture method. Bifidobacterium and Lactobacillus sp. responded positively to the addition of enzymatically derived oligosaccharides and their numbers increased significantly. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Serotonin N-hydroxycinnamoyltransferase (SHT) is a key enzyme in the synthesis of feruloylserotonin (FS) and 4-coumaroylserotonin (CS). These serotonin derivatives show strong antioxidant activity, making them valuable for both nutritional and pharmacological use in humans. Ectopic expression of SHT under the control of the endosperm specific-glutelin and prolamin promoters from rice was produced via Agrobacterium-mediated transformation. SHT expression was confirmed by Southern blot analysis, followed by Northern blotting and SHT enzyme activity analyses using total RNA and protein, respectively, extracted from transgenic seeds. The glutelin A3 (GluA3) promoter produced low SHT mRNA expression in rice seeds, whereas the prolamin promoter expressed high levels of SHT mRNA. In spite of the ectopic expression of SHT in rice seeds, both transgenic genotypes accumulated levels of serotonin derivatives similar to those found in wild-type rice. Furthermore, our data suggest that serotonin, rather than phenylpropanid-CoAs, is the rate-limiting substrate in the biosynthesis of serotonin derivatives in SHT-overexpressing transgenic rice seeds.
A compact, low-noise and inexpensive preamplifier circuit has been designed and fabricated to optimally readout a common cathode (1 x 16) channel 4H-SiC Schottky photodiode array for use in ultraviolet experiments. The readout uses an operational amplifier with 10 pF capacitor in the feedback loop in parallel with a low leakage switch for each of the channels. This circuit configuration allows for reiterative sample, integrate and reset. A sampling technique is given to remove Johnson noise, enabling a femtoampere level readout noise performance. Commercial-off-the-shelf acquisition electronics are used to digitize the preamplifier analog signals. The data logging acquisition electronics has a different integration circuit, which allows the bandwidth and gain to be independently adjusted. Using this readout, photoresponse measurements across the array between spectral wavelengths 200 nm and 370 nm are made to establish the array pixels external quantum efficiency, current responsivity and noise equivalent power. Published by Elsevier B.V.
Silicon RF power amplifiers (PAs) are in various RF front end modules (FEMs) today for handset and WLAN applications. Even though III-V semiconductor-based RF PAs can still offer superior frequency and breakdown performance with higher POUT and power-added-efficiency (PAE) and faster time-to-market, silicon-based RF PAs do have the advantages in offering higher monolithic integration with added functionalities (e.g., on-chip digital control and selection on power level, modulation, frequency band, matching, predistortion, etc.), which can translate to lower cost and smaller sizes attractive for broadband multi-mode multi-band handset transmitters. Therefore, some key techniques for designing high-efficiency 4G/5G/WLAN broadband wireless silicon PAs will be discussed.
Although gain of chromosome 5p is one of the most frequent DNA copy-number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study, we showed that the microRNA processor Drosha (located on chromosome 5p) demonstrates frequent copy-number gain and overexpression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/overexpression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in 18 cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of 14 that were differentially expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha-overexpressing samples/cell lines was the highest-ranked change (by adjusted p value) in both analyses, an observation validated by northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Aim: An RNA-seq analysis recently identified a 236-nucleotide transcript upstream from malS in Salmonella enterica serovar Typhi. Here, we investigated its molecular characteristics and function. Materials & methods: RACE and northern blotting were used to determine the molecular characteristics of the sequence, and mutagenesis, microarray, immunoblotting and an invasion assay were used to investigate the functions of the transcript. Results: The transcript was identified as the malS 5'-untranslated region (UTR), which could influence the expression of the flagellar and SPI-1 genes and the invasion of HeLa cells by S. Typhi. Deletion of bax increased the expression of the invasion genes and the invasive capacity of S. Typhi, whereas the expression of the malS 5'-UTR reduced the expression of bax. Conclusion: The malS 5'-UTR reduces the expression of bax and increases the invasive capacity of S. Typhi.
This paper presents the design of a compact 60-GHz phase shifter that provides a 5-bit digital phase control and 360 degrees phase range for beam-forming systems. The phase shifter is designed using the proposed cross-coupled bridged T-type topology and switched-varactor reflective-type topology. The topologies are analyzed using a small-signal equivalent circuit model. Furthermore, the design equations are derived and investigated. To validate the theoretical analysis, 60-GHz 5-bit 360 degrees phase shifters are designed in a commercial 65-nm CMOS technology. The fabricated 360 degrees phase shifter features good performance of 32 phase states from 57 to 64 GHz with an rms phase error of 4.4 degrees, a total insertion loss of 14.3 +/- 2 dB, an rms gain error of 0.5 dB, P-1 dB of better than 9.5 dBm, and the power consumption of almost zero. To the best of our knowledge, the designed 360 degrees phase shifter with the size of 0.094 mm(2) is the smallest 5-bit passive phase shifter at frequencies around 60 GHz.
By differential high-throughput RNA sequencing (dRNA-seq) we have identified "product RNAs" (pRNAs) as short as 8-12 nucleotides that are synthesized by Bacillus subtilis RNA polymerase (RNAP) in vivo using the regulatory 6S-1 RNA as template. The dRNA-seq data were confirmed by in vitro transcription experiments and northern blotting. In our libraries, we were unable to detect statistically meaningful numbers of reads potentially representing pRNAs derived from 6S-2 RNA. However, pRNAs could be synthesized in vitro from 6S-2 RNA as template by the B. subtilis sigma(A) RNAP. 6S-1 pRNA levels are low during exponential, increase in stationary and burst during outgrowth from stationary phase, demonstrating that pRNA synthesis is a conserved regulatory mechanism, but a more dynamic and fine-tuning process than previously thought. Most pRNAs have a length of 8-15 nt, very few up to 24 nt. The average length of pRNAs tended to increase from stationary to outgrowth conditions. Synthesis of pRNA is initiated at C40 of 6S-1 RNA and U41 of 6S-2 RNA, yielding pRNAs with a 5'-terminal G or A residue, respectively. A B. subtilis 6S-1 RNA mutant strain encoding a pRNA with a 5'-terminal A residue showed the same relative distribution of similar to 14-nt pRNAs between the different growth states, but generally displayed lower pRNA levels than the reference strain encoding wild-type 6S-1 RNA. A similar to two-fold lower affinity of the C40U mutant 6S-1 RNA towards sigma(A) RNAP may have contributed to this reduction in pRNA levels. We infer that 6S-1 pRNA synthesis, although evolutionarily optimized for initiation with a + 1G residue, is not primarily regulated at the transcription initiation level via growth phase-dependent variations in the cellular GTP pool.
The "central dogma" of molecular biology describes how information contained in DNA is transformed into RNA and finally into proteins. In order for proteins to maintain their functionality in both the parent cell and subsequent generations, it is essential that the information encoded in DNA and RNA remains unaltered. DNA and RNA are constantly exposed to damaging agents, which can modify nucleic acids and change the information they encode. While much is known about how cells respond to damaged DNA, the importance of protecting RNA has only become appreciated over the past decade. Modification of the nucleobase through oxidation and alkylation has long been known to affect its base-pairing properties during DNA replication. Similarly, recent studies have begun to highlight some of the unwanted consequences of chemical damage on mRNA decoding during translation. Oxidation and alkylation of mRNA appear to have drastic effects on the speed and fidelity of protein synthesis. As some mRNAs can persist for days in certain tissues, it is not surprising that it has recently emerged that mRNA-surveillance and RNA-repair pathways have evolved to clear or correct damaged mRNA.
A cDNA clone of Eucommia ulmoides Oliv. encoding auxin binding protein 1 (ABP1), one of the putative receptors of auxin, was isolated, and the seasonal expression of ABP1 in relation to IAA and ABA annual variation was investigated by different technical approaches including RT-PCR, real-time PCR, northern blotting, western blotting, and immunolocalization. In the cambial region, ABP1 expression at both the protein and the mRNA level was found to be high, low, and remarkably scarce in the active, quiescent, and resting stages, respectively, during cambium periodicity. The signal abundance of ABP1 follows the opposite pattern to ABA accumulation and correlates with auxin responsiveness of the cambial tissues, suggesting a role for ABP1 in mediating auxin-dependent regulation of cambial activation in the activity-dormancy cycle. This paper attempts to explain why IAA would 'boost' the reactivation of a quiescent cambium, and not that of a resting cambium. Results also show that ABP1 expression is improved by IAA, while inhibited by ABA.
The monkey is an important experimental model in the pharmacological evaluation of new drugs. We isolated monkey multidrug resistance-associated protein 2 (MRP2) cDNA to examine expression profiles among various tissues and measured ATPase activity to assess substrate specificity. The amino acid sequence encoded by monkey MRP2 cDNA was very similar (96% identity) to the reported human MRP2 cDNA (GenBank accession no. NM_000392). The tissue distribution of MRP2 in monkeys was partially different from that in humans. We found relatively high expression of MRP2 in the monkey kidney and small intestine using Northern blotting. Substrate specificity was compared between human and monkey MRP2. The affinity of 17 beta-estradiol 17-(beta-D-glucuronide), methotrexate, vinblastine, and probenecid to monkey MRP2 was higher than that to human MRP2. Functional and expression differences between human and monkey MRP2 should be incorporated into the evaluation of candidate drugs. (C) 2008 Elsevier B.V. All rights reserved.
Introduction: Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect.Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells.Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.
PurposeDespite being the third most common ABCA4 variant observed in patients with Stargardt disease, the functional effect of the intronic ABCA4 variant c.5461-10T>C is unknown. The purpose of this study was to investigate the molecular effect of this variant. MethodsFibroblast samples from patients carrying the ABCA4 variant c.5461-10T>C were analysed by isolating total RNA, followed by real-time polymerase chain reaction (RT-PCR) using specific primers spanning the variant. For detection of ABCA4 protein, fibroblast samples were lysed and analysed by SDS-PAGE followed by immunoblotting using a monoclonal ABCA4 antibody. ResultsThe ABCA4 variant c.5461-10T>C causes a splicing defect resulting in the reduction of full-length mRNA in fibroblasts from patients and the presence of alternatively spliced mRNAs where exon 39-40 is skipped. A reduced level of full-length ABCA4 protein is observed compared to controls not carrying the variant. ConclusionsThis study describes the functional effect and the molecular mechanism of the pathogenic ABCA4 variant c.5461-10T>C. The variant is functionally important as it leads to splicing defects and a reduced level of ABCA4 protein.
Objective/Background: Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. Methods: Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation. Expression of MMPs 1, 2, 3, 7, 8, 9, and 12, and tissue inhibitor of metalloproteinase (TIMP)1, and TIMP2 were measured at the mRNA level using quantitative reverse transcription polymerase chain reaction. At the protein level, MMPs, collagen I, and collagen III, and their degradation products carboxy-terminal collagen cross-links (CTX)-I and CTX-III, were quantified via enzyme linked immunosorbent assay. In addition, immunohistochemistry and gelatine zymography were performed. Results: In AAA, significantly enhanced mRNA expression was observed for MMPs 3, 9, and 12 compared with controls (p <= .001). MMPs 3, 9, and 12 correlated significantly with macrophages (p = .007, p = .018, and p = .015, respectively), and synthetic smooth muscle cells with MMPs 1, 2, and 9 (p = .020, p = .018, and p = .027, respectively). At the protein level, MMPs 8, 9, and 12 were significantly elevated in AAA (p = .006, p = .0004, and p < .001, respectively). No significant correlation between mRNA and protein was observed for any MMP. AAA contained significantly reduced intact collagen I (twofold; p = .002), whereas collagen III was increased (4.6 fold; p < .001). Regarding degraded collagen I and III relative to intact collagens, observations were inverse (1.4 fold increase for CTX-1 [p < .001]; fivefold decrease for CTX-III [p = .004]). MMPs 8, 9, and 12 correlated with collagen I (p = .019, p < .001, and p = 0.003, respectively), collagen III (p = .015, p < .001, and p < .001, respectively), and degraded collagen I (p = .012, p = .049, and p = .001, respectively). Conclusion: No significant relationship was found between mRNA and protein and MMP levels. MMPs 9 and 12 were overexpressed in AAA at the mRNA and protein level, and MMP-8 at the protein level. MMP-2 was detected in synthetic SMCs. Collagen I and III showed inverse behaviour in AAA. In particular, MMPs 8, 9, and;12 appear to be associated with collagen I, collagen III, and their degradation products. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Purpose of review One of the most important challenges in the intestinal ( ITx) and multivisceral transplant ( MVTx) is to achieve a successful abdominal wall closure. Recent findings A tension-free primary closure should be our aim. In most of the cases, we need to perform a component separation technique, alone or combined, to the use of a synthetic mesh. If those options are not feasible, the abdominal wall composite vascularized allograft transplant ( AW-CVA) utilizing direct orthotopic vascularization can be considered. The nonvascularized abdominal rectus fascia has also become an alternative method used worldwide, proving to be simple and well tolerated procedure. Furthermore, the use of the AW has been recently proposed as a new tool for a sentinel monitoring of the intestinal or pancreas allograft. Summary There are different validated options for abdominal wall closure following intestinal transplantation. The long-term benefits of transplanting the abdominal wall, full or partial thickness and vascularized or nonvascularised, were shown. New developments might help to expand their applications in different areas such as reconstructive surgery and immunology.
The Arabidopsis thaliana late embryogenesis abundant gene AtEm6 is required for normal seed development and for buffering the rate of dehydration during the latter stages of seed maturation. However, its function in salt stress tolerance is not fully understood. In this investigation, cell suspension cultures of three plant species rice (Oryza sativa L.), cotton (Gossypium hirsutum L.), and white pine (Pinus strobes L.) were transformed using Agrobacterium tumefaciens strain LBA4404 harboring pBI-AtEm6. Integration of the AtEm6 gene into the genome of rice, cotton, and white pine has been confirmed by polymerase chain reaction, Southern blotting, and northern blotting analyses. Three transgenic cell lines from each of O. sativa, G. hirsutum, and P. strobus were used to analyze salt stress tolerance conferred by the overexpression of the AtEm6 gene. Our results demonstrated that expression of the AtEm6 gene enhanced salt tolerance in transgenic cell lines. A decrease in lipid peroxidation and an increment in antioxidant enzymes ascorbate peroxidase, glutathione reductase and superoxide dismutase activities were observed in the transgenic cell lines, compared to the non- transgenic control. In rice, AtEM6 increased expression of Ca2+-dependent protein kinase genes OsCPK6, OsCPK9, OsCPK10, OsCPK19, OsCPK25, and OsCPK26 under treatment of salt. These results suggested that overexpression of the AtEM6 gene in transgenic cell lines improved salt stress tolerance by regulating expression of Ca2+-dependent protein kinase genes. Overexpression of the AtEM6 gene could be an alternative choice for engineering plant abiotic stress tolerance.
A novel gene, named NgAOX1a, was isolated from Nicotiana glutinosa by RT-PCR (reverse transcription-PCR). The full-length cDNA of NgAOX1a was 1448 bp, including a 1062-bp ORF (open reading frame), a 124 bp 5' UTR (untranslated region) and a 262 bp 3' UTR. The ORF encodes a 353-amino-acid protein which contains two conserved cysteine residues, four iron-binding motifs, five alpha-helix regions and six conserved histidine residues. The phylogenetic tree showed that NgAOX1a belongs to the AQX1 (alternative oxidase 1)-type group. Alignment analysis showed that NgAOX1a shares a high similarity with other known AOXs. Four exons and three introns were detected in the genomic DNA sequence, and Southern-blotting analysis suggested that NgAOX1a is a single-copy gene. A series of putative cis-acting elements were examined in the 5'-flanking region of NgAOX1a. Northern-blotting analysis showed that the transcript levels of NgAOX1a can be markedly accumulated when tobacco seedlings are treated with various abiotic stimuli, such as exogenous signalling molecules for plant defence response, salicylic acid and H2O2, and the exogenous TCA (tricarboxylic acid) cycle metabolite citrate. However, it could be suppressed by abiotic stress, such as CoCl2, an inhibitor of ethylene, which indicates that the expression of NgAOX1a may be regulated by ethylene. In addition, NgAOX1a can also be strongly induced by three viral pathogens, tobacco mosaic virus, potato virus X and potato virus Y. These results indicate that NgAOX1a may be involved in multi-signal transduction pathways and may play an important role in defence response.
To identify genes expression in Chenopodium album exposed to NaCl stress and screen ESTs related to salt stress, a subtractive suppression hybridization (SSH) library of C. album under salt stress was constructed in the present study. Random EST sequencing produced 825 high-quality ESTs with GenBank ID GE746311-GE747007, which had 301 bp of average size and were clustered into 88 contigs and 550 singletons. They were classified into 12 categories according to their function annotations. 635 ESTs (76.97%) showed similarities to gene sequences in the non-redundancy database, while 190 ESTs (23.03%) showed low or no similarities. The transcriptional profiles of 56 ESTs randomly selected from 347 unknown or novel ESTs of SSH library under varying NaCl concentration and at different time points were analyzed. The results indicated that a high proportion of tested ESTs were activated by salt stress. Four in 56 ESTs responded to NaCl were also enhanced in expression level when exposed to ABA and PEG stresses. The above four ESTs were validated by northern blotting which was consistent with the results of RT-PCR. The results suggested that genes corresponded to these ESTs might be involved in stress response or regulation. The complete sequences and detailed function of these ESTs need to be further studied.
Phosphorylation of protein kinases has profound effects on their activity and interaction with other proteins. Tyrosine phosphorylation was reported to be involved in various physiological processes in plants; however, no typical receptor tyrosine kinase has been isolated from plants thus far. Dual-specificity kinases are potentially responsible for the phosphorylation of both tyrosine and serine/threonine of target proteins. A cDNA clone encoding a putative dual-specificity protein kinase was isolated by screening the cDNA GAL4 activation domain (AD) fusion library of soybean (Glycine max L.), and its entire length was obtained using 5'-rapid amplification of cDNA ends. The predicted polypeptide of 330 amino acid residues, designated as GmSTY1, contains all 11 conserved subdomains, which share common characteristics with both the serine/ threonine and tyrosine protein kinases reported thus far. In addition, three potential N-linked glycosylation sites (NXS/T), as well as phosphorylation motifs (SXXXS/T), were observed, suggesting that GmSTY1 may be post-translationally modified. Furthermore, a potential N-myristoylation motif (MGARCSK) was found, suggesting that the GmSTY1 protein could associate with membranes in vivo. Southern blotting analysis revealed a single-copy of GmSTY1 in the genome. Northern blotting analysis showed that this gene was upregulated by drought and salt treatment in a time-dependent manner; however, exogenous abscisic acid (ABA) could not significantly affect the mRNA accumulation of GmSTY1. Interestingly, the transcript of this gene was remarkably downregulated by cold treatment during the early stages of the response, but upregulated later. These results indicate that the protein kinase was possibly regulated by abiotic stresses in an ABA-independent pathway.
Mitogen-activated protein kinase (MAPK) cascades are signalling modules that transduce extracellular signalling to a range of cellular responses. Plant MAPK cascades have been implicated in development and stress response. In this study, we isolated a novel group C MAPKK gene, ZmMKK4, from maize. Northern blotting analysis revealed that the ZmMKK4 transcript expression was up-regulated by cold, high salt and exogenous H(2)O(2), but down-regulated by exogenous abscisic acid (ABA). Over-expression of ZmMKK4 in Arabidopsis conferred tolerance to cold and salt stresses by increased germination rate, lateral root numbers, plant survival rate, chlorophyll, proline and soluble sugar contents, and antioxidant enzyme [peroxidase (POD), catalase (CAT)] activities compared with control plants. Furthermore, ZmMKK4 enhanced a 37 kDa kinase activity after cold and salt stresses. RT-PCR analysis revealed that the transcript levels of stress-responsive transcription factors and functional genes were higher in ZmMKK4-over-expressing plants than in control plants. In addition, ZmMKK4 protein is localized in the nucleus. Taken together, these results indicate that ZmMKK4 is a positive regulator of salt and cold tolerance in plants.
Citrullus colocynthis (L.) Schrad. is commonly known as colocynth. The fruit pulp of colocynth has medicinal properties while the seeds have nutritive qualities. C. colosynthis is resistant to high temperatures and grows in the desert regions of North Africa, the Middle East and Western Asia. C. colocynthis likely carries genes of interest that could be explored for inducing abiotic stress resistance in transgenic plants. Although the tissue culture and molecular biology of this species have been explored, the latter has been primarily used to resolve taxonomic relationships with other members of the Citrullus genus and curcubits. Genetic mining of the plant is scarce while genetic transformation protocols are also rare. The aim of the present review is to present a brief overview of the biotechnological perspectives of C. colocynthis.
Purpose of review This review provides an update and summary of recent neuropsychological findings in epilepsy focusing on three major clinical topics among the many developments in the field. We will critically outline the current state with regard to cognition in new-onset epilepsies, social cognition in epilepsy, and the long-term outcome of epilepsy surgery and the cognitive outcomes of superselective surgical procedures. Recent findings Current studies indicate that neuropsychological impairments are prevalent already at the onset of epilepsy and even before, social cognition (i.e., emotion recognition and theory of mind) is impaired in different epilepsy populations, the long-term outcome of epilepsy surgery is mostly characterized by a stable or even improved cognitive status, and superselective epilepsy surgeries are associated with a promising neuropsychological outcome. Summary The high prevalence of cognitive deficits around epilepsy onset challenges the assumption that epilepsy is the major cause of cognitive problems and calls for early neuropsychological diagnostics. Social cognition seems to be a relevant domain that is not yet routinely considered in epilepsy. The cognitive long-term outcome of epilepsy surgery is mostly positive. Stereotactic thermocoagulation and gamma knife surgery appear to be cognitively safe procedures.
microRNAs (miRNAs) play a crucial role in tissue development and the pathology of many diseases, however, the effects and roles of miRNAs in the development of semen abnormalities in infertile males have not yet been investigated. In this study, we analyzed and compared the miRNA expression profiles of abnormal semen from 86 infertile males with normal semen from 86 healthy males using an miRNA microarray. In total, 52 miRNAs were differentially expressed between the abnormal semen of infertile males and the normal semen of healthy males. The differential expression of selected miRNAs was validated by real time qRT-PCR and northern blotting: miR-574-5p, miR-297, miR-122, miR-1275, miR-373, miR-185 and miR-193b were upregulated (fold change >1.5, p<0.001) and miR-100, miR-512-3p, miR-16, miR-19b, miR-23b and miR-26a were downregulated (fold change <0.667, p<0.001) in the semen of infertile males with semen abnormalities. In conclusion, this study provides new insights into specific miRNAs that arc associated with semen abnormalities in infertile males.
Background: Respiratory morbidity in Australian Indigenous children is higher than their non-Indigenous counterparts, irrespective of urban or remote residence. There are limited studies addressing acute respiratory illness (ARI) in urban Indigenous children, particularly those that address the upper airway microbiome and its relationship to disease. We aimed to describe the prevalence of upper airway viruses and bacteria in symptomatic and asymptomatic urban-based Australian Indigenous children aged less than 5 years. Methods: A cross-sectional analysis of data collected at baseline in an ongoing prospective cohort study of urban Aboriginal and Torres Strait Islander children registered with a primary health care service in the northern suburbs of Brisbane, Australia. Clinical, demographic and epidemiological data and bilateral anterior nasal swabs were collected on enrolment. Polymerase chain reaction was performed on nasal swabs to detect 17 respiratory viruses and 7 bacteria. The primary outcome was the prevalence of these microbes at enrolment. Logistic regression was performed to investigate differences in microbe prevalence between children with and without acute respiratory illness with cough as a symptom (ARIwC) at time of specimen collection. Results: Between February 2013 and October 2015, 164 children were enrolled. The median age at enrolment was 18. 0 months (IQR 7.2-34.3), 49.4% were boys and 56 children (34.2%) had ARIwC. Overall, 133/164 (81%) nasal swabs were positive for at least one organism; 131 (79.9%) for any bacteria, 59 (36.2%) for any virus and 57 (34.8%) for both viruses and bacteria. Co-detection of viruses and bacteria was more common in females than males (61.4% vs 38.6%, p = 0.044). No microbes, alone or in combination, were significantly associated with the presence of ARIwC. Conclusions: The prevalence of upper airways microbes in asymptomatic children is similar to non-Indigenous children with ARIwC from the same region. Determining the aetiology of ARIwC in this community is complicated by the high prevalence of multiple respiratory pathogens in the upper airways.
We identified a Nodulin-related protein 1 (NRP1) encoded by At2g03440, which was previously reported to be RPS2 interacting protein in yeast-two-hybrid assay. Northern blotting showed that AtNRP1 expression was suppressed by heat stress (42A degrees C) and induced by low temperature (4A degrees C) treatment. Strong GUS staining was observed in the sites of meristematic tissues of pAtNRP1:: GUS transgenic plants, such as shoot apex and root tips, young leaf veins, stamens and stigmas of flowers, and abscission layers of young siliques. To study AtNRP1 biological functions, we have characterized both loss-of-function T-DNA insertion and transgenic overexpression plants for AtNRP1 in Arabidopsis. The T-DNA insertion mutants displayed no obvious difference as compared to wild-type Arabidopsis under heat stress, but the significant enhanced susceptibility to heat stress was revealed in two independent AtNRP1-overexpressing transgenic lines. Further study found that the decreased thermtolerance in AtNRP1-overexpressing lines accompanied significantly decreased accumulation of ABA after heat treatment, which was probably due to AtNRP1 playing a role in negative-feedback regulation of the ABA synthesis pathway. These results support the viewpoint that the application of ABA inhibits nodulation and nodulin-related gene expression and threaten adverse ambient temperature can impact the nodulin-related gene expression.
Although a great deal of progress has been made toward understanding the role of abscisic acid (ABA) in fruit ripening, many components in the ABA signalling pathway remain to be elucidated. Here, a strawberry gene homologous to the Arabidopsis gene ABI1, named FaABI1, was isolated and characterized. The 1641bp cDNA includes an intact open reading frame that encodes a deduced protein of 546 amino acids, in which putative conserved domains were determined by homology analysis. Transcriptional analysis showed that the levels of FaABI1 mRNA expression declined rapidly during strawberry fruit development as evidenced by real-time PCR, semi-quantitative reverse transcriptionPCR, and northern blotting analyses, suggesting that the Ser/Thr protein phosphatase PP2C1 encoded by FaABI1 may be involved in fruit ripening as a negative regulator. The results of Tobacco rattle virus-induced gene silencing and PBI121 vector-mediated overexpression suggested that the down- and up-regulation of FaABI1 mRNA expression levels in degreening strawberry fruit could promote and inhibit ripening, respectively. Furthermore, alteration of FaABI1 expression could differentially regulate the transcripts of a set of both ABA-responsive and ripening-related genes, including ABI3, ABI4, ABI5, SnRK2, ABRE1, CHS, PG1, PL, CHI, F3H, DFR, ANS, and UFGT. Taken together, the data provide new evidence for an important role for ABA in regulating strawberry fruit ripening in the processes of which the type 2C protein phosphatase ABI1 serves as a negative regulator. Finally, a possible core mechanism underlying ABA perception and signalling transduction in strawberry fruit ripening is discussed.
In this paper, the concept of multi-objective optimization is introduced in the automation of the placement task in analog integrated circuits layout design. To bridge the difficulties found on state-of-the-art works on fulfilling proximity constraints, here, cells are organized into proximity groups which implement the desired set of symmetry and proximity requirements. Then, an innovative archived-based multi-objective simulated annealing algorithm, operating over an absolute representation, is proposed to optimize the placement of each proximity group. In contrast to traditional single-objective placement approaches, the resulting Pareto fronts of placements, representing the tradeoffs between the optimization objectives of each group, are combined, bottom-up, through the design hierarchy, until a final front is obtained. This way, the problem's complexity is reduced, and split over multiple executions of the optimization kernel with less design variables, and also, analog designer becomes aware of the design tradeoffs. The proposed multi-objective and hierarchical methodology was implemented, and, experimental results prove that previous efforts on single-objective absolute representations are no match for the obtained floorplans. Furthermore, the obtained Pareto fronts contain the solutions found with the most recent published topological representations for the well-known Microelectronics Center of North Carolina benchmark sets, and, allowed an improvement of placement area up to 23% on a previously optimized folded cascode operational amplifier for the United Microelectronics Corporation 0.13 gm fabrication process. (C) 2015 Elsevier Ltd. All rights reserved.
This study examined whether child abuse history in teen mothers impacts offspring externalizing problems indirectly, through its influence on attachment and maternal hostility. In a longitudinal sample of 112 teen mother-child dyads, mothers reported on their own abuse experiences, attachment and maternal hostility were assessed via direct observations, and externalizing problems were measured using maternal reports. Compared with mothers with no abuse history, mothers with a history of sexual and physical abuse were more likely to have an insecurely attached infant, which predicted higher externalizing problems in preschool, which in turn predicted subsequent increases in externalizing problems in Grade 3. Furthermore, relative to the no abuse history group, mothers with a history of sexual and physical abuse showed more hostility toward their child at preschool, which in turn predicted elevated externalizing problems in Grade 3. Mothers' history of either sexual or physical abuse alone did not have significant indirect effects on externalizing problems. Fostering secure attachment and reducing risk for maternal hostility might be important intervention goals for prevention programs involving at-risk mothers with abuse histories. (C) 2016 Elsevier Ltd. All rights reserved.
Background This study assessed the knowledge of personal safety skills among children with developmental disabilities and their parents' perceptions of children's knowledge. Method This exploratory study examined the mental health records of 37 children with developmental disabilities referred for an abuse risk reduction group in a community mental health setting. Qualitative analysis of children's responses to questions about personal safety skills (knowledge related to physical development and personal safety, an appropriate and inappropriate touch and safety skills to respond to an inappropriate touch) indicated participants' varied and inconsistent levels of knowledge. Results Consistent with the literature, the results indicate risk factors for sexual abuse among children with developmental disabilities, including children's difficulty distinguishing between an appropriate and inappropriate touch and the lack of knowledge regarding appropriate venues for disclosing an inappropriate touch. Among parents, a lack of certainty regarding their children's knowledge and the ability to keep themselves safe was identified. Conclusion Results support the need for education about personal safety for children with developmental disabilities and their families.
Introduction: Posttraumatic stress symptoms (PTS) are associated with increased risk of obstetric complications among pregnant survivors of trauma, abuse and interpersonal violence, but little is known about how PTS affects women's actual experiences of obstetric care. This study investigated the rate at which abuse history was detected by obstetricians, whether abuse survivors experienced more invasive exams than is typically indicated for routine obstetric care, and whether psychological distress was associated with abuse survivors' sense of self-efficacy when communicating their obstetric care needs.Methods: Forty-one pregnant abuse survivors completed questionnaires about abuse history, current psychological distress and self-efficacy for communicating obstetric care needs and preferences. Electronic medical records (EMRs) were reviewed to examine frequency of invasive prenatal obstetric procedures (e.g. removal of clothing for external genital examination, pelvic exams and procedures) and to examine the detection rate of abuse histories during the initial obstetric visit.Results: The majority of participants (83%) reported at least one past incident of violent physical or sexual assault. Obstetricians detected abuse histories in less than one quarter of cases. Nearly half of participants (46%) received invasive exams for non-routine reasons. PTS and depression symptoms were associated with lower self-efficacy in communicating obstetric care preferences.Discussion: Women most at risk for experiencing distress during their obstetric visits and/or undergoing potentially distressing procedures may also be the least likely to communicate their distress to obstetricians. Results are discussed with implications for improving screening for abuse screening and distress symptoms as well as need for trauma-sensitive obstetric practices.
This paper tests the hypothesis that the association between childhood maltreatment and adult personality dysfunction is at least partially attributable to insecure attachment, that is that attachment style mediates the relationship between childhood maltreatment and adult personality dysfunction. Associations between childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), anxious and avoidant attachment in romantic relationships, as measured by the Experiences in Close Relationships-Revised (ECR-R), and five personality domains, as measured by the Severity Indices of Personality Problems (SIPP-118), were examined in a sample of 72 psychiatric inpatients. The SIPP-118 domains included relational capacities, identity integration, self-control, responsibility, and social concordance. The direct effect of childhood trauma on all SIPP-118 domains was not significant after controlling for the indirect effect of attachment. In regression modeling, a significant indirect effect of childhood trauma via adult attachment style was found for SIPP-118 relational capacities, identity integration, self-control, and social concordance. Specifically, anxious attachment was a significant mediator of the effect of childhood trauma on self-control, identity integration, and relational domains. These results suggest that childhood trauma impacts a broad range of personality domains and does so in large part through the pathway of anxious romantic attachment style.
Background: Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. Methods: Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p < .05 with a false discovery rate correction. Results: Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. Conclusions: Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility.
The significant co-occurrence between men's violence against female partners and child abuse and neglect is well documented. It is less clear how child safety should be managed in family violence research with their mothers. This issue is salient to isafe, a New Zealand-based Internet intervention study testing improvement in safety decisions and mental health outcomes for women experiencing intimate partner violence. This article discusses the legislative, professional, and ethical considerations that contribute to the development of the child safety protocols and discusses the development of the isafe protocol. Hypothetical scenarios of the application of the isafe protocol are used to illuminate the issues and provide a basis for future discussion.
Child sexual abuse (CSA) is a global public health problem with major consequences for the individual child and society. An earlier Swedish study showed that the school nurses did not initially talk about nor mention CSA as one form of child abuse. For the child to receive adequate support, the disclosure is a precondition and is dependent on an available person prepared to listen. The aim of the study was to explore the ability of the school nurses to detect and support sexually abused children. It is a secondary analysis of focus group interviews with school nurses. Thematic analysis was performed. Results showed that the school nurses avoided addressing CSA due to arousal of strong emotions, ambivalence, and a complicated disclosure process. In order to detect CSA and support abused children, attentiveness of sexual abuse as a possible cause of physical and mental illhealth is crucial.
The current study examined the mediating effects of the teacher and peer relationships between parental abuse/neglect and a child's emotional/behavioral problems. A total of 2070 student surveys from the panel of the Korean Child Youth Panel Study (KCYPS) were analyzed by path analysis. The key findings of this study are outlined below. Firstly, parental physical and emotional abuse and neglect had significant effects on children's problems. The direct effect of parental abuse on emotional/behavioral problems was higher than the direct effect of parental neglect on emotional/behavioral problems. Secondly, the teacher relationship partially mediated the effects of the parental abuse/neglect on emotional/behavioral problems. Thirdly, the peer relationship also partially mediated the effects of parental abuse/neglect on children's emotional/behavioral problems. The indirect effect of parental neglect via teacher relationships and peer relationships was stronger than the indirect effect of parental abuse. This study is significant in that it identified that parental abuse/neglect was mediated by the teacher and peer relationship, thereby suggesting an implication for effective intervention with children who have suffered abuse and neglect. In terms of the teacher and peer relationship, understanding the influence of parental abuse and neglect on children's problems was discussed, and the limitations and recommendations for future study were suggested. (C) 2016 Elsevier Ltd. All rights reserved.
Abuse-related trauma remains a global health issue. However, there is paucity in nationwide reports. We aim to estimate the incidence of abuse-related trauma forward medical care and identify its characteristics and clinical course in Taiwan. Patients with trauma between 2005 and 2007 that occurred 3 months before or after a diagnosis of abuse were identified from a randomly sampled nationwide longitudinal health insurance database of 1 million beneficiaries. The patients' demographic data, injury pattern, and medical resource utilization were measured, stratified by age and sex, and compared using chi-square test. Risk factors of next trauma event were identified using Cox regression analysis. Ninety-three patients (65 females) were identified (mean age, 20.6 +/- 16.3 years), including 61.3% under 18 years of age. For the first trauma event, 68 patients (73.1%) visited the emergency room, 63 (67.7%) received intervention, and 14 (15.1%) needed hospital care. Seven (7.5%), all less than 11 years old, had intracranial hemorrhage and required intensive care. Thirty-three (35.5%) left with complications or sequelae, or required rehabilitation, but all survived. Of the 34 victims of sexual abuse, 32 were aged less than 18 years. Men received more mood stabilizers or antipsychotics (50.0% vs 10.7%, P = 0.030) and reeducative psychotherapy (25.0% vs 0, P = 0.044). Risk factors for a next trauma event were injury involving the extremities (hazard ratio [HR]: 5.27 [2.45-11.33]) and use of antibiotics (HR: 4.21 [1.45-12.24]) on the first trauma event. Abuse-related trauma has heterogeneous presentations among subgroups. Clinicians should be alert in providing timely diagnosis and individualized intervention.
Purpose of review This review addresses some of the more salient articles in the field of child maltreatment published in 2015, with a goal of helping the general practitioner understand the evolution of research in the field of child abuse pediatrics (a board-certified specialty since 2009). Recent findings Researchers continue to refine the database for child abuse pediatrics. Several articles focus on the inconsistencies in approach to the evaluation of possible physical child abuse between hospitals and practitioners. Multiple researchers aim to develop a protocol that standardizes the response to findings of a sentinel injury, such as a rib fracture, abdominal trauma, or unexplained bruising in a nonambulatory infant. Professionals are also working to improve our understanding about the impact of trauma on children and how best to ameliorate its effects. Summary With solid, evidence-based literature published on various topics in the field of child abuse pediatrics, experts work to refine and unify the clinician's approach to the evaluation of possible physical abuse.
When Abusive Head Trauma (AHT) is suspected in a child, a dilated eye examination by an ophthalmologist is an essential part of the medical workup, as the presence and pattern of retinal hemorrhages can have a high positive predictive rate for abusive head injury. This article proposes to review the clinical presentation, pathophysiology, natural history, sequelae, and differential diagnosis of retinal hemorrhages and other ocular lesions associated with AHT.
The frequency and severity of physical abuse influences children's outcomes, yet little theory-based research has explored what predicts its course. This study examined the potential role of social information processing (SIP) factors in the course of abuse. Mothers with histories of perpetrating physical abuse (N = 62) completed measures of SIP, and the frequency and severity of mother-perpetrated physical abuse were collected from Child Protection Services records. Poorer problem-solving capacities were significantly related to greater frequency of physical abuse. Hostile attributions toward children were positively associated with abuse severity. Controlling for demographics and co-occurrence of neglect, SIP factors together accounted for a significant proportion of variance in the frequency of physical abuse, but not severity. With the exception of unrealistic expectations, preliminary evidence supported a link between maternal SIP and the course of abuse perpetration. Future research directions and implications for intervention are discussed.
Shaken baby syndrome is a term often used by the physicians and public to describe abusive trauma inflicted on infants and young children. Advances in the understanding of the mechanisms and the associated clinical spectrum of injury has lead us to modify our terminology and address it as "abusive trauma" (AT). Pediatric abusive head trauma is defined as an injury to the skull or intracranial contents of an infant or a young child (<5 y age) due to inflicted blunt impact and/or violent shaking. This chapter focuses on the imaging aspects of childhood abusive trauma along with a brief description of the mechanismand pathophysiology of abusive injury. The diagnosis of AT is not always obvious, and abusive injuries in many infants may remain unrecognized. Pediatricians should be cognizant of AT since pediatricians play a crucial role in the diagnosis, management and prevention of AT.
This article reviews the evolution of the diagnosis and treatment of Hodgkin lymphoma (HL) since its discovery in 1832. The morphological, phenotypic and molecular characteristics of both nodular lymphocyte-predominant HL and classical HL are revised in the light of recent molecular information and possible impact on the identification of risk groups as well as the use of targeted therapies. The seminal contribution of Gianni Bonadonna to developing new treatment strategies for both advanced and early-stage HL is highlighted.
An analytic design guide to design a three-stage cascade CMOS operational amplifier compensated by AC boosting frequency compensation (ACBC) method is presented in this paper. The procedure allows electrical parameters such as gain bandwidth (GBW) product or phase margin to be related to the value of circuit elements such as aspect ratio or biasing currents of transistors. The presented design guide is suited for pencil-and-paper design and yields accurate performance without unnecessary circuit constraint introduction. Simulation results using TSMC 0.18 mu m CMOS process verifies accuracy and robustness of proposed procedure. Various load capacitors and circuit conditions are simulated and, based on obtained results, the presented design guide is comprehensive and efficient since it leads us from frequency response parameters to aspect ratio of MOSFETs.
Programmable AC power sources have been widely used to implement and support a wide range of Test Procedure Specifications (TPS's). Traditionally, these power sources use analog control circuits to provide key control and protection functions like load regulation, current limit and frequency conversion. While this is a proven design, it suffers from a number of drawbacks. With the advent of recent advances in DSP technologies, a full digital implementation of an AC power source design supporting high switching frequencies is now feasible. This paper discussed some of the advantages derived from an all-digital implementation of a programmable poser source and the benefits this provides for ATE system use.
This paper describes a new calibration system developed at INMETRO to guarantee traceability of low-frequency alternating current (ac) voltage calibrations (<1 kHz) to a programmable Josephson ac waveform synthesizer. The automated full-synchronous system allows the synchronization of a commercial calibrator or signal synthesizer with a programmable Josephson voltage synthesizer system to be made by employing digital sampling and signal processing techniques, aided by adaptive digital control. It allows accurate determination of the spectral content of ac signals with minimum human intervention. System operation, measurement techniques, and data analysis are detailed.
The voltage source converters (VSC) are the key power interfaces between the individual ac grids and dc grids in the hybrid power system. When the ac grid is unbalanced, the grid currents are distorted and the harmonic is induced. Meanwhile, the oscillations in the active and reactive power are also increased, which may damage these interfaces. In order to ensure the safety of the converters and the grid facility, a flexible control strategy is proposed for the ac/dc hybrid grid in this paper. At first, the current harmonic for the VSC is theoretically analyzed under unbalanced conditions. Furthermore, the methods to separate the positive- and negative-sequence components of the ac grid voltages are summed up and analyzed. Based on the theoretical analysis, different protected control methods are compared. A new control method, which can flexibly control oscillations of the active and reactive power by introducing a parameter k, has been proposed. The estimation of maximum current in each phase is discussed; meanwhile, the relationship between the voltage ripple on dc link and the parameter k is given. Finally, the validity and advantages of the proposed method are verified by the simulating and experimental results.
Based on single-phase ac-ac converter with controllable phase and amplitude (ACCPA), a three-phase ACCPA without third harmonic trap was proposed for power transmission control in grid by adopting a symmetrical relationship of three phase. The three-phase ACCPA is comprised of two parts, which are used to adjust the phase and amplitude of three-phase output voltage, respectively, and continuously. Its front part is made up of three buck-type ac converters, and the back part is a three-phase boost-type ac converter. The operation principle of three-phase ACCPA, the adjustable ranges of the phase and amplitude of the front part, and the calculation formulas of control parameters under ideal conditions were studied and deduced in detail. Furthermore, the control accuracy of the phase angle was discussed for the three-phase ACCPA with digital control, and then, the method to select close-loop control parameters was obtained. The control strategy of three-phase ACCPA was presented and a prototype was fabricated. The experimental waveforms and testing results verified the correctness of the theoretical analysis and the feasibility of the control strategy.
This article deals with the simulation of the power converter with voltage-source inverter and sine-filter. The repetitive control system was designed. The existing power converter has a control system which makes Fourier transform of the output voltage to inject these harmonics with opposite phase. The new proposed system based on repetitive controller which is much simpler and with smaller CPU load. The higher harmonics elimination works perfect and the power converter produces output voltage with less than 5% THD under linear or non-linear load. This paper describes the improved control system structure and its implementation in MATLAB Simulink environment. The advantages of the repetitive algorithm facing Fourier transform harmonic compensation are shown. The performance of the new control method is shown in simulation results. The algorithm is carried out in C language using MATLAB S-Function block so it is suitable for implementation in the real-time control systems.
Various species of amoebas belonging to the genus Acanthamoeba are widely distributed in many parts of the world. Some strains of these protozoans may exist as parasites and pose risks to human health as causative agents of serious human diseases. Currently in China there IS a lack of information about the distribution of Acanthamoeba strains in the environment. Accordingly, 261 environmental water samples taken from rivers, sewage, and pharmaceutical factory drains were collected in Qinghai Province, China. The material was filtered and then analysed with both LAMP and PCR assays. Of the samples examined, Acanthamoeba DNA was found in 32 (14.68%) samples with the use of LAMP; in 13 of these samples, DNA from this amoeba was also detected using PCR. Sequencing of selected positive samples confirmed that the PCR products were fragments of the Acanthamoeba 18S rRNA gene and that isolates represent the T4 genotype, known as the Most common strain related to AK cases. The results indicate that surface water, as well as water taken from sewage And pharmaceutical drains, may be a source of acanthamoebic strains potentially pathogenic for humans in China. It has been also demonstrated that LAMP assays is more sensitive than PCR and can be regarded as useful tool for screening the environment for Acanthamoeba spp. (C) 2017 Elsevier B.V. All rights reserved.
Particle accelerators consist of an enormous number of components and many of them operate with pulse voltage or current. Such accelerator components require precise voltage or current to keep the beams very stable. For this reason, many pulse power supplies used for accelerators have own subsystems to improve their performances. One example is a power supply for the scanning magnets of a pencil beam proton therapy. They use not only high-voltage inverters for the high-speed ramping but also low-voltage inverters for the precise current control. However, the use of intelligent digital controllers possibly simplifies such precise power supplies. We propose a method for precise current control using a digital control system. Our previous work has successfully controlled the pulse current of power supplies for synchrotron main magnets. In the next step, we have modified our previous method for faster power supplies such as ones for scanning magnets. In addition, we developed a control board using a high-performance FPGA so that our method can be implemented in the board. In this paper, we describe the details of our proposed method, and the experiments using a small-scale power supply and the developed control board.
This paper presents the design of a compact, wearable, rechargeable acceleration recorder to support long-term monitoring of ambulatory patients with motor disorders, and of software to display and analyze its output. The device consists of a microcontroller, operational amplifier, accelerometer, SD card, indicator LED, rechargeable battery, and associated minor components. It can operate for over a day without charging and can continuously collect data for three weeks without downloading to an outside system, as currently configured. With slight modifications, this period could be extended to several months. The accompanying software provides flexible visualization of the acceleration data over long periods, basic file operations and compression for easier archiving, annotation of segments of interest, and functions for calculation of various parameters and detection of immobility and vibration frequencies. Applications in analysis of gait and other movements are discussed.
A high performance interface circuit of sigma-delta accelerometer with low harmonic distortion used many kinds of circuit processing techniques is presented in this work. Multi-bit, dynamic element matching, correlated-double-sampling and electrostatic force feedback linearization circuit are used simultaneously in order to achieve the design indicators. Because of the usage of multi-bit, the design to operational amplifier (OPA) becomes easier, and only a single-stage folded-cascode amplifier is used in the modulator, the OSR is only 64. It highly reduced the difficulty of circuit. The test results indicate that the chip area is only about 10mm(2) and the power dissipation is 10mW with a sampling frequency of 60 kHz. The dynamic range (DR) of the system can be lower than -130 dB, the SNR and SNDR reach to -120 dB and -110 dB respectively with a resolution about 17 bits when referred to 3g full scale DC acceleration under CMOS 0.5 mu m process. The dc nonlinearity of it is 0.2%. This paper realizes an approach which can both simplify the design of the interface circuit and improve the performance of it.
In this article we address the increasingly important yet understudied phenomenon of nonnative accentedness on decision making. In three experimental studies, we investigated whether messages about a company delivered in nonstandard-American-accented speech influenced choice. In Study 1, we found that individuals were more likely to choose a company or a product when a message was read in a standard American English accent than when the message was delivered with a Mandarin Chinese or a French accent. In Study 2, we found that expectations regarding company messages are violated when speakers have accents and that, in turn, expectation violations mediated the relationship between accent and choice. In Study 3, we replicated the findings of the effect of accent on choice using Indian and British accents. We also hypothesized and found support for a conditional indirect effects model such that implicit pro-American bias moderated the indirect relationship between accent and choice as mediated by expectation violations. Theoretical and practical implications of this topic of study are discussed.
Acceptance is a key construct in both rational emotive behavior therapy (REBT) and acceptance and commitment therapy (ACT). The objectives of this study were to assess and compare the properties of ACT acceptance with those of REBT acceptance in predicting emotions. A sample of 112 subjects, comprising different educational and occupational status, completed three measures of acceptance (REBT and ACT), two of mindfulness, as well as completing depression and anxiety scales. Both ACT acceptance as process and REBT acceptance could predict significant ACT acceptance as outcome. Mindfulness as a trait also predicted the level of ACT outcome acceptance as well as the level of REBT acceptance, but mindfulness as process predicted only ACT outcome acceptance. The results show that REBT acceptance, ACT acceptance and mindfulness can explain anxiety and depression in different ways. The results show that the difference between ACT acceptance and REBT acceptance primary concern the process of acceptance, most likely due to the underlying cognitive processing. The outcome acceptance and emotional level are similar in the two conditions. Future research should employ multiple cognitive measurements.
Immigrant and refugee women from diverse ethnic backgrounds encounter multiple barriers in accessing mental healthcare in various settings. A systematic review on the prevalence of mental health disorders among culturally and linguistically diverse (CALD) women in Australia documented the following barriers: logistical, language and communication, dissonance between participants and care providers and preference for alternative interventions. This article proposes recommendations for policies to better address the mental health needs of immigrant and refugee women. Key policy recommendations include: support for gender specific research, implementation and evaluation of transcultural policies, cultural responsiveness in service delivery, review of immigration and refugee claims policies and social integration of immigrants.
OBJECTIVE: Cervical imaging practices are poorly understood in young children with traumatic brain injury (TBI). We therefore sought to identify child-level and hospital-level factors associated with performance of cervical imaging of children with TBI from falls and abusive head trauma (AHT) and to describe across-hospital variation in cervical imaging performance. We hypothesized that imaging decisions would be influenced by hospital volume of young injured children. METHODS: We performed a retrospective study of children younger than 2 years of age with TBI from 2009 to 2013 in the Premier Perspective Database. After adjustment for observed patient characteristics, we evaluated variation in advanced cervical imaging (computed tomography or magnetic resonance imaging) in children with AHT and TBI from falls. RESULTS: Of 2347 children with TBI, 18.7% were from abuse and 57.1% were from falls. Fifteen percent of children with TBI underwent advanced cervical imaging. Moderate or severe head injuries were associated with increased odds of cervical imaging in AHT (odds ratio 7.10; 95% confidence interval 2.75, 18.35) and falls (odds ratio 2.25; 95% confidence interval 1.19, 4.27). There was no association between annual hospital volume of injured children and cervical imaging performance. The adjusted probability of imaging across hospitals ranged from 4.3% to 84.3% in AHT and 3.1 to 39.0% in TBI from falls (P < .001). CONCLUSIONS: These results highlight variation across hospitals in adjusted probability of cervical imaging in AHT (nearly 20-fold) and TBI from falls (over 10-fold) not explained by observed patient characteristics. This variation suggests opportunities for further research to inform imaging practices.
ObjectiveThe aim of this study was to explore the preferred acculturation strategies adopted by Indian subcontinental adolescents living in Australia. The study also examined the demographic, ethnocultural, and psychological factors that could influence subcontinental migrant groups' attitudes towards acculturation and their acculturation strategies. MethodA cross-sectional design was used in which the dependent variables were the four acculturation strategies. Multivariate data analysis was conducted. Pearson's correlation, analysis of variance, and step-wise multiple regression analyses were performed to establish the relationships among the study variables. ResultsIntegration was the most preferred strategy and marginalisation was the least preferred strategy for all ethnic groups. Acculturation preferences are predicted partly by the adolescents' ethnicity, their ethnic identity, friendship choices, acculturative stress, sense of mastery (self-concept) and gender. The findings provide significant information on the acculturation practices of Indian subcontinental adolescents, including their ethnic identity search and commitment, their psychological well-being and their integration strategies. ConclusionsEducational institutions could benefit from increased awareness of the needs of these culturally diverse groups, especially if this information is incorporated into teacher training materials. The inclusion of intercultural relations courses in the academic curriculum would promote harmonious relations between culturally diverse ethnic groups.
In order to improve the dynamic responses of multimode controlled primary-side regulation flyback converter, a novel digital control method is proposed in this paper. A new DAC sampling method, which can capture the output voltage during dynamic transition, is introduced. Based on it, a dynamic module which can monitor the variation of the output voltage to improve the dynamic performance is proposed. In a 5-V/1-A primary-side regulation flyback converter, the maximum undershoot voltage and overshoot voltage of the proposed control scheme in this study are 0.472 and 0.192 V, respectively. They are much lower compared to 1.296 and 0.584 V in the traditional control scheme. The maximum undershoot and overshoot recovery times are reduced from 10.86 to 1.29 ms and 126.3 to 53.68 ms, respectively. The proposed control scheme was then verified by a FPGA controlled prototype.
This study proposes high-performance voltage controller design that employs a capacitor current control model for single-phase stand-alone inverters. The single-phase stand-alone inverter is analyzed via modeling, which is then used to design the controller. A design methodology is proposed to maximize the bandwidth of the feedback controller. Subsequently, to compensate for the problems caused by the bandwidth limitations of the controller, an error transfer function that includes the feedback controller is derived, and the stability of the repetitive control scheme is evaluated using the error transfer function. The digital repetitive controller is then implemented. The simulation and experimental results show that the performance of the proposed controller is high in a 1.5 kW single-phase stand-alone inverter prototype.
This work presents a novel mixed-signal control scheme for a boost power factor correction (PFC) rectifier. The digital controller modulates the inductor peak current to produce a low-distortion ac line current in discontinuous conduction mode (DCM) and continuous conduction mode (CCM), without the need for average current sensing. A lookup table (LUT) optimizes efficiency at low input currents, by allowing operation at 125-500-kHz DCM based on calculated thresholds. At high input currents, the converter operates at 1-MHz CCM for reduced inductor footprint. An analog off-time generator with a digital frequency locked loop facilitates CCM operation, eliminating the need for slope compensation in the current loop and reduces frequency variations. The LUT is programmed with an adaptive output voltage of 250/450 V for low/highmains line voltage (85-265Vrms) to optimize efficiency over a broad range of conditions. The 150-W PFC prototype operates up to 1 MHz with a peak efficiency of 95% and a total harmonic distortion of 5%.
The theoretical and experimental analysis of a modified version of the SEPIC dc-dc converter used as preregulator operating in discontinuous conduction mode (DCM) is presented in this paper. The proposed converter presents a low input current ripple operating in DCM, and the switch voltage is lower than the output voltage. The switch voltage reduction increases the converter reliability and a low drain-to-source on-resistance (RDSon) MOSFET can be used depending on the converter specification. Moreover, a digital control technique is applied to the proposed converter in order to reduce the third-harmonic input current distortion resultant of the operation in DCM. Finally, a 100-W prototype was developed operating with efficiency equal to 95.6%.
In high-performance magnetic resonance imaging systems, the gradient driver is required to supply the gradient coil with a large current (>600 A) and a high voltage (>2000 V) to achieve a strong gradient field and a fast slew rate. In addition, extremely high fidelity for reproducing the current command from the central system is very critical to imaging quality. This paper presents the solutions for the different elements of the driver: 1) high-bandwidth (BW) power inverter; 2) ripple cancelation filter; 3) multioutput power supply (PS); and 4) digital control. A high-BW power inverter requires a stacked-bridges structure to achieve a high output ripple frequency with the existing commercial power semiconductor modules. The high voltage and the high frequency for large power modules can be obtained easier and with lower loss using the new silicon carbide devices. The control needs a digital implementation and a very fast processor. Digital control provides compensation and feedforward to improve the response. A capability improvement is obtained by reducing the switching frequency when large currents with a very low-frequency variation are needed. The control can handle it very well, but the filter has to be designed to eliminate more than one ripple frequency. Finally, many PS solutions have been used for multiple isolated outputs, but digital control compensation permits the use of much simpler unregulated PS and keeps the performance. A 2 MVA, 900 A/1200 V, platform has been built and fully tested. The experimental results proved the validity of the proposed structure and the modulation technique.
Drug release belongs to the most challenging aspects of nanoparticles addressing molecular biology and medicine. Besides targeted delivery, obvious challenges are related to high drug load and continuous slow drug release. Based on our recently developed concept of inorganic-organic hybrid nanoparticles (IOH-NP), we here present [ZrO](2+)[AAP](2-) IOH-NPs containing the analgetic phosphate prodrug acetaminophen phosphate for drug release. [ZrO](2+)[AAP](2-) combines an uncomplex synthesis in water with a high prodrug load of 68 wt.%.[ZrO](2+)[AAP](2-) nanoparticles exhibit a diameter of 37(11) nm and can be readily obtained as colloidally highly stable suspension in water. The chemical composition is studied in detail based on infrared spectroscopy, energy-dispersive X-ray analysis, thermogravimetry and elemental analysis. Moreover, the release of acetaminophen from [ZrO](2+)[AAP](2-) is studied by means of model experiments indicating the carbon content of the nanoparticles and, in alternative, the fluorescence of labeled nanoparticles. Both data show a continuous release of 80 wt.% of the analgetic acetaminophen on a time scale up to 48 h. (C) 2016 Elsevier Inc. All rights reserved.
We have reported that orally administrated acetate contributed to suppression of lipogenesis in the liver and to reduction of lipid accumulation in the adipose tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The aim of this study was to investigate the effect of acetate on skeletal muscle and adipose tissues. Treatment with acetate showed a higher rate of oxygen consumption and a smaller size of lipid droplets in white adipose and brown adipose tissues. An analysis by Northern blotting revealed that the transcripts of myoglobin and Glut4 genes in the abdominal muscle of the OLETF rats were increased by acetate treatment, while the transcripts of lipolytic genes increased in the white adipose and brown adipose tissues. It is possible that acetate has effects on lipid metabolism in the skeletal muscles and the adipose tissues, and has functions that work against obesity and obesity-linked type 2 diabetes.
Acetate has been found to have an inhibitory effect on the activity of carbohydrate-responsive element-binding protein (ChREBP) in cultured hepatocytes, this being a transcription factor that regulates several genes required for the conversion of glucose to fatty acids in the liver. The aim of this study was to investigate whether an oral administration of acetate would contribute to reducing lypogenic genes and protecting against obesity. We orally injected 5.2mg/kg BW of acetate to obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The treatment with acetate showed a marked reduction in lipid accumulation in the adipose tissue, protection against accumulation of fat in the liver, and improved glucose tolerance. An analysis by Northern blotting revealed that the transcripts of several lipogenic genes in the liver of OLETF rats were decreased by the acetate treatment. On the basis of those results, it was indicated that acetate was a potential compound to improve obesity and obesity-linked type 2 diabetes.
Research was carried out for the appraisal of toxic and anti-enzymetic action of acetone extracts of Datura inoxia and Azadirachta indica against Tribolium castaneum, Trogoderma granarium and Sitophilus granarius in the grain research training and storage management cell of department of entomology and in protein molecular biology laboratory (PMBL) department of biochemistry (UAF) during the year 2014. Various dilution levels viz., 5.0, 10.0, 15.0 and 20.0% of both plants extracts were assessed against test insects. Toxic effect of plant extracts in T. castaneum, T. granarium and S. granarius was observed after an exposure period of 2, 4, 6, 8 and 10 days while inhibition of different enzymes acetylcholinesterase (AChE), a-carboxylesterase (alpha-CE), beta-carboxylesterase (beta-CE), acid phosphatases (ACP) and alkaline phosphatases (ALP) were calculated spectrophotometrically in the survivors of toxicity assay. The results evidenced that both plant extracts had lethal effects against three stored grain insect species. Comparison of means of mortality in T. castaneum, T. granarium and S. granarius proved that A. indica extract was more effective, causing maximum 38.41, 24.35 and 28.56% mortality, respectively. D. inoxia resulted in 15.12, 13.52 and 14.07% maximum mortality in T. castaneum, T. granarium and S. granarius, respectively. The results also revealed significant inhibition of AChE, alpha-CE, beta-CE, ACP and ALP upon exposure to various concentrations of tested plants. Plant extract of A. indica proved more efficient for the inhibition of all test enzymes in three stored grain insect pests. The results suggest the ability of using these plants extracts for wheat flour and grains protection as a safe alternative to insecticides.
Bacterial community analyses of samples from a pilot plant for the treatment of acid mine drainage (AMD) from the lignite-mining district in Lusatia (East Germany) had previously demonstrated the dominance of two groups of acidophilic iron oxidizers: the novel candidate genus "Ferrovum" and a group comprising Gallionella-like strains. Since pure culture had proven difficult, previous studies have used genome analyses of co-cultures consisting of "Ferrovum" and a strain of the heterotrophic acidophile Acidiphilium in order to obtain insight into the life style of these novel bacteria. Here we report on attempts to undertake a similar study on Gallionella-like acidophiles from AMD. Isolates belonging to the family Gallionellaceae are still restricted to the microaerophilic and neutrophilic iron oxidizers Sideroxydans and Gallionella. Availability of genomic or metagenomic sequence data of acidophilic strains of these genera should, therefore, be relevant for defining adaptive strategies in pH homeostasis. This is particularly the case since complete genome sequences of the neutrophilic strains G. capsiferriformans ES-2 and S. lithotrophicus ES-1 permit the direct comparison of the metabolic capacity of neutrophilic and acidophilic members of the same genus and, thus, the detection of biochemical features that are specific to acidophilic strains to support life under acidic conditions. Isolation attempts undertaken in this study resulted in the microaerophilic enrichment culture ADE-12-1 which, based on 16S rRNA gene sequence analysis, consisted of at least three to four distinct Gallionellaceae strains that appear to be closely related to the neutrophilic iron oxidizer S. lithotrophicus ES-1. Key hypotheses inferred from the metabolic reconstruction of the metagenomic sequence data of these acidophilic Sideroxydans strains include the putative role of urea hydrolysis, formate oxidation and cyanophycin decarboxylation in pH homeostasis.
In this study, laccase from Trametes versicolor was immobilized in poly(acrylamide-crotonic acid)/sodium alginate [P(AAm-CrA)/alginate], poly(acrylamide-crotonic acid)/K-carrageenan [(P(AAm-CrA)/K-car)], poly(acrylamide-citraconic acid)/sodium alginate (P(AAm-CA)/alginate), and poly(acrylamide-citraconic acid)/K-carrageenan (P(AAm-CA)/K-car) semi-interpenetrating network by entrapment method. Optimum pH and temperatures values were determined between 5.0-6.0 and 40-50 degrees C for free laccase (FL) and immobilized laccases, respectively. After 42 days of storage at 4 degrees C, FL and immobilized laccases retained their original activities in the range of 55%-73%. Percent decolorization of Acid Orange 52 by free enyzme and enyzmes immobilized in hydrogels was found between 63% and 39%. Percent decolorization of Acid Orange 52 in the presence of mediator by free enyzme was found 73% and enyzmes immobilized in hydrogels were found as 73%. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
c-Myc overexpression has been implicated in several malignancies including gastric cancer. Here, we report that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer via c-Myc activation both in vivo and in vitro. c-Myc mRNA and protein levels were assessed in ten primary and five local recurrent gastric cancer samples by quantitative real-time polymerase chain reaction and western blotting analysis. The gastric cancer cell line MGC803 was exposed to bile salts (100mol/L glycochenodeoxycholic acid and deoxycholic acid) in anacidmedium (pH 5.5) for 10min daily for 60weeks to develop an MGC803-resistant cell line. Control MGC803 cells were grown without acids or bile salts for 60weeks as a control. Cell morphology, proliferation, colony formation and apoptosis of MGC803-resistant cells were analyzed after 60weeks. To determine the involvement of c-Myc in tumor progression and telomere aging in MGC803-resistant cells, we generated xenografts in nude mice and measured xenograft volume and in vivo telomerase activity. The c-Myc and hTERT protein and mRNA levels were significantly higher in local recurrent gastric cancer samples than in primary gastric cancer samples. MGC803-resistant cells showed a marked phenotypic change under normal growth conditions with more clusters and acini, and exhibited increased cell viability and colony formation and decreased apoptosis in vitro. These phenotypic changes were found to be dependent on c-Myc activation using the c-Myc inhibitor 10058-F4. MGC803-resistant cells also showed a c-Myc-dependent increase in xenograft growth and telomerase activity in vivo. In conclusion, these observations support the hypothesis that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer and that these effects are dependent on c-Myc activity. These findings suggest that acidified bile acids play an important role in the malignant progression of local recurrent gastric cancer.
Thermoelectric (TE) materials are important for the sustainable development because they enable the direct harvesting of low-quality heat into electricity. Among them, conducting polymers have attracted great attention arising from their advantages, such as flexibility, nontoxicity, easy availability, and intrinsically low thermal conductivity. In this work, a novel and facile method is reported to significantly enhance the TE property of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) films through sequential post-treatments with common acids and bases. Compared with the as-prepared PEDOT:PSS, both the Seebeck coefficients and electrical conductivities can be remarkably enhanced after the treatments. The oxidation level, which significantly impacts the TE property of the PEDOT:PSS films, can also be well tuned by controlling the experimental conditions during the base treatment. The optimal PEDOT:PSS films can have a Seebeck coefficient of 39.2 mu V K-1 and a conductivity of 2170 S cm(-1) at room temperature, and the corresponding power factor is 334 mu W (m(-1) K-2). The enhancement in the TE properties is attributed to the synergetic effect of high charge mobility by the acid treatment and the optimal oxidation level tuned by the base treatment.
Background: Carbapenem-resistant Acinetobacter baumannii has emerged as an important cause of infection in burn patients. This study aimed to characterize the antimicrobial susceptibility pattern, determine the prevalence of oxacillinase and metallo-beta-lactamase (MBL) genes, and type the A. baumannii isolates obtained from burn patients. Methods: During a 1-year period, a total of 40 nonduplicated isolates of A. baumannii were obtained from burn patients who were hospitalized in the Taleghani Burn Hospital in Ahvaz, in the southwest of Iran. Testing for antimicrobial susceptibility was carried out by disk diffusion and E-test. To screen MBL production, a double disk synergy and MBL E-test were performed. The presence of bla(OXA-23-like), bla(OXA-24-like), bla(OXA-51-like) and bla(OXA-58-like), bla(VIM), bla(IMP) and bla(SPM), and bla(NDM) was sought by polymerase chain reaction (PCR). Repetitive extragenic palindromic sequence-based PCR was carried out for determination of isolates clonality. Results: Overall, 92.5% of isolates were carbapenem-resistant. Polymyxin B, colistin, and ampicillin-sulbactam were the most effective agents in vitro, with a susceptibility rate of 100%, 97.5%, and 72.5%, respectively. According to the double disk synergy and E-test, 55.6% and 97.3% of isolates were MBL producers, respectively. Furthermore, 70% of isolates harbored bla(OXA-23-like) and 20% were positive for bla(OXA-24-like). However, no encoding genes were detected for bla(VIM), bla(IMP) and bla(SPM), bla(NDM), and bla(OXA-58-like). Repetitive extragenic palindromic sequence-based PCR revealed that carbapenem-resistant isolates belonged to four clones, including A, B, C, and D; the predominant clones were B and C. Conclusion: The rate of carbapenem resistance was high, and it appeared that bla(OXA-23-like) and bla(OXA-24-like) contributed to the carbapenem resistance of A. baumannii isolates. This result suggests that the two predominant clones of A. baumannii were spread among burn patients. In order to prevent future dissemination of resistant isolates among burn patients, an effective infection control plan is necessary. Copyright (C) 2017. Published by Elsevier Taiwan LLC.
The aim of the present study was to investigate the resistance of Acinetobacter baumannii, which was induced by cefepime (FEP), cefoperazone-sulbactam (SCF), tazobactam (TZP), levofloxacin (LEV), amikacin (AK), imipenem (IPM), and ciprofloxacin (CIP), in vitro. Multi-step drug resistance selection of 16 A. baumannii strains was performed using seven antibacterial agents (FEP, TZP, CIP, AK, IPM, SCF, and LEV). The minimum inhibitory concentration (MIC) was determined using the agar dilution method. Random amplified polymorphic DNA polymerase chain reaction was performed to analyze the genotypes and the carrying rates of aac(3)-I, aac(6)-I, ant(3)-I, aph(3)-Via, OXA-23, OXA-24, AmpC, TEM-1, metallo--lactamase gene (IMP), armA, rmtA, rmtB, parC, gyrA and adeB. Expression of adeB was determined using semi-quantitative reverse transcription-polymerase chain reaction (Semi-qRT-PCR). Among the 16 strains, 15 strains with drug resistance (93.8%) were obtained following in vitro induction. Notable increases (8- to 128-fold) were noted in the MIC and different genotypes were showed in RAPD of the strains before and after performing the drug resistant test. PCR data revealed significant differences (P<0.05) between the carrying rates of resistant genes before and after drug induction, with the exception of rmtA, OXA-24, TEM-1, and IMP. Significant increases were demonstrated in the comparative adeB grayscale in strains that underwent drug induction when compared with the sensitive strains (55.69 +/- 43.11% vs. 10.08 +/- 26.35%; P=0.001). Findings of the present study suggest that the active efflux pump, adeB, has an important role in multidrug resistance of the A. baumannii induced by antibacterial agents in vitro.
We characterized 72 isolates with reduced susceptibility to carbapenems (50 Acinetobacter spp., 13 Proteus mirabilis, five Escherichia coli, one Morganella morganii, one Enterobacter cloacae, one Providencia rettgeri, and one Pseudomonas aeruginosa) from a hospital in Sofia, Bulgaria. Different -lactamase genes were identified by polymerase chain reaction and sequencing. Bacterial strain typing was performed by enzymatic macrorestriction and pulsed-field gel electrophoresis (PFGE) typing as well as multilocus sequence typing for selected isolates. The majority of Acinetobacter baumannii (46/50) and one Acinetobacter pittii isolate harbored carbapenemase genes bla(OXA-23) or bla(OXA-72); two A. baumannii contained both genes. PFGE typing of all A. baumannii showed the presence of nine different clones belonging to eight sequence types ST350, ST208, ST436, ST437, ST449, ST231, ST502, and ST579. Molecular characterization of the remaining isolates confirmed the presence of one NDM-1-producing E. coli-ST101 clone (five isolates) and one P. mirabilis clone (13 isolates) with VIM-1 and CMY-99. Furthermore, NDM-1 was identified in P. rettgeri and M. morganii and VIM-2 in the P. aeruginosa isolate. The permanent introduction of OXA-23/72 carbapenemase-producing A. baumannii clones into the hospital and the repeated occurrence of one VIM-1-producing P. mirabilis and one NDM-1-producing E. coli-ST101 clone over a period of more than 1 year is of concern and requires intensified investigations.
Background Acotiamide is widely used to improve symptoms in patients with functional dyspepsia (FD) in multiple large-scale clinical studies, but there are few reports about the drug's mechanism of action. The aim of this study was to assess the effects of acotiamide on gastric accommodation and gastric emptying, gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a placebo-controlled study. Methods We conducted a randomized, double-blind placebo-controlled study. Fifty Japanese FD patients were randomly assigned to either placebo (n = 25) or acotiamide 100 mg x 3/day for 2 weeks (n = 25). At baseline and at 2 weeks of treatment, we evaluated the patients' gastric motility using scintigraphy to determine the accommodation and emptying values, gastrointestinal symptom rating scale (GSRS), HR-QOL (SF-8), and anxiety and depression scale (HADS). Results Four patients failed to complete the medication regimen and were omitted from analysis; data from 24 placebo patients and 22 acotiamide patients were analyzed. Acotiamide significantly increased gastric accommodation compared to the placebo (p = 0.04 vs. p = 0.08; respectively). Acotiamide significantly accelerated gastric emptying (50 % half-emptying time) (p = 0.02 vs. p = 0.59). Acotiamide significantly improved the total GSRS scores compared to placebo (p = 0.0007 vs. p = 0.14). HR-QOL did not differ significantly between the two groups, but acotiamide significantly improved the HADS anxiety score compared to placebo (p = 0.04 vs. p = 0.20). Conclusions Our placebo-controlled study demonstrated that acotiamide significantly increased both gastric accommodation and gastric emptying in Japanese FD patients. Acotiamide also improved the patients' dyspeptic symptoms and anxiety score.
The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (>< 0.5 ccm/year), employing a p-value < 0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.
This work presents a method to determine mechanical transfer functions from forces, acting on the stator teeth of an electrical machine, to surface velocities at sound radiating surfaces. The method allows an efficient analysis of drive trains in their target application and real environment. The determined transfer functions are used in a transient acoustic model for the simulation of electrical drive trains. The proposed model takes care of the nonlinear power electronics, the digital control and sensors, as well as of tolerance afflicted geometries of electrical machines and real and in tolerance deviating material properties. The model is validated by means of vibration measurements. The benefits of a closed simulation in time domain are declared. Exemplary applications of the proposed model are discussed and the potential of the acoustic evaluation during the design process of an electrical machine is illustrated.
Conversion of mechanical forces, vibrations and sound which have energy in the range of milli- to tens of watts (also referred to as "small kinetic energies" in this paper) into electricity has received global attention owing to the potential in powering electronic devices. However, most of the small kinetic energy generators can only generate electric power below 1 mu W/cm(3). As a result, an energy storage device is required to accumulate the energy generated until it reaches a sufficient level. Herein, we report the exceptionally-high acoustoelectric conversion ability of randomly-orientated electrospun poly(vinylidenefluoride-co-trifluoroethylene) nanofiber nonwoven webs. The optimized device under sound is able to generate peak voltage and current of 14.5 V and 28.5 mu A with a volume power density output of 306.5 mu W/cm(3) (5.9 mW/cm(3) based on nanofiber web thickness). Without accumulation in any energy storage unit, the electricity generated by the nanofiber device is sufficient to light up tens of commercial LEDs, run electrochemical reactions and protect metals from corrosion. Such a novel acoustoelectric generator may offer an effective solution to recycling noise pollution into usable electricity.
Intergeneric hybridization is an important strategy to introgress alien genes into common wheat for its improvement. But presence of cross ability barrier mechanism regulated by Kr1 gene played a major destructive role for hybridization than other reported genes. In order to know the underlying molecular mechanism and to dissect out this barrier, a new annealing system, ACP (anneling control primer) system was used in chromosome 5B (containing Kr1 gene) specific Recombinant Inbred Line (RIL) population. Two differentially expressed fragments for Kr1 gene was identified, cloned and sequenced. Further the expression was confirmed by northern blotting analysis. Sequence analysis of the resulted clones revealed classes of putative genes, including stress responsive and signal transduction.
Objective: To unravel the interplay between HIV-1 and its host cell, the effect of HIV-1 infection on cellular gene expression was investigated. Methods: HIV-1(SF33)-infected and uninfected H9 T cells were screened by differential display and RNase protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)-infected P4-CCR5 HeLa cells, which were also examined after PDS5A siRNA knockdown in regard to HIV-1 replication by quantitative RT-PCR, p24 ELISA and LTR-driven beta-galactosidase expression. The PDS5A knockdown effect on cellular gene expressions was studied by microarray analysis. PDS5A tissue expression was determined by Northern blotting. Results: Regulator of cohesion maintenance, homolog A (PDS5A) was found to be down-regulated by HIV-1. When PDS5A was suppressed by siRNA, HIV-1 replication was unaffected. PDS5A was found to be highly expressed in skeletal muscle tissue, and to lesser degrees in pancreas, heart, placenta, lung, kidney, liver and brain. Microarray analysis of PDS5A knockdown revealed 91 differential gene products over-representing cell cycle, transport and protein stability regulation, including 4 genes (PP2A, RANTES, PCAF, TCF7L2) previously reported to interact with HIV-1. Conclusion: The data show a downregulation of proliferation-associated host gene PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication. Copyright (C) 2011 S. Karger AG, Basel
Powder coatings have been receiving attention because they are environmentally friendly. They do not contain solvents in their composition, and their components have decorative and corrosion-protection functions, among many others. However, the presence of polymers in their composition increases the risk of combustion in adverse situations. In this context, this study aims to develop and characterize acrylic-based powder paints with the addition of 2 wt % and 4 wt % montmorillonite clays (MMT) as Cloisite 30B (MMT-30B) and Cloisite 15A (MTT-15A), employed as flame retardants. The characterization of the coatings was carried out by thermogravimetric analysis (TGA), X-ray diffraction, and scanning electron microscopy. After application of the coatings on carbon steel substrates, flammability tests were performed. The coatings with 2 wt % MMT-30B showed overall better results, especially in the flammability tests. Flames spread less on these coatings than on the other systems. However, when the surface and bottom temperatures were analyzed by the cone calorimeter test, the samples prepared with 4 wt % MMT-15A were considered safer to be applied in fire scenarios. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45031.
Purpose/Background: The aim of this study was to evaluate the effects of quetiapine XR and lithium on actigraphy-measured circadian parameters in patients with bipolar II depression. Methods/Procedures: This was an 8-week, open-label, prospective, randomized comparative study. The assessments included the 17-item Hamilton Depression Rating Scale score and actigraphic measures concerning the previous 7 days, collected at each visit (weeks 0 [baseline], 1, 2, 4, 6, and 8); the actigraphic data were analyzed with a cosinor analysis. Findings/Results: Medication, time, and the interaction between medication and time were significantly associated with acrophase for the entire group (Ps = 0.003, 0.020, and 0.042, respectively). More specifically, acrophase was significantly delayed at weeks 1 and 6 (Ps = 0.004 and 0.039, respectively) in the quetiapine XR group. The F statistics significantly increased over time for the entire group (P < 0.001), and there was a significant increase in F statistics on weeks 4 and 6 in the quetiapine XR group (Ps = 0.016 and 0.020, respectively) and on weeks 4 and 8 in the lithium group (Ps = 0.001 and 0.016, respectively). In addition, scores on the 17-item Hamilton Depression Rating Scale were significantly associated with the F statistics during 8 weeks for the entire group (P = 0.008). Implications/Conclusions: Both quetiapine XR and lithium affected several circadian parameters, including peak activity time and robustness of circadian rhythm, but exerted different effects on acrophase in patients with bipolar II depression. In particular, clinical depressive symptoms were associated with robustness of circadian rhythm during the course of the 8-week treatment.
Actinobacteria are Gram-positive bacteria commonly found in soil, freshwater and marine ecosystems. In this investigation, bias in codon usages of ninety actinobacterial genomes was analyzed by estimating different indices of codon bias such as Nc (effective number of codons), SCUO (synonymous codon usage order), RSCU (relative synonymous codon usage), as well as sequence patterns of codon contexts. The results revealed several characteristic features of codon usage in Actinobacteria, as follows: 1) C- or G-ending codons are used frequently in comparison with A- and U ending codons; 2) there is a direct relationship of GC content with use of specific amino acids such as alanine, proline and glycine; 3) there is an inverse relationship between GC content and Nc estimates, 4) there is low SCUO value (<0.5) for most genes; and 5) GCC-GCC, GCC-GGC, GCC-GAG and CUC-GAC are the frequent context sequences among codons. This study highlights the fact that: 1) in Actinobacteria, extreme GC content and codon bias are driven by mutation rather than natural selection; (2) traits like aerobicity are associated with effective natural selection and therefore low GC content and low codon bias, demonstrating the role of both mutational bias and translational selection in shaping the habitat and phenotype of actinobacterial species. (C) 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Mirror neurons (MNs) are a fascinating class of cells originally discovered in the ventral premotor cortex (PMv) and, subsequently, in the inferior parietal lobule (IPL) of the macaque, which become active during both the execution and observation of actions. In this review, I will first highlight the mounting evidence indicating that mirroring others' actions engages a broad system of reciprocally connected cortical areas, which extends well beyond the classical IPL-PMv circuit and might even include subcortical regions such as the basal ganglia. Then, I will present the most recent findings supporting the idea that the observation of one's own actions, which might play a role in the ontogenetic origin and tuning of MNs, retains a particular relevance within the adult MN system. Finally, I will propose that both cortical and subcortical mechanisms do exist to decouple MN activity from the motor output, in order to render it exploitable for high-order perceptual, cognitive, and even social functions. The findings reviewed here provide an original framework for envisaging the main challenges and experimental directions of future neurophysiological and neuroanatomical studies of the monkey MN system.
In this paper a new framework is introduced to develop a coupled active and reactive market in distribution networks. Distributed energy resources (DERs) such as synchronous machine-based distributed generations and wind turbines offer their active and reactive powers to the proposed market. For the considered DERs, multicomponent reactive power bidding structures are introduced based on their capability curves. Also, the hourly speed variations of wind turbines are considered in the proposed model. A distribution company buys active and reactive powers from a wholesale market and sells them via this market. The demand side is active, and responsive loads or aggregators can participate in the market using a demand bidding/buyback program. The objective function of the proposed market is to minimize the active and reactive power costs of DERs and distribution companies, the penalty cost of CO2 emission, and the cost of running a demand bidding/buyback program. The effectiveness of the proposed method is examined on a 22-bus 20-kV radial distribution test system.
A highly reconfigurable merged analog baseband (MABB) with not only tunable bandwidth (BW), gain, and order but also reconfigurable power, noise, and linearity is proposed for multistandard integrated wireless receivers in this brief. The MABB could arrange the total gain to different stages for noise and linearity tradeoffs by introducing the merged biquad topology. To save power, the operational amplifier (Opamp) for the proposed MABB can reduce the GBW, as long as it meets the GBW requirement for different BW, gain, and order. A flexible power-efficient high-GBW Opamp with an adaptive common-mode bias circuit is also proposed for the eighth-order active-RC MABB. The proposed MABB covers a cutoff frequency range from 200 kHz to 20 MHz, whereas the gain could be tuned between 0 and 72 dB. The proposed highly reconfigurable MABB is suitable for multistandard integrated wireless receivers.
With the development of integrated circuits, the fully integrated continuous time filter has been focused widely. A Nth-order universal filter based on Current Feedback Operational Amplifier (CFOA) is proposed. Compared with available circuits, the proposed circuit using less components (2n CFOAs, n capacitors, and 3n resistors) can realize the universal filter functions without changing circuit configuration, and the operating frequency of proposed filter circuit is at least 10 MHz. All of capacitors in proposed circuit are grounded, this is another benefit from integration point of view. PSPICE simulations have been carried out using 0.18 mu m CMOS technology, and sensitivity analysis of proposed Nth-order low-pass filter circuit is completed. (C) 2015 Elsevier GmbH. All rights reserved.
This paper presents different state feedback approaches of finite control set model predictive control (FCS-MPC) applied to a grid-connected voltage-source converter (VSC) with an LCL filter. Besides converter-side current feedback, two multivariable control approaches and line-side current control are introduced and compared based on theoretical and experimental evaluation. As the LCL filter introduces an additional resonance frequency to the system, the use of different active damping (AD) methods in combination with FCS-MPC is discussed. Furthermore, practical control implementation issues are discussed. The presented methods reveal the great potential, high dynamic performance, and flexibility of FCS-MPC, enabling multivariable control as well as both reduced switching losses and low harmonic current distortion at the same time. Eventually, the feasibility of the theoretical control concepts is shown in a laboratory environment.
Capacitor current feedback active damping is extensively used in grid-connected converters with an LCL filter. However, systems tends to become unstable when the digital control delay is taken into account, especially in low switching frequencies. This paper discusses this issue by deriving a discrete model with a digital control delay and by presenting the stable region of an active damping loop from high to low switching frequencies. In order to overcome the disadvantage of capacitor current feedback active damping, this paper proposes a modified approach using grid current and converter current for feedback. This can expand the stable region and provide sufficient active damping whether in high or low switching frequencies. By applying the modified approach, the active damping loop can be simplified from fourth-order into second-order, and the design of the grid current loop can be simplified. The modified approach can work well when the grid impedance varies. Both the active damping performance and the dynamic performance of the current loop are verified by simulations and experimental results.
The high-power grid-connected inverters with LCL filters have been widely used. Current control plays a key role in the grid-connected inverter control system. To cope with the inherent resonance of the LCL filter, active damping (AD) methods are usually employed. However, the AD performance is impaired by control delays which are introduced in the digital control implementation process. Besides, the lag phase due to control delays limits the system bandwidth and stability margin. The effects of control delays are more noteworthy in the high-power grid-connected inverter due to its low switching frequency. This paper investigates the current control strategy based on multisampling for the high-power grid-connected inverter with the LCL filter. First, the multisampled AD scheme is studied, which can reduce control delays effectively and improve AD performance. Besides, the multisampled control without additional damping whether passive or active is researched. Through the inverter-side current feedback, the system can realize single-current-loop control based on multisampling. Thus, the control system is simplified and it can be stable, and achieve better dynamic performance. Finally, experimental results show that the proposed control schemes are effective.
Resonant poles of LCL filters may challenge the entire system stability especially in digital-controlled pulse width modulation (PWM) inverters. In order to tackle the resonance issues, many active damping solutions have been reported. For instance, a notch filter can be employed to damp the resonance, where the notch frequency should be aligned exactly to the resonant frequency of the LCL filter. However, parameter variations of the LCL filter as well as the time delay appearing in digital control systems will induce resonance drifting, and thus break this alignment, possibly deteriorating the original damping. In this paper, the effectiveness of the notch filter-based active damping is first explored, considering the drifts of the resonant frequency. It is revealed that when the resonant frequency drifts away from its nominal value, the phase lead or lag introduced by the notch filter may make itself fail to damp the resonance. Specifically, the phase lag can make the current control stable despite of the resonant frequency drifting, when the grid current is fed back. In contrast, in the case of an inverter current feedback control, the influence of the phase lead or lag on the active damping is dependent on the actual resonant frequency. Accordingly, in this paper, the notch frequency is designed away from the nominal resonant frequency to tolerate the resonance drifting, being the proposed robust active damping. Simulations and experiments performed on a 2.2-kW three-phase grid-connected PWM inverter verify the effectiveness of the proposed design for robust active damping using digital notch filters.
Control of the LCL-type three-phase grid-connected converter is difficult due to high resonance peak of the LCL filter. Active damping is the state-of-the-art solution to this problem, but the damping performance will be affected by the inherent time delay of digital control, especially for high-power low switching frequency applications. Based on a discrete-time stability analysis of an LCL-type converter with capacitor-current-feedback active damping, a simple and effective time delay compensation method, which is based on area equalization concept, is proposed. The method can reduce the negative impact of the computation delay significantly. It has the potential to serve as a general solution to time delay compensation of a digitally controlled PWM converter. The validity of the proposed method is proved by experimental results.
The wind power generation techniques are continuing to develop and increasing numbers of doubly fed induction generator (DFIG)-based wind power systems are connecting to the on-shore and off-shore grids, local standalone weak networks, and microgrid applications. The impedances of the weak networks are too large to be neglected and require careful attention. Due to the impedance interaction between the weak network and the DFIG system, both subsynchronous resonance (SSR) and high-frequency resonance (HFR) may occur when the DFIG system is connected to the series or parallel compensated weak network. This paper will discuss the SSR and the HFR phenomena based on the impedance modeling of the DFIG system and the weak networks, and the cause of these two resonances will be explained in details. The following factors will be discussed in this paper: 1) transformer configuration; 2) different power scale of DFIG system with different parameters; 3) L or LCL filter adopted in the grid side converter (GSC); 4) rotor speed; 5) current closed-loop controller parameters; and 6) digital control delay. On the basis of the analysis, active damping strategies for HFR using virtual impedance concept will be proposed.
Energy storage systems (ESSs) are generally planned based on the active power. While, reactive power is another important aspect of the ESSs that has not been adequately addressed and discussed. Moreover, ESSs are often managed individually, but coordinated planning on the ESSs and distributed generators (DGs) may result in more suitable outcomes. In order to address these issues, a coordinated ESS and DG planning is presented in this paper. In the proposed planning, the place and capacity of the ESSs and DGs are determined at the same time. The active and reactive powers are included in the planning for both the ESSs and DGs. In other words, the optimal active and reactive capacities are denoted for both the ESSs and DGs on the network. The proposed coordinated ESS and DG planning is carried out on a radial distribution network under deregulated electricity market. Objective function of the proposed planning is to maximize the profit of distribution company (DISCO) subject to the secure operation of the network. The planning is expressed as a nonlinear, mixed integer optimization problem and solved by advanced PSO as a strong Meta-heuristic optimization technique. Simulation results demonstrate the great impacts of the proposed planning on the network. The results demonstrate the priority of the proposed coordinated DG and ESS planning compared to the individual ESS planning. Additionally, it is verified that considering reactive power of the DGs and ESSs changes the results of the planning and provides more realistic and reasonable outputs. The proposed planning significantly increases DISCO profit while guarantees the safe operation of the network through satisfying several security constraints.
In this paper we present an analysis of the voltage amplifier needed for double differential (DD) sEMG measurements and a novel, very simple circuit for implementing DD active electrodes. The three-input amplifier that standalone DD active electrodes require is inherently different from a differential amplifier, and general knowledge about its design is scarce in the literature. First, the figures of merit of the amplifier are defined through a decomposition of its input signal into three orthogonal modes. This analysis reveals a mode containing EMG crosstalk components that the DD electrode should reject. Then, the effect of finite input impedance is analyzed. Because there are three terminals, minimum bounds for interference rejection ratios due to electrode and input impedance unbalances with two degrees of freedom are obtained. Finally, a novel circuit design is presented, including only a quadruple operational amplifier and a few passive components. This design is nearly as simple as the branched electrode and much simpler than the three instrumentation amplifier design, while providing robust EMG crosstalk rejection and better input impedance using unity gain buffers for each electrode input. The interference rejection limits of this input stage are analyzed. An easily replicable implementation of the proposed circuit is described, together with a parameter design guideline to adjust it to specific needs. The electrode is compared with the established alternatives, and sample sEMG signals are obtained, acquired on different body locations with dry contacts, successfully rejecting interference sources.
The performance of some Fourier transform based fundamental current detection algorithms is evaluated and compared in this paper. Some difficult conditions are imposed by a load which draws a highly distorted current with a slight fluctuation, i. e. with non-equal semi-periods. The implemented algorithms are Recursive Discrete Fourier Transform (RDFT), Discrete Fourier Transform (DFT) implemented through a Finite Impulse Response (FIR) filter and respectively the Fast Fourier Transform (FFT) with Butterfly operation and radix-2 decimation in time (DIT). A digital signal processor (DSP) based solution is used for real-time implementation, namely a dSPACE 1103 controller development board. MATLAB/Simulink software is used for the design of the algorithms because it provides specialized tools and blocks. For the performance comparison one used criteria like total harmonic distortion (THD) and settling time of detected fundamental current and also the run time for the DSP. This study may be useful as a guide for engineers in selecting the suitable Fourier transform based control algorithm for active power filters or other grid-synchronized equipments which are operating in difficult load conditions.
A high-efficiency, high-power-density buffer architecture is proposed for power pulsation decoupling in power conversion between dc and single-phase ac. We present an active decoupling solution that yields improved efficiency and reduced circuit complexity compared to existing solutions. In the proposed architecture, the main energy storage capacitor is connected in series with an active buffer converter across the dc bus. The series-stacked capacitor blocks the majority of the dc bus voltage to reduce the voltage stress on the buffer converter, such that fast, low-voltage transistors can be employed for the buffer converter. Moreover, the series capacitor provides the majority of the power pulsation decoupling through a wide voltage swing, and the buffer converter only needs to process a small fraction of the total power of the entire architecture, allowing a very small active circuit volume and very high system efficiency. The circuit operation and design constraints are analyzed in detail. In the proposed buffer architecture, the series stacking of a nearly lossless capacitor and a lossy converter presents a challenge of capacitor voltage balancing and power loss compensation. We propose a control scheme exploiting the small ripple in the bus voltage and dc input current to compensate for the power loss in the buffer converter while maintaining the voltage balance. Light-load techniques are also introduced to ensure that the buffer architecture meets strict ripple requirements while providing sufficient loss compensation. A 2-kW hardware prototype based on low-voltage GaN switches has been built to demonstrate the performance of the proposed solution. A power density of 25W/cm(3) (410 W/in(3)) by rectangular box volume and an efficiency above 98.9% across a wide load range has been experimentally verified.
A power divider/combiner circuit, which simultaneously achieves wide bandwidth, flat gain characteristics, and bidirectional operation, is proposed for multichannel broadband system applications. The proposed circuit utilizes cascode-based bidirectional amplifier cores, which steer the operation modes between a divider and a combiner depending on the control input, and a two-stage distributed-amplifier topology with artificial transmission lines. Implemented in a 130-nm silicon-germanium BiCMOS technology platform, the proposed divider/combiner provides the advantage of seamless integration with digital control blocks. The power divider/combiner exhibits the flat in-band gain of 9 dB and the operational bandwidth of 2-22 GHz, which covers S-, C-, X-, and Ku-bands. In addition, it shows the amplitude imbalance of 0.8 dB, the phase imbalance of 3.5 degrees, the port-to-port isolation of 22 dB, the output 1-dB compression point of 3 dBm, and good impedance matching under 100-mW dc power consumption.
Equivalently implementing a generalized memristor by using common components and then making a nonlinear circuit with a reliable property, are conducive to experimentally exhibit the nonlinear phenomena of the memristive chaotic circuit and show practical applications in generating chaotic signals. Firstly, based on a memristive diode bridge circuit, a new first-order actively generalized memristor emulator is constructed with no grounded restriction and ease to realize. The mathematical model of the emulator is established and its fingerprints are analyzed by the pinched hysteresis loops with different sinusoidal voltage stimuli. The results verified by experimental measurements indicate that the emulator uses only one operational amplifier and nine elementary electronic circuit elements and is an active voltage-controlled generalized memristor. Secondly, by parallelly connecting the proposed emulator to a capacitor and then linearly coupling with an RC bridge oscillator, a memristor based chaotic circuit without any inductance element is constructed. The dynamical model of the inductorless memristive chaotic circuit is established and the phase portraits of the chaotic attractor with typical circuit parameters are obtained numerically. The dissipativity, equilibrium points, and stabilities are derived, which indicate that in the phase space of the inductorless memristive chaotic circuit there exists a dissipative area where are distributed two unstable nonzero saddle-foci and a non-dissipative area containing an unstable origin saddle point. Furthermore, by utilizing the bifurcation diagram, Lyapunov exponent spectra, and phase portraits, the dynamical behaviors of the inductorless memristive chaotic circuit are investigated. Results show that with the evolution of the parameter value of the coupling resistor, the complex nonlinear phenomena of the coexisting bifurcation modes and coexisting attractors under two different initial conditions of the state variables can be found in the inductorless memristive chaotic circuit. Finally, a prototype circuit with the same circuit parameters for numerical simulations is developed, from which it can be seen that the prototype circuit has a simple circuit structure and is inexpensive and easy to practically fabricate with common components. Results of both the experimental measurements and the numerical simulations are consistent, verifying the validity of the theoretical analyses.
Transformation of research in all biological fields necessitates the design, analysis and, interpretation of large data sets. Preparing students with the requisite skills in experimental design, statistical analysis, and interpretation, and mathematical reasoning will require both curricular reform and faculty who are willing and able to integrate mathematical and statistical concepts into their life science courses. A new Faculty Learning Community (FLC) was constituted each year for four years to assist in the transformation of the life sciences curriculum and faculty at a large, Midwestern research university. Participants were interviewed after participation and surveyed before and after participation to assess the impact of the FLC on their attitudes toward teaching, perceived pedagogical skills, and planned teaching practice. Overall, the FLC had a meaningful positive impact on participants' attitudes toward teaching, knowledge about teaching, and perceived pedagogical skills. Interestingly, confidence for viewing the classroom as a site for research about teaching declined. Implications for the creation and development of FLCs for science faculty are discussed. (C) 2016 by The International Union of Biochemistry and Molecular Biology
An active matrix organic light emitting diode (AMOLED) display driver IC, enabling real-time thin-film transistor (TFT) nonuniformity compensation, is presented with a hybrid driving method to satisfy fast driving speed, high TFT current accuracy, and a high aperture ratio. The proposed hybrid column-driver IC drives a mobile UHD (3840 x 2160) AMOLED panel, with one horizontal time of 7.7 mu s at a scan frequency of 60 Hz, simultaneously senses the TFT current for back-end TFT variation compensation. Due to external compensation, a simple 3T1C pixel circuit is employed in each pixel. Accurate current sensing and high panel noise immunity is guaranteed by a proposed current-sensing circuit. By reusing the hybrid column-driver circuitries, the driver embodies an 8 bit current-mode ADC to measure OLED V-I transfer characteristic for OLED luminance-degradation compensation. Measurement results show that the hybrid driving method reduces the maximum current error between two emulated TFTs with a 60 mV threshold voltage difference under 1 gray-level error of 0.94 gray level (37 nA) in 8 bit gray scales from 12.82 gray level (501 nA). The circuit-reused current-mode ADC achieves 0.56 LSB DNL and 0.75 LSB INL.
\There are many factors that affect the performance of active power filter, which is a key factor for command current tracking control. Aiming at the deficiency of traditional PR controller, this paper puts forward an improved PR controller-vector resonant controller. The controller has the advantages of stronger anti-interference ability and greater gain at the resonance point, and it can improve the accuracy of harmonic compensation in the current compensation control. In this paper, the digital controller in the digital control system has been given a detailed design. Finally, the experimental results show that the control strategy can further reduce the harmonic content and improve the compensation accuracy.
This paper presents a power electronic converter used to redistribute the power among the phases in unbalanced power systems, which is supposed to be designed based on the involved degree of unbalance. A bidirectional converter is chosen for this purpose, whose modeling is presented in the dq0 system. This solution can be considered as part of a unified control system, where conventional active power filters may be solely responsible for compensating harmonics and/or the tuning of passive filters becomes easier, with consequent reduction in involved costs in a decentralized approach. The adopted control strategy is implemented in digital signal processor TMS320F2812, while experimental results obtained from an experimental prototype rated at 17.86 kVA are properly discussed considering that the converter is placed at the secondary side of a transformer supplying three distinct single-phase loads. It is effectively shown that the converter is able to balance the currents in the transformer phases, thus leading to the suppression of the neutral current.
This paper reports a source follower-based active RC filter topology for RF front-ends in wideband systems. In the proposed active RC filter, the noise figure and bandwidth are improved through adopting the proposed sub-1 Omega Z(out) source follower, which replaces the conventional operational amplifier-based unity gain buffer and through simply changing its location in the filter. Applying the proposed scheme to the conventional Sallen-Key filter also improves the stopband rejection performance. Furthermore, the proposed filter topology ultimately suppresses the DC offset voltage and flicker noise of the unity gain buffer, which is the only active circuit in the filter. The proposed biquad filter is implemented in 0.18 mu m CMOS and the measurements exhibit >26 dBm IIP3, +12 dBm input P-1dB, and <15 dB noise figure over 50-450 MHz of a 6 bit tunable frequency range. The proposed biquad filter consumes 14 mA from a 1.8 V supply and the chip occupies 1000x500 mu m(2).
Recently, we have reported on a compact microcontroller-based unit developed to accurately synchronize excimer laser pulses (Mingesz et al. 2012 Fluct. Noise Lett. 11, 1240007 (doi:10.1142/S021947751240007X)). We have shown that dithering based on random jitter noise plus pseudorandom numbers can be used in the digital control system to radically reduce the long-term drift of the laser pulse from the trigger and to improve the accuracy of the synchronization. In this update paper, we present our new experimental results obtained by the use of the delay-controller unit to tune the timing of a KrF excimer laser as an addition to our previous numerical simulation results. The hardware was interfaced to the laser using optical signal paths in order to reduce sensitivity to electromagnetic interference and the control algorithm tested by simulations was applied in the experiments. We have found that the system is able to reduce the delay uncertainty very close to the theoretical limit and performs well in real applications. The simple, compact and flexible system is universal enough to also be used in various multidisciplinary applications.
The current-mode first-order allpass filter (APP) using only the active elements has been studied in the present paper. The proposed circuit comprises two operational transconductance amplifiers (OTAs) and one operational amplifier (OA) which is suitable to future development into an integrated circuit. The pole frequency and phase response can be electronically adjusted with changing the dc bias currents of OTAs. The APF has high output impedance, which is easy to cascade in high-order filter or drive load without using a buffering device. The current-mode quadrature oscillator is included to show the usability of the proposed filter. The results of PSPICE simulation are accordant with the theoretical analysis.
An 8th-order Cheybshev-II ladder active-RC BPF was fabricated in a 40 nm CMOS low-leakage digital process. A new technique to design for zero capacitance spread (ZCS) is reported to enable the application of integrator frequency compensation (IFC). Combined with wideband op-amps employing a current-reusing, split-path feed-forward compensation (FFC) technique, significant power savings is achieved in a standard 40 nm CMOS process. The BPF measures a center frequency (CF) of 85-225 MHz and four programmable bandwidth-to-center frequency (BW/CF) ratios of 5%-40%. Both the CF and BW/CF ratio are digitally programmable. It also measures a maximum in-band IIP3 of 31 dBm at 0 dB gain and a maximum in-band frequency-response deviation of 0.2 dB while consuming 33 mA from a 1.5 V supply.
Aims: Activin E is a newly identified member of the transforming growth factor-beta superfamily. To assess the role of activin E in glucose/energy metabolism, we investigated the transcriptional regulation of activin E in the liver. Main methods: Northern blotting, Western blotting, quantitative real-time polymerase chain reaction (PCR), reporter assays and chromatin immunoprecipitation assays were used in this study. Key findings: Insulin up-regulated activin E expression at the mRNA and protein level in HepG2 cells. Reporter assays revealed that the putative, functional, promoter sequence of human activin E gene was responsible for the effect of insulin. Mutational analysis of the promoter revealed that CCAAT/enhancer-binding proteins (C/EBPs) play a key role in regulating activin E expression and in the stimulatory effect of insulin on activin E transcription. Chromatin immunoprecipitation assays revealed that the C/EBPs can bind to the activin E promoter in HepG2 cells. The expression of activin E mRNA was up-regulated in the liver of diet-induced obese mice. Significance: These observations suggest that activin E plays a pathophysiological role in glucose metabolism. (C) 2009 Elsevier Inc. All rights reserved.
Background and purpose: Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. Methods: Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). Results: The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 2.4 years (UH, 2.8 +/- 3.0; LH, 1.5 +/- 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients (P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). Conclusions: We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia.
This paper presents the A-Diakoptics methodology (Diakoptics based on actors) for the high performance simulation of microgrids. Microgrids are clusters of loads and microsources that operate within a single controllable system, which provides electricity and heat to its local area even if they get separated from the distribution system. Several commercial solutions are addressing this topic using numerous methods; however, to keep the computing time required to solve the system when the size of the system grows represents a major challenge. In this paper, this challenge is addressed by separating the distribution grid in independent subnetworks. Then, for the computational implementation, each subnetwork is assigned to an independent solver using the actor model. As a result, the solution algorithm is composed of multiple parallel and concurrent solvers. These exchange information using high-speed communication interfaces for reducing the computational burden without losing accuracy. A-Diakoptics is an advanced algorithm that combines existing methods for simulating large distribution systems; these methods are upgraded to make them suitable for parallel processing and to cover the basic needs for the simulation of smart grid applications.
This paper presents a digital control technique to achieve valley switching in a bidirectional flyback converter used to drive a dielectric electroactive polymer-based capacitive incremental actuator. This paper also provides the design of a low input voltage (24 V) and variable high output voltage (0-2.5 kV) bidirectional dc-dc flyback converter for driving a capacitive incremental actuator. The incremental actuator consists of three electrically isolated-mechanically connected capacitive actuators. It requires three high-voltage (HV) (2-2.5 kV) bidirectional dc-dc converters to accomplish the incremental motion by charging and discharging the capacitive actuators. The bidirectional flyback converter employs a digital controller to improve the efficiency and charge/discharge speed using the valley switching technique during both charge and discharge processes, without the need to sense signals on the output HV side. Experimental results verifying the bidirectional operation of a HV flyback converter are presented using a 3-kV polypropylene-film capacitor as the load. The energy-loss distributions of the converter are presented when 4- and 4.5-kV HV MOSFETs are used on HV side. The flyback prototype with a 4 kV MOSFET demonstrated 89% charge energy efficiency to charge the capacitive load from 0 V to 2.5 kV, and 84% discharge energy efficiency to discharge it from 2.5 kV to 0 V.
The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.
Background: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation: A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 degrees C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm(3), 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient's four limbs. MRI acquired after 3 weeks showed that the previously reported alterations were no longer present. Conclusion: This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM.
Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acutephase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapyunresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients.
Objective and design Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. Materials Acute kidney injury in mice was induced by cisplatin. Treatments Mice were administered with DEX 25 mu g/kg or atipamezole 250 mu g/kg (once a day, for 3 days) after cisplatin treatment. Methods The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80(+) macrophages, CD3(+) T cells, and NF-kappa B were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction. Results DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-kappa B activation and decreased expression of TNF-alpha, IL-1 beta, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to alpha(2) adrenoceptor-dependent pathway. Conclusion We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.
Background: Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf(+/+)). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1(+/-)). Methods: Three groups of 25 +/- 5-week-old healthy male mice (Wt Igf(+/+)) were included in the protocol: untreated controls (Wt). Controls that received CCl4 (Wt + CCl4) and Wt + CCl4 were treated subcutaneously with IGF-1 (2 mu g/100 g body weight/day) for 10 days (Wt + CCl4 + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1(+/-)) groups were studied: untreated Hz, Hz + CCl4, and Hz + CCl4 + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean +/- SEM. Results: An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl4 + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl4. Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. Conclusions: IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver damage, could be a feasible therapeutic option.
Adenoviruses cause a variety of diseases that range from mild to fatal in vulnerable patients. Its evolution occurs as a process of selection pressure; for example, genetic recombination generates intermediate strains that can be more infectious or pathogenic than parental strains. This study sought to determine the diversity of circulating adenoviruses in Paraguayan children less than 5 years of age hospitalized with acute lower respiratory infection, by using molecular biology and bioinformatics tools, though amplification of penton, hexon and fiber genes in 26 samples of nasopharyngeal aspirates. It was demonstrated the circulation of three species: B (4/26), C (21/26), and D (1/26), as well as recombination events corresponding to the HAdV-D isolate, with at least three different genotypes (D49, D9 y D15). The HAdV-D are associated with gastrointestinal or ocular diseases, and less commonly with respiratory infections. Recently, however, it has been reported changes in behavior of these viruses due to recombination, allowing them to expand their host cell repertoire. These data extend the knowledge about the genetic diversity of HAdV in Paraguay and strongly support the importance of genomic analysis using bioinformatics tools in epidemiological surveillance of emerging recombinant strains of HAdV.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. While survival rates for ALL have improved, central nervous system (CNS) relapse remains a significant cause of treatment failure and treatment-related morbidity. Accordingly, there is a need to identify more efficacious and less toxic CNS-directed leukemia therapies. Extensive research has demonstrated a critical role of the bone marrow (BM) microenvironment in leukemia development, maintenance, and chemoresistance. Moreover, therapies to disrupt mechanisms of BM microenvironment-mediated leukemia survival and chemoresistance represent new, promising approaches to cancer therapy. However, in direct contrast to the extensive knowledge of the BM microenvironment, the unique attributes of the CNS microenvironment that serve to make it a leukemia reservoir are not yet elucidated. Recent work has begun to define both the mechanisms by which leukemia cells migrate into the CNS and how components of the CNS influence leukemia biology to enhance survival, chemoresistance, and ultimately relapse. In addition to providing new insight into CNS relapse and leukemia biology, this area of investigation will potentially identify targetable mechanisms of leukemia chemoresistance and self-renewal unique to the CNS environment that will enhance both the durability and quality of the cure for ALL patients.
RNA-sequencing of the patient's bone marrow detected fusion transcripts in which the coding sequence of the FAM53B gene (from 10q26) was fused to a genomic sequence (from 19q13) that mapped upstream of the SLC7A10 locus. Reverse transcription-polymerase chain reaction together with Sanger sequencing verified the presence of this fusion transcript. The FAM53B fusion transcript is not expected to produce any chimeric protein. However, it may code for a truncated FAM53B protein consisting of the first 302 amino acids of FAM53B together with amino acids from the 19q13 sequence. Functionally, the truncated FAM53B would be similar to the protein encoded by the FAM53B sequence with accession no. BC031654.1 (FAM53B protein accession no. AAH31654.1). Furthermore, the truncated protein contains the entire conserved domain of the FAM53 protein family. The chromosome aberration t(10;19)(q26;q13) detected in this study was previously reported in a single case of ALL, in which it was also the sole karyotypic change. Both patients entered complete hematological and cytogenetic remission following treatment.
Purpose ETV6/RUNX1(+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. Materials and Methods Sixty-three patients were diagnosed with ETV6/RUNX1(+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETI/6/RUNX1(+) fusion, and the presence of additional cytogenetic abnormalities. Results The 5-year event-free survival was 84.1 +/- 4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9 4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5 +/- 6.9%. Conclusion ETV6/RUNX1(+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end of remission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.
IntroductionThe translocation t(12;21)(p13;q22) resulting in the fusion gene ETV6-RUNX1, is the most frequent gene fusion in childhood B lymphoblastic leukemia. In the Nordic Society of Paediatric Haematology and Oncology ALL-2008 treatment protocol, treatment stratification in B-lineage ALL is based on results of minimal residual disease (MRD) analysis with fluorescence-activated cell sorting (FACS). In this study, we determined whether RT-qPCR of the ETV6-RUNX1 fusion transcript can be a reliable alternative for MRD analysis. MethodsSeventy-eight bone marrow samples from 29 children at diagnosis and day 15, 29, and 78 during treatment were analyzed for MRD with FACS and with quantitative reverse transcription polymerase chain reaction (RT-qPCR). Fusion transcript MRD was defined as the ETV6-RUNX1/GUSB ratio at the follow-up time point (day 15/29/78) divided with the ETV6-RUNX1/GUSB ratio at diagnosis (%). ResultsMRD analysis with FACS and with RT-qPCR of ETV6-RUNX1 fusion transcript showed strong correlation. All cases showed concordant results at the treatment stratifying time points day 29 and day 78, when comparing the two methods with a cutoff set to 0.1%. ConclusionRT-qPCR is a valuable addition and could also be an alternative to FACS in cases where FACS is not achievable for MRD analysis.
Glucocorticoids (GCs) induce apoptosis in lymphoid lineage cells and are therefore used in the therapy of acute lymphoblastic leukemia (ALL) and related malignancies. MicroRNAs (miRNAs) and the related mirtrons are similar to 22 nucleotide RNAs derived from polymerase-II transcripts and implicated in the control of essential biological functions, including apoptosis. Whether GCs regulate miRNA-encoding transcription units is unknown. We investigated miRNA/mirtron expression and GC regulation in 8 leukemia/lymphoma in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time reverse transcription (RT)-PCR and northern blotting to detect mature miRNAs and/or their precursors. We found that mature miRNA regulations can be inferred from expression data of their host genes. Although a simple miRNA-initiated canonical pathway to GC-induced apoptosis or cell cycle arrest did not emerge, we identified several miRNAs/mirtrons that were regulated by GC in patients and cell lines, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing miR15 similar to 16 clusters. In an in vitro model, overexpression of miR15b similar to 16 mimics increased and silencing by miR15b similar to 16 inhibitors decreased GC sensitivity. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context-dependent manner.
Treatment of acute myelogenous leukemia (AML) over the past four decades remains mostly unchanged and the prognosis for the majority of patients remains poor. Most of the significant advances that have been observed are in defining cytogenetic abnormalities, as well as the genetic and epigenetic profiles of AML patients. While new cytogenetic and genetic aberrations such as the FLT3-ITD and NPM1 mutations are able to guide prognosis for the majority of patients with AML, outcomes are still dismal and relapse rates remain high. It is thought that relapse in AML is in part driven by minimal residual disease (MRD) that remains in the patient following treatment. Thus, there is a need for sensitive and objective methodology for MRD detection. Methodologies such as multiparameter flow cytometry (MFC), quantitative real-time polymerase chain reaction (RQ-PCR), digital PCR (dPCR), or next-generation sequencing (NGS) are being employed to evaluate their utility in MRD assessment. In this review, we will provide an overview of AML and the clinical utility of MRD measurement. We will discuss optimal timing to MRD measurement, the different approaches that are available, and efforts in the standardization across laboratories.
The mammalian target of rapamycin (mTOR) has recently been implicated in leukaemic cell growth, tumour-associated angiogenesis and expression of vascular endothelial growth factor (VEGF). We examined whether mTOR plays a role as regulator of growth and VEGF-expression in acute myeloid leukaemia (AML). Three mTOR-targeting drugs, rapamycin, everolimus (RAD001) and CCI-779, were applied. The effects of these drugs on growth, survival, apoptosis and VEGF expression in primary AML cells and various AML cell lines were examined. Growth of AML cells and AML-derived cell lines was assessed by (3)H-thymidine incorporation, survival was examined by light- and electron microscopy, by Tunel assay and by AnnexinV-staining, and the expression of VEGF by Northern blotting, RT-PCR and ELISA. Rapamycin was found to counteract growth in the AML cell lines U937 and KG1a as well as in primary AML cells in 14/18 patients examined. The effects of rapamycin and its derivatives were dose-dependent (IC(50): 10 pM-100 nM). It was also found that exposure to mTOR-targeting drugs resulted in apoptosis and in decreased expression of VEGF in leukaemic cells. mTOR-targeting drugs exert antileukaemic effects on AML cells in vitro through multiple actions, including direct inhibition of proliferation, induction of apoptosis and suppression of VEGF. Based on this study and other studies, mTOR can be regarded as a potential drug target in AML.
Background/Purpose: Mutations in the tet oncogene family member 2 gene (TET2) are frequently found in adult patients with acute myeloid leukemia (AML). Reports of TET2 mutations in children are limited. We assessed the prevalence of TET2 mutations in Taiwanese children with AML and analyzed their prognosis. Methods: Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled at the National Taiwan University Hospital. The analysis for TET2 mutations was performed using direct sequencing. Clinical characteristics and overall survival (OS) were compared between patients with and without TET2 alterations. Results: Intronic and missense mutations were identified. No nonsense or frameshift mutations were observed. Two putative disease-causing missense mutations (S609C and A1865G) were identified in one patient. We estimated the prevalence of TET2 mutations in the current patient population to be 1.4%. The most common polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L (6%). Patients with polymorphism I1762V had an increased 10-year survival rate compared with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square test; OS was not different when examined using the Kaplan-Meier method (p = 0.104). Conclusion: The prevalence of TET2 mutations in children with AML compared with adults with AML was lower and less complex. Patient prognosis associated with TET2 mutations in children requires further investigation. Copyright (C) 2015, Formosan Medical Association. Published by Elsevier Taiwan LLC.
Several studies have reported previously that acute myeloid leukemia (AML) may express WT1 detected by RT-PCR and/or Northern blotting. The diagnostic utility of WT1 expression in AML using immunohistochemistry has not been reported previously. Paraffin-embedded tissue sections from 55 AML, 12 acute lymphoblastic leukemia (ALL), and 10 normal bone marrow specimens were immunostained for WT1 (anti-N terminus antibody). 22/55 AML cases (40%) demonstrated nuclear immunopositivity for WT1, including 20/47 bone marrow trephines and 2/4 granulocytic sarcomas. All the ALL and normal bone marrow specimens were negative. A significant proportion of AML expresses nuclear immunostaining for WT1, a finding that has only been described previously in Wilms' tumor and desmoplastic small round cell tumor. This finding is important for the correct interpretation of immunohistochemical findings in the diagnosis of "small round cell'' tumors of childhood, especially in cases of extramedullary deposits of AML, in which traditional myeloid markers may be negative.
The karyotype is critical for the evaluation of acute myeloid leukemia (AML) at diagnosis. Cytogenetic abnormalities detected in AML are one of the most powerful independent prognostic factors. It impacts on the choice of treatment in clinical trials. All chromosomes can be targeted, common chromosomal abnormalities are recurrent and may be associated with a cytological well-defined type. In 40% of the cases, the karyotype is normal and must be associated with molecular biology studies that can refine the prognosis. The usefulness of the karyotype is more limited during the follow-up of the patient due to its limited sensitivity, but it is still useful in the clinical management of relapse. Since 2001, the WHO (World Health Organization) classification of hematological malignancies integrates cytogenetic data in the classification of AML. Karyotype is therefore mandatory in the diagnosis of AML.
Purpose: To correlate visual acuity outcomes and clinical features with quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN). Methods: Retrospective, consecutive case series. Results: In total, 14 eyes of 13 patients were diagnosed with ARN, based on the American Uveitis Society criteria, and were followed for a mean of 324.5 days (median 250.5 days, SD +/- 214 days). Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of 14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%) and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 x 10(6)/mL (median 2.10 x 10(6)/mL, range: 0-5.60 x 10(7)/mL). Eyes with quantitative PCR DNA copy number of 5.0 x 10(6)/mL (n = 6 eyes) had worse baseline visual acuity (logMAR 1.48 +/- 0.71 vs 0.94 +/- 0.76, p = 0.196) and final visual acuity (logMAR 2.10 +/- 0.60 vs 0.82 +/- 0.81, p = 0.007) compared with patients with a DNA copy number <5.0 x 10(6)/mL (n = 8 eyes). Patients with a DNA copy number of 5.0 x 10(6)/mL were more likely to have at least 5 clock hours of retinitis on funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p = 0.08). Conclusions: Quantitative DNA copy number of 5.0 x 10(6)/mL is associated with more extensive retinitis, worse visual acuity, and development of retinal detachment in patients with acute retinal necrosis.
This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis on the Mendelian randomization design. The Mendelian randomization approach uses genetic variants associated with lifelong high plasma YKL-40 levels that are largely unconfounded and not prone to reverse causation. Thus, the approach mimics a controlled double-blind randomized trial, but it uses genetic variants rather than a drug and placebo, and like a blinded trial, it allows inference about causality. Moreover, the review also covers background on the molecular biology and functions of YKL-40, YKL-40 levels in healthy individuals and reference range, and the role of YKL-40 as a biomarker of cardiovascular and alcoholic liver disease. YKL-40 is a plasma protein named after its three N-terminal amino acids, Y (tyrosine), K (lysine) and L (leucine), and its molecular weight of 40kDa. It is produced by local inflammatory cells in inflamed tissues, such as lipid-laden macrophages inside the vessel wall and perhaps also hepatic stellate cells. Observational studies show that plasma YKL-40 levels are elevated in patients with cardiovascular and liver disease and are associated with disease severity and prognosis. Furthermore, elevated plasma YKL-40 levels in apparently healthy individuals are associated with a 2-fold increased risk of future ischemic stroke and venous thromboembolism, but not with myocardial infarction, suggesting that YKL-40 could play a role in the formation of embolisms rather than atherosclerosis per se. Further, elevated YKL-40 levels combined with excessive alcohol consumption are associated with 10-years risk of alcoholic liver cirrhosis of up to 7%, suggesting that YKL-40 can be used as a strong noninvasive marker of predicting alcoholic liver cirrhosis. Importantly, in Mendelian randomization studies, genetically elevated plasma YKL-40 levels were not associated with risk of cardiovascular and alcoholic liver disease, thus suggesting that plasma YKL-40 does not play a causal role in the development of these diseases. Despite this, plasma YKL-40 levels may play a role in disease progression after diagnosis, and inhibition of YKL-40 activity might be a novel therapy in some cardiovascular and liver diseases.
Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.
Introduction: The recent approval of adalimumab (trade name Humira, Abbvie inc.) by the FDA for the treatment of noninfectious intermediate, posterior and panuveitis marks the first on label' non-corticosteroid drug available to ophthalmologists. Immunomodulatory (IMT) and biologic agents have long been shown to be effective in inducing remission of chronic uveitis but have remained as orphan drugs due to lack of financial incentive and perceived need. Areas covered: Here we provide detail into the background and use of adalimumab for uveitic patients. Topics include pharmacology, therapeutic indications and usage, dosage, drug safety, physician monitoring, side effects and adverse events. Expert opinion: We see the approval of adalimumab for uveitis as an important milestone improving upon the accepted standards of care for patients with this severe, sight threatening disease. We implore medical professionals to consider the use of IMT and biologic treatments for patients with recurrent non-infectious uveitis, referring to ocular immunology and uveitis specialists when necessary.
Aims: Trophoblast fusion in the placenta is prerequisite to successful pregnancy and the pathological conditions related to it. The presence of syncytin-1, is not sufficient to explain the complete event and ADAM12 is a major co-player candidate. Via differential splicing, the ADAM12 gene produces a short and a long form, being the ADAM12-S and the ADAM12-L respectively. Methods and results: We investigated the localisation of both variants in the human placenta using whole mount in situ hybridisation, immunohistochemistry and Northern blotting in 1st (n = 8) and 3rd (n = 8) trimester placentae and in the case of NB in several cell lines. In Northern blotting, 1st and 3rd trimester placentae were positive for the ADAM12-S and Bewo, 293HEK, JAR, leucocytes, macrophages, 1st and 3rd trimester placentae were positive for ADAM12-L. In whole mount in situ hybridisation, the 1st and 3rd trimester placental syncytium was positive for both variants. In immunohistochemistry, ADAM12-L localised in the cytotrophoblast of both 1st and 3rd trimester placentae, while ADAM12-S localised in the complete syncytium, often including the cytotrophoblast. Conclusion: The different localisation of ADAM12-S and ADAM12-L indicates a possible different role making ADAM12-L a candidate for the fusion event, while the syncytial localisation of the ADAM12-S makes it a candidate for cell-cell and cell-matrix interactions between the placental syncytium and the maternal interface. (C) 2011 Elsevier GmbH. All rights reserved.
This paper proposes an adaptive controller with an improved high-frequency injection method for sensorless synchronous reluctance drive systems. A mathematical model is presented to show that the use of a high-frequency injection method that takes into account the effects of unequal mutual-inductances and the influence of speed reduces the rotor position estimation error. The adaptive speed control algorithm offers improved transient performance in comparison to typical proportional-integral (PI) controllers that are employed in sensorless drive systems. To demonstrate the viability, the proposed adaptive controller and the modified high-frequency injection method are implemented using a TMS-320F-28335A digital signal processor to control a 500 W prototype synchronous reluctance motor drive. Experimental results are presented to show that the transient, load disturbance, and tracking responses of the proposed drive system are superior in comparison to a drive that uses a PI controller. Both experimental and theoretical analyses clearly indicate that the proposed high-frequency injection method with an adaptive speed-loop controller offers improved performance in adjustable speed synchronous reluctance drive systems.
In this paper, a current sensorless adaptive secondary-side control is proposed for the series resonant converter (SRC), making it a good candidate for MHz 48 voltage regulators. By means of varying ac equivalent resistance, the output voltage regulation is achieved by controlling the duty cycle of the synchronous MOSFET. By taking advantage of the secondary-side control, SRCs can operate under zero-voltage switching at any input voltage and load conditions. A current sensorless adaptive digital control is proposed to control the current-type synchronous MOSFETs, which automatically compensates the delay caused by the current-sensor circuit and the gate driver, and also eliminates the current sensor in the power path. A hybrid control strategy is introduced to overcome the efficiency degradation caused by the secondary-side control.
A recursive smoothing filter employing a bank of fading-memory polynomial sub-filters is presented. Variance estimates are used to mix the outputs of the sub-filters, imparting variable gain and phase characteristics that permit it to automatically adapt to signal parameter changes. The proposed adaptive technique does not involve the estimation of plant parameters; therefore, it may be used in both open-loop and closed-loop configurations. In open-loop estimation problems, variable gain/bandwidth allows it to reduce the impact of random errors caused by sensor noise and the impact of bias errors caused by model mismatch during ` maneuvers'. In feedback control problems, variable phase/delay allows it to act as a lag filter for an improved steady-state response (i.e. greater noise attenuation) and act as a lead filter, or a proportionalderivative controller, for an improved transient response (i.e. increased closed-loop damping) for input discontinuities. Copyright (C) 2015 John Wiley & Sons, Ltd.
In this paper, a novel mixed iterative adaptive dynamic programming (ADP) algorithm is developed to solve the optimal battery energy management and control problem in smart residential microgrid systems. Based on the data of the load and electricity rate, two iterations are constructed, which are P-iteration and V-iteration, respectively. The V-iteration is implemented based on value iteration, which aims to obtain the iterative control law sequence in each period. The P-iteration is implemented based on policy iteration, which updates the iterative value function according to the iterative control law sequence. Properties of the developed mixed iterative ADP algorithm are analyzed. It is shown that the iterative value function is monotonically nonincreasing and converges to the solution of the Bellman equation. In each iteration, it is proven that the performance index function is finite under the iterative control law sequence. Finally, numerical results and comparisons are given to illustrate the performance of the developed algorithm.
This paper proposes a dimmable energy-efficient light-emitting diode (LED) driver for applications in interior lighting. High efficiency is achieved by an adaptive voltage regulation, which minimizes power losses in the linear current regulator. A digital control mechanism employing a resistive digital-to-analog converter for feeding the analog feedback input of a dc-dc converter is introduced. It is shown that the digital control methodology gives maximum design flexibility and enhances control over regulation speed and stability. In an experimental setup, the proposed concept is verified and evaluated. Operating at an input voltage of 24 V, the LED driver provides a relatively wide output voltage range of 3.5-38 V. Output current is regulated to 700 mA with a steady-state precision of more than 98.8%, whereas pulsewidth modulation dimming with a frequency of 1 kHz and shortest on-time of 4 mu s is employed. A peak efficiency of the complete system of 93.9% is achieved.
Environmental governance systems are under greater pressure to adapt and to cope with increased social and ecological uncertainty from stressors like climate change. We review principles of social cognition and decision making that shape and constrain how environmental governance systems adapt. We focus primarily on the interplay between key decision makers in society and legal systems. We argue that adaptive governance must overcome three cooperative dilemmas to facilitate adaptation: (1) encouraging collaborative problem solving, (2) garnering social acceptance and commitment, and (3) cultivating a culture of trust and tolerance for change and uncertainty. However, to do so governance systems must cope with biases in people's decision making that cloud their judgment and create conflict. These systems must also satisfy people's fundamental needs for self-determination, fairness, and security, ensuring that changes to environmental governance are perceived as legitimate, trustworthy, and acceptable. We discuss the implications of these principles for common governance solutions (e.g., public participation, enforcement) and conclude with methodological recommendations. We outline how scholars can investigate the social cognitive principles involved in cases of adaptive governance.
Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.
In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels.
CRISPR-Cas are self-/nonself-discriminating systems found in prokaryotic cells. They represent a remarkable example of molecular memory that is hereditarily transmitted. Their discovery can be considered as one of the first fruits of the systematic exploration of prokaryotic genomes. Although this genomic feature was serendipitously discovered in molecular biology studies, it was the availability of multiple complete genomes that shed light about their role as a genetic immune system. Here we tell the story of how this discovery originated and was slowly and painstakingly advanced to the point of understating the biological role of what initially was just an odd genomic feature.
In this chapter has been proposed a robust sensorless cascade control scheme for a Permanent Magnet Synchronous Motor (PMSM) drive. A Discrete Time Variable Structure Control (DTVSC) is considered and the rotor position and speed are obtained through an Adaptive Extended Kalman Filter (AEKF). The performance of the filter is improved by an on line adjustment of the input and measurement noise covariances obtained by a suitably defined estimation algorithm. The proposed solution is experimentally tested on a commercial PMSM drive equipped with a control system based on a floating point Digital Signal Processor (DSP).
This paper presents a power system harmonic elimination using the mixed adaptive linear neural network and variable step-size leaky least mean square (ADALINE-VSSLLMS) control algorithm based active power filter (APF). The weight vector of ADALINE along with the variable step-size parameter and leakage coefficient of the VSSLLMS algorithm are automatically adjusted to eliminate harmonics from the distorted load current. For all iteration, the VSSLLMS algorithm selects a new rate of convergence for searching and runs the computations. The adopted shunt-hybrid APF (SHAPF) consists of an APF and a series of 7th tuned passive filter connected to each phase. The performance of the proposed ADALINE-VSSLLMS control algorithm employed for SHAPF is analyzed through a simulation in a MATLAB/Simulink environment. Experimental results of a real-time prototype validate the efficacy of the proposed control algorithm.
The proposed frequency-locked loop (FLL) utilizes the flat frequency response characteristics of the moving window filter (MWF) in closed-loop and adaptive sampling pulse adjustment for capacitance measurement. An operational amplifier (op-amp) based relaxation oscillator generates a square wave whose fundamental sine wave is extracted by MWF. Then, the fundamental sine wave is tracked by the FLL to estimate its frequency which is inversely proportional to the unknown capacitance. The FLL employs another MWF to track the center frequency and its variation due to capacitance. The MWF offers an almost flat frequency response around the center frequency in closed-loop. However, the small magnitude and phase errors observed in the flat frequency response had been corrected by adjusting the sampling pulses adaptively. Experimental investigation demonstrates the capabilities of the scheme for wider and accurate capacitance measurement.
The proof of principle of an acquisition system of +/-50ppm repeatability, 10 V range, real-time delay less than 1.2 its is presented. The system will be integrated into the digital control loop of a high -voltage modulator under design at ETH Zurich and University of Laval for the new particle accelerator under study at CERN, the Compact LInear Collider (CLIC). Initial specifications are presented and translated into system requirements. Main design choices are discussed and Pspice simulation results are reported to prove that the proposed system meets the demanding requirements.
In comparison with conventional operational amplifier, ring amplifier can achieve better power efficiency for switched capacitor circuits. However, the cascade-inverter architecture of ring amplifier may suffer from undesirable oscillation which has a great impact on transient stability. This paper presents a latched-based ring amplifier which is capable of decreasing the probability of oscillation. Besides, two auto-zero schemes are employed in different pipelined stages to reduce the common-mode voltage offset and to increase the stability. The prototype ADC was fabricated in a 90-nm CMOS technology. The measured SNDR and SFDR are 52.06 dB and 63.15 dB, respectively, for a Nyquist frequency input sampled at 35 MS/s, and the ADC consumes 3.65 mW.
Background/Aims: The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods: Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1-/-). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1-/-mice. However, albumin overload resulted in severe albuminuria in Adcy1-/-mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. Copyright (C) 2010 S. Karger AG, Basel
The endogenous oxytocin system plays a vital role in facilitating parturition, lactation and social interaction in humans and other mammals. It also impacts on a number of important endocrine, immune and neurotransmitter systems. A well-regulated oxytocin system has been proposed to increase resilience, and therefore reduce the likelihood of an individual developing mental illness or substance dependence. This review discusses the adverse external influences that can modulate oxytocin receptor and protein levels and impact on substance use and mental health. The paper highlights the impact of adversity such as poor maternal care, parental substance use and child abuse or neglect. We review clinical and preclinical data on the impact of adversity on the basis of the time of exposure from infancy and early childhood, to adolescence, adulthood to older age. Previous research suggests that dysregulation of the endogenous oxytocin system may be implicated in determining susceptibility to stress, anxiety, addiction and mental health conditions. The impact of external influence seems to be strongest in specific time periods where the system shows experience-based development or natural fluctuations in oxytocin levels. Interventions that target the oxytocin system during or soon after exposure to adversity may prove protective. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Background and aims Deficits in social cognitive abilities including emotion recognition and theory of mind (ToM) can play a significant role in interpersonal difficulties observed in alcohol use disorder (AUD). This meta-analysis aims to estimate mean effect sizes of deficits in social cognition inAUD and examines the effects of demographic and clinical confounding factors on the variability of effect sizes across studies. Methods A literature review was conducted on research reports published from January 1990 to January 2016. Twenty-five studies investigating ToM and facial emotion recognition performances of 756 individuals with AUD and 681 healthy controls were selected after applying inclusion and exclusion criteria. Weighted effect sizes (d) were calculated for ToM, decoding and reasoning aspects of ToM, total facial emotion recognition and recognition of each of six basic emotions. Results Facial emotion recognition was significantly impaired [d=0.65,95% confidence interval (CI)=0.42-0.89], particularly for disgust and anger. AUDwas also associated with deficits in ToM (d=0.58, 95% CI=0.36-0.81). These deficits were evident in tasks measuring both decoding (d=0.46, 95% CI=0.19-0.73) and reasoning (d=0.72, 95% CI=0.37-1.06) aspects of ToM. The longer duration of alcohol misuse and more depressive symptoms were associated with more severe deficits in recognition of facial emotions. Conclusions Alcohol use disorder appears to be associated with significant impairment in facial emotion recognition and theory of mind.
Aims To investigate whether: (1) childmaltreatment is associated with life-time cannabis use, early-onset cannabis use, daily cannabis use and DSM-IV cannabis abuse in young adulthood; and (2) behaviour problems, tobacco use and alcohol use at age 14 are associated with cannabis use. Design Birth cohort using linked government agency child protection data to define exposure to child maltreatment. Setting The Mater-University of Queensland Study of Pregnancy in Brisbane, Australia. Participants Of the original cohort of 7223 mother and child pairs, obtained from consecutive presentations for prenatal care at a hospital serving a cross-section of the community, 3778 (52.3%) of the young people participated at age 21 years. Measurements Exposure to child maltreatment was established by substantiated government agency reports. Cannabis outcomes were by self-report questionnaire and Composite International Diagnostic Interview (CIDI)-Auto at age 21. Associations were adjusted for a range of potential confounders. Additional adjustment was carried out for variables measured at age 14-youth behaviour problems [Achenbach Child Behavior Checklist (CBCL)], tobacco use and alcohol use. Findings After adjustment, substantiated child maltreatment was associated with any life-time cannabis use [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.08-2.39], cannabis use prior to age 17 (OR = 2.47, 95 % CI = 1.67-3.65), daily cannabis use (OR = 2.68, 95% CI = 1.49-4.81) and DSM-IV cannabis abuse/dependence (OR = 1.72, 95% CI = 1.07-2.77). Externalizing behaviour and tobacco and alcohol use at age 14 were associated significantly with almost all cannabis outcomes (P < 0.05), with internalizing behaviour associated inversely (P < 0.05). Conclusions Children in Australia who are documented as having been maltreated are more likely to go on to use cannabis before the age of 17, use cannabis as an adult, use cannabis daily and meet DSM-IV criteria for cannabis dependence. Externalizing behaviour in adolescence appears partly to mediate the association with adult cannabis use.
The purpose of this project was to examine the emotional health and wellbeing of Canadian caregivers of persons with significant mental health or addictions problems. We assessed the emotional health of caregivers by care-receiver condition type (i.e. mental health or addictions vs. physical or other health problems), levels of caregiver stress and methods particularly for reducing stress among caregivers of persons with mental health or addictions disorders. Weighted cross-sectional data from the 2012 General Social Survey (Caregiving and Care Receiving) were modelled using weighted descriptive and logistic regression analyses to examine levels of stress and the emotional health and well-being of caregivers by care-receiver condition type. Caregivers of persons with mental health or addictions problems were more likely to report that caregiving was very stressful and that they felt depressed, tired, worried or anxious, overwhelmed; lonely or isolated; short-tempered or irritable; and resentful because of their caregiving responsibilities. The results of this study suggest that mental health and addictions caregivers may experience disparate stressors and require varying services and supports relative to caregivers of persons with physical or other health conditions.
Defined as sexually explicit material that elicits erotic thoughts, feelings, and behaviours, internet pornography is a prevalent form of media that may facilitate problematic use and craving for engagement. Research suggests that superordinate cognitions and information processing, such as desire thinking and metacognition, are central to the activation and escalation of craving in addictive behaviours. The current study aimed to contribute to the literature by testing the proposed metacognitive model of desire thinking and craving in a sample of problematic pornography users, while revising the model by incorporating negative affect. From a theoretical perspective, environmental cues trigger positive metacognitions about desire thinking that directly influence desire thinking, resulting in the escalation of craving, negative metacognitions, and negative affect. Participants were recruited via an online survey and screened for problematic internet pornography use. Path analyses were used to investigate relationships among the aforementioned constructs in a final sample of 191 participants. Consistent with previous research, results of this study validated the existence of metacognitive processes in the activation of desire thinking and escalation of craving, while indicating that desire thinking has the potential to influence negative affect. Additionally, results supported the role of significant indirect relationships between constructs within the revised model of metacognition, desire thinking, and psychopathology. Collectively, the findings demonstrate the clinical value of a metacognitive conceptualisation of problematic pornography use. Exploring the metacognitive mechanisms that underpin problematic internet pornography use may give rise to the development of new treatment and relapse prevention strategies. (C) 2017 Elsevier Ltd. All rights reserved.
In many low-to-mid power applications, critical mode boost power factor corrector converters are widely used because of its low switching loss and simple control. However, near the zero crossing of the input line voltage, an input current distortion and a low power factor are caused by delayed switching period and negative input currents. Generally, an additional on-time method according to the input voltage is used to compensate the input current distortion. However, a detailed quantitative analysis for the exact additional on time has not been studied till now. In this paper, the explicit form of the optimized additional on time has been obtained using a quantitative analysis and the advantage of the digital control. From a state trajectory and "net input charge" analysis, it is shown that the optimized on time should be related to not only the input voltage, but also the output power. Also, in order to improve the efficiency in a high input and light load condition, circulating currents are reduced in the inevitable dead angle with a gate turning-off technique. By using digital control, the optimized additional on time and the gate turn-off technique have been implemented with the 90-230 V-rms input and 380 V/200 W output prototype.
For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively. A total of 1325 lymph nodes were collected from 49 patients, grouped into 3 groups: lower mediastinal, paracardial, and abdominal. The former 2 groups were examined by monoclonal antibodies against Ber-Ep4 and CD44v6. The incidence of LNMM in mediastinal group was 37% (18/49) for Ber-Ep4 and 33% (16/49) for CD44v6. While in routine histological diagnosis, the number of patients with the positive lymph nodes was 7 (14%). When combining IHC with histopathology (HE) staining, the incidence of positive mediastinal lymph nodes was increased to 24%, with a total number of 37 lymph nodes from 28 patients (57%). Micrometastases indicated by Ber-Ep4 and CD44v6 were associated with the depth of tumor invasion (P=0.020 and 0.037, respectively), histopathological nodal status (P=0.024 and 0.01, respectively), and Lauren classification (P=0.038 and, respectively). Expression of CD44v6 and Ber-Ep4 was positively correlated (r=0.643, P<0.001). The 3- and 5-year survival rates for all patients were 66% and 50%, respectively. The patients with LNMM had a lower 3-year survival rate of 51%, compared to 80% from no LNMM group; 5-year survival rate was also lower in LNMM group, which is 29% versus 68% (P=0.006) in the no LNMM group. Patients with positive Ber-Ep4 cells had a lower survival, but not statistically significant (P=0.058). CD44v6-positive group had a significantly reduced survival (P<0.001). In patients group with negative lower mediastinal lymph nodes, patients without LNMM obtained a significant survival benefit (P=0.021). Our study demonstrated that routine test for LNMM is necessary for patients with negative lymph nodes. As a positive prognostic factor, thorough lower mediastinal lymphadenectomy in an invasive approach should be considered when necessary. Ber-Ep4 and CD44v6 were shown to be great markers for detecting LNMM.
Aims: Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV-related ACC-like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in-situ hybridization, and clinicopathological information for all cases is presented. Methods and results: Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease. Conclusion: We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable.
The aim of the present study was to investigate the role of chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor, chemokine (C-X-C motif) receptor 4 (CXCR4) in the pathogenesis of adenomyosis (AD). Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction analysis were used to measure the protein and mRNA expression of CXCL12 and CXCR4 in eutopic endometrial and ectopic foci tissue samples. Samples from a total of 36 patients with AD (study group) were compared with endometrial tissue samples from 33 patients who underwent uterine fibroids surgery (control group) during the same period. All data are presented as the mean +/- standard deviation and were analyzed with SPSS software (version 16.0). Analysis of variance was used for between group analysis and pairwise comparison was performed using Fisher's least significant difference post hoc test. The results of the present study revealed that CXCL12 and CXCR4 protein expression was significantly increased in ectopic foci tissue compared with eutopic endometrial tissue samples from patients with AD. CXCL12 and CXCR4 protein expression in ectopic foci and eutopic endometrial tissue samples were significantly increased compared with the control group (P< 0.05 for between group comparisons). No significant differences were identified in CXCL12 and CXCR4 protein expression between the proliferative and secretory phases within each group. Furthermore, CXCL12 and CXCR4 mRNA expression was significantly increased in ectopic foci tissue and eutopic endometrial tissue compared with the control group (P< 0.05 for between group comparisons). CXCL12 mRNA expression was markedly increased in ectopic foci tissue compared with eutopic endometrial tissue of patients with AD. The expression of CXCR4 mRNA was significantly increased in eutopic endometrial tissue compared with ectopic foci tissue and the control group (P< 0.05 for between group comparisons). No significant differences were identified in CXCL12 and CXCR4 mRNA expression between proliferative and secretory phase within each group. In conclusion, CXCL12 and CXCR4 may induce the ectopia, and promote the spread and localized growth of endometrial cells in the development of AD.
Objective: We investigated the expression and potential roles of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, IL-37, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF) in patients with adenomyosis. Materials and methods: This prospective study examined 16 women with histologically proven adenomyosis and 52 women without adenomyosis, all of whom were undergoing a hysterectomy for non-endometrial pathology at the Department of Gynaecology, the First Hospital of Jilin University, Changchun, China, from December 2011 to September 2012. Serum samples were collected from the patients, and the concentrations of serum IL-2, IL-4, IL-6, IL-10, IL-17A, IL-37, IFN-gamma, and TNF were measured by Enzyme-Linked Immunosorbent Assay (ELISA). We then calculated specificity and sensitivity of cytokines, taking Cancer Antigen (CA) 125 as a reference, distinguishing cases from controls by receiver operating characteristic (ROC) curve. The correlation between individual cytokines and CA 125 was also analysed. Results: IL-37 was detectable in 69.2% and the other cytokines in 30.8% of sera samples from the 52 controls. All the eight cytokines were detectable in the sera samples from 16 patients with adenomyosis. Significantly higher levels of serum IL-37 and IL-10 and significantly lower levels of serum IL-17A and TNF were detected in adenomyosis patients when compared with controls (p< 0.05). Conclusions: Serum levels of IL-10, IL-17A, IL-37, and TNF varied significantly between cases and controls, and could be involved in the pathogenesis of adenomyosis.
Objectives: Inflammatory response and cytokine activation are markedly stimulated in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine, released by all cell types, binds to a class of G protein-coupled receptors to induce various skeletal muscle effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly adenosine A2B receptors, could stimulate IL-6 gene expression in rat L6 skeletal muscle cells. Materials and Methods: The rat L6 skeletal muscle cells were cultured in 25 cm2 flasks. These differentiated cells were treated and then quantitative reverse transcription-polymerase chain reaction (Probe-based) was used to analyze IL-6 gene expression level among different treatment conditions. Results: Adenosine-5'-N-ethyluronamide (NECA), a stable adenosine analogue, concentration-and time-dependently stimulates IL-6 gene expression in skeletal muscle cells. The effect of NECA is inhibited by a selective adenosine A2B receptor antagonist, PSB 603. By using cyclic adenosine monophosphate (cAMP)-arising reagent forskolin, cAMP is found to be involved in the up-regulation of IL-6 induction. Conclusion: Here, a novel relationship between adenosine and IL-6 up-regulation has been demonstrated for the first time; IL-6 up-regulation induced by NECA is mediated by adenosine A2B receptor activation in skeletal muscle and is dependent on mainly a cAMP pathway. Adenosine A2B receptors are, thus, potentially important pharmacological targets in treating inflammation and related diseases in skeletal muscle tissues.
Adenosine triphosphate- binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate- binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate- binding cassette gene expression profiles ( signatures), based on the expression of all 49 human adenosine triphosphate- binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate- binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate- binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients- breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real- time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate- binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate- binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 ( official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers.
Background:To perform a molecular epidemiological analysis of viral conjunctivitis among excess conjunctivitis cases recorded at the University Hospital of Patras, Greece, for the period March to June 2012. Methods: A structured questionnaire containing demographic and clinical data was developed in order to collect retrospective data on the cases. Eye swab specimens were collected and molecular detection of adenoviruses was performed by nested PCR. Positive results were confirmed by sequencing. To determine the relatedness between the isolated sequences, a phylogenetic analysis was conducted. Results: The epidemiological analysis (including retrospective data) included 231 conjunctivitis cases (47.1% male, and 52.8% female). Based on clinical features 205 of the cases were diagnosed of viral origin (46.3% male and 53.7% female), 4 of bacterial origin (50% male and 50% female) while 22 were undefined conjunctivitis. The outbreak excess cases (included 156 cases) affected all age groups regardless gender predilection. For the positive samples indicated that 29 samples (72.5%) were AdV17, and 5 (12.5%) as AdV54. Conclusions: Molecular analysis could define the cause of viral conjunctivitis, while epidemiological data contributed to the assessment of the risk factors and underlined possible preventive measures. This study is one of the very few on viral conjunctivitis in Greece. This outbreak underscores the need for a national surveillance system for acute infectious conjunctivitis outbreaks. The epidemiological as well as molecular investigation on HAdV ocular infections is rather absent in Greece, which has no surveillance system for viral conjunctivitis.
The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai. Variable number tandem repeats of DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by PCR-AGE. Several allele repeats of the genes were observed in the screened subjects. Statistical significance was observed for the 10R/10R genotype of the DAT1 3'UTR VNTR between cases and controls.
Objective-Endothelial activation is implicated in atherogenesis and diabetes. The role of peroxisome proliferator-activated receptor-delta (PPAR-delta) in endothelial activation remains poorly understood. In this study, we investigated the anti-inflammatory effect of PPAR-delta and the mechanism involved. Methods and Results-In human umbilical vein endothelial cells (HUVECs), the synthetic PPAR-delta ligands GW0742 and GW501516 significantly inhibited tumor necrosis factor (TNF)-alpha-induced expression of vascular cell adhesion molecule-1 and E-selectin (assayed by real-time RT-PCR and Northern blotting), as well as the ensuing endothelial-leukocyte adhesion. Activation of PPAR-delta upregulated the expression of antioxidant genes superoxide dismutase 1, catalase, and thioredoxin and decreased reactive oxygen species production in ECs. Chromatin immunoprecipitation assays showed that GW0742 switched the association of BCL-6, a transcription repressor, from PPAR-delta to the vascular cell adhesion molecule ( VCAM)-1 promoter. Small interfering RNA reduced endogenous PPAR-delta expression but potentiated the suppressive effect of GW0742 on EC activation, which suggests that the nonliganded PPAR-delta may have an opposite effect. Conclusions-We have demonstrated that ligand activation of PPAR-delta in ECs has a potent antiinflammatory effect, probably via a binary mechanism involving the induction of antioxidative genes and the release of nuclear corepressors. PPAR-delta agonists may have a potential for treating inflammatory diseases such as atherosclerosis and diabetes.
Aims/hypothesis The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. Methods Male Sprague-Dawley rats received N-omega-nitro-Larginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. Results Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. Conclusions/interpretation Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.
Leptin is an adipocytokine that regulates body weight, and maintains energy homeostasis by promoting reduced food intake and increasing energy expenditure. Leptin expression and secretion is regulated by various factors including hormones and fatty acids. Butyrate is a short-chain fatty acid that acts as source of energy in humans. We determined whether this fatty acid can play a role in leptin expression in fully differentiated human adipocytes. Mature differentiated adipocytes were incubated with or without increasing concentrations of butyrate. RNA was extracted and leptin mRNA expression was examined by Northern blot analysis. Moreover, the cells were incubated with regulators that may affect signals which may alter leptin expression and analyzed with Northern blotting. Butyrate stimulated leptin expression, and stimulated mitogen activated protein kinase (MAPK) and phospho-CREB signaling in a time-dependent manner. Prior treatment of the cells with signal transduction inhibitors as pertusis toxin, G(i) protein antagonist, PD98059 (a MAPK inhibitor), and wortmannin (a PI3K inhibitor) abolished leptin mRNA expression. These results suggest that butyrate can regulate leptin expression in humans at the transcriptional level. This is accomplished by: 1) G(i) protein-coupled receptors specific for short-chain fatty acids, and 2) MAPK and phosphatidylinositol-3-kinase (P13K) signaling pathways.
Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases - 109 and - 100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.
Background: Autologous fat grafting is a prevalent technique used for softtissue augmentation; however, the poor survival rate of the grafted tissue remains a drawback of this method. Although adipose-derived stem cells (ASCs) are an attractive candidate for enhancing graft retention, the poor posttransplantation viability of these cells limits their application. Here we investigated whether overexpression of the antiapoptotic protein heat-shock protein 70 (Hsp70) could enhance ASCs' therapeutic potential for fat transplant survival. Methods: Recombinant adenoviral vectors were used to overexpress Hsp70 in ASCs isolated from a healthy woman. The Hsp70 expression was assessed by quantitative real- time polymerase chain reaction and Western blot analyses. The adipose tissue granules aspirated from anotherwomanweremixed with ASCs expressing green fluorescent protein (GFP)-tagged Hsp70 (group A) or GFP alone (group B), untreated ASCs (group C), and phosphate-buffered saline (group D). Fat mixtures were then injected subcutaneously into the backs of nude mice, and graft survival was compared after 3 months. Results: Adipose-derived stem cells transduced with recombinant adenoviral vectors exhibited significantly increased Hsp70 expression in vitro. Meanwhile, weight retention analyses demonstrated that fat grafts using the group A cell population exhibited significantly higher survival rates than the other treatment groups in vivo. Moreover, histological analyses revealed that fat grafts containing GFP-Hsp70-expressing ASCs yielded significantly lower levels of tissue fibrosis and fat cysts/vacuoles, higher capillary densities, and increased numbers of viable adipocytes than the control groups. Conclusions: Our data indicate that Hsp70 overexpression enhances the efficacy of ASC therapy by improving the survival and quality of the transplanted fat tissues.
Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1 alpha-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1 alpha transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1 alpha gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH >IH >RA; P>>SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1 alpha activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1 alpha transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.
Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31(-)/CD45(-)/CD34(+)/CD146(-) cells (adventitial stromal/stem cells [ASCs]) and CD31(-)/CD45(-)/CD34(-)/CD146(+) cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n=67) and PCs (n=73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n=429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH(br)ASC (most primitive); (b) ALDH(dim)ASC; (c) ALDH(br)PC; (d) ALDH(dim)PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and coexpression networks. Stem Cells2017;35:1273-1289
Extensive research has been performed to determine the effect of freezing protocol and cryopreservation agents on the viability of adipose tissue-derived stromal/stem cells (ASCs) as well as other cells. Unfortunately, the conclusion one may draw after decades of research utilizing fundamentally similar cryopreservation techniques is that a barrier exists, which precludes full recovery. We hypothesize that agents capable of inducing a subset of heat shock proteins (HSPs) and chaperones will reduce the intrinsic barriers to the post-thaw recovery of ASCs. ASCs were exposed to 43 degrees C for 1 h to upregulate HSPs, and the temporal HSP expression profile postheat shock was determined by performing quantitative polymerase chain reaction (PCR) and western blotting assays. The expression levels of HSP70 and HSP32 were found to be maximum at 3 h after the heat shock, whereas HSP90 and HSP27 remain unchanged. The heat shocked ASCs cryopreserved during maximal HSPs expression exhibited increased post-thaw viability than the nonheat shocked samples. Histochemical staining and quantitative reverse transcription-PCR indicated that the ASC differentiation potential was retained. Thus, suggesting that the upregulation of HSPs before a freezing insult is beneficial to ASCs and a potential alternative to the use of harmful cryoprotective agents.
The long-term effect of feeding the catecholamine analog ractopamine (RAC; ractopamine hydrochloride, Elanco Animal Health, Indianapolis, IN) on the expression of genes involved in energy and lipid metabolism in subcutaneous adipose tissue was studied. Large White pigs (84 kg) were fed corn- and soybean meal-based diets supplemented with 0, 20, or 60 mg/kg of RAC for 14, 28, or 42 d. Expression (mRNA abundance) in adipose tissue of sterol regulatory binding protein-1 (SREBP-1), PPAR alpha, PPAR gamma 2, fatty acid synthase (FAS), glucose transporter 4 (GLUT4), and stearoyl-CoA desaturase was determined by Northern blotting. Feed intakes did not differ, and RAC (20 and 60 mg/kg) improved BW gain at d 14, 28, and 42 (P < 0.05) and increased loin eye area (measured on d 42 only; P < 0.05). Expression of SREBP-1 and PPAR gamma 2 declined (P < 0.05) with RAC by d 28 and 42, whereas expression of PPAR alpha was increased (P < 0.05) on d 14, 28, and 42. After 14 d, expression of FAS and GLUT4 was decreased (P < 0.05) with 60 mg/kg of RAC, whereas both RAC concentrations attenuated FAS expression on d 28 and 42. Overall, adipose tissue stearoyl-CoA desaturase expression was not affected by RAC but showed somewhat less expression (P < 0.15) on d 28 at 60 mg/kg of RAC. Although prolonged, chronic RAC feeding most likely downregulates adipose tissue membrane beta-adrenergic receptors, mRNA abundances of anabolic lipid metabolism transcription factors, glucose transporters, and enzymes (SREBP-1, PPAR gamma 2, FAS, GLUT4) were still attenuated up to d 42. Conversely, a transcription factor related to oxidative metabolism expression (PPAR alpha) was enhanced. We conclude that even after 42 d, RAC still decreased expression of lipogenic genes in adipose tissue by yet undefined cyclic adenosine monophosphate-directed mechanisms, but in contemporary lean pigs, this effect is likely of limited practical significance.
Conveyor systems allow quick and efficient transportation for a wide variety of materials, which make them very popular in the material handling and packaging industries. Many kinds of conveying systems are available and used according to the various needs of different industries. Adjustable speed drives are used for the operation of the conveyors used in a number of industries. We can use adjustable electric drives in a number of industrial applications. A typical adjustable speed drive consists of an induction motor and a power electronic converter. In most cases, motor speed is commanded so that the control system requires an actual speed signal for closing the speed loop. In industrial applications, speed sensors, as well as sensorless solutions, are used. Due to the possibility of current speed sensor noises and for maintenance and economic aspects, the trend is to substitute speed sensors by computational solutions. Comprehensive reviews of the sensorless drives show that there are still some persistent problems associated with the sensorless control, that needs new solutions. In ASDs, the advanced control approach of IM is the FOC method, used in modern industrial drives. The current stator controller is the integral part of various FOC systems. In the classical FOC solution, PI or hysteresis controllers are generally used. However, PCCs are reported to have better properties. System sensitivity to inaccuracy and changes of motor equivalent circuit parameters are another problem in electrical drives. Almost all of the FOC systems are very sensitive to such inaccuracies; therefore, some parameters should be estimated online, and a robust structure of the control is required. The real-time implementation of the system is an important task even for electric drives or power converters.
Four groupA streptococcal glycolipopeptide vaccine candidates with different lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of the compounds was evaluated by macrophage and dendritic cell uptake studies and by in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates showed significant induction of the IgG response.
Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques. Advances in particle engineering now allow highly tunable physicochemical properties of particle-based vaccines, including composition, size, shape, surface characteristics, and degradability. Enhanced collaborative efforts between researchers in immunology and materials science are expected to rise to next-generation vaccines. This process will be significantly aided by a greater understanding of the immunological principles guiding vaccine antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted adjuvants and particle physicochemical properties, this review aims to provide an overview of the current literature to guide and focus rational particle-based vaccine design efforts.
Critical issues about scientific reproducibility have been raised about biomedical research, including the reliability of data and analyses within a given study. The case example in this article examined a reproducibility issue pertaining to the use of administrative data systems for evaluation of child maltreatment (CM) prevention, making use of a prevention study conducted over a decade ago that provided a unique opportunity. The place-randomization study, which randomized counties to condition, found that community-wide implementation of a parenting and family support intervention produced positive impact on county-wide rates for substantiated CM cases and out-of-home placements, documented through a state information system. The key consideration is whether and to what extent the administrative record data re-examined retroactively a decade later for the original study's time period would yield comparable results to those based on data acquired at the time of the study. The results indicated that despite small changes over time, the same data patterns and statistical effects were reproducible for the two archival outcome variables. For substantiated CM, the reproduced analyses reflected higher effect sizes and a clear pattern of reduction as a function of intervention. For out-of-home placements, effect sizes were quite comparable to the original ones, reflecting preventive impact. Overall, this case study illustrated the verifiability of data reproducibility in the context of a population outcome evaluation, which underscores the importance of reliable population-prevalence measurement as an essential part of a comprehensive public health strategy aimed at the prevention of CM. (C) 2016 Elsevier Ltd. All rights reserved.
Aims: Ancient DNA (aDNA) extracted from historical bones is damaged and fragmented into short segments, present in low quantity, and usually copurified with microbial DNA. A wide range of DNA quantification methods are available. The aim of this study was to compare the five most common DNA quantification methods for aDNA. Materials and Methods: Quantification methods were tested on DNA extracted from skeletal material originating from an early medieval burial site. The tested methods included ultraviolet (UV) absorbance, real-time quantitative polymerase chain reaction (qPCR) based on SYBR (R) green detection, real-time qPCR based on a forensic kit, quantification via fluorescent dyes bonded to DNA, and fragmentary analysis. Differences between groups were tested using a paired t-test. Results: Methods that measure total DNA present in the sample (NanoDrop (TM) UV spectrophotometer and Qubit (R) fluorometer) showed the highest concentrations. Methods based on real-time qPCR underestimated the quantity of aDNA. The most accurate method of aDNA quantification was fragmentary analysis, which also allows DNA quantification of the desired length and is not affected by PCR inhibitors. Conclusions: Methods based on the quantification of the total amount of DNA in samples are unsuitable for ancient samples as they overestimate the amount of DNA presumably due to the presence of microbial DNA. Real-time qPCR methods give undervalued results due to DNA damage and the presence of PCR inhibitors. DNA quantification methods based on fragment analysis show not only the quantity of DNA but also fragment length.
Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-termeffects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.
Several studies have confirmed that maltreatment and abuse in childhood are related to conduct problems. Less is known about such relationships with concurrent adversities in adolescence and, also, when compared with other severe adversities and possible multiple additive effects. The study encompassed a community population of 4881 adolescents 15-16 years of age 50.1 % boys and 49.9 % girls. Youth with and without conduct problem scores within the deviant range on the Strength and Difficulties Questionnaire (SDQ) was compared on 12 concurrent adversities. Based on self-reports, 4.4 % of the adolescents had conduct problem scores within the deviant range and more girls (5.1 %) than boys (3.7 %). In the deviant conduct problem group, 65.1 % had experienced two or more concurrent adversities compared with 26.3 % of youths in the non-deviant group (OR 5.23, 95 % CI 3.91-7.01). Likewise, the deviant conduct problem group was from 1.71 to 8.43 times more at the risk of experiencing the different adversities. Parental mental health problems and experiences of violence were multivariately strongest associated with conduct problem scores within the deviant range on the SDQ. A strong multiple additive relationship with adversities was found. Two-thirds of youth with SDQ conduct problem scores within the deviant range reported two or more concurrent adversities. Clinicians should seek information about kinds and amount of possible traumatic adversities in youth with conduct problems and offer evidence based treatment.
Objective: To investigate the association between the perception of expressed emotion and psychopathology of school-going adolescents in a non-clinical sample. Methods: The cross-sectional field study was conducted in Kocaeli, Turkey, and comprised high-school students during the 2014-15 school years. Data was collected using the Information Collection Form, Strengths and Difficulties Questionnaire and Shortened Level of Expressed Emotion Scale. SPSS 21 was used for data analysis. Results: Of the 487 subjects, 295(60.57%) were girls and 192(39.43%) were boys. The overall median age was 16 (inter-quartile range: 15-17 years). There were significant positive relationships between the scales in terms of emotional problems (p<0.001), behavioural problems (p<0.001), Attention-deficit/hyperactivity disorder (p<0.001), and peer relationship problems (p<0.001). There was also a negative significant relationship between pro-social behaviours and expressed emotion (p<0.001). Conclusion: The concept of perceived expressed emotion in non-clinical adolescents is useful in alarming clinicians and preventing mental disorders.
This study proposes and tests a new model that seeks to explain associations between religion, spirituality and health outcomes among adolescents. Specifically, we test for mediating effects of perceived spirituality on religion-health relations. Using data from the 4-H Study of Positive Youth Development, we find that perceived spirituality mediates religion-health relations, but that varies based on youths' conceptualisation of spirituality. With findings confirming that perceived spirituality potentially promote youths' psychosocial health, we offer some future research directions and implications regarding relations between youths' spirituality, religion and health behaviours.
Purpose The aim of this study is to find out the overall prevalence rates for the major forms of abuse among adolescents in the Kingdom of Saudi Arabia and the differences in prevalence by age, gender and living arrangement. Methods The cross-sectional study was conducted in secondary high schools in five of the 13 main regions of Kingdom of Saudi Arabia during 2012. Through a multistage stratified sampling technique, a sample (n = 16 939) of adolescents (15-19 years) were identified and invited to participate. The ISPCAN Child Abuse Screening Tool-Child was used for data collection. The previous year's occurrence of violence exposure, psychological, physical and sexual abuse, and neglect were assessed. Results Nearly 90% of the adolescents were between 16 and 18 years of age, and over 80% were cared for by both of their biological parents. Annual prevalence of various forms of abuse in the year before the 2012 assessment ranged between 0.10 and 0.65, with the lowest rate for sexual abuse and the highest for psychological abuse. Significantly, greater rates of all forms of abuse/exposure were found when participants lived with their mother or father only (versus with both), and even greater rates for all when they lived with their biological parent and a step-parent. Rates for violence exposure, psychological abuse and neglect were significantly greater for girls, and rate of sexual abuse was greater for boys. Conclusions More attention should be given to the effect of adolescent maltreatment particularly among girls. In addition, sexual abuse prevention programme should be targeted among boys.
Background Studies of children with food allergy typically only include the mother and have not investigated the relationship between the amount of allergen needed to elicit a clinical reaction (threshold) and health-related quality of life (HRQL). Our aims were (i) to compare self-reported and parent-reported HRQL in different age groups, (ii) to evaluate the impact of severity of allergic reaction and threshold on HRQL, and (iii) to investigate factors associated with patient-reported and parent-reported HRQL. Methods Age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQ) were completed by 73 children, 49 adolescents and 29 adults with peanut, hazelnut or egg allergy. Parents (197 mothers, 120 fathers) assessed their child's HRQL using the FAQLQ-Parent form. Clinical data and threshold values were obtained from a hospital database. Significant factors for HRQL were investigated using univariate and multivariate regression. Results Female patients reported greater impact of food allergy on HRQL than males did. Egg and hazelnut thresholds did not affect HRQL, but lower peanut threshold was associated with worse HRQL. Both parents scored their child's HRQL better than the child's own assessment, but whereas mother-reported HRQL was significantly affected by limitations in the child's social life, father-reported HRQL was affected by limitations in the family's social life. Severity of allergic reaction did not contribute significantly to HRQL. Conclusion The risk of accidental allergen ingestion and limitations in social life are associated with worse HRQL. Fathers provide a unique perspective and should have a greater opportunity to contribute to food allergy research.
Pre-ejection period (PEP) reactivity to reward has been posited as a specific index of behavioral approach and incentive motivation, suggesting it might be uniquely associated with the affective and motivational deficits of anhedonia. This study evaluated PEP reactivity to a reward task as a predictor of depressive symptoms among adolescents, examining global depressive symptoms as well as specific anhedonic and nonanhedonic symptoms clusters. Participants included 76 adolescents, ages 11-15 years (52% female). This study found marginal support for an association between PEP reactivity to reward and concurrent anhedonia symptoms, but no association with nonanhedonic or the global scale. Findings are discussed in terms of potential associations between peripheral psychophysiological measures and dopaminergic functioning and also the utility of this measure for future research on anhedonia.
Several studies have recently demonstrated that the volumes of specific brain regions are reduced in children and adolescents with post-traumatic stress disorder (PTSD) compared with those of healthy controls. Our study investigated the potential association between early traumatic experiences and altered brain regions and functions. We conducted a systematic review of the scientific literature regarding functional magnetic resonance imaging and a meta-analysis of structural magnetic resonance imaging studies that investigated cerebral region volumes in pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial volumes that fit the inclusion criteria were extracted and combined in a meta-analysis that assessed differences between groups. The meta-analysis found reduced total corpus callosum areas and reduced total cerebral and intracranial volumes in the patients with PTSD. The total hippocampus (left and right hippocampus) and gray matter volumes of the amygdala and frontal lobe were also reduced, but these differences were not significant. The functional studies revealed differences in brain region activation in response to stimuli in the post-traumatic stress symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD exhibited structural and functional brain abnormalities and that some of the abnormalities occurred in different brain regions than those observed in adults.
Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to positive relative to neutral images were extracted in basal ganglia regions of interest. Participants also completed a behavioral reward-processing task outside the scanner. Depression symptoms were assessed at the time of the MRI and again 2 years later. Greater reward reactivity across behavioral and neurobiological measures moderated the association of maltreatment with baseline depression. Specifically, faster reaction time (RT) to cues paired with monetary reward relative to those unpaired with reward and greater BOLD signal in the left pallidum was associated with lower depression symptoms in maltreated youth. Longitudinally, greater BOLD signal in the left putamen moderated change in depression scores over time, such that higher levels of reward response were associated with lower increases in depression over time among maltreated youths. Reactivity to monetary reward and positive social images, at both behavioral and neurobiological levels, is a potential marker of resilience to depression among adolescents exposed to maltreatment. These findings add to a growing body of work highlighting individual differences in reactivity to reward as a core neurodevelopmental mechanism in the etiology of depression.
While exposure to adverse family experiences (AFEs), subset of adverse childhood experiences (ACEs), has been associated with childhood obesity, less is known about the impact of exposures to each type of AFE. Using 2011-2012 National Survey of Children's Health data, we evaluated associations between exposure to individual AFEs and overweight/obesity status in children 10 years or older, adjusting for socio-demographic factors. Caregivers reported their child's height, weight, and exposure to nine AFEs; body mass index (BMI) was classified by Center for Disease Control and Prevention's (CDC) guidelines. At Mayo Clinic, we calculated frequencies and weighted estimates of socio-demographic factors and AFEs. Unadjusted and adjusted weighted multinomial logistic regression models were employed to assess the independent associations of each AFE and the different AFE composite scores with BMI category. Exposure to two or more AFEs was independently associated with increased odds of overweight (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.13, 1.56) and obese (OR, 1.45; 95% CI, 1.21, 1.73) status after adjustment for age, household income, parents' education-level, race and sex. Death of parent (OR, 1.59; 95% CI, 1.18, 2.15) and hardship due to family income (OR, 1.26; 95% CI, 1.06, 1.50) were independently associated with obesity status with adjustment for other AFEs and socio-demographic factors. Our results suggest that, in addition to cumulative exposure to AFEs, exposure to certain childhood experiences are more strongly associated with childhood obesity than others. Death of parent and hardship due to family income are individual AFEs, which are strongly predictive of obesity. (C) 2016 Elsevier Inc. All rights reserved.
BackgroundIncreasing evidence supports that mentalization deficits may have a role in the genesis of young age depression; however, few studies examined this issue in clinical populations. MethodsOutpatients aged 14-21, suffering from various psychiatric disorders, were assessed using the Mentalization Questionnaire (MZQ), the Beck Depression Inventory (BDI), and the Childhood Trauma Questionnaire (CTQ), using data from age-matched healthy students for comparison. The relationship between CTQ, MZQ, and BDI scores was examined at the cross-sectional level, including mediation analyses, and longitudinally, in a subsample who underwent a psychotherapy intervention. ResultsOf 83 subjects, 33 (39.8%) had mentalization levels that were 1 standard deviation below those of comparison subjects. In the whole sample, the levels of mentalization were inversely associated with BDI (r=-.68, p<.001) and CTQ scores (r=-.30, p=.006). Moreover, MZQ scores mediated a large part of the effect of childhood trauma on depression (total effect: 10.6, 95% CI: 5.3, 15.9; direct effect: 6.5, 95% CI: 2.1, 10.8; indirect effect: 4.1, 95% CI: 1.5, 7.4). This effect was almost entirely explained by the Affect Regulation subscale. In patients re-evaluated after four sessions (n=37), the decrease in BDI scores correlated with the increase in MZQ scores (r=.40, p=.02). ConclusionsIn a juvenile clinical sample, deficits of mentalization abilities were associated with the severity of depression and explained part of the depressogenic effects of childhood trauma.
Social network sites (SNSs) are relatively new phenomena, and the relationship between SNSs and psychopathology remains unclear. The purpose of this study was to evaluate the type of SNSs depressed adolescents use and the incidence of depressive disclosure on SNSs among them. The study was designed to be cross-sectional. The sample consisted of 53 adolescents diagnosed with depressive disorder, as confirmed by K-SADS-PL, and 55 non-depressed adolescents. The Children's Depression Inventory, Social Anxiety Scale and Social Network Use Questionnaire were administered. The primary finding was that the amount of time spent on the Internet and on SNSs was significantly higher among depressed adolescents than non-depressed adolescents. Additionally, depressed adolescents reported significantly higher disclosure of anhedonia, worthlessness, guilt, loss of concentration, irritability and thoughts of suicide on SNSs. The intensity of the depression sharing was significantly higher in the depressed group. Depressed young people use social networks to express their symptoms. Adolescents' disclosure on social networks may be able to guide relatives, friends and mental health professionals.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) and anxiety are frequently comorbid disorders associated with different types of abnormal performance on neuropsychological tests. Although some studies have shown that comorbid anxiety alters ADHD test performance, results inconsistently show both improvements and worsening of different abilities, with failures to replicate across different anxiety disorders. Alternatively, trait anxiety may reflect a more stable influence on ADHD test performance than various diagnosable anxiety disorders. Method: To better understand the possible enhancing or deleterious effects of anxiety on ADHD cognitive impairments, this study examined the effect of individual differences in trait anxiety measured by the Multidimensional Anxiety Scale for Children (MASC) on a battery of computerized, rapid-performance tests measuring attention and impulsivity-related performance in 98 Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Combined-Subtype ADHD adolescents and 123 healthy controls. It was hypothesized that trait anxiety would attenuate response inhibition and attention deficits in ADHD. Results: ADHD-diagnosed adolescents with higher trait anxiety performed better on indices of sustained attention, reaction time, and motor variability, and had altered overall test-performance strategy, while response inhibition was affected in both ADHD and non-ADHD. Conclusions: This study provides the first evidence that pathological levels of anxiety are not needed to see differences in ADHD neuropsychological test performance. Instead, mildly elevated trait anxiety confers a protective influence by reducing the degree of impairment seen in ADHD. These findings suggest that better performing ADHD adolescents might have optimized levels of cortical arousal, and raise new questions about how best to identify the neurobiological substrates responsible for the beneficial effects.
BackgroundNeglect is often overlooked in adolescence, due in part to assumptions about autonomy and misinterpretation of behaviors being part of normal adolescent development. Emotional maltreatment (abuse or neglect) has a damaging effect throughout the lifespan, but is rarely recognized amongst adolescents. Our review aims to identify features that adolescents experiencing neglect and/ or emotional maltreatment report. MethodA rapid review methodology searched 8 databases (1990-2014), supplemented by hand searching journals, and references, identifying 2,568 abstracts. Two independent reviews were undertaken of 279 articles, by trained reviewers, using standardised critical appraisal. Eligible studies: primary studies of children aged 13-17 years, with substantiated neglect and/ or emotional maltreatment, containing self-reported features. Results19 publications from 13 studies were included, demonstrating associations between both neglect and emotional maltreatment with internalising features (9 studies) including depression, post traumatic symptomatology and anxiety; emotional maltreatment was associated with suicidal ideation, while neglect was not (1 study); neglect was associated with alcohol related problems (3 studies), substance misuse (2 studies), delinquency for boys (1 study), teenage pregnancy (1 study), and general victimization for girls (1 study), while emotionally maltreated girls reported more externalising symptoms (1 study). Dating violence victimization was associated with neglect and emotional maltreatment (2 studies), while emotional abuse of boys, but not neglect, was associated with dating violence perpetration (1 study), and neither neglect nor emotional maltreatment had an association with low self-esteem (2 studies). Neither neglect nor emotional maltreatment had an effect on school performance (1 study), but neglected boys showed greater school engagement than neglected girls (1 study). ConclusionsIf asked, neglected or emotionally maltreated adolescents describe significant difficulties with their mental health, social relationships, and alcohol or substance misuse. Practitioners working with youths who exhibit these features should recognize the detrimental impact of maltreatment at this developmental stage, and identify whether maltreatment is a contributory factor that should be addressed.
Background: Rumination predicts depression in adults and adolescents. The development of rumination has been linked to parenting practices, but only limited research has investigated this and research has tended to rely on self-report parenting measures. Aims: To investigate the relationship between female adolescent rumination and maternal modelling, criticism and positivity using an observational measure of parental behaviour. Method: A cross-sectional design was used. Daughters aged 16-18 years and their mothers (n = 154 dyads) completed questionnaire measures of rumination and affect. Mothers of girls with rumination scores in the upper and lower quartile (both n = 26) also completed the Five Minute Speech Sample, which was used to measure maternal criticism and positivity. Results: Mothers of low rumination girls made significantly more positive comments about their daughters than the mothers of high ruminators. Mothers made very few critical comments. Self-reported rumination was not correlated in mothers and daughters, suggesting a lack of support for the potential role of modelling. Conclusion: Overall, low maternal positivity was associated with rumination in female adolescents. There was no evidence that maternal rumination or criticism were associated with adolescent rumination. The results suggest a number of implications for future research, including the need for prospective longitudinal studies using observational parenting measures.
An Internet-based relapse prevention supplement to adolescent substance abuse treatment programming is a promising modality to reinforce treatment gains and enhance recovery; however, an evidence base is lacking. To assess the efficacy of the online Navigating my Journey (NmJ) program. 129 adolescent-aged participants (ages 13-23) receiving substance abuse treatment participated in a randomized parallel group study comparing two conditions: experimental (NmJ) versus attention control (viewed wellness articles from the Nemours Foundation at their discretion). Participants in the experimental condition were asked to complete 12 core lessons over 3 months. Lesson content was developed to teach evidence-based relapse prevention skills. Data were collected at four time points: baseline, 1-month follow up, 3-month follow up, and 6-month follow up. We used a linear mixed modeling approach to test for differences between conditions on each outcome. Participants in the experimental condition reported a significantly greater increase in motivation to reduce or not misuse drugs from baseline to 3-month follow up and from baseline to 6-month follow up, compared to the control participants. Participants in the experimental condition also reported a greater decrease in drug use score from baseline to 3-month follow up, compared to the control participants. An analysis of age as a potential moderator suggested that the intervention may be more effective for older adolescents. Greater use of the program was associated with greater self-efficacy and lower self-reported substance use over time. Relapse prevention treatment with adolescents may be facilitated by theory-based online interventions. NCT02125539.
Carotenoids are plant secondary metabolites that comprise two main groups: carotenes and xanthophylls. The latter group includes zeaxanthin which is synthesized by beta-carotene hydroxylase catalyzing the hydroxylation of the beta-rings of beta-carotene molecules. To develop tools to alter carotenoid biosynthesis in plants, we isolated a cDNA clone encoding a candidate beta-carotene hydroxylase, CrtH1, from the flower petals of Adonis aestivalis. CrtH1 protein has homology to beta-carotene hydroxylases from other organisms, and possesses the four histidine motifs conserved in this family of enzymes. Sequence analysis predicted the presence of a putative plastid transit peptide at the amino terminus and four transmembrane helical regions. Southern-blot analysis showed CrtH1 to be encoded by a multicopy gene family with at least three members in A. aestivalis. Analysis of CrtH1 transcript abundance by Northern blotting indicates it is highly expressed in flower petals, roots and stems, with relatively low expression in leaves and developing seeds. CrtH1 was able to catalyze the formation of zeaxanthin and its intermediate precursor beta-cryptoxanthin from beta-carotene in functional assays conducted in E. coli. Expression of CrtH1 in Arabidopsis thaliana wild type and a mutant deficient for endogenous beta-carotene hydroxylases enhanced the biosynthesis of violaxanthin in the seeds.
The cDNA AmphiARF , encoding a novel member of ARF family was for the first time identified from the gut cDNA library of amphioxus Branchiostoma becheri tsingtauense . The deduced amino acid sequence includes the motifs involved in GTP binding (DVGG, NKQD and SAK) and hydrolysis (GXDXXGK), and a glycine at position 2 for N-terminal myristoylation, which are all characteristic of ARFs. However, it has a 46 amino acid C-terminal extension (positions 183-227), which was not found in any ARF family previously described including ARF-like proteins. This suggests that AmphiARF is a new member of ARF family, which was also supported by the phylogenetic analysis. It is highly likely that the extended C-terminal of AmphiARF is a novel addition occurring after cephalochordate/vertebrate split. Northern blotting analysis revealed that AmphiARF transcript was present in all tissues examined, consistent with the involvement of ARFs in the fundamental role like vesicular trafficking of proteins.
In whole cell patch-clamp recordings, we characterized the L-type Ca2+ currents in bovine adrenal zona fasciculata (AZF) cells and explored their role, along with the role of T-type channels, in ACTH- and angiotensin II (ANG II)-stimulated cortisol secretion. Two distinct dihydropyridine-sensitive L-type currents were identified, both of which were activated at relatively hyperpolarized potentials. One activated with rapid kinetics and, in conjunction with Northern blotting and PCR, was determined to be Ca(v)1.3. The other, expressed in approximately one-half of AZF cells, activated with extremely slow voltage-dependent kinetics and combined properties not previously reported for an L-type Ca2+ channel. The T-type Ca2+ channel antagonist 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2) inhibited Ca(v)3.2 current in these cells, as well as ACTH- and ANG II-stimulated cortisol secretion, at concentrations that did not affect L-type currents. In contrast, nifedipine specifically inhibited L-type currents and cortisol secretion, but less effectively than TTA-P2. Diphenylbutylpiperidine Ca2+ antagonists, including pimozide, penfluridol, and fluspirilene, and the dihydropyridine niguldipine blocked Ca(v)3.2 and L-type currents and inhibited ACTH-stimulated cortisol secretion with similar potency. This study shows that bovine AZF cells express three Ca2+ channels, the voltage-dependent gating and kinetics of which could orchestrate complex mechanisms linking peptide hormone receptors to cortisol secretion through action potentials or sustained depolarization. The function of the novel, slowly activating L-type channel is of particular interest in this respect. Regardless, the well-correlated selective inhibition of T- and L-type currents and ACTH- and ANG II-stimulated cortisol secretion by TTA-P2 and nifedipine establish the critical importance of these channels in AZF cell physiology.
Background Although it has been well established that atrial natriuretic peptide gene-disrupted (ANPS(-/-)) mice are a useful model of salt-sensitive hypertension, surprisingly little is known about the control of their intrarenal renin-angiotensin system (RAS) and pressure-natriuresis mechanism, key components in blood pressure, fluid and electrolyte regulation. The aim of this study was to determine whether ANP disruption results in changes in the renal and adrenal local RAS and the acute pressure natriuresis mechanism. Methods Renal and adrenal renin, angiotensin type 1 (AT(1))((A and B)) and angiotensin type 2 (AT(2)) receptor messenger RNA expression levels were determined by northern blotting or real time reverse transcriptase polymerase chain reaction. Plasma aldosterone and renal and adrenal angiotensin II peptide levels were determined by radioimmunoassay. To examine the acute pressure natriuresis response, changes in renal interstitial hydrostatic pressure (RIHP) were assessed after manipulations of renal arterial pressure (RAP) in anaesthetized mice. Results Renal and adrenal renin mRNA and angiotensin II levels were lower in ANPS(-/-) and (+/-) mice compared with (+/+) mice. ANP(-/-) mice also had greater renal AT(1A) and adrenal AT2 mRNA levels compared with the other genotypes. RAP and RIHP were significantly higher in (-/-) mice compared with (+/+) mice. Furthermore, there was a blunted slope of the RAP-RIHP relationship after increases in RAP in ANP(-/-) mice. Conclusion These data indicate that ANP disruption results in a blunting of the dynamic properties of the acute pressure-natriuresis mechanism at increased levels of RAP, as well as a reduced expression of renal and adrenal local RAS.
Background: Anaphylaxis is a life-threatening emergency of which reliable epidemiological data are lacking. This study aimed to analyze how quickly patients presenting with anaphylaxis were treated in emergency and whether treatment followed the European Academy of Allergy and Clinical Immunology (EAACI) guidelines. Methods: Patient data were collected between April 2009 and April 2013. Emergency doctors completed a questionnaire for adult patients presenting at the emergency department (ED) of the St. Pierre hospital in Brussels with anaphylaxis. Inclusion criteria were based on the Sampson criteria of anaphylaxis. Data were analyzed using a Microsoft Excel database. Results: About 0.04% (100/230878) of all emergency visits in adults presented with anaphylaxis. 64% of patients received their first medical help later than 30 min after symptom onset. 67% of patients received adrenaline, 85% oral antihistamines, and 89% received IV glucocorticosteroids. 46/100 patients were discharged directly from the ED, of which 87% received further medical prescriptions for self-administration: 67% corticosteroids, 83% antihistamines, and 9% intramuscular adrenaline. 74% were instructed to consult an allergologist for adequate diagnosis. 54/100 patients were hospitalized. Conclusion: The majority of patients were treated according to the EAACI guidelines for management of anaphylaxis, but only a minority received the recommended adrenaline auto-injector for self-administration at discharge. Because the majority of patients received medical help later than 30 min after symptom onset, adrenaline auto-injector prescription is a necessity. The low rate of doctors prescribing adrenaline auto-injectors in the ED setting underlines the need to train doctors of various backgrounds in prevention and treatment of anaphylaxis and the close collaboration with allergologists.
BACKGROUND: Allergy immunotherapy can result in systemic allergic reactions and even life-threatening anaphylaxis requiring epinephrine administration. OBJECTIVE: The objective of this study was to describe epinephrine use in the clinical trial development programs of 3 rapidly dissolving sublingual immunotherapy tablets (SLITtablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Horsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan). METHODS: Data on epinephrine use were collected from 13 timothy grass SLIT-tablet trials (MK-7243; <= 2800 bioequivalent allergen units/75,000 SQ-T dose, n =2497; placebo, n = 2139), 5 short ragweed SLIT-tablet trials (MK-3641; <= 12 Amb a 1-U, n =1725; placebo, n =770), and 11 house dust mite (HDM) SLIT-tablet trials (MK-8237; <= 12 SQ-HDM; n=3930; placebo, n =2246). RESULTS: In grass SLIT-tablet trials, epinephrine was used 13 times (grass SLIT-tablet, n =10; placebo, n =3). Eight administrations were for grass SLIT-tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was used 9 times in 8 subjects (ragweed SLIT-tablet, n =7; placebo, n =1 =2 administrations for protracted anaphylaxis]). Four administrations were for ragweed SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was administered 13 times (HDM SLIT-tablet, n =8; placebo, n =5). Four administrations were for HDM SLITtablet- related AEs: 1 for systemic allergic reaction and 3 for local events. Of the 16 epinephrine administrations for events related to SLIT-tablet treatment, 11 occurred within the first week of treatment (7 administrations on day 1) and 5 were subject self-administered. CONCLUSIONS: Epinephrine administrations in response to SLIT-tablet-related reactions in clinical trials are uncommon, typically occur within the first week of treatment, and are rarely self-administered. All SLIT-tablet-related events treated with epinephrine were nonserious. (C) 2016 American Academy of Allergy, Asthma & Immunology
3 beta-Hydroxysteroid dehydrogenase type II deficiency (3 beta HSD2) congenital adrenal hyperplasia is a rare cause of ambiguous genitalia, resulting in abnormal virilisation in both 46XY and 46XX. We describe a case of 46XY ambiguous genitalia that was misdiagnosed as androgen insensitivity syndrome. The correct diagnosis was made after adrenarche. Genotyping demonstrated compound heterozygosity in two alleles, the previously described c.244G >A (p.Ala82Thr), and a novel 931C >.T(p. Gln311*) variant. We suggest that adrenarche unmasked the condition by driving cortisol production to rates that caused the mutant 3bHSD2 enzyme to become rate limiting for cortisol production. This case illustrates how markedly different the effects of this condition may be on androgen production compared with glucocorticoid and mineralocorticoid production. It also demonstrates how current guidelines based on urinary steroids and cortisol sufficiency may not arrive at the correct diagnosis, and underlines the importance of gene testing in the work-up of disorders of sexual differentiation.
Background: Attachment anxiety and avoidance have been found to be associated with worry. A substantial body of research suggests that intolerance of uncertainty (IOU) is a phenomenon which predicts level of worry, yet the relationship between attachment, IOU and worry remains to be investigated. Methods: The present study recruited 281 participants from the community within Australia to complete an online survey incorporating the Intolerance of Uncertainty Scale, the Experiences in Close Relationships Scale-Revised, and the Penn State Worry Questionnaire. Results: The analyses revealed attachment anxiety and attachment avoidance were positively correlated with IOU, and that attachment anxiety, attachment avoidance and IOU were positively correlated with worry. Furthermore, IOU was found to mediate the relationship between attachment anxiety and worry, even when attachment avoidance was entered as a covariate. By contrast, for the relationship between attachment avoidance and worry, intolerance of uncertainty only mediated the association if attachment anxiety was ignored. Conclusions: The results of the study suggest that IOU may play a key role in the relationship between adult attachment difficulties and the experience of worry. These findings may have significant implications for the conceptualisation and psychological treatment of attachment related difficulties. (C) 2017 Elsevier Ltd. All rights reserved.
Context: Psychosocial factors can impact lung transplant outcomes. However, it is currently unknown whether abuse survivorship influences lung transplant survival. Objective: To characterize the abuse history of adult lung transplant patients and determine whether such history is associated with mortality. Patients and Other Participants: Adult lung transplant recipients evaluated from 2000 to 2004. Main Outcome Measures: The main outcome was post-lung transplantation survival. The secondary outcomes included demographic, transplantation, or psychological assessment differences between those with a history of abuse survivorship and those without. Results: Thirty-three lung transplant recipients (35.5% male, median age: 55 years) were included. A history of abuse survivorship was common (24.2%) and was associated with decreased survival following lung transplantation (P = .003). There was no difference in sex, marital status, or smoking history between abuse survivors and those who denied being the victim of abuse. Abuse survivors had a higher Personality Assessment Screener total score, a measure of maladaptive personality traits (P = .02). Conclusion: Abuse survivorship is common in lung transplant patients and associated with increased posttransplant mortality and increased maladaptive personality traits. This preliminary evidence suggests that lung transplant patients should be screened for abuse history and provided with appropriate treatment of survivorship issues to potentially improve their health outcomes from transplantation.
Background: Symptom clusters have not previously been explored among individuals with atrial fibrillation of any type. Objective: The purpose of this study is to determine the number of symptom clusters present among adults with chronic atrial fibrillation and to explore sociodemographic and clinical factors potentially associated with cluster membership. Methods: This was a cross-sectional secondary data analysis of 335 Australian community-dwelling adults with chronic (recurrent paroxysmal, persistent, or permanent) atrial fibrillation. We used self-reported symptoms and agglomerative hierarchical cluster analysis to determine the number and content of symptom clusters present. Results: There were slightly more male (52%) than female participants, with a mean (SD) age of 72 (11.25) years. Three symptom clusters were evident, including a vagal cluster (nausea and diaphoresis), a tired cluster (fatigue/lethargy, weakness, syncope/dizziness, and dyspnea/breathlessness), and a heart cluster (chest pain/discomfort and palpitations/fluttering). We compared patient characteristics among those with all the symptoms in the cluster, those with some of the symptoms in the cluster, and those with none of the symptoms in the cluster. The only statistically significant differences were in age, gender, and the use of antiarrhythmic medications for the heart cluster. Women were more likely to have the heart symptom cluster than men were. Individuals with all of the symptoms in the heart cluster were younger (69.6 vs 73.7 years; P = .029) than those with none of the symptoms in the heart cluster and were more likely to be on antiarrhythmic medications. Conclusion: Three unique atrial fibrillation symptom clusters were identified in this study population.
This review discusses the unmet needs of patients with attention deficit/hyperactivity disorder (ADHD) who are transitioning into adulthood. Although awareness and recognition of ADHD in children, adolescents, and adults have improved in recent years, there is often an interruption in management of the disorder when adolescent patients transition to adult health care services. This review has the following objectives: (1) to identify key issues patients with ADHD (with or without an early diagnosis) face during transition into adulthood; (2) to review the current clinical practice and country-specific approaches to the management of the transition into adulthood for patients with ADHD; (3) to discuss challenges facing clinicians and their patients when drug treatment for ADHD is initiated; (4) to review current ADHD guidelines on transition management in Hong Kong, Singapore, South Korea, Turkey, and Africa; and (5) to examine economic consequences associated with ADHD. The review suggests that the transition period to adult ADHD may be an underresearched and underserved area. The transition period plays an important role regarding how ADHD symptoms may be perceived and acted upon by adult psychiatrists. Further studies are needed to explore the characteristics of the transition period. If only a fraction of adolescents go on to have mental disorders during adulthood, especially ADHD, it is crucial to identify their characteristics to target appropriate interventions at the beginning of the course of illness. There continues to be low recognition of adult ADHD and a severe lack of medical services equipped to diagnose and care for patients with ADHD transitioning from child to adult services.
Recent studies have examined non-suicidal self-injury in community and clinical samples, but there is no published research on non-suicidal self-injury in individuals with autism spectrum disorder. This lack of research is surprising, since individuals with autism spectrum disorder have high rates of risk factors for non-suicidal self-injury, including depression and poor emotion regulation skills. Using an online survey, we examined non-suicidal self-injury methods, frequency, severity, functions, and initial motivations in adults with autism spectrum disorder (n=42). We also compared their non-suicidal self-injury characteristics to those of a gender-matched group of adults without autism spectrum disorder (n=42). Of the participants with autism spectrum disorder, 50% reported a history of non-suicidal self-injury. This proportion is higher than non-suicidal self-injury rates previously reported for college students, adult community samples, and adolescents with autism spectrum disorder, which suggests that adults with autism spectrum disorder have increased risk for engaging in non-suicidal self-injury. Women with autism spectrum disorder were significantly more likely to endorse non-suicidal self-injury, relative to men with autism spectrum disorder. A history of non-suicidal self-injury was not related to current depression or emotion dysregulation for the participants with autism spectrum disorder. Non-suicidal self-injury characteristics among the adults with autism spectrum disorder were similar to non-suicidal self-injury in adults without autism spectrum disorder. These preliminary findings highlight the need for increased awareness and further research about non-suicidal self-injury within autism spectrum disorder.
Field programmable gate arrays (FPGAs) have established themselves as one of the preferred digital implementation platforms in a plethora of current industrial applications, and extensions and improvements are still continuously being included in the devices. This paper reviews recent advancements in FPGA technology, emphasizing the novel features that may significantly contribute to the development of more efficient digital systems for industrial applications. Special attention is paid to the design paradigm shift caused by the availability of increasingly powerful embedded (and soft) processors, which transformed FPGAs from hardware accelerators to very powerful system-on-chip (SoC) platforms. New analog resources, floating-point operators, and hard memory controllers are also described, because of the great advantages they provide to designers. Software tools are being strongly influenced by the design paradigm shift, which requires fromthem a much better support for software developers. Focusing mainly on this issue, recent advancements in software resources [intellectual property (IP) cores and design tools] are also reviewed. The impact of new FPGA features in industrial applications is analyzed in detail in three main areas, namely digital real-time simulation, advanced control techniques, and electronic instrumentation, with focus on mechatronics, robotics, and power systems design. The way digital systems are being currently designed in these areas is comprehensively reviewed, and a critical analysis of how they could significantly benefit from new FPGA features is presented.
Research documents how exposure to adversity in childhood leads to negative health outcomes across the lifespan. Less is known about protective factors - aspects of the individual, family, and community that promote good health despite exposure to adversity. Guided by the Resilience Portfolio Model, this study examined protective factors associated with physical health in a sample of adolescents and adults exposed to high levels of adversity including child abuse. A rural community sample of 2565 individuals with average age of 30 participated in surveys via computer assisted software. Participants completed self-report measures of physical health, adversity, and a range of protective factors drawn from research on resilience. Participants reporting a greater burden of childhood victimization and current financial strain (but not other adverse life events) had poorer physical health, but those with strengths in emotion regulation, meaning making, community support, social support, and practicing forgiveness reported better health. As hypothesized, strengths across resilience portfolio domains (regulatory, meaning making, and interpersonal) had independent, positive associations with health related quality of life after accounting for participants' exposure to adversity. Prevention and intervention efforts for child maltreatment should focus on bolstering a portfolio of strengths. The foundation of the work needs to begin with families early in the lifespan. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Given growing numbers of older adults with mental and substance use disorders (MSUDs), this study examined the association between ten types of adverse childhood experiences (ACEs) and lifetime MSUDs among those aged 50+. Methods: Data (N=14,738 for the 50+ age group) came from the 2012 to 2013 National Epidemiologic Survey on Alcohol and Related Conditions. Using multivariable binary logistic regression analyses, we examined relationships between ten ACEs and six lifetime MSUDs (major depressive disorder (MDD) and anxiety, post-traumatic stress, alcohol use, drug use, and nicotine use disorders). Gender differences were examined using tests of interaction effects and gender-separate logistic regression models. Results: Of the sample, 53.2% of women and 50.0% of men reported at least one ACE. For both genders, parental/other adult's substance abuse was the most prevalent (22.6%), followed by physical abuse, and emotional neglect. Child abuse and neglect and parental/other adult's mental illness and substance abuse had small but consistently significant associations with MSUDs (e.g., odds ratio = 1.28, 95% CI= 1.12-1.46 for parental/other adult's substance misuse and MDD). Although the relationship between total number of ACEs andMSUDs was cumulative for both men and women, the associations of physical abuse, sexual abuse, emotional neglect, and parental separation/divorce with MSUDs were stronger among men. Conclusions: This study underscores the significant yet modest association between ACEs and lifetime MSUDs in late life. More research is needed to investigate why ACEs seem to have greater effects on older men and to discern the sources of gender differences in ACEs' effects.
Background: Adverse childhood experiences (ACEs) have been associated with an increased risk of a variety of diseases, including cancer. However, research has largely ignored how ACEs impact cancer screening, a potential intermediate outcome. As such, the present study examined the association between ACEs and ever and recent use of Papanicolaou (Pap) test, among women aged 21 and older. Materials and Methods: Analyses used the 2009 Tennessee Behavioral Risk Factor Surveillance System (n = 1527) to model odds of ever and recently (within the last 3 years) engaging in Pap tests screening from nine different adversities. Bivariate and multivariate logistic regression models were run to accomplish this. Results: In bivariate and multivariate models, living in a household in which adults treated each other violently increased odds of ever receiving a Pap test. In bivariate models, physical and sexual abuse was associated with decreased odds of receiving a recent Pap test. After accounting for confounders, only the latter association remained significant. Conclusions: Results highlight a potential mechanism by which early childhood experiences can impact the development of cervical cancer. Providers of care should consider modifications to their screening practices, including screening for child abuse, to better serve all women.
Substantial research shows that early adversity, including child abuse and neglect, is associated with diminished health across the life course and across generations. Less well understood is the relationship between early adversity and adult socioeconomic status, including education, employment, and income. Collectively, these outcomes provide an indication of overall life opportunity. We analyzed data from 10 states and the District of Columbia that used the adverse childhood experiences (ACE) module in the 2010 Behavioral Risk Factor Surveillance System to examine the association between ACEs and adult education, employment, and income. Compared to participants with no ACEs, those with higher ACE scores were more likely to report high school non-completion, unemployment, and living in a household below the federal poverty level. This evidence suggests that preventing early adversity may impact health and life opportunities that reverberate across generations. Current efforts to prevent early adversity might be more successful if they broaden public and professional understanding (i.e., the narrative) of the links between early adversity and poverty. We discuss our findings within the context of structural policies and processes that may further contribute to the intergenerational continuity of child abuse and neglect and poverty. (C) 2016 The Authors. Published by Elsevier Ltd.
Adverse childhood experiences (ACEs) have been linked to increased use of tobacco products later in life. However, studies to date have ignored smokeless tobacco products. To address this, data from the 2011 Behavioral Risk Factor Surveillance System, which interviewed adults 18 years and over (N = 102,716) were analyzed. Logistic regression models were fit to estimate odds ratios of ever smoking, current smoking and current smokeless tobacco use in relation to ACEs. Results showed that less than 4 % of respondents currently used smokeless tobacco products, while 44.95 and 18.57 % reported ever and current smoking, respectively. Physical abuse (OR 1.40; 95 % CI 1.14, 1.72), emotional abuse (OR 1.41; 95 % CI 1.19, 1.67), sexual abuse (OR 0.70; 95 % CI 0.51, 0.95), living with a drug user (OR 1.50; 95 % CI 1.17, 1.93), living with someone who was jailed (OR 1.50; 95 % CI 1.11, 2.02) and having parents who were separated or divorced (OR 1.31; 95 % CI 1.09, 1.57) were associated with smokeless tobacco use in unadjusted models. After accounting for confounders, physical abuse (OR 1.43; 95 % CI 1.16, 1.78), emotional abuse (OR 1.32; 95 % CI 1.10, 1.57), living with a problem drinker (OR 1.30; 95 % CI 1.08, 1.58), living with a drug user (OR 1.31; 95 % CI 1.00, 1.72) and living with adults who treated each other violently (OR 1.30; 95 % CI 1.05, 1.62) were associated with smokeless tobacco use. Living with someone who was mentally ill (OR 0.70; 95 % CI 0.53, 0.92) was associated with smokeless tobacco use after accounting for confounders and all ACEs. Results indicated that some childhood adversities are associated with use of smokeless tobacco products. Special attention is needed to prevent tobacco use of different types among those experiencing ACEs.
Objective: To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register (www.ukaed.info). Methods: Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile (LAEP). Results: The number of seizure-free patients in the last 4 weeks was overall CBZ/VPA /LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/VPA/LTG/LEV=59%/71%/67%/57%. Mean LAEP scores were CBZ/VPA/LTG/LEV/CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly higher in patients reporting depression and in patients with active epilepsy than in patients without depression and remission. Central nervous system (CNS) adverse effects including memory problems, difficulty concentrating, depression, unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of anger was significantly more frequent in LEV, and depression was significantly more frequent in CBZ compared to the other drugs. Conclusion: In this Internet-based register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were similar. Self-reported CNS adverse effects were significantly more frequent than in controls. In addition, anger was associated with LEV and depression with CBZ. Confounding factors were depression and uncontrolled epilepsy.
Background: Aeluropus lagopoides is a salt and drought tolerant grass from Poaceae family, distributed widely in arid regions. There is almost no information about the genetics or genome of this close relative of wheat that stands harsh conditions of deserts. Objectives: The main aim of this research was to isolation and characterization of salt and drought inducible genes from A. lagopoides by Differential Display Amplified fragment length polymorphism (DD-AFLP) method. Material and Methods: In this research A. lagopoides was grown under salt or drought conditions and after modifying the DD-AFLP method several fragments were isolated and after nomination their induction was studied by reverse northern blotting. Results: DD-AFLP led to the improvement of a non-radioactive method for which many parameters were optimized. Having screened approximately 1600 transcript-derived fragments, 1.4 percent of them showed varied expression levels in response to high salt or drought treatments. The relative abundance of twenty one selected differentially expressed fragments was inspected by reverse northern blotting that affirmed the potential of this applied method. Sequence comparisons revealed that some of the isolated genes are involved in osmotic adjustment, regulation of transcription, cation transportation and stress responses. These data clearly show that the modified DD-AFLP method was a successful and reliable approach for the isolation of differentially expressed genes.
We had previously reported that Vibrio hollisae produces aerobactin in response to iron starvation. In the present study, we identified in V hollisae ATCC33564 the aerobactin system cluster which consists of eight genes, hatCDB, iucABCD and iutA. The hatCDB genes encode proteins homologous to components of bacterial ATP binding cassette transport systems for ferric aerobactin. The iucABCD and iutA orthologs code for aerobactin biosynthesis enzymes and the ferric aerobactin receptor, respectively. In accordance with their iron-regulated expression, putative Fur box sequences were found within the respective promoter regions of hatC, iucA and iutA. The monocistronic iutA transcript was detected by northern blotting. Moreover, phenotypic comparison between the wild-type strain and its targeted gene disruptants supported the biological functions that were expected for the respective operons and genes on the basis of the homology search. The arrangement of the aerobactin gene clusters thus far found in Vibrio and enterobacterial species was compared and discussed from an evolutionary point of view. (c) 2006 Elsevier SAS. All rights reserved.
Active Electronically Scanned Array (AESA) technology will enable next generation radars achieve better jamming resistance capability and low probability of intercept by spreading their emissions over a wide frequency range. These radars systems consist of a large number of transmit/receive modules (TRMs) which are electronically scanned in a tight time-synchronized manner. This requires digital control to move closer to the radio front end on the antennas. Other emerging technologies, such as cognitive radars and MIMO radars, will continue to drive the need for complex timing, synchronization, and high mix RF and digital measurement requirements. To meet these challenges, radar engineers will need a platform based approach which delivers capabilities such as multi-channel phase aligned measurements over wide bandwidths and high-throughput streaming. This paper discusses the fundamentals of AESA radars and trends in radar systems. It analyzes the impact of these trends on test system architecture and explains how the advances in PXI modular instrumentation can meet these challenging requirements.
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
ObjectiveThe aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2-year follow-up, and which subtype of affect lability was associated with suicidal ideation. MethodA total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2-year follow-up. Affect lability was assessed by the French version of the Affect Lability Scale. ResultsBipolar patients with high affect lability were more likely to report suicidal ideation during follow-up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation. ConclusionReducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.
Objective: To examine the association between gestational age (GA) at birth across the normal GA spectrum (37-41 weeks) and the temperament and health of 3-month old infants.Methods: The sample comprised 242 low-risk mothers and infants without chronic illnesses or severe pregnancy complications. Infant temperament was defined by three constructs: Negative Affectivity (NA), Extraversion, and Regulation, assessed by parents' reports on the Infant Behavior Questionnaire. Infants' health was defined as the number of nonroutine doctors' visits attended by the infants since their release from the hospital after birth. Analyses employed a continuous measure of GA to assess outcomes across GAs and a categorical measure (37, 38, 39-41 weeks GA) to examine contrasts.Results: Extraversion was positively related to GA primarily due to the lower scores of infants born at 37 weeks compared to infants born at 39-41 weeks GA. NA showed a similar effect. The odds of infants born at 37 weeks attending a nonroutine medical visit were 2.8 times that of infants born full-term.Discussion: Infants born at 37 weeks GA express less affect and use more nonroutine medical services than do infants born at 39-41 weeks GA. The findings underscore the importance of considering the risks of pregnancy prolongation with the developmental risk associated with early-term delivery.
Background: The ability to recognize emotional expression is essential for social interactions, adapting to the environment, and quality of life. Emotion recognition is impaired in people with Alzheimer's disease (AD), thus rehabilitation of these skills has the potential to elicit significant benefits. Objective: This study sought to establish whether emotion recognition capacity could be rehabilitated in people with AD. Methods: Thirty-six participants with AD were assigned to one of three conditions: an experimental group (EG) that received 20 sessions of rehabilitation of emotion recognition and 20 sessions of cognitive stimulation therapy (CST), a control group (CG) that received 40 sessions of CST, and a treatment as usual group (TAU). Results: A positive treatment effect favoring the EG was found; participants were better able to correctly identify emotions (p = 0.021), made fewer errors of commission (p = 0.002), had greater precision of processing (p = 0.021), and faster processing speed (p = 0.001). Specifically, the EG were better able to identify sadness (p = 0.016), disgust (p = 0.005), and the neutral expression (p = 0.014), with quicker processing speed for disgust (p = 0.002). These gains were maintained at one month follow-up with the exception of processing speed for surprise, which improved. Conclusion: Capacity to recognize facial expressions of emotions can be improved through specific rehabilitation in people with AD, and gains are still present at a one month follow up. These findings have implications for the design of rehabilitation techniques for people with AD that may lead to improved quality of life and social interactions for this population.
In response to Palermo (2016, Australian Psychologist, in press) comments, some aspects of the target paper are further elaborated here. In particular, given Palermo's timely emphasis on the potential social and cultural implications of research demonstrating the beneficial consequences of negative affect, the historical background, and practical implications of the experimental evidence are elaborated. Furthermore, the reviewer also comments on the applicability of alternative theoretical conceptualizations to the data reported here, and this issue also receives further attention. Overall, it is concluded that there is now strong and convergent evidence for the often beneficial consequences of mild negative affect, and these findings deserve serious consideration in practical applications of psychology, and in our conceptions of what represents a healthy and balanced emotional life. Embracing and accepting periods of negative affectivity should be recognised as a normal and healthy part of the human condition, and the cultural bias towards positive affect should be tempered by an appreciation of the adaptive benefits of dysphoria.
The subtle relationship between feeling and thinking, affect and cognition has fascinated philosophers and writers since time immemorial, yet, empirical research on this topic was relatively neglected by psychologists until recently. There have been many claims emphasising the beneficial cognitive and behavioural consequences of positive affect. Many recent works suggest that negative affect may also facilitate optimal performance in many situations, consistent with evolutionary theories suggesting the adaptive signalling function of various affective states. This paper reviews traditional and current psychological theories linking affect to social thinking and behaviour. A variety of empirical studies from our laboratory will also be presented, demonstrating that in many situations, negative affect promotes optimal performance in cognitive and social tasks, including tasks such as memory, social judgements, motivation, and strategic interpersonal behaviours. These results will be interpreted in terms of a dual-process theory that predicts that negative affect promotes a more accommodative, vigilant, and externally focused thinking strategy. The relevance of these findings for recent affect-cognition theories will be discussed, and the practical implications of negative affect promoting improved social thinking and performance in a number of applied fields will be considered.
Background: One in twenty-five people suffer from a mood disorder. Current treatments are sub-optimal with poor patient response and uncertain modes-of-action. There is thus a need to better understand underlying mechanisms that determine mood, and how these go wrong in affective disorders. Systems biology approaches have yielded important biological discoveries for other complex diseases such as cancer, and their potential in affective disorders will be reviewed. Scope of review: This review will provide a general background to affective disorders, plus an outline of experimental and computational systems biology. The current application of these approaches in understanding affective disorders will be considered, and future recommendations made. Major conclusions: Experimental systems biology has been applied to the study of affective disorders, especially at the genome and transcriptomic levels. However, data generation has been slowed by a lack of human tissue or suitable animal models. At present, computational systems biology has only be applied to understanding affective disorders on a few occasions. These studies provide sufficient novel biological insight to motivate further use of computational biology in this field. General significance: In common with many complex diseases much time and money has been spent on the generation of large-scale experimental datasets. The next step is to use the emerging computational approaches, predominantly developed in the field of oncology, to leverage the most biological insight from these datasets. This will lead to the critical breakthroughs required for more effective diagnosis, stratification and treatment of affective disorders. (C) 2016 Elsevier B.V. All rights reserved.
Individuals can apply different processing strategies to deal with situations they encounter. One central question in social-cognition research refers to the factors that determine reliance on different processing strategies. Parting from a functional perspective, which holds that processing strategies need to be adjusted to the requirements of the situation, we argue that individuals' mood carries information about the benign versus problematic nature of the situation and thus that mood can regulate cognitive processing. Focusing on mental abstraction, we propose that positive mood contributes to a processing style characterized by reliance on prior knowledge in the form of general knowledge structures, whereas negative mood elicits a processing style characterized by attention to details and consideration of new situation-specific information.
Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV-1 infection are extraordinarily mutated. One goal of HIV-1 vaccine development is to induce antibodies that are similar to the most potent and broad BNAbs isolated from infected subjects. The most effective BNAbs have very high mutation frequencies, indicative of the long periods of continual activation necessary to acquire the BNAb phenotype through affinity maturation. Understanding the mutational patterns that define the maturation pathways in BNAb development is critical to vaccine design efforts to recapitulate through vaccination the successful routes to neutralization breadth and potency that have occurred in natural infection. Studying the mutational changes that occur during affinity maturation, however, requires accurate partitioning of sequence data into B-cell clones and identification of the starting point of a B-cell clonal lineage, the initial V(D)J rearrangement. Here, we describe the statistical framework we have used to perform these tasks. Through the recent advancement of these and similar computational methods, many HIV-1 ancestral antibodies have been inferred, synthesized and their structures determined. This has allowed, for the first time, the investigation of the structural mechanisms underlying the affinity maturation process in HIV-1 antibody development. Here, we review what has been learned from this atomic-level structural characterization of affinity maturation in HIV-1 antibodies and the implications for vaccine design.
Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-Meier analysis revealed significantly shorter overall (P=0.005) and recurrence-free survival (P=0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the -fetoprotein (AFP) level. The patient subgroup with higher AFP levels (20ng/mL) exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (<20ng/mL). Multivariate analysis defined UQCRH as an independent poor prognostic factor. Conclusively, our results indicate that UQCRH overexpression is correlated with poor outcomes of HCC patients. Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH overexpression could be a useful indicator for clinical treatment.
Recent forecasts suggest that African countries must triple their current electricity generation by 2030. Our multicriteria assessment of wind and solar potential for large regions of Africa shows how economically competitive and low-environmental-impact renewable resources can significantly contribute to meeting this demand. We created the Multicriteria Analysis for Planning Renewable Energy (MapRE) framework to map and characterize solar and wind energy zones in 21 countries in the Southern African Power Pool (SAPP) and the Eastern Africa Power Pool (EAPP) and find that potential is several times greater than demand in many countries. Significant fractions of demand can be quickly served with "no-regrets" options-or zones that are low-cost, low-environmental impact, and highly accessible. Because no-regrets options are spatially heterogeneous, international interconnections are necessary to help achieve low-carbon development for the region as a whole, and interconnections that support the best renewable options may differ from those planned for hydropower expansion. Additionally, interconnections and selecting wind sites to match demand reduce the need for SAPP-wide conventional generation capacity by 9.5% in a high-wind scenario, resulting in a 6-20% cost savings, depending on the avoided conventional technology. Strategic selection of low-impact and accessible zones is more cost effective with interconnections compared with solutions without interconnections. Overall results are robust to multiple load growth scenarios. Together, results show that multicriteria site selection and deliberate planning of interconnections may significantly increase the economic and environmental competitiveness of renewable alternatives relative to conventional generation.
X-linked agammaglobulinemia (XLA) has been associated with a broad range of infections, but enteroviral disease represents one of the most damaging infections. The risk of enteroviral infection in XLA is lower now than in the setting of intramuscular immunoglobulin or in patients without immunoglobulin replacement, but the rate of infection has not declined significantly in the era of intravenous immunoglobulin replacement. Enteroviruses can cause inflammation of nearly every organ, but in XLA, infections often manifest as dermatomyositis or chronic meningoencephalitis. Difficulty and delay in recognizing symptoms and lack of specific therapy contribute to the poor outcomes. Furthermore, cerebrospinal fluid detection of enteroviruses is not very sensitive. Reluctance to perform brain biopsies can lead to significant delays. The other feature compromising outcomes is the lack of specific therapy. High-dose peripheral and intraventricular immunoglobulin have been used, but failure is still common. New antienteroviral drugs are in development and show promise for immunodeficient patients with life-threatening infections with enterovirus. (C) 2016 American Academy of Allergy, Asthma & Immunology.
This paper presents a 1V -70dB THD audio Automatic Gain Control (AGC) circuits. The proposed AGC is based on feedback topologies and the gain is digital controlled. A pi-type resistors network is used in the Programmable Gain Amplifier (PGA) as the passive feedback device to realize gain linearity in decibels and increase the gain accuracy. The hysteresis comparator eliminate the chattering effects when the output signal of Peak Detector changes rapidly around the threshold. The design is implemented in 0.18 mu m CMOS and occupies an active area of 0.41mm2. The power consumption of AGC is about 0.17mW at 1V supply voltage. The gain of PGA in the AGC loop ranges from 0dB to 40dB in 2dB step with gain error not more than 0.2dB. The integrated noise in the audio range (20 Hz similar to 20 kHz) is 2.28 mu VRMS when the gain is set at 40dB. The total harmonic distortion (THD) is below -70dB over the audio frequencies at 0.4-Vpp differential output.
Background: Age might affect the change in care needs in patients with hepatocellular carcinoma after treatment during their transition process from hospital to home. However, there have been no studies that focus on this. Objective: The aim of this study is to examine changes in unmet supportive care needs in young (G65 years old) and elderly (Q65 years old) groups of patients with hepatocellular carcinoma from before discharge to 2 months after discharge. Methods: A longitudinal prospective study design was used with recruited participants at a teaching hospital in Taiwan. Data were collected 3 times: within 3 days before discharge and at 1 and 2 months after discharge. A set of questionnaires was used to assess participants' levels of supportive care needs, symptom distress, anxiety, and depression. Results: A total of 104 patients completed the data collection process. Supportive care needs decreased monthly after discharge, with health system and information being the domain with the highest level of unmet needs in the 2 groups. The young group had a higher level of overall unmet needs before discharge, but they had a lower level of overall needs compared with the elderly group after 2 months of discharge. Conclusions: Age could be a significant potential factor to affect change in unmet needs during transition. Implications for Practice: Comprehensive assessment in care needs especially in the health system and information and physical and daily living domains before discharge is recommended to design personalized education programs before discharge.
The proportion of workers in their 50s, 60s, and 70s is larger than ever before. Current work-force trends indicate global increases in retirement ages and that many individuals are working until later ages than in decades past, and older people are applying for jobs and at later ages. Research to date on age discrimination in selection has focused primarily on disparate treatment or intentional discrimination. However, based on accumulated knowledge about age-related changes in cognitive and physical abilities as well as changes in personality and work motivation across the life course, we suggest that more attention be paid to the possibility of age-based subgroup differences on selection procedures, manifested as adverse impact and differential prediction. We provide recommendations to guide future human resource management research and practice. (C) 2016 Elsevier Inc. All rights reserved.
Objective: Patients over 60 years of age have higher mortality and morbidity after major liver resections. Nitric oxide (NO) derived from the catalytic activity of Nos2 plays a beneficial role in liver regeneration (LR) after partial hepatectomy (PH). In this experiment, we evaluated the effect of Nos2 knockout (KO) on LR in aged mice after PH. Materials and Methods: In this experimental study, 52 two-year-old Nos2 KO and 46 the same age wild-type (WT) C57BL/6J mice were subjected to 2/3 PH. Liver tissues were collected at 11 time points after PH. Mice survival ratio and liver coefficient (liver-weight/ body-weight) was calculated. Transcript and protein levels were estimated by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results: The aged Nos2 KO mice had lower survival ratio (P=0.039) and liver coefficient (P=0.002) at the termination phase. Nos2 transcript level was obviously increased after PH in WT mice and undetected in the Nos2 KO mice. During LR, the expression at the transcript level of Cyclin D1, Cyclin A2 and Cyclin B1 and protein expression level of proliferation marker Ki67 and proliferation-associated transcription factors JNK1, NF-kB and STAT3 were decreased or delayed. The expression of pro-apoptotic proteins, CAS-PASE3, CASPASE9 and BAX, was increased in the Nos2 KO mice. Conclusion: Decreased survival ratio and impaired LR in aged Nos2 KO mice is probably due to decreased liver cell proliferation and increased liver cell apoptosis.
The health benefits of playing football and the importance of exercise and social contact for healthy ageing are well established, but few older adults in the UK take enough exercise. Football is popular, flexible in format and draws players into engrossing, effortful and social exercise, but the physical demands of play at full speed may make it unsustainable for some older adults. Restricted to walking pace, will play still be engaging? Will health benefits be retained? Will physical demands remain manageable? This pilot study aims to investigate: (1) the experience of older adults playing walking football every week, is it sustainable and rewarding, (2) the intensity and locomotor pattern of walking football, (3) the scale and nature of walking football health benefits and (4) possible cognitive benefits of playing walking football through measures of processing speed, selective and divided attention and updating and inhibition components of executive function. 'Walking football' and 'waiting list' groups were compared before and after 12 weeks of one-hour per week football. Walking football was found to be engaging, sustainable for older adults and moderately intensive; however, selective health and cognitive benefits were not found from this brief intervention.
The question of specific properties of life compared to nonliving things accompanied biology throughout its history. At times this question generated major controversies with largely diverging opinions. Basically, mechanistic thinkers, who tried to understand organismic functions in terms of nonliving machines, were opposed by those who tried to describe specific properties or even special forces being active within living entities. As this question included the human body, these controversies always have been of special relevance to our self-image and also touched practical issues of medicine. During the second half of the twentieth century, it seemed to be resolved that organisms are explainable basically as physicochemical machines. Especially from the perspective of molecular biology, it seemed to be clear that organisms need to be explained solely by the chemical functions of their component parts, although some resistance to this view never ceased. This research program has been working quite successfully, so that science today knows a lot about the physiological and chemical processes within organisms. However, again new doubts arise questioning whether the mere continuation of this analytical approach will finally generate a fundamental understanding of living entities. At the beginning of the twenty-first century the quest for a new synthesis actually comes from analytical empiricists themselves. The hypothesis of the present paper is that empirical research has been developed far enough today, that it reveals by itself the materials and the prerequisites to understand more of the specific properties of life. Without recourse to mysterious forces, it is possible to generate answers to this age-old question, just using recent, empirically generated knowledge. This view does not contradict the results of reductionistic research, but rather grants them meaning within the context of organismic systems and also may increase their practical usefulness. Although several of these properties have been discussed before, different authors usually concentrated on a single one or some of them. The paper describes ten specific properties of living entities as they can be deduced from contemporary science. The aim is to demonstrate that the results of empirical research show both the necessity as well as the possibility of the development of a new conception of life to build a coherent understanding of organismic functions.
Important energy reductions can be achieved in the building sector by providing occupants with feedback about their energy-consumption levels. Recent studies link the success of energy-feedback methods to the level of occupant engagement with people in their social circles and the resulting peer pressure to conform to certain social norms. Despite promising results, the literature remains limited in scope to individual rather than groups of buildings. This has limited the design of feedback initiatives leveraging social connections that exist, or that can be induced, within and between buildings. The current paper addresses the identified gap by proposing a multilayer agent-based model that serves as a test bed to simulate and optimize feedback methods applied on any building stock (e.g.,community and city). Monte Carlo and sensitivity analyses show that connecting occupants of different buildings, while increasing their engagement with the feedback mechanism, can lead to energy reductions exceeding 10%. The findings confirm the role of social networks in energy-conservation diffusion, setting the stage for large-scale and socially engaging energy-conservation initiatives. (C) 2017 American Society of Civil Engineers.
Extensively employed in reproductive science, the term fetal-maternal interface describes how maternal and fetal tissues interact in the womb to produce the transient placenta, purporting a theory of pregnancy where mother', fetus', and placenta' are already-separate entities. However, considerable scientific evidence supports a different theory, which is also elaborated in feminist and new materialist literatures. Informed by interviews with placenta scientists as well as secondary sources on placental immunology and the developmental origins of health and disease, I explore evidence not of interfacing during pregnancy, but of intra-action, or the mutual emergence of entities in simultaneous practices of differentiation and connection. I argue that attending to evidence that can be figured as intra-action enables us to recognize, account for, and attend to diffuse responsibilities for fetal-maternal outcomes that extend beyond mothers to the biosocial milieus of pregnancy. In reimaging the intra-action of placentas, a new understanding of what constitutes a healthy pregnancy' becomes possible.
Background: The collection of subgingival plaque samples with paper points is time-consuming and accident-sensitive. However, the collection of saliva is simple and contains pathogens of all intraoral surfaces. The aim of this study is to investigate whether a sampling strategy with mouthrinse (mouthrinse sample [MSP]; test) leads to results comparable with standard sampling method (multiple site test from the deepest pocket of each quadrant [MT4]; control). Methods: In 50 patients with periodontitis, subgingival plaque was sampled from the deepest pocket of each quadrant by using paper points and by gaining saliva with saline mouthrinse. Analysis was performed using a commercially available polymerase chain reaction test for 11 periodontal pathogens. Results: Detection frequency of Aggregatibacter actinomycetemcomitans (MT4/MSP: 42%/36%), Porphyromonas gingivalis (78%/66%), Tannerella forsythia (98%/84%), Treponema denticola (94%/74%), Parvimonas micra (86%/62%), Campylobacter rectus (90%/76%), Eubacterium nodatum (64%/30%), Prevotella intermedia (58%/54%), and Eikenella corrodens (90%/82%) was higher with MT4 than MSP. For Fusobacterium nucleatum (100%/100%), there was no difference between test and control. Only detection frequency of Capnocytophaga species (68%/74%) was higher with MSP than MT4. Differences were significant for P. gingivalis, T. forsythia, T. denticola, P. micra, C. rectus, and E. nodatum. Conclusions: There is no significant difference between MT4 and MSP for detection frequency of key pathogen A. actinomycetemcomitans. Key pathogens P. gingivalis, T. forsythia, T. denticola, P. micra, C. rectus, and E. nodatum show statistically higher detection frequencies with MT4.
This paper proposes a probabilistic optimization method that produces optimal bidding curves to be submitted by an aggregator to the day-ahead electricity market and the intraday market, considering the flexible demand of his customers (based in time dependent resources such as batteries and shiftable demand) and taking into account the possible imbalance costs as well as the uncertainty of forecasts (market prices, demand, and renewable energy sources (RES) generation). The optimization strategy aims to minimize the total cost of the traded energy over a whole day, taking into account the intertemporal constraints. The proposed formulation leads to the solution of different linear optimization problems, following the natural temporal sequence of electricity spot markets. Intertemporal constraints regarding time dependent resources are fulfilled through a scheduling process performed after the day-ahead market clearing. Each of the different problems is of moderate dimension and requires short computation times. The benefits of the proposed strategy are assessed comparing the payments done by an aggregator over a sample period of one year following different deterministic and probabilistic strategies. Results show that probabilistic strategy reports better benefits for aggregators participating in power markets.
This paper examines the association between the Great Recession and four measures of the risk for maternal child abuse and neglect: (1) maternal physical aggression; (2) maternal psychological aggression; (3) physical neglect by mothers; and (4) supervisory/exposure neglect by mothers. It draws on rich longitudinal data from the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study of families in 20 U.S. cities (N = 3177; 50% African American, 25% Hispanic; 22% non-Hispanic white; 3% other). The study collected information for the 9 year follow-up survey before, during, and after the Great Recession (2007-2010). Interview dates were linked to two macroeconomic measures of the Great Recession: the national Consumer Sentiment Index and the local unemployment rate. Also included are a wide range of socio-demographic controls, as well as city fixed effects and controls for prior parenting. Results indicate that the Great Recession was associated with increased risk of child abuse but decreased risk of child neglect. Households with social fathers present may have been particularly adversely affected. Results also indicate that economic uncertainty during the Great Recession, as measured by the Consumer Sentiment Index and the unemployment rate, had direct effects on the risk of abuse or neglect, which were not mediated by individual-level measures of economic hardship or poor mental health. (C) 2016 Elsevier Ltd. All rights reserved.
A growing body of research suggests that bipolar spectrum disorders (BSDs) are associated with high aggression. However, little research has prospectively examined how aggression may affect time to onset of hypomanic/manic versus major depressive episodes. In a longitudinal study, we tested the hypothesis that aggression would prospectively predict a shorter time to the onset of hypomanic/manic episodes and a longer time to the onset of major depressive episodes, based on the behavioral approach system theory of BSDs. Young adults (N=120) diagnosed with cyclothymia, bipolar II disorder, or bipolar disorder not otherwise specified were followed every 4 months for an average of 3.55 years. Participants completed measures of depressive and manic symptoms, family history of mood disorder, impulsivity, and aggression at baseline and were followed prospectively with semistructured diagnostic interview assessments of hypomanic/manic and major depressive episodes and treatment seeking for mood problems. Cox proportional hazard regression analyses indicated that overall, physical, and verbal aggression predicted a longer time to major depressive episode onset, even after controlling for baseline depressive and manic symptoms, family history of mood disorder, treatment seeking for mood problems, and impulsivity. Aggression, however, did not significantly predict time to onset of hypomanic/manic episodes, controlling for the same covariates. The findings suggest that approach-related behaviors may be utilized to delay the onset of major depressive episodes among people with BSDs.
Fipronil is an important member of the phenylpyrazole group of insecticides and is widely used for various crops and vegetables to control insects, thereby exposing birds, animals, and humans to fipronil. Currently, there is limited information on the effects of fipronil exposure in Japanese quail. Therefore, our aim was to assess the reproductive toxicological effects of fipronil in the Japanese quail in a 15-day gavage study and then its recovery over a period of 60 days. Fipronil-administration led to significant losses in both feed intake and body weight. Whereas, the gonadosomatic index was not affected, and histological changes observed in the testes were reversible, particularly by day 45 and day 60 of recovery. Cloacal gland atrophy, reduced foam quantity and a reduction in fertility, sexual and aggressive behaviors, and serum testosterone with elevated estradiol (E2) hormone levels were also observed. All these changes gradually reversed during various recovery periods. Further, alterations in hepatic vitellogenin (Vtg) and estrogen receptor alpha (ER alpha) gene expression, assessed by quantitative polymerase chain reaction, were also observed. Specifically, ER alpha 1 was induced after fipronil administration, while the Vtg transcript was elevated during both exposure and recovery periods. Our results showed that fipronil exposure has a profound negative influence on reproductive traits in the male Japanese quail and exhibits an estrogenic activity that can raise the incidence of infertility in males. Nevertheless, most of the changes could be reversed after a recovery period of 30-45 days. (C) 2016 Elsevier Ltd. All rights reserved.
Although previous studies in inmates, forensic and psychiatric samples suggest the relation between childhood trauma and suicide behavior as well as between childhood trauma and violent delinquency, the understanding of possible underlying mechanisms is still fragmentary. In a naturalistic study design, we tested if suicidal attempts and violent crimes are differently associated with adverse childhood experiences and levels of appetitive aggression in male forensic psychiatry inpatients. Adverse childhood experiences and appetitive aggression styles were collected by means of self-report measures, suicide attempts were taken from the medical history and violent crimes were appraised by official court records. The data were analyzed by the means of generalized linear models. Results revealed that appetitive aggression and adverse childhood experiences were significant predictors of suicide attempts, whereas violent crimes were associated solely with appetitive aggression. Suicide attempts and violent delinquency in forensic patients seem to be both positively associated with high levels of appetitive aggression, whereas their etiological pathways might differ with regard to adverse childhood experiences. Considering these interrelations to a greater extent might improve both diagnostics and treatment of forensic patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Sphingomyelin phosphodiesterase 3 (Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue.
Background: Dendritic cells (DCs) form a key link between innate and adaptive immune responses. The aim of this study is to analyze presence and distribution of immature (im) and mature (m) DCs in gingival tissue samples obtained from patients diagnosed with aggressive periodontitis (AgP), chronic periodontitis (CP), and clinically healthy periodontium (control group). Methods: Gingival tissue samples obtained from patients with: 1) AgP (aged= 35 years); and 3) control group (aged >18 years) (n = 10 per group) were collected. Two-way analysis of variance and posterior Fisher least significant difference test were used to observe differences between the means of cells positively marked for imDC (S100, CD1a, and CD207) and mDC (CD208) immunomarkers. Results: imDCs were more numerous in AgP than CP and control groups, being statistically significant only for S100+ cells. Conversely, mDCs were visualized in higher numbers in CP than AgP and control groups (both P <0.05). Considering frequency of immunostained cells, the number of S100+ cells was greater than CD207+ and CD1a+ cells, followed by a lesser number of CD208+ cells, in all groups. Conclusions: Considering that the ability of DCs to regulate immunity is dependent on DC maturation, results suggest that predominance of imDCs appears to be involved in AgP pathogenesis, probably due to lack of ability to induce immune cell activation. Further studies are necessary to elucidate the role of DC maturation in regulating immune responses in periodontal disease.
Fragile x syndrome (FXS) is the most common form of inherited mental retardation disease. This is caused due to expansion of CGG triplet in 5'-untranslated region of fragile x mental retardation 1 (FMR-1) gene. In most of the cases, abnormally large size of the CGG repeat (>200) undergoes hypermethylation, which in turn silences the FMR-1 gene causing thereby complete lack of its protein product called fragile x mental retardation protein (FMRP). Lack of FMRP due to gene silencing or production of faulty protein due to point mutation in KH2 domain of FMRP alters the translational process in neurons and leads to expression of mental retardation phenotype on the patients. The FMRP is expressed ubiquitously in all tissues; however, it is predominantly expressed in neurons and testis. It possesses heterogeneity and is found in many isoforms due to alternative splicing of the FMR-1 transcript. Based on our data from the Western-, slot-, Northern blotting and immunohistochemical studies, we report here the down regulation of Fmr-1 gene and FMRP in mice brain in age-dependent manner. The present finding is important in respect to FMRP-dependent various brain functions i.e., learning, memory, cognition etc. that decrease with advancing age.
Background: Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. Methods: This study included treatment seeking crack cocaine dependents women (n = 127) and elderly women without a psychiatric diagnosis (ELD, n = 49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. esults: CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. Conclusions: These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience. (C) 2016 Elsevier Inc. All rights reserved.
Significance: With the growing population of baby boomers, there is a great need to determine the effects of advanced age on the function of the immune system. Recent Advances: It is universally accepted that advanced age is associated with a chronic low-grade inflammatory state that is referred to as inflamm-aging, which alters the function of both immune and nonimmune cells. Mononuclear phagocytes play a central role in both the initiation and resolution of inflammation in multiple organ systems and exhibit marked changes in phenotype and function in response to environmental cues, including the low levels of pro-inflammatory mediators seen in the aged. Critical Issues: Although we know a great deal about the function of immune cells in young adults and there is a growing body of literature focusing on aging of the adaptive immune system, much less is known about the impact of age on innate immunity and the critical role of the mononuclear phagocytes in this process. Future Directions: In this article, there is a focus on the tissue-specific monocyte and macrophage subsets and how they are altered in the aged milieu, with the hope that this compilation of observations will spark an expansion of research in the field.
Rationale: Leukocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells are involved in tissue repair and regeneration. Objective: Main objective of this study was to examine the relationship between LTL and progenitor cells and their impact on adverse cardiovascular outcomes. Methods and Results: We measured LTL by quantitative polymerase chain reaction in 566 outpatients (age: 63 +/- 9 years; 76% men) with coronary artery disease. Circulating progenitor cells were enumerated by flow cytometry. After adjustment for age, sex, race, body mass index, smoking status, and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (P< 0.001). After adjustment for the aforementioned factors, both short LTL (< Q1) and low CD34+ levels (< Q1) predicted adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization, or cerebrovascular events) independently of each other, with a hazard ratio of 1.8 and 95% confidence interval of 1.1 to 2.0, and a hazard ratio of 2.1 and 95% confidence interval of 1.3 to 3.0, respectively, comparing Q1 to Q2-4. Patients who had both short LTL (< Q1) and low CD34+ cell count (< Q1) had the greatest risk of adverse outcomes (hazard ratio = 3.5; 95% confidence interval, 1.7-7.1). Conclusions: Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating progenitor cell levels are independent and additive predictors of adverse cardiovascular outcomes in coronary artery disease patients. Our results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular events, independent of conventional risk factors.
One of the most significant reliability issues in switching-mode power supplies is electrolytic capacitor degradation caused by aging. This paper proposes an output voltage transient analysis method to detect capacitor wear-out at the output stage of a step-down dc-dc converter. Changes in the converter output voltage dynamics are evaluated by analyzing the output voltage step response with respect to a decrease in the capacitance. The sensitivity of the method is assessed with respect to parameter variations using an equivalent main circuit model. The feasibility of the presented method is verified by experimental tests using a converter prototype. The results show that the presented method is practical and adequate for detecting capacitor degradation in various operating conditions.
The detection of degradations and resulting failures in electronic components/systems is of paramount importance for complex industrial applications including nuclear power reactors, aerospace, automotive, and space applications. There is an increasing acceptance of the importance of detection of failures and degradations in electronic components and of the prospect of system-level health monitoring to make a key contribution to detecting and predicting any impending failures. This paper describes a parametric system identification-based health-monitoring method for detecting aging degradations of passive components in switch-mode power converters (SMPCs). A nonparametric system response is identified by perturbing the system with an optimized multitone sinusoidal signal of the order of mVs. The parametric system model is estimated from nonparametric system response using recursive weighted least-square (WLS) algorithm. Finally, the power-stage component values, including their parasitics, are extracted from numerator and denominator coefficients based on the assumed Laplace system model. These extracted component values provide direct diagnostic information of any degradation or anomalies in the components and the system. A proof of concept is initially verified on a simple point-of-load (POL) converter but the same methodology can be applied to other topologies of SMPC.
Background-Circulating levels of chemerin are significantly higher in hypertensive patients and positively correlate with blood pressure. Chemerin activates chemokine-like receptor 1 (CMKLR1 or ChemR23) and is proposed to activate the "orphan" G protein-coupled receptor 1 (GPR1), which has been linked with hypertension. Our aim was to localize chemerin. CMKLR1, and GPR1 in the human vasculature and determine whether 1 or both of these receptors mediate vasoconstriction. Methods and Results-Using immunohistochemistry and molecular biology in conduit arteries and veins and resistance vessels, we localized chemerin to endothelium, smooth muscle, and adventitia and found that CMKLR1 and GPR1 were widely expressed in smooth muscle. C9 (chemerin149-157) contracted human saphenous vein (pD(2)=7.30 +/- 0.31) and resistance arteries (pD(2)=7.05 +/- 0.54) and increased blood pressure in rats by 9.1 +/- 1.0 mm Hg at 200 nmol. Crucially, these in vitro and in vivo vascular actions were blocked by CCX832, which we confirmed to be highly selective for CMKLR1 over GPR1. C9 inhibited cAMP accumulation in human aortic smooth muscle cells and preconstricted rat aorta, consistent with the observed vasoconstrictor action. Downstream signaling was explored further and, compared to chemerin. C9 showed a bias factor=approximate to 5000 for the Gi protein pathway, suggesting that CMKLR1 exhibits biased agonism. Conclusions-Our data suggest that chemerin acts at CMKLR1, but not GPR1, to increase blood pressure. Chemerin has an established detrimental role in metabolic syndrome, and these direct vascular actions may contribute to hypertension, an additional risk factor for cardiovascular disease. This study provides proof of principle for the therapeutic potential of selective CMKLR1 antagonists.
Biofilm formation usually increases antimicrobial resistance capacity of Staphylococcus aureus, which poses considerable challenges to successful eradication of staphylococcal infections. Very little is known about the biofilm-forming capacity and antibiotic resistance pattern of dominant S. aureus clonal lineages in China. In this study, the disk diffusion method and the microtiter plate assay were, respectively, performed to determine the antibiotic resistance and biofilm-forming capacity of 84 different S. aureus isolates belonging to 10 dominant clonal lineages in China. It was shown that isolates of different clonal lineages had obvious variations in biofilm-forming capacity. Resistance to individual antibacterial agents was most frequently observed to erythromycin (72.6%) and azithromycin (72.6%). Then, all tested isolates were further screened for the presence of 16 resistance genes by polymerase chain reaction (PCR), and no significant correlation was found between clonal lineage and the distribution of resistance genes. Overall, our results indicate that biofilm producers of S. aureus have a greater likelihood to carry more antibiotic resistance genes than non-biofilm producers (p<.01), further implying that biofilm may promote the dissemination of antibiotic resistance determinants. Practical applicationsStaphylococcus aureus is the leading cause of nosocomial infections and often associated with food poisoning worldwide. Biofilm formation of S. aureus influences the efficacy of antimicrobial therapy and promotes the persistence of infections; however, the knowledge about biofilm formation capacity of isolates belonging to different clonal lineages is little. Therefore, this study on biofilm formation capacity and antibiotic resistance pattern of dominant S. aureus clonal lineages could help to fix this information gap.
Gene editing technologies are a group of recent innovations in plant breeding using molecular biology, which have in common the capability of introducing a site-directed mutation or deletion in the genome. The first cases of crops improved with these technologies are approaching the market; this has raised an international debate regarding if they should be regulated as genetically modified crops or just as another form of mutagenesis under conventional breeding. This dilemma for policymakers not only entails issues pertaining safety information and legal/regulatory definitions. It also demands borrowing tools developed in the field of social studies of science and technology, as an additional basis for sound decision making.
BACKGROUNDWeeds can be a greater constraint to crop production than animal pests and pathogens. Pre-emergence herbicides are crucial in many cropping systems to control weeds that have evolved resistance to selective post-emergence herbicides. In this study we assessed the potential to evolve resistance to the pre-emergence herbicides prosulfocarb + S-metolachlor or pyroxasulfone in 50 individual field Lolium rigidum populations collected in a random survey in Western Australia prior to commercialisation of these pre-emergence herbicides. RESULTSThis study shows for the first time that in randomly collected L. rigidum field populations the selection with either prosulfocarb + S-metolachlor or pyroxasulfone can result in concomitant evolution of resistance to both prosulfocarb + S-metolachlor and pyroxasulfone after three generations. CONCLUSIONSIn the major weed L. rigidum, traits conferring resistance to new herbicides can be present before herbicide commercialisation. Proactive and multidisciplinary research (evolutionary ecology, modelling and molecular biology) is required to detect and analyse resistant populations before they can appear in the field. Several studies show that evolved cross-resistance in weeds is complex and often unpredictable. Thus, long-term management of cross-resistant weeds must be achieved through heterogeneity of selection by effective chemical, cultural and physical weed control strategies that can delay herbicide resistance evolution. (c) 2016 Society of Chemical Industry
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress signaling. However, its molecular mechanism remains to be elucidated. In this investigation, cell suspension cultures of two different plant species rice (Oryza sativa L.) and white pine (Pinus strobes L.) were transformed using Agrobacterium tumefaciens strain LBA4404 harboring pBI-AtZIP60. Integration of the AtbZIP60 gene into the genome of rice and white pine has been confirmed by polymerase chain reaction (PCR), southern blotting, and northern blotting analyses. Six transgenic cell lines from O. sativa and three transgenic cell lines from P. strobus were used to analyze the salt, drought, and cold tolerance conferred by the overexpression of the AtbZIP60 gene. Our results demonstrated that expression of the AtbZIP60 gene enhanced salt, drought, and cold tolerance in rice and white pine transgenic cell lines. In rice, transcription factor AtbZIP60 increased expression of Ca2+-dependent protein kinase genes OsCPK6, OsCPK9, OsCPK10, OsCPK19, OsCPK25, and OsCPK26 under treatment of salt, drought, and cold. These results demonstrated that overexpression of the AtbZIP60 gene in transgenic cell lines improved salt, drought, and cold stress tolerances by regulating expression of Ca2+-dependent protein kinase genes. Overexpression of the AtbZIP60 gene could be an alternative choice for engineering plant abiotic stress tolerance.
An efficient transformation system for Chinese cabbage cotyledon explants was developed using Agrobacterium tumefaciens strains LBA4404 harbouring the plasmid pMOG411 and the plasmid pBin Omega SCK respectively. Various factors affecting the transformation efficiency and subsequent regeneration were identified. The age of seedlings, growth conditions and status of Agrobacterium suspension, preculture of explants, cocultivation time, ratio between Agrobacterium and explants, acetosyringone and concentration of kanamycin had a significant influence on transformation frequency and plant regeneration. The presences of the antibacterial peptide gene and the cowpea trypsin inhibitor gene in those selected shoots in kanamycin medium were confirmed by PCR, Southern blotting and Northern blotting, The frequency of regeneration from cotyledons was analyzed in eight parental lines of Chinese cabbage and five lines were suitable for obtaining transformed plants, among which Qingmaye C and Qingmaye D were more responsive than other lines.
'Mexican' lime (Citrus aurantifolia Swingle) was transformed with constructs that contained chimeric promoter-gus gene fusions of phloem-specific rolC promoter of Agrobacterium rhizogenes, Arabidopsis thaliana sucrose-H+ symporter (AtSUC2) gene promoter of Arabidopsis thaliana, rice tungro bacilliform virus (RTBV) promoter and sucrose synthase l (RSs1) gene promoter of Oryza sativa (rice). Histochemical beta-glucuronidase (GUS) analysis revealed vascular-specific expression of the GUS protein in citrus. The RTBV promoter was the most efficient promoter in this study while the RSs1 promoter could drive low levels of gus gene expression in citrus. These results were further validated by reverse transcription real-time polymerase chain reaction and northern blotting. Southern blot analysis confirmed stable transgene integration, which ranged from a single insertion to four copies per genome. The use of phloem-specific promoters in citrus will allow targeted transgene expression of antibacterial constructs designed to battle huanglongbing disease (HLB or citrus greening disease), associated with a phloem-limited Gram-negative bacterium.
To improve the transformation efficiency of wheat (Triticum aestivum L.) mediated by Agrobacterium tumefaciens, we explored the possibility of employing the basal portion of wheat seedling (shoot apical meristem) as the explants. Three genotypes of wheat were transformed by A. tumefaciens carrying beta-1, 3-glucanase gene. After vernalization, the seeds to be transformed were germinated. When these seedlings grew up to 2 similar to 5 cm, their coleoptile and half of the cotyledon were cut out, and the basal portions were infected by A. tumefaciens. A total 27 T-0 transgenic plants were obtained, and the average transformation efficiency was as high as 9.82%. Evident segregation occurred in some of the T-1 plants, as was indicated by PCR and Southern blotting analysis. Investigation of the T-2 plants revealed that some transformed plants had higher resistance to powdery mildew than the controls. Northern blotting revealed that beta-1, 3-glucanase gene was normally expressed in the T-2 plants, which showed an increased resistance to powdery mildew. The results above indicate that the exogenous gene has been successfully integrated into the genome of wheat, transmitted and expressed in the transgenic progeny. From all the results above, it can be concluded that Agrobacterium inoculum to the basal portion of wheat seedling is a highly efficient and dependable transformation method. It can be developed into a practicable method for transfer of target gene into wheat.
Constantly elevated temperatures cause an array of physio-biochemical changes in tomato (Lycopersicum esculentum Mill.) which make the fruit ripen quickly and up to 50 % yield loss. The development of tomato cultivars, using genetic engineering approaches which delay ripening, offers a new way to keep tomatoes healthy under heat stress. Over-expression of small heat shock protein gene, viscosity 1 (vis 1) plays a role in increasing juice viscosity, early ripening and tissue soften which emphasizes the importance of this gene in premature ripening. The aim of this work was therefore to develop a useful system for silencing the vis1 gene using small interfering RNA strategy. Agrobacterium strain GV3101 harbouring the binary vector pICBV19 containing the gus and bar genes was used to adapt the transformation process in this study. The primers were designed to amplified the first exon of the vis 1 gene and the amplified fragment was used for cloning into the pFGC5941 at XhoI/NcoI site at sense orientation then additional fragment was subsequently cloned at BamHI/XbaI to form sense/antisense cloned fragment interrupted by the CHSA-intron Agrobacterium strain LBA4404 with the binary vector pFGC5941 which harbors vis1 gene under the control of the 35S promoter containing bar gene under the control of a mannopine synthase 2'(Mas2') as selectable marker, was used to reduce the expression of vis1 gene in fruit. Polymerase chain reaction (PCR), RT-PCR and northern blotting analysis were applied to detect putative transgenic plants. Significantly, silencing of vis 1 gene was potently occur and new transgenic tomato cultivars were produced with enhanced ripening qualities for recommendation for growing under heat stress.
To induce virus resistance in tobacco and rice we constructed hairpin RNA expression system harbouring inverted repeat fragments of coat protein cDNA of Potato virus Y (PVY) or Rice stripe virus (RSV). These structures were driven by three promoters [cauliflower mosaic virus 35S (CaMV 35S), polyubiqutin gene of maize (Ubi), and Pharbitis nil leucine zipper gene (PNZIP)] which have different tissue-specific activity. PVY resistance ratios were 65.18, 24.33 and 83.54 % in transgenic tobacco plants harboring p35S-PVY, pUbi-PVY and pPNZIP-PVY. RSV resistance was 16.21, 28.61 and 29.33 % in transgenic rice plants harboring p35S-RSV, pUbi-RSV and pPNZIP-RSV. Northern blotting and GUS assay demonstrated that virus resistance levels were related to promoter activity. Therefore, choice of the more effective and tissue-specific promoter to reinforce transcription of hpRNAs will favour the cultivation of highly virusresistant transgenic plants.
Potato is one of the main targets for genetic improvement by gene transfer. The aim of the present study was to establish a robust protocol for the genetic transformation of three dihaploid and four economically important cultivars of potato using Agrobacterium tumefaciens carrying the in vivo screenable reporter gene for green fluorescent protein (gfp) and the marker gene for neomycin phosphotransferase (nptII). Stem and leaf explants were used for transformation by Agrobacterium tumefaciens strain LBA4404 carrying the binary vector pHB2892. Kanamycin selection, visual screening of GFP by epifluorescent microscopy, PCR amplification of nptII and gfp genes, as well as RT-PCR and Southern blotting of gfp and Northern blotting of nptII, were used for transgenic plant selection, identification and analysis. Genetic transformation was optimized for the best performing genotypes with a mean number of shoots expressing gfp per explant of 13 and 2 (dihaploid line 178/10 and cv. 'Baltica', respectively). The nptII marker and gfp reporter genes permitted selection and excellent visual screening of transgenic tissues and plants. They also revealed the effects of antibiotic selection on organogenesis and transformation frequency, and the identification of escapes and chimeras in all potato genotypes. Silencing of the gfp transgene that may represent site-specific inactivation during cell differentiation, occurred in some transgenic shoots of tetraploid cultivars and in specific chimeric clones of the dihaploid line 178/10. The regeneration of escapes could be attributed to either the protection of non-transformed cells by neighbouring transgenic cells, or the persistence of Agrobacterium cells in plant tissues after co-cultivation.
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress signaling, pathogen defense, and flower development. However, molecular mechanism involved in plant salt tolerance via overexpression of transcription factor AtbZIP60 is elusive. In this investigation, cell suspension cultures of four different plant species cotton (Gossypium hirsutum L.), Virginia pine (Pinus virginiana L.), white pine (Pinus strobus L.), and Arabidopsis (Arabidopsis thaliana) were transformed via Agrobacterium tumefaciens LBA4404 harboring pBI-AtZIP60. Integration of AtbZIP60 into the genome of G. hirsutum, P. virginiana, P. strobes, and A. thaliana has been confirmed by polymerase chain reaction, Southern blotting, and northern blotting analyses. Six transgenic cell lines from each of four species were used to analyze the salt tolerance conferred by the overexpression of AtbZIP60. Our results demonstrated that expression of AtbZIP60 enhanced salt tolerance of transgenic cells in all transgenic lines, and that improved salt tolerance was associated with increased activities of both H+-ATPase and acid phosphatase and decreased lipid peroxidation (thiobarbituric acid reactive substances) in transgenic cell lines from cotton (Gh1, Gh2, Gh3, Gh4, Gh5, and Gh6), Virginia pine (Pv1, Pv2, Pv3, Pv4, Pv5, and Pv6), white pine (Ps1, Ps2, Ps3, Ps4, Ps5, and Ps6), and Arabidopsis (At1, At2, At3, At4, At5, and At6). This investigation demonstrated that the expression of AtbZIP60 gene in transgenic cell lines reduced salt-induced oxidative damage by increasing the activities of both H+-ATPase and acid phosphatase, and that the overexpression of AtbZIP60 gene could be valuable for engineering plant salt tolerance.
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress signaling. However, its involvement in plant salt tolerance is not fully understood. In this investigation, cell suspension cultures of three different plant species: tobacco (Nicotiana tabacum), rice (Oryza sativa L.), and slash pine (Pinus elliottii Engelm.) were transformed via Agrobacterium tumefaciens LBA4404 harboring pBI-AtbZIP60deltaC. Integration of AtbZIP60deltaC into the genome of tobacco, rice, or slash pine has been confirmed by polymerase chain reaction, Southern blotting, and Northern blotting analyses. Six transgenic cell lines from each of three species were used to analyze the salt tolerance conferred by the overexpression of AtbZIP60deltaC. Our results demonstrated that expression of AtbZIP60deltaC enhanced salt tolerance of transgenic cells in all transgenic lines and that improved salt tolerance was associated with increased activities of both ascorbate peroxidase and superoxide dismutase, and decreased lipid peroxidation (thiobarbituric acid reactive substances). This investigation has demonstrated that the expression of AtbZIP60deltaC gene in transgenic cell lines attenuated salt-induced oxidative damage by increasing the activities of antioxidant enzymes and the overexpression of AtbZIP60deltaC gene could be an alternative choice for engineering plant salt tolerance.
The aim of the present study was to produce marker-free transgenic potato resistant to PVY by using a construct generating self-complementary hairpin RNAs. The method has two steps: 1) establishing a robust protocol for the genetic transformation of economically important cultivars of potato by using gfp and nptII genes; 2) applying the protocol for the transfer of marker-free hairpin construct and analysis of transgenic plants by PCR. In the first step internodes were transformed by Agrobacterium tumefaciens LBA4404 with pH82892 construct. Kanamycin, visual screening of GFP, PCR of nptII and gfp as well as RT-PCR and Southern blotting of gfp and Northern blotting of nptII were used for transgenic plant selection. Good regeneration and transformation efficiency were obtained for the cvs. Baltica and Desiree while the cvs. Agave and Delikat showed lower figures. In the second step A. tumefaciens with construct: 35SCaMV enhancer and promoter, two repeated inverted PVY-CP sequences separated by an intron and pAnos terminator was used Regenerated plants without selection, were analysed by PCR using primers in the: 35S promoter, promoter and hairpin region, or in both repeated PVY-CP sequences. A large number of transgenic plants were identified for the most responsive cv. Baltica (17 out of 33) and Desiree (23 out of 66), but only I for the cv. Agave (out of 3) and none for the cv. Delikat. This simple two-step strategy might be applied to generate marker-free transgenic plants in other cvs. or plant species.
The disciplinary structure of research on complex problems related to human activities is supported by the fundaments of the social, life, and hard sciences. In this work, we looked at the development of scientific research in the field of biofuels, as a sustainable source of energy, searching for references regarding its scientific roots and social relevance. Scientific communications on biofuels published between 1998 and 2007 were analyzed using a combination of bibliometric methods and text mining techniques. This field of research was characterized as interdisciplinary, with marked social relevance. Our bibliometric analysis shows that, in this research subject, 132 different, interacting fields of knowledge overlap, with dominance of Chemistry, Engineering and Agricultural Sciences. Through the use of text mining techniques, this field was configured into three groups of Disciplinary Dimensions. The first and most influential group includes the Agricultural Sciences, Social Sciences, and Environmental Sciences. The second group, which gives the field its technological basis, includes Chemistry, Engineering, and Microbiology. The third group includes disciplines with emerging involvement in the field of biofuels: Biology and Biochemistry, Animal and Plant Sciences, Molecular Biology and Genetics, Economics, Material Sciences, Nanosciences and Nanotechnology, Geosciences, Physics, Humanities, Multidisciplinary Sciences, Mathematics, and Computer Sciences. This study suggests that the first group of Disciplinary Dimensions conforms to the elements that socially validate the progress of research in the field of biofuels. This study also proposes a metric that can be used to measure the interdisciplinarity and the social framing of any other research field.
The transport sector is one of the main sources of greenhouse gases, adding in Spain near a quarter of the total national emissions, the majority in road transport. Therefore, road contribution to climate change should be mitigated to achieve the proposed goals in the fight against climate change. Policies and strategies suggest several preventive mitigation options, but have paid little attention to compensatory mitigation. We have conducted a theoretical case study in a Spanish province, Segovia, estimating the carbon dioxide emissions in the road network between 2015 and 2050, and analysing different compensation possibilities through conservation agriculture, agroforestry, afforestation and hedgerow plantation. We have calculated carbon sequestration in the reference period and costs per tonne for each option, estimating the budget range of offsetting road carbon emission, and funding possibilities, especially through fuel taxes. The paper demonstrates that offsetting carbon emissions produced by roads in this area is technically possible and highly desirable, unifying carbon sequestration, biodiversity improvement and rural development. The main challenge is funding, which depends largely on the political will and the awareness of the citizens. (C) 2017 Elsevier B.V. All rights reserved.
African horse sickness (AHS) is a fatal disease of equids relevant to the global equine industry. Detection of AHS virus (AHSV) during outbreaks has become more rapid and efficient with the advent of group specific reverse transcriptase quantitative polymerase chain reaction (GS RT-qPCR) assays to detect AHSV nucleic acid. Use of GS RT-qPCR together with recently described type specific (TS RT-qPCR) assays cannot only expedite diagnosis of AHS but also facilitate further evaluation of the dynamics of AHSV infection in the equine host. A potential limitation to the application of these assays is that they detect viral nucleic acid originating from any AHS live attenuated vaccine (LAV), which is the vaccine type routinely administered to horses in South Africa. The aim of this study was to contrast the dynamics and duration of the RNAaemia to the serological responses of horses following immunization with a commercial polyvalent AHSV-LAV using GS and TS RT-qPCR assays and serum neutralisation tests. The results of the study showed extended RNAemia in vaccinated horses, and that more horses tested positive on GS RT-qPCR with lower Cq values after receiving the AHSV-LAV containing types 1, 3 and 4 prior to the vaccine containing types 2, 6, 7 and 8, rather than when the vaccine combinations were reversed. Furthermore, lower Cq values were obtained when vaccines were administered 4 weeks apart as compared with a longer interval or 12 weeks apart. These findings are of particular relevance in regions where AHSV-LAVs are used as the use of these vaccines may complicate the accurate interpretation of diagnostic testing results. (C) 2017 Elsevier Ltd. All rights reserved.
BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.
Background: The presence of gross deletions in the human immunodeficiency virus nef gene (g Delta nef) is associated with long-term nonprogression of infected patients. Here, we investigated how quickly genetic defects in the nef gene are associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors. Methods: This study was divided into three phases over a 20-yr period; baseline, KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene amplicons were obtained using reverse transcription polymerase chain reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and these were then sequenced. The proportion of g Delta nef, premature stop codons, and not in-frame insertion or deletion of a nucleotide was compared between three phases, control, and ART patients. Results: The proportion of defective nef genes was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p < 0.01). Small in-frame deletions or insertions were significantly more frequent among patients treated with KRG alone compared with controls (p < 0.01). Significantly fewer instances of genetic defects were detected in samples taken during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected were g Delta nef and small in-frame deletions after 7 mo and 67 mo of KRG intake, respectively. Conclusion: KRG treatment might induce genetic defects in the nef gene. This report provides new insight into the importance of genetic defects in the pathogenesis of AIDS. (C) 2017 The Korean Society of Ginseng, Published by Elsevier Korea LLC.
Background: CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. Methods: Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). Results: Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. Conclusion: CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.
Three novel differential amplifier topologies using double gate a-IGZO TFTs on flexible substrate are presented in this paper. The designs exploit positive feedback and a load with self-biased top gate to achieve the highest static gain in single stage a-IGZO amplifiers reported to date. After fabrication, the three amplifiers exhibit respectively a static gain of 14 dB, 21.5 dB, and 30 dB, with a bandwidth of 2 kHz, 400 Hz, and 150 Hz. Also, for each circuit the input referred noise has been measured to be 420 mu V-rms, 195 mu V-rms, and 146 mu V-rms, respectively. Based on these results, the a-IGZO amplifier providing the highest gain is suitable as front-end for heart rate measurements and, with some further optimization verified in simulation, can also be used for other bio-potential applications, like electro hysterogram and electro cardiogram.
Typical variable air volume (VAV) terminals spend the majority of time at their minimum airflow set points. These are often higher than the minimum ventilation requirements defined by code, resulting in excess energy use and a risk of over-cooling the spaces. We developed and tested a time-averaged ventilation (TAV) control strategy in an institutional building on the UC Berkeley campus to address this issue. Whenever a zone does not require cooling, TAV alternates the VAV damper between partially open and fully closed so that the average airflow matches a predefined ventilation setpoint. Compared to the existing, base case scenario using single-max VAV logic, this strategy reduced the mean zone airflow fraction from 0.44 to 0.27 during the intervention period. The corresponding reductions in average heating, cooling, and fan power were 41%, 23%, and 15% respectively. In addition to being programmed directly in a native control system, TAV may be applied via sMAP as a low-cost retrofit strategy in any building that has a BACnet network and direct digital control (DDC) to each VAV terminal. (C) 2016 Elsevier B.V. All rights reserved.
Numerous studies have reported an association between fine particulate matter (PM2.5) and human health. Often these relationships are influenced by environmental factor that varies spatially and/or temporally. To our knowledge, there are no studies in Canada that have considered energy generation and fuel sales as PM2.5 effects modifiers. Determining exposure and disease-specific risk factors over space and time is crucial for disease prevention and control. In this study, we evaluated the association of PM2.5 with diabetes, asthma, and High Blood Pressure (HBP) incidence in Canada. Then we explored the impact of the energy generation and fuel sales on association changes. We fit an age-period-cohort as the study design, and We applied an over-dispersed Poisson regression model to estimate the risk. We conducted a sensitivity analysis to explore the impact of variation in clean energy rates and fuel sales on outcomes changes. The study included 117 health regions in Canada between 2007 and 2014. Our findings showed strong association of PM2.5 with diabetes, asthma, and HBP incidence. A two-year increase of 10 mu g/m(3) in PM2.5 was associated with an increased risk of 534% (95% CI: 2.28%; 12.53%) in diabetes incidence, 2.24% (95% CI: 0.93%; 538%) in asthma incidence, and 8.29% (95% CI: 3.44%; 19.98%) in HBP incidence. Our sensitivity analysis findings suggest higher risks of diabetes, asthma and HBP incidence when there is low clean energy generation. On the other hand, we found lower risk when we considered high rate of clean energy generation. For example, considering only diabetes incidence, we found that the risk in health regions with low rates of clean electricity is approximately 700% higher than the risk in health regions with high rates of clean electricity. Furthermore, our analysis suggested that the risk in regions with low fuel sales is 66% lower than the risk is health regions with low rates of clean electricity. Our study provides support for the creation of effective environmental health public policies that take into account the risk factors present in Canadians health regions. (C) 2017 Elsevier B.V. All rights reserved.
Effectively analyzing and then treating energy-related air pollution requires examining every factor, from the pollution source to the end of treatment. This paper applies index decomposition analysis and a whole process treatment perspective to identify the factors facilitating air pollution reduction across three stages: source prevention, process control, and end-of-pipe treatment. Empirical research using data from China's Jiangsu Province and its 13 cities reveals differences in local approaches to pollution prevention. At the provincial level, end-of-pipe treatment remains the primary approach to control air pollution emissions, indicating that the pattern of "pollute first, govern later" has not yet been fundamentally reversed. At the city level, 13 cities can be divided into four types, based on their approach to air pollution treatment: the leading type, process-dependent type, end-dependent type, and lagging type. Of these, 7 cities are using multiple control approaches, reflecting the comprehensive effect of whole process treatment. The Jiangsu Province should consider further strengthening effective whole process air pollution treatment models, by transitioning to pollution control, adjusting industrial structure, promoting technological progress, and consuming clean energy. (C) 2016 Elsevier Ltd. All rights reserved.
The paper presents the design and some results for an experimental platform aimed to control the air pressure inside a small tank. The basic idea is to allow to the control algorithm to select an appropriate characteristic of the controller driving the air compressor, from an available set. In this first approach, the goal is to make functional the hardware circuits and to design the software support inside an Integrated Development Environment with a Very High Level Programming Language. After some functional tests, future work is intended to implement artificial intelligent based algorithms in order to exploit the multicharacteristics features with a fuzzy decisions set for selecting an optimal control. The main parts of the controller are an industrial pressure sensor, a PIC (TM) 16F877 microcontroller from Microchip (TM) and the air pressure part consisting, mainly, from a car compressor and a small tank. Additional elements make the operation safe. The solution with the microcontroller is put in operation in parallel with another one, using an industrial digital controller from Honeywell (TM). The platform is intended both for research activities, dealing with all kind of control algorithms implemented in software, associated with pneumatic systems, and for academic purpose, joining in an unique structure sensors, microelectronics, interface techniques, industrial controllers, motors, pneumatic elements and software.
BACKGROUNDFilling creams can provide an adequate substrate for spoilage yeasts because some yeasts can tolerate the high osmotic stress in these products. To discover the source of spoilage of a cream-filled baked product, end products, raw materials, indoor air and work surfaces were subjected to microbiological and molecular analyses. The efficacy of disinfectants against spoilage yeasts was also assessed. RESULTSThe analyses on end products revealed the presence of the closest relatives to Zygosaccharomyces bailii with counts ranging from 1.40 to 4.72logcfug(-1). No spoilage yeasts were found in the indoor air and work surfaces. Polymerase chain reaction-denaturing gradient gel electrophoresis analysis, carried out directly on filling creams collected from unopened cans, showed the presence of bands ascribed to the closest relatives to Z.bailii sensu lato, although with counts<1logcfug(-1). Susceptibility testing of yeast isolates to disinfectants showed a significantly lower effect of 10% alkyl dimethyl benzyl ammonium chloride. Different responses of isolates to the tested disinfectants were seen. CONCLUSIONTo guarantee the quality of end products, reliable and sensitive methods must be used. Moreover, hygiene and the application of good manufacturing practices represent the most efficient way for the prevention and minimization of cross-contamination. (c) 2016 Society of Chemical Industry
The l(1)-optimal digital autopilot needed to control of the roll for an aircraft under an arbitrary unmeasured disturbances is addressed in this paper. This autopilot has to achieve a desired lateral motion control via minimizing the upper bound on the absolute value of the difference between the given and true roll angles. It is ensured by means of the two digital l(1)-optimal controllers of PI type The main result consists in establishing the fact that this controller can be robust in the presence of parametric and nonparametric uncertainties.
Autoimmune regulator (Aire) is essential in the perinatal period to prevent the multiorgan autoimmunity. Here we show that Aire-regulated single positive thymocyte trafficking in neonatal period is critical for thymic egress. Reduced thymic emigration was found in Aire(-/-) mice during neonatal period, leading to enhanced homeostatic expansion of peripheral T cells as early as 2 weeks of age. In neonatal Aire(-/-) mice, thymic expression of CCR7 ligands were dramatically reduced, resulting in decreased thymocyte motility and thymocyte emigration. This reduction of thymic egress in Aire(-/-) mice was alleviated beyond 3 weeks of age by an early upregulation of S1P(1) signaling. As the numbers and quality of thymic emigrants are essential for the establishment and maintenance of peripheral tolerance, the reduced thymic emigration during neonatal period may deteriorate autoimmunity caused by the emigration of autoreactive T cells.
BACKGROUND: Characterizing associations between the upper and lower airways is important for asthma management. OBJECTIVES: This study aimed to assess the determinants of incomplete asthma control in patients with allergic rhinitis (AR) and asthma. METHODS: Multiple factors including age, sex, atopy, smoking history, medication use, Asthma Control Questionnaire (ACQ) score, FEV1, fraction of exhaled nitric oxide (F-ENO), and rhinitis questionnaire score were examined. AR was defined by rhinitis symptoms and the sensitization to inhaled allergens. ACQ was used to dichotomize the subjects into the incompletely controlled group (ACQ score >= 0.75) and the well-controlled group. The factors that contribute to incomplete asthma control were assessed by a multivariate analysis. RESULTS: A total of 260 patients with AR and asthma were enrolled and 108 patients (42%) were classified as incomplete asthma control. The incompletely controlled group was older (P<.05), and had more airflow limitation, more airway inflammation, and more severe rhinitis symptoms (all P<.001). In contrast, the well-controlled group was more likely to be taking nasal corticosteroids (NCSs) (P<.01). In a multivariate model adjusted by age, asthma treatment, airflow limitation, and FENO, persistence and severity of rhinitis (odds ratio [OR], 2.57; 95% CI, 1.41-4.70, and OR, 2.00; 95% CI, 1.10-3.65) and nonuse of NCSs (OR, 3.83; 95% CI, 1.50-9.81) were independently associated with incomplete asthma control. CONCLUSIONS: The persistence and severity of AR and the use of NCSs were associated with the level of asthma control in patients with AR and asthma. Further studies are required to determine whether appropriate treatment of rhinitis would improve asthma control. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h) 2-high and T(h) 2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. Methods: Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. Results: Half of patients (n = 108; 52.6%) had a classical T(h) 2-high ("IL-4-, IL-5-and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4-and/or IL-13-high"pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F-and IL-25-high"profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high"(n = 16), "IL-6-high"(n = 8), "IL-22-high"(n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high"pattern or patients with only high IL-4 and/or IL-13. Conclusion: We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes.
Aluminium (Al) toxicity is a worldwide problem in agricultural practice. Based on evidence that Al resistance may be an inducible process and that rice is one of the most Al-resistant crops, the gene transcriptional responses to Al were investigated in two contrasting rice cultivars (resistant XN1 versus sensitive XX2) using differential display reverse transcription-PCR (DDRT-PCR) in combination with northern blotting analysis. A total of 37 genes were identified as differentially expressed, of which five have been previously known as Al regulated while the others are novel genes. Among the up-regulated genes, four encode ion transporters, two are involved in signal transduction, and five in the synthesis of cysteine and metallothionein. These could be members that are potentially involved in Al adaptation or resistance. On the other hand, the transcription of 17 genes was strongly inhibited under Al stress. These genes are associated with cytoskeletal dynamics and metabolism, and could be possible targets associated with Al toxicity. All of these differentially expressed genes may represent candidates that function in Al responses. The results suggest, at the transcriptional level, that cytoskeletal disruption may be associated with Al toxicity, whereas ion transport and sulphur metabolism could play major roles in Al adaptation or tolerance in rice.
Properly designed alarm systems can benefit operators in conducting routine and emergency tasks. With the digitization of main control rooms, the alarm interface can be designed in various ways that are different from the traditional "alarm tile" style. An innovative alarm bar interface is proposed in this paper. A preliminary lab experiment was conducted to compare the traditional alarm tile and the new alarm bar interfaces. Sixteen university students were recruited to participate in the experiment, in which two emergency scenarios, Loss of Coolant Accident and Steam Generator Tube Rupture, were tested. The experiment task included two parts: alarm detection and identification. The subjective ratings supported the innovative alarm bar design for better parameter trend perception. The objective performance measures showed that the simpler design of the alarm tile interface better aided the alarm detection performance, whereas the alarm bar interface had almost the same alarm identification performance as the alarm tile interface. Relevance to industry: An alarm system is critical for a complex industrial system. The experimental results show that design evaluation is more complex than it may seem. Although it has not been proved to be overwhelmingly superior to the tile design, the alarm bar design shows promise for aiding operators and needs to be further validated. (C) 2014 Elsevier B.V. All rights reserved.
PurposeMore than 25% of US adults experience mental health or substance use conditions annually, yet less than half receive treatment. This study explored how rural participants with behavioral health conditions pursue and receive care, and it examined how these factors differed across American Indian (AI) and geographic subpopulations. MethodsWe undertook a qualitative follow-up study from a statewide survey of unmet mental health and substance use needs in South Dakota. We conducted semistructured phone interviews with a purposive sample of key informants with varying perceptions of need for mental health and substance use treatment. ResultsWe interviewed 33 participants with mental health (n = 18), substance use (n = 9), and co-occurring disorders (n = 6). Twenty participants (61.0%) lived in rural communities that did not overlap with AI tribal land. Twelve participants (34.3%) were AI, 8 of whom lived on a reservation (24.2%). The discrepancy between actual and perceived treatment need was related to how participants defined mental health, alcohol, and drug use problems. Mental health disorders and excessive alcohol consumption were seen as a normal part of life in rural and reservation communities; seeking mental health care or maintaining sobriety was viewed as the result of an individual's willpower and frequently related to a substantial life event (eg, childbirth). Participants recommended treatment gaps be addressed through multicomponent community-level interventions. DiscussionThis study describes how rural populations view mental health, alcohol, and drug use. Enhancing access to care, addressing discordant perceptions, and improving community-based interventions may increase treatment uptake.
Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for traumatic brain injury (TBI); however, it remains unclear whether outcomes differ for those with and without a history of preinjury abuse. A meta-analysis was performed to examine this issue. The PubMed, Embase, and PsycINFO databases were searched for research that compared the neuroradiological, cognitive, or psychological outcomes of adults with and without a documented history of alcohol and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were analyzed using a random-effects model: Hedges's g effect sizes measured the mean difference in outcomes of individuals with/without a history of preinjury abuse, and Bayes factors assessed the probability that the outcomes differed. Patients with a history of alcohol and/or substance abuse had poorer neuroradiological outcomes, including reduced hippocampal (g=-0.82) and gray matter volumes (g=-0.46 to -0.82), and enlarged cerebral ventricles (g=-0.73 to -0.80). There were limited differences in cognitive outcomes: Executive functioning (g=-0.51) and memory (g=-0.39 to -0.43) were moderately affected, but attention and reasoning were not. The findings for fine motor ability, construction, perception, general cognition, and language were inconclusive. Postinjury substance and alcohol use (g=-0.97 to -1.07) and emotional functioning (g=-0.29 to -0.44) were worse in those with a history of alcohol and/or substance abuse (psychological outcomes). This study highlighted the type and extent of post-TBI differences between persons with and without a history of alcohol or substance abuse, many of which may hamper recovery. However, variation in the criteria for premorbid abuse, limited information regarding the history of abuse, and an absence of preinjury baseline data prevented an assessment of whether the differences predated the TBI, occurred as a result of ongoing alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance abuse and TBI.
Pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) enzymes are responsible for the operation of ethanolic fermentation pathway that appears to correlate to an extent with anoxia tolerance in plants. This study was undertaken with the objective of (a) analysing the rice pdc gene family and (b) altering the efficacy of the ethanolic fermentation process, through production of transgenic rice plants over- and under-expressing pyruvate decarboxylase (employing Ospdc1 gene from rice) as well as over-expressing alcohol dehydrogenase (employing Ghadh2 gene from cotton) proteins. Correlations noted in this study between the pattern of expression of the Pdc alpha-subunit and Ospdc2 transcript as well as between the Pdc beta-subunit and Ospdc1 transcript suggest the possibility that alpha-subunit is encoded by Ospdc2 and that beta-subunit is encoded by Ospdc1. The fact that levels of Pdc beta-subunit were particularly high in pUH-sPdc1 (plasmid construct designed for over-expression of Ospdc1) seedlings while levels of beta-subunit levels were negligible or lower in pUH-asPdc1 (plasmid construct designed for under-expression of Ospdc1) seedlings also support these observations. Transgenics raised for over-expression of Pdc and Adh and under-expression of Pdc were confirmed for the transgene presence and effects by PCR, Southern blotting, Northern blotting, Western blotting and isozyme assays. Pdc and Adh over-expressing rice transgenics at early seedling stage under unstressed control growth conditions showed slight, consistent advantage in root vigour as compared to that of wild-type seedlings. (C) 2007 Elsevier Masson SAS. All rights reserved.
Background: Prior research has repeatedly shown that alcohol dependence is associated with a large range of impairments in psychological processes, which could lead to interpersonal deficits. Specifically, it has been suggested that these interpersonal difficulties are underpinned by reduced recognition and sharing of others' emotional states. However, this pattern of deficits remains to be clarified. This study thus aimed to investigate whether alcohol dependence is associated with impaired abilities in decoding contextual complex emotions and with altered sharing of others' emotions. Methods: Forty-one alcohol-dependent individuals (ADI) and 37 matched healthy individuals completed the Multifaceted Empathy Test, in which they were instructed to identify complex emotional states expressed by individuals in contextual scenes and to state to what extent they shared them. Results: Compared to healthy individuals, ADI were impaired in identifying negative (Cohen's d=0.75) and positive (Cohen's d=0.46) emotional states but, conversely, presented preserved abilities in sharing others' emotional states. Conclusions: This study shows that alcohol dependence is characterized by an impaired ability to decode complex emotional states (both positive and negative), despite the presence of complementary contextual cues, but by preserved emotion-sharing. Therefore, these results extend earlier data describing an impaired ability to decode noncontextualized emotions toward contextualized and ecologically valid emotional states. They also indicate that some essential emotional competences such as emotion-sharing are preserved in alcohol dependence, thereby offering potential therapeutic levers.
Some addicted patients have social cognition deficits that require therapists to have special skills to ensure treatment success. Specific remediation techniques that teach addicted patients to look at the relevant emotional cues when interacting with people should be tested as adjunctive treatment.
Considerable evidence has identified biased cognitive processing of alcohol-related stimuli as an important factor in the maintenance of alcohol-seeking and relapse among individuals suffering from alcohol use-disorders (AUDs). In addition, a large body of research has demonstrated that exposure to alcohol cues can elicit powerful alcohol cravings. Little is known, however, about the possible relationship between attentional bias and cue-induced cravings, and even less is known about these processes in social drinkers without a personal history of AUDs. The goal of this study was to examine the possibility that attentional biases toward alcohol-related stimuli would predict elevated cue-induced alcohol craving in this population. Young adult social drinkers (N = 30, Mean age = 22.8 +/- 1.9, 61% female) recruited from an urban university population completed a visual dot probe task in which they were presented with alcohol and neutral stimulus pictures that were immediately followed by a visual probe replacing one of the pictures. Attentional bias was measured by calculating reaction times to probes that replaced alcohol stimuli vs. neutral stimuli. Participants then completed a classic alcohol cue-exposure task and reported cravings immediately before and after alcohol and neutral cue-exposures. Not surprisingly, exposure to alcohol cues elicited significant cravings. Consistent with the study hypothesis, larger attentional biases toward alcohol stimuli predicted higher levels of alcohol craving. Findings demonstrate that heightened attention to alcohol stimuli can significantly impact motivation to consume in healthy young adults, and suggest a possible pathway linking cognitive processes early in the drinking trajectory to the later development of AUDs. (C) 2017 Elsevier Ltd. All rights reserved.
AimsTo examine the association between a life-time history of insomnia and hypersomnia compared with no sleep disturbance and substance use patterns and amounts before and after a substance use treatment episode. DesignSecondary analysis of data from the Drug Abuse Treatment Outcome Studies conducted from 1991 to 1994. SettingData were collected at 96 substance use treatment programs in 11 United States cities, including short-term in-patient, long-term residential, methadone maintenance and out-patient drug-free treatment modalities. ParticipantsStudy samples included 7168 adults at treatment entry and 2965 at 12months post-treatment entry whose primary substance use at entry was alcohol (14.7%), cocaine (62.7%) or heroin (22.6%). MeasurementsLife-time history of insomnia and hypersomnia was assessed via self-report. Type and frequency of substance use were assessed at treatment entry. Substance use was also assessed 12months following treatment completion. Associations were examined using linear and logistic regression with age, sex, race, education level, depression history, treatment modality and in-treatment substance use as covariates. FindingsLife-time history of insomnia, hypersomnia, both or neither was reported by 26.3, 9.5, 28.0 and 36.2% of participants, respectively. Compared with no sleep disturbance, life-time insomnia and hypersomnia were associated at treatment entry with unique substance use patterns and a higher frequency of any substance use (P<0.001). All types of sleep disturbance were associated with higher rates of cocaine use at 12-month post-entry (odds ratios: 1.30-1.57). ConclusionsThere is evidence of an adverse association between substance use and sleep disturbance including higher frequency of all substance use before substance abuse treatment and higher rates of cocaine use after a treatment episode.
Rationale Social cognition influences social interactions. Alcohol reportedly facilitates social interactions. However, the acute effects of alcohol on social cognition are relatively poorly studied. We investigated the effects of alcoholic or non-alcoholic beer on emotion recognition, empathy, and sexual arousal using the dynamic face emotion recognition task (FERT), Multifaceted Empathy Test (MET), and Sexual Arousal Task (SAT) in a double-blind, random-order, cross-over study in 60 healthy social drinkers. We also assessed subjective effects using visual analog scales (VASs), blood alcohol concentrations, and plasma oxytocin levels. Alcohol increased VAS ratings of stimulated, happy, talkative, open, and want to be with others. The subjective effects of alcohol were greater in participants with higher trait inhibitedness. Alcohol facilitated the recognition of happy faces on the FERT and enhanced emotional empathy for positive stimuli on the MET, particularly in participants with low trait empathy. Pictures of explicit sexual content were rated as less pleasant than neutral pictures after non-alcoholic beer but not after alcoholic beer. Explicit sexual pictures were rated as more pleasant after alcoholic beer compared with non-alcoholic beer, particularly in women. Alcohol did not alter the levels of circulating oxytocin. Alcohol biased emotion recognition toward better decoding of positive emotions and increased emotional concern for positive stimuli. No support was found for a modulatory role of oxytocin. Alcohol also facilitated the viewing of sexual images, consistent with disinhibition, but it did not actually enhance sexual arousal. These effects of alcohol on social cognition likely enhance sociability. www.clinicaltrials.gov/ct2/show/NCT02318823 RefTarget Address="http://www.clinicaltrials.gov/ct2/show/NCT02318823" TargetType="URL"/>
Background and aimsHIV-infected people with substance use disorders are least likely to benefit from advances in HIV treatment. Integration of extended-release naltrexone (XR-NTX) into HIV clinics may increase engagement in the HIV care continuum by decreasing substance use. We aimed to compare (1) XR-NTX treatment initiation, (2) retention and (3) safety of XR-NTX versus treatment as usual (TAU) for treating opioid use disorder (OUD) and/or alcohol use disorder (AUD) in HIV clinics. DesignNon-blinded randomized trial of XR-NTX versus pharmacotherapy TAU. SettingHIV primary care clinics in Vancouver, BC, Canada and Chicago, IL, USA. ParticipantsFifty-one HIV-infected patients seeking treatment for OUD (n=16), AUD (n=27) or both OUD and AUD (n=8). MeasurementsPrimary outcomes were XR-NTX initiation (receipt of first injection within 4weeks of randomization) and retention at 16weeks. Secondary outcomes generated point estimates for change in substance use, HIV viral suppression [HIV RNA polymerase chain reaction (pcr)<200 copies/ml] and safety. FindingsTwo-thirds (68%) of participants assigned to XR-NTX initiated treatment, and 88% of these were retained on XR-NTX at 16weeks. In comparison, 96% of TAU participants initiated treatment, but only 50% were retained on medication at 16weeks. Mean days of opioid use in past 30 days decreased from 17.3 to 4.1 for TAU and from 20.3 to 7.7 for XR-NTX. Mean heavy drinking days decreased from 15.6 to 5.7 for TAU and 12.5 to 2.8 for XR-NTX. Among those with OUD, HIV suppression improved from 67 to 80% for XR-NTX and 58 to 75% for TAU. XR-NTX was well tolerated, with no precipitated withdrawals and one serious injection-site reaction. ConclusionsExtended-release naltrexone (XR-NTX) is feasible and safe for treatment of opioid use disorder and alcohol use disorder in HIV clinics. Treatment initiation appears to be lower and retention greater for XR-NTX compared with treatment as usual ( NCT01908062).
In this paper, a three-stage operational amplifier with low-power consumption for ALD has been designed. Based on TSMC 0.55 mu m CMOS process, using HSPICE 2008 software for circuit simulation, the results showed that the proposed op-amp has more than 100dB open loop gain, meanwhile the static power consumption is less than 900 mu w. The circuit's phase margin is 103degrees, CMRR is 51dB and power supply rejection ratio is 57dB.
One-step aldol condensation of methyl acetate with formaldehyde (or trioxane) for preparing methyl acrylate at 623 K-653 K has stimulated researchers' attention in recent years. Herein, a new methodology for one-step synthesis of methyl acrylate from methyl acetate and trioxane promoted by generated trifluoromethanesulfonate ionic liquid, via aldol condensation, at mild temperature was developed. The kinetic and thermodynamic studies on this new process were also firstly investigated systematically. Experiments were conducted in a batch reactor under the temperatures of 283 K-298 K and reaction times of 10 min - 100 min, wherein the side reactions could be ignored. The proposed mechanism based kinetic model was established and simulated with experimental data. The model showed good agreement with experimental results within the range of acceptable deviation, thereby the pre exponential factor and activation energy of each reaction step were obtained. Moreover, the equilibrium constant and enthalpy change of each reversible reaction were also calculated through Van't Hoff formula. (C) 2017 Elsevier B.V. All rights reserved.
Background: Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. Methods: We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3(-/-)), caspase-1 knockout (Casp-1(-/-)), and interleukin-1 receptor knockout (IL-1R(-/-)) mice treated with vehicle or aldosterone (600 mu gkg(-1)d(-1) for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Results: Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1 levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1 secretion by bone marrow-derived macrophages by activating nuclear factor-B signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1 in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Conclusions: Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.
Aldosterone has been shown to stimulate renal TGF-beta(1) expression. However, the mechanisms for aldosterone-induced TGF-beta(1) expression have not been clearly determined in mesangial cells. We examined the role of extracellular-signal regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) in the aldosterone-induced TGF-beta(1) expression in rat mesangial cells. TGF-beta(1) protein in the conditioned medium released from rat mesangial cells was measured by sandwich ELISA, TGF-beta(1) mRNA expression was analyzed by Northern blotting, AP-1 DNA binding activity was measured by EMSA and the ERK1/2, JNK activity was analyzed by western blotting. Aldosterone significantly stimulated TGF-beta(1) protein production and TGF-beta(1) mRNA expression in mesangial cells in a dose-dependent manner. Aldosterone significantly increased AP-1 DNA binding activity in mesangial cells. Pre-treatment of cells with AP-1 inhibitor, curcumin, blocked aldosterone-induced AP-1 DNA binding activity as well as aldosterone-induced TGF-beta(1) production. Aldosterone increased phosphorylation of ERK1/2 and JNK in mesangial cells. Pre-treatment of cells with ERK1/2 inhibitor, PD98059, or JNK inhibitor, SP600125 significantly inhibited aldosterone-induced ERK1/2 and JNK activity and subsequently TGF-beta(1) production, respectively. We conclude that aldosterone-induced TGF-beta(1) expression in mesangial cells is regulated by the ERK1/2, JNK and AP-1 intracellular signaling pathways.
The objective of this study was to measure the effect of selection for tolerance on the severity of the Aleutian disease (AD) lesions in mink. Sensitivity and specificity of antibody detection in the blood by counter-immunoelectrophoresis (CIEP) relative to the presence of Aleutian mink disease virus (AMDV) in the spleen by PCR in naturally infected farmed mink were also estimated. Carcasses of 680 sero-positive (CIEP-P) black mink from 28 farms in Nova Scotia, Canada, and from 132 sero-negative (CIEP-N) mink from 14 of these farms were collected at pelting time. A total of 116 of the CIEP-P mink were from three farms where animals have been selected for tolerating AD for almost 20 years. The severity of the AD lesions was assessed by histopathological examination of kidneys, lungs, heart, brain and liver on a scale of 0 to 4. Sensitivity and specificity of CIEP relative to PCR were 0.97 and 0.85, respectively, and 16.5% of CIEP-N mink were PCR positive, which could be one of the reasons for the failure of virus eradication by CIEP in Canada. The CIEP-N and tolerant CIEP-P animals had 9.39 and 6.23 greater odds of showing lower lesion severity, respectively, than the CIEP-P animals (P < 0.01). The CIEP-N mink had a slightly higher chance (P = 0.07) of showing lower lesion severity (odds ratio 1.51) compared with tolerant CIEPP mink. The results suggested that tolerant mink had significantly reduced severity of AD lesions despite having anti-viral antibodies and carrying the virus. (C) 2017 The Authors. Published by Elsevier Ltd.
The objective of this study was to assess the sensitivity of the Omni Klentaq-LA DNA polymerase for detecting Aleutian mink disease virus (AMDV) in mink blood and tissues by PCR without DNA extraction. The presence of AMDV DNA was directly tested by Klentaq in the plasma, serum, whole blood, and spleen homogenates of 188 mink 4 and 16 months after inoculation with the virus. Samples from bone marrow, small intestine, liver, lungs, kidneys, and lymph nodes of 20 of the same mink were also tested by Klentaq. DNA was extracted from paired samples of plasma and the aforesaid tissues by a commercial nucleic acid extraction kit (Dynabeads Silane) and tested by PCR. Compared with the extracted DNA, Klentaq detected a significantly greater number of samples in the whole blood, serum, plasma, spleen, and small intestine. It was concluded that Klentaq is a preferred system for directly detecting AMDV DNA in mink blood and tissues. The lower success rate of extracted DNA compared with Klentaq could be the result of DNA losses during the extraction process. This is an important factor in chronically infected mink, which have a low AMDV copy number in the bloodstream. Direct AMDV detection also reduces the cost of PCR amplification and lowers the risk of sample contamination.
Background: Childhood adversities and emotional dysregulation are connected with chronic pain, alexithymia, and depression. Longitudinal studies exploring the impact of their co-occurrence on the pain situation are rare.Aims: The influence of alexithymia, depression, baseline pain situation, and treatment options on the course of chronic pain in a clinical sample was studied.Methods: The baseline data was collected from chronic pain patients (n=154) before their first pain clinic visit, and the follow-up data after 1 year by self-report questionnaires. Study variables consisted of pain intensity, pain disability, alexithymia (TAS-20), depression (BDI-II), and treatment interventions. Statistical analyses were performed to find out differences between baseline and follow-up, as well as between alexithymic and non-alexithymic patients, and to estimate the effect of the treatment provided.Results: At follow-up, the majority of the patients had pain intensity and disability severe enough to disrupt with their daily living. None of treatment interventions was related to better outcome. Alexithymic patients reported more pain disability and depression at both baseline and at follow-up. The effect of alexithymia on pain disability was mediated by depression. The use of opioids was connected to alexithymia and depressiveness. Alexithymia and depression made a substantial contribution to poorer outcome.Conclusions: Severe pain intensity and disability with depression and alexithymia predicted difficulties in achieving improvement. Depression and alexithymia probably impair compliance with treatment and adherence to interventions. Their co-occurrence with a more severe pain situation and with the use of opioids indicates psychological problems underlying the pain experience.
Background and objectives: Alexithymia is a multidimensional personality construct including the components difficulties identifying feelings (DIF), difficulties describing feelings (DDF), and externally oriented thinking (EOT). Different features of alexithymia are thought to reflect specific deficits in the cognitive processing and regulation of emotions. The aim of the present study was to examine for the first time patterns of deployment of attention as a function of alexithymia components in healthy persons by using eye-tracking technology. It was assumed that EOT is linked to avoidance of negative images. Methods: 99 healthy adults viewed freely pictures consisting of anxiety-related, depression-related, positive, and neutral images while gaze behavior was registered. Alexithymia was assessed by the 20 Item Toronto Alexithymia Scale. Measures of anxiety, depression, and (visual-perceptual) intelligence were also administered. Results: A main effect of emotion condition on dwell times was observed. Viewing time was lowest for neutral images, longer for depression-related and happy images, and longest for anxiety-related images. Gender and EOT had significant effects on dwell times. EOT correlated negatively with dwell time on depression-related (but not anxiety-related) images. There were no correlations of dwell times with depression, trait anxiety, intelligence, DIF, or DDF. Limitations: Alexithymia was assessed exclusively by self-report. Conclusions: Our results show that EOT but not DIF or DDF influences attention deployment to simultaneously presented emotional pictures. EOT may reduce attention allocation to dysphoric information. This attentional characteristic of EOT individuals might have mood protecting effects but also detrimental impacts on social relationships and coping competencies. (C) 2016 Elsevier Ltd. All rights reserved.
In legume plants, uricase gene (Nodulin-35) plays a positive role in metabolism of ureide and amide compounds in symbiotic nitrogen-fixing in the nodules. In this study, a pot experiment was performed to examine the effects of ammonium application on the transcription of MsU2 gene and distribution of major nitrogen compounds in alfalfa Medicago sativa. Data showed that alfalfa plant has a significant difference in contents of nitrogen compounds in xylem saps compared with soybean plant, and belongs to typical amide type legume plants with little ureide accumulation, and the accumulation of asparagines and ureide in the tissues of alfalfa is mainly gathered in the nodules. Northern blotting showed that excessive ammonium significantly inhibited the transcription of MsU2 gene in the nodules and roots, and mRNA accumulation of MsU2 gene in the plants exposed to excessive ammonium decreased gradually with culture time extension, indicating that application of ammonium significantly inhibited the transcription of MsU2 gene in the alfalfa plants. Although the application of excessive ammonium increased the contents of amino acids in various tissues of alfalfa, the accumulation of allantoin reflecting the strength of uricase activity is remarkably reduced in the xylem saps, stems and nodules when alfalfa plants exposed to excessive ammonium, suggesting that application of excessive ammonium generated a negative effect on symbiosis fixing-nitrogen system due to inhibition of ammonium ion on uricase activity in the nodules of alfalfa. This result seems to imply that application of excessive ammonium in legume plants should not be proposed to avoid affecting the ability of fixing nitrogen in the nodules of legume plants, and reasonable dose of ammonium should be recommended to effectively utilize the fixed N from atmosphere in legume plant production.
The imminent depletion of fossil fuels and the surging global demand for renewable energy have led to the search for nonconventional energy sources. After a few decades of trial and error, the world is now testing the sources of the third generation of fossil fuels, which contain for most parts microalgae. With more than 80% oil content, being adaptable in growth parameters and highly versatile, microalgae are highly promising sources of biofuels in the present time. The present article makes a sweeping attempt to highlight the various methods employed for cultivation of microalgae, techniques to harvest and extract biomass from huge algal cultures, as well as their downstream production and processing procedures. The advantages, limitations, and challenges faced by each of them have been described to some extent. Major concerns pertaining to biofuels are supposed to be their environmental sustainability and economic viability along with their cost effectiveness. This would require a great deal of empirical data on existing systems and a great deal of optimization to generate a more robust one. We have concluded our article with a SWOT analysis of using algae for biodiesel production in a tabulated form. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
The natural variation of environmental factors in freshwater basins determines their biodiversity. Among them, calcium is a key physiological compound for freshwater invertebrates. It is required for shell formation, muscle contraction, it mediates gene expression and allows counteracting acidosis during stress periods, among other functions. Although the distribution of different freshwater species has been suggested to be linked with the environmental calcium concentration, as yet no research studies have confirmed this. Identifying whether environmental calcium concentrations might determine the invasion success of alien species would be critical in developing and implementing effective management strategies to control them. Here, a multidisciplinary approach integrating field surveys, analytical chemistry techniques, molecular biology analyses and a lab-scale experiment was taken to decipher whether the environmental calcium Concentration might hamper the establishment of Corbicula fluminea in northwestern Iberian rivers. A Principal Component Analysis on water chemistry variables from 13 water bodies identified environmental calcium concentration, among others, as one key factor that best characterized the distribution area of C. fluminea. The calcium content in animals' bodies from two representative rivers was dependent on the environmental calcium concentration of freshwater basins; the lower the concentration, the lower the body's content. The expression of stress- and calcium homeostasis-related genes was higher in C fluminea from low calcium concentration environments than in those from calcium-rich freshwater basins. Finally, under experimental conditions, lower water calcium concentrations decreased C fluminea growth rates. The present data suggest, for the first time, that environmental calcium concentration may act as a determinant factor on the invasion success of C. fluminea in freshwater environments. Our results provide new clues for the identification of basins with increased risk of potential invasion by C fluminea based on environmental calcium levels. (C) 2016 Elsevier B.V. All rights reserved.
Munchausen syndrome by proxy (MSBP), also known as fabricated or induced illness in a child by a caretaker, is a form of abuse where a caregiver deliberately produces or feigns illness in a person under his or her care, so that the proxy will receive medical care that gratifies the caregiver. The affected children are often hospitalized for long periods and endure repetitive, painful and expensive diagnostic attempts. We present an analytically confirmed case of MSBP by alimemazine. A 3-year-old boy was brought repetitively to a Pediatric Emergency Department by his mother because he presented limb tremors, dysarthria, obnubilation, and ataxia and generalized tonic-clonic seizures coinciding with intermittent fever. Neither the rest of the physical examination nor the complementary tests showed any significant alterations. MSBP was suspected and a routine systematic toxicological analysis in urine and blood was requested. Alimemazine was detected in all biological samples. The administration of this drug was never mentioned by the mother and the subsequent interview with her corroborated the suspicion of MSBP. Clinically, after separation from the mother, the child's neurological symptoms gradually improved until the complete disappearance of the cerebellar symptoms. Alimemazine was quantified in serum, urine, gastric content and cerebrospinal fluid samples by gas chromatography-mass spectrometry (maximum serum level was 0.42 mu g/ml). Hair quantification of alimemazine was performed by ultra-performance liquid chromatography-tandem mass spectrometry in different segments of hair. The results confirmed regular substance use during the at least eight last months (8.8, 14.7, 19.7 and 4.6 ng/mg hair starting from most proximal segment). This patient represents the first case published with analytical data of alimemazine in blood, urine, gastric content, cerebrospinal fluid and hair, which allowed us to prove an acute and repetitive poisoning with alimemazine as evidence of MSBP. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary technique available in all laboratories of pathology. This method is generally used for diagnostic purposes, but several studies have investigated the sensitivity and specificity of different immunohistochemical anti-bodies as a surrogate test in the determination of predictive biomarkers in non-small cell lung cancer (NSCLC), particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical examination of the works comparing the consistency of IHC expression and conventional molecular techniques to identify genetic alterations with predictive value in NSCLC is discussed. Summarizing, data on sensitivity and specificity of antibodies against ALK and ROS1 are very consistent and time has come to trust in IHC at least as a cost-effective screening tool to identify patients with rearranged tumors in clinical practice. On the other hand, mutant-specific antibodies against EGFR demonstrate a good specificity but a lowto- fair sensitivity, raising some cautions on their employment as robust predictive biomarkers. A brief comment on preliminary experiences with antibodies against BRAF, RET, HER2 and c-MET is also included.
Allatostatins are important regulatory neuropeptides which are widely distributed in invertebrates and execute their functions through either neural or Immoral routes. However, the regulatory mechanism of the gene expression is unclear. In this paper, we report a naturally occurring amisense transcript, named as asMacro-AST A, of the crustacean FGLamide allatostatin gene (Macro-AST A) from the prawn, Macrobrachium rosenbergii. The asMacro-ASTA contains an 843-bp sequence fully complementary to the 3'end of the Macro-ASTA. To our knowledge, this is the first report of a natural antisense transcript in crustacean and the first endogenous antisense transcript of all identified allatostatin genes. Northern blotting analysis demonstrated that the gene was expressed in the thoracic ganglia where the sense gene was also expressed. Furthermore, we have detected a RNA-RNA duplex between the sense-antisense complementary region by using RNasc protection analysis and RT-PCR. These results suggest that the antisense gene may play a role in the regulation of Macro-AST A gene expression. (c) 2006 Elsevier Inc. All rights reserved.
Traditional digital controls mostly use digital-analog converters to convert input and output voltages into digital coding to achieve control. This paper proposes the use of two digital ramps with two different frequencies to replace a digital-analog converter. This approach can produce seven bit resolution for the DPMW signal. In addition, we use an all-digital DLL phase correction concept to further enhance the resolution of the DPWM signal by an additional three bits, resulting in 10-bit DPWM signal resolution. The proposed circuit uses 0.35 mu m CMOS processes, with a core area of 0.987 mm(2), a system switching frequency of 500 KHz, an input voltage range of 3.3-4.2 V, and an output voltage range of 5 V. Output voltage measurement accuracy reaches 99%, while the system reaches efficiency of 91% with output loads of up to 500 mA. (C) 2015 Elsevier Ltd. All rights reserved.
Background: Knockdown resistance (kdr), caused by alterations in the voltage-gated sodium channel (Na-v), is one of the mechanisms responsible for pyrethroid (PY) resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different mutations were described in the IIIS6 Na-v segment in populations from Asia, North America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6 Na-v segments. The Phe1534Cys kdr mutation in the IIIS6 Na-v segment is the most prevalent in populations of Ae. aegypti worldwide, also found in Ae. albopictus from Singapore. Herein, we investigated the DNA diversity corresponding to the IIS6 and IIIS6 Na-v segments in natural populations of Ae. albopictus from Brazil. Methods: DNA from eight Brazilian Ae. albopictus natural populations were individually extracted and pooled by states of origin, amplified, cloned and sequenced for the corresponding IIS6 and IIIS6 Na-v segments. Additionally, samples from each location were individually genotyped by an allelic specific PCR (AS-PCR) approach to obtain the genotypic and allelic frequencies for the 1534 Na-v site. Results: No non-synonymous substitutions were observed in the IIS6 sequences. However, the Phe1534Cys kdr mutation was evidenced in the Ae. albopictus Na-v IIIS6 segment sequences from Parana (PR) and Rondonia (RO) states, but not from Mato Grosso (MT) state. The 1534Cys(kdr) allele varied from 3% (Marilena/PR and Porto Velho/RO) to 10% ( Foz do lguacu/ PR). To our knowledge, this paper reports the first occurrence and provides distribution data of a possible kdr mutation in Ae. albopictus in South America. Conclusion: The emergence of a likely kdr mutation in Ae. albopitus natural populations is a signal of alert for vector control measures since PY are the most popular insecticides adopted by residents. Additionally, once the kdr allele is present, its frequency tends to increase faster under exposition to those compounds. Although the Asian tiger mosquito is not incriminated as an important vector of dengue, chikungunya and Zika viruses in South America, its importance in this regard has been extensively discussed since Ae. albopictus is rapidly spreading and can also migrate between sylvatic and urban environments. Therefore, insecticide resistance monitoring initiatives should also be extended to Ae. albopictus in Brazil in order to maintain chemical compounds as an efficient vector control tool when needed.
Introduction: Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma [PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a diagnostic clue to these entities. Targeted therapies against BRAF-V600 protein have shown promising results in GNT. The aim of this study was to assess the utility of BRAF-V600E immunohistochemistry (IHC, clone VE1) in daily practice in a series of 140 glial, and GNT compared to molecular biology (MB) techniques. Methods: We performed BRAF-V600E IHC on all 140 cases. We used Sanger sequencing and allele-specific quantitative PCR (ASQ-PCR) to detect BRAF-V600E mutation when sufficient amount of materiel was available. Results: BRAF-V600E immunostaining was detected in 29.5% of cases (41/140 cases; 61.5% GG/GC/AGG (32/52), 33% PXA, 6.6% pilocytic astrocytomas). In 47 cases, MB could be performed: Sanger sequencing and ASQ-PCR in 34 cases, ASQ-PCR only in 11 cases, and Sanger sequencing only in two cases. In initial tumors, Sanger sequencing identified BRAF-V600E mutation in 19.5% tumors (seven of 36 tested cases). ASQ-PCR showed mutation in 48.5% tumors (17/35 tested cases). In six cases (5 GG, one PXA), the results were discordant between IHC and MB; the five GG cases were immunopositive for BRAF-V600E but wild type with both MB techniques. In another 7 GG, the percentage of mutated (ganglion) cells was low, and Sanger sequencing failed to detect the mutation, which was detected by IHC and ASQ-PCR. Conclusions: In tumors with few mutated cells (e.g., GG), anti-BRAF-V600E IHC appears more sensitive than Sanger sequencing. The latter, although considered as the gold standard, is not to be used up-front to detect BRAF mutation in GG. The combination of IHC and ASQ-PCR appears more efficient to appraise the indication of targeted therapies in these glioneuronal tumors.
BACKGROUND: It is unclear whether allergen immunotherapy (AIT) can be safely initiated during the pollen season (coseasonal initiation [CSI]) because of a potential increased risk of systemic allergic reactions. OBJECTIVE: To systematically review publications reporting the safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) CSI to validate or invalidate the perception of increased safety risk. METHODS: PubMed, EMBASE, Ovid, Literatura Latino Americana em Ciencias da Saude (LILACS), and Cochrane Library databases were searched without limits for studies of any design reporting SCIT or SLIT CSI for pollen allergen. Congress abstracts were included. RESULTS: Nineteen eligible studies were identified: 8 SCIT (n = 947 subjects total; n[340 double-blind placebo-controlled [DBPC]) and 11 SLIT (n = 2668 subjects total; n = 565 DBPC). Study characteristics and safety reporting were heterogeneous. No epinephrine administrations were reported. Discontinuation frequencies were 6% or less and 10% or less with SCIT and SLIT CSI, respectively. In SCIT studies, systemic allergic reaction frequency was 0% to 7% with "up to peak season" or CSI, 0% to 6% with "after peak season" or out-of-season initiation, and 0% to 7% with placebo. In SCIT studies, serious treatment-related adverse event (AE) frequency with CSI ranged from 0% to 2%; few severe AEs were reported. In SLIT studies, systemic allergic reaction frequency ranged from 0% to 4% with CSI, 0% with out-of-season initiation, and 0% to 2% with placebo. Overall, 2 serious treatment-related AEs with SLIT CSI were reported. Severe AE frequency in SLIT studies ranged from 0% to 8% with CSI, 0% to 12% with out-of-season initiation, and 0% to 8% with placebo. CONCLUSIONS: No increase in AEs of concern was observed with SCIT or SLIT CSI; however, additional data with standardized regimens and doses are needed. (C) 2016 American Academy of Allergy, Asthma & Immunology
Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.
BackgroundClinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. MethodsA Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. ResultsThe Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for pollen season', high pollen season' (or peak pollen period') and high pollen days'. ConclusionThis EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.
There is no universally accepted grading system to classify the severity of systemic allergic reactions (SARs), including anaphylaxis. Although a consensus definition for anaphylaxis was established in 2005, the signs and symptoms required to define a reaction as anaphylaxis are inconsistently applied in research and clinical practice. As a result, it is difficult to compare and evaluate safety outcomes in surveys, clinical practice and trials, and pharmacovigilance data. In 2010, the World Allergy Organization (WAO) proposed a uniform grading system to classify allergen immunotherapy SARs. The basis of the grading system is the organ system(s) involved and reaction severity. The final grade is determined by the physician/health care professional after the event is over. Although the 2010 WAO grading system was developed to classify allergen immunotherapy SARs, with appropriate modifications, it can be used to classify SARs from any cause. The purpose of this Rostrum is to present a proposed modification of the 2010 WAO SAR grading system that will make it applicable to all SARs due to any cause. The modified grading system allows for classification of less severe SARs, which may be underreported or overreported in clinical trials and surveillance studies, depending on the criteria specified for adverse event reporting. The universal use of the proposed modified SAR grading system will allow for better safety comparisons across different venues and treatment protocols. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:58-62)
Keratinocytes (KCs) play a key role in all phases of skin sensitization. We recently identified interleukin-18 (IL-18) production as useful end point for determination of contact sensitization potential of low molecular weight chemicals. The aim of this study was to identify genes involved in skin sensitizer-induced inflammasome activation and to establish their role in IL-18 production. For gene expression analysis, cells were treated for 6 h with p-phenylenediamine (PPD) as reference contact allergen; total RNA was extracted and examined with a commercially available Inflammasome Polymerase Chain Reaction (PCR) array. Among genes induced, NLRP12 (Nod-like receptor P12) was selected for further investigation. NLRP12 promoter region contains Blimp-1 (B-lymphocyte-induced maturation protein-1)/PRDM1 binding site, and from the literature, it is reported that Blimp-1 reduces NLRP12 activity and expression in monocytes/macrophages. Their expression and role in KCs are currently unknown. To confirm NLRP12 expression and to investigate its relationship with Blimp-1, cells were exposed for different times (3, 6 and 24 h) to the extreme sensitizer 2,4-dinitrochlorobenzene (DNCB) and the strong sensitizer PPD. Allergens were able to induce both genes, however, with different kinetic, with DNCB more rapidly upregulating Blimp-1 and inducing IL-18 production, compared to PPD. NLRP12 and Blimp-1 expression appeared to be inversely correlated: Blimp-1 silencing resulted in increased NLRP12 expression and reduced contact allergen-induced IL-18 production. Overall results indicate that contact allergens of different potency differently modulate Blimp-1/NLRP12 expression, with strong allergen more rapidly downregulating NLRP12, thus more rapidly inducing IL-18 production. Data confirm that also in KCs, NLRP12 has an inhibitory effect on inflammasome activation assessed by IL-18 maturation.
Background There is limited understanding of how maternal diet affects breastmilk food allergen concentrations, and whether exposure to allergens through this route influences the development of infant oral tolerance or sensitization. Objective To investigate how maternal dietary egg ingestion during early lactation influences egg protein (ovalbumin) levels detected in human breastmilk. Methods In a randomized controlled trial, women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (>4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. The permeability of the mammary epithelium was assessed by measuring the breastmilk sodium : potassium ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and prior to the introduction of egg in solids at 16 weeks. Results Average maternal egg ingestion was associated with breastmilk ovalbumin concentration. Specifically, for each additional egg ingested per week, there was an average 25% increase in ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin concentrations were significantly higher in the ` high-egg' group (>4 eggs per week) compared with the ` egg-free' group (P = 0.04). However, one-third of women had no breastmilk ovalbumin detected. No detectable associations were found between mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant plasma egg-specific IgG4 levels were also positively associated with maternal egg ingestion, with an average 22% (95% CI: 3-45%) increase in infant egg-specific IgG4 levels per additional egg consumed per week (P = 0.02). Conclusions and Clinical Relevance Increased maternal egg ingestion is associated with increased breastmilk ovalbumin, and markers of immune tolerance in infants. These results highlight the potential for maternal diet to benefit infant oral tolerance development during lactation.
The ocular surface is constantly exposed to environmental irritants, allergens and pathogens, against which it can mount a prompt immune response to preserve its integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal immune system must also discriminate between harmless and potentially dangerous antigens, a seemingly complicated task. Despite its unique features, the ocular surface is a mucosal lining, and as such, it shares some homeostatic and pathophysiological mechanisms with other mucosal surfaces. The purpose of this review is to explore the mucosal homeostatic immune function of the ocular surface in both the healthy and diseased states, with a special focus on mucosal immunology concepts. The information discussed in this review has been retrieved by PubMed searches for literature published from January 1981 to October 2016.
Allergic rhinitis (AR) is a common illness in children and can impair their quality of life. Furthermore, many children remain symptomatic despite maximizing systemic antihistamine and topical therapies. It is at this clinical juncture that immunotherapy may be considered. The efficacy and safety associated with both subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as treatment options for pediatric patients, with specific focus on current literature as it relates to SLIT in children, including those with perennial allergic rhinitis. Although there is more extensive experience with SLIT treatment in Europe, grass and ragweed tablet forms of SLIT are approved in the US. Approaches to the care of pediatric patients with allergic rhinitis are presented. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:46-51)
Background: Allergic rhinitis (AR) is the most common chronic disease among children. To characterize the disease, a modified classification of severity (m-ARIA) has recently been validated in AR children. When medical treatment fails, surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our objective was to assess the prevalence of NOD and their influence in medical treatment response among children with persistent AR (PER). Methods: In a prospective, real-life study, 130 paediatric PER patients (13.1 +/- 2.8years, females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were assessed for their response (R, responders; NR, non-responders) to medical treatment (intranasal steroids and antihistamines or antileukotrienes) by direct questioning and nasal symptom visual analogue scale, the presence of NOD (septal deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal symptoms, rhinitis severity (modified ARIA criterion) and asthma control (International Consensus On Pediatric Asthma criterion). Results: After 2months of treatment, the NR group presented a higher prevalence of obstructive septal deformity and severe inferior turbinate enlargement when compared with the R group. Higher septal deformity and turbinate enlargement scores were strongly associated with treatment refractoriness. The prevalence of severe PER was also higher for the NR group. Higher asthma control scores were associated with the probability of treatment-induced improvement. Conclusions: In paediatric PER patients, medical therapy refractoriness was associated with NOD, mainly septal deformity and turbinate enlargement. In those patients, ENT examination will facilitate an early NOD diagnosis in order to indicate potential corrective surgery.
Background Over the past decade, regulatory bodies and scientific societies recommended, as primary efficacy outcome, a score that reflects both symptom severity and use of rescue medication for clinical trials in allergy immunotherapy (AIT). Objective We sought to compare the results obtained with two subject-specific scores, the Combined Score (CS) and the Adjusted Symptom Score (AdSS), for assessment of AIT in seasonal allergic rhinoconjunctivitis due to birch and grass pollen allergens. Methods CS and AdSS were evaluated in subjects receiving a 300IR dose of allergen extract daily, by sublingual route, in four clinical trials with the 5-grass pollen tablet (NCT00367640, NCT00409409, NCT00955825 and NCT00418379) and one with the birch pollen solution (NCT01731249). The CS is derived from the Rhinoconjunctivitis Total Symptom Score (RTSS) and the Rescue Medication Score (RMS) giving equal weight to symptoms and medication use. The AdSS is a symptom score adjusting for rescue medication use. Efficacy end-points were analysed using an analysis of covariance linear model. Results In all trials, despite the different constructs of the two scores, Combined Score or Adjusted Symptom Score were similarly reduced in the 300IR group compared to the placebo group. Treatment effect was consistently demonstrated with both scores, CS and AdSS, used as either daily scores or average of the daily scores over the pollen season. Minor differences with the same statistical conclusions were observed between the results, leading to the same interpretation. Conclusions and Clinical Relevance The two scores, combined and adjusted scores, for evaluation of clinical efficacy of AIT have led to similar results, with similar statistical conclusions and similar interpretation.
Background: Limited accessibility to providers may delay appropriate control of asthma exacerbations. The objective of our study is to estimate the contributors to the hospital/emergency department (ED) visits among adults with asthma focusing on the availability of healthcare providers. Methods: We conducted a pooled cross-sectional analysis using the 2011-2013 Asthma Call-Back Survey linked with 2012-2016 Area Health Resource Files. We employed multivariable logistic regression with dichotomous outcomes of hospitalization and ED visits. Key covariates were the availability of county-level healthcare provider variables per 100,000 persons such as the number of lung disease specialists (including pulmonary care specialists, and allergy and immunology specialists), the number of hospitals, the number of safety-net facilities including rural health centers (RHCs) and federally qualified health centers (FQHCs), and the number of primary care physicians (PCPs). Results: Among 25,621 adults, proportions of hospital visits and ED visits were 3.3% and 13.2%, respectively. An additional RHC reduced by 3% the odds of having an ED visit (odds ratio [OR] = 0.97, p=.004). Patients with cost barriers to seeing a PCP were 60% (OR = 1.60, p=.028) more likely to have a hospital visit than those without. In addition, patients with cost barriers to seeing a specialist were 90% (OR = 1.90, p=.007) and 111% (OR =2.11, p=.001) more likely to have a hospital visit and ED visit, respectively, than those without. Conclusions: Hospital and ED visits among adults with asthma are partially related to the availability of providers, and more related to financial barriers. Therefore, financial support for the vulnerable asthma population might be a target for policy makers interested in reducing hospitalizations and ED visits.
Background: Porphyromonas gingivalis (Pg) capsule enables evasion from phagocytosis, invasion of keratinocytes, and bacterial survival. In mixed infection, the capsule also participates in coaggregation, which may lead to characteristic virulence not present in the monoinfection. The aim of this study is to evaluate the role of Pg capsule as a virulence factor in coaggregated mixed infection with Fusobacterium nucleatum (Fn). Methods: Mixed infections containing Fn and non-capsulated or capsulated strains of Pg were compared with the same infection with lactose as coaggregation inhibitor. Murine experimental periodontitis was used to assess disease severity. Primary polymorphonuclear leukocytes and keratinocytes were used to examine phagocytosis and bacterial invasion, respectively. Results: Mixed infection with capsulated Pg augmented alveolar bone loss compared with that of mixed infection with non-capsulated Pg. Addition of lactose led to attenuation of bone loss in the capsulated mixed infection and to intensification of bone loss in the non-capsulated mixed infection. In the latter mixed infection, Fn evaded phagocytosis, whereas in the capsulated mixed infection Pg displayed a greater capacity for invasion of keratinocytes. Conclusions: Pg capsule was found to serve as a unique virulence factor in mixed infection with Fn. Capsule-dependent coaggregation led to augmented invasion of Pg and may be responsible for the severity of disease after mixed infection with Fn.
Background: Leukotoxin (Ltx) expressed by Aggregatibacter actinomycetemcomitans is a powerful exotoxin, which can cause imbalance in host response. Immunoreactivity to Ltx is a marker for presence of leukotoxic A. actinomycetemcomitans, a presence that may modify the disease pattern of colonized individuals. The aim of the present study is to examine presence of systemic immunoreactivity to A. actionmycetemcomitans Ltx with respect to clinical and inflammatory findings in individuals with or without periodontitis (N = 88). Methods: Periodontal status was examined in patients with severe periodontitis (n = 49) and healthy controls (n = 39), and patients received periodontal treatment. Systemic biomarkers associated with inflammation and infections as well as clinical parameters were analyzed at baseline and 3 and 6 months after treatment. Results: Presence of immunoreactivity against Ltx was associated with impaired remission of disease after periodontal treatment. This immunoreactivity was also significantly associated with increased systemic levels of A. actinomycetemcomitans-specific immunoglobulins and increasing age. Conclusion: Presence and levels of systemic immunoreactivity against A. actinomycetemcomitans Ltx are associated with decreased remission after otherwise successful periodontal treatment.
Among athletes and coaches, there is a common perception that high training loads and competitions, applied chronically, with inadequate nutritional control and/or recovery periods, may reduce the immune resistance, increasing susceptibility to infection episodes, mainly upper respiratory tract infection (URTI). In this sense, this study is focused on reviewing the interactions between immunological parameters with the overtraining syndrome, specifically in team sports, considering its intermittent nature. Thus, a review of national and international journals related to the topic was held. The correlations between exercise, immune system and susceptibility to URTI have been evaluated mainly in individual and endurance sports compared to the team sports. The modulations of leukocytes throughout the season, against the totalization of training loads and competitions, when analyzed specifically for neutrophils and monocytes, are possibly related to tissue repair processes and incidence of URTI. Modulations related to lymphocytes seem to be more directly related to the incidence of URTI. Moreover, an understanding of all the proposed markers, including immunological markers, in association with the performance indicators and control of training, appears to be a more promising avenue for clinical diagnosis of the athlete's immune status and prevention of overtraining syndrome than the search for a unique marker of overtraining.
Background Adrenaline auto-injectors (AAI) should be provided to individuals considered to be at high risk of anaphylaxis. There is some evidence that the rate of AAI prescription is increasing, but the true extent has not been previously quantified. Aim To estimate the trends in annual GP-issued prescriptions for AAI among UK children between 2000 and 2012. Design and setting Retrospective cohort study using data from primary care practices that contributed to The Health Improvement Network (THIN) database. Method Children and young people aged between 0-17 years of age with a prescription for AAIs were identified, and annual AAI device prescription rates were estimated using Stata (version 12). Results A total of 1.06 million UK children were identified, providing 5.1 million person years of follow-up data. Overall, 23 837 children were deemed high risk by their GPs, and were prescribed 98 737 AAI devices. This equates to 4.67 children (95% confidence interval [CI] = 4.66 to 4.69), and 19.4 (95% CI = 19.2 to 19.5) devices per 1000 person years. Between 2000 and 2012, there has been a 355% increase in the number of children prescribed devices, and a 506% increase in the total number of AAI devices prescribed per 1000 person years in the UK. The number of devices issued per high-risk child during this period has also increased by 33%. Conclusion The number of children being prescribed AAI devices and the number of devices being prescribed in UK primary care between 2000 and 2012 has significantly increased. A discussion to promote rational prescribing of AAIs in the NHS is needed.
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.
During the last two decades, hyper-immunoglobulin (Ig) E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a singlecentre out-patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non-IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1-4) validated that non-IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low-IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.
Purpose of review Although chronic rhinosinusitis with nasal polyps, asthma, and allergy share common inflammatory mechanisms, there is no evidence of cause-and-effect relationship. In this review, we present new studies investigating the complex immunology that links these diseases. Advances in new therapies as well as evidence regarding indication and timing of surgery, especially of more complex cases, are highlighted. Recent findings New studies have endotyped patients in an effort to describe the exact inflammatory profile of each phenotype, whereas described cytokines seem to play a significant role in amplification of T2 inflammation, directly or via innate lymphoid cells. New mAbs that block specific cytokines of these pathways have been developed and seem to show reduced asthma severity as well as improved sinonasal outcomes. Moreover, it has been shown that operating early in the course of disease leads not only to bigger improvements in SNOT-22 outcomes but also to reduced asthma incidence postoperatively in refractory cases. Summary Applying data from current studies in clinical practice, we could better manage refractory cases with asthma and polyps, both medically and surgically. Treatment has to be patient-centered, and this demands a multidisciplinary-team approach of the airway diseases.
BACKGROUND: The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined. OBJECTIVE: We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR. METHODS: A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis. RESULTS: Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. CONCLUSIONS: Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated. (C) 2016 American Academy of Allergy, Asthma & Immunology
A recreational scuba diver wore a second scuba regulator against his face during a scuba dive, attached by an elastic rubber cord necklace. After surfacing, the diver's left face became swollen. Through a process of elimination all other items of scuba equipment were excluded as potential causes. A dive with the same equipment minus the necklace confirmed the involvement of the necklace in the pathogenesis of the hypersensitive reaction. In vitro ImmunoCap IgE assay was positive to latex (1.30 kUa/L), subsequent patch testing for contact dermatitis provoked a reaction for benzophenone-4, (a UV stabalizer) and Fourier Transform Infra Red spectroscopy identified the elastic as ethylene propylene rubber, containing additional unidentified compounds. Allergy to natural rubber latex occurs in as many as 6% of Americans and Australians. Around three million American residents are thought to scuba dive each year. Recreational divers are, therefore, advised to check such necklaces, which are typically worn around the throat, for frayed ends and exposed rubber filaments.
Allogenic lymphocyte immunotherapy (LIT) as a treatment for unexplained recurrent spontaneous abortion (URSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. Eighteen randomized, placebo-controlled trials with LIT for URSA were included in the meta-analysis. Live birth rates for each group were extracted, and the overall odds ratio (OR) for LIT was calculated. The success rate of treatment group was significantly higher (OR 3.74, 95% CI 3.07 similar to 4.57). LIT performed before and during pregnancy had dramatically improved the live birth rate in women with URSA (OR 4.67, 95% CI 3.70 similar to 5.90). The overall OR was 5.25 (95% CI 4.16 similar to 6.64), which supports a low dose of lymphocytes for treating URSA. Our results indicate that LIT provides a significantly beneficial effect over placebo for URSA. LIT given before and during pregnancy is superior to LIT given only before pregnancy, and the lower doses per treatment (less than 100 x 10(6) lymphocytes or 100 mL peripheral blood) achieved a better outcome.
Objectives. To perform a state of the art about immunological features in renal transplantation, immunosuppressive drugs and their mechanisms of action and immunologically high risk transplantations such as ABO and HLA-incompatible transplantation. Material and methods. An exhaustive systematic review of the scientific literature was performed in the Medline database and Embase using different associations of the following keywords (MESH): "allogenic response; allograft; immunosuppression; ABO incompatible transplantation; donor specific antibodies; HLA incompatible; desensitization; kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta analysis and guidelines were selected and analyzed. This search found 4717 articles. After reading titles and abstracts, 141 were included in the text, based on their relevance. Results. The considerable step in comprehension and knowledge allogeneic response this last few years allowed a better used of immunosuppression and the discover of news immunosuppressive drugs. In the first part of this article, the allogeneic response will be described. The different classes of immunosuppressive drugs will be presented and the actual management of immunosuppression will be discussed. Eventually, the modalities and results of immunologically high-risk transplantations such as ABO and HLA incompatible transplantations will be reported. Conclusions. The knowledge and the control of allogeneic response to allogeneic graft allowed the development of renal transplantation. (C) 2016 Elsevier Masson SAS. All rights reserved.
Alloparenting, defined as care provided by individuals other than parents, is a universal behavior among humans that has shaped our evolutionary history and remains important in contemporary society. Dysfunctions in alloparenting can have serious and sometimes fatal consequences for vulnerable infants and children. In spite of the importance of alloparenting, they still have much to learn regarding the underlying neurobiological systems governing its expression. Here, they review how a lack of alloparental behavior among traditional laboratory species has led to a blind spot in our understanding of this critical facet of human social behavior and the relevant neurobiology. Based on what is known, they draw from model systems ranging from voles to meerkats to primates to describe a conserved set of neuroendocrine mechanisms supporting the expression of alloparental care. In this review we describe the neurobiological and behavioral prerequisites, ontogeny, and consequences of alloparental care. Lastly, they identified several outstanding topics in the area of alloparental care that deserve further research efforts to better advance human health and wellbeing. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 214-232, 2017
Objective: Anxiety and mood disorders (AMD) are the most frequent mental disorders in the human population. They have recently shown increasing prevalence, and commonly disrupt personal and working lives. Objective: The aim of our study was to analyze the spectrum of circulating steroids in order to discover differences that could potentially be markers of affective depression or anxiety, and identify which steroids could be a predictive component for these diseases. Methods: We studied the steroid metabolome including 47 analytes in 20 men with depression (group D), 20 men with anxiety (group AN) and 30 healthy controls. OPLS and multivariate regression models were used for statistical analysis. Results: Discrimination of group D from controls by the OPLS method was absolute, as was group AN from controls (sensitivity = 1.000 (0.839, 1.000), specificity = 1.000 (0.887, 1.000)). Relatively good predictivity was also found for discrimination between group D from AN (sensitivity = 0.850 (0.640, 0.948), specificity = 0.900 (0.699, 0.972)). Conclusion: Selected circulating steroids, including those that are neuroactive and neuroprotective, can be useful tools for discriminating between these affective diseases in adult men. (C) 2016 Published by Elsevier Inc.
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associated with an increased risk of developing behavioural and mood disorders, particularly during adolescence. These pathologies involve the premature loss or alteration of trophic steroid hormones reaching the fetus leading to impaired neurodevelopment. While the specific programming mechanisms are yet to be fully elucidated, in adult life, dysfunctions of allopregnanolone action are prevalent in individuals with depression, post-traumatic stress disorder and anxiety disorders. The objective of this study was to assess if changes in concentrations of the neurosteroid, allopregnanolone, may be a fetal programming factor in priming the brain towards a negative behavioural phenotype during the childhood to adolescent period using a guinea pig model. Pregnant guinea pigs received either vehicle (45% (2-hydroxypropyI)-beta-cyclodextrin) or the 5 alpha-reductase inhibitor, finasteride (25 mg/kg maternal weight) from gestational age 60 until spontaneous delivery (similar to 71 days gestation). Male and female offspring from vehicle and finasteride treated dams were tested at postnatal day 20 (juvenile-equivalence) in an open field arena, and hippocampus and amygdala subsequently assessed for neurological changes in markers of development and GABA production pathways 24 h later. Females with reduced allopregnanolone exposure in utero displayed increased neophobic-like responses to a change in their environment compared to female controls. There were no differences in the neurodevelopmental markers assessed; MAP2, NeuN, MBP, GFAP or GAD67 between intrauterine finasteride or vehicle exposure, in either the hippocampus or amygdala whereas GAT1 staining was decreased. This study indicates that an intrauterine reduction in the supply of allopregnanolone programs vulnerability of female offspring to anxiety-like disorders in juvenility without impacting long term allopregnanolone concentrations. (C) 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
High-temperature requirement A (HtrA; DegP) from Escherichia coli, an important element of the extracytoplasmic protein quality-control system, is a member of the evolutionarily conserved family of serine proteases. The characteristic feature of this protein is its allosteric mode of activation. The regulatory loops, L3, L2, L1 and LD, play a crucial role in the transmission of the allosteric signal. Yet, the role of LD has not been fully elucidated. Therefore, we undertook a study to explain the role of the individual LD residues in inducing and maintaining the proteolytic activity of HtrA. We investigated the influence of amino acid substitutions located within the LD loop on the kinetics of a model substrate cleavage as well as on the dynamics of the oligomeric structure of HtrA. We found that the mutations that were expected to disturb the loop's structure and/or interactions with the remaining regulatory loops severely diminished the proteolytic activity of HtrA. The opposite effect, that is, increased activity, was observed for G174S substitution, which was predicted to strengthen the interactions mediated by LD. HtrAG174S protein had an equilibrium shifted toward the active enzyme and formed preferentially high-order oligomeric forms.
Modern microsurgical techniques have made possible a broad spectrum of novel means for the reconstruction of complex bone and soft tissue defects. These techniques, in combination with developments in transplant immunology, have led to successful hand and facial allotransplantation and achievement of the highest rung in the reconstructive ladder - truly replacing like with like. The utilization of contemporary microsurgical technique in the context of vascularized composite allotransplantation (VCA) (1) permits successful technical execution and feasibility of VCA, (2) facilitates the study of immunologic tolerance in VCA preclinical models, and (3) optimizes functional VCA outcomes.
In this paper, a new Voltage-Mode (VM) first-order All-Pass Filter (APF) topology composed of only a grounded capacitor is proposed. The proposed APF uses a single, minus-type, second-generation, current conveyor (CCII-), which can be constructed by only five MOS transistors. It has low power consumption. The resonance frequency of the proposed APF can be adjusted by changing only a resistor value. However, it needs a single matching condition. As an application, a quadrature oscillator example is given. A non-ideality analysis for the proposed APF is also given. A number of time domain and frequency domain simulation results and an experimental test result are included to confirm the theory. (C) 2015 Sharif University of Technology. All rights reserved.
The transcription factor encoded by the gene Knotted1 is a nuclear homeodomain protein, regulating meristematic cells at the shoot apical meristem. It has been demonstrated that Knotted1 (KN1) expression specifies stem cell fate in adventitious shoot induction in herbaceous plants. This gene may thus potentially identify the initiation of meristem development in adventitious shoot induction in difficult-to-regenerate plants such as Prunoideae. We isolated an almond (Prunus dulcis Mill.) KN1-type gene using degenerate primers targeting the most conserved regions of Knotted1 gene. The 5' and 3' ends of the isolated sequence were obtained by rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR), and the gene was named P. dulcis Knotted1-like (PdKn1). PdKn1 transcripts were detected by reverse transcription (RT)-PCR mainly in shoot apical and axillary meristems. The RT-PCR and RT-quantitative PCR PdKn1 expression in almond leaf explants was found to anticipate the organization of adventitious shoot meristems. Apricot RNA isolated from induced leaf explants cross-hybridized with the almond probe PdKn1 in Northern blotting. We suggest that almond PdKn1 may be a useful marker to study the adventitious regeneration system by revealing the potential organogenic conditions, not only in almond but also in other Prunoideae.
Laminin (Lm) alpha 4 chain, a constituent of Lm-411 and Lm-421, is mainly localized to mesenchyme-derived tissues, and is suggested to have a role in formation and function of endothelium, transmigration of inflammatory cells through endothelium, and invasion of certain tumors. In this study, we evaluated the distribution of alpha 4 chain Lms in 33 conventional (clear cell) renal cell carcinomas (RCCs) (31 primary tumors, two metastases), two papillary RCCs, and two oncocytomas by immunohistochemistry. In all tumors, immunoreactivity for Lm alpha 4 chain was found in vasculature and stroma. Basement membranes were detected around tumor cell islets in 34/37 tumors. They showed immunoreactivity for Lm alpha 4 chain in 28/34 cases. Northern blotting, inhibition of protein secretion with monensin, and immunoprecipitation combined with Western blotting showed that Caki-2, ACHN, and Caki-1 renal carcinoma cell lines produce alpha 4 chain Lms. In cell adhesion assay, recombinant human Lm-411 did not promote adhesion of renal carcinoma cells but inhibited adhesion to fibronectin (Fn). In cell migration assay, the cells migrated more on Lm-411 than on Fn. The results suggest that alpha 4 chain Lms have a de- adhesive function and could thus play a role in detachment, migration and invasion of renal carcinoma cells in vivo.
The AMPA receptor subunit GluR2 is downregulated in neurons following a wide range of neurological insults. Here we report that suppression of GluR2 gene promoter activity is associated with kainate (KA)-induced downregulation of GluR2 subunit levels in primary cultured cortical neurons. RT-PCR and Northern blotting showed a significant decrease in GluR2 mRNA in cultured neurons after KA exposure. Transfection of cultured neurons with an expression vector pGL3-GluR2(-298/+283), where the reporter gene firefly luciferase was driven by the GluR2 promoter, revealed that KA exposure suppressed the transcriptional activation of the GluR2 promoter. Furthermore, the expression of the RE1-silencing transcription factor (REST) was increased in KA-exposed cortical neurons; enhanced binding of REST to RE1-like silencer element in the proximal promoter of the GluR2 subunit gene was evidenced by electrophoresis mobility shift assay. Chromatin immunoprecipitation showed that suppressed activity of the GluR2 promoter in cultured neurons after KA exposure was related to deacetylation of histone H4. These results indicate that REST as a crucial factor binds to RE1-like silencer element in the GluR2 promoter, suppressing transcription of the GluR2 subunit gene during KA exposure. Our data suggest that transcriptional suppression of the G1uR2 subunit gene may contribute at least in part to downregulation of GluR2 subunit protein in neurons during KA exposure. Because our experiments showed a reduction of glutamate release in KA-exposed cortical neurons, REST may play a latent role in delayed neuronal death or in seizure-induced tolerance. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
alpha-Glucans are present in virtually all domains of life, and these glucose chains linked by alpha-1,4- and alpha-1,6-linked branches form the most important storage carbohydrates in cells. It is likely for this reason that alpha-glucans are not generally considered as bioactive molecules as beta-glucans are. Nevertheless, it is known that depending on their source, many alpha-glucans play important roles as modulators of immune response. Recent efforts have attempted to elucidate the mechanisms through which alpha-glucans exert their immunostimulant effects; however, the main challenge is the accurate identification of the receptors of immune cells involved in their recognition. Here, we review the adjuvant properties reported for some polysaccharides and ultimately focus on alpha-glucans and how their structural characteristics, such as molecular weight, solubility and derivatization, influence their immunostimulatory properties. As a final point, we discuss the potential and associated challenges of using these polysaccharides as adjuvants, particularly in mucosal vaccination. (C) 2017 Elsevier Ltd. All rights reserved.
Changes in the gastrointestinal microbial community are frequently associated with chronic diseases such as Inflammatory Bowel Diseases. However, understanding the relationship of any individual taxon within the community to host physiology is made complex due to the diversity and individuality of the gut microbiota. Defined microbial communities such as the Altered Schaedler Flora (ASF) help alleviate the challenges of a diverse microbiota by allowing one to interrogate the relationship between individual bacterial species and host responses. An important aspect of studying these relationships with defined microbial communities is the ability to measure the population abundance and dynamics of each member. Herein, we describe the development of an improved ASF species-specific and sensitive real-time quantitative polymerase chain reaction (qPCR) for use with SYBR Green chemistry to accurately assess individual ASF member abundance. This approach targets hypervariable regions V1 through V3 of the 16S rRNA gene of each ASF taxon to enhance assay specificity. We demonstrate the reproducibility, sensitivity and application of this new method by quantifying each ASF bacterium in two inbred mouse lines. We also used it to assess changes in ASF member abundance before and after acute antibiotic perturbation of the community as well as in mice fed two different diets. Additionally, we describe a nested PCR assay for the detection of lowly abundant ASF members. Altogether, this improved qPCR method will facilitate gnotobiotic research involving the ASF community by allowing for reproducible quantification of its members under various physiological conditions. (C) 2017 Elsevier B.V. All rights reserved.
Because of their prominent roles in regulation of gene expression, it is important to understand how levels of Krupple-like transcription factors SP1 and SP3 change in germ cells during spermatogenesis. Using immunological techniques, we found that both factors decreased sharply during meiosis. SP3 declined during the leptotene-to-pachytene transition, whereas SP1 fell somewhat later, as spermatocytes progressed beyond the early pachytene stage. SP3 reappeared for a period in round spermatids. For Sp1, the transition to the pachytene stage is accompanied by loss of the normal, 8.2-kb mRNA and appearance of a prevalent, 8.8-kb variant, which has not been well characterized. We have now shown that this pachytene-specific transcript contains a long, unspliced sequence from the first intron and that this sequence inhibits expression of a reporter, probably because of its many short open-reading frames. A second testis-specific Sp1 transcript in spermatids of 2.4 kb also has been reported previously. Like the 8.8-kb variant, it is compromised translationally. We have confirmed by Northern blotting that the 8.8-, 8.2-, and 2.4-kb variants account for the major testis Sp1 transcripts. Thus, the unexpected decline of SP1 protein in the face of continuing Sp1 transcription is explained, in large part, by poor translation of both novel testis transcripts. As part of this work, we also identified five additional, minor SpI cap sites by 5' rapid amplification of cDNA ends, including a trans-spliced RNA originating from the Glcci1 gene.
Modern drives consist of alternating current electric motors, and the field-oriented control (FOC) of such motors enables fast, precise, and robust regulation of a drive's mechanical variables such as torque, speed, and position. The control algorithm, implemented in a microprocessor, requires feedback from motor currents, and the quality of this feedback is essential to a drive's control properties. Motor phase currents are sampled and processed in order to extract their mean over a digital control interval. Afterwards, the mean phase currents are transformed into a rotating field-oriented reference frame to enable controlling the mechanical variables. The field-oriented frame rotates continuously, but in practice the transformation is carried out using a discrete angular position. This paper investigates how the discretization impacts the computed field-oriented currents in high speed drives, where the rotor displacement during a control interval is substantial. A continuous-time model of field-oriented currents is indicated as a reference to quantify errors. An original approach to normalize variables and to solve the model analytically is proposed in order to investigate how the errors related to rotor position discretization are influenced by drive operating conditions. The analytical solution is validated by computer simulation. The results show that the currently applied methodology of computing field-oriented current components, due to an invalid assumption, introduces errors of a few percent when a drive operates at high speed. These errors can be compensated using the presented solution. (C) 2016 Elsevier Inc. All rights reserved.
This article draws upon recent geographical work on assemblage to reconsider how we understand alternative food economies. In particular it brings attention to the devices upon which these economies relyspecifically plastics. Since the mid-twentieth century, plastics have developed close and complex relations with our agrifood systems; they facilitate commodity valuation and product circulation worldwide but are also recognised as problematic due to their environmental and human health impacts. Despite this paradox and the attention plastics increasingly receive, we know little of their relations with alternative food initiatives (AFIs). How do plastics inhabit alternative food economies? What associations and circulations become performed? What do these markets look like from a device-oriented perspective? To address these questions, the paper draws on fieldwork undertaken in Brisbane (Australia) with two AFIsa weekly organic market and an online box program/wholesaler. Using visualisation and an assemblage approach discloses the presences, flows, functions, and tensions of plastics in AFIs. In this way, plastics are revealed but also act to reveal alternative food economies. This analysis steps away from evaluations of AFIs' (in)effective challenge to neoliberalisation to consider them as complex, processual, sometimes ambivalent efforts that not only distribute good food' but engage in important ways with things like plastics.
Background: We developed and validated a kinetic microplate hemolytic assay (HA) to quantify classical and alternative complement activity in a single dilution of human plasma or serum. Methods: The assay is based on monitoring hemolysis of sensitized sheep (or uncoated rabbit) red blood cells by means of a 96-well microplate reader. The activity of the calibrator was evaluated by reference to 200 healthy adults. The conversion of 50% hemolysis time into a percentage of activity was obtained using a calibration curve plotted daily. Results: The linearity of the assay as well as interference (by hemolysis, bilrubinemia and lipemia) was assessed for classical pathway (CP). The within-day and the between-day precision was satisfactory regarding the performance of commercially available liposome immunoassay (LIA) and ELISA. Patients with hereditary or acquired complement deficiencies were detected (activity was measured <30%). We also provided a reference range obtained from 200 blood donors. The agreement of CP evaluated on samples from 48 patients was 94% with LIA and 87.5% with ELISA. The sensitivity of our assay was better than that of LIA, and the cost was lower than either LIA or ELISA. In addition, this assay was less time consuming than previously reported HAs. Conclusions: This assay allows the simultaneous measurement of 36 samples in duplicate per run of a 96-well plate. The use of a daily calibration curve allows standardization of the method and leads to good reproducibility. The same technique was also adapted for the quantification of alternative pathway (AP) activity.
NO-mediated alternative pathway plays an important role in protecting wheat seedlings against drought stress through dissipating excessive reducing equivalents generated by photosynthesis. Alternative pathway (AP) has been proven to be involved in responses to various stresses. However, the mechanisms of AP in defense response to drought stress are still lacking. The aims of this work are to investigate the role of AP in drought tolerance and how AP is induced under drought stress using two wheat cultivars with different drought tolerance. Our results showed that Longchun22 cultivar is more tolerant to drought than 98SN146 cultivar. Seedlings exposed to drought led to a significant increase in AP, and it increased more in Longchun22. Furthermore, chlorophyll fluorescence parameters (Fv/Fm, I broken vertical bar PSII, qP) decreased significantly in drought-treated seedlings, especially in 98SN146, indicating that photoinhibition occurred under drought stress. Pretreatment with SHAM, the malate-oxaloacetate shuttle activity and photosynthetic efficiency were further inhibited in drought-treated seedlings, resulting in more serious oxidative damage as indicated by higher levels of malondialdehyde and hydrogen peroxide. Moreover, NO modulated AP under drought stress by increasing AOX1a expression and pyruvate content. Taken together, these results indicate that NO-mediated AP is involved in optimizing photosynthesis under drought stress by avoiding the over-reduction of photosynthetic electron transport chain, thus reducing reactive oxygen species production and oxidative damage in wheat leaves.
A hallmark of male germ cell gene expression is the generation by alternative polyadenylation of cell-specific mRNAs, many of which utilize noncanonical A(A/U)UAAA-independent polyadenylation signals. Cleavage factor I (CFlm), a component of the pre-mRNA cleavage and polyadenylation protein complex, can direct A(A/U)UAAA-independent polyadenylation site selection of somatic cell mRNAs. Here we report that the CFlm subunits NUDT21/CPSF5 and CPSF6 are highly enriched in mouse male germ cells relative to somatic cells. Both subunits are expressed from spermatogenic cell mRNAs that are shorter than the corresponding somatic transcripts. Complementary DNA sequencing and Northern blotting revealed that the shorter Nudt21 and Cpsf6 mRNAs are generated by alternative polyadenylation in male germ cells using proximal poly(A) signals. Both sets of transcripts contain CFlm binding sites within their 3 '-untranslated regions, suggesting autoregulation of CFlm subunit formation in male germ cells. CFIm subunit mRNA and protein levels exhibit distinct developmental variation during spermatogenesis, indicating stage-dependent translational and/or posttranslational regulation. CFIm binding sites were identified near the 3 ' ends of numerous male germ cell transcripts utilizing A(A/U)UAAA-independent sites. Together these findings suggest that CFIm complexes participate in alternative polyadenylation directed by noncanonical poly(A) signals during spermatogenesis.
To identify a novel regulatory factor involved in brain development or synaptic plasticity, we applied the differential display PCR method to mRNA samples from NMDA-stimulated and un-stimulated neocortical cultures. Among 64 cDNA clones isolated, eight clones were novel genes and one of them encodes a novel zinc-finger protein, HIT-4, which is 317 amino acid residues (36-38 kDa) in length and contains seven C(2)H(2) zinc-finger motifs. Rat HIT-4 cDNA exhibits strong homology to human ZNF597 (57% amino acid identity and 72% homology) and identity to rat ZNF597 at the carboxyl region. Furthermore, genomic alignment of HIT-4 cDNA indicates that the alternative use of distinct promoters and exons produces HIT-4 and ZNF597 mRNAs. Northern blotting revealed that HIT-4 mRNA (similar to 6 kb) is expressed in various tissues such as the lung, heart, and liver, but enriched in the brain, while ZNF597 mRNA (similar to 1.5kb) is found only in the testis. To evaluate biological roles of HIT-4/ZNF597, targeted mutagenesis of this gene was performed in mice. Homozygous (-/-) mutation was embryonic lethal, ceasing embryonic organization before cardiogenesis at embryonic day 7.5. Heterozygous (+/-) mice were able to survive but showing cell degeneration and vacuolization of the striatum, cingulate cortex, and their surrounding white matter. These results reveal novel biological and pathological roles of HIT-4 in brain development and/or maintenance.
Many basic cellular processes are shared across vast phylogenetic distances, whereas sex-determining mechanisms are highly variable between phyla, although the existence of two sexes is nearly universal in the animal kingdom. However, the evolutionarily conserved DMRT1/dsx/mab3 with a common zinc finger-like DNA-binding motif, DM domain, share both similar structure and function between phyla. Here we report that six transcripts of the chicken DMRT1 were generated in gonads by multiple alternative splicing. By cDNA cloning and genomic structure analysis, we found that there were nine exons of DMRT1, which were involved in alternatively splicing to generate the DMRT1 transcripts. Northern blotting and reverse transcription (RT) PCR analysis revealed that the expression of chicken DMRT1 was testis-specific in adults. Whole-mount in situ hybridizations and RT-PCR indicated that DMRT1 b was specially expressed in embryo gonads and higher in male than female gonads at stage 31. The female gonad had stronger DMRT1 c expression than the male one, whereas DMRT1 f was detectable only in the male gonad at stage 31 of the key time of sex gonadal differentiation. The differential expression of these transcripts during gonadal differentiation provides new insight into roles of alternative splicing of DMRT1 in governing sex differentiation of the chicken.
The pre-mRNA of the fragile X mental retardation 1 gene (FMR1) is subject to exon skipping and alternative splice site selection, which can generate up to 12 isoforms. The expression and function of these variants in vivo has not yet been fully explored. In the present study, we investigated the distribution of Fmr1 exon 12 and exon 15 isoforms. Exon 12 encodes an extension of KH2 domain, one of the RNA binding domains in the FMR1 gene product (FMRP) and we show that exon 12 variant proteins differentially interact with kissing complex RNA. Alternative splicing at exon 15 produces FMRPs differing in RNA binding ability and each is distinguished by unique post-translational modifications. Using semiquantitative RT-PCR and Northern blotting, we found that particular Fmr1 exon 12 and exon 15 isoforms change during neuronal differentiation. Interestingly, Fmr1 exon 12 variants display tissue-specific and developmental differences, while exon 15-containing transcripts vary less. Altogether, the spatio-temporal plasticity of FMR1 mRNA is consistent with complex RNA processing that is mis-regulated in fragile X syndrome. (C) 2009 Elsevier Inc. All rights reserved.
Abcc4 gene codes for a protein (ABCC4) involved in the transportation of different classes of drugs outside the cells. Various important drugs transported by ABCC4 include antiviral and anticancer drugs as well as endogenous molecules such as bile acids, cyclic nucleotides, folates, prostaglandins and steroids. Alternative splicing generates multiple mRNAs that encode protein isoforms having diverse functions. In this study, we have identified a novel transcript of mouse Abcc4 gene using a combination of bioinformatics and molecular biology techniques. This transcript was found to be different from the reported transcript in having a different first exon that was found to be located on previously identified first intron. Newly identified transcript was found to be expressed across different tissues we studied and in different developmental stages. Expression level of novel and reported transcripts was studied using quantitative real-time PCR. After conceptually translating the novel transcript, various post-translational modifications were studied. Translation efficiency and predicted half life of encoded protein isoforms were analysed in silico. Molecular modelling was performed to compare the structural differences in both isoforms. The diversity at N-termini in these protein isoforms explains the diverse function of ABCC4 in mouse. (C) 2016 Elsevier B.V. All rights reserved.
Our aim of the project is to demonstrate all the protections and interlocks available in the critical equipments of power station such as Boiler, Turbine, the Alternator, and how these critical equipments are protected from abnormal conditions and parameters. The failure of any one of these equipments will lead to loss of power generation. The cost of these equipments is huge. Boiler has got protection against abnormal drum level, abnormal live steam pressure, abnormal live steam temperature, abnormal furnace pressure. Turbine has got protection against abnormal condenser vacuum, abnormal lubricating oil pressure, abnormal axial shiftand abnormal turbine speed. Similarly the generator has also got the following protections 1.10.5kv earth fault, 220kv earth fault, differential protection, incomplete phase condition, rotor earth fault, stator inter turn fault, over current protection, stator overvoltage, rotor overvoltage. These protections are classified as class a, class b and class c protections. Distributed digital controls and numerical protections relays play vital role in providing protections to critical equipments to demonstrate these protections in real sense in our project kit. However an effort has been made to demonstrate the functioning of these protections with the aid of a programmable logic controller. Also a few suggestions to improve the existing system are also discussed.
Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the 'altricial-precocial' spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems.
Hardness cations are ubiquitous and abundant in source water, while the effect of hardness on the performance of coagulation for dissolved organic matter (DOM) removal in water treatment remains unclear due to the limitation of methods that can characterise the subtle interactions between DOM, coagulant and hardness cations. This work quantified the competition between coagulant Al3+ and hardness cations to bind onto DOM using absorbance spectroscopy acquired at different Al3+ concentrations in the absence and presence of Ca2+ or Mg2+. The results indicate that, in the presence of either Mg2+ or Ca2+, an increasing depression of the binding of Al3+-DOM could be observed in the differential spectra of DOM with the increasing of Mg2+ or Ca2+ at a level of 10, 100 and 1000 mu M, with the observation being more significant at higher pH from 6.5 to 8.5. The results of zeta potentials of DOM indicate that the competition of hardness cations results in the negative DOM being less efficiently neutralised by Al3+. This study demonstrates that the removal of DOM by coagulation would significantly deteriorate with the presence of hardness cations, which would compete with coagulant Al3+ to neutralise the unsaturated sites in DOM. (C) 2017 Elsevier Ltd. All rights reserved.
Background and ObjectivePeriodontal disease is a chronic infectious disease that results in bone loss. Many epidemiological studies have reported the progression of periodontal tissue destruction in patients with diabetes; however, the associated mechanism remains unclear. In this study, we comprehensively investigated how diabetes affects the periodontal tissue and alveolar bone loss using a ligature-induced periodontitis model in streptozotocin-induced diabetic (STZ) mice. Material and MethodsDiabetes was induced by intraperitoneal injection with streptozotocin in 6-wk-old C57/BL6J male mice. A silk ligature was tied around the maxillary left second molar in 9-wk-old wild-type (WT) and STZ mice. Bone loss was evaluated at 3 and 7 d after ligation. mRNA expression levels in the gingiva between the two groups were examined by DNA microarray and quantitative polymerase chain reaction at 1, 3 and 7 d post-ligation. Tartrate-resistant acid phosphatase and alkaline phosphatase staining of the periodontal tissue was performed for evaluation of osteoclasts and osteoblasts in histological analysis. ResultsIn the gingiva, hyperglycemia upregulated the osteoprotegerin (Opg) mRNA expression and downregulated Osteocalcin mRNA expression. In the ligated gingiva, tumor necrosis factor- (Tnf-) mRNA expression was upregulated at 1 d post-ligation in STZ mice but not in WT mice. At 3 d post-ligation, alveolar bone loss was observed in STZ mice, but not in WT mice. Significantly severe alveolar bone loss was observed in STZ mice compared to WT mice at 7 d post-ligation. Bone metabolic analysis using DNA microarray showed significant downregulation in the mRNA expression of glioma-associated oncogene homologue 1 (Gli1) and collagen type VI alpha 1 (Col6a1) at the gingiva of the ligated site in STZ mice compared to that in WT mice. Quantitative polymerase chain reaction showed that Gli1 and Col6a1 mRNA expression levels were significantly downregulated in the gingiva of the ligated site in STZ mice compared to WT mice. Histological analysis showed lower alkaline phosphatase activity in STZ mice. In addition, an increased number of tartrate-resistant acid phosphatase-positive multinucleated cells were observed at the ligated sites in STZ mice. ConclusionsThese results suggest that an imbalance of bone metabolism causes osteoclastosis in insulin-deficient diabetes, and that alveolar bone loss could occur at an early phase under this condition.
The lung alveolar epithelium consists of type I and type II pneumocytes. In vivo, the type II cell is the progenitor cell from which the type I cell originates. When freshly-isolated type II cells are cultured under conventional conditions they rapidly lose their phenotypic properties and attain characteristics of type I cells. Taking advantage of this transdifferentiation, we sought to identify genes that are differentially expressed during culture of rat type II cells. Using suppression subtractive hybridization (SSH), a vacuolar-type H+ stop-ATPase (V-ATPase) C2 subunit gene (Atp6v1c2) was found to be enriched in freshly isolated rat type II cells compared to those cultured for 4 days. Northern blotting and reverse-transcription polymerase chain reaction (RT-PCR) confirmed the differential expression of Atp6v1c2 during in vitro culture of isolated type II cells. Expression of Atp6v1c2 was significantly reduced early during in vitro culture: almost 90% reduction was observed after 24 h of incubation as determined by real-time PCR. In situ hybridization showed that Atp6v1c2 is expressed in both bronchiolar and alveolar lung epithelial cells, an expression pattern similar to that of surfactant protein B (SP-B). Multi-tissue Northern blotting revealed a unique tissue distribution with Atp6v1c2 expression limited to lung, kidney and testis. The presence and expression of Atp6v1c2 gene transcript isoforms, resulting from alternative splicing, were also investigated. Elucidation of differential expression of Atp6v1c2 in type II cells and further studies of its regulation may provide information useful in understanding the molecular mechanism underlying phenotypic and functional changes during transdifferentiation of alveolar epithelial cells.
Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus causing hemangiomas and myeloid tumors in chickens. Interleukin-6 (IL-6) is a multifunctional pro-inflammatory interleukin involved in many types of cancer. We previously demonstrated that IL-6 expression was induced following ALV-J infection in chickens. The aim of this study is to characterize the mechanism by which ALV-J induces IL-6 expression, and the role of IL-6 in tumor development. Our results demonstrate that ALV-J infection increases IL-6 expression in chicken splenocytes, peripheral blood lymphocytes, and vascular endothelial cells. IL-6 production is induced by the ALV-J envelope protein gp85 and capsid protein p27 via PI3K- and NF-kappa B-mediated signaling. IL-6 in turn induced expression of vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR-2, in vascular endothelial cells and embryonic vascular tissues. Suppression of IL-6 using siRNA inhibited the ALV-J induced VEGF-A and VEGFR-2 expression in vascular endothelial cells, indicating that the ALV-J-induced VEGF-A/VEGFR-2 expression is mediated by IL-6. As VEGF-A and VEGFR-2 are important factors in oncogenesis, our findings suggest that ALV-J hijacks IL-6 to promote tumorigenesis, and indicate that IL-6 could potentially serve as a therapeutic target in ALV-J infections.
Insulin-degrading enzyme (IDE) is a zinc metalloprotease, known to degrade insulin peptide and amyloid-beta (A beta); the key protein involved in Alzheimer's disease (AD). Considering the important role played by IDE in disease progression of AD and type 2 diabetes mellitus (T2DM), we endeavored to identify the Caenorhabditis elegans (C. elegans) IDE orthologous genes and test them for their role in AD related outcomes. We employed bioinformatics, reverse genetics and molecular biology approaches towards identification and functional characterization of putative IDE candidates in C. elegans. Using in-silico analysis we have identified seven C elegans genes that possess HXXEH motif, an identifying marker of IDE. We further carried out functional analysis of the identified genes in A beta expressing C elegans strain CL4176 [myo-3/A beta 1-42 long 3'-UTR] via studying effect on A beta induced toxicity, cholinergic neuroanatomy, content of acetylcholine/acetylcholine-esterase, extent of reactive oxygen species and expression of FOXO transcription factor DAF-16. Our findings reveal that amongst the identified putative IDE orthologs, a functionally uncharacterized gene C28F5.4 had a profound effect on the tested endpoints. Knocking down C28F5.4 modulated the AD associated conditions by decreasing A beta induced toxicity, severely compromising cholinergic neuroanatomy, reducing expression of acetylcholine-transporter, decreasing acetylcholine content, elevating ROS, with no effect on DAF-16 stress-response protein. These studies provide crucial insight into the structural/functional orthology of IDEs across human and nematode species and further our understanding of the involvement of these proteins and insulin pathway in AD. Further studies could aid in identifying novel drug-targets and in understanding the common modulating factors between AD and T2DM. (C) 2016 Elsevier B.V. All rights reserved.
Alzheimer's disease (AD) has been associated with magnesium ion (Mg2+) deficits and interleukin-1 beta (IL-1 beta) elevations in the serum or brains of AD patients. However, the mechanisms regulating IL-1 beta expression during Mg (2+) dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1 beta reduction using a recently developed compound, magnesium-L-threonate (MgT). Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system, we delineated the signaling pathways by which MgT suppressed the expression of IL-1 beta in glial cells. In detail, we found that MgT incubation stimulated the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and peroxisome proliferator-activated receptor gamma (PPAR gamma) signaling pathways by phosphorylation, which resulted in IL-1 beta suppression. Simultaneous inhibition of the phosphorylation of ERK1/2 and PPAR gamma induced IL-1 beta upregulation in MgT-stimulated glial cells. In accordance with our in vitro data, the intracerebroventricular (i.c.v) injection of MgT into the ventricles of APP/PS1 transgenic mice and treatment of Ab precursor protein (APP)/PS1 brain slices suppressed the mRNA and protein expression of IL-1 beta. These in vivo observations were further supported by the oral administration of MgT for 5 months. Importantly, Mg (2+) influx into the ventricles of the mice blocked the effects of IL-1 beta or amyloid beta-protein oligomers in the cerebrospinal fluid. This reduced the stimulation of IL-1 beta expression in the cerebral cortex of APP/PS1 transgenic mice, which potentially contributed to the inhibition of neuroinflammation. Cellular & Molecular Immunology (2017) published online 9 November 2015
The current study determined the ability of a p75(NTR) antagonistic cyclic peptide to rescue cells from beta amyloid (A beta) (1-40)-induced death. p75(NTR)-, p140(trkA)-NIH-3T3 cells or E17 foetal rat cortical neurones were incubated with I-125-NGF or I-125-A beta (1-40) and increasing concentrations of the cyclic peptide (CATDIKGAEC). Peptide ability to displace I-125-NGF or I-125-A beta (1-40) binding was determined. Duplicate cultures were preincubated with CATDIKGAEC (250 nM) or diluent and then stimulated with A beta (1-40). Peptide ability to displace A beta (1-40) binding, interfere with A beta (1-40)-induced signalling and rescue cells from A beta-mediated toxicity was determined by immunoprecipitation and autoradiography, Northern blotting, JNK activation, MTT and trypan blue assays. The peptide inhibited NGF and A beta (1-40) binding to p75(NTR), but not to p140(trkA). A beta (1-40) induced c-jun transcription (57.3% +/- 0.07%) in diluent-treated p75(NTR)-cells, but not in cells preincubated with the cyclic peptide. Also, at 250 nM, the peptide reduced A beta (1-40)-induced phsophorylation of JNK by 71.8% +/- 0.03% and protected neurones against A beta-induced toxicity as determined by: trypan blue exclusion assay (53% +/- 11% trypan blue-positive cells in diluent pretreated cultures vs. 28% +/- 5% in cyclic peptide-pretreated cultures); MTT assay (0.09 +/- 0.03 units in diluent-pretreated cells vs. 0.12 +/- 0.004 units in cyclic peptide-pretreated cells); and visualization of representative microscopic fields. Our data suggest that a cyclic peptide homologous to amino acids 28-36 of NGF known to mediate binding to p75(NTR) can interfere with A beta (1-40) signalling and rescue neurones from A beta (1-40)-induced toxicity.
Although frontal presentations of Alzheimer's disease (fv-AD) have already been described in the literature, we still know little about patients' social cognitive abilities, especially their theory of mind (ToM). We report the case of FT, a 61-year-old woman who was diagnosed with fv-AD. Two assessments of social cognition, using a false-belief task, the Reading the Mind in the Eyes test, and a task probing knowledge of social norms, were performed one year apart. FT exhibited cognitive ToM and social knowledge deficits from the onset. Affective ToM was initially preserved, but deteriorated as the disease progressed.
Alzheimer's disease (AD), since its characterization as a precise form of dementia with its own pathological hallmarks, has captured scientists' attention because of its complexity. The last 30 years have been filled with discoveries regarding the elusive aetiology of this disease and, thanks to advances in molecular biology and live imaging techniques, we now know that an important role is played by calcium (Ca2+). Ca2+, as ubiquitous second messenger, regulates a vast variety of cellular processes, from neuronal excitation and communication, to muscle fibre contraction and hormone secretion, with its action spanning a temporal scale that goes from microseconds to hours. It is therefore very challenging to conceive a single hypothesis that can integrate the numerous findings on this issue with those coming from the classical fields of AD research such as amyloid-beta (A beta) and tau pathology. In this contribution, we will focus our attention on the Ca2+ hypothesis of AD, dissecting it, as much as possible, in its subcellular localization, where the Ca2+ signal meets its specificity. We will also follow the temporal evolution of the Ca2+ hypothesis, providing some of the most updated discoveries. Whenever possible, we will link the findings regarding Ca2+ dysfunction to the other players involved in AD pathogenesis, hoping to provide a crossover body of evidence, useful to amplify the knowledge that will lead towards the discovery of an effective therapy. (C) 2016 Elsevier Ltd. All rights reserved.
AimsTo explore the common effects of the clusterin (CLU) rs11136000 variant on the default mode network (DMN) in amnestic mild cognitive impairment (aMCI) subjects and remitted geriatric depression (RGD) subjects. MethodsFifty-one aMCI subjects, 38 RGD subjects, and 64 cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at both baseline and a 35-month follow-up. Posterior cingulate cortex seed-based functional connectivity (FC) analysis was used to obtain the DMN patterns. ResultsA CLU genexdiseasextime interaction for aMCI subjects was mainly detected in the core cortical midline structures of the DMN, and the interaction for RGD subjects was mainly detected in the limbic system. However, they overlapped in two frontal regions, where consistent effects of the CLU gene on FC alterations were found between aMCI and RGD groups. Furthermore, the alterations of FC with frontal, parietal, and limbic regions compensated for episodic memory impairments in CLU-CT/TT carriers, while no such compensation was found in CLU-CC carriers. ConclusionThe CLU gene could consistently affect the DMN FC with frontal regions among individuals at risk for Alzheimer's disease, and the CLU-T allele was associated with more compensatory neural processes in DMN changes.
Young individuals better memorize initially seen faces with emotional rather than neutral expressions. Healthy older participants and Alzheimer's disease (AD) patients show better memory for faces with positive expressions. The socioemotional selectivity theory postulates that this positivity effect in memory reflects a general age-related preference for positive stimuli, subserving emotion regulation. Another explanation might be that older participants use compensatory strategies, often considering happy faces as previously seen. The question about the existence of this effect in tasks not permitting such compensatory strategies is still open. Thus, we compared the performance of healthy participants and AD patients for positive, neutral, and negative faces in such tasks. Healthy older participants and AD patients showed a positivity effect in memory, but there was no difference between emotional and neutral faces in young participants. Our results suggest that the positivity effect in memory is not entirely due to the sense of familiarity for smiling faces.
Chronic neuroinflammation is thought to potentiate medial temporal lobe (MTL) atrophy and memory decline in Alzheimer's disease (AD). It has become increasingly important to find novel immunological biomarkers of neuroinflammation or other processes that can track AD development and progression. Our study explored which pro- or anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD neuropathology over 24 months. Using Alzheimer's Disease Neuroimaging Initiative data (N = 285), CSF inflammatory biomarkers from mass spectrometry and multiplex panels were screened using step-wise regression, followed up with 50%/50% model retests for validation. Neuronal Pentraxin 2 (NPTX2) and Chitinase-3-like-protein-1 (C3LP1), biomarkers of glutamatergic synaptic plasticity and microglial activation respectively, were the only consistently significant biomarkers selected. Once these biomarlcers were selected, linear mixed models were used to analyze their baseline and longitudinal associations with bilateral MTL volume, memory decline, global cognition, and established AD biomarkers including CSF amyloid and tau. Higher baseline NPTX2 levels corresponded to less MTL atrophy [R-2 = 0.287, p < 0.001] and substantially less memory decline [R-2 = 0.560, p < 0.001] by month 24. Conversely, higher C3LP1 modestly predicted more MTL atrophy [R-2 = 0.083, p < 0.001], yet did not significantly track memory decline over time. In conclusion, NPTX2 is a novel pro -inflammatory cytokine that predicts AD-related outcomes better than any immunological biomarker to date, substantially accounting for brain atrophy and especially memory decline. C3LP1 as the microglial biomarker, by contrast, performed modestly and did not predict longitudinal memory decline. This research may advance the current understanding of AD etiopathogenesis, while expanding early diagnostic techniques through the use of novel pro -inflammatory biomarkers, such as NPTX2. Future studies should also see if NPTX2 causally affects MTL morphometry and memory performance. (C) 2016 Elsevier Inc. All rights reserved.
Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (A beta) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4(+)CD25(+) T cells) and Teffs (CD4(+)CD25(-) T cells) in an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of A beta plaques. In contrast, adoptive transfer of Teffs diminished behavioral function and cytokine production. Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61). Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with F-18-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. Importantly, the deposition of A beta plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer's disease treatment.
Introduction: Subjective cognitive decline (SCD) could indicate preclinical Alzheimer's disease, but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. Methods: We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties, and 35 community-recruited controls with low self-reported cognitive difficulties. Results: Increased anxiety and amyloid beta deposition were observed in both groups with high self-reported difficulties, whereas subclinical depression and (hippocampal) atrophy were specifically associated with medical help seeking. Cognitive tests showed no group differences. Discussion: These results further validate the concept of SCD in both community-and clinic-based groups. Yet, recruitment methods influence associated biomarkers and affective symptomatology, highlighting the heterogeneous nature of SCD depending on study characteristics. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
this paper presents an amplitude modulation transmitter for 50 MHz application with low power consumption. The transmitter consists of Gilbert cell mixer, cross coupled with symmetric load voltage controlled oscillator, two stage operational amplifier and a high pass filter implemented in TSMC CMOS 0.18 mu m process. A 200 mV RF input of 50 MHz and 500 mV LO output of 1.5 GHz are applied at both RF and LO ports of the mixer with conversion gain of 14.25 dB results to a 300 mV IF output of 1.2 GHz. The reference voltage V-dd = 1.8 V, the tuning range of oscillator is 0 to 2 GHz and the amplifier has a gain of 42.1 dB, phase margin of 56 degrees, unity gain bandwidth of 1.43 GHz and slew rate of 291 V/mu s. The overall power consumption is 74.3 mW and a chip size of 9.68 nm(2). The chip is connected to an I/O pad with rectangular pad frame of size 0.46 mu m(2).
Using a field-programmable gate array (FPGA) development board, a digital signal processor (DSP) builder, and the phase-to-amplitude conversion principle, a low-cost system for measuring the amplitude-to-amplitude (AM/AM) and amplitude-to-phase (AM/PM) distortion curves of radio frequency (RF) power amplifiers (PAs) is presented. The state of the art based on the measurements and preliminary studies of AM/AM and AM/PM distortion curves is discussed. A full digital control of the test bed simulated/emulated in Matlab/Simulink is introduced to recalculate the known AM/AM and AM/PM measurements stored as look-up table (LUT). Finally, the low-cost system comprises the memory polynomial model (MPM) that involves the nonlinearity order and memory effects of real PAs. (C) 2015 Elsevier B.V. All rights reserved.
Considerable interest in the relationship between biodiversity and disease has recently captured the attention of the research community, with important public policy implications. In particular, malaria in the Amazon region is often cited as an example of how forest conservation can improve public health outcomes. However, despite a growing body of literature and an increased understanding of the relationship between malaria and land use/land cover change (LULC) in Amazonia, contradictions have emerged. While some studies report that deforestation increases malaria risk, others claim the opposite. Assessing malaria risk requires examination of dynamic processes among three main components: (i) the environment (i.e. LULC and landscape transformations), (ii) vector biology (e.g. mosquito species distributions, vector activity and life cycle, plasmodium infection rates), and (iii) human populations (e.g. forest-related activity, host susceptibility, movement patterns). In this paper, we conduct a systematic literature review on malaria risk and deforestation in the Amazon focusing on these three components. We explore key features that are likely to generate these contrasting results using the reviewed articles and our own data from Brazil and Peru, and conclude with suggestions for productive avenues in future research. This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.
How can a firm develop, distribute, and use knowledge more effectively and efficiently in ways that increase its ability to pursue an ambidextrous orientation? Synthesizing insights from social cognition and upper-echelons perspectives, we offer a new theoretical vantage point that brings the role of top management teams' cognitive structure to the fore and, in particular, the enabling influence of transactive memory systems. We argue that transactive memory provides a top management team with a system for generating, distributing, and integrating knowledge based on members' specific areas of expertise in ways that increase its ability to both differentiate and integrate strategic agendas for ambidexterity. From a multisource study of top management teams in a sample of technology-based small-to-medium-sized firms, we find that while top management teams with well-developed transactive memory systems are able to pursue an ambidextrous orientation, the impact of transactive memory is also shaped by diverse organizational experience and functional expertise within these teams. We discuss the scope and significance of these findings for theory, future research, and managerial practice.
Electrical arcs emit extremely high intensity light across a wide spectrum that can damage the eye's delicate structures, such as the cornea or the retina. Developing industry safety standards to mitigate light hazards is a critical component of arc flash safety. Accurate measurement of light intensity is the first step in understanding the level of eye protection needed. Traditionally, light measurement devices are an assembly of light-detecting resistors made from cadmium sulfide (CdS) or silicon (Si) cells. However, their response times are inadequate for capturing the peak light intensity or the dynamic changes during the initial arc flash. In addition, the brightness of an arc flash is greater than the measurable light levels from traditional light measurement devices. Furthermore, the light sensitivity of traditional sensors does not match the Commission Internationale de l'Eclairage luminosity function V (lambda) curve, which defines the human eye's sensitivity to bright light as a function of wavelength under typical ambient light conditions. This paper discusses a novel light measurement technique to overcome the limitations of traditional approaches. This design is capable of measuring the light intensity of the arc flash as perceived by the human eyes. These results can be used to evaluate the potential of an arc flash to harm the eyes.
Background: Evidence for extreme ambient temperature effects on the risk of mental disorders (MDs) is limited. In this study, we evaluated the short-term effects of daily mean temperature on hospital admissions of MDs in Shanghai, China. Methods: We obtained daily hospital admission data for MDs, daily meteorological and ambient pollution data in Shanghai from January 2008 to December 2015. Adjusted for time trend, air pollution, relative humidity and other confounders, a quasi-Poisson generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to analyze the lag-exposure-response relationship between daily mean temperature and hospital admissions for MDs. Results: Total daily hospital admissions for MDs during the study period were 93,971. With a reference of median temperature (18.3 degrees C), there was a significant positive association between the temperature above threshold (24.6 degrees C) and MD hospital admission visits at a lag of 0-1 days. The relative risks of extreme hot temperatures (33.1 degrees C, 99% percentile) over the lag 0-1 days compared to median temperature were 1.266 (95% confidence intervals: 1.074-1.493). No effect of cold weather on the hospital admissions for MDs was observed. Conclusions: This study suggests that extreme hot temperature poses significant risks on MD; health counseling and cooling measures should be considered for the susceptible population. (C) 2017 Elsevier B.V. All rights reserved.
Beyond the universality of the symmetry concept, there are different emphases on its application in different branches of science. Chemistry, being between particle physics and astrophysics, represents a bridge in, and a utilitarian approach to, the application of the symmetry concept, which has proved immensely fruitful in twentieth-century science. Some pivotal discoveries, especially in structural chemistry, molecular biology, and materials science, emerged by relaxing some of the stipulations of the classical teachings about symmetry. This highly personal presentation relies on ideas expressed by a number of notable individuals in recent science, among them J. Desmond Bernal, Francis Crick, Ronald J. Gillespie, Aleksandr I. Kitaigorodskii, Alan L. Mackay, George A. Olah, Linus Pauling, Roger Penrose, Dan Shechtman, James D. Watson, Steven Weinberg, and Eugene P. Wigner.
Recently, most of sonokembang, Pterocarpus indicus trees are dying in Malang. In 2012, the death rate of trees reached ca. 11%. In addition, death of trees spread to other regencies in East Java. Euplatypus parallelus is a specific species of ambrosia beetles that were the causal agents to the dying and wilting of sonokembang trees in Malang. Wilting is caused mainly by the pathogenic fungi carried by ambrosia beetles. To confirm the microbial communities related to E. parallelus that attack sonokembang, E. parallelus and some attacked trees were collected in Malang city. Isolation and identification of these species were conducted at the Laboratory of Mycology, Faculty of Agriculture, University of Brawijaya and Laboratory of Molecular Biology, Islamic State University, Malang. Results showed that there were nine microbes including five genera of fungi, two genera of yeasts and one genus of bacterium were identified. The microbial communities that were found namely Aspergillus spp., Penicilium spp., Trichoderma spp., Fusarium spp., Acremonium spp., Gliocladium spp. (fungi), Streptomyces spp. (bacteria), Saccharomyces spp., and Candida spp. (yeast).
The modifiable areal unit problem and the ecological fallacy are known problems that occur when modelling multiscale spatial processes. We investigate how these forms of spatial aggregation error can guide a regionalization over a spatial domain of interest. By regionalization' we mean a specification of geographies that define the spatial support for areal data. This topic has been studied vigorously by geographers but has been given less attention by spatial statisticians. Thus, we propose a criterion for spatial aggregation error, which we minimize to obtain an optimal regionalization. To define the criterion we draw a connection between spatial aggregation error and a new multiscale representation of the Karhunen-Loeve expansion. This relationship between the criterion for spatial aggregation error and the multiscale Karhunen-Loeve expansion leads to illuminating theoretical developments including connections between spatial aggregation error, squared prediction error, spatial variance and a novel extension of Obled-Creutin eigenfunctions. The effectiveness of our approach is demonstrated through an analysis of two data sets: one using the American Community Survey and one related to environmental ocean winds.
ObjectiveWe examined the relationship between American Indian men's attitudes toward pregnancy prevention, STI/HIV prevention, and sexual risk behavior. Attention was given to: (1) attitudes and intentions to use condoms and sexual risk behavior; (2) STI/HIV prevention characteristics and sexual risk behavior; (3) attitudes toward abstinence and monogamy and sexual risk behavior; and (4) decision-making in relationships and sexual risk behavior. Study DesignOur sample included 120 heterosexual American Indian men aged 18 to 24 living on a reservation. Data were collected during in-depth interviews. A community-based participatory research framework was used to ensure the relevancy and acceptability of the study given the sensitivity of the topic. Principal FindingsResults demonstrated that attitudinal factors were associated with sexual risk behavior, particularly inconsistent condom use. Attitudes associated with consistent condom use suggested greater levels of positive dispositions toward prevention and intention to use condoms. Consistent condom use was associated with more cautious attitudes toward sex with multiple sex partners. Study results suggested that American Indian men who reported sex with multiple partners exhibited a set of attitudes and beliefs toward pregnancy prevention and STI/HIV prevention that corresponded with a disposition resulting from their behaviors, in that engaging in sexual risk behavior elevated their levels of risk perception. ConclusionsOur findings suggest that heterosexual American Indian men living in rural environments need sexual and reproductive health programs and clinical services that address differing attitudes toward condom use within the context of multiple sex partners and sexual risk behavior.
Nitrile-converting enzymes, including nitrilase and nitrile hydratase (NHase), have received increasing attention from researchers of industrial biocatalysis because of their critical role as a tool in organic synthesis of carboxylic acids and amides from nitriles. To date, these bioconversion approaches are considered as one of the most potential industrial processes using resting cells or purified enzymes as catalysts for production of food additives, pharmaceutical, and agrochemical precursors. This review focuses on the distribution and catalytic mechanism research of nitrile-converting enzymes in recent years. Molecular biology aspects to improve the biocatalytic performance of microbial nitrilase and NHase are demonstrated. The process developments of microbial nitrilase and NHase for organic synthesis are also discussed.
Aminoacylase 1 (ACY1) is important for regulating the proliferation of numerous types of cancer. However, the expression and mechanisms underlying the function of ACY1 in colorectal cancer remain unclear. In order to investigate the expression and function of ACY1 in colorectal cancer, tumor tissue and blood samples were collected for analysis from 132 patients diagnosed with colorectal cancer. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting identified significantly increased expression of ACY1 mRNA in colorectal tumor tissue (P<0.05 vs. adjacent normal tissue) and notably increased ACY1 protein levels. This ACY1 mRNA expression was found to be positively correlated with tumor stage. In addition, plasma ACY1 concentration was increased in patients with colorectal cancer compared with healthy controls. Furthermore, in vitro knockdown of ACY1 in human colorectal cancer HT-29 cells was shown to inhibit proliferation and increase apoptosis. This effect was found to be associated with the activation of ERK1 and TGF-beta 1 signaling. In conclusion, the results of the present study suggest that ACY1 promotes tumor progression, and thus may be a potential target for the diagnosis and treatment of colorectal cancer.
Bacillus thuringiensis insecticidal crystal proteins bind to cell-surface receptors which represent a family of aminopeptidases [APN (aminopeptidase N)] present on the brush border membrane of insect midgut cells of susceptible insects leading to pore formation and death of the insect. We report here for the first time the presence of a novel APN in the fat body of the moth Achaea janata. Northern blotting detected at least one APN-specific transcript in the fat body, whereas two transcripts of different sizes were detected in the midgut. We have cloned two full-length APN cDNAs of 3015 bp and 2850 bp from fat body and midgut respectively, which encode proteins of 1004 and 950 amino acids. These two APNs share only 33% amino acid sequence identity, but both display the typical APN features, such as the N-terminal signal peptide, several putative glycosylation sites, C-terminal glycosylphosphatidylinositol anchor signal, the APN-specific zinc-binding/gluzincin motif HEXXHX18E and gluzincin motif GAMENWG. The fat body APN manifested a variation in its expression with respect to tissue and developmental stage. In spite of the abundance of the APN transcript in the fat body, fairly low APN activity was detected in this tissue. The fat-body-and midgut-specific APNs showed differential interaction with various Cry1A toxins. Besides, the level of toxicity of different Cry subtypes varied enormously with mode/site of delivery, such as intrahaemocoelic injections and feeding bioassays. These data indicate that the fat body might be a potential alternative Cry toxin target site in the moth.
The long-term cardiac effects of amiodarone resemble many aspects of hypothyroidism. The anti-arrhythmic potential of amiodarone may therefore be the result of a drug-induced, local hypothyroid-like condition. To investigate this controversial issue, we compared gene expression profiles in the hearts of rats treated with amiodarone with those of rats with hypothyroidism. Wistar male rats were assigned to 3 groups (n = 6-8): Control, systemic hypothyroidism (Hypothyroidism) and amiodarone treatment (Amiodarone, 150 mg/kg/day, p.o., 4 weeks). Electrocardiogram (ECG) recordings, gene profiling by DNA microarray and Northern blotting were carried out. Amiodarone, like Hypothyroidism, caused significant prolongation of RR and QT intervals in ECGs. Microarray analysis of 8435 genes in the left ventricular myocardium revealed a significant similarity in expression profiles between Hypothyroidism and Amiodarone (R=0.63, p<0.00001). The gene expression profiles of Hypothyroidism and Amiodarone showed closer correlation when top 100 up-regulated and 100 down-regulated genes in Hypothyroidism, (total 200 genes)were analyzed (R=0.78,p<0.00001). Northern blots of left ventricular myocardium, showed a parallel decrease in mRNAs for myosin heavy chain (MHC)-alpha and a parallel increase for myosin heavy chain (MHC)-beta in Hypothyroidism and Amiodarone. In the liver and pituitary, in contrast, Northern blots showed quite different changes in the transcripts of the representative T3-responsive genes in the Hypothyroidism and Amiodarone. In conclusion, long-term treatment with amiodarone causes cardioselective hypothyroid-like alterations in gene expression profiles. The potent anti-arrhythmic activity of amiodarone may be attributable, in part at least, to this unique transcriptional remodeling. (C) 2007 Elsevier B.V. All rights reserved.
RNA interference (RNAI) is a powerful tool for functional gene analysis, which has been successfully used to down-regulate the levels of specific target genes. In this study a microRNA 159a-based binary vector was constructed which can be used for hpRNA expression. Hairpin (hp) RNA expression cassettes carrying the gene sequences are typically constructed on binary plasmid and delivered into plant cells by Agrobacteriurn-mediated genetic transformation. This system allows simple insertion of 21- nt target gene sequences into microRNA backbone, to facilitate the processing of microRNA hpRNA by the endogenous machinery of host, thereby producing artificial microRNA carrying the sequence of target gene(s). The functionality of new vector system was tested by silencing viral gene in transgenic plants. Strong down regulation of viral gene was observed in virus infected tobacco plants transformed with PAmiR(159) vector. The processing of amiRNA leading to viral-specific siRNA was confirmed by northern blotting. This vector system provides an important addition to the plant molecular biologists' toolbox, which will significantly facilitate the use of RNAi technology for analyses of various gene functions in plant cells.
Context: Amitriptyline, a tricyclic antidepressant is used for the management of psychological disorders and various types of pain. In the previous work, it is founded that amitriptyline inhibited the migration of polymorphonuclear (PMN) into the site of inflammation. Aims: To evaluate the effect of amitriptyline on the expression of some inflammatory mediators such as intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). Methods: An in vitro model system of LPS-stimulated human endothelial cells and U-937 macrophages and also in vivo model of carrageenan-induced paw edema in rat were used. The expression of inflammatory mediator genes was determined by qRT-Real-time PCR. In endothelial cells, soluble forms of ICAM-1 and VCAM-1 were quantified by ELISA. Results: The expression of ICAM-1, VCAM-1, COX2, iNOS, sICAM-1 and sVCAM-1 significantly decreased by amitriptyline. The finding of this study also confirmed that intraperitoneal (i.p.) injection of amitriptyline inhibited carrageenan-induced inflammation in rat paw edema. Conclusions: The results of the present study provide further evidence for the anti-inflammatory effect of amitriptyline. This effect appears to be mediated by down-regulation of inflammatory genes.
A cDNA sequence OsMT3 was initially isolated from the subtractive cDNA library of ammonium-fed rice (Oryza sativa L.) leaves, which was further confirmed by Northern blot to be highly ammonium-up-regulated as compared to nitrate. Its full-length cDNA was cloned by RT-PCR, and in silico analysis reveals that the cDNA includes an open reading frame of 186 bp and encodes a rice metallothionein type 3 peptide. Northern blotting analysis showed that OsMT3 gene predominantly expressed in rice leaves, weakly in stems, and barely in buds and roots. The gene transcripts in leaves were significantly induced by polyethylene glycol (PEG), low temperature, NaCl and Cu2+, but not by Pb2+. Activities of three anti-oxidative enzymes (superoxide dismutase, catalase and peroxidases) and two non-enzymic antioxidants (reduced ascorbate and reduced glutathione) little differed in ammonium-and nitrate-fed rice leaves, indicating that the induced OsMT3 expression was not mediated by ammonium-elicited oxidative signals.
Background: The aim of this study was to investigate the application of mucous membrane keratinocyte cultures on amniotic membrane and on poly(L-lactic acid) (PLLA) Purasorb PL38 to cover tissue loss in the oral cavity. Developments in molecular biology techniques and tissue engineering allow the culturing and identification of cells that can be anchored in the wound to achieve integrity of the tissue. Transplantation of tissues obtained from the patient's own cells is superior to allogenous transplantation where there is a possibility of transfection, rejection and the need for long-term immunosuppression. Methods: In 9 patients (15 procedures) keratinocytes cultured on amniotic membrane and PLLA were transplanted to cover antro-oral fistulas and bone loss after osteoradionecrosis. Results: In all 6 patients with outlasting antro-oral fistulas, the defects were healed. In 3 patients with 5 cases of tissue loss after osteoradionecrosis, we obtained healing of the wound in only 1 case. Histological examination of the cultures indicated that cultured cells formed well-differentiated layers, very similar to the keratinocytes of mucous membranes, although those seeded on amniotic membrane formed a single layer of cells, while those seeded on the PLLA scaffold were arranged on 2 or more layers: these differences were shown to be statistically significant with a morphometric analysis. Conclusions: Autologous transplants of epithelium cultured on amniotic membrane and PLLA constitute a new and effective way of covering nonhealing tissue loss in the oral cavity in chosen cases, using modern methods of tissue engineering.
In this paper, we presented a novel operational amplifier (op-amp) only with solution-processed n-type amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). The a-IGZO TFTs and common-source amplifier were fabricated on glass substrate through the solution process and confirmed to show stable electrical characteristics suitable for display driving circuits. Based on the experimental results, we designed an op-amp to have an overall gain of 30.5 dB, a cut-off frequency of 1.47 kHz, and a unit gain frequency of 6.65 kHz when supply voltage was +/- 15 V. Finally, by constituting the comparator, the proposed op-amp is expected to be used in power control and driving systems for display applications.
In this paper, we present an operational amplifier (op-amp) and a pulsewidth-modulation (PWM) controller fabricated with amorphous indium-gallium-zinc oxide thin-film transistors (a-InGaZnO TFTs), to build an adaptive dc-dc converter for display driving systems. The fabricated a-InGaZnO TFT presents electrical characteristics suitable for accomplishing an op-amp composed only with n-type TFTs to have an overall gain of 24.5 dB, a cutoff frequency of 6 kHz, and a unit gain frequency of 32 kHz operating at +/- 15 V. The fabricated op-amp is used to construct a comparator and an error amplifier on the glass, which are combined to realize a PWM controller. The resulting PWM controller can successfully control the output voltage of an external dc-dc converter that follows the input voltage to the error amplifier, and can operate at 100 Hz to control the duty ratio from 24.3% to 66.1% when the reference voltage varies from 2 to 6 V, respectively.
Background and ObjectiveBacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival crevicular fluid. Furthermore, some gram-negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms. Material and MethodsThe Ca9-22 cell line was used as an in vitro counterpart of gingival epithelial cells. Cell death was measured as the amount of total DNA in the dead cells using SYTOX Green dye, which penetrates through membranes of dead cells and emits fluorescence when it intercalates into double-stranded DNA. AMP-activated protein kinase (AMPK) activity, the amount of autophagy, and acetylation of histone H3 were determined using western blot. Gene expression levels of microtubule-associated protein 1 light chain 3b (lc3b) were determined using quantitative reverse transcription-polymerase chain reaction. ResultsButyrate-induced cell death occurred in a dose-dependent manner whether cells were starved or fed. However, the induction of cell death was two to four times higher when cells were placed under starvation conditions compared to when they were fed. Moreover, both starvation and butyrate exposure induced AMPK activity and autophagy. While AMPK inactivation resulted in decreased autophagy and butyrate-induced cell death under conditions of starvation, AMPK activation resulted in butyrate-induced cell death when cells were fed. Combined with the results of our previous report, which demonstrated butyrate-induced autophagy-dependent cell death, the results of this study suggest that the combination of starvation and butyrate exposure activates AMPK inducing autophagy and subsequent cell death. Notably, this combination markedly induced LC3B production and the induction was attenuated by AMPK inhibition. LC3B knockdown, in turn, significantly decreased butyrate-induced cell death. Therefore, AMPK-dependent LC3B induction apparently plays an important role in butyrate-induced cell death. There was a lack of correspondence between the levels of AMPK activation and LC3B induction; this may reflect the histone deacetylase-inhibitory capacity of butyrate on histone proteins. ConclusionTaken together, starvation and butyrate exposure promote autophagy via AMPK signaling, while the histone deacetylase-inhibitory effects of butyrate alter chromatin to transcriptionally active state, resulting in strong LC3B induction and subsequent cell death. These findings may help improve the understanding of the cellular processes underlying periodontal disease initiation.
MicroRNAs (miRs) have emerged as important clinical biomarkers with both diagnostic and prognostic value for relevant diseases, such as cancer. MiRs pose unique challenges for detection and are currently detected by northern blotting, real-time PCR, and microarray techniques. These expensive, complicated, and time-consuming techniques are not feasible for on-site miR determination. In this study, amperometric magnetobiosensors involving RNA-binding viral protein p19 as a selective biorecognition element were developed for miR quantification. The p19-based magnetosensors were able to detect 0.4 fmol of a synthetic target and endogenous miR-21 (selected as a model for its role in a wide variety of cancers) in only 2 h in total RNA extracted from cancer cells and human breast-tumor specimens without PCR amplification and sample preprocessing. These results open up formidable perspectives for the diagnosis and prognosis of human cancers and for drug-discovery programs.
In this brief, a 1-V potentiostat circuit for a glucose sensor has been proposed. Test results of this 1-V potentiostat demonstrate high linearity with respect to glucose concentration, which is comparable with conventional potentiostat designs. This high linearity is achieved with the help of a transconductance enhanced bulk-driven operational amplifier. The overall current consumption of the circuit is around 22 mu A. The potentiostat is tested as a glucose biosensor for glucose concentration ranging from 0 to 30 mM. The design is realized in a 0.35-mu m bulk-CMOS process, and the area for the core layout is 0.13 mm(2). The proposed low-power potentiostat can be incorporated in an implantable glucose sensor system due to its low-power operation and small footprint.
Here we report a homologue of the apolipoprotein D gene (AniphiApoD) in amphioxus, Branchiostoma belcheri tsingtauense, the first such finding in a basal chordate cephalochordate. The main features of the protein predicted from AmphiApoD are characteristic of the apolipoprotein D. Phylogenetic analysis places AmphiApoD at the base of the phylogenetic tree, suggesting that AmphiApoD is the archetype of the vertebrate ApoD genes. Both whole mount in situ hybridization and Northern blotting and RT-PCR as well as in situ hybridization histochemistry reveal that AmphiApoD is expressed in tissues derived from mesoderm and endoderm including notochord and hind-gut, which contrasts with the strong expression patterns of ApoD genes in the ectodermal derivatives in mammals and birds. The expression profiles of the ApoD gene may have been changed to be expressed in the endo-mesodermal derivatives in amphioxus after the vertebrate and cephalochordate lineages diverged; alternatively, the ApoD gene may first have been expressed in the endo-mesoderm during embryogenesis in the last common ancestor of all chordates, and subsequently came to be expressed in the ectodermal derivatives of vertebrates including mammals and birds. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
In vertebrates, many responses to stress as well as homeostatic maintenance of basal metabolism are regulated by plasma glucocorticoid hormones (GCs). Despite having crucial functions, levels of GCs are typically variable among individuals. We examined the contribution of several physiological factors to individual variation in plasma corticosterone (CORT) and the number of corticotropinreleasing hormone (CRH) neurons in the magnocellular preoptic area of the brain in free-living Allegheny Mountain dusky salamanders. We addressed three hypotheses: the current-condition hypothesis, the facilitation hypothesis and the trade-off hypothesis. Differential white blood cell count was identified as a strong contributor to individual variation in baseline CORT, stress-induced CORT and the number of CRH neurons. In contrast, we found no relationship between CORT (or CRH) and body condition, energy stores or reproductive investment, providing no support for the current-condition hypothesis or the tradeoff hypothesis involving reproduction. Because of the difficulties of interpreting the functional consequences of variation in differential white blood cell counts, we were unable to distinguish between the facilitation hypothesis or the trade-off hypothesis related to immune function. However, the strong association between differential white blood cell count and hypothalamic-pituitary-adrenal/interrenal (HPA/I) activation suggests that a more thorough examination of immune profiles is critical to understanding variation in HPA/I activation.
Resource availability can significantly alter host-parasite dynamics. Abundant food can provide more resources for hosts to resist infections, but also increase host tolerance of infections by reducing competition between hosts and parasites for food. Whether abundant food favors host resistance or tolerance (or both) might depend on the type of resource that the parasite exploits (e.g., host tissue vs. food), which can vary based on the stage of infection. In our study, we evaluated how low and high resource diets affect Cuban tree frog (Osteopilus septentrionalis) resistance and tolerance of a skin-penetrating, gut nematode Aplectana sp. at each stage of the infection. Compared to a low resource diet, a high resource diet enhanced frog resistance to worm penetration and tolerance while worms traveled to the gut. In contrast, a low resource diet increased resistance to establishment of the infection. After the infection established and worms could access food resources in the gut, a high resource diet enhanced host tolerance of parasites. On a high resource diet, parasitized frogs consumed significantly more food than non-parasitized frogs; when food was then restricted, mass of non-parasitized frogs did not change, whereas mass of parasitized frogs decreased significantly. Thus, a high resource diet increased frog tolerance of established worms because frogs could fully compensate for energy lost to the parasites. Our study shows that host-parasite dynamics are influenced by the effect of resource availability on host resistance and tolerance, which depends on when parasites have access to food and the stage of infection.
A full length amphioxus cDNA, encoding a novel phosducin-like protein (Amphi-PhLP), was identified for the first time from the gut cDNA library of Branchiostoma belcheri. It is comprised of 1 550 bp and an open reading frame (ORF) of 241 amino acids, with a predicted molecular mass of approximately 28 kDa. In situ hybridization histochemistry revealed a tissue-specific expression pattern of Amphi-PhLP with the high levels in the ovary, and at a lower level in the hind gut and testis, hepatic caecum, gill, endostyle, and epipharyngeal groove, while it was absent in the muscle, neural tube and notochord. In the Chinese Hamster Ovary (CHO) cells transfected with the expression plasmid pEGFP-N1/Amphi-PhLP, the fusion protein was targeted in the cytoplasm of CHO cells, suggesting that Amphi-PhLP is a cytosolic protein. This work may provide a framework for further understanding of the physiological function of Amphi-PhLP in B. belcheri.
Promethins have been shown to be present in the vertebrates examined so far, yet little is known to date about them in invertebrates. Here we isolated a cDNA encoding a promethin-like homolog from the gut cDNA library of the amphioxus Branchiostoma belcheri, a cephalochordate occupying a nodal position transient from invertebrates to vertebrates. It contained a 504 bp open reading frame corresponding to a protein of 167 amino acids. Primary structural examination showed that the deduced promethin-like homolog was a transmembrane protein with three potential transmembrane helices, resembling the vertebrate promethins. Phylogenetic analysis showed that B. belcheri promethin-like homolog was located at the base of the vertebrate counterparts, suggesting that it represents the archetype of vertebrate promethins. Both Northern blotting and in situ hybridization histochemistry revealed a tissue-specific expression pattern of promethin-like gene, like that of mammalian promethins. This is the first report on invertebrate promethin-like homolog, paving the way for further insights into the evolution and function of promethins.
An amphioxus cDNA, AmphiGM2AP, encoding GM2 activator protein was isolated from the gut cDNA library of Branchiostoma belcheri. It is 907 by long, and its longest open reading frame codes for a precursor protein consisting of 242 amino acid residues with a signal peptide of 14 amino acids. The deduced amino acid sequence includes a conserved domain typical of GM2APs between residues 53 and 224, a single N-linked glycosylation site at position 65 and 8 conserved cysteines. Phylogenetic analysis showed that amphiGM2AP forms a club together with invertebrate GM2APs, indicating that AmphiGM2AP is evolutionarily closely related to invertebrate GM2APs rather than vertebrate ones. Both Northern blotting and in situ hybridization histochemistry analyses revealed a tissue-specific expression pattern of AmphiGM2AP in adult amphioxus with the strongest expression in the digestive system, which is in contrast to the widespread expression pattern of human, mouse and sheep GM2AP genes. It is suggested that AmphiGM2AP is possibly involved in the take-in of digested food components like lipid molecules.
A nifU- like gene exhibiting similarity to nifU of nitrogen fixation gene cluster was identified for the first time from the gut cDNA library of amphioxus Branchiostoma belcheri. Both RT- PCR and Northern blotting as well as in situ hybridization histochemistry verified that the cDNA represents an amphioxus nifU- like gene rather than a microbial contaminant. The nifUlike gene encodes a protein of 164 amino acid residues including a highly- conserved U- type motif ( C-X-26 -C-X-43 -C), and shares 66 - 86% identity to NifU- like proteins from a variety of species including vertebrates, invertebrates and microbes. It is expressed in a tissue- specific manner in the digestive system including epipharyngeal groove, endostyle, hepatic caecum and hindgut and in the gill, ovary and testis. Taken together, it is highly likely that NifU- like protein plays some tissue- dependent and critical role in amphioxus.
A nifU-Iike gene exhibiting similarity to nifU of nitrogen fixation gene cluster was identified for the first time from the gut cDNA library of amphioxus Branchiostoma belcheri. Both RT-PCR and Northern blotting as well as in situ hybridization histochemistry verified that the cDNA represents an amphioxus nifU-Iike gene rather than a microbial contaminant. The nifU-like gene encodes a protein of 164 amino acid residues including a highly conserved U-type motif (C-X-26-C-X-43-C), and shares 66-86% identity to NifU-like proteins from a variety of species including vertebrates, invertebrates and microbes. It is expressed in a tissue-specific manner in the digestive system including epipharyngeal groove, endostyle, hepatic caecum and hind-gut and in the gill, ovary and testis. Taken together, it is highly likely that NifU-like protein plays some tissue-dependent and critical role in amphioxus.
The cDNA AmphiP23,encoding an amphioxus p23, was identified from the gut cDNA library of amphioxus Branchiostoma belcheri. It contains a 513 bp open reading frame corresponding to a deduced protein of 170 amino acids. Phylogenetic analysis shows that vertebrate and invertebrate p23/p23-like proteins are each grouped together, with AmphiP23 falling at the base of vertebrate p23/p23-like clade, suggesting that the divergence of vertebrate and invertebrate p23 genes probably occurs prior to the split of invertebrate/vertebrate from a common ancestor around 550 million years ago. Northern blotting reveals a ubiquitous expression pattern of AmphiP23 in all adult tissues examined, while whole mount in situ hybridization demonstrates a tissue- and stage-specific expression pattern of AmphiP23 in developing embryos and larvae. Presumably, the ubiquitous expression pattern of AmphiP23 in adult amphioxus represents the ancestral type of p23 gene prior to its split to human paralogs p23 and tsp23, while the tissue- and stage-specific expression pattern during early embryonic development implicates a role of AmphiP23 in anterior/posterior patterning. (c) 2006 Elsevier Inc. All rights reserved.
We investigated the developmental expression pattern of AmphiCAM in cephalochordate amphioxus (Branchiostoma belcheri tsingtauense) We cultured and sampled the animals at different developmental stages (eggs and larvae), and used in-situ hybridization and northern blotting to document the spatial and temporal changes in AmphiCaM expression The alimentary tract dominates the development from the late neurula stage to the adult stage AmphiCaM expression increased significantly in the alimentary tract during the late neurula stage and remained elevated in the adults Our results indicate that AmphiCaM is involved in the differentiation of the alimentary tract in amphioxus, and furthermore, provide an insight into the change in function of CaM genes during evolution
Trypsin has been documented in a variety of species including both vertebrates and invertebrates, but little is known about it in amphioxus, a model organism for insights into the origin and evolution of vertebrates. Here we identified a trypsin gene in Branchiostoma japonicum. The cDNA was 978 bp long with an ORF encoding a deduced protein of 272 amino acids. The deduced protein had an N-terminal signal peptide of 15 amino acids, a 16 activation peptide with the typical cleavage site Arg/Ile, a Tryp_SPc domain with the catalytic triad His(72)-Asp(118)-Ser(215) and the S1 substrate binding residue Asp(209), which are all characteristic of trypsinogens. The recombinant trypsin protein was able to hydrolyse the trypsin prototypic substrate BAEE, which was inhibited by the trypsin-specific inhibitor soybean trypsin inhibitor. Both northern blotting and tissue-section in situ hybridization demonstrated that trypsin gene was expressed in a tissue-specific manner, with most abundant levels in the hepatic caecum, mid-gut and ovary. And the whole mount in situ hybridization showed that it began to express in the middle third of the full-length primitive gut in 2-day larvae, where the hepatic caecum will form later during development. Phylogenetic analysis indicated that both amphioxus and ascidian trypsins are more closer to each other than to vertebrate trypsins, suggesting a continuous evolutionary divergence of vertebrate trypsins after split from protochordate/vertebrate common ancestor.
Amphiregulin and epiregulin belong to the epidermal growth factor (EGF) family, and act as mitogenic stimulators via binding to EGF receptors (EGFRs). Amphiregulin and epiregulin are thought to play a role in regenerative responses in the gastrointestinal tract. In this study, we investigated secretion of amphiregulin and epiregulin in human colonic subepithelial myofibroblasts (SEMFs). The mRNA expression and protein secretion of amphiregulin and epiregulin were evaluated by Northern blotting and Western blotting, respectively. The trophic effects of amphiregulin and epiregulin on SEMFs were analyzed by MTT assays. Amphiregulin and epiregulin mRNAs were not detected in unstimulated SEMFs. Among the various cytokines and growth factors, interleukin-1 beta, tumor necrosis factor-alpha, and EGF strongly induced amphiregulin and epiregulin mRNA expression. These responses were markedly reduced by AG1478, a specific inhibitor of EGF receptor tyrosine kinases. Amphiregulin and epiregulin secretion were also detected at the protein level. MTT assays demonstrated that amphiregulin and epiregulin stimulate the proliferation of SEMFs. We demonstrated expression of amphiregulin and epiregulin in SEMFs. Amphiregulin and epiregulin may play an important role in the mechanism underlying wound healing in damaged colonic mucosa.
Purpose: To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE). Methods: Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center. Results: Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 mu g/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes). Conclusions: EFE can be easily confirmed using primary 23-G vitrectomy.
Several frequency compensation schemes have been proposed to stabilize multistage amplifiers with negative feedback. The performance of these amplifiers can be analyzed by inspecting their inputoutput transfer function as representation of their frequency response. With many circuit elements affecting the output response, it is relatively difficult to obtain the real transfer function of multistage amplifiers based on only the original small-signal expressions. Instead, certain techniques such as Miller's theorem are used to approximate important parameters such as DC gain and dominant pole. These methods are not generally helpful for approximating the nondominant poles which have a critical role on the loop stability of nano-scale amplifiers. With this issue in mind, this work proposes a systematic methodology to achieve the pole expressions of multistage amplifiers with frequency compensation. The key in the proposed technique is to model the equivalent impedance of the compensation loop at the output. The effectiveness of the proposed approach has been verified through comparison between the transfer functions obtained from theory and those transfer functions found in the literature. (C) 2016 Elsevier GmbH. All rights reserved.
Recently, there are revolutionary achievements in silicon-based conventional terahertz (THz) and millimeter-wave (mm-wave) integrated circuits, particularly with the advancement of CMOS technology. However, unlike Radio Frequency Integrated Circuits (RFICs), innovative designs and lack of various circuit techniques still remain unknown in THz gap. In this paper, a multi-band THz amplifier is presented in 40 nm CMOS technology with adaptive band selection technique. The smart amplifier is able to adjust the band of operation with respect to input signal power and frequency. In addition, the circuit performance will be adjusted to achieve maximum power gain. In order to achieve multi-band external neutralization, self-healing technique is vastly utilized by means of tunable transmission lines (TTLs). The proposed smart system contains tunable transmission lines, a 5-stage amplifier core, two Successive Approximation Register-based analog-to-digital converters (SAR ADCs), a digital control core and two on-chip power sensing blocks. The fabricated amplifier achieves P-1 of 1 dBm, P-sat of 6.1 dBm and power gain of 14.8 dB +/- <1.5 dB from 197 to 288 GHz frequency range. The proposed amplifier demonstrates the highest operation frequency among all published state-of-arts in all CMOS technologies.
A signal- and transient-current boosting (STCB) circuit is proposed and applied to a single-stage amplifier driving large capacitive loads. The proposed STCB circuit provides gain-bandwidth product (GBW) extension, slew-rate (SR) improvement and gain enhancement to the amplifier, with only slight alterations to the frequency response and transient response of the single-stage amplifier driving large capacitive loads. No on-chip capacitor or resistor is required. The STCB amplifier is fabricated in a commercial 0.18-mu m CMOS technology. The active chip area is 0.00705 mm(2). The supply is 1.8 V, and the current consumption is 20.3 mu A. The capacitive load (C-O) ranges from about 4.4 nF to 19 nF. The measured results with a similar to 19-nF load show the small-signal figure-of-merit (FOMS = GBW . C-O/power) and the large-signal large-figure-of-merit (FOML = SR . C-O/power) are 150345 MHz . pF/mW and 31213 V/mu s . pF/mW, respectively, which correspond to improvements of 1.52 times and 1.36 times, respectively, to the prior art. The achieved phase margin and gain margin are 80.8 degrees and 36.3 dB, respectively.
Reconfigurable analog/mixed signal (AMS) platforms in scaled CMOS technology nodes are gaining importance due to the increased design cost, effort and shrinking time-tomarket. Similar to field programmable gate arrays (FPGA) for digital designs, a Programmable ANalog Device Array (PANDA) provides a flexible and versatile solution with transistor-level granularity and reconfiguration capability for rapid prototyping and validation of analog circuits. This paper presents design and synthesis methodology of a PANDA design on 65 nm CMOS technology, consisting of a 24 x 25 cell array, reconfigurable interconnect, configuration memory and serial programming interface. To implement AMS circuits on the PANDA platform, this paper further proposes a CAD tool for technology mapping, placement, routing and configuration bit-stream generation. Several representative building blocks of AMS circuits, such as amplifiers, voltage and current references, filters, are successfully implemented on the PANDA platform. Dynamic reconfiguration capability of PANDA is demonstrated through input offset cancellation of an operational amplifier using an FPGA in a closed loop. Initial measurement results of PANDA implemented circuits demonstrate the potential of the methodology for rapid prototyping and hardware validation of analog circuits.
Analog layout generation in the advanced CMOS design is challenging by its increasing layout constraints and performance requirements. This situation becomes more intricate by the growing parasitic variability and manufacturing reliability. To facilitate the feasibility of template-based layout migration, this paper first introduces a layout preservation, which extracts placement and routing behaviors from an existing layout into a crossing graph via constrained Delaunay triangulation. And later this crossing graph can be migrated into multiple layouts with placement and routing reconnection. The proposed approach also provides a refinement for wire to optimize the performance metrics. This approach is applied to a variable-gain amplifier, a folded-cascode operational amplifier, and a low dropout regulator. The experimental results demonstrate more possibility on layout migration, such that averagely more than 75% routing of migrated layout is generated by our approach. Additionally, it exhibits the productivity with qualified performance on different designs.
This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRS(MDD)) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRS(MDD) on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRS(MDD) was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRS(MDD) was mainly shown on the right amygdala, while the interaction effect of SES and GPRS(MDD) was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.
The amyloid-beta (A beta) peptide, the proteolytic fragment of A beta precursor protein (APP), aggregates and forms neuritic plaques, a major hallmark of Alzheimer's disease (AD). The limiting step in generating the A beta peptide from APP is cleavage by the P-secretase enzyme, BACE1 Regulation of the BACE1 gene is likely to play an important role in AD etiology and treatment. We therefore studied the activity of a 4.1-kb F-flanking region (-3765/+364, +1 being the transcription start site) of the BACE1 gene, both in 5'- and T-deletion series and through Northern blotting. We show that the BACE1 promoter has regulatory activity throughout the 4.1-kb length, both positive and negative, and that this activity can be quantitatively modeled according to promoter sequence length, with the specific model depending on the presence of negative regulatory elements as the 5'-most portion of the sequence. We also examined a previously identified 141-bp proximal fragment (+224/+364) of the BACE1 promoter and two constituent (91- and 50-bp) subfragments. We report that the 91-bp fragment (+224/+314) is the most likely seat of neuronal expression of the BACE1 gene and that it is the portion of the 141-bp fragment that accounts for observed DNA-protein interactions in brain extracts. The 50-bp fragment (+315/+364), which showed significant reporter gene activity from the empty vector, binds nuclear proteins in a cell type-specific manner and contains the AP2 site as shown by the electrophoretic mobility shift assay. Overall, the 141-bp fragment had no strong matches within GenBank, and the 91-bp fragment is predicted to have several potential stem-loop sites. Taken together, BACE1 gene promoter activity is differentially regulated, and the 91-bp fragment represents a novel promoter region for cell type-specific regulation. This fragment might be a useful target to regulate BACE1 expression leading to A beta production and to understand the neuropathogenesis of AD.
Objective: Emotion processing abilities might be reduced in amyotrophic lateral sclerosis (ALS). Previous studies of emotion processing in ALS have inconsistent results, and are limited by variations in task difficulty, modalities examined, and participants' cognitive status. The current study used a battery of emotion processing tasks at differing levels of difficulty and across different modalities (facial affect and voice prosody) to assess the extent of emotion processing deficits in nondemented ALS. Method: 33 ALS participants with intact basic cognition and 22 healthy controls completed the abbreviated Comprehensive Affect Testing System (CATS), which assesses simple and complex facial affect recognition, affective prosody recognition, cross-modal face-prosody integration, and semantic comprehension of affect. Participants also completed measures of executive function, mood, and functional impairment. Results: ALS participants showed impairments on complex facial affect recognition, affective prosody recognition, and cross-modal integration. In contrast, simple facial affect recognition and semantic comprehension of affect were intact. ALS participants did not have significant mood symptoms, and neither mood nor functional impairment was related to emotion processing. Performance on the cross-modal composite was related to executive function, however, this relationship was not apparent for facial or prosody recognition within a single modality. Conclusions: These results indicate that people living with ALS without dementia often have subtle difficulties with recognizing emotions in both faces and voices, even in the context of intact basic cognition. Clinicians should be aware of the potential for these emotion processing difficulties to be present in ALS and to affect interpersonal behavior and quality of life.
Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unclear. Several studies using anatomical MRI yielded a number of discrepancies in their results, and a few PET studies investigated the effect of ALS on cerebral glucose metabolism. The aim of this study was threefold: to highlight the patterns of grey matter (GM) atrophy, hypometabolism and hypermetabolism in patients with ALS, then to understand the neurobehavioral significance of hypermetabolism and, finally, to investigate the regional differences between the morphologic and functional changes in ALS patients, using a specially designed voxel-based method. Thirty-seven patients with ALS and 37 age-and sex-matched healthy individuals underwent both structural MRI and (18)[F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for partial volume effects. Structural and metabolic abnormalities were examined in ALS patients compared with control subjects using two-sample t tests in statistical parametric mapping (SPM). Then, we extracted the metabolic values of clusters presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM atrophy and hypometabolism patterns were directly compared with a one-paired t test in SPM. Results: We found GM atrophy as well as hypometabolism in motor and extra motor regions and hypermetabolism in medial temporal lobe and cerebellum. We observed negative correlations between the metabolism of the right and left parahippocampal gyri and episodic memory and between the metabolism of right temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal pole, left hippocampus and right thalamus, while hypometabolism predominated in a single cluster in the left frontal superior medial cortex. Conclusions: Our findings provide direct evidence of regional variations in the hierarchy and relationships between GM atrophy and hypometabolism in ALS. Moreover, the (18)FDG-PET investigation suggests that cerebral hypermetabolism is deleterious to cognitive function in ALS.
This study aims to explore the potential impairment of Theory of Mind (ToM; i.e., the ability to represent cognitive and affective mental states to both self and others) and the clinical, neuropsychological and Quality of Life (QoL) correlates of these cognitive abnormalities in the early stages of amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disease recently recognized as a part of the same clinical and pathological spectrum of frontotemporal lobar degeneration. Twenty-two consecutive, cognitively intact ALS patients, and 15 healthy controls, underwent assessment of executive, verbal comprehension, visuospatial, behavioral, and QoL measures, as well as of the ToM abilities by Emotion Attribution Task (EAT), Advanced Test of ToM (ATT), and Eyes Task (ET). ALS patients obtained significantly lower scores than controls on EAT and ET. No significant difference was found between the two groups on ATT. As regard to type of ALS onset, patients with bulbar onset performed worse than those with spinal onset on ET. Correlation analysis revealed that EAT and ET were positively correlated with education, memory prose, visuo-spatial performances, and "Mental Health" scores among QoL items. Our results suggest that not only "cognitive" but also "affective" subcomponents of ToM may be impaired in the early stages of ALS, with significant linkage to disease onset and dysfunctions of less executively demanding conditions, causing potential impact on patients' "Mental Health."
We consider an image motion stabilization system embedded into a space telescope for a scanning optoelectronic observation of terrestrial targets. Developed model of this system is presented taking into account physical hysteresis of piezoceramic driver and a time delay at a forming of digital control. We have presented elaborated algorithms for discrete filtering and digital control, obtained results on analysis of the image motion velocity oscillations in the telescope focal plane, and also methods for terrestrial and in-flight verification of the system.
The optimal biogas system design model (OBSDM) described in this paper is intended to be used as a decision-making tool to increase awareness of the potential of biogas technology for different applications in Sub-Saharan Africa (SSA). The decision-making tool identifies the most suitable biodigester design based on user defined inputs, including energy and fertiliser requirements; feedstock (type, amount, and rate of supply); water supply; land use (area, soil type, ground water level); climate (temperature and rainfall); construction materials available locally; and the priorities (based on sustainability criteria) of the intended biogas user. The output of the model provides a recommended design with estimates of the expected costs, energy and fertiliser production, and links to contact biodigester suppliers. In order to test the model, data from household surveys conducted in rural regions of Kenya and Cameroon were used as inputs to the model. An innovative fixed dome biodigester design, which uses stabilised soil blocks instead of bricks, was identified as optimal for both Kenyan and Cameroonian rural households. The expected performance of the optimal biogas system design from the model output was consistent with survey data on existing biogas systems in the region. (C) 2017 Elsevier Ltd. All rights reserved.
To create possibilities for a more sustainable wastewater management, a novel system consisting of electrodeionization (EDI) and solid oxide fuel cells (SOFCs) is proposed in this study. This system is integrated with anaerobic digestion/landfills to capture energy from carbonaceous and nitrogenous pollutants. Both EDI and SOFCs showed good performances. EDI removed 95% and 76% ammonium-nitrogen (NH4+-N) from diluted (0.025 M) to concentrated (0.5 M) synthetic ammonium wastewaters, respectively, accompanied by hydrogen production. SOFCs converted the recovered fuels, biogas mixtures of methane and carbon dioxide, to electricity. Under the optimal conditions of EDI (3.0 V applied voltage and 7.5 mm internal electrode distance (IED), and SOFCs (750 degrees C operating temperature), the system achieved 60% higher net energy output as compared to conventional systems. The estimated energy benefit of this proposed system showed that the net energy balance ratio is enhanced from 1.11 (existing system) to 1.75 (this study) for a local Hong Kong active landfill facility with 10.0 g L-1 chemical oxygen demand (COD) and 0.21 M NH4+-N. Additionally, an average of 80% inorganic ions (heavy metals and nutrient elements) can be removed from the raw landfill leachate by EDI cell. The results are successful demonstrations of the upgrades of anaerobic processes for energy extraction from wastewater streams. (C) 2017 Elsevier Ltd. All rights reserved.
There is a rapid growing interest in using biomass as an alternative source for clean and sustainable energy production. In this work, a hybrid system was developed to combine anaerobic digestion (AD) and gasification for energy recovery from yard waste and woody biomass. The feasibility of the proposed hybrid system was validated experimentally and numerically and the energy efficiency was maximized by varying energy input in the drying process. The experiments were performed in two stages. At the first stage, AD of yard waste was conducted by mixing with anaerobic sludge. At the second stage, co-gasification was added as post-treatment for the AD residue for syngas production. The co-gasification experiments of AD residue and woody biomass were conducted at varying mixing ratios and varying moisture contents of AD residue. Optimal energy efficiency was found to be 70.8% at mixing ratio of 20 wt% AD residue with 30 wt% moisture content. Two kinetic models were then adapted for prediction of biogas produced in AD process and syngas produced in gasification process, respectively. Both experimental and numerical results showed that full utilization of biomass could be realized to produce energy through the combination of these two technologies. (C) 2017 Elsevier Ltd. All rights reserved.
Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative participants with HSIL occupying aehalf the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.
Aims: Verrucous carcinoma (VC) is a variant of well-differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke-Lowenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV-induced lesion. Methods and results: Ten cases of VC and four cases of BLT were included. Several techniques were used for HPV detection: in-situ hybridization for HPV6, 11, 16 and 18, six different polymerase chain reaction (PCR) protocols for detection of at least 89 HPV types from alpha-, beta-, gamma- and mu-PV genera and in-situ hybridization for high-risk HPV E6/E7 mRNA; p16 immunohistochemistry and morphometric analysis were also performed. Alpha-, gamma- and mu-PVs were not found in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression was not present in any of the lesions. Among microscopic features, only the absence of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from BLT. Conclusions: Our results suggest that anal VC, similarly to VC at other sites, is not associated with HPV infection, and must be distinguished from BLT, which is associated with low-risk HPV. Only with well-set diagnostic criteria will it be possible to ascertain clinical behaviour and optimal treatment for both lesions.
The objective of this work is to minimize testing cost of analog and RF circuits for which complete specification tests are available. We use an integer linear program (ILP) to eliminate as many tests as possible without exceeding the required defect level. The method leverages correlation among specifications, thereby avoiding the tests for specifications that are sufficiently covered by tests for other specifications. First, Monte Carlo simulation determines probabilities for each test covering all other specifications it was not originally intended for. These probabilities and the given defect level then define an ILP model for eliminating unnecessary tests. An hypothetical example illustration of ten specifications demonstrates that depending on the defect level requirement up to half of the tests may be eliminated. Monte Carlo simulation using spice for probabilistic characterization of tests versus specifications followed by ILP optimization for two commercially available integrated circuits, an operational amplifier and a radio frequency power controller (RFPC), are presented as evidence of effectiveness of the technique.
The Water Cherenkov Detector Array (WCDA) is one of the core detectors in the Large High Altitude Air Shower Observatory (LHAASO), and it consists of 3600 photomultiplier tubes (PMTs). Both high resolution time and charge measurement are required over a large dynamic range from 1 photoelectron (P.E.) to 4000 P.E. The prototype of an analogue front-end Application Specific Integrated Circuit (ASIC) fabricated using Global Foundry 0.35 mu m CMOS technology is designed to read out the PMT signal in the WCDA. This ASIC employs leading edge discrimination and an (RC)4 shaping structure. Combined with the following Time-to-Digital Converter (TDC) and Analog-to-Digital Converter (ADC), both the arrival time and charge of the PMT signal can be measured. Initial test results indicate that time resolution is better than 350 ps and charge resolution is better than 10% at 1 P.E. and better than 1% with large input signals (300 P.E. to 4000 P.E.). Besides, this ASIC has a good channel-to-channel isolation of more than 84 dB and the temperature dependency of charge measurement is less than 5% in the range 0-50 degrees C
A low pass (LP) and complex band pass (CBP) reconfigurable analog baseband circuit for software-defined radio (SDR) receivers is presented. It achieves 1-15 MHz LP bandwidth, 2-8 MHz CBP bandwidth and 0-36 dB gain range with 1 dB step. Nulling-resistor Miller feed-forward (NRMFF) differential-mode compensation, passive left half-plane (LHP) zero common-mode compensation and Quasi-Floating Gate (QFG) technique are proposed to improve the high frequency performance and driving capability of the embedded fully differential operational amplifier (Op-Amp). The analog baseband circuit has been implemented in 65 nm CMOS. It achieves 15.2 dB m/27.1 dB m IB/OB-IIP3, -2 dB m IP1dB and 71 dB m IIP2 while consuming 3.6-9.1 mW from a 1.2 V power supply and 0.75 mm(2) chip area. (C) 2014 Elsevier Ltd. All rights reserved.
This paper presents the results of study on utilization of Z-copy Voltage Controlled Current Follower Differential Input Transconductance Amplifier (ZC-VCCFDITA) active element in a single purpose filtering structure. This active element has three voltage-controlled parameters (intrinsic resistance of current input, voltage gain and transconductance of output section) and is very useful for design of oscillators, signal generators and frequency filters with just one active element. In this paper, the important parameters of possible behavioural model of ZC-VCCFDITA are shown and a particular solution of the controllable band-pass filter is presented. Theoretical, calculated, simulated and moreover also measured results are mutually compared.
Automation of analog integrated circuit (IC) design process is very important because of the optimization contradictions. In this study, benefits of multi-objective evolutionary algorithms are presented on two stage operational amplifier design using Harmony Search Algorithm (HSA) and Non-dominated Sorting Genetic Algorithm (NSGA-II). HSA is a new kind of multi-objective evolutionary algorithm which was inspired from the musicians those are looking for the best combination of musical sounds of different instruments that produces most pleasing sound. NSGA-II is an advanced version of genetic algorithm. It combines both current parents and their child population to select new parents. These kinds of design automation tools are required for analog circuit design because there are several contradictions in the design. In this work, transistor sizes which effects all constraints indirectly were automatically synthesized by HSA an NSGA-II.
Noise optimization is a challenging problem for nanoscale metal-oxide-silicon field-effect transistor circuits. This brief presents a technique that uses transconductance-to-drain current (g(m)/I-D)-dependent transistor-noise parameters to explore the design space and to evaluate tradeoff decisions. An expression for the corner frequency of the folded-cascode amplifier is derived. The design process demonstrated in this brief using the folded-cascode amplifier is applicable to a wide class of amplifier circuits.
This paper reviews the importance of device-circuit interactions (DCI) and its consideration when designing thin film transistor circuits and systems. We examine temperature-and process-induced variations and propose a way to evaluate the maximum achievable intrinsic performance of the TFT. This is aimed at determining when DCI becomes crucial for a specific application. Compensation methods are then reviewed to show examples of how DCI is considered in the design of AMOLED displays. Other designs such as analog front-end and image sensors are also discussed, where alternate circuits should be designed to overcome the limitations of the intrinsic device properties.
This paper presents analog building blocks that find potential applications in display panels. A buffer (source-follower), subtractor, adder, and high-gain amplifier, employing only n-type enhancement amorphous gallium-indium-zinc-oxide thin-film transistors (a-GIZO TFTs), were designed, simulated, fabricated, and characterized. Circuit simulations were carried out using a neural model developed in-house from the measured characteristics of the transistors. The adder-subtractor circuit presents a power consumption of 0.26 mW, and the amplifier presents a gain of 34 dB and a power consumption of 0.576 mW, with a load of 10 M Omega//16 pF. To the authors' knowledge, this is the highest gain reported so far for a single-stage amplifier with a-GIZO TFT technology.
This paper presents a new environment for characterizing foundry CMOS device models and analog basic blocks. This environment can also be used to design some analog basic building blocks. It designs analog circuits by dividing them into a set of basic building blocks connected together, where each block is optimized separately considering other blocks' loading and/or boundary conditions. It can run over different technologies using foundry models and simulation measurements without approximations, hand calculations or simplified equations. The efficiency of the complete flow is evaluated through designing a single-ended two-stage operational amplifier over 180nm, 130nm, 90nm, 65nm and 40nm technologies.
Circuit parameters and configuration are very important when studying the synergistic effects total dose/SET. We explore a method combining dynamic parameter measurement and spectrum analysis which lead to a better understanding of this complex phenomenon. In this paper symbolic circuit analysis is used to obtain the relationship between input, output and noise injection due to photocurrent generation in the form of a rational function using symbolic variables in the complex frequency domain. This simulation technique was able to predict the impact of (i) total dose level, (ii) circuit parameters, and (iii) the injected energy on the ASET shapes. Basic mechanisms as field collapse and collection efficiency were also predicted and assessed.
This paper presents an optimization-based design methodology for fully differential amplifiers (FDAs) including the effects of real common-mode feedback (CMFB) circuits as constraints in the design flow. The sizing procedure is performed separately for the main amplifier and for the CMFB circuit, reducing the number of free variables and exploring the design space in a more efficient way. Also, this methodology can be employed to design single and two-stages FDAs whereas a second pole compensation scheme is necessary. In order to validate the proposed methodology, a two-stage fully differential amplifier with a no capacitor feed-forward (NCFF) compensation technique was designed in 0.13 mu m CMOS technology with a 1.2 V power supply. The presented results also include a pole-zero pair mismatch analysis and proposes a solution in order to compensate the generated pole-zero doublet that might affect the performance of the amplifier. We can show that this approach reduces the overall static power consumption while satisfying the design specifications.
Four parts of opamp OP1177ARZ manufactured by Analog Devices have been tested. The chips have been compared visually and with specialized software. Forms of ionization response in three checkpoints have been registered, and maps of response amplitudes on the crystal surface have been constructed. It has been fixed, that crystals samples are various in spite of identical crystals marking. So TID behavior of various samples has been observed.
A systematic method is proposed to approach complete fault coverage for catastrophic faults in analog circuits. In the proposed method, a fault propagation graph is first created from the circuit netlist. Standard graph theory techniques are then employed to identify a minimal set of observation points (MOP) such that, by monitoring these points, complete fault coverage can be achieved, i.e., all potential catastrophic faults of the circuit can be detected theoretically. The developed method is valuable because of the increasingly critical quality requirements for modern IC applications and the lack of existing methods that can achieve sub-ppm test escapes in the state-of-the-art. A widely used benchmark circuit, a CMOS operational amplifier, is utilized to demonstrate and validate the method. Simulation results show that all catastrophic faults can be detected by monitoring the identified MOP.
An analog front-end (AFE) for a multifunction environmental sensor is proposed. The AFE is designed to be able to sense 1 mu V, 1 fC, and 1 pA level signals in a low-frequency band around DC, and consists of an instrumentation amplifier (IA), a charge amplifier (CA), and a continuous time delta-sigma (CT-Delta Sigma) ADC. To reduce the low-frequency noise of operational amplifier (OPAMP) which is used for signal path, this paper proposes a weak-inversion biasing technique. The designed IA achieved 26 nVrms input-referred noise (IRN) in the band of 0.1-10 Hz with 0.22 mm(2) die area. The designed CA achieved 25 aCrms IRN in charge sensing mode and 19 fArms IRN in current sensing mode in the band of 0.01-1 Hz, respectively, and occupies 0.12 mm(2) die area. The AFE has been fabricated in a 0.18 mu m CMOS process with 4.5 mm(2) die area. The current consumption at 2.56 kHz output data rate (ODR) is 2.5 mA, reducing to 2 mu A at 0.01 Hz ODR.
This paper presents an accurate design approach for two-stage CMOS operational amplifiers developed based on the usual design procedure. It eliminates the errors existed in design results by employing the accurate MOS model and carrying out the design procedure iteratively. The specifications of the amplifier designed by this approach match exactly with the user specified values. A design example in 0.18 mu m CMOS technology is given to illustrate the effectiveness of the proposed design approach.
Analog ICs are widely used in communication, sense and power systems of spacecraft. They are produced with variety of technologies (CMOS, BiCMOS, functional options). This paper provides TID degradation analysis for most common analog ICs - operational amplifiers, voltage comparators and linear stabilizers. General trends in radiation behavior and recommendations for analog IC's radiation testing are presented.
The article presents functional schemes of two IPmodules included into a new (2016) radiation-hardened structured arrays (SA) MH2XA010. The microcircuits of the main modifications of op amps (OAs) with current negative feedback (CNF) can be realized on the base of SA (due to the interconnection wiring of elements). The terminal parameters of op amps are considered, the practical recommendations for choosing the steady-state behaviors, the active and passive elements of SA, providing the peak values of the slew rate and the upper frequency limit of op amp in a wide range of changes of transfer ratios are given. The properties of a new subclass of op amps based on SA MH2XA010 -circuits with the so called generalized current negative feedback, combining the properties of classical op amps with voltage feedback and op amps with CNF are examined.
The article suggests a new method of the errors evaluation from the several common-mode signals in the differential difference operational amplifiers (DDAs), based on the theory of autonomous multiport circuit. These errors of DDA in its main connection circuits can be described by feeding a special current autonomous parameter to the classical equivalent circuit of DDA. This parameter is connected with the highimpedance node of DDA and depends on the level of the common-mode components in the inputs of some input differential stages and also on the parameters spread of the elements. The paper shows that in DDAs the common-mode rejection ratio (CMRR) significantly worsens in comparison with classical op-amp. The parametric and circuitry methods of CMRR increase in the DDAs based on the inherent compensation of parasitic impedances are considered.
An architectural performance comparison of bandgap voltage reference variants, designed in a 0.18 mu m CMOS process, is performed with respect to single event transients. These are commonly induced in microelectronics in the space radiation environment. Heavy ion tests (Silicon, Krypton, Xenon) are used to explore the analog single-event transients and have revealed pulse quenching mechanisms in analogue circuits. The different topologies are compared, in terms of cross-section, pulse duration and pulse amplitude. The measured results, and the explanations behind the findings, reveal important guidelines for designing analog integrated circuits, which are intended for space applications. The paper includes an analysis on how pulse quenching occurs within the indispensable current mirror, which is used in every analog circuit.
The paper presents a high-voltage integrated-circuit driver capable of producing analog voltages up to 300 V, using Dalsa's 0.8-mu m HV CMOS/DMOS process, suitable for MEMS and medical systems. The IC driver includes a HV operational amplifier (op-amp) with a class-B output stage, and HV analog switches with improved off-isolation performance. In contrast to previous frequency compensation schemes, where only one dominant pole occurs below the unity-gain bandwidth, the HV op-amp employs a novel frequency compensation topology with three poles and two zeros located within the unity-gain bandwidth, and is capable of driving large capacitive loads from 100 pF to 10 nF. Theoretical analysis of off-isolation of the HV analog switches is also reported and confirms the improvement in off-isolation performance.
Functional errors in analog portion of mixed signal circuits become more severe and improvements in verification methods are increasingly important. Current verification methods fall into two categories, simulation-based verification and formal verification (Barke et al. [1]), focusing on verifying analog circuit function/performance, This paper proposes a novel approach verifying analog circuit design using causal reasoning. Causal reasoning is the inductive reasoning process to create a new design. The flow begins with mining the causal reasoning steps (design plan) that produced the circuit, including starting ideas, design step sequence, and their justifications (Jiao et al., 2015 [2]).. Then, topological features corresponding to the starting ideas and design step sequence are verified individually by replacing the related devices with ideal behavior model. Performance is evaluated through Cadence Spectre simulation. Comparison with new circuit performance reveals incorrect functional issues and/or performance potentials for improvement. They are negative causes of certain starting ideas or design steps, which might have been omitted during the design process. The paper discusses three operational amplifier designs realized in 0.2-mu m CMOS technology to illustrate the verification approach. (C) 2016 Elsevier B.V. All rights reserved.
This paper presents a new family of Class-AB operational transconductance amplifier (OTA) circuits based on single-stage topologies with non-linear current amplifiers. The proposed variable-mirror amplifier (VMA) architecture is mainly characterized by generating all Class-AB current in the output transistors only, by exhibiting very low sensitivity to both technology and temperature deviations, and by avoiding the need for any internal frequency-compensation mechanism. Hence, this family of OTAs is well-suited for low-power switched-capacitor circuits and specifically optimized for switched-OpAmp fast on-off operation and multi-decade load-capacitance specifications. Analytical expressions valid in all regions of operation are presented to minimize VMA settling time in discrete-time circuits. Also, a complete OTA design example integrated in 0.18 mu m 1P6M MiM 1.8 V CMOS technology is supplied with detailed simulation and experimental results. Compared to resistor-free state-of-art Class-AB OpAmp and OTA literature, the proposed architecture returns the highest measured figure-of-merit value.
This paper presents a digital testing strategy for characterizing an analog circuit block. The operational amplifier (op amp) is evaluated due to its wide application in electronic circuits and systems. In the proposed strategy, the op amp device under test (DUT) is configured to respond to a testing pulse, and the associated output is digitized by a digital buffer to reduce the high cost of generating a high-frequency clock. The testing procedure is divided into two modes to estimate the reference slew rate and then to evaluate the practical slew rate to moderate the difficulty of designing a digital buffer that has a highly precise delay time. The testing concept, accuracy, time, and hardware are also comprehensively investigated to describe the proposed testing strategy. The digital compatibility, the simplicity, and the testing capability of the high-performance op amp are the main advantages of the proposed testing strategy. Easily available discrete devices were experimentally employed to verify the functionality of the proposed testing strategy. An integrated application to test the op amp DUT embedded in a second-order Sallen-Key low-pass filter was simulated with the HSPICE tool to verify the testing feasibility and the effectiveness of the proposed strategy.
We report a pulse width modulation (PWM) buck converter that is able to achieve a power conversion efficiency (PCE) of >80% in light loads (80% efficiency for a wide range of load conditions from 45 mu A to 4.1 mA, while generating 1 V output from 2.5-3.3 V supply. The converter occupies 0.375 mm(2) in 0.18 mu m CMOS processes and requires two external components: 1.2 mu F capacitor and 6.8 mu H inductor.
ADC/DAC radiation failures are mainly due to radiation-induced degradation of precision parameters of the transfer characteristic such as gain, zero offset, full-scale voltage, integral and differential non-linearity, conversion error. ADC/DAC radiation failure specifics is that even a slight deviation of electrical parameter of internal elements (comparator threshold, internal reference voltage, switch leakage, operational amplifier gain, etc.) often leads to significant degradation of ADC/DAC accuracy. ADC/DAC radiation test procedure and facilities are developed and test results are introduced.
The work proposes an improved technique to design a low power 8-bit asynchronous successive approximation register (ASAR), an analog-to-digital converter (ADC). The proposed ASAR ADC consists of a comparator, ASAR (digital control logic block), and a capacitivedigital-to-analog convertor (C-DAC). The comparator is a preamplier-based improved positive feedback latch circuit which has a built-in sample and hold (S/H) functionality and saves an enormous amount of power. The implemented digital control logic block performing the successive approximation (SA) algorithm is totally unrestrained of the external clock pulse. The outputs from the comparator are given to a XOR logic whose outputs serve as an internally generated clock (ready signal) to trigger the digital control block. Hence, an external clock is not required to initiate the digital control block making its operation asynchronous. By implementing this, the ADC can circumvent the usage of an oversampled clock and can operate on a single low-speed sample clock. This, in turn, saves power and it cuts down the required resilience in sampling rates. The proposed ADC has been designed and simulated using UMC-0.18 mu m CMOS technology which dissipates 32.18 mu W power when operated on a single 1V power supply and achieves complete 8-bit conversion in 1.09 mu s. The relative accuracy of capacitor ratio, aperture jitter and FOM are 0.39%, 1.2 ns and 125 fJ/conversion-step, respectively.
Due to technology scaling, the design of the conventional-type analog-to-digital converter (ADC), which uses an operational amplifier as one of its building blocks, becomes more difficult. In this brief, new techniques to design time-based ADC (TADC), which uses a voltage-controlled oscillator (VCO), are proposed. The VCO is followed by a time-to-digital converter, implemented in a Sigma Delta architecture. A novel architecture, using a multibit, nonlinear internal quantizer and a feedback digital-to-time converter, implemented by using phase interpolation, is employed to compensate the nonlinear transfer curve of the VCO. Dynamic element matching and calibration are used to improve the robustness of the TADC against mismatch. The TADC uses an implicit sample and hold that relaxes the bounds on input frequency. A TADC implemented in 0.13-mu m CMOS technology achieves a measured signal-to-noise + distortion ratio of 60.2 dB and a dynamic range of 11 b for a bandwidth of 2 MHz.
This paper presents a 14.9-bit 3.57-MS/s algorithmic ADC that uses iterative gain enhancement, a technique that uses multiple clock phases to increase the effective op-amp gain in a switched-capacitor circuit. Using an op-amp that gives only 30-dB loop gain in a feedback circuit without gain enhancement, application of the iterative gain enhancement technique boosts the loop gain to 81 dB. The algorithmic ADC uses a capacitor sharing and scaling technique, which saves power and reduces errors. The ADC has an active area of 0.75 mm2 in 0.25-mu m CMOS and dissipates 16.2 mW. Iterative gain enhancement increases the SNDR from 44.6 dB to 78.5 dB and the SFDR from 45.9 dB to 96.2 dB. Reducing the number of gain-enhancement iterations for the LSBs increases the conversion rate from 3.57 MS/s to 4.65 MS/s with only minor performance degradation.
A wide-bandwidth (BW) power-efficient continuoustime Sigma Delta modulator (CT Sigma Delta M) is presented. The modulator introduces a third-order filter implemented with a lossless integrator and a multiple-feedback single-amplifier biquadratic filter with embedded loop stability compensation. An active summing block is implemented by employing a common-gate current buffer followed by a transimpedance amplifier. This combination relaxes the specification requirements of the operational amplifier by making its required BW independent of the closed-loop gain. The proposed technique achieves optimum BW with reduced power consumption, making it functional for over gigahertz operation. Fabricated in a standard 40-nm CMOS technology, and clocked at 3.2 GHz, the CT Sigma Delta M achieves a signal-to-noiseand-distortion ratio of 65.5 dB over 75-MHz BWwhile consuming 22.8 mW of power. The obtained Walden's figure of merits is 98 fJ/conv-step.
A 400-800 MHz spectrum sensing system is designed and implemented using 0.18-mu m CMOS technology for cognitive radios in the UHF TV band. Based on envelope detection, the system employs a down converter, a digitally controlled oscillator, a low-pass filer (LPF), a rectifier, a comparator, and a digital control unit to realize spectrum sensing with 10-bit frequency representation. With variable-gain function of the LPF, signal strength can be measured and presented with a 5-bit signal strength index.
This study presents a self-testing platform with a foreground digital calibration technique for successive approximation register (SAR) analog-to-digital converters (ADCs). A high-accuracy digital-to-analog converter (DAC) with digital control is used for the proposed self-testing platform to generate the sinusoidal test signal. This signal is then implemented using an Arduino board, and the clock signal is generated to test the ADCs. In addition, fast Fourier transform and recursive discrete Fourier transform (RDFT) processors are adopted for dynamic performance evaluation and calibration of the ADCs. The third harmonic distortion caused by the non-linearity of the track-and-hold circuit, the mismatch of the DAC capacitor array, and the direct current (DC) offset of the comparator can be calculated using the processors to improve the ADC performance. The advantages of the proposed platform include its low cost, high integration, and no need for an extra analogy compensation circuit to deal with calibration. In this work a 12 bit SAR ADC and an RDFT processor are used in the Taiwan Semiconductor Manufacturing Co., Ltd. (TSMC) 0.18 mu m standard complementary metal-oxide-semiconductor (CMOS) process with a sampling rate of 18.75 kS/s to validate the proposed method. The measurement results show that the signal-to-noise and distortion ratio is 55.07 dB before calibration and 61.35 dB after calibration.
This paper describes a versatile composite amplifier in which a current feedback amplifier (CFA) drives an operational amplifier (OPA). In the conventional OPA-CFA composite amplifier, an OPA drives a CFA resulting in a composite structure that combines the DC input stability of the OPA and the high speed capability of the CFA. The proposed composite configuration combines different features of the CFA and OPA, specifically the constant bandwidth property of the CFA and the high power and high current output capacity of the OPA. The new circuit is easily implemented in the standard inverting and non-inverting configurations using commercially available devices, and the accuracy and constant bandwidth features were experimentally verified. Local feedback around the associated CFA ensures that the proposed composite amplifier possesses a higher level of bandwidth constancy than a single CFA.
The paper presents the structure and the principle of operation of the improved' Howland current pumps (or voltage-controlled current sources (VCCSs) for a grounded load). In particular, under review is the VCCS employing power operational amplifier (op amp) and the VCCS using low power op amp and an additional power transistor, extending working dynamic range. On the basis of analysis of the operational principle, the equations for transfer functions of both circuits and formulas for the related dynamic electrical parameters are obtained. Moreover, using these formulas, a design procedure is developed, and recommendations for simulation modelling are given. The efficiency of the proposed procedure is verified by simulation modelling and experimental testing of sample electronic circuits of VCCSs. Copyright (c) 2013 John Wiley & Sons, Ltd.
Analogical reasoning is an important mechanism for social cognition in typically developing children, and recent evidence suggests that some forms of analogical reasoning may be preserved in autism spectrum disorder. An unanswered question is whether children with autism spectrum disorder can apply analogical reasoning to social information. In all, 92 children with autism spectrum disorder completed a social content analogical reasoning task presented via photographs of real-world social interactions. Autism spectrum disorder participants exhibited performance that was well above chance and was not significantly worse than age- and intelligence quotient-matched typically developing children. Investigating the relationship of social content analogical reasoning performance to age in this cross-sectional dataset indicated similar developmental trajectories in the autism spectrum disorder and typically developing children groups. These findings provide new support for intact analogical reasoning in autism spectrum disorder and have theoretical implications for analogy as a metacognitive skill that may be at least partially dissociable from general deficits in processing social content. As an initial study of social analogical reasoning in children with autism spectrum disorder, this study focused on a basic research question with limited ecological validity. Evidence that children with autism spectrum disorder can apply analogical reasoning ability to social content may have long-range applied implications for exploring how this capacity might be channeled to improve social cognition in daily life.
The paper aim draws together two ideas that have figured in different strands of discussion in business ethics: the ideas of intuition and of reflection. They are considered in company with the third, complementary, idea of analysis. It is argued that the interplay amongst these is very important in business ethics. The relationship amongst the three ideas can be understood by reference to parts of modern cognitive psychology, including dual-process theory and the Social Intuitionist Model. Intuition can be misleading when based on fast and frugal heuristics, and reasoning needs social exchange if it is to support moral judgment effectively, but in the complex institutional environment of business, reflection and analysis can underpin social communication and feedback to develop sound intuition. Reflection and analysis are both more deliberate, systematic judgment processes than intuition, but are distinguished by the fact that reflection embraces hypothetical thinking and imagination, while analysis is careful, step-by-step reasoning. Examples of business ethics problems illustrate the need for both of these processes, and also suggest how they themselves can be enhanced in the same social exchange process that underpins the development of good intuition.
In this paper the results of layout design and circuit-topological computer simulation of some elements of analytical microsytem-on-chip with the "silicon-on-insulator" (SOI)-structures are presented. These elements were: an input cascade, a basic element of operational amplifier and a ring oscillator based on standard bulk CMOS technology and CMOS technology with the SOI-structures. Also the polysilicon-on-insulator resistive elements were studied in the wide temperature range. Such elements can be used as regular elements matrix for analog and digital signal processing in the integrated circuits and initial processing of analytical information microsystem-on-chip or as sensitive elements of the intellectual sensors of microsystemon-chip.
During development of adenovirus-based vaccines, samples have to be analyzed in order to either monitor the production process or control the quality and safety of the product. An important quality attribute is the total concentration of intact adenoviruses, which currently is determined by quantitative polymerase chain reaction (qPCR) or anion exchange-HPLC. Capillary Electrophoresis (CE) was evaluated as alternative to the current methods with the aim to have one single method that allows reliable and fast quantification of adenovirus particles throughout the full process. Intact adenoviruses samples from downstream processing and upstream processing were analyzed directly by CE with UV-detection at 214 nm. Only the samples with high amounts of DNA required a simple sample pretreatment by benzonase. Adenovirus particles were separated from matrix components such as cell debris, residual cell DNA, and/or proteins on a PVA-coated capillary using a BGE consisting of 125 mM Tris, 338 mM tricine and 0.2% v/v polysorbate-20 at pH 7.7. Full factorial design of experiments was used for method optimization as part of the analytical quality by design (AQbD) method development approach. The method was validated for the quantification of adenoviruses on five representative samples from the manufacturing process in the range of 0.5 x10(11)-1.5 x10(11) adenovirus particles per ml (similar to 80 to 250 pmo1/1). The CE method showed intermediate precision of 7.8% RSD on concentration and an accuracy (spiked recovery) of 95-110%. CE proved highly useful for process development support and is being implemented for in-process control testing for adenovirus vaccine manufacturing.
The anaerobic ammonium oxidation (anammox) process has been recognized as a promising sewage treatment approach. Considering the susceptibility, it is meaningful to study the behaviors of anammox bacteria under the unfavorable conditions. Here, we found that anammox bacteria more probably tended to aggregation by the regulation of c-di-GMP against the unfavorable environmental stresses (low temperature, aerobic condition and low pH). Further using multiple protein sequence alignment, we systematically examined the functionality of thirteen genes encoding putative c-di-GMP metabolic enzymes in anammox organism Candidatus Jettenia caeni, revealing most of the predicted enzymes were predicted to be active. Particularly, ectopic expression of jcaA, a gene encoding a protein with both GGDEF domain and EAL domain, suggested that it encoded a functional enzyme capable of both synthesizing and degrading c-di-GMP, which was clearly confirmed by in vitro enzymatic assays and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the catalytic mechanism was simulated by the means of three-dimensional homology modeling and molecular docking. The identification of cdi-GMP turnover and its role in granulation for anammox organism provides a new perspective for regulation of its aggregation capability and further promotion of anammox performance in the application of wastewater treatment process. (C) 2017 Elsevier Ltd. All rights reserved.
Henoch-Schonlein purpura (HSP) is a systemic vasculitis mediated by autologous immune complex. Animal models of HSP are scarce. Here, we describe the characteristics of HSP rabbit model in the acute and recovery phase. First, we constructed the HSP rabbit models, and then assessed immunologic indicators of models by enzyme-linked immunosorbent assay and immunoturbidimetry. Histomorphological characteristics were analyzed by haematoxylin-eosin, immunofluorescence and special staining. In the acute stage (24 h) after antigen challenge, the model group rabbits featured skin ecchymosis and abnormal laboratory examination results. Three weeks following the allergic reaction, purple spots improved markedly, and edema and blood seeping decreased, but obvious inflammation was present in the skin, kidneys, joints, gastrointestinal, lung and liver. Serological results of CD4, CD/CD8, IL-2, IL-4, and TNF-alpha, IgA, IgG, TropI, Alb and T were still abnormal. IgA and C3 expressed in skin and kidney and eosinophils expressed in skin and lungs were increased. The rabbit model can mimic human HSP lesions in symptoms, pathology, and immunology and may provide valuable insight into the pathogenesis of HSP and serve as a tool for future therapeutic development targeting HSP.
Anaphylaxis is an increasingly prevalent life-threatening allergic condition that requires people with anaphylaxis and their caregivers to be trained in the avoidance of allergen triggers and in the administration of adrenaline autoinjectors. The prompt and correct administration of autoinjectors in the event of an anaphylactic reaction is a significant challenge in the management of anaphylaxis. Unfortunately, many people do not know how to use autoinjectors and either fail to use them or fail to use them correctly. This is due in part to deficiencies in training and also to the lack of a system encouraging continuous practice with feedback. Assistive smartphone healthcare technologies have demonstrated potential to support the management of chronic conditions such as diabetes and cardiovascular disease, but there have been deficiencies in their evaluation and there has been a lack of application to anaphylaxis. This paper describes AllergiSense, a smartphone app and sensing system for anaphylaxis management, and presents the results of a randomized, controlled, prepost evaluation of AllergiSense injection training and feedback tools-with healthy participants. Participants whose training was supplemented with AllergiSense injection feedback achieved significantly better practiced injections with 90.5% performing correct injections compared to only 28.6% in the paper-only control group. In addition, the results provide insights into possible self-efficacy failings in traditional training and the benefits of embedding self-efficacy theory into the technology design process.
Background The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. Objective To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. Methods Patients presenting to the emergency department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time-points. Traditional anaphylaxis biomarkers, histamine and mast cell tryptase, were measured by ELISA and ImmunoCAP, respectively. Plasma myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L concentrations by cytometric bead array, and both compared to healthy controls. Results In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine positive, and 47 (70%) were mast cell tryptase positive. At enrolment, myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4, 10.5) fold higher in moderate and severe patients, respectively, compared with healthy controls, and remained stable over the first 5 h following symptom onset. At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower in moderate and severe patients, respectively, than healthy controls, and was stable over the first 5 h. There were no associations between myeloperoxidase or soluble CD62L concentrations and either histamine or mast cell tryptase concentrations. Conclusions and Clinical Relevance These results provide compelling evidence for the involvement of neutrophils during acute human anaphylaxis, suggesting they are activated early in the reaction, regardless of mast cell activation. This important finding increases our understanding of the basic mechanisms of anaphylaxis, a necessary precursor to improving treatment and prevention.
BACKGROUND: Anaphylaxis diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive and 82% specific when retrospectively validated. OBJECTIVE: To prospectively evaluate the diagnostic accuracy of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for diagnosis of anaphylaxis in the emergency department (ED). METHODS: We conducted a prospective observational study of patients seen in our institution's ED from April 2010 to March 2013. Patients seeking care for an allergic reaction and possible anaphylaxis were enrolled. Patients and providers completed questionnaires regarding onset, trigger, and signs and symptoms. Records were reviewed independently and blindly by 2 board-certified allergist-immunologists, and their final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard. Two-by-two tables were built, and test characteristics were calculated. RESULTS: Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%), of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement between allergist-immunologists was substantial (k = 0.7). Test characteristics (95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio, 3.26; and negative likelihood ratio, 0.07. CONCLUSIONS: Prospectively, the NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower specificity (71%) than on retrospective assessment. These criteria are likely to be useful for the diagnosis of anaphylaxis in the ED. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background: High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom-and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age-and sex-matched controls without any history of DHRs. Method: Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Results: Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) lg/l vs. 2.8 (1.6-4.3) lg/l vs. 2.6 (1.8-3.6) lg/l, respectively, (p >0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) lg/l, mild anaphylaxis 3.0 (1.9-4.9) lg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) lg/l were also comparable (p >0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. Conclusion: The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.
BACKGROUND: Anaphylaxis is a potentially life-threatening systemic allergic reaction. Studies suggest that the incidence of anaphylaxis is increasing; however, recent trends in emergency department (ED) visits for anaphylaxis in the United States have not been studied. OBJECTIVE: To examine trends in the incidence and rates of anaphylaxis-related ED visits from 2005 through 2014. METHODS: We retrospectively analyzed data from a national administrative claims database including commercially insured and Medicare Advantage patients. We identified all ED visits for anaphylaxis and calculated rates as number of anaphylaxis-related ED visits per 100,000 enrollees. Rates were compared over time and by age and trigger. RESULTS: During the 10-year time period, 56,212 ED visits for anaphylaxis were identified. The median (interquartile range) age was 36 (17-52 years) years, and 58% were female. Most cases (57%) were due to unspecified triggers, 27% were associated with food, 12% were medication related, and 4% were due to insect venom. The overall rate of anaphylaxis per 100,000 enrollees increased by 101%, from 14.2 in 2005 to 28.6 in 2014 (P<.001). Rates of ED visits for anaphylaxis increased in all age groups, but the greatest increase was in children aged 5 to 17 years (196% increase; P<.001). The rate of food-related anaphylaxis increased by 124% (P<.001), and the rate of medication-related anaphylaxis increased by 212% (P<.001). CONCLUSIONS: ED visits for anaphylaxis increased between 2005 and 2014. Increases in ED visits were greatest among children. (C) 2016 American Academy of Allergy, Asthma & Immunology
BACKGROUND: The prescribing pattern of epinephrine over time is an indicator of the secular trend of anaphylaxis. However, it is not well known in a population level in the United States. OBJECTIVE: To evaluate the trend of prescriptions for epinephrine autoinjectors in Olmsted County, Minn, residents. METHODS: Outpatient prescriptions for epinephrine were identified among residents of Olmsted County, Minn, between January 1, 2004, and December 31, 2010. We used the first prescription per patient per year, and the first prescription per patient during the study period to calculate incidence rates. Incidence rates per 100,000 person-years were calculated using patients prescribed epinephrine per year as the numerator and age-and sex-specific counts of the population of Olmsted County as the denominator. The relationships of age group, sex, and year of prescription with incidence rates were assessed by fitting Poisson regression models using the SAS procedure GENMOD. RESULTS: The overall incidence rate of epinephrine autoinjector prescriptions during the study period was 757 per 100,000 person-years (95% confidence interval: 740-774). The prescription rates per patient per year increased over time, with an annual rate of increase of 8% (P < .001), but the rates per patient remained stable (P = .077). For each year, incidence rates overall were higher in women compared with men (P < .001). From ages 0 to 19, incidence rates were higher in boys compared with girls. At age 20 and above, incidence rates were higher in women compared with men. CONCLUSIONS: The overall rate of epinephrine autoinjector prescriptions increased, but the rate of first-time prescriptions was stable from 2005 to 2010. In childhood, boys were more likely to receive a prescription than girls, but this reversed in later ages. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background: Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen of increased interest worldwide which has been detected in northern Africa. Anaplasma platys is also present in this region and could possibly have a zoonotic potential. However, only one recent article reports on the human esposure to A. phagocytophilum in Morocco and no data are available on canine exposure to both bacteria. Therefore, we conducted a cross-sectional epidemiological study aiming to assess both canine and human exposure to Anaplasma spp. in Morocco. A total of 425 dogs (95 urban, 160 rural and 175 working dogs) and 11 dog owners were sampled from four cities of Morocco. Canine blood samples were screened for Anaplasma spp. antibodies by an enzyme-linked immunosorbent assay (ELISA) and for A. phagocytophilum and A. platys DNA by a real-time polymerase chain reaction (RT-PCR) targeting the msp2 gene. Human sera were tested for specific A. phagocytophilum immunoglobulin G (IgG) using a commercial immunofluorescence assay (IFA) kit. Results: Anaplasma spp. antibodies and A. platys DNA were detected in 21.9 and 7.5% of the dogs, respectively. Anaplasma phagocytophilum DNA was not amplified. Anaplasma platys DNA was significantly more frequently amplified for working dogs. No statistically significant differences in the prevalence of Anaplasma spp. antibodies or A. platys DNA detection were observed between sexes, age classes or in relation to exposure to ticks. A total of 348 Rhipicephalus sanguineus (sensu lato) ticks were removed from 35 urban and working dogs. The majority of dog owners (7/10) were seroreactive to A. phagoyctophilum IgG (one sample was excluded because of hemolysis). Conclusions: This study demonstrates the occurrence of Anaplasma spp. exposure and A. platys infection in dogs, and A. phagocytophilum exposure in humans in Morocco.
The lateral ponticle and epitransverse process are rare anatomical variations found on the atlas vertebra of the cervical spine. When a lateral ponticle occurs, an abnormal bony bridge extends from the superior articular facet to the transverse process. This bony bridge bisects the transverse foramen wherein the vertebral artery normally lies. In this case report, we describe a C1 specimen from an adult male with a lateral ponticle on the right side and an epitransverse process on the left side. Additionally, an articular facet-like structure was also found on the lateral ponticle's surface. Relevant literature regarding the lateral ponticle across age groups, sex, race, and species is also reviewed. We postulate that genesis of the lateral ponticle of the atlas occurs in utero, specifically during the lateral ossification of the ventral sclerotomes. To our knowledge, an articular facet-like structure on such a ponticle has not been reported previously. Moreover, simultaneous occurrence of a lateral ponticle and contralateral epitransverse process has, to our knowledge, not been reported before.
The intervertebral disc (IVD) is a joint unique in structure and functions. Lying between adjacent vertebrae, it provides both the primary support and the elasticity required for the spine to move stably. Various aspects of the IVD have long been studied by researchers seeking a better understanding of its dynamics, aging, and subsequent disorders. In this article, we review the surgical anatomy, imaging modalities, and molecular biology of the lumbar IVD. Clin. Anat. 30:251-266, 2017. (c) 2017 Wiley Periodicals, Inc.
Granulomatosis with Polyangiitis (GPA) (formerly known as Wegener's granulomatosis) is a vasculitis of unknown etiology affecting predominantly small- to medium-sized vessels, usually involving the upper and lower respiratory tract and kidneys. Anti-neutrophil cytoplasmic autoantibodies are probably the initial cause of the inflammatory process that leads to the typical necrotizing lesions. In this issue of the European Journal of Immunology, Szczeklik etal. [Eur. J. Immunol. 2017. 47: 724-733] report some interesting findings on the possible involvement of T-cell subsets in the pathogenesis of the disease. This prospective study, performed on a large cohort of patients, identifies Th17 lymphocytes as the possible pathogenic subset of GPA, and Treg cells as the possible suppressors of the inflammatory process. These two subsets in peripheral blood could be used as cellular biomarkers of disease activity, and this would result particularly useful in the follow-up of patients once the immunosuppressive treatment has been initiated.
Purpose of Review The ANCA-associated vasculitides are a group of small vessel vasculitides characterized by autoantibodies recognizing the neutrophil cytoplasmic antigens PR3 and MPO. We examine the current clinical and molecular immunology understanding of ANCA-associated vasculitides and discuss the current needs in our understanding of the pathogenic mechanisms of these rare diseases. Recent Findings The majority of efforts to understand the pathogenesis of these diseases have focused on dissecting neutrophil biology because the neutrophil is the primary expressor of ANCA autoantigens. However, a number of important genetic, clinical, and cellular biology observations suggest that attempts to understand the pathogenesis of ANCA vasculitides should move away from emphasis on the role of the neutrophil and instead re-focus on the potential role of other immune cell mediators. Summary Whether or not neutrophils are the key determinant of ANCA-associated vasculitis pathogenesis should be revisited in detail. A neutrophil-centric view of the pathogenesis of these diseases cannot fully account for important genetic, clinical, and cellular biology observations that implicate important and under-appreciated roles for monocytes and T cells. Refocusing on these findings will likely lead to new discovery of novel therapeutic targets and the identification of clinically useful biomarkers for disease activity.
We studied date palm phytochelatin synthase type I (PdPCS1), which catalyzes the cytosolic synthesis of phytochelatins (PCs), a heavy metal binding protein, in plant cells. The gene encoding PdPCS1 (Pdpcs) consists of 8 exons and 7 introns and encodes a protein of 528 amino acids. PCs gene history was studied using Notung phylogeny. During evolution, gene loss from several lineages was predicted including Proteobacteria, Bilateria and Brassicaceae. In addition, eleven gene duplication events appeared toward interior nodes of the reconciled tree and four gene duplication events appeared toward the external nodes. These latter sequences belong to species with a second copy of PCs suggesting that this gene evolved through subfunctionalization Pdpcs1 gene expression was measured in seedling hypocotyls exposed to Cd, Cu and Cr using quantitative real-time polymerase chain reaction (qPCR). A Pdpcsl overexpression was evidenced in P. dactylifera seedlings exposed to metals suggesting that 1-the Pdpcsl gene is functional, 2-there is an implication of the enzyme in metal detoxification mechanisms. Additionally, the structure of PdPCS1 was predicted using its homologue from Nostoc (cyanobacterium, NsPCS) as a template in Discovery studio and PyMol software. These analyses allowed us to identify the phytochelatin synthase type I enzyme in date palm (PdPCS1) via recognition of key consensus amino acids involved in the catalytic mechanism, and to propose a hypothetical binding and catalytic site for an additional substrate binding cavity.
Aim In the 19th/early 20th century, overfishing caused a drastic decline and finally extinction of the local sturgeon populations in the eastern Atlantic. To date, it is not known whether it was Acipenser sturio or the primarily North American Acipenser oxyrinchus that occurred here. The aim of the study was to show the historical pattern of sturgeon distribution and their diversity in this area over the last 2500 years. This question is essential for international restoration programmes. Location North-east Atlantic. Methods The study is based on 438 archaeological sturgeon remains from the estuaries of the rivers Rhine, Ems, Weser, Elbe and Eider. All bones were analysed morphologically and in 38 cases genetically by the amplification of two mitochondrial DNA fragments. Results The data from the bones older than 1000 years show that only 1.4% derive from A. sturio. In the south, this species was slightly more frequent. From the Elbe northwards, A. oxyrinchus was for a long time by far the dominant sturgeon species. Main conclusions The genetic identification of the oldest sturgeon bone shows A. oxyrinchus occurred in the north-eastern Atlantic already 6000 years ago. Consequently, the immigration of this species from North America to Europe occurred even earlier, potentially during the last glacial. The north-south occurrence of the two sturgeon species suggests that the distribution was the result of interspecific competition under different and changing environmental conditions. As previously published, genetic data from about 100- to 200-year-old museum specimens show strong dominance of A. sturio in the North Sea area, obviously A. oxyrinchus has been replaced in the time between 1000 and 200 years ago. Therefore, the Holocene distribution of sturgeons in the northeast Atlantic had a complex pattern. Determining the ecological bases of this distribution is important for the justification and success of restoration programmes.
The importance of the performance of frequency regulation has already been acknowledged by regulators and Independent System Operators (ISOs). A performance-based frequency regulation market model considering both regulation capacity and regulation mileage constraints is proposed in this paper. In the proposed market, high-performance regulation resources have higher priorities to be selected in the market. Market clearing prices are derived with Lagrange relaxation. The analysis of the components of market clearing prices accurately indicates the correlation between regulation capacity and regulation mileage. To accommodate the proposed regulation market design, AGC allocation algorithm is adjusted based on the market clearing results. The clearing procedure of the market model is demonstrated on an illustrative case. The proposed market design is tested and verified with market simulations and system dynamic simulations. Simulation results are discussed and compared to show the effectiveness of the proposed market design. (C) 2016 Elsevier Ltd. All rights reserved.
The increased penetration of renewable energy sources in existing power systems has led to necessary developments in electricity market mechanisms. Most importantly, renewable energy generation is increasingly made accountable for deviations between scheduled and actual energy generation. However, there is no mechanism to enforce accountability for the additional costs induced by power fluctuations. These costs are socialized and eventually supported by electricity customers. We propose some metrics for assessing the contribution of all market participants to power regulation needs, as well as an attribution mechanism for fairly redistributing related power regulation costs. We discuss the effect of various metrics used by the attribution mechanisms, and we illustrate, in a game-theoretical framework, their consequences on the strategic behavior of market participants. We also illustrate, by using the case of Western Denmark, how these mechanisms may affect revenues of the various market participants.
In ancillary service electricity markets, opportunity costs account for the profit forgone by a generator due to the use of generating capacity for ancillary service provision instead of energy sales. They are calculated for each generator providing ancillary services and are included in the determination of market-clearing prices by market operators throughout the U.S. Recent interest in the use of smart heating, ventilating, and air-conditioning systems for ancillary service provision prompts an investigation into their associated opportunity costs. This paper proposes a definition for these costs and method of accounting for them through time. This is done by recognizing the impacts intra-hour consumption modification associated with ancillary service provision have on daily energy efficiency and costs. A numeric example is presented to demonstrate the method. It is found that marginal ancillary service opportunity costs vary over time and that properly adjusting energy consumption at an hour of interest can reduce the total opportunity cost of providing ancillary services.
Androgen insensitivity syndrome (AIS) is characterized by deficient or absent virilization in 46,XY individuals despite normal or even elevated androgen levels. AIS is usually caused by mutations in the androgen receptor (AR) gene. We aimed at contrasting clinical, biochemical, and molecular genetic characteristics of three patients (P1-P3) with clinically evident partial (PI) and complete (P2, P3) AIS with and without AR gene mutations. AR expression was studied in cultured genital skin fibroblasts (GSF) by Western immunoblotting, ligand binding analyses, Northern blotting, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), and RT-PCR spanning exons 1-8. AR gene DNA sequence was analyzed by single-strand conformation analysis (SSCA), and DNA sequencing. GSF revealed reduced (P1) or absent (P2, P3) ligand binding. Northern blots showed either slightly reduced hybridization of the 10.5-kb AR transcript (P3) or no hybridization (P1, P2), as confirmed by semiquantitative RT-PCR. RT-PCR spanning exons 1-8 detected single AR mRNA bands in P1-P3 excluding splicing errors. Western analyses showed either low (P1) or no (P2, P3) AR protein. While SSCA initially did not reveal any molecular abnormality, sequencing showed a novel CAG (Gln) to TAG (stop) mutation at codon 59 (P3) and a previously described 2-bp deletion at codon 472, leading to a frameshift and premature stop in codon 499 (P2). Intriguingly, P1 showed an unaltered DNA sequence of the coding region of the AR gene including all intronexon boundaries. In conclusion, patients with clinically evident complete AIS are likely to harbor an AR gene mutation, demanding that the two polymorphic regions must always be included in molecular analyses of the AR gene. Moreover, our data support the concept that in a subset of AIS patients, particularly those with partial AIS, molecular alterations outside the coding region of the AR gene must be presumed.
In this study, we attempted to explore the effect and possible mechanism of Andrographolide on OVA-induced asthma. OVA challenge induced significant airway inflammatory cell recruitment and lung histological alterations, which were ameliorated by Andrographolide. The protein levels of cytokines in bron-choalveolar fluid (BALF) and serum were reduced by Andrographolide administration as well as the mRNA levels in lung tissue. Mechanically, Andrographolide markedly hampered the activation of nuclear factor-kappa B (NF-kappa B) and NLRP3 inflammasome both in vivo and vitro thus decreased levels of TNF-alpha and IL-1 beta. Finally, we confirmed that ROS scavenging was responsible for Andrographolide's inactivation of NF-kappa B and NLRP3 inflammasome signaling. Our study here revealed the effect and possible mechanism of Andrographolide on asthma, which may represent a new therapeutic approach for treating this disease.
Introduction: Therapeutic options for myelodysplastic syndromes (MDS) are limited to hypomethylating agents (HMA) and lenalidomide. Rigosertib, a small molecule which blocks RAS-mediated activation of proteins containing a common RAS binding domain, appears to be a promising novel drug.Areas covered: Discovery, mechanism of action of rigosertib, and results of clinical trials are described. More than 500 patients have been treated and the safety, pharmacokinetics, and efficacy of rigosertib are summarized. These studies are placed in the context of the history of therapeutic development in MDS and the promise of new, tailored treatments based on emerging knowledge of the heterogeneity and molecular biology of the disease.Expert opinion: In summary, the Phase III study failed to meet the primary endpoint but clearly showed significant improvement in survival in a subset of very high risk MDS patients who were primary HMA failures. A new Phase III trial designed to validate these findings is now ongoing. Oral rigosertib, in a Phase II trial, produced transfusion independence in similar to 35% patients with lower risk MDS with or without recombinant erythropoietin. A methylation based signature appears to distinguish between the two groups. Validation of these early encouraging observations through future clinical trials is eagerly anticipated.
Background Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. Objective To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. Methods This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for >2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q(2)oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. Results Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m(2), respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q(2)oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). Conclusions and Clinical Relevance This study reveals that German H1-antihistamine-refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.
AimsThymomas and thymic squamous cell carcinomas (TSQCCs) are rare thymic epithelial tumours. Data on angiogenesis and vascular phenotype in these tumours are limited, and no study has taken histological World Health Organization (WHO) subtypes into account. The aim of this study was to compare vascularization, pericytes coverage and expression of angiogenic growth factors in different WHO-defined subtypes of thymoma Methods and resultsVascular density, diameter and architecture and expression of -smooth muscle actin (SMA), platelet-derived growth factor (PDGF) receptor- (PDGFR), vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) were investigated in WHO type A, AB, B1, B2 and B3 thymomas and TSQCCs, by the use of immunostaining, quantitative morphometry, and tumour vessel isolation by trypsin digestion. Expression levels of angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), VEGF-A, PDGF-B and Hif-1 were examined by quantitative reverse transcription polymerase chain reaction. A and AB thymomas were characterized by a dense network of capillary-like vessels with tight pericyte coverage, whereas B thymomas showed a loose vascular network with increasing vascular diameters and increasing expression of SMA and PDGFR from B1 to B3 thymomas and TSQCCs. VEGFR1 and VEGFR2 were expressed in vessels of all analysed tumour entities, and at higher levels in epithelial cells of A and B3 thymomas and TSQCCs. mRNA of Ang-2, but not of Ang-1, was significantly up-regulated in all thymoma subtypes, with the highest levels being found in A thymomas. In TSQCCs, Ang-1 and VEGF were the predominantly up-regulated growth factors. Hif-1 was only up-regulated in B3 thymomas and TSQCCs. ConclusionThymomas and TSQCCs differ significantly in their vascular architecture and expression of key angiogenic growth factors. The findings could help to improve the differential diagnosis of difficult-to-classify thymic epithelial tumours, and indicate different mechanisms of tumour angiogenesis and functional differences of tumour vessels of major thymoma subtypes and TSQCCs.
Objective: To determine if the molecular profiles of endometriotic lesions contain informative measures of inflammation and immune dysfunction that may contribute to better understanding of the interplay between immune dysfunction and inflammation and their contribution to endometriosis pathogenesis. Design: Immune and inflammation transcriptomic analysis with the use of the Nanostring nCounter GX Human Immunology V2 platform (579 human immune and inflammation-related genes and 15 housekeeping genes). Setting: Academic university and teaching hospital. Intervention(s): None. Patient(s): Stage III-IV endometriosis patients with infertility (n = 8) and fertile disease-free control women undergoing tubal ligation (n = 8). Menstrual stage was matched to secretory phase in all participants. Main Outcome Measure(s): Immune and inflammation transcriptomics quantification from ectopic endometriotic lesions and matched eutopic endometrium from patients. Endometria of fertile women served as control subjects. Result(s): Our results displayed endometriotic lesions as molecularly distinct entities compared with eutopic endometrium and endometrium of control samples; 396 out of 579 screened immune and inflammation-related genes were significantly different in ectopic tissues compared with control endometrium. Most importantly, eutopic endometrium of the patients displayed a unique molecular profile compared with the control endometrium (91/579 genes were significantly different), particularly of genes involved in regulation of cell apoptosis and decidualization. Conclusion(s): We characterize differential expression of immune-inflammation genes in endometriosis patients, and show molecular distinction of eutopic endometrium of patients compared with control fertile women. (C) 2016 by American Society for Reproductive Medicine.
Fish protein hydrolysate was prepared from muscle of small red scorpionfish (Scorpaena notata) by treatment with a protease from the fungus Penicillium digitatum. Protein hydrolysate was found to strongly inhibit the angiotensin I converting enzyme and exhibited high antioxidative activity through 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay. After ultrafiltration, peptides were isolated by a two-step procedure: size exclusion chromatography on a Toyopearl HW-40 followed by reversed-phase high-performance liquid chromatography with a high purification yield of 2.5 mg of peptide per gram of initial protein. Two major peptides were then identified by nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS), corresponding to the following sequences: Leu-Val-Thr-Gly-Asp-Asp-Lys-Thr-Asn-Leu-Lys (1,204.665 Da) and Asp-Thr-Gly-Ser-Asp-Lys-Lys-Gln-Leu (992.511 Da). These peptides, mainly composed of hydrophilic amino acids, showed high antioxidative and angiotensin I converting enzyme inhibitory activities. These data suggest that the two novel peptides isolated from the muscle hydrolysate of small red scorpionfish can be a beneficial ingredient for functional foods or pharmaceuticals against hypertension and oxidative stress. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Ca2+-activated Cl-channels play a crucial role in various physiological processes. However, the role of TMEM16A in vascular endothelial dysfunction during hypertension is unclear. In this study, we investigated the specific involvement of TMEM16A in regulating endothelial function and blood pressure and the underlying mechanism. Reverse transcription-polymerase chain reaction, Western blotting, coimmunoprecipitation, confocal imaging, patch-clamp recordings, and TMEM16A endothelial-specific transgenic and knockout mice were used. We found that TMEM16A was expressed abundantly and functioned as a Ca2+-activated Cl-channel in endothelial cells. Angiotensin II induced endothelial dysfunction with an increase in TMEM16A expression. The knockout of endothelial-specific TMEM16A significantly lowered the blood pressure and ameliorated endothelial dysfunction in angiotensin II-induced hypertension, whereas the overexpression of endothelial-specific TMEM16A resulted in the opposite effects. These results were related to the increased reactive oxygen species production, Nox2-containing NADPH oxidase activation, and Nox2 and p22phox protein expression that were facilitated by TMEM16A on angiotensin II-induced hypertensive challenge. Moreover, TMEM16A directly bound with Nox2 and reduced the degradation of Nox2 through the proteasome-dependent degradation pathway. Therefore, TMEM16A is a positive regulator of endothelial reactive oxygen species generation via Nox2-containing NADPH oxidase, which induces endothelial dysfunction and hypertension. Modification of TMEM16A may be a novel therapeutic strategy for endothelial dysfunction-associated diseases.
1. Angiotensin (Ang) II plays a major role in vascular remodelling. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the tissue remodelling processes. The aim of the present study was to investigate whether AngII modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo. 2. Angiotensin II (200 ng/kg per min, s.c.) or AngII + losartan (10 mg/kg per day, s.c.) or normal saline was administered continuously by osmotic minipumps to Sprague-Dawley rats for 1 week. In addition, the effect of endogenous AngII on TIMP-2 expression was evaluated in renovascular hypertensive rats (two kidney, one clip (2K1C) and one kidney, one clip (1K1C) models). Control rats (sham 2K1C and sham 1K1C rats) underwent sham-clipping of the left renal artery. At the end of the treatment, plasma renin activity was measured by radioimmunoassay, aortic TIMP-2 mRNA expression was evaluated by real-time polymerase chain reaction and/or northern blotting and protein expression was evaluated by immunohistochemistry. Systolic blood pressure (SBP) was measured twice a week by the tail-cuff method. 3. Exogenous AngII administration produced the expected increase in SBP (P = 0.02) compared with the control saline-treated group. The increase in SBP was abolished in AngII + losartan-treated rats. Administration of AngII caused a significant increase in TIMP-2 expression (P = 0.01) in rat aortic smooth muscle cells that was abolished in AngII + losartan-treated rats. In renovascular hypertensive rats, SBP was higher (P < 0.0001) in 2K1C and 1K1C rats compared with the corresponding sham-operated rats. Plasma renin activity was higher (P < 0.01) in 2K1C rats compared with the other groups. The expression of TIMP-2 was significantly (P < 0.05) increased only in 2K1C rats. 4. Our in vivo data demonstrate that exogenous and endogenous AngII increases TIMP-2 expression in rat aortic smooth muscle cells. This effect is not dependent on the AngII-induced increase in blood pressure and is mediated by angiotensin AT(1) receptors.
Angiotensin II is critical in pre-eclampsia pathogenesis. In addition, microRNA-155 regulates angiotensin II type I receptor expression. We have explored the function of microRNA-155 in pre-eclamptic pregnant women. Human umbilical vein endothelial cells were isolated and cultured from healthy puerperant women and pre-eclampsia patients. The cells were transfected with a mature microRNA-155 plasmid. The effect of microRNA-155 was assessed by Northern blotting, in situ hybridization, quantitative real-time PCR, immunofluorescent staining and Western blotting. In addition, activation of extracellular signal-regulated kinase 1/2 was assessed by co-immunoprecipitation and Western blotting. Severely pre-eclamptic pregnant women expressed less mature miR-155 compared to healthy pregnant women. In addition, angiotensin H type 1 receptor expression decreased substantially in healthy cells and miR-155-transfected cells compared to miR-155-mutant-transfected cells and cells from pre-eclamptic patients. Mature miR-155 reduced angiotensin II-induced extracellular signal-regulated kinase 1/2 activation. In conclusion, endogenous mature miR-155 expression may be an important contributor to the pathogenesis of severe pre-eclampsia.
Renin substrate, biological renin activity, and/or renin-secreting cells in kidneys evolved at an early stage of vertebrate phylogeny. Angiotensin (Ang) I and II molecules have been identified biochemically in representative species of all vertebrate classes, although variation occurs in amino acids at positions 1, 5, and 9 of Ang I. Variations have also evolved in amino acid positions 3 and 4 in some cartilaginous fish. Angiotensin receptors, AT(1) and AT(2) homologues, have been identified molecularly or characterized pharmacologically in nonmammalian vertebrates. Also, various forms of angiotensins that bypass the traditional renin-angiotensin system (RAS) cascades or those from large peptide substrates, particularly in tissues, are present. Nonetheless, the phylogenetically important functions of RAS are to maintain blood pressure/blood volume homeostasis and ion-fluid balance via the kidney and central mechanisms. Stimulation of cell growth and vascularization, possibly via paracrine action of angiotensins, and the molecular biology of RAS and its receptors have been intensive research foci. This review provides an overview of: (1) the phylogenetic appearance, structure, and biochemistry of the RAS cascade; (2) the properties of angiotensin receptors from comparative viewpoints; and (3) the functions and regulation of the RAS in nonmammalian vertebrates. Discussions focus on the most fundamental functions of the RAS that have been conserved throughout phylogenetic advancement, as well as on their physiological implications and significance. Examining the biological history of RAS will help us analyze the complex RAS systems of mammals. Furthermore, suitable models for answering specific questions are often found in more primitive animals.
1. Several eel species have undergone extensive declines at both local and global level. The aim of this study was to identify the reasons for the collapse of the European eel (Anguilla anguilla) stock in an important area for biodiversity conservation (Comacchio Lagoon, Italy), in order to support the development of eel conservation plans. 2. The records of silver eel catches from Comacchio describe the total migratory population and cover the period 1781- 2013. The data are accompanied by information related to habitat loss and other local factors. The role of local factors on the decline of the local stock was investigated, while additional information from the literature was also used to discuss the effects of global factors (including glass eel harvest for aquaculture, climateoceanographic changes, habitat loss, pollution and parasitism) on the three eel species A. anguilla, Anguilla japonica and Anguilla rostrata. 3. The records from Comacchio provided significant information about the effects of local factors on the local eel populations in the past. However, the current population collapse, which started in the 1970s, could not be explained by local factors. 4. The literature on global factors suggests that the three eel species are under combined threat from various factors. The correlations between European aquaculture production data compared with the Comacchio yields and published data from other European eel and glass eel fisheries were found to be highly significant. Aquaculture, which depends entirely on wild- caught glass eels, seems to play a key role in the decline of natural stocks. 5. Conservative estimates using FAO data showed that the current numbers of glass eels needed to support aquaculture production in Europe and Asia exceeds 2 x 109 specimens. This requirement, largely supplied by A. anguilla glass eels, can explain the decline of eel populations since the glass eel trade has been expanded at an international level. Copyright # 2016 John Wiley & Sons, Ltd.
Even simple geometric shapes are seen as animate and goal-directed when they move in certain ways. Previous research has revealed a great deal about the cues that elicit such percepts, but much less about the consequences for other aspects of perception and cognition. Here we explored whether simple shapes that are perceived as animate and goal-directed are prioritized in memory. We investigated this by asking whether subjects better remember the locations of displays that are seen as animate vs. inanimate, controlling for lower-level factors. We exploited the 'Wolfpack effect': moving darts (or discs with 'eyes') that stay oriented toward a particular target are seen to be actively pursuing that target, even when they actually move randomly. (In contrast, shapes that stay oriented perpendicular to a target are correctly perceived to be drifting randomly.) Subjects played a 'matching game' - clicking on pairs of panels to reveal animations with moving shapes. Across four experiments, the locations of Wolfpack animations (compared to control animations equated on lower-level visual factors) were better remembered, in terms of more efficient matching. Thus perceiving animacy influences subsequent visual memory, perhaps due to the adaptive significance of such stimuli. (C) 2017 Elsevier B.V. All rights reserved.
For more than a century researchers have used enculturated animals-those extensively trained or reared by humans-to explore the effects of learning and environment on the capacities for linguistic abilities outside of the human line. Unfortunately, due to many controversies, the findings of these studies frequently have been dismissed or outright ignored. However, experimental exploration of the capacities of nonhumans is the only option to determine which, if any, language-associated capacities are unique to humans. Researchers continue to publish findings from language projects that move our understanding forward, including descriptions of capacities, such as gestural comprehension, declarative communication, and categorization, that are frequently considered to be specific biological adaptations.
Social network analysis has become a prominent tool to study animal social life, and there is an increasing need to develop new systems to collect social information automatically, systematically, and reliably. Here we explore the use of a freely accessible Automated Learning Device for Monkeys (ALDM) to collect such social information on a group of 22 captive baboons (Papio papio). We compared the social network obtained from the co-presence of the baboons in ten ALDM testing booths to the social network obtained through standard behavioral observation techniques. The results show that the co-presence network accurately reflects the social organization of the group, and also indicate under which conditions the co-presence network is most informative. In particular, the best correlation between the two networks was obtained with a minimum of 40 days of computer records and for individuals with at least 500 records per day. We also show through random permutation tests that the observed correlations go beyond what would be observed by simple synchronous activity, to reflect a preferential choice of closely located testing booths. The use of automatized cognitive testing therefore presents a new way of obtaining a large and regular amount of social information that is necessary to develop social network analysis. It also opens the possibility of studying dynamic changes in network structure with time and in relation to the cognitive performance of individuals.
In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ ml CRISP-3, 150 mu g/ ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 x 10(9) spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)- 1 beta, IL- 8, tumour necrosis factor (TNF)- alpha, interferon (INF)-gamma, anti-inflammatory cytokines IL- 1RN and IL- 10, and inflammatory- modulating cytokine IL- 6). Seminal plasma treatment increased the mRNA expression of IL- 1 beta (p =.019) and IL- 8 (p =.0068), while suppressing the mRNA expression of TNF (p =.0013). Lactoferrin also suppressed the mRNA expression of TNF (p =.0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro-inflammatory response seen in susceptible mares.
Existing research suggests that various forms of family violence such as domestic violence and child abuse tend to coexist or cluster. Although the link between animal cruelty and domestic violence is well publicized, little research has examined various forms of animal abuse and possible links between corresponding forms of interpersonal offenses. The present study examined a subsample obtained from the FBI's Behavioral Analysis Unit. (BAU) III - Crimes Against Children, which included the criminal histories of 150 adult males arrested for animal cruelty, neglect or sexual abuse in the, U.S. between 2004 and 2009. The sample was described in terms of demographic and criminal characteristics. Results indicated that 41% of the offenders in the sample were arrested for interpersonal violence at least once, 18% were arrested for a sex offense such as rape or child molestation, and 28% were arrested for another interpersonal crime such as violating a restraining order or harassment. Significant relationships were discovered between Active animal cruelty (such as beating or stabbing) and both interpersonal violence and substance abuse as well as between sexually abusing animals and sexual offending against humans. These results point to the need for increased collaboration between animal welfare agencies and the social service and legal entities responsible for protecting domestic violence victims, children, elders, and others at risk groups. (C) 2016 Published by Elsevier Ltd.
This review presents an overview of some of the pre-clinical and clinical issues that have contributed to the failures of potential novel neuropsychiatric drugs, which have prompted a re-examination of the role of animal models of neuropsychiatric disorders. Advances both in basic neuroscience and technology have driven the development of animal models of aspects of neuropsychiatric disorders. Genetics and environmental factors have been the primary contributors to the development of new animal models. Neuroimaging has contributed to the search for biomarkers by which neuropsychiatric disorders may be identified and differentiated, its progression monitored and that the effects of therapy assessed. Parallel to these theoretical and practical advancements have been the changes in the diagnosis and classification of neuropsychiatric disorders from DSM-4 to DSM-5, and emergence of the NIH initiatives such as MATRICS; CNTRICS and RDoC. These latter changes are shifting our concepts of neuropsychiatric disorders away from phenomenology to their biology and thus aligning physiology with psychology. (C) 2017 Elsevier Ltd. All rights reserved.
We tested the two main evolutionary hypotheses for an association between immunity and personality. The risk of-parasitism hypothesis predicts that more proactive (bold, exploratory, risk-taking) individuals have more vigorous immune defenses because of increased risk of parasite exposure. In contrast, the pace-of-life hypothesis argues that proactive behavioral styles are associated with shorter lifespans and reduced investment in immune function. Mechanistically, associations between immunity and personality can arise because personality differences are often associated with differences in condition and stress responsiveness, both of which are intricately linked with immunity. Here we investigate the association between personality (measured as proactive exploration of a novel environment) and three indices of innate immune function (the non-specific first line of defense against parasites) in wild superb fairy-wrens Malurus cyaneus. We also quantified body condition, hemoparasites (none detected), chronic stress (heterophil:lymphocyte ratio) and circulating corticosterone levels at the end of the behavioral test (CORT, in a subset of birds). We found that fast explorers had lower titers of natural antibodies. This result is consistent with the pace-of-life hypothesis, and with the previously documented higher mortality of fast explorers in this species. There was no interactive effect of exploration score and duration in captivity on immune indices. This suggests that personality-related differences in stress responsiveness did not underlie differences in immunity, even though behavioral style did modulate the effect of captivity on CORT. Taken together these results suggest reduced constitutive investment in innate immune function in more proactive individuals. (C) 2016 Elsevier Inc. All rights reserved.
Mild therapeutic hypothermia is a candidate for the treatment of traumatic brain injury (TBI). However, the role of mild hypothermia in neuronal sprouting after TBI remains obscure. We used a fluid percussion injury (FPI) model to assess the effect of mild hypothermia on pericontusion neuronal sprouting after TBI in rats. Male Sprague-Dawley rats underwent FPI or sham surgery, followed by mild hypothermia treatment (33 degrees C) or normothermia treatment (37 degrees C) for 3 h. All the rats were euthanized at 7 days after FPI. Neuronal sprouting that was confirmed by an increase in growth associated protein-43 (GAP-43) expression was evaluated using immunofluorescence and Western blot assays. The expression levels of several intrinsic and extrinsic sprouting-associated genes such as neurite outgrowth inhibitor A (NogoA), phosphatase and tensin homolog (PTEN), and suppressor of cytokine signaling 3 (SOCS3) were analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Our results revealed that mild hypothermia significantly increased the expression level of GAP-43 and dramatically suppressed the expression level of interleukin-6 (IL-6) and SOCS3 at 7 days after FPI in the ipsilateral cortex compared with that of the normothermia TBI group. These data suggest that post-traumatic mild hypothermia promotes pericontusion neuronal sprouting after TBI. Moreover, the mechanism of hypothermia-induced neuronal sprouting might be partially associated with decreased levels of SOCS3.
OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration, and apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was detected by fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939 and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3) and 1 negative control plasmid were constructed to infect QBC939 cells. The infection efficiency, expression of ANXA5, apoptosis and cell cycle of QBC939 cell were measured separately. RESULTS: The expression of ANXA5 in QBC939 cell was significantly higher than RBE cell. Expressed ANXA5 protein in the QBC939-KD cell (QBC939 cell treated by RNAi) was significantly lower than QBC939-BC (QBC939 cell) and QBC939-NC cells (QBC939 cell treated by scramble plasmid). The ratio of G0/1 phase cells and apoptosis rate increased in QBC939-KD cell. The proliferation activity and invasion ability decreased in QBC939-KD cell compared with QBC939-NC and QBC939-BC cells. CONCLUSIONS: ANXA5 play important role in the migration and apoptosis of CCA cells. Inhibiting the expression of ANXA5 significantly reduce the proliferation, migration and invasion ability of QBC939 cells, and increase the apoptosis of QBC939 cells.
The tumor suppressor p16INK4a has functions beyond cell-cycle control via cyclin-dependent kinases. A coordinated remodeling of N- and O-glycosylation, and an increase in the presentation of the endogenous lectin galectin-1 sensing these changes on the surface of p16INK4a-expressing pancreatic carcinoma cells (Capan-1), lead to potent pro-anoikis signals. We show that the p16INK4a-dependent impact on growth-regulatory lectins is not limited to galectin-1, but also concerns galectin-3. By monitoring its expression in relation to p16INK4a status, as well as running anoikis assays with galectin-3 and cell transfectants with up- or downregulated lectin expression, a negative correlation between anoikis and the presence of this lectin was established. Nuclear run-off and northern blotting experiments revealed an effect of the presence of p16INK4a on steady-state levels of galectin-3-specific mRNA that differed from decreasing the transcriptional rate. On the cell surface, galectin-3 interferes with galectin-1, which initiates signaling toward its pro-anoikis activity via caspase-8 activation. The detected opposite effects of p16INK4a at the levels of growth-regulatory galectins-1 and -3 shift the status markedly towards the galectin-1-dependent pro-anoikis activity. A previously undescribed orchestrated fine-tuning of this effector system by a tumor suppressor is discovered.
BACKGROUND: Little is known about anorectal function and quality of life after chemoradiation followed by local excision, which is an alternative to total mesorectal excision for selected patients with early rectal cancer. OBJECTIVE: The purpose of this study was to prospectively assess anorectal function and health-related quality of life of patients with T2N0 rectal cancer who were treated with an alternative approach. DESIGN: This was a prospective, phase II trial. SETTINGS: The study was multicentric (American College of Surgeons Oncology Group trial Z6041). INTERVENTIONS: Patients with stage cT2N0 rectal adenocarcinomas were treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by local excision. MAIN OUTCOME MEASURES: Anorectal function and quality of life were assessed at enrollment and 1 year postoperatively with the Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment of Cancer Therapy-Colorectal Questionnaire. Results were compared, and multivariable analysis was performed to identify predictors of outcome. RESULTS: Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year. Compared with baseline, no significant differences were found on Fecal Incontinence Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were significantly worse in the lifestyle (p < 0.001), coping/behavior (p < 0.001), and embarrassment (p = 0.002) domains. There were no differences in the Functional Assessment of Cancer Therapy overall score, but the physical wellbeing subscale was significantly worse and emotional well-being was improved after surgery. Treatment with the original chemoradiation regimen predicted worse depression/self-perception and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex was predictive of worse scores in the Functional Assessment of Cancer Therapy overall score and trial outcome index. LIMITATIONS: Small sample size, relatively short follow-up, and absence of information before cancer diagnosis were study limitations. CONCLUSIONS: Chemoradiation followed by local excision had minimal impact on anorectal function 1 year after surgery. Overall quality of life remained stable, with mixed effects on different subscales. This information should be used to counsel patients about expected outcomes.
Numerous patients with anorectal malformations (ARMs) continue to experience fecal incontinence and constipation following surgical procedures. One of the most important factors that influences defecation is the striated muscle complex (SMC). Wnt signaling regulates the expression of myogenic regulatory factors, which serve an important role in muscle development. Therefore, the present study aimed to investigate the expression pattern of Wnt3a protein (by immunohistochemistry and western blot analysis) and mRNA [by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)] in the SMC of ARM model rats that were exposed to ethylenethiourea. Immunostaining revealed that the expression of Wnt3a exhibits space-and time-dependent changes in the developing SMC of ARM model rat embryos. Immunohistochemistry demonstrated that on embryonic day 17 (E17), Wnt3a-positive cells were observed in the SMC in normal embryos, and expression levels gradually increased as the rat embryos developed. Similar changes in Wnt3a protein expression were detected in ARM model rat embryos; however, the expression of Wnt3a was significantly reduced compared with the normal rat embryos. Western blotting and RT-qPCR also revealed lower expression levels of Wnt3a protein and mRNA, respectively, in the SMC of ARMs model rat embryos compared with normal rat embryos. These data revealed that the expression of Wnt3a in ARM embryos was notably reduced, indicating a potential role for Wnt3a in the maldevelopment of the SMC in patients with ARMs.
Purpose: A subgroup of individuals with anorexia nervosa (AN) displays social difficulties; however, it is not clear if individuals with comorbid autism spectrum disorders account for these difficulties. Methods: We compared social function using the Autism Diagnostic Observation Schedule in 43 young females with first-episode AN who did not have comorbid autism spectrum disorder, 28 individuals recovered from adolescent-onset AN, and 41 healthy comparison individuals (age range 14-22 years). We measured adaptive behavior with the Vineland-II parent questionnaire, and aspects of social cognition with psychological tests, such as the Reading-the-Mind-in-the-Eyes test, Profile of Nonverbal Sensitivity short version, The Awareness of Social Inference Test, Animated Triangles, and the CANTAB Affective Go/No-go task. Results: Participants with first-episode AN and those recovered from AN displayed difficulties in social function, which were not associated with body mass index or other state factors of the disorder in those with first-episode AN. Mood problems and anxiety were not associated with these difficulties. Parents rated participants with first-episode AN lower than recovered and control participants on the Socialization Domain of Vineland-II. Finally, only participants recovered from AN demonstrated deficits in specific domains of social cognition: perceiving nonverbal bodily gesture and vocal prosody. Conclusions: Young females with first-episode AN and those recovered from AN displayed impairments in social function, which may represent more stable traits of the disorder. Only participants recovered from AN demonstrated deficits in social cognition. (C) 2016 Society for Adolescent Health and Medicine. All rights reserved.
This study examines whether the perception of peripersonal action-space and interpersonal social-space is modified in patients with restrictive-type anorexia in two experimental conditions using videos. First, participants stopped the video of an approaching stimulus when they felt the distance to be comfortable for interacting with it (first-person perspective). Second, participants stopped the video when an observed individual approaching a stimulus, or being approached by it, was at a comfortable distance (third-person perspective). In the first-person perspective, the results showed an estimation of peripersonal space that did not differ from controls when an object was approaching and an increase in interpersonal space compared with controls when a male or female individual was approaching. In the third-person perspective, both individual-object and individual-individual distances were larger in anorexic patients. These results indicate a specific deficit in adjusting interpersonal distances in both the first-person and third-person perspectives. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
We tested wild birds in Poland during 2008-15 for avian influenza virus (AIV). We took 10,312 swabs and feces samples from 6,314 live birds representing 12 orders and 84 bird species, mostly from orders Anseriformes and Charadriiformes, for testing and characterization by various PCR methods. From PCR-positive samples, we attempted to isolate and subtype the virus. The RNA of AIV was detected in 1.8% (95% confidence interval [CI], 1.5-2.1%) of birds represented by 48 Mallards (Anas platyrhynchos), 11 Mute Swans (Cygnus olor), 48 Common Teals (Anas crecca), three Black-headed Gulls (Chroicocephalus ridibundus), one Common Coot (Fulica atra), one Garganey (Spatula querquedula), and one unidentified bird species. Overall, the prevalence of AIV detection in Mallards and Mute Swans (the most frequently sampled species) was 2.0% (95% CI, 1.4-2.5%) and 0.5% (95% CI, 0.2-0.8%), respectively; the difference was statistically significant (P = 0.000). Hemagglutinin subtypes from H1 to H13 were identified, including H5 and H7 low pathogenic AIV subtypes. Mallards and Common Teals harbored the greatest diversity of subtypes. We observed seasonality of viral detection in Mallards, with higher AIV prevalence in late summer and autumn than in winter and spring. In addition, two peaks in AIV prevalence in summer (August) and autumn (November) were demonstrated for Mallards. The prevalence of AIV in Mute Swans did not show any statistically significant seasonal patterns.
Background: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects. Methods: We conducted a randomized, double-blind, placebo-controlled trial of riluzole monotherapy for the treatment of BDep. Nineteen subjects aged 18 to 70 years with bipolar disorder currently experiencing a depressive episode were tapered off of excluded medications and randomized to receive riluzole (50-200 mg/d) or placebo for 8 weeks. Rating scale scores (Montgomery-angstrom sberg Depression Rating Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Young Mania Rating Scale) were obtained weekly. Results: No significant differences in depressive symptoms were observed between subjects treated with riluzole and those receiving placebo (P = 0.12). Anxiety scores were significantly lower in the placebo group (P = 0.046). An interim analysis was conducted that resulted in stopping the study because of futility; no subjects had achieved treatment response. Conclusions: Although we found no change in severity of depressive symptoms in BDep patients receiving riluzole compared with placebo, this trial was limited by the relatively high number of subject withdrawals and the small sample size. Thus, while riluzole monotherapy did not demonstrate efficacy for BDep, further studies examining riluzole as adjunctive therapy for this disorder may be warranted.
A system of generating tunable orbital angular momentum (OAM) radio beams and a method of measuring the OAM states are proposed and experimentally investigated. The OAM beams, which are generated by a uniform circular array, can be dynamically configured by controlling the digital signals in the baseband. A 2-D near-field scanning platform is built to measure the OAM states of the system. The platform can provide multiple feed ports for the transmitting array. Iteration is used to calibrate the amplitude and phase of each feed port. The experimental results demonstrate the feasibility of the proposed methods on generating and measuring tunable OAM beams.
Cortical networks underpinning attentional control and mentalizing converge at the right temporoparietal junction (rTPJ). It is debated whether the rTPJ is fractionated in neighboring, but separate functional modules underpinning attentional control and mentalizing, or whether one overarching cognitive mechanism explains the rTPJ's role in both domains. Addressing this question, we combined attentional control and mentalizing in a factorial design within one task. We added a social context condition, in which another individual's mental states became apparently task-relevant, to a spatial cueing paradigm. This allowed for assessing cue validity-and context-dependent functional activity and effective connectivity of the rTPJ within corresponding cortical networks. We found two discriminable rTPJ subregions, an anterior and a posterior one. Yet, we did not observe a sharp functional dissociation between these two, as both regions responded to attention cueing and social context manipulation. The results suggest that the rTPJ is part of both the ventral attention and the ToM network and that its function is defined by context-dependent coupling with the respective network. We argue that the rTPJ as a functional unit underpins an overarching cognitive mechanism in attentional control and mentalizing and discuss how the present results help to further specify this mechanism.
Purpose: To Compare tendon-to-bone healing in remnant-preserving and conventional anterior cruciate ligament reconstruction. Methods: 72 New Zealand rabbits were randomly assigned to conventional ACL reconstruction group (group A), remnant-preserving and tensioning ACL reconstruction group (group B), and remnant-preserving and graft through remnant sleeve ACL reconstruction group (group C), with 24 rabbits (48 knees) in each group. The incidence and degree of bone tunnel enlargement in each group were analyzed using CT 3D reconstruction. Graft tendon-bone healing was monitored by HE and Masson staining, and osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) mRNA expression in the bone tissue surrounding the graft. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the ratio of OPG/RANKL expression. Results: Histological analysis showed that group C had the best graft tendon-bone healing, followed by group B and group A at all time-points post-surgery. At weeks 3 and 6 post-surgery, OPG mRNA levels and OPG/RANKL values were higher in groups B and C compared to group A (P < 0.05). RANKL mRNA levels of groups B and C were lower than group A (P0.05). At 3 weeks post-surgery, the incidence and degree of bone tunnel enlargement were greater in group A compared to groups B and C (P < 0.05). Conclusion: Both remnant-preserving construction approaches promoted graft tendon-bone healing, the underlying mechanism may be associated with the upregulation of OPG mRNA and downregulation of RANKL mRNA in bone tunnel early post-operation.
Words activate cortical regions in accordance with their modality of presentation (i.e., written vs. spoken), yet there is a long-standing debate about whether patterns of activity in any specific brain region capture modality invariant conceptual information. Deficits in patients with semantic dementia highlight the anterior temporal lobe (ATL) as an amodal store of semantic knowledge but these studies do not permit precise localisation of this function. The current investigation used multiple imaging methods in healthy participants to examine functional dissociations within ATL. Multi-voxel pattern analysis identified spatially segregated regions: a response to input modality in anterior superior temporal gyrus (aSTG) and a response to meaning in more ventral anterior temporal lobe (vATL). This functional dissociation was supported by resting-state connectivity that found greater coupling for aSTG with primary auditory cortex and vATL with the default mode network. A meta-analytic decoding of these connectivity patterns implicated aSTG in processes closely tied to auditory processing (such as phonology and language) and vATL in meaning-based tasks (such as comprehension or social cognition). Thus we provide converging evidence for the segregation of meaning and input modality in the ATL.
Humans cannot help but attribute human emotions to non-human animals. Although such attributions are often regarded as gratuitous anthropomorphisms and held apart from the attributions humans make about each other's internal states, they may be the product of a general mechanism for flexibly interpreting adaptive behavior. To examine this, we used functional magnetic resonance imaging (fMRI) in humans to compare the neural mechanisms associated with attributing emotions to humans and non-human animal behavior. Although undergoing fMRI, participants first passively observed the facial displays of human, non-human primate and domestic dogs, and subsequently judged the acceptability of emotional (e.g. 'annoyed') and facial descriptions (e.g. 'baring teeth') for the same images. For all targets, emotion attributions selectively activated regions in prefrontal and anterior temporal cortices associated with causal explanation in prior studies. These regions were similarly activated by both human and non-human targets even during the passive observation task; moreover, the degree of neural similarity was dependent on participants' self-reported beliefs in the mental capacities of non-human animals. These results encourage a non-anthropocentric view of emotion understanding, one that treats the idea that animals have emotions as no more gratuitous than the idea that humans other than ourselves do.
Introduction: C1q play an important role in clearance of immune complexes and apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen and development of anti-C1q antibody formation. Anti-C1q antibody is well studied in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE patients and their clinical manifestations is not clear. Aim: The aim of this study was to investigate associations between anti-C1q antibody and clinical as well as serological markers of SLE. Materials and Methods: Retrospective study of SLE patients fulfilling either American College of Rheumatology (ACR) 1990 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria were recruited from inpatients and outpatients services of the Clinical immunology and Rheumatology Department, Christian Medical College at Vellore, India between March 2013 and January 2015. Anti-C1q antibody was assayed by ELISA (Demeditec Diagnostics GmbH, Germany). Logistic regression analysis was performed to find the association of anti-C1q antibodies with serological and clinical parameters in SLE including Lupus Nephritis (LN). Results: Sixty nine patients (54.76%) out of 126 SLE patients had LN. Anti-C1q levels were higher in patients with LN as compared to those without (p<0.05). Anti-C1q antibody was also significantly associated with positive C1q immunofluorescence staining in renal biopsy specimens (p<0.05). Overall, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) {OR 1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and mucocutaneous manifestation {OR 4.72 (1.38-16.05)} were independently associated with anti-C1q levels in serum. Conclusion: Renal SLEDAI, low C4 and mucocutaneous manifestations were independently associated with raised anti C1q antibody in SLE patients.
The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1 beta (IL-1 beta) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKa expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1 beta release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1 beta levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling.
Gloverin is an antibacterial peptide which has been previously isolated in Hyalophora gloveyi, and is known to exert an inhibition effect on the growth of Gram-negative bacteria (GNB). When the expressed genes in the immunized Bombyx mori were screened, gloverin like gene (BmGLP) was found and it was thought to respond against the bacterial invasion. This study presents some data about the gene organization and expression of this candidate for a novel antibacterial peptide in Bombyx mori. The complete sequence, which was determined via RACE, revealed that this BmGLP was identical to the recently reported clone BmGloverin2 mRNA. The transcription of this gene was increased transiently, but to a high degree, around 7 similar to 11 hours after infection, as evidenced by the results of Northern blotting hybridization analysis. Based on the tentative coding sequence, we amplified the genomic sequence and determined that the gene harbored 3 introns. Interestingly, we found retrotransposon relative sequences in introns 1 and 3. Both Southern blotting analysis and sequencing data indicated that the BmGLP2 gene had another relative- or pseudo- sequences in its genome. We also attempted the generation of recombinant peptides in a prokaryotic cell system, but we obtained only truncated peptides and were unable to determine the existence of. any antibacterial activity with the cell extract under physiological conditions. In further studies, the expression system and activity test conditions should be made more representative of the actual insect organism. Finally, we have proposed the possibility that some type of evolutionary link connects retrotransposons activity in insect immunity gene variation.
The gene expression level for immune system genes was evaluated at different lifecycle stages in the white shrimp (Litopenaeus vannamei). The gene-coding pattern recognition protein, -glucan binding protein-high density lipoprotein (BGBP), from haemocytes, the effector proteins peroxinectin and clotting protein (CP), the antibacterial proteins Lysozyme, Penaeidin 3 and prophenoloxidase (proPO), and the small heat-shock protein 10 were studied. The expression of BGBP was detected from the Nauplii 3 substage and beyond (except for PL1). Peroxinectin and CP were constitutively transcribed throughout the different substages. Lysozyme, Penaeidin and proPO were also detected throughout the experimental stages (except eggs and nauplii). Lysozyme was transcribed during most of the shrimp substages, from Zoea 2 and beyond. Penaeidin 3 exhibited the lowest expression level of the genes evaluated; however, its transcription was similar to those of adults from post-larvae 11 and forward. proPO was higher transcribed during last post-larval substages. Heat-shock protein-10 was detected in all shrimp substages and exhibited higher expression at the PL substages compared to the first larval substages. Evidence suggests that the shrimp immune system is partially activated from the early larval substages, but is not completed until the shrimp have undergone the metamorphic substages.
Despite several conventional potent antibacterial therapies, bacterial infections pose a significant threat to human health because they are emerging as the leading cause of death worldwide. Due to the development of antibiotic resistance in bacteria, there is a pressing demand to discover novel approaches for developing more effective therapies to treat multidrug-resistant bacterial strains and biofilm-associated infections. Therefore, attention has been especially devoted to a new and emerging branch of science "nanotechnology" to design non-conventional antimicrobial chemotherapies. A range of nanomaterials and nano-sized carriers for conventional antimicrobial agents have fully justified their potential to combat bacterial diseases by reducing cell viability, by attenuating quorum sensing, and by inhibiting/or eradicating biofilms. This communication summarizes emerging nano-antimicrobial therapies in treating bacterial infections, particularly using antibacterial, quorum quenching, and anti-biofilm nanomaterials as new approaches to tackle the current challenges in combating infectious diseases.
Antibiotics are widely used in mariculture industry, and this study attempts to determine the extent of water and sediment pollution by aritibiotic residues in 13 major mariculture sites in China. Through chemical and molecular biology analysis, the results showed that the total concentrations of sulfonamides and tetracyclines were in the range 62.0-373.8 ng L-1 and 0.2-259.1 ng L-1 respectively in water samples, and in the range 0.19-1.59 ng g(-1) dry weight and 3.45-74.84 ng g(-1) dry weight respectively, in sediments samples. The occurrence of antibiotic resistance genes (ARGs) was detected in all sites. Compared with the tetracyclines resistance genes, the absolute copy number and relative abundance of the sulfonamides resistance genes were 4.3 times and 2.3 times higher in water and sediment from the mariculture sites, With the dominant resistance genes being sul2. The abundance of sul3 in the water phase was significantly correlated with the concentrations of sulfamerazine, while the abundance of sul2 in the sediment phase was significantly with sulfadiazine concentrations. The abundance of tetM in the sediment phase was significantly correlated with the concentrations of oxytetracycline. The findings demonstrate the persistence of antibiotic residues and ARGs in major mariculture sites in Southeast China. (C) 2016 Elsevier B.V. All rights reserved.
The alga Cladophora glomerata can erupt in nuisance blooms throughout the lower Great Lakes. Since bacterial abundance increases with the emergence and decay of Cladophora, we investigated the prevalence of antibiotic resistance (ABR) in Cladophora-associated bacterial communities up-gradient and down-gradient from a large sewage treatment plant (STP) on Lake Ontario. Although STPs are well-known sources of ABR, we also expected detectable ABR from up-gradient wetland communities, since they receive surface run-off from urban and agricultural sources. Statistically significant differences in aquatic bacterial abundance and ABR were found between down-gradient beach samples and up-gradient coastal wetland samples (ANOVA, Holm-Sidak test, p < 0.05). Decaying and free-floating Cladophora sampled near the STP had the highest bacterial densities overall, including on ampicillin-and vancomycin-treated plates. However, quantitative polymerase chain reaction analysis of the ABR genes ampC, tetA, tetB, and vanA from environmental communities showed a different pattern. Some of the highest ABR gene levels occurred at the 2 coastal wetland sites (vanA). Overall, bacterial ABR profiles from environmental samples were distinguishable between living and decaying Cladophora, inferring that Cladophora may control bacterial ABR depending on its life-cycle stage. Our results also show how spatially and temporally dynamic ABR is in nearshore aquatic bacteria, which warrants further research.
The seasonal variation and removal efficiency of antibiotic resistance genes (ARGs), including tetracycline resistance genes (tetG, tetM, and tetX) and macrolide (ermB, ermF, ereA, and mefA), were investigated in two typical swine wastewater treatment systems in both winter and summer. ARGs, class 1 integron gene, and 16S rRNA gene were quantified using real-time polymerase chain reaction assays. There was a 0.31-3.52 log variation in ARGs in raw swine wastewater, and the abundance of ARGs in winter was higher than in summer. tetM, tetX, ermB, ermF, and mefA were highly abundant. The abundance of ARGs was effectively reduced by most individual treatment process and the removal efficiencies of ARGs were higher in winter than in summer. However, when examining relative abundance, the fate of ARGs was quite variable. Anaerobic digestion reduced the relative abundance of tetX, ermB, ermF, and mefA, while lagoon treatment decreased tetM, ermB, ermF, and mefA. Sequencing batch reactor (SBR) decreased tetM, ermB, and ermF, but biofilters and wetlands did not display consistent removal efficiency on ARGs in two sampling seasons. As far as the entire treatment system is concerned, ermB and mefA were effectively reduced in both winter and summer in both total and relative abundance. The relative abundances of tetG and ereA were significantly correlated with intI1 (p<0.01), and both tetG and ereA increased after wastewater treatment. This may pose a great threat to public health.
The objectives of this study were to determine the kinetic parameters of purified recombinant Bla(Mab) and Bla(Mmas) by spectrophotometry, analyze the genetic environment of the bla(Mab) and bla(Mmas) genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that Bla(Mab) and Bla(Mmas) have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. Bla(Mmas) hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. Bla(Mab) and Bla(Mmas) showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A -lactamases by the presence of a more flexible loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3 end of MAB_2874, which may constitute the bla(Mab) and bla(Mmas) promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of -lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.
Natural tetracycline (TC) antibiotics were the first major class of therapeutics to earn the distinction of 'broad-spectrum antibiotics' and they have been used since the 1940s against a wide range of both Gram-positive and Gram-negative pathogens, mycoplasmas, intracellular chlamydiae, rickettsiae and protozoan parasites. The second generation of semisynthetic tetracyclines, such as minocycline and doxycycline, with improved antimicrobial potency, were introduced during the 1960s. Despite emerging resistance to TCs erupting during the 1980s, it was not until 2006, more than four decades later, that a third-generation TC, named tigecycline, was launched. In addition, two TC analogues, omadacycline and eravacycline, developed via (semi)synthetic and fully synthetic routes, respectively, are at present under clinical evaluation. Interestingly, despite very productive early work on the isolation of a Streptomyces aureofaciens mutant strain that produced 6-demethyl-7-chlortetracycline, the key intermediate in the production of second- and third-generation TCs, biosynthetic approaches in TC development have not been productive for more than 50 years. Relatively slow and tedious molecular biology approaches for the genetic manipulation of TC-producing actinobacteria, as well as an insufficient understanding of the enzymatic mechanisms involved in TC biosynthesis have significantly contributed to the low success of such biosynthetic engineering efforts. However, new opportunities in TC drug development have arisen thanks to a significant progress in the development of affordable and versatile biosynthetic engineering and synthetic biology approaches,. and, importantly, to a much deeper understanding of TC biosynthesis, mostly gained over the last two decades.
abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as complementarity-determining regions and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing "unusual residues" (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species. abYsis is useful for any researcher specializing in antibody engineering, especially those developing antibodies as drugs. abYsis is available at www.abysis.org. (C) 2016 Published by Elsevier Ltd.
The introduction of more sensitive techniques, such as LuminexA (R) for HLA antibody screening of patients awaiting organ transplantation has resulted in a better understanding of transplantation immunology and improvements in clinical practice. The interpretation of the results obtained only by LuminexA (R) can lead to inaccurate evaluation of a patient's antibody status and unjustified rejection of a potential organ donor. The aim of this study was to demonstrate the benefits of performing HLA antibody screening in the sera of patients on the waiting list for organ transplantation by two different assays, complement dependent cytotoxicity (CDC) and LuminexA (R). A retrospective analysis was performed on 563 pretransplant serum samples from 141 patients on the kidney transplantation waiting list in Rijeka, tested from March 2012 until March 2015. All samples were tested in parallel by the CDC assay and the LuminexA (R)-based assay. Out of the 563 samples tested 302 (53.7%) tested negative for HLA antibodies and 88 (15.6%) positive by both assays. From 173 (30.7%) samples with discordant results 149 (26.5%) were CDC negative and LuminexA (R) positive, while 24 (4.3%) were CDC positive and LuminexA (R) negative. Among the Luminex positive patients seven did not experience any immunizing events. Evaluation of the HLA antibody status in patients on a waiting list for organ transplantation should be based on the results of the both CDC and LuminexA (R) (or other sensitive) assays in accordance to information about patient's clinical status and exposure to immunizing events.
Effects in the liver of fatal intoxication with the binary toxin ricin are unclear. We report a robust neutrophil influx into the liver of C57BL/6 mice after lethal parenteral ricin challenge, occurring in peri-portal and centro-lobular hepatic areas within 2 h, followed by the abrupt disappearance of hepatic macrophages/Kupffer cells. Chemokine profiles determined by microarray, ribonuclease protection assays, northern blotting, and enzyme-linked immunosorbent assays showed rapid (2 h) upregulation and persistence of those for neutrophils (CXCL1/KC, CXCL2/MIP-2) and monocytes (CCL2/MCP-1). Red blood cell pooling (8-12 h), loss of hepatocyte glycogen (8-48 h) associated with progressive hypoglycemia, fibrin deposition (24-48 h), and death (72-96 h) followed. Monoclonal antibody to ricin A chain, administered intravenously, blunted hypoglycemia, and abrogated death. This outcome was observed when anti-ricin antibody was given before toxin exposure as well as when administered approximately 10 h after toxin exposure. Targeting antibody to specific amino-acid sequences on the ricin A chain (HAEL and QXXWXXA) was critical to the therapeutic effect. Re-emergence of liver macrophages/Kupffer cells and replenishment of glycogen in previously depleted hepatocytes preceded full recovery of the host. These data identify critical events for liver injury and healing in ricin intoxication, as well as a new means and specific targets for post- exposure therapeutic intervention.
HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching. For human vaginal explants, we developed a replication-competent, secreted NanoLuc reporter virus system and showed that CD4 binding site bnAbs b12 IgG1 and CH31 IgG1 and IgA2 isoforms potently blocked HIV-1JR-CSF and HIV-1Bal26 infection. However, IgG1 and IgA nnAbs, either alone or together, did not inhibit infection despite the presence of FcR-expressing effector cells in the tissue. In macaques, the CH31 IgG1 and IgA2 isoforms infused before high-dose SHIV challenge were completely to partially protective, respectively, while nnAbs (CH54 IgG1 and CH38 mIgA2) were non-protective. Importantly, in both mucosal models IgG1 isotype bnAbs were more protective than the IgA2 isotypes, attributable in part to greater neutralization activity of the IgG1 variants. These findings underscore the importance of potent bnAb induction as a primary goal of HIV-1 vaccine development. (C) 2016 The Authors. Published by Elsevier B.V.
Immunoglobulin therapy is a key element in the management of most patients with primary immunodeficiency disease. Allergist/immunologists should be familiar with the appropriate evaluation of candidates for immunoglobulin, the characteristics of immunoglobulin products, and how to use them to provide the best care to their patients. Available immunoglobulin products appear to be equally efficacious, but they are not interchangeable. Minimizing the risk of serious adverse events and controlling minor side effects is important to ideal patient care. Immunoglobulin may be administered intravenously or subcutaneously. Individualizing the choice of immunoglobulin product, mode of administration, and site of care can optimize the clinical outcome and minimize the burden of care. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.
Somatic mutations within the antibody variable domains are critical to the immense capacity of the immune repertoire. Here, via a deep mutational scan, we dissect how mutations at all positions of the variable domains of a high-affinity anti-VEGF antibody G6.31 impact its antigen-binding function. The resulting mutational landscape demonstrates that large portions of antibody variable domain positions are open to mutation, and that beneficial mutations can be found throughout the variable domains. We determine the role of one antigen-distal light chain position 83, demonstrating that mutation at this site optimizes both antigen affinity and thermostability by modulating the interdomain conformational dynamics of the antigen-binding fragment. Furthermore, by analyzing a large number of human antibody sequences and structures, we demonstrate that somatic mutations occur frequently at position 83, with corresponding domain conformations observed for G6.31. Therefore, the modulation of interdomain dynamics represents an important mechanism during antibody maturation in vivo.
Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and noncurable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential noninvasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. We provide an overview of differentially expressed protein, antigen, and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.
Immune defenses are expected to be crucial for survival under the considerable parasite pressures experienced by wild animals. However, our understanding of the association between immunity and fitness in nature remains limited due to both the complexity of the vertebrate immune system and the often-limited availability of immune reagents in nonmodel organisms. Here, we use methods and reagents developed by veterinary researchers for domestic ungulates on blood samples collected from a wild Soay sheep population, to evaluate an unusually broad panel of immune parameters. Our evaluation included different innate and acquired immune cell types as well as nematode parasite-specific antibodies of different isotypes. We test how these markers correlate with one another, how they vary with age-group and sex, and, crucially, whether they predict over-winter survival either within or among demographic groups. We found anticipated patterns of variation in markers with age, associated with immune development, and once these age trends were accounted for, correlations among our 11 immune markers were generally weak. We found that females had higher proportions of naive T cells and gamma-delta T cells than males, independent of age, while our other markers did not differ between sexes. Only one of our 11 markers predicted overwinter survival: sheep with higher plasma levels of anti-nematode IgG antibodies were significantly more likely to survive the subsequent high mortality winter, independent of age, sex, or weight. This supports a previous finding from this study system using a different set of samples and shows that circulating antibody levels against ecologically relevant parasites in natural systems represent an important parameter of immune function and may be under strong natural selection. Our data provide rare insights into patterns of variation among age-and sex groups in different T-cell subsets and antibody levels in the wild, and suggest that certain types of immune response-notably those likely to be repeatable within individuals and linked to resistance to ecologically relevant parasites-may be most informative for research into the links between immunity and fitness under natural conditions.
The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection. These candidate vaccines, despite employing disparate viral vectors and immunization strategies, consistently identify a role for functional or non-traditional antibody activities as correlates of immunity. However, the precise mechanism(s) of action of these binding antibodies, their specific characteristics, and their ability to be selectively induced and/or potentiated to result in complete protection merits parallel investigation to neutralizing antibody-based vaccine design approaches. Ultimately, while neutralizing and functional antibody-based vaccine strategies need not be mutually exclusive, defining the specific characteristics of protective functional antibodies may provide a target immune profile to potentially induce more robust immunity against HIV. Specifically, one approach to guide the development of functional antibody-based vaccine strategies, termed systems serology, offers an unbiased and comprehensive approach to systematically survey humoral immune responses, capturing the array of functions and humoral response characteristics that may be induced following vaccination with high resolution. Coupled to machine learning tools, large datasets that explore the antibody-ome offer a means to step back from anticipated correlates and mechanisms of protection and toward a more fundamental understanding of coordinated aspects of humoral immune responses, to more globally differentiate among vaccine candidates, and most critically, to identify the features of humoral immunity that distinguish protective from non-protective responses. Overall, the systematic serological approach described here aimed at broadly capturing the enormous biodiversity in antibody profiles that may emerge following vaccination, complements the existing cutting edge tools in the cellular immunology space that survey vaccine-induced polyfunctional cellular activity by flow cytometry, transcriptional profiling, epigenetic, and metabolomic analysis to offer a means to develop both a more nuanced and a more complete understanding of correlates of protection to support the design of functional vaccine strategies.
Acute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFN promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFN drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of FcRI, which mediates effector responses to therapeutic antibodies. Importantly, IFN was able to up-regulate CD38, the target of the therapeutic antibody daratumumab. Because the antigen (CD38) and effector receptor (FcRI) were both simultaneously up-regulated on the AML blasts, we tested whether IFN treatment of the AML cell lines THP-1 and MV4-11 could stimulate them to target one another after the addition of daratumumab. Results showed that IFN significantly increased daratumumab-mediated cytotoxicity, as measured both by Cr-51 release and lactate dehydrogenase release assays. We also found that the combination of IFN and activation of FcR led to the release of granzyme B by AML cells. Finally, using a murine NSG model of subcutaneous AML, we found that treatment with IFN plus daratumumab significantly attenuated tumor growth. Taken together, these studies show a novel mechanism of daratumumab-mediated killing and a possible new therapeutic strategy for AML.
Bacillus thuringiensis (Bt) is known as the most successful microbial insecticide against different orders of insect pests in agriculture and medicine. Moreover, Bt toxin genes also have been efficiently used to enhance resistance to insect pests in genetically modified crops. In light of the scientific advantages of new molecular biology technologies, recently, some other new potentials of Bt have been explored. These new environmental features include the toxicity against nematodes, mites, and ticks, antagonistic effects against plant and animal pathogenic bacteria and fungi, plant growth-promoting activities (PGPR), bioremediation of different heavy metals and other pollutants, biosynthesis of metal nanoparticles, production of polyhydroxyalkanoate biopolymer, and anticancer activities (due to parasporins). This review comprehensively describes recent advances in the Bt whole-genome studies, the last updated known Bt toxins and their functions, and application of cry genes in plant genetic engineering. Moreover, the review thoroughly describes the new features of Bt which make it a suitable cell factory that might be used for production of different novel valuable bioproducts.
The aim of this study was to investigate the effect of costimulation blockade with cytotoxic T-lymphocyte-associated-antigen 4-immunoglobulin (CTLA4Ig) and anti-CD40L monoclonal antibody (anti-CD40L mAb) on an experimental autoimmune myocarditis (EAM) mouse model. Characteristics of myocardial tissue were observed by hematoxylin and eosin (H&E) staining. The messenger RNA (mRNA) levels of CTLA4, CD40L, IFN-gamma, and IL-4 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Serum concentrations of IFN-gamma and IL-4 were determined by ELISA. After immune intervention, the inflammatory score, mRNA levels of CTLA4 and CD40L, and IFN-gamma level were decreased. Furthermore, these parameters in the combinational intervention group (blockade by CTLA4Ig and anti-CD40L mAb) were significantly decreased, compared to the single intervention group (blockade by CTLA4Ig or anti-CD40L mAb). However, after costimulation, blockade serum IL-4 levels were increased. Therefore, costimulation blockade by combination CTLA4Ig and anti-CD40L mAb could more effectively inhibit the inflammatory response of EAM than single use of CTLA4Ig or anti-CD40L mAb.
Objective: Arginine-specific cysteine proteases (Rgps) from Porphyromonas gingivalis are important virulent factors of periodontal diseases. However, there is no therapeutic drug that inhibits proinflammatory events induced by these enzymes. In this study, we investigated proinflammatory activities of Rgps and activated coagulation factor X (FXa) and examined the effect of DX-9065a, a new selective inhibitor of FXa, on proinflammatory events induced by these proteinases. Methods: Human gingival fibroblasts were stimulated with Rgps and FXa in the presence or absence of DX-9065a, and then interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) release, their mRNA expression, and nuclear factor kappa B (NF-kappa B) activation were assessed using an enzyme-linked immunosorbent assay (ELISA), northern blotting, and a gel-mobility shift method, respectively. Results: Rgps and FXa activated IL-6 and MMP-1 release in human gingival fibroblasts through their amidolytic activities and in mitogen-activated protein kinase (MAPK) and NF-kappa B dependent manners. DX-9065a inhibited FXa-mduced IL-6 mRNA expression and NF-kappa B activation. DX-9065a inhibited amidolytic activities of FXa and Rgps in vitro and ex vivo. Conclusion: Rgps and FXa are potent inflammatory mediators and DX-9065a may be a useful therapeutic drug for periodontal disease.
In this study, drug target was identified using KEGG database and network analysis through Cytoscape software. Designed series of novel benzimidazoles were taken along with reference standard Flibanserin for insilico modeling. The novel 4-(1H-benzo[d]imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a-j) analogs were synthesized and evaluated for their antidepressant activity. Reaction of 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanoic acid (1) with 4-(1H-benzo [d] imidazol-2-yl)-4-oxobutanoyl chloride (2) furnished novel 4-(1H-benzo [d] imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a-j). All the newly synthesized compounds were characterized by IR, H-1-NMR, and mass spectral analysis. The antidepressant activities of synthesized derivatives were compared with standard drug clomipramine at a dose level of 20mg/kg. Among the derivatives tested, most of the compounds were found to have potent activity against depression. The high level of activity was shown by the compounds 3d, 3e, 3i, and it significantly reduced the duration of immobility time at the dose level of 50mg/kg.
ObjectiveTo explore the prevalence and clinical profile of males and females who develop antidepressant treatment-emergent mania (ATEM). MethodFrom an original sample of 754 patients with BD, we identified ATEM+ cases (n = 75) and ATEM- controls (n = 135) that met stringent criteria. We specifically examined the combinations of clinical factors that best classified males and females as ATEM+ cases. ResultsSeventy-five individuals were classified as ATEM+; 87% of ATEM events occurred during antidepressant monotherapy. Regression analyses demonstrated that the presence of an alcohol and/or substance use disorder [Odds Ratio (OR) 6.37], a history of one or more suicide attempts (OR 4.19) and higher number of depressive episodes per year of illness (OR 1.71) correctly classified 73% of males. In contrast, 84% of females were correctly classified on the basis of a positive history of thyroid disorder (OR 3.23), a positive family history of BD I (OR 2.68) and depressive onset polarity (OR 2.01). ConclusionUsing stringent definitions of ATEM status to reduce the probability of inclusion of false-positive cases and false-negative controls, we identified for the first time that the risk profiles for the development of an ATEM differ significantly according to gender.
Approximately 40% of patients treated for depression do not respond to a trial of an antidepressant. The aim of the proposed study was to evaluate the efficacy and safety of switching to vilazodone in patients with major depressive disorder who are unresponsive or only partially responsive to a trial of citalopram. Seventy-nine adults with major depressive disorder were enrolled in an open-label study of citalopram (20mg/day) for 6 weeks. Those still symptomatic after 6-weeks of citalopram were randomly assigned to either a higher dose of citalopram (40mg/day) or to vilazodone in a double-blind trial for 6 weeks. Of those who received citalopram 20mg/day for 6 weeks, 20.3% were responders' (defined as 50% reduction on the Montgomery-angstrom sberg Depression Rating Scale). Of the 42 who did not respond, 23 were assigned to citalopram 40mg/day and 19 were randomized to 40mg/day of vilazodone. Both groups showed decreases in all outcome measures, but there were no significant differences between groups. Initial nonresponders to a low dose of citalopram seem equally likely to respond to a higher dose of citalopram or to vilazodone. Whether to increase an selective serotonin reuptake inhibitor or switch to a different antidepressant may be best determined on the basis of their adverse event profile.
Background: Major depressive disorder (MDD) is often resistant to treatment with usual approaches. Patients with MDD have shown hypofunction of the frontotemporal cortex in verbal fluency test (VFT)-related near-infrared spectroscopy (NIRS). Methods: We examined whether the reactions to drug treatment in treatment-naive patients with MDD could be predicted by NIRS outcomes at the initial investigation. All subjects underwent psychological testing to determine levels of anxiety and depression. VFT was used to examine the functioning of the frontotemporal lobes. We administered selective serotonin reuptake inhibitors (SSRIs) for 12 weeks. Subjects included 28 patients with MDD with response to SSRIs (Response group), 19 with no response (Non-Response group), and 63 age-, sex-, and education years-matched healthy controls (HC). Results: We found in the frontotemporal region that hemodynamic responses were significantly smaller in patients with Response and Non-Response groups than in HC before treatment. We also found in the medial frontal region that hemodynamic responses were significantly larger in patients with Response groups than in patients with Non-Response group before treatment. Patients with MDD scored significantly higher anxiety and depressive states than those in HC on several measures. The Response and Non-Response groups also had higher scores in future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of Anxiety Cognition Scale (DACS). According to the stepwise regression analysis, one variable was determined as independent predictors of response: confusion (Post-POMS). Limitations: The number of patients and healthy controls was relatively small, and we will increase the number of participants in future studies. NIRS has reduced spatial resolution, which confuses the identification of the measurement position when using NIRS alone. Conclusion: Cognitive vulnerabilities are associated with predictors of SSRI treatment response. Different hemodynamic activities in the frontotemporal cortex predict response to SSRI treatment in MDD.
No study has investigated psychological dependence on antidepressants in patients with panic disorder, which was addressed in this study. This study was carried out in four psychiatric clinics in Tokyo, Japan. Individuals were eligible if they were outpatients aged 18 years or older and fulfilled the diagnostic criteria for panic disorder (ICD-10). Assessments included the Japanese Versions of the Severity of Dependence Scale (SDS), the Self-Report Version of Panic Disorder Severity Scale (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report. Eighty-four individuals were included; of these, 30 patients (35.7%) showed psychological dependence on antidepressants (i.e. a total score of >= 5 in the SDS). A multiple regression analysis showed that PDSS scores and illness duration were correlated positively with SDS total scores. A binary regression model showed that absence of remission (i.e. a total score of >= 5 in the PDSS) and longer duration of illness increased the risk of dependence on antidepressants. Approximately one-third of the patients with panic disorder, receiving antidepressants, fulfilled the criteria for psychological dependence on these drugs. The results underscore the need for close monitoring, especially for those who present severe symptomatology or have a chronic course of the illness. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Objective: To assess systematically the effects of antidepressants and untreated maternal depression on human placenta and the developing fetus.Methods: Pertinent medical literature information was identified using MEDLINE/PubMed, SCOPUS and EMBASE. Electronic searches, limited to human studies published in English, provided 21 studies reporting primary data on placental and fetal effects of antidepressant exposure or untreated gestational depression.Results: The impact of antidepressants and non-medicated maternal depression on placental functioning and fetal biochemical architecture seems to be demonstrated, although its clinical significance remains unclear. More robust data seem to indicate that exposure to either antidepressants or untreated maternal depression may induce epigenetic changes and interfere with the physiological fetal behavior. Two cases of iatrogenic fetal tachyarrhythmia have also been reported.Conclusions: Future research should clarify the clinical relevance of the impact of antidepressant and untreated maternal depression exposure on placental functioning. Moreover, ultrasound studies investigating fetal responses to antidepressants or maternal depressive symptoms are mandatory. This assessment should be performed during the whole duration of gestational period, when different fetal behavioral patterns become progressively detectable. Analyses of biochemical and epigenetic modifications associated with maternal mood symptoms and antidepressant treatment should also be implemented.
Antibodies against the toxin portion of recombinant immunotoxins (RIT) reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SS1P to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SS1P modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies (ADA), whereas mice immunized with SS1P, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.Cellular & Molecular Immunology (2017) published online 19 October 2015
Objectives - Whether and when to immunologically treat epilepsy patients with suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. Methods - This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy. Results - All patients had seizures, amygdala and/or - hippocampal enlargement, subjective cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were impaired in executive or memory functions, 39% (10/25) depressed, 81% were on antiepileptic drugs when pulse therapy started. After a median follow-up of 18 months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27) showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical changes did not correlate to each other. Outcomes could not be predicted. Conclusion - Immunological treatment of suggested AB-negative LE showed reasonable seizure control, MRI and cognitive improvements. Treatment success was not predictable from clinical features, nor definitely attributable to immunological treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we suggest that in presence of mild manifestations, and after initiating antiepileptic drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be documented before immunosuppressive treatment is initiated.
ERp57 is a member of a protein disulfide isomerase family and is a chaperone responsible for the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum and in the assembly of the major histocompatibility complex class I in the endogenous pathway of antigen presentation. This study reports the identification of a full length ERp57 cDNA in rainbow trout that encodes a putative 477aa mature protein with an additional signal sequence of 16aa. The trout protein shared 75% identity with the human homolog, but interestingly did not include either a C terminal endoplasmic reticulum retention signal, Q/KEDL in humans, or a nuclear localization signal which is highly conserved in mammals. Amino acid sequence alignment revealed conservation of four classical domains in trout ERp57 and two conserved active CXXC redox motifs. Trout ERp57 protein was identified as a single band around 57 kDa. Southern blotting analysis revealed that there two copies of the ERp57 gene in the trout genome and northern blotting showed a wide tissue distribution of gene expression in various tissues with the highest expression in liver and egg. This study showed for the first time in teleost that ERp57 transcript is upregulated in response to immune stimuli such as double stranded RNA or phytohemagglutinin. Furthermore, upon treatment with ER stress inducer A23187, trout ERp57 protein expression levels were increased both in peripheral blood leukocytes and the RTS11 macrophage like cell line after 6 and 8 h respectively. These findings suggest a possible conserved function for trout ERp57 in the ER and during the activation of the immune response. (C) 2012 Elsevier Ltd. All rights reserved.
The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8(+) cytotoxic and CD4(+) helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected /transformed cells (CD8(+) cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4(+) T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8(+) cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets.
In the treatment of hemophilia A, the 20%-30% risk of developing of anti-factor VIII (FVIII) antibodies, or inhibitors, is the dominant concern among healthcare providers. Immune tolerance induction remains the only effective method of eradicating inhibitors in approximately 75% of patients, but is accompanied by significant emotional and economical burden. While certain risk factors, such as the type of FVIII mutation, offer some insight, there remains no strategy to confidently predict the development of an inhibitor. Moreover, even if such a predictive tool existed, there is currently no proven protocol for tolerance induction of a previously untreated patient. In recent years, the growing body of knowledge concerning the fundamental immunology of inhibitors has shed light on potential therapeutic interventions. In this review, we highlight these new findings and their influences on translational medicine.
Mycobacterium tuberculosis produces dideoxymy-cobactin- 838 (DDM-838), a lipopeptide that potently activates T cells upon binding to the MHC-like antigen-presenting molecule CD1a. M. tuberculosis produces DDM-838 in only trace amounts and a previous solid-phase synthesis provided sub-milligram quantities. We describe a high-yielding solution-phase synthesis of DDM-838 that features a Mitsunobu substitution that avoids yield-limiting epimerization at lysine during esterification, and amidation conditions that prevent double-bond isomerization of the Z-C20:1 acyl chain, and provides material with equivalent antigenicity to natural DDM-838. Isomers of DDM-838 that varied in stereochemistry at the central lysine and the C20:1 acyl chain were compared for their ability to be recognised by CD1a-restricted T cell receptors (TCRs). These TCRs, derived from unrelated human donors, exhibited a similar spectrum of reactivity towards the panel of DDM-838 isomers, highlighting the exquisite sensitivity of lipopeptide-reactive T cells for the natural DDM stereochemistry.
The presence of anti-HLA antibodies in the serum of a patient result from an immune response produced during an immunizing event as transfusion, pregnancy or graft. These antibodies can be cytotoxic by activating the complement pathway via C1q and may cause organ rejection during the transplant. Some male patients awaiting kidney transplantation are seropositive for anti-HLA antibodies when they have no immunizing antecedent event. These antibodies are qualified as natural antibodies. Our work is to assess the cytotoxicity of natural anti-HLA antibodies in patients followed at the immunology laboratory of the blood transfusion service and hemovigilance (STSH) as part of the kidney transplant. Patients and methods. - We evaluated the cytotoxicity of HLA antibodies detected in male Moroccan patients without immunization history using C1q Screen One Lambda reagent for Luminex (TM) Results. - Non-immunized men were positive for HLA antibodies screening in 25.4%. These antibodies are not cytotoxic. Conclusion. - Our study showed a positivity rate of natural HLA antibody low than the literature (25.4% against 63%). It appears that these natural antibodies are not cytotoxic and their involvement in renal transplant remains to be determined. (C) 2016 Association Societe de nephrologie. Published by Elsevier Masson SAS. All rights reserved.
Glycyrrhiza uralensis has acquired significant importance due to its medicinal properties and health function. In this study, the quality of G. uralensis adventitious roots was evaluated in terms of genetic stability, active compounds, and anti-inflammatory activity. Monomorphic banding pattern obtained from the mother plant and tissue cultures of G. uralensis with randomly amplified polymorphic DNA markers confirmed the genetic stability of adventitious roots. Neoliquiritin (neoisoliquiritin), ononin, liquiritin, and glycyrrhizic acid were identified from G. uralensis adventitious roots on the basis of high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. This study also revealed that adventitious roots possessed a better anti-inflammatory effect than native roots. To increase the contents of G. uralensis active components, elicitors were used in the adventitious roots culture. The combination of methyl jasmonate and phenylalanine synergistically stimulated the accumulation of glycyrrhetinic acid (0.22 mg/g) and total flavonoid (5.43 mg/g) compared with single treatment. In conclusion, G. uralensis adventitious roots can be an exploitable system for the production of licorice. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Background: One of the most significant contributors to morbidity and death in patients with burns is infection, which accounts for 30%-75% of post-burn fatalities. Because of concerns for the development of antibiotic resistance in burn-related pathogens, the aims of this study were to identify antibiotic resistance trends for the four most common burn-related pathogens over a six-year period. Patients and Methods: The study used prospectively collected and de-identified aggregate data for all burn patients admitted to the burn unit between 2009 and 2014. The database query included patient demographics along with all data regarding cultures from any source (wound, sputum, urine, stool, blood), which included isolated pathogens and antibiotic resistance profiles. Profiles were then constructed using mean inhibitory concentration standards to determine whether each pathogen was susceptible (S), intermediate (I), or resistant (R) to each antibiotic. The aggregated data were then used to construct a heat map for the four most common pathogens and their resistance profiles over the six-year study period. Results: There were 368 patients with burns (248 with positive cultures, 120 with negative cultures) in this study. The positive culture group was significantly older (38 vs. 25y, p<0.001) and had longer hospitalizations (17 vs. 11 d, p<0.01) compared with the negative group. Analysis of antibiotic resistance heat maps constructed for the four most commonly isolated pathogens (methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, methicillin-resistant S. aureus, Pseudomonas aeruginosa) indicated a lack of notable resistance patterns for any of the individual pathogens. Conclusions: Taken together, these results indicate that there are no discernible patterns of antibiotic resistance across time (six years) for the four most common burn-related pathogens. We conclude that antibiotic choice in burn patients based on previous in-hospital trends may be a flawed strategy. Emerging genomic technology to deliver point-of-care pathogen-specific antibiotic sensitivities via polymerase chain reaction may be needed to more appropriately guide antibiotic choice.
Antimicrobial peptides are central effector molecules in skin immunology. The functions of antimicrobial peptides in skin diseases include the ability to act as cytokines or growth factors, driving disorders such as psoriasis and rosacea, as well as their action as natural antibiotics to control bacteria that influence diseases such as atopic dermatitis and acne.
Purpose. The impact of an antimicrobial stewardship initiative on time to first antibiotic dose and clinical outcomes in bacteremic patients was, evaluated. Methods. A single-center, retrospective study was conducted for adult inpatients who received antibiotics before and after implementation of a rapid administration of antimicrobials by an infectious diseases specialist (RAIDS) protocol. Patients admitted to an inpatient service from June to October 2011 (pre-RAIDS protocol) and from December 2011 to February 2012 (post-RAIDS protocol) were eligible for inclusion if (1) they were age 18 years or older, (2) their infection occurred two or more days after hospital admission, and (3) they had a blood culture growing an organism other than common skin contaminants (i.e., coagulase-negative staphylococci, Bacillus species). The primary outcome was the time to the first antibiotic dose (TFAD), defined as the time that elapsed from a positive blood culture result to administration of the first empirical antimicrobial dose. Results. A total of 111 bacteremic patients were included in the analysis. Implementation of the RAIDS protocol led to significantly faster antibiotic order entry, verification, and administration of empirical antibiotics in patients with bacteremia. The median TFAD was approximately 8 hours faster in the post-RAIDS group than in the pre-RAIDS group (9:09 hr:min versus 1:23 hr:min, p < 0.001). Patients in the post-RAIDS group had a significant reduction in infection-related mortality (p = 0.047), though all cause 30-day mortality was similar. Conclusion. Early notification of an infectious diseases pharmacist about positive blood cultures using the RAIDS protocol led to increased appropriateness of empirical drug selection and a dramatic reduction in the administration of antibiotics and was associated with decreased infection related mortality.
Background:Extrapulmonary tuberculosis (EPTB) constitutes about 15% to 20% of all cases of tuberculosis (TB). The confirmation of EPTB has always been a challenge to laboratory personnel. We aim to evaluate the diagnostic potential of immunostaining with anti-MPT64 in various EPTB specimens.Materials and Methods:We studied a total of 51 TB cases and 38 non-TB control specimens comprising of fine-needle aspirates and formalin-fixed biopsies. These were investigated using a combination of the Ziehl-Neelsen method, the Lowenstein-Jensen culture, immunostaining with anti-MPT64 and anti-BCG, and nested-polymerase chain reaction (PCR) for IS6110. Results of all the tests were compared using nested-PCR as the gold standard.Results:Diagnostic validation of immunostaining for anti-MPT64 was performed using nested-PCR as the gold standard. The overall sensitivity, specificity, and positive and negative predictive values for immunostaining with anti-MPT64 were 100%, 97%, 97%, and 100%, respectively.Conclusions:Immunostaining using anti-MPT64 is a rapid and sensitive method for establishing an early and specific diagnosis of Mycobacterium tuberculosis infection. The technique is simple to be incorporated into routine pathology laboratories.
Panax notoginseng, an important herbal medicine, has wide uses for its bioactive compounds and health function. In this work, we compared the content of saponin in cultivation and adventitious root. The total content of saponins in adventitious root (8.48 mg.g(-1)) was found lower than in the native one (3-year-old) (34.34 mg.g(-1)). To enhance the content of bioactive compounds, we applied elicitors jasmonic acid (JA) and methyl dihydrojasmonate (MDJ) to the adventitious root culture. It was observed that the highest total content of saponins (71.94 mg.g(-1)) was achieved after treatment with 5 mg.L-1 JA, which was 2.09-fold higher than native roots and 8.45-fold higher than the control group. The findings from high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis showed that six new compounds were present after the treatment with the elicitors. Furthermore, we found that JA and MDJ significantly upregulated the expression of the geranyl diphosphate synthase, farnesyl diphosphate synthase, squalene synthase, squalene epoxidase, dammarenediol synthase, and CYP716A47 and CYP716A53v2 (CYP450 enzyme) genes; downregulated the expression of the cycloartenol synthase gene; and increased superoxide dismutase and peroxidase activities. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Bioactive antioxidant peptides are more and more attracting the attention of food manufacturers for their potential to transform food in functional food, able to prevent a variety of chronic diseases associated with oxidative stress. In the present study proteins extracted from different vegetable sources (KAMUT (R) khorasan wheat, emmer, lupine and pea) were hydrolyzed with commercial enzymes and Lactobacillus spp. strains. Hydrolysates were separated by size exclusion chromatography and purified fractions were analyzed for their antioxidant activity. Peptides from the fractions with the highest activity were identified by nanoLC-ESI-QTOF-MS and thirteen peptides were selected for synthesis on the basis of their sequence. Four peptides (VLPPQQQY, TVTSLDLPVLRW, VTSLDLPVLRW, FVPY) were found able to scavenge superoxide anion and hydroxyl radicals, organic nitro-radicals (ABTS, DPPH) and to inhibit lipid peroxidation. The impact of this work is targeted to add hydrolysed vegetable proteins to reformulated functional food or to produce health-promoting ingredients and nutraceuticals. (C) 2017 Elsevier Ltd. All rights reserved.
BackgroundThere are few studies on the association between nutrient intake and telomere length, which may reflect cumulative oxidative stress and indicate biological ageing. In the present study, we evaluated longitudinal associations between the consumption of micronutrients, including antioxidant nutrients and B vitamins involved in one-carbon transfer pathways, and leukocyte telomere length (LTL). MethodsThe study included 1958 middle-aged and older Korean men and women (age range at baseline: 40-69 years) from a population-based cohort. We collected dietary information at baseline using a semiquantitative food frequency questionnaire (June 2001 to January 2003) and assessed the consumption of micronutrients, including vitamins A, B-1, B-2, B-3, B-6, B-9 (folate), C and E, as well as calcium, phosphorus, potassium, iron and zinc. We measured LTL using a real-time polymerase chain reaction at the 10-year follow-up examination (February 2011 to November 2012). ResultsIn the multiple regression model adjusted for potential confounders, LTL was positively associated with the consumption of vitamin C (P < 0.05), folate (P = 0.05) and potassium (P = 0.05) in all participants. In the age-stratified analysis, the association between the consumption of vitamin C (P < 0.01), folate (P < 0.05) and potassium (P < 0.05) with LTL was significant only among participants aged <50 years. ConclusionsOur findings suggest that the earlier consumption of vitamin C, folate and potassium, which are abundant in fruits and vegetables, can delay biological ageing in middle-aged and older adults.
Rationale: Cigarette smoke extract inhibits chloride secretion in human bronchial epithelial cells. Oxidants decrease gene expression, protein expression, and function of the cystic fibrosis transmembrane conductance regulator (CFTR). Objectives: Because cigarette smoke is a rich source of oxidants, we verified the hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and in vivo. Methods: The effects of cigarette smoke exposure on Calu-3 and T84 cell CFTR expression and function were observed. Also studied were the nasal potential differences (PDs) in 26 men (9 smokers, 17 nonsmokers) who had no detectable CFTR gene mutations as determined during investigations for infertility. CFTR expression and function were determined by Northern blotting, Western blotting, and cAMP-dependent I-125 efflux assays. Extensive CFTR genotyping was performed in each subject. Nasal PD measurements were made at baseline and during amiloride, chloride-free buffer, and isoproterenol perfusions. Main Results: Cigarette smoke decreased CFTR expression and function in Calu-3 and T84 cell lines. Furthermore, the nasal PDs of cigarette smokers showed a pattern typical of CFTR deficiency with a blunted response to chloride-free buffer and isoproterenol compared with nonsmokers (-9.6 +/- 4.0 vs. -22.3 +/- 10.1 mV; p < 0.001). Conclusions: We conclude that cigarette smoke decreases the expression of CFTR gene, protein, and function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may contribute to the physiopathology of cigarette-induced diseases such as chronic bronchitis.
AIM: To investigate the molecular mechanism and functional consequences of heme oxygenase-1 (HO-1) activation by lansoprazole in endothelial cells and macrophages. METHODS: Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species (ROS) formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed using in vivo bioluminescence imaging. RESULTS: Lansoprazole increased HO-1 mRNA levels in endothelial cells and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH-mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity. CONCLUSION: Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002. (C) 2009 The WIG Press and Baishideng. All rights reserved.
Plasma gelsolin (pGSN) is a multifunctional protein involved mainly in severing and clearing of actin filaments. Its level correlates with inflammation and several diseases making it a potential biomarker of diagnostic and prognostic values. The pGSN level in groups of treated and untreated HIV-1-infected Indian patients is investigated in this study. This study aims at investigating the levels of pGSN in HIV-1-infected patients across different age, sex, severity of disease, and treatment status. Blood samples of 213 patients were analyzed for CD4 counts by flow cytometry and pGSN was quantified by enzyme-linked immunosorbent assay (ELISA). The level of pGSN is significantly increased in HIV-1 infected patients (227.2 +/- 54.3g/ml) compared to healthy volunteers (167.9 +/- 61.8g/ml). The level correlates with CD4 cell counts as patients with lower CD4 counts showed higher pGSN levels and vice versa. Gender does not affect pGSN level; however, antiretroviral (ARV) treatment reduces pGSN toward normal. Within low CD4 cell count group, the untreated patients have 52% higher pGSN than healthy volunteers, whereas with treatment, the difference reduces to 24%. Similarly, high CD4 cell count (>350 cells/mm(3)) group of patients showed 44% increase in pGSN in untreated patients compared to 21% increase in treated patients. There is an upregulation of pGSN in HIV-1 infection and it is inversely correlated with CD4 cell counts. Treatment with ARV drugs decreases pGSN levels toward normal. The monitoring of pGSN level in HIV-1-infected patients could be an important indicator of severity of disease and recovery during treatment.
Antisynthetase syndrome (ASS) is recognized as a subgroup of idiopathic inflammatory myopathies (IIMs). It is associated with autoantibodies directed against aminoacyl-transfer ribonucleic acid (tRNA) synthetase enzymes. We report the first case of anti-PL-7/anti-SSA 52kD ASS presenting as acute digital ischemia, an association not described previously. Occlusive vasculopathy is a rare but serious manifestation that can be seen at presentation in patients with ASS and may herald the onset of severe interstitial lung disease (ILD). Comprehensive evaluation should be performed to confirm the presence of subclinical myositis. Extensive myositis-specific antibody testing is strongly recommended even if initial screening autoimmune serologies are unrevealing.
The advertising as a form of business promotion has more and more widely in different applications, and the lighting lamps is one of the key equipments in the entire outdoor advertising facilities. In order to improve advertising effectiveness and facilities security, especially for the outdoor advertising lighting applications in some remote areas, occasionally occur the advertising lamps stolen and damaged. A novel advertising lighting anti-thefts security system based on digital control technologies is designed and implementation in this paper. The designed system can achieve the real-time online status monitoring of advertising lighting lamps, once the abnormal situation the system can be issued on-site sound and light alarms and remote on-line notification, etc., which greatly improving the anti-theft security performance of outdoor advertising lighting.
Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its efficacy remains unclear. We therefore identified nine randomized controlled trials (RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group) to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome. Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004), grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD (RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI 0.180.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95% CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00, P = 0.05) without compromising overall survival or increased risk of infections. Further studies are required to evaluate the optimal dosage and formulation of ATG in different conditioning regimens of transplantation with varied sources of graft and donor.
We previously described a Dermacentor varibialis (DV) cDNA that encodes a ubiquitously expressed and tick saliva-secreted functional histamine release factor (HRF) homolog. In this study gene specific primers based on DVHRF open reading frame nucleotide sequence were utilized to amplify three orthologs, from the wood tick, D. andersoni (DA), the black legged tick, the southern cattle tick, Boophilus microplus (BM) and the lone star tick, Amblyomma americanum (AA). At nucleotide level, sequence comparisons revealed 98 89 and 84% similarity to DVHRF for DAHRF, AAHRF and BMHRF, respectively, while predicted polypeptide comparisons revealed 98, 96 and 91% similarity for DAHRF, AAHRF and BMHRF respectively. Phylogenetically, the tick HRF clade, while distinct (100% bootstrap value), is closely related to other arthropods, but distantly related to vertebrate and protozoan clades. Consistent with sequence similarity analysis, a DVHRF-specific northern blotting probe hybridized a similar to 900 base pair (bp) mRNA band on all RNA blots. Likewise a mouse polyclonal antibody to E. coli-expressed recombinant (r) DVHRF, cross-reacted baculovirus-expressed non-fusion rAAHRF, rDAHRF, and rBMHRF. As revealed by northern blotting analysis of larvae and nymph RNA, DVHRF mRNA is expressed in both immature and mature ticks indicating that its transcription is not developmentally regulated. Unlike rHRF/TCTP proteins of other organisms, the calcium-binding function may not be conserved for tick HRF homologs as revealed by the (CaCl2)-Ca-45 + overlay assay. Apparent global expression of DVHRF and its orthologs make this protein family an ideal target antigen for development of novel tick control strategies targeting multiple tick species.
Purpose of review Aciclovir (ACV) is the first-line drug for the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term administration of ACV for the treatment of severe infections in immunocompromised patients can lead to the development of drug resistance. Furthermore, the emergence of isolates resistant to ACV is increasingly recognized in immunocompetent individuals with herpetic keratitis. This review describes the mechanisms involved in drug resistance for HSV and VZV, the laboratory diagnosis and management of patients with infections refractory to ACV therapy. Recent findings Genotypic testing is more frequently performed for the diagnosis of infections caused by drug-resistant HSV or VZV isolates. Molecular biology-based systems for the generation of recombinant viruses have been developed to link unknown mutations with their drug phenotypes. Fast and sensitive methods based on next-generation sequencing will improve the detection of heterogeneous viral populations of drug-resistant viruses and their temporal changes during antiviral therapy, which could allow better patient management. Novel promising compounds acting on targets that differ from the viral DNA polymerase are under clinical development. Summary Antiviral drug resistance monitoring for HSV and VZV is required for a rational use of antiviral therapy in high-risk populations.
Objective: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD).Methods: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network.Results: The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics.Conclusions: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.
Children with autism spectrum disorder (ASD) experience internalizing and externalizing problems at higher rates than typically developing children, which could worsen social impairment. The present study compared impairment scores (social responsiveness scale, 2nd edition; SRS-2 scores) in 57 children (3-17 years, 82.5% male) with ASD, either with or without heightened levels of anxiety or ADHD symptoms, all per parent report. Children with heightened anxiety problems showed higher scores on four SRS-2 subscales (Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior). Children with heightened ADHD traits showed higher scores on two subscales (Social Communication and Social Awareness). These findings suggest similarities and differences in how social deficits in ASD may worsen with anxiety or ADHD symptoms.
BackgroundHigh levels of maltreatment are found in children who are identified because their parents visit the emergency department due to partner violence, substance abuse or suicide attempt. However, it is unknown if these children experience psychosocial problems. This study aims to assess their levels of post-traumatic stress, anxiety, depression, behavioural problems and health-related quality of life. MethodsA cross-sectional study was conducted in six hospitals. All consecutive families of which a parent visited the emergency department due to partner violence, substance abuse or suicide attempt between 1 July 2012 and 1 March 2014 with children aged 1.5-17years were approached for participation. Parents and children aged 8years and older filled out questionnaires measuring post-traumatic stress [13-item version of Children's Revised Impact of Event Scale (CRIES-13)], anxiety, depression (Revised Child Anxiety and Depression Scale), behavioural problems [Child Behavior Checklist (CBCL) and Youth Self-Report (YSR)] and health-related quality of life (PedsQL). Scores of participants were compared with reference data obtained in children in similar age ranges from representative Dutch community samples (CRIES-13, Revised Child Anxiety and Depression Scale, PedsQL and CBCL) and to a normed cutoff score (CRIES-13). ResultsOf 195 eligible families, 89 (46%) participated in the study. Participating children did not score different from community children, both on child-reported and parent-reported instruments. Standardized mean differences of total sum scores were 0 (CRIES-13 and CBCL 1.5-5), 0.1 (YSR), 0.2 (CBCL 6-18) and -0.3 (PedsQL) and not statistically different from community children. Thirty-five percent of the participating children scored above the cutoff score on the CRIES-13, indicating post-traumatic stress disorder, but this difference was not statistically significant from community children (mean difference 8%; 95% CI -4-22%). ConclusionsWe found no differences in psychosocial problems between children whose parents visited the emergency department due to partner violence, substance abuse or suicide attempt and children from community samples. Because 35% of the children scored in the range of post-traumatic stress disorder, we advise healthcare providers to pay attention to post-traumatic stress symptoms
There is increasing interest in describing different variants and subtypes that characterize the heterogeneity of behavior, problems with the aim of supporting early detection and prevention, as well as facilitating research into etiological differences. This work examines the course of co-occurrence of callous-unemotional traits (CU), anxiety (ANX) and oppositionality (ODD-s) levels in a longitudinal community sample. A sample of 622 3 year-old preschoolers, followed up until age 7, was assessed annually with dimensional measures of callous-unemotional traits, oppositional defiant disorder and anxiety and related psychological constructs answered by parents, teachers and, performed by children. Growth-Mixture-Modeling yielded six trajectories (null 58.9%, ANXincreasing 4.9%, CU + ANX + ODD 2.4%, CU + ODD-decreasing 8.1%, ODD-increasing 16.4%, and ANX-decreasing 9.2%) that represent the variants previously described with older subjects. The specifier ODD "with limited prosocial emotion" (CU + ODD decreasing and increasing) showed deficits in executive functioning, attention, aggressive behavior and social cognition in comparison with null trajectory. The secondary variant showed a more severe clinical picture and presented more difficulties in executive functioning, worse environmental characteristics, and worse outcomes at age 7. It is possible to identify the heterogeneity of disruptive behavior problems from preschool age. The identification of homogeneous groups in this category of disorders may help to design more suitable treatments with specific components for specific difficulties, and to progress in the etiological research of each class. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Psychosocial distress is common among cancer patients. Significant associations between coping and social support with distress and quality of life in adult cancer patients have been identified before, but little is known about the interrelationships between distress, medical coping, and social support in adolescents and young adults (AYAs). Objective: The aims of this study are to investigate the prevalence of psychological distress in Chinese AYAs with cancer and examine the associations among distress, anxiety and depression, medical coping, and social support in the same population. Methods: A total of 610 AYA patients were recruited for this study; 551 patients completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), the Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and the Social Support Rating Scale. Results: The prevalence of psychological distress was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21-to 25-year-old patients; the DT scores were positively correlated with anxiety and depression (PG. 01) but negatively correlated with medical coping and social support (PG. 01). Conclusion: The prevalence of psychological distress in AYA cancer patients was higher than that in the general cancer population. Medical coping and social support can lower the prevalence of psychological distress in AYA cancer patients. Implications for Practice: Findings suggest the need for evidence-based intervention strategies to enhance medical coping and social support in AYA cancer patients. Nurses are crucial to implementing psychological interventions in AYA cancer patients.
This study identified predictors of anxiety and depression in patients with acute coronary syndrome. Predictors included illness beliefs, fear/threat at the time of the cardiac event, threat reappraisal over time and social support. A total of 97 participants completed questionnaires in hospital and 1- and 6-month follow-up. Perceived threat and fear at the time of the cardiac event predicted affective response at both time points, partly mediated by threat reappraisal. Contemporaneous measures of illness beliefs contributed additional variance, although not always in the predicted direction: high concern and control over the illness were associated with emotional distress. Assessment of patients for risk of negative emotional outcomes of acute coronary syndrome needs to consider their beliefs about their illness and the degree of threat and fear experienced at the time of the event. Interventions need to help people cope with negative emotional states as well as challenging inappropriate illness beliefs.
The purpose of this study was to evaluate the effects of a home-based (HB) exercise program on anxiety levels and metabolic functions in patients with anxiety disorders in Taiwan. Purposive sampling was used to recruit 86 participants for this randomized, experimental study. Participants were asked to complete a pretest before the 3-month exercise program, a posttest at 1 week, and a follow-up test at 3 months after the exercise program. Study measures included four Self-Report Scales and biophysical assessments to collect and assess personal data, lifestyle behaviors, anxiety levels, and metabolic control functions. Of the 86 study participants, 83 completed the posttest and the 3-month follow-up test, including 41 in the experimental group and 42 in the control group. Participants in the experimental group showed significant improvements in body mass index, high-density lipoprotein cholesterol levels, and the level of moderate exercise after the program relative to the control group, as analyzed by generalized estimating equations mixed-model repeated measures. State and trait anxiety levels were also significantly improved from pretest to follow-up test in the experimental group. Finally, the prevalence of metabolic syndrome declined for participants in the experimental group. The HB exercise program produced positive effects on the metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders. Health providers should consider using similar HB exercise programs to help improve the mental and physical health of patients with anxiety disorders in their communities.
Research shows that anxiety may relate to any or all of the following: goal conflict resolution; distraction, and the automatic detection of threat-related stimuli. To investigate these relationships we used a modified Stroop task where fearful and happy emotional target faces are overlaid with either emotionally neutral, emotionally congruent or emotionally incongruent distracting words. A trait anxiety related speed-accuracy trade-off seemed to primarily reduce accuracy during incongruent trials with target fearful faces overlaid with the emotionally conflicting word happy. We offer an explanation of this effect based upon theories of how positive stimuli and threat-related stimuli differentially affect information processing. Future studies should seek to verify how the anxiety related speed-accuracy trade-off mechanism is activated, and elucidate how and when positive stimuli affect anxiety more than threat-related stimuli do. (C) 2017 Elsevier Ltd. All rights reserved.
Context: Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce.Objective: To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects.Materials and methods: Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20g per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field and formalin tests.Results: 2064H was shown to bind to the serotonin 2C (5-HT2C) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [H-3]-mesulergine with an IC50 value of 179ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first minute of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test.Discussion and conclusion: Overall, manipulating the 5-HT2C receptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds.
Symptoms of post-traumatic stress disorder are common in fibromyalgia patients. This study compared post-traumatic stress disorder symptoms in fibromyalgia patients and healthy controls and determined whether patient-control differences in post-traumatic stress disorder symptoms mediated differences in mental health. In all, 30 patients and 30 healthy controls completed questionnaires assessing symptoms of post-traumatic stress disorder and mental health. Fibromyalgia patients had greater symptoms of post-traumatic stress disorder and mental health than controls. Patient-control differences in mental health symptoms were fully or partially mediated by differences in post-traumatic stress disorder symptoms. Healthcare providers should understand the role of trauma as management of trauma symptoms may be one strategy for improving mental health.
Monitoring distress assessment in cancer patients during the treatment phase is a component of good quality care practice. Yet, there is a dearth of prospective studies examining distress. In an attempt to begin filling this gap and inform clinical practice, we conducted a prospective, longitudinal study examining changes in distress (anxiety, depression, and problems in living) by age and gender and the roles of age and gender in predicting distress. Newly diagnosed Brazilian cancer patients (N = 548) were assessed at three time points during chemotherapy. Age and gender were identified on the first day of chemotherapy (T1); anxiety, depression, and problems in living were self-reported at T1, the planned midway point (T2), and the last day of chemotherapy (T3). At T1, 37 and 17% of patients reported clinically significant levels of anxiety and depression, respectively. At T3, the prevalence was reduced to 4.6% for anxiety and 5.1% for depression (p70 years (p < .03). Female patients reported greater emotional, physical, and family problems than their male counterparts (p < .04). For most patients, elevated levels of distress noted in the beginning of treatment subsided by the time of treatment completion. However, middle-aged and female patients continued to report heightened distress. Evidence-based psychosocial intervention offered to at risk patients during early phases of the treatment may provide distress relief and improve outcomes over the illness trajectory while preventing psychosocial and physical morbidity due to untreated chronic distress.
Individuals with high levels of worry are more likely than others to attend to possible threats, although the extent of top-down attentional control processes on this bias is unknown. We compared the performance of high (n = 26) and low worriers (n = 26) on a probe discrimination task designed to assess attention to threat cues, under cognitive load or no-load conditions. The expected difference between groups was confirmed, with high worriers being more likely to attend to threat cues than low worriers. Importantly however, there were no significant effects involving condition (cognitive load vs. no-load), nor any significant association with self-perceived attentional control ability. These results suggest that pathological worriers are more likely to attend to threat than are individuals with low levels of worry, regardless of task demands on limited cognitive control resources. This finding is consistent with the dominance of habitual bottom-up influences over top-down control processes in biased attention to threat.
Cognitive models of anxiety propose that heightened anxiety vulnerability is characterized by a tendency to interpret ambiguous situations as threatening. The presence of such an interpretive bias has been confirmed in younger adults, using assessment measures that bypass the limitations of self-report and objectively assess interpretive processing. A recent pioneering study published in 2015 has sought to determine whether this anxiety-linked interpretive bias also is evident in older adults. However, their evidence supporting this hypothesis comes only from self-report measures and memory measures. The present study was designed to provide a stronger test of the hypothesis by objectively assessing interpretive process in high (n = 48) and low (n = 48) trait anxious older adults, using a text comprehension approach that circumvents reliance on self-report or memory measures. The findings were fully consistent with the hypothesis that older adults with higher levels of trait anxiety, compared to those with lower levels of trait anxiety, impose more threatening meanings on ambiguous information. These findings provide the first evidence, from an assessment approach that overcomes the limitations of self-report and memory measures, that elevated anxiety vulnerability in older adults is characterized by a negative interpretive bias.
Extensive studies have reported cognitive abnormalities in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Another line of evidence suggests that stress also affects cognitive functions. In this study, we investigated whether there were associations between stress hormones and cognitive functions in ASD and typically developing (TD) children. Cognitive functions in ASD and TD children were evaluated with a battery of psychological tests for working memory, behavioral flexibility, and social cognition for emotional assessments of others. ASD children exhibited higher hair and salivary cortisol, which reflects chronic and acute stress hormone levels of subjects, respectively, than TD children. Autism-spectrum quotient (AQ) was positively correlated with hair cortisol and the scores of Spence Children's Anxiety Scale in ASD children. In addition, a negative correlation was present between spatial working memory performance and hair cortisol in ASD, but not in TD, children. These results suggest that chronic stress hormone elevation may have relationships with some aspects of cognitive dysfunction in ASD subjects. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of IBRO.
According to Attachment Theory (Bowlby, 1980), individual differences in adult attachment styles are based on attachments formed during infancy with primary caregivers. Adults who form secure attachments feel safe and secure in their relationships. Those who form insecure attachments do not. According to Self-Compassion Theory (Neff, 2003a, 2003b), and supported by research, self-compassion (i.e., compassionate attitudes and behaviors towards oneself) is associated with a variety, of positive psychological outcomes, while a lack of self-compassion is associated with psychological distress (e.g., Barnard & Curry, 2011). Additionally, the fear of self-compassion has been negatively associated with self-compassion (Joeng,& Turner, 2015). In this current study, we extend the research on attachment and self-compassion by examining how self-compassion and fear of self-compassion mediate two types of insecure attachment styles, anxious attachment and avoidant attachment, and two indicators of emotional distress, depression and anxiety, among 473 Korean college students. Structural equation modeling indicated that self-compassion independently mediated, and fear of self-compassion and self-compassion serially mediated, the paths from anxious and avoidant attachment to depression and anxiety in expected directions. Results are interpreted from the perspective of Korean culture, including the influence of Confucianism on the expression of self-compassion. (C) 2017 Elsevier Ltd. All rights reserved.
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-proteasome system, is highly expressed in several types of cancers; however, its roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The purpose of this study was to clarify the functional activities of UBE2S in OSCCs. We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC tissues by quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry (IHC). The correlations between UBE2S expression and clinical classifications of OSCCs were analyzed using the IHC scoring system. We also used UBE2S knockdown OSCC cells for functional assays (proliferation assay, flow cytometry, and Western blotting). UBE2S was overexpressed in OSCCs in vitro and in vivo and was correlated significantly (P < 0.05) with the primary tumoral size. The cellular growth was decreased and the cell-cycle was arrested in the G2/M phase in the UBE2S knockdown (shUBE2S) cells. The expression level of P21, a target of the ubiquitin-proteasome system, was increased in the shUBE2S cells because of lower anaphase activity that promotes complex subunit 3 (APC3), an E3 ubiquitin ligase, compared with shMock cells. These findings might promote the understanding of the relationship between UBE2S overexpression and oral cancer proliferation, indicating that UBE2S would be a potential biomarker of and therapeutic target in OSCCs. (C) 2017 Elsevier Inc. All rights reserved.
Objective: To detect the distribution and expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in Melanoma 2 (AIM2) inflammasomes in periapical lesions and to analyse the possible microbial stimuli outside of teeth. Design: The distribution of NLRP3 and AIM2 inflammasomes in sixteen periapical lesions was investigated by immunohistochemistry. Meanwhile, the relative gene expression levels of NLRP3 and AIM2 in sixteen periapical lesions and three health periodontal tissue were quantified by real-time polymerase chain reaction (PCR). Moreover, forty-seven teeth without sinus tracts were obtained in the clinic and included in bacterial analysis using PCR. Then, the mRNA levels of apoptosis-associated speck like protein (ASC), caspase-1, interleukin-1 beta (IL-1 beta), NLRP3 and AIM2 in THP-1-derived macrophages treated with lipopolysaccharides (LPS) of Porphyromonas were also quantified by real-time PCR, and the IL-1 beta secretion level was investigated using enzyme-linked immunosorbent assay (ELISA). Results: NLRP3 and AIM2 were positively expressed in periapical lesions and were mainly distributed in inflammatory cells. Most of the samples that demonstrated up-regulation of NLRP3 mRNA also demonstrated up-regulation of caspase-1 mRNA. Microbial analysis revealed that Porphyromonas endodontalis was the most commonly detected species and was detected in 27 of 47 cases (57.4%), followed by Fusobacterium nucleatum (20/47, 42.6%), Porphyromonas gingivalis (19/47, 40.4%), Tannerella forsythia (19/47, 40.4%), Actinomyces sp. (17/47, 36.17%), Treponema denticola (10/47,21.28%), Actinomyces israelii (9/47,19.15%), Prevotella intermedia (6/47, 12.77%), Enterococcus faecalis (1/47,2.13%) and Enterococcus faecium (0/47,0). Furthermore, we found that LPS of P. gingivalis induced THP-1 cells to produce IL-1 beta and to activate NLRP3 and AIM2 inflammasomes. Conclusions: Our results suggest that the NLRP3 and AIM2 proteins play a part in the pathogenesis of periapical periodontitis. Anaerobes, such as P. endodontalis, P. gingivalis, E nucleatum and T. forsythia, were the main detected microbial stimuli that might activate inflammasomes in periapical tissues. (C) 2017 Elsevier Ltd. All rights reserved.
Aims: Ligands for the vitamin D receptor (VDR) regulate apolipoprotein A-I (apo A-I) gene expression in a tissue-specific manner. The vitamin D metabolite 24, 25-dihydroxycholecalciferol (24, 25-(OH)(2)D(3)) has been shown to possess unique biological effects. To determine if 24, 25-(OH)(2)D(3) modulates apo A-I gene expression, HepG2 hepatocytes and Caco-2 intestinal cells were treated with 24, 25-(OH)(2)D(3) or its precursor 25-OHD(3). Main methods: Apo A-I protein levels and mRNA levels were measured by Western and Northern blotting, respectively. Changes in apo A-I promoter activity were measured using the chlorampenicol acetytransferase assay. Key findings: Treatment with 24, 25-(OH)(2)D(3), but not 25-OHD(3), inhibited apo A-I secretion in HepG2 and Caco-2 cells and apo A-I mRNA levels and apo A-I promoter activity in HepG2 cells. To determine if 24, 25(OH)(2)D(3) represses apo A-I gene expression through site A, the nuclear receptor binding element that is essential for VDRs effects on apo A-I gene expression, HepG2 cells were transfected with plasmids containing or lacking site A. While the site A-containing plasmid was suppressed by 24, 25-(OH)(2)D(3), the plasmid lacking site A was not. Likewise, treatment with 24, 25-(OH)(2)D(3) suppressed reporter gene expression in cells transfected with a plasmid containing site A in front of a heterologous promoter. Finally, antisense-mediated VDR depletion failed to reverse the silencing effects of 24, 25-(OH)(2)D(3) on apo A-I expression. Significance: These results suggest that the vitamin D metabolite 24, 25-(OH)(2)D(3) is an endogenous regulator of apo A-I synthesis through a VDR-independent signaling mechanism. (C) 2010 Elsevier Inc. All rights reserved.
Apolipoprotein E (apoE) is predominantly a lipid transport protein involved in membrane repair and synaptic plasticity in brain. Its genotype is associated with late-onset sporadic and familial Alzheimer's disease (AD). Its expression increases when any injury takes place in the nervous system and in age-related disorders including AD. However, it is not clearly understood how the level of apoE changes in the normal aging brain. Therefore, we have analyzed the effect of age on apoE protein and mRNA level in the cerebral cortex of young, adult, and old male AKR strain mice. Western, northern, and RT-PCR results reveal that the level of apoE protein and mRNA is higher in young as compared to adult and then remains unchanged in old mouse cerebral cortex. This indicates that during normal aging, apoE level is maintained in old similar to adult and suggests involvement of other factors in maintaining apoE-mediated brain functions in old.
A critical process in apoptosis is the permeabilization of the mitochondrial outer membrane (MOM). This process is known to be regulated by the multi-domain Bcl-2 family proteins. For example, the pro-apoptotic proteins Bax and Bak are responsible for forming pores at MOM. The anti-apoptotic proteins (including Bcl-2, Mcl-1 and Bcl-xL), on the other hand, can inhibit this pore-forming process. Interestingly, although these two subgroups of proteins perform opposite apoptotic functions, their structures are very similar. This raises two highly interesting questions: (1) Why do these structurally similar proteins play opposite roles in apoptosis? (2) What are the roles of different functional domains of a Bcl-2 family protein in determining its apoptotic property? In this study, we generated a series of deletion mutants and substitution chimera, and used a combination of molecular biology, bio-informatics and living cell imaging techniques to answer these questions. Our major findings are: (1) All of the Bcl-2 family proteins appear to possess an intrinsic pro-apoptotic property. (2) The N-termini of these proteins play an active role in suppressing their pro-apoptotic function. (3) The apoptotic potency is positively correlated with membrane affinity of the alpha 5/6 helix domains. (4) Charge distribution flanking the alpha 5/6 helices is also important for the apoptotic potency. These findings explain why different members of Bcl-2 family proteins with similar domain composition can function oppositely in the apoptotic process.
BACKGROUND CONTEXT: Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society. PURPOSE: Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells. STUDY DESIGN/ SETTING: This is an "in vitro" fundamental or basic science study. METHODS: Nucleus pulpous cells derived from 15 patients undergoing spinal surgery were treated with interleukin (IL)-1 beta and Fas ligand or etoposide in the presence of NCCM. We determined proor antiapoptotic events using activated caspase assays and determined genomic regulation of apoptosis using polymerase chain reaction arrays validated usingWestern blotting methods. We interrogated cellular apoptotic regulation using JC-1 dye and flow cytometry and performed enzyme-linked immunosorbent assays to evaluate NP inflammatory cytokine secretion. RESULTS: Notochordal cell-conditioned medium inhibits cytotoxic stress-induced caspase-9 and -3/7 activities and maintains the mitochondrial membrane potential in human NPcells, thereby suppressing the intrinsic apoptotic pathway. Gene expression analysis revealed the X-linked inhibitor of apoptosis protein as a key player responsible for evading etoposide-induced apoptosis in the presence ofNCCM, and we verified these data using Western blotting. Enzyme-linked immunosorbent assay results revealed distinct differences in IL-6 and IL-8 secretions by NP cells in response to etoposide in the presence of NCCM. CONCLUSIONS: Here we demonstrate for the first time that NCCM reduces cytotoxic stressinduced apoptosis in human NP cells. Soluble factors present in NCCM could be harnessed for the development of novel therapeutics for the treatment of DDD. (C) 2017 Elsevier Inc. All rights reserved.
PCD (programmed cell death) is important mechanism for development, homeostasis and disease. To analyze the gene expression pattern in brain cells undergoing PCD in response to serum deprivation, we analyzed the cDNA microarray consisting of 2,300 genes and 7 housekeeping genes of cortical cells derived from mouse embryonic brain. Cortical cells were induced apoptosis by serum deprivation.for 8 hours. We identified 69 up-regulated genes and 21 down-regulated genes in apoptotic cells. Based on the cDNA microarray data four genes were selected and analyzed by RT-PCR and northern blotting. To characterize the role of UNC-51-like kinase (ULK2) gene in PCD, we investigated cell death effect by ULK2. And we examined expression of several genes that related with PCD. Especially GAPDH was increased by ULK2. Theses findings indicated that ULK2 is involved in apoptosis through p53 pathway.
Background and Aim: The tumor-suppressing role of Ras-association domain family 1A (RASSF1A) has been described in several systems. In this study, we tested its tumor-suppressing ability and the potential molecular mechanisms in hepatocellular carcinoma (HCC) from Qidong County. Methods: Reverse transcription polymerase chain reaction and Northern blotting were employed to detect the expression of RASSF1A in HCC. After establishing stable RASSF1A (wild type or mutant) expressing 'qi dong gan ai yan jiu suo' ([Qidong Institute of Liver Cancer] QGY)-7703 cell lines, we tested the effects of RASSF1A expression on cell growth by cell proliferation rate, cell colony formation, and cell cycle progression. We also tested the effects of RASSF1A expression on tumorigenesis in nude mice and on cellular sensitivity to mitomycin treatment. Results: The RASSF1A transcript was not found in 75% (three of four) of HCC cell lines and 67% (32/48) of HCC primary biopsies. The stepwise regression analyses indicated that the loss of RASSF1A expression was more frequent in patients who were hepatitis B virus surface antigen positive (HBsAg+) compared to those who were HBsAg(-), both in tumor and corresponding non-cancerous tissues. The wild-type (wt)-RASSF1A expression in the QGY-7703 cell line resulted in fewer and smaller clones, decreased xenograft tumor volume and weight, and G(1)/S arrest in vitro and in vivo. The wt-RASSF1A expression also decreased the cyclin D1 protein expression, which appeared to be at the level of post-transcriptional control. In addition, the wt-RASSF1A expression increased cell growth inhibition and the percentage of cells with sub-G(1) DNA content when the cells were treated with mitomycin. Conclusion: RASSF1A is a tumor suppressor in HCC. The loss of RASSF1A expression may be related to HBsAg+ in hepatocarcinogenesis. Its inactivation may play an important role in the development of HCC.
Background: Neutrophil function is critical for initiation and progression of infecto-inflammatory diseases. Key quorum-sensing plaque bacteria, such as Fusobacterium nucleatum, act as bridging species between early and late colonizer pathogens, such as Porphyromonas gingivalis, as the biofilm ages and periodontal inflammation increases. This study is designed to determine impact of different F. nucleatum strains on neutrophil function. Methods: Cells of human promyelocytic leukemia cell line-60 were differentiated into neutrophil-like cells and cultured with F. nucleatum strains of subspecies (ssp.) nucleatum ATCC 25586, ssp. polymorphum ATCC 10953, and ssp. vincentii ATCC 49256. Neutrophil phagocytosis of F. nucleatum strains and neutrophil apoptosis were analyzed by flow cytometry. Superoxide generation was measured by cytochrome C reduction in the presence and absence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) (1 mu M) stimulation. Proinflammatory cytokine release was determined after 2, 6, and 24 hours of culture in the presence/absence of different F. nucleatum strains. Expression of Toll-like receptor (TLR) 2, TLR4, and nuclear factor (NF)-kappa B mRNA levels were analyzed using real-time quantitative polymerase chain reaction. Each experiment was repeated at least three times in triplicate. Data were analyzed using analysis of variance followed by post hoc Bonferroni correction. Results: All strains of F. nucleatum significantly increased phagocytic capacity of neutrophils. Neutrophil phagocytosis of F. nucleatum ssp. polymorphum was significantly greater than that of F. nucleatum ssp. vincentii and ssp. nucleatum (P < 0.001). F. nucleatum ssp. nucleatum and ssp. polymorphum significantly blocked fMLP-induced superoxide generation (P < 0.001). Although F. nucleatum vincentii also reduced superoxide generation (25%), the impact was not as strong as that of ssp. nucleatum (83%) and ssp. polymorphum (100%). All F. nucleatum strains stimulated significant increase in neutrophil apoptosis compared with control (P < 0.001) and significantly increased expression of NF-B-k mRNA in neutrophils (P < 0.05). Levels of interleukin-8 and tumor necrosis factor-alpha produced by neutrophils were significantly increased in all F. nucleatum groups compared with control (P < 0.001). Conclusions: These findings suggest that different strains of F. nucleatum impact neutrophil function in different ways. Two of three subspecies blocked neutrophil superoxide generation in response to a secondary stimulus, preventing oxidative killing by neutrophils. The direct role of bridging species in pathogenesis of periodontitis may be greater than previously suspected in which they create a favorable environment for pathogenic transition of the dental ecosystem.
Background/Aims: High-glucose (HG)-induced mesangial apoptosis and fibrogenesis possibly involves reactive oxygen species (ROS) formation and activated mitochondrial stress. We investigated the therapeutic effect of the antioxidant N-acetylcysteine (NAC) on cellular apoptosis and matrix accumulation in HG-treated rat mesangial cells (RMCs). Methods: RMCs were cultured in media containing 5 (control) or 35 m M (HG) glucose. Cellular apoptosis was assayed by TdT-mediated dUTP nick-end labeling staining. Collagen and transforming growth factor-1 gene expression were measured by reverse transcriptase-polymerase chain reaction or Northern blotting. Mitochondrial capacity and intracellular ROS generation was assayed by fluorescence microscopy and flow cytometry, respectively. Cellular ATP production and malondialdehyde (MDA) formation were determined by a luciferin-luciferase reaction and high-performance liquid chromatography, respectively. Cytochrome c release, caspase activation and poly(ADP) ribose polymerase cleavage were assayed by Western blotting. Results: HG-treated RMCs displayed enhanced cellular apoptosis (65%) and collagen gene expression (1.8-fold increase); these reactions could be significantly suppressed by 1 m M NAC (p < 0.05). Intracellular ROS generation, production of ATP and MDA, and caspase-3, -8 and -9 activities were significantly increased in HG-treated RMCs, and were effectively attenuated by addition of NAC. Conclusion: It is concluded that NAC prevents HG-induced mesangial apoptosis and fibrogenesis pathways by the reduction of oxidative stress. Copyright (c) 2008 S. Karger AG, Basel
Background: Many microRNAs (miRNAs) have recently been shown to demonstrate critical roles in differentiation, proliferation and migration of vascular smooth muscle cells (VSMCs). Methods and Results: In this study, a certain amount of miRNA expression in VSMCs was evaluated by real-time polymerase chain reaction, and it was found that microRNA-30e (miR-30e) was expressed more strongly than other common vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of function study was performed in vitro and in vivo. It was found that miR-30e in VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore, ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of endogenous miR-30e by luciferase reporter assay, and it was confirmed that overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of IkBa, which is crucial for the NF.B signal pathway. Conclusions: The results of this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs partially through targeting Ube2i and downregulating the I kappa Ba/NF kappa B signaling pathway.
Ascorbic acid plays an important role in the growth and immunity of the sea cucumber, Apostichopus japonicus, a valuable commercial species in China, South Korea, and Japan. In this study, we investigated the dietary ascorbic acid requirements of two newly discovered color morphs of A. japonicus, white and purple, and compared them with that of the common green morph. Six test diets were formulated containing 0, 50, 100, 200, 400, and 800 mg ascorbic acid equivalent per kg, as 1-ascorbyl-2-polyphosphate. The color morphs were fed the test diets for 60 days, and their growth, energy budget, and immunological performance recorded. Dietary ascorbic acid levels had a significant effect on the growth of A. japonicus (P= 200 mg/kg (P < 0.05). Superoxide dismutase (SOD) and catalase (CAT) activities, and total anti-oxidative capacity (T-AOC) were generally higher at dietary ascorbic acid levels of 100, 200, and 400 mg/kg compared with the other treatments. SOD and CAT activities and T-AOC were significantly and positively correlated with SGR, indicating that supplementary dietary ascorbic acid had a beneficial effect on growth and immunity. SGR, energy intake, and the proportion of energy allocated to growth decreased significantly in the white and purple morphs when ascorbic acid levels reached 800 mg/kg (P < 0.05); as did those of the green morph, but not to a significant level. Immune indicators decreased and MDA content increased slightly at 800 mg/kg, indicating that high levels of dietary ascorbic acid do not benefit growth or immunity. The SOD and CAT activities were higher in the purple morph than the green and white morphs, indicatingits superior immune system capacity. Optimum growth and immunity of A. japonicus were achieved at similar to 100 mg/kg of ascorbic acid in the white morph and 200 mg/kg in the green and purple morphs.
Background: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. Methods: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2: 3; mean age =55). Sixty-two percent of samples were adenocarcinomas (used for analysis); the rest consisted of 9% goblet cell, 15% mucinous; 6% pseudomyxoma, and less than 5% carcinoids and 2% neuroendocrine. Tests included sequencing [Sanger, next generation sequencing (NGS)], protein expression/ immunohistochemistry (IHC), and gene amplification [fluorescent in situ hybridization (FISH) or CISH]. Results: Profiling across all appendiceal cancer histological subtypes for IHC revealed: 97% BRCP, 81% MRP1, 81% COX-2, 71% MGMT, 56% TOPO1, 5% PTEN, 52% EGFR, 40% ERCC1, 38% SPARC, 35% PDGFR, 35% TOPO2A, 25% RRM1, 21% TS, 16% cKIT, and 12% for TLE3. NGS revealed mutations in the following genes: 50.4% KRAS, 21.9% P53, 17.6% GNAS, 16.5% SMAD4, 10% APC, 7.5% ATM, 5.5% PIK3CA, 5.0% FBXW7, and 1.8% BRAF. Conclusions: Appendiceal cancers show considerable heterogeneity with high levels of drug resistance proteins (BCRP and MRP1), which highlight the difficulty in treating these tumors and suggest an individualized approach to treatment. The incidence of low TS (79%) could be used as a backbone of therapy (using inhibitors such as 5FU/capecitabine or newer agents). Therapeutic options includeTOPO1 inhibitors (irinotecan/topotecan), EGFR inhibitors (erlotinib, cetuximab), PDGFR antagonists (regorafenib, axitinib), MGMT (temozolomide). Clinical trials targeting pathways involving KRAS, p53, GNAS, SMAD4, APC, ATM, PIK3CA, FBXW7, and BRAF may be also considered. Overall, appendiceal cancers have similar patterns in their molecular profile to pancreatic cancers (can we say this, any statistical analysis done?) and have differential expression from colorectal cancers. These findings indicate the need to evaluate patient samples for patterns in marker expression and alteration, in order to better understand the molecular biology and formulate a personalized therapy approach in these difficult to treat cancers (supported by a grant from Caris Life Sciences).
Background and aims: Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect. Methods: After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology. Results: Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group. Conclusions: This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent. (C) 2017 Elsevier B.V. All rights reserved.
Apples are a widely consumed fruit and have a high polyphenol content. The aim of this study was to analyse the combined effects of osmotic dehydration (OD) and ohmic heating (OH) with a pulsed vacuum (PV) on polyphenol retention during the stored refrigeration of apple cubes. Treatments were performed using a 65 degrees Brix sucrose solution at 30, 40 or 50 degrees C for 120 min, and then, samples were stored for 28 days at 5 degrees C. OH provides an electric field of 13 V cm(-1), and a pulsed vacuum was applied for 5 min at the beginning of the process. The results indicated that a lower temperature process (30-40 degrees C) resulted in the retention of more polyphenol compounds after treatment than a higher temperature process (50 degrees C). Nevertheless, during refrigerated storage, we observed that 50 degrees C preserved these compounds better due to polyphenol oxidase inactivation. PVOD/OH treatment at 50 degrees C was determined to be the best retention of polyphenols from the fresh apple for dehydrating apples.
We developed a 2.5x6.6 mm(2) 2-D array transducer with integrated transmit/receive application-specific integrated circuit (ASIC) for real-time 3-D intracardiac echocardiography (4-D ICE) applications. The ASIC and transducer design were optimized so that the high-voltage transmit, low-voltage time-gain control and preamp, subaperture beamformer, and digital control circuits for each transducer element all fit within the 0.019-mm(2) area of the element. The transducer assembly was deployed in a 10-Fr (3.3-mm diameter) catheter, integrated with a GE Vivid E9 ultrasound imaging system, and evaluated in three preclinical studies. The 2-D image quality and imaging modes were comparable to commercial 2-D ICE catheters. The 4-D field of view was at least 90 degrees x 60 degrees x 8 cm and could be imaged at 30 vol/s, sufficient to visualize cardiac anatomy and other diagnostic and therapy catheters. 4-D ICE should significantly reduce X-ray fluoroscopy use and dose during electrophysiology ablation procedures. 4-D ICE may be able to replace transesophageal echocardiography (TEE), and the associated risks and costs of general anesthesia, for guidance of some structural heart procedures.
Animals domesticated for working closely with humans (e.g. dogs) have been shown to be remarkable in adjusting their behaviour to human attentional stance. However, there is little evidence for this form of information perception in species domesticated for production rather than companionship. We tested domestic ungulates (goats) for their ability to differentiate attentional states of humans. In the first experiment, we investigated the effect of body and head orientation of one human experimenter on approach behaviour by goats. Test subjects (N = 24) significantly changed their behaviour when the experimenter turned its back to the subjects, but did not take into account head orientation alone. In the second experiment, goats (N = 24) could choose to approach one of two experimenters, while only one was paying attention to them. Goats preferred to approach humans that oriented their body and head towards the subject, whereas head orientation alone had no effect on choice behaviour. In the third experiment, goats (N = 32) were transferred to a separate test arena and were rewarded for approaching two experimenters providing a food reward during training trials. In subsequent probe test trials, goats had to choose between the two experimenters differing in their attentional states. Like in Experiments 1 and 2, goats did not show a preference for the attentive person when the inattentive person turned her head away from the subject. In this last experiment, goats preferred to approach the attentive person compared to a person who closed their eyes or covered the whole face with a blind. However, goats showed no preference when one person covered only the eyes. Our results show that animals bred for production rather than companionship show differences in their approach and choice behaviour depending on human attentive state. However, our results contrast with previous findings regarding the use of the head orientation to attribute attention and show the importance of cross-validating results.
Understanding verbal descriptions of everyday actions could involve the neural representation of action direction (avoidance and approach) toward persons and things. We recorded the electrophysiological activity of participants while they were reading approach/avoidance action sentences that were directed toward a target: a thing/a person (i.e., "Petra accepted/rejected Ramn in her group"/ "Petra accepted/rejected the receipt of the bank"). We measured brain potentials time locked to the target word. In the case of things, we found a N400-like component with right frontal distribution modulated by approach/avoidance action. This component was more negative in avoidance than in approach sentences. In the case of persons, a later negative event-related potential (545-750 ms) with left frontal distribution was sensitive to verb direction, showing more negative amplitude for approach than avoidance actions. In addition, more negativity in approach-person sentences was associated with fear avoidance trait, whereas less negativity in avoidance-person sentences was associated with a greater approach trait. Our results support that verbal descriptions of approach/avoidance actions are encoded differently depending on whether the target is a thing or a person. Implications of these results for a social, emotional and motivational understanding of action language are discussed.
In this note, we propose symbolic models for networks of discrete-time nonlinear control systems. If each subsystem composing the network admits an incremental input-to-state stable Lyapunov function and if some small gain theorem-type conditions are satisfied, a network of symbolicmodels, each one associated with each subsystem composing the network, is proposed and shown to be approximately bisimilar to the original network with any desired accuracy.
Background: Approximate string matching is the problem of finding all factors of a given text that are at a distance at most k from a given pattern. Fixed-length approximate string matching is the problem of finding all factors of a text of length n that are at a distance at most k from any factor of length l of a pattern of length m. There exist bit-vector techniques to solve the fixed-length approximate string matching problem in time O(m [l/w]n) and space O(m [l/w] under the edit and Hamming distance models, where w is the size of the computer word; as such these techniques are independent of the distance threshold k or the alphabet size. Fixed-length approximate string matching is a generalisation of approximate string matching and, hence, has numerous direct applications in computational molecular biology and elsewhere. Results: We present and make available libFLASM, a free open-source C++ software library for solving fixed-length approximate string matching under both the edit and the Hamming distance models. Moreover we describe how fixed-length approximate string matching is applied to solve real problems by incorporating libFLASM into established applications for multiple circular sequence alignment as well as single and structured motif extraction. Specifically, we describe how it can be used to improve the accuracy of multiple circular sequence alignment in terms of the inferred likelihood-based phylogenies; and we also describe how it is used to efficiently find motifs in molecular sequences representing regulatory or functional regions. The comparison of the performance of the library to other algorithms show how it is competitive, especially with increasing distance thresholds. Conclusions: Fixed-length approximate string matching is a generalisation of the classic approximate string matching problem. We present libFLASM, a free open-source C++ software library for solving fixed-length approximate string matching. The extensive experimental results presented here suggest that other applications could benefit from using libFLASM, and thus further maintenance and development of libFLASM is desirable.
A high-efficiency method is proposed to suppress magnetic core imbalance in phase-shifted full-bridge (PSFB) converters. Compared with conventional solutions, such as controlling peak current mode (PCM) or adding DC blocking capacitance, the proposed method has several advantages, such as lower power loss and smaller size, because the additional current sensor or blocking capacitor is removed. A time domain model of the secondary side is built to analyze the relationship between transformer core imbalance and cathode voltage of secondary side rectifiers. An approximate control algorithm is designed to achieve asymmetric phase control, which reduces the effects of imbalance. A 60 V/15 A prototype is built to verify the proposed method. Experimental results show that the numerical difference of primary side peak currents between two adjacent cycles is suppressed from 2 A to approximately 0 A. Meanwhile, compared with the PCM solution, the efficiency of the PSFB converter is slightly improved from 93% to 93.2%.
We investigated the changes in the expression profiles of the partially resistant apricot (Prunus armeniaca L.) cultivar Goldrich following inoculation with Plum pox virus (PPV) using cDNA-amplification fragment length polymorphism, (AFLP). Altered expression patterns were detected and twenty-one differentially expressed cDNA had homologies with genes in databases coding for proteins involved in metabolism, signal transduction, defense, stress and intra/intercellular connections. Seven of the modified expressed patterns were further investigated by semi-quantitative RT-PCR or Northern blotting. The expression patterns of five of these genes were confirmed in the partially resistant P armeniaca cv. 'Goldrich' and assessed in a susceptible genotype. One of these cDNAs, coding for a putative class III chitinase, appeared to be repressed in infected plants of the partially resistant genotype and expressed in the susceptible one which could be related to the partially resistant phenotype. On the contrary, the expression patterns of the genes coding for a transketolase, a kinesin-like and an ankyrin-like protein, were clearly linked to the susceptible interaction. These candidate genes could play a role either in the compatible interaction leading to virus invasion or to the quantitative resistance of apricot to PPV (c) 2006 Elsevier B.V. All rights reserved.
Some fruits have a reduced harvesting period or a high degree of perishability, which results in a very short shelf life. Therefore, in order to extend the shelf life of foodstuffs, maintaining low the level at which microbial spoilage and deterioration reactions can occur, fresh fruits have to be treated, obtaining semi-finished products. Those products are commonly used as starting materials by some food industries, like jams', gelatines' and marmalades' ones, due to the extension of their productions throughout the whole year. Among the possible techniques, the Southern Italy industry under study uses three different techniques to produce, package and preserve semi-finished fruits: one based on individually quick freezing, one on low-pressure superheated steam drying with far-infrared radiation, and one on an ohmic aseptic treatment. In the last years, food industries have focused their attention not only towards high quality products but also towards environmental friendly productions. Therefore, the aim of this work is to use a Life Cycle Assessment (LCA) approach to compare the environmental emissions of the three different production and preservation techniques used by the industry under study. The environmental impacts were evaluated using a detailed LCA analysis, normalizing all the consumptions and emissions to the functional unit (one apricots' kg on dry basis). Data were analysed using SimaPro 8.0.5 software, whereas the Ecoinvent database and information collected from the chosen industrial site were used for the life cycle inventory, according to the reference standard for LCA (i.e., ISO 14040-14044). (C) 2017 Elsevier Ltd. All rights reserved.
In this article we investigate if the Swedish consumer prices for electricity are adjusted equally fast regardless of whether the NordPool power market prices are decreased or increased. Due to relatively moderate variations in the variables, we have applied quantile regression, since it is mainly the large changes (above the median) that essentially tend to have a considerable effect on the consumer prices. Moreover, in order to adjust for stochastic- and deterministic trends, autocorrelation, structural breaks as well as to measure APT effects in the short- and in the medium-run, we apply a wavelet decomposition approach. Our results show evidence that significantly positive asymmetric price transmission (APT) effects exist in this market. More specifically, in the short-run (based on the wavelet decomposition D1 for 1-2 months cycles), we find that that there is a higher propensity to rapidly and systematically increase the consumer prices subsequently to an increase in the NordPool market price, compared with the propensity to decrease their customers prices subsequently to a corresponding drop in the NordPool market prices. However, no significant APT effects were detected in the medium- or in the long-run (i.e. the asymmetric price transmission effects are observed only in the short-run). In summary, we could isolate significant APT effects in the short-run (1-2 months decomposition cycles), and for large changes in the dependent variable (percentiles = 0.9). Therefore, only large changes in the NordPool prices lead to feedback effects in the form of asymmetric price transmission effects. Our evidence supports the notion of firms' downward stickiness of retail prices for maximizing profit, which are not expected to be found on a fully efficient market. Although our finding shows that the price inefficiency is short-lived, these large temporal inefficiencies are still costly for the consumers. It should be noted that blunt traditional powerless methods do not detect these APT effects, while our wavelet quantile methods are powerful and make a significant contribution in the literature by providing new empirical evidence.
DNA vaccines had been widely used in animal models against various viral infections, while it was not so convincing for many infectious diseases especially bacterial disease in aquaculture. Interleukin-8(IL-8) as one of the CXC chemokines, its immunological role and adjuvant potential which had been proved in mammals were rarely reported in fish species. In this study, recombination plasmid pcDNA3.1/IL-8(pcIL-8) was conducted and the capacity of IL-8 as molecular adjuvant was explored from several aspects by co-injecting with a DNA vaccine encoding a-enolase(pcENO) against Streptococcus iniae infection in channel catfish. The results suggested that co-injection of pcIL-8 with DNA vaccine increased the innate immunity and specific antibody levels, as well as increased the immune-related genes involving in pro-inflammatory response, humoral and cellular immunity. Moreover, pcIL-8 enhanced the immunoprotection of pcENO with the relative percent survival(RPS) of 60% to 80% against S. iniae infection at 4 week post vaccination(p.v.), with the significantly higher RPS of 73.33% in pcENO+pcIL-8 group compared with that of pcENO alone(53.33%) at challenge test of 8 weeks p.v. Taken together, these results indicate pcIL-8 as a molecular adjuvant co-injected with DNA vaccine not only improves the immunoprotection but also maintains long period of immunity for channel catfish against S. iniae infection. Our study signifies that IL-8 holds promise to serve as a potential adjuvant in DNA vaccines against bacterial infections for long time.
Fish from aquaculture is becoming more important for human consumption. Sustainable aquaculture procedures were developed as an alternative to overcome the negative environmental impacts of conventional aquaculture procedures and wild fisheries. The objective of this contribution is to determine what consumers expect from sustainable aquaculture and whether they prefer sustainable aquaculture products. A combination of qualitative research methods, with think aloud protocols and in-depth interviews, as well as quantitative methods, using choice experiments and face-to-face interviews, was applied. Data was collected in three different cities of Germany. Results revealed that sustainable aquaculture was associated with natural, traditional, local, and small scale production systems with high animal welfare standards. Overall, participants paid a lot of attention to the declaration of origin; in particular fish products from Germany and Denmark were preferred along with local products. Frequently used sustainability claims for aquaculture products were mostly criticized as being imprecise by the participants of the qualitative study; even though two claims tested in the choice experiments had a significant positive impact on the choice of purchase. Similarly, existing aquaculture-specific labels for certified sustainable aquaculture had an impact on the buying decision, but were not well recognized and even less trusted. Overall, consumers had a positive attitude towards sustainable aquaculture. However, communication measures and labelling schemes should be improved to increase consumer acceptance and make a decisive impact on consumers' buying behavior. (C) 2017 Elsevier Ltd. All rights reserved.
This study evaluated the control of streptococcosis outbreaks in Brazil, isolated from diseased sorubim and identified as Lactococcus garvieae by genetic sequencing. This report determined the potential for lactococcosis control in sorubim Pseudoplatystoma sp. with two vaccines: an aqueous-based, whole-cell inactivated vaccine (bacterin) and an oil-adjuvanted bacterin. Their efficacy was evaluated at 30 days post-vaccination (d.p.v.) by challenge with L. garvieae, and the antibody production response at 15, 30 and 60 d.p.v. and the non-specific immune response were compared amongst treatments. High protection levels (P < 0.05) were achieved with the oil-adjuvanted vaccine with a relative percentage survival value of 81.7% at 30 d.p.v. Additionally, the oil-adjuvanted vaccine increased the immunogenicity of the bacterin as indicated by greater agglutination antibody titres from 15 until 60 d.p.v. This is the first report of a positive effect of vaccine administration on the specific immunity of sorubim, and the study showed that a specific antibody plays an important role in sorubim defence against lactococcosis because the innate immune responses were similar in all of the studied animals. These results demonstrated that oil-adjuvanted vaccine can be an effective alternative for the protection of sorubim from L. garvieae disease.
Peyronie's disease (PD) is a localized disorder of the connective tissue of the tunica albuginea (TA) whose etiology has not been elucidated. Although several studies have implicated genetic susceptibility and/or mechanical trauma as triggering events for PD, the underlying molecular mechanisms remain largely unknown. Aquaporin 1 (AQP1) is a water channel protein potentially implicated in connective tissue resistance to mechanical stress, acting primarily by increasing tension within the collagen network. Although it represents a potentially attractive molecular target in PD, to date no studies had ever addressed whether AQP1 is detectable and/or differentially expressed in the TA of these patients. Herein the present study, through immunohistochemical and biochemical approaches, we were able to detect AQP1 expression in the TA of control and PD affected patients. We demonstrated that AQP1-like immunoreactivity and expression are significantly increased in plaques of PD patients Vs controls, implying that AQP1 overexpression might be the consequence of a localized maladaptive response of the connective tissue to repeated mechanical trauma. In summary, these data support the idea that AQP1 might represent a potentially useful biomarker of mechanical injury in the TA and a promising target for the treatment of PD.
The dogfish ortholog of aquaporin 4 (AQP4) was amplified from cDNA using degenerate PCR followed by cloning and sequencing. The complete coding region was then obtained using 5' and 3' RACE techniques. Alignment of the sequence with AQP4 amino acid sequences from other species showed that dogfish AQP4 has high levels (up to 65.3%) of homology with higher vertebrate sequences but lower levels of homology to Agnathan (38.2%) or teleost (57.5%) fish sequences. Northern blotting indicated that the dogfish mRNA was approximately 3.2 kb and was highly expressed in the rectal gland (a shark fluid secretory organ). Semi-quantitative PCR further indicates that AQP4 is ubiquitous, being expressed in all tissues measured but at low levels in certain tissues, where the level in liver >gill >intestine. Manipulation of the external environmental salinity of groups of dogfish showed that when fish were acclimated in stages to 120% seawater (SW) or 75% SW, there was no change in AQP4 mRNA expression in either rectal gland, kidney, or esophagus/cardiac stomach. Whereas quantitative PCR experiments using the RNA samples from the same experiment, showed a significant 63.1% lower abundance of gill AQP4 mRNA expression in 120% SW-acclimated dogfish. The function of dogfish AQP4 was also determined by measuring the effect of the AQP4 expression in Xenopus laevis oocytes. Dogfish AQP4 expressing-oocytes, exhibited significantly increased osmotic water permeability (P-f) compared to controls, and this was invariant with pH. Permeability was not significantly reduced by treatment of oocytes with mercury chloride, as is also the case with AQP4 in other species. Similarly AQP4 expressing-oocytes did not exhibit enhanced urea or glycerol permeability, which is also consistent with the water-selective property of AQP4 in other species.
Aquaporins (AQPs) are a family of small membrane proteins that transport water molecules across the plasma membrane along the osmotic gradient. Mammals express 13 subtypes of AQPs, including the recently reported "subcellular AQPs", AQP11 and 12. Each organ expresses specific subsets of AQP subtypes, and in the inner ear, AQPs are essential for the establishment and maintenance of two distinct fluids, endolymph and perilymph. To evaluate the contribution of AQPs during the establishment of inner ear function, we used quantitative reverse transcription polymerase chain reaction to quantify the expression levels of all known AQPs during the entire development and maturation of the inner ear. Using systematic and longitudinal quantification, we found that AQP11 was majorly and constantly expressed in the inner ear, and that the expression levels of several AQPs follow characteristic longitudinal patterns: increasing (Aqp0, 1, and 9), decreasing (Aqp6, 8, and 12), and peak of expression on E18 (Aqp2, 5, and 7). In particular, the expression level of Aqp9 increased by 70-fold during P3-P21. We also performed in situ hybridization of Aqp11, and determined the unique localization of Aqp11 in the outer hair cells. Immunohistochemistry of AQP9 revealed its localization in the supporting cells inside the organ of Corti, and in the root cells. The emergence of AQP9 expression in these cells was during P3-P21, which was coincident with the marked increase of its expression level. Combining these quantification and localization data, we discuss the possible contributions of these AQPs to inner ear function.
Background: Tick-borne diseases greatly impact human and animal health worldwide, and vaccines are an environmentally friendly alternative to acaricides for their control. Recent results have suggested that aquaporin (AQP) water channels have a key function during tick feeding and development, and constitute good candidate antigens for the control of tick infestations. Methods: Here we describe the effect of vaccination with the Ixodes ricinus AQP1 (IrAQP) and a tick AQP conserved region (CoAQP) on I. ricinus tick larval mortality, feeding and molting. Results: We demonstrated that vaccination with IrAQP and CoAQP had an efficacy of 32% and 80%, respectively on the control of I. ricinus larvae by considering the cumulative effect on reducing tick survival and molting. Conclusions: The effect of the AQP vaccines on larval survival and molting is essential to reduce tick infestations, and extended previous results on the effect of R. microplus AQP1 on the control of cattle tick infestations. These results supports that AQP, and particularly CoAQP, might be a candidate protective antigen for the control of different tick species. (C) 2017 Elsevier Ltd. All rights reserved.
Our previous work supports a role for aquaporin-8 (AQP8) water channels in rat hepatocyte bile formation mainly by facilitating the osmotically driven canalicular secretion of water. In this study, we tested whether a condition with compromised canalicular bile secretion, i.e., the estrogen-induced intrahepatic cholestasis, displays defective hepatocyte AQP8 functional expression. After 17 alpha-ethinylestradiol administration (5 mg center dot kg body wt(-1)center dot day(-1) for 5 days) to rats, the bile flow was reduced by 58% (P < 0.05). By subcellular fractionation and immunoblotting analysis, we found that 34 kDa AQP8 was significantly decreased by similar to 70% in plasma (canalicular) and intracellular (vesicular) liver membranes. However, 17 alpha-ethinylestradiol-induced cholestasis did not significantly affect the protein level or the subcellular localization of sinusoidal AQP9. Immunohistochemistry for liver AQPs confirmed these observations. Osmotic water permeability (P-f) of canalicular membranes, measured by stopped-flow spectrophotometry, was significantly reduced (73 +/- 1 vs. 57 +/- 2 mu m/s) in cholestasis, consistent with defective canalicular AQP8 functional expression. By Northern blotting, we found that AQP8 mRNA expression was increased by 115% in cholestasis, suggesting a posttranscriptional mechanism of protein level reduction. Accordingly, studies in primary cultured rat hepatocytes indicated that the lysosomal protease inhibitor leupeptin prevented the estrogen-induced AQP8 downregulation. In conclusion, hepatocyte AQP8 protein expression is downregulated in estrogen-induced intrahepatic cholestasis, presumably by lysosomal-mediated degradation. Reduced canalicular membrane AQP8 expression is associated with impaired osmotic membrane water permeability. Our data support the novel notion that a defective expression of canalicular AQP8 contributes as a mechanism for bile secretory dysfunction of cholestatic hepatocytes.
Four black fly species of the Simulium striatum species group have been recorded in Thailand. These species are morphologically highly similar in all developmental stages except for the number and arrangement of the pupal gill filaments. In this study, we used multiple characters sources, including morphology, cytology, molecular biology and ecology, to test the hypothesis of conspecificity for S. quinquestriatum (Shiraki), S. nakhonense Takaoka & Suzuki and S. chiangmaiense Takaoka & Suzuki. A molecular study based on the cytochrome c oxidase subunit I (COI) was unable to separate these taxa. In contrast, the elongation complex protein 1 (ECP1) sequences clearly differentiate S. quinquestriatum from S. chiangmaiense and S. nakhonense. However, the latter two taxa could not be differentiated based on molecular DNA sequences. Simulium chiangmaiense and S. nakhonense are also similar in the larval habitat characteristics and have undifferentiated polytene chromosome banding patterns. Morphological examination of the number and arrangement of the pupal gill filaments found a number of intermediate forms. Therefore, S. chiangmaiense and S. nakhonense are apparently the same biological species that is polymorphic for the number and arrangement of gill filaments. Thus, we synonymized S. chiangmaiense with S. nakhonense.
This study evaluated the ambient noise effect of onshore and offshore aquaculture systems on oxidative status and on some immune parameters in gilthead sea bream (Sparus aurata) juveniles. The experiment was performed for 40 days, projecting two different playlists of acoustic stimuli: offshore aquaculture noise condition that created the typical acoustic field in proximity of an offshore sea cage for fish farming, using a random sequence of quite sea background and boat noises; and onshore aquaculture noise condition that represented the acoustic field inside an open concrete tank for fish farming. A third group without any acoustic projection was used as a control. After 40 days from the beginning of acoustic noise, fish exposed to the offshore aquaculture condition showed significantly higher levels of total oxidant status, lysozyme activity, antiprotease activity and white blood cells together with a lower albumin/globulin ratio in comparison to fish from the control group; whereas fish exposed to the onshore condition showed analytical data placed between the other groups, though never significantly different. These results demonstrate that the offshore aquaculture noise, and in particular the sea soundscape, adversely influences the oxidative status and the immune function of gilthead sea bream determining a mild stress condition that could affect the sea bream welfare.
The potential recovery of high-value products from brewery yeast waste confers value to this industrial residue. Aqueous two-phase systems (ATPS) have demonstrated to be an attractive alternative for the primary recovery of biological products and are therefore suitable for the recovery of invertase from this residue. Sixteen different polyethylene glycol (PEG)-potassium phosphate ATPS were tested to evaluate the effects of PEG molecular weight (MW) and tie-line length (TLL) upon the partition behavior of invertase. Concentrations of crude extract from brewery yeast waste were then varied in the systems that presented the best behaviors to intensify the potential recovery of the enzyme. Results show that the use of a PEG MW 400 g mol(-1) system with a TLL of 45.0% (w/w) resulted in an invertase bottom phase recovery with a purification factor of 29.5 and a recovery yield of up to 66.2% after scaling the system to a total weight of 15.0 g. This represents 15.1 mg of invertase per mL of processed bottom phase. With these results, a single-stage ATPS process for the recovery of invertase is proposed. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 886-894, 2016
The function of AZI1 in systemic acquired resistance of Arabidopsis was confirmed by investigation of the phenotypic features of wild-type Col-0, AZI1 T-DNA knockout and AZI1 overexpressing plants after infection with virulent and avirulent Pseudomonas syringae. Real-time quantitative PCR and Northern blotting analyses showed that the transcript abundances of PR genes increased significantly in local and systemic leaves of wild-type Col-0 and AZI1 overexpressing plants challenged with avirulent P. syringae, whereas the mRNA accumulation of PR genes was obviously attenuated in local and systemic leaves of AZI1 T-DNA knockout plants after localized infiltration with avirulent Psm avrRpm1. The changes of metabolomic profiles in distal leaves of three types of materials infected with avirulent P. syringae were determined by H-1 NMR spectrometry and data mining showed that the soluble carbonhydrates might function as signal substances in the systemic immunity of Arabidopsis. At the same time, the expression of the sugar signaling genes in local and distal leaves after infection of avirulent P. syringae was compared. As a result, it was found that the transcript abundances of sugar signaling genes, including SUS1, SUS2, SUS3, SUS6, SUT1, HXK1, HXK2, SNRK1.2, ERD6, TPS1, TOR, SNRK1.1, SNRK1.3 and bZIP11, were obviously changed in distal leaves of different materials with the modulated AZI1 activities, indicating sugar-related genes are involved in regulation of the systemic immunity mediated by AZI1. These results also illustrated that the immune system associated with sugar molecules probably was an important part of the systemic acquired resistance in Arabidopsis. (C) 2016 Elsevier Masson SAS. All rights reserved.
The shape of the inflorescence in Arabidopsis thaliana ecotype Columbia is a raceme with individual flowers developing acropetally. The ecotype Landsberg harboring the erecta (er) mutation shows a corymb-like inflorescence, namely a compact inflorescence with a flattened arrangement of flower buds at the tip. To gain insight into inflorescence development, we previously isolated corymb-like inflorescence mutants, named corymbosal (crm1), and found that the corymb-like inflorescence in crm1-1 was due to reduced cell elongation of pedicels and stem internodes. Double mutants of crm1 with er and crm2, and crm1-1 crm2-1 er-105 triple mutants show an additive phenotype. crm1-1 is caused by a mutation in BIG, which is required for polar auxin transport. CRM1/BIG is expressed in inflorescence meristems, floral meristems and vascular tissues. We analyzed a collection of 12 reduced lateral root formation (rlr) mutants, which are allelic to crm1-1, and categorized the mutants into three classes, depending on the plant developmental defects. Although all 12 alleles had new stop codons, the phenotype of heterozygous crm1-1/doc1-1 and Northern blotting suggest that new crm1/big mutant alleles are hypomorphic. Auxin-responsive DR5rev::GFP expression was decreased in crm1-1 vasculature of pedicels and stem internodes. PINFORMED1 (PIN1) and CRM1/BIG are expressed in vasculature of pedicels and stem internodes. The severity of corymb-like inflorescence in crm1/big mutants correlated with increased levels of PIN1. Our results suggest that CRM1/BIG controls the elongation of the pedicels and stem internodes through auxin action.
Quantitative real-time PCR (qRT-PCR) has become a routine and robust technique for measuring the expression of genes of interest, validating microarray experiments and monitoring biomarkers. However, concerns have been raised over the accuracy of qRT-PCR in China as well as in the rest of the world. We have previously used qRT-PCR to study the response of ANR1 and other root-expressed MADS-box genes to fluctuations in the supply of nitrate, phosphate and sulphate under hydroponic growth conditions. In this study, we have used both Northern blotting and qRT-PCR analyses to confirm the nutritional regulation of MADS-box genes in Arabidopsis thaliana and test whether both technologies produce the same results. The information obtained indicated that the qRT-PCR results are consistent with those obtained by Northern blotting hybridization for all the tested root-expressed MADS-box genes, in response to different nitrate, phosphate and sulphate growth conditions. Furthermore, our novel results showed that the expressions of AGL12, AGL18, and AGL19 were all down regulated in response to S and P re-supply in both qRT-PCR and Northern blotting analyses.
Arabidopsis thaliana is a long established model species for plant molecular biology, genetics and genomics, and studies of A. thaliana gene function provide the basis for formulating hypotheses and designing experiments involving other plants, including economically important species. A comprehensive understanding of the A. thaliana genome and a detailed and accurate understanding of the expression of its associated genes is therefore of great importance for both fundamental research and practical applications. Such goal is reliant on the development of new genetic and genomic resources, involving new methods of data acquisition and analysis. We present here the genome-wide analysis of A. thaliana gene expression profiles across different organs and developmental stages using high-throughput transcriptome sequencing. The expression of 25 706 protein-coding genes, as well as their stability and their spatiotemporal specificity, was assessed in 79 organs and developmental stages. A search for alternative splicing events identified 37 873 previously unreported splice junctions, approximately 30% of them occurred in intergenic regions. These potentially represent novel spliced genes that are not included in the TAIR10 database. These data are housed in an open-access web-based database, TraVA (Transcriptome Variation Analysis, http://travadb.org/), which allows visualization and analysis of gene expression profiles and differential gene expression between organs and developmental stages.
The presented research hypothesis-driven laboratory exercise teaches advanced undergraduate students state of the art methods and thinking in an integrated molecular physiology context. Students understand the theoretical background of iron acquisition in the model plant Arabidopsis thaliana. They design a flowchart summarizing the key steps of the experimental approach. Students are made familiar with current techniques such as qPCR. Following their experimental outline, students grow Arabidopsis seedlings up to the age of six days under sufficient and deficient iron supply. The Arabidopsis plants are of two different genotypes, namely wild type and fit loss of function mutants. fit mutants lack the essential transcription factor FIT, required for iron acquisition and plant growth. Students monitor growth phenotypes and root iron reductase activity in a quantitative and qualitative manner. Then, students determine gene expression regulation of FIT, FRO2, and a reference gene by reverse transcription-quantitative PCR (RT-qPCR). Finally, students interpet their results and build a model summarizing the connections between morphological, physiological and molecular iron deficiency responses. Learning outcomes and suggestions for integrating the course concept are explained. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
Hypersensitive response (HR) is a form of programmed cell death (PCD) and the primary immune response that prevents pathogen invasion in plants. Here, we show that a microRNA miR164 and its target gene NAC4 (At5g07680), encoding a NAC transcription factor, play essential roles in the regulation of HR PCD in Arabidopsis thaliana. Cell death symptoms were noticeably enhanced in NAC4-overexpressing (35S:NAC4) and mir164 mutant plants in response to avirulent bacterial pathogens. NAC4 expression was induced by pathogen infection and negatively regulated by miR164 expression. NAC4-binding DNA sequences were determined by in vitro binding site selection using random oligonucleotide sequences. Microarray, chromatin immunoprecipitation and quantitative real time polymerase chain reaction (qRT-PCR) analyses, followed by cell death assays in protoplasts, led to the identification of NAC4 target genes LURP1, WRKY40 and WRKY54, which act as negative regulators of cell death. Our results suggest that NAC4 promotes hypersensitive cell death by suppressing its target genes and this immune process is fine-tuned by the negative action of miR164.
Hydrogen peroxide (H2O2) acts as a signaling molecule modulating the expression of various genes in plants. However, the reference gene(s) used for gene expression analysis of H2O2 signaling is still arbitrary. A reliable result obtained by quantitative real-time RT-PCR (RT-qPCR) highly depends on accurate transcript normalization using stably expressed reference genes, whereas the inaccurate normalization could easily lead to the false conclusions. In this report, by using geNorm and NormFinder algorithms, 12 candidate reference genes were evaluated and compared in root and shoot tissues of Arabidopsis upon different doses of H2O2. The results revealed that, in our experimental conditions, three novel reference genes (TIP41-like, UKN, and UBC21) were identified and validated as suitable reference genes for RT-qPCR normalization in both root and shoot tissues under oxidative stress. This conclusion was further confirmed by publicly available microarray data of methyl viologen and drought stress. In comparison with a single reference gene (EF-1a), the expression pattern of ZAT12 modulated by H2O2, when using TIP41-like, UKN, and UBC21 as multiple reference gene(s), was similar with the previous reports by using northern blotting. Thus, we proposed that these three reference genes might be good candidates for other researchers to include in their reference gene validation in gene expression studies under H2O2-related oxidative stress.
Cotton (Gossypium L.) fiber is a unique experimental system for studying plant cell elongation and cell wall biogenesis. Arabinogalactan proteins (AGPs) are extracellular proteoglycans and play important roles in various aspects of plant growth and development. In the present work, four AGP genes, GhAGP2, GhAGP3, GhAGP4, and GhFLA1, were cloned from cotton fiber through 5' and 3' rapid amplification of cDNA ends (RACE). All these genes code for classical AGPs containing N-terminal signal sequence, a central domain rich in Ala, Ser, Thr, Pro/Hyp, and C-terminal hydrophobic transmembrane domain. Additionally all the four putative proteins contain two AGP-like domains, one fasciclin-like domain and a putative C-terminal glycosylphosphatidylinositol lipid anchor signal sequence. Northern blotting analysis with gene-specific probes indicates the transcripts of GhAGP2 and GhFLA1 accumulate in Gossypium hirsutum fiber from 5 to 20 days post anthesis, whereas GhAGP3 and GhAGP4 are abundantly expressed during the developmental stage switching from elongation to the secondary cell wall synthesis. Furthermore, quantitative reverse transcription polymerase chain reaction analysis demonstrates that all these fasciclin-like AGP genes are specifically expressed not only in G. hirsutum fibers but also in Gossypium barbadense fibers. The fasciclin-like domains are typically found in adhesion proteins of animal cell, and the specific expression patterns together with presence of fasciclin-like domains suggest roles for fasciclin-like AGPs in cell-to-cell communication during cotton fiber elongation and secondary cell wall development.
Eicosanoids derive from essential polyunsaturated fatty acids (PUFA) and play crucial roles in immunity, development, and reproduction. However, potential links between dietary PUFA supply and eicosanoid biosynthesis are poorly understood, especially in invertebrates. Using Daphnia magna and its bacterial parasite Pasteuria ramosa as model system, we studied the expression of genes coding for key enzymes in eicosanoid biosynthesis and of genes related to oogenesis in response to dietary arachidonic acid and eicosapentaenoic acid in parasite exposed and non-exposed animals. Gene expression related to cyclooxygenase activity was especially responsive to the dietary PUFA supply and parasite challenge, indicating a role for prostanoid eicosanoids in immunity and reproduction. Vitellogenin gene expression was induced upon parasite exposure in all food treatments, suggesting infection-related interference with the host's reproductive system. Our findings highlight the potential of dietary PUFA to modulate the expression of key enzymes involved in eicosanoid biosynthesis and reproduction and thus underpin the idea that the dietary PUFA supply can influence invertebrate immune functions and host-parasite interactions. (C) 2016 Elsevier Inc. All rights reserved.
World experts of different disciplines, from molecular biology to macroecology, recognize the value of cave ecosystems as ideal ecological and evolutionary laboratories. Among other subterranean taxa, spiders stand out as intriguing model organisms for their ecological role of top predators, their unique adaptations to the hypogean medium and their sensitivity to anthropogenic disturbance. As the description of the first eyeless spider (Stalita taenaria), an array of papers on subterranean spider biology, ecology and evolution has been published, but a comprehensive review on these topics is still lacking. We provide a general overview of the spider families recorded in hypogean habitats worldwide, we review the different adaptations of hypogean spiders to subterranean life, and we summarize the information gathered so far about their origin, population structure, ecology and conservation status. Finally, we point out the limits of the knowledge we currently have regarding hypogean spiders, aiming to stimulate future research.
Arbuscular mycorrhiza (AM) formed between plant roots and fungi is one of the most widespread symbiotic associations in nature. To understand the molecular mechanisms of AM formation, we profiled 30 symbiosis-related genes expressed in Amorpha fruticosa roots colonized by Glomus mosseae and in non-mycorrhizal roots at different stages using differential-display RT-PCR (DDRT-PCR). The expressed genes were confirmed by reverse Northern blotting. Eleven fragments were sequenced and putatively identified by homologous alignment. Of the eleven AM-related genes, five were obtained at the early-stage of plant-fungus interaction and six at the later stage. Three expressed sequence tag (ESTs) sequences were found to originate from the fungi and eight from the host plant by use of PCR evaluation of gDNA of both plant and fungi. The target genes included an ATP-binding cassette sub-family transporter gene, a transposon-insertion display band, and a photosynthesis-related gene. The results provided information on the molecular mechanisms underlying the development of mycorrhizal symbiosis between woody plants and AM fungi.
Arbuscular mycorrhizal fungi (AMF) occur in the majority of terrestrial, and some aquatic, habitats worldwide. They are important for the functioning of individual plants and of entire ecosystems. Here, we review trends in research on species-(species recognition, phylogenetic relationships, autecology) and community-level AMF diversity patterns and aim to identify ways of improving the complementarity of these approaches. Research into many aspects of AMF diversity has flourished in parallel with the increasing availability of molecular biology techniques. However, despite their shared goal of understanding AMF biodiversity, species- and community-level perspectives, and the morphological and molecular approaches that underpin them, currently have limited capacity for information exchange. We indicate critical research gaps in AMF species and community characterisation and outline important research directions. We propose steps that could link research using different methods and targeting different aspects of diversity, in order to maximise our understanding of AMF. (C) 2016 Elsevier Ltd and British Mycological Society. All rights reserved.
Archaea are widespread organisms colonizing almost every habitat on Earth. However, the molecular biology of archaea still remains relatively uncharacterized. RNA metabolism is a central cellular process, which has been extensively analyzed in both bacteria and eukarya. In contrast, analysis of RNA metabolism dynamic in archaea has been limited to date. To facilitate analysis of the RNA metabolism dynamic at a system-wide scale in archaea, we have established non-radioactive pulse labeling of RNA, using the nucleotide analog 4-thiouracil (4TU) in two commonly used model archaea: the halophile Euryarchaeota Haloferax volcanii, and the thermo-acidophile Crenarchaeota Sulfolobus acidocaldarius. In this work, we show that 4TU pulse labeling can be efficiently performed in these two organisms in a dose-and time-dependent manner. In addition, our results suggest that uracil prototrophy had no critical impact on the overall 4TU incorporation in RNA molecules. Accordingly, our work suggests that 4TU incorporation can be widely performed in archaea, thereby expanding the molecular toolkit to analyze archaeal gene expression network dynamic in unprecedented detail.
Relative to other historic documents, newspapers have received little attention from researchers as a source of archaeological data. Now that many historic newspapers have been digitized and placed online, this traditionally underutilized resource has the potential to yield new information about archaeological sites, especially those in heavily developed urban areas where sites are inaccessible or have been destroyed. In this article, a methodology is proposed by which archived newspapers might be searched for data about archaeological sites. A case study using newspapers from Allen County, Indiana and its principal city, Fort Wayne, demonstrates the utility of the methodology by producing evidence about many previously unrecorded archaeological sites.
Some species of the Arcobacter genus are considered emerging foodborne and waterborne en. However, the presence of Arcobacter spp. in vegetables very little is known, because most studies have focused on foods of animal origin. On the other hand, quinolones are considered as first-line drugs for the treatment of infection by campylobacteria in human patients, but few data are currently available about the resistance levels to these antibiotics among Arcobacter species. Therefore, the aim of this study was to investigate the presence and diversity of arcobacters isolated from fresh vegetables such as lettuces, spinaches, chards and cabbages. Resistance to quinolones of the isolates was also investigated. One hundred fresh vegetables samples purchased from seven local retail markets in Valencia (Spain) during eight months were analysed. The study included 41 lettuces, 21 spinaches, 34 chards and 4 cabbages. Samples were analysed by culture and by molecular methods before and after enrichment. By culture, 17 out of 100 analysed samples were Arcobacter positive and twenty-five isolates were obtained from them. Direct detection by PCR was low, with only 4% Arcobacter spp. positive samples. This percentage increased considerably, up 20%, after 48 h enrichment. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), 17 out of the 25 isolates were identified as A. butzleri and 8 as A. cryaerophilus. Only two A. butzleri isolates showed resistance to levofloxacin and ciprofloxacin. The sequencing of a fragment of the QRDR region of the gyrA gene from the quinolones-resistant isolates revealed the presence of a mutation in position 254 of this gene (C-T transition). This study is the first report about the presence of pathogenic species of Arcobacter spp. in chards and cabbages and confirms that fresh vegetables can act as transmission vehicle to humans. Moreover, the presence of A. butzleri quinolone resistant in vegetables could pose a potential public health risk. (C) 2017 Elsevier Ltd. All rights reserved.
This work aimed to determine the presence of Arcobacter spp. in shellfish and to determine its susceptibility to quinolones. One hundred samples (41 mussels, 37 clams, and 22 cockles) were purchased from different local retail shops in Valencia, Spain, from September 2013 to June 2015. All samples were analyzed simultaneously by culture, after an enrichment step, and by polymerase chain reaction (PCR), directly and after enrichment. The susceptibility to levofloxacin and ciprofloxacin of the isolates was tested using the disk-diffusion test and E-test strips method. To clarify the mechanism of quinolone resistance, a fragment of the quinolone resistance-determining region of the gyrA gene was sequenced. Thirty-seven samples were positive and 49 isolates were obtained by culture, and Arcobacter spp. DNA was detected in 32% of the samples by PCR. However, after 48-h enrichment, the number of positive samples increased, and 68 of the 100 samples yielded the specific Arcobacter spp. PCR product. In addition, 49 isolates were identified by PCR-restriction fragment length polymorphism. The most commonly found species was Arcobacter butzleri (25 isolates, 51.03%) followed by Arcobacter cryaerophilus (19 isolates, 38.77%) and Arcobacter defluvii (5 isolates, 10.20%). Only three isolates of A. butzleri were resistant to both antibiotics. A mutation C to T transition in the position 254 of the gyrA gene was present in the three resistant isolates. This study confirms that pathogenic arcobacters are frequently found in edible shellfish samples. Moreover, this is the first time that A. butzleri and A. cryaerophilus have been isolated from cockles.
Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ER beta largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4(+) T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ER beta-dependent manner. Moreover, arctigenin was recognized to be an agonist of ER beta, which could bind to ER beta with a moderate affinity, promote dissociation of ER beta/HSP90 complex and nuclear translocation and phosphorylation of ER beta, and increase the transcription activity. Following activation of ER beta, arctigenin inhibited the activity of mTORC1 by disruption of ER beta-raptor-mTOR complex assembly. Deficiency of ER beta markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ER beta, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ER beta might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.
A method that can be used to more easily perform human body communication, (HBC) has been developed. In the proposed method, Arduino technology is used as a wearable device. Baseband communication is used in this study. Baseband communication uses an operational amplifier to amplify the signal generated by the Arduino, device and uses a comparator to remove noise. This study experimented with a biological tissue equivalent phantom. An application was developed to measure temperature and confirm the transmission and reception of a string. We successfully transmitted a string using HBC with a simple circuit. In addition, changes in impedance and voltage in the electrode were measured. Our experimental results confirm effective HBC in the 300 Hz band.
Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide ( NO) generation due to decreased endothelial NO synthase ( eNOS) activity is a crucial parameter characterizing ECD. L-arginine is the sole precursor for NO biosynthesis. Among several transporters that mediate L-arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major determinant of eNOS activity in CRF. We studied glomerular and aortic arginine uptake, CAT-1, and CAT-2 messenger ribonucleic acid ( mRNA) expression, and CAT-1 protein in: ( a) rats 6 weeks following 5/6 nephrectomy ( CRF), (b) sham-operated animals, and ( c) rats with CRF treated orally with either atorvastatin or arginine in drinking water (modalities which have been shown to enhance eNOS activity and improve endothelial function). Both glomerular and aortic arginine transport were significantly decreased in CRF. Treatment with either arginine or atorvastatin abolished the decrease in arginine uptake in CRF rats. Using reverse transcriptase-polymerase chain reaction and Northern blotting, we found a significant increase in glomerular and aortic CAT-1 mRNA expression in CRF. Western blotting revealed that CAT-1 protein was decreased in CRF, but remained intact following arginine and atorvastatin administration. Renal and systemic arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These findings provide a possible novel mechanism to eNOS inactivation and endothelial dysfunction in uremia.
We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or indirectly via maternal social cognition. Participants were 207 (105 European-American and 102 African-American) mothers and their children (52% females). Sensitive maternal behavior was rated and aggregated across a series of tasks when infants were 6 months, 1 year and 2 years old. At 6 months, mothers were interviewed about their empathy, attributions about infant behavior and beliefs about crying to assess their parenting-related social cognition. Mothers with long alleles for AVPR1a and DRD4 engaged in more mother-oriented social cognition (i.e. negative attributions and beliefs about their infants' crying, beta = 0.13, P < 0.05 and beta = 0.16, P < 0.05, respectively), which in turn predicted less sensitive maternal behavior (beta = -0.23, P < 0.01). Both indirect effects were statistically significant independent of one another and covariates [95% confidence interval (CI): -0.22, -0.03 and beta = -0.03 for AVPR; 95% CI: -0.20, -0.03 and beta = -0.04 for DRD4]. There were no significant direct effects of AVPR1a or DRD4 on maternal sensitivity (beta = 0.02, P = .73 and beta = -0.10, P = .57, respectively). The results did not vary for African-American and European-American mothers (Delta chi(2) = 18.76, Delta df = 16, P = 0.28). Results support the view that one mechanism by which maternal genes are associated with parental behavior is via social cognition.
New Findings What is the central question of this study? Can the change in plasma arginine vasopressin concentration (P-[AVP]) in response to osmotic stimulation (P-Osm) serve as a biomarker for NMDA receptor signalling in schizophrenia and depression and thereby distinguish between these mental illnesses? What is the main finding and its importance? In response to hyperosmotic challenge, depressed subjects showed increased P-[AVP] response compared with healthy control and schizophrenic subjects. However, schizophrenic subjects were not different from healthy control subjects in this small sample. The P-[AVP] response to P-Osm' is a suitable biomarker to distinguish depressed versus schizophrenic patients when used with psychiatric screening. This is the first objective physiological measure for schizophrenia or depression. Altered NMDA receptor activity and glutamate signalling might underlie the pathogenesis of both schizophrenia and depression in subgroups of patients. In schizophrenia, pharmacological modelling, post-mortem and imaging data suggest reduced NMDA signalling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signalling. We conducted a proof-of-concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function. For this purpose, we used a translational approach, based on findings from animal studies that NMDA receptor is a key mediator of arginine vasopressin (AVP) release into the bloodstream. Using hypertonic saline to increase plasma osmolality (P-Osm) and thereby induce AVP release, as done in animal studies, we found that in depressed patients the NMDA receptor-mediated AVP release induced by hypertonic saline infusion was significantly increased [0.24 (0.15) pgml(-1)mosmol(-1), P<0.05] compared with schizophrenia patients [0.07 (0.07) pgml(-1)mosmol(-1)]. Slopes for healthy control subjects were 0.11 (0.09) pgml(-1)mosmol(-1) which was less than the depressed group. These findings are consistent with implicated NMDA receptor-related abnormalities in depression and schizophrenia in subgroups of patients and provide the first in vivo evidence of this dichotomy.
Arginine (Arg) presents a potent growth hormone (GH) releasing activity. in vivo and in vitro studies carried out in our laboratory have demonstrated that acute treatment with Arg also increases GH gene expression. Taking into account the recognizable diabetogenic role of GH and that Arg increases insulin release, this study aimed at evaluating the effects of oral chronic administration of Arg on GH gene expression, by Northern blotting analysis, and on the insulin sensitivity, by means of the Insulin Tolerance Test (ITT), blood glucose decay rate (kitt) and insulin plasma concentration. We demonstrated that rats that consumed Arg (similar to 35 mg/day) in drinking water, during 4 weeks, presented an increase in GH mRNA content (p < 0.01), a decreased peripheral response to insulin, as shown by the reduced blood glucose decay rate (p < 0.05), and a higher insulin plasma concentration (p < 0.01) than control group. Arg treatment did not modify the animals' food and water intake, while it decreased the heart rate and the arterial blood pressure compared to control group (P < 0.05). According to the results presented herein we conclude that chronic oral administration of arginine increases GH gene expression and induces insulin resistance. The arterial blood pressure decrease has already been pointed out in the literature, and seems to occur in response to the dilating effect of nitric oxide generated from Arg, as well as from NO generation in central and peripheral neuronal populations that express NOS and are involved in the autonomic regulation of the cardiac function. (c) 2006 Elsevier Inc. All rights reserved.
Antimicrobial peptides are important components of the host innate immune responses by exerting broad-spectrum microbicidal activity against pathogenic microbes. The first mollusk big defensin (designated AiBD) cDNA was cloned from bay scallop Argopecten irradians by expressed sequence tag (EST) and rapid amplification of cDNA ends (RACE) techniques. The scallop AiBD consisted of 531 nucleotides with a canonical polyadenylation signal sequence AATAAA and a poly(A) tail, encoding a polypeptide of 122 amino acids. The high similarity of AiBD deduced amino acid sequence with big defensin from Tachypleus tridentatus and Branchiostoma belcheri tsingtaunese indicated that AiBD should be a member of big defensin family. The expression of AiBD in various tissues was measured by using Northern blotting analysis. mRNA transcripts of AiBD could be detected in haemocytes of unchallenged scallops. The temporal expression of AiBD in haemolymph after Vibrio anguilarum challenge was recorded by quantitative real time PCR. The relative expression level of AiBD in haemolymph was up-regulated evenly in the first 8 h, followed by a drastic increase, and increased 131.1-fold at 32 h post-injection. These results indicated that AiBD could be induced by bacterial challenge, and it should participate in the immune responses of A. irradians. Biological activity assay revealed that recombinant AiBD could inhibit the growth of both Gram-positive and Gram-negative bacteria, and also showed strong fungicidal activity towards the expression host. Recombinant expression of AiBD made it possible to further characterize its functions involved in immune responses, and also provided a potential therapeutic agent for disease control in aquaculture. (c) 2006 Elsevier Ltd. All rights reserved.
Background: Long-acting injectable antipsychotics are treatment options for acute and long-term treatment of patients with schizophrenia. In a previously published 12-week randomized, double-blind, placebo-controlled clinical trial of patients with schizophrenia experiencing an acute psychotic episode, aripiprazole once-monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at week 10. Methods: To examine the efficacy of AOM 400 across a broader representation of schizophrenia symptoms, including agitation, a post hoc analysis of this trial was carried out to assess the change in PANSS Marder factor domains (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression) and the PANSS excited component (equivalent to Marder factor domain uncontrolled hostility/excitement plus the tension item) by comparing differences in change from baseline between AOM 400 and placebo using a mixed model for repeated measures. Results: The differences between treatment and placebo for all factors were statistically significant, with improvements seen as early as week 1 or 2, and maintained through week 12. Thus, AOM 400, supplemented with oral aripiprazole in the first 2 weeks, showed significantly greater efficacy versus placebo in acutely ill patients with schizophrenia in all 5 Marder illness domains, as well as in agitation as conceptualized by the PANSS excited component score. Conclusions: These findings indicate that AOM 400 is efficacious across the spectrum of schizophrenia symptoms in acutely ill patients, with implications for both short-term and, by extension, long-term patient outcomes.
This paper develops Bayesian inference of extreme value models with a flexible time-dependent latent structure. The generalized extreme value distribution is utilized to incorporate state variables that follow an autoregressive moving average (ARMA) process with Gumbel-distributed innovations. The time-dependent extreme value distribution is combined with heavy-tailed error terms. An efficient Markov chain Monte Carlo algorithm is proposed using a state-space representation with a finite mixture of normal distributions to approximate the Gumbel distribution. The methodology is illustrated by simulated data and two different sets of real data. Monthly minima of daily returns of stock price index, and monthly maxima of hourly electricity demand are fit to the proposed model and used for model comparison. Estimation results show the usefulness of the proposed model and methodology, and provide evidence that the latent autoregressive process and heavy-tailed errors play an important role to describe the monthly series of minimum stock returns and maximum electricity demand.
Superconducting synchronous generators (SCSGs) are drawing more attention in large direct-drive wind turbine applications. Despite low weight and compactness, the short circuit torque of an SCSG may be too high for wind turbine constructions due to a large magnetic air gap of an SCSG. This paper aims at assessing the effects of armature winding segmentation on reducing the short circuit torque of 10-MW SCSGs. A concept of armature winding segmentation with multiple power electronic converters is presented. Four SCSG designs using different topologies are examined. Results show that armature winding segmentation effectively reduce the short circuit torque in all the four SCSG designs when one segment is shorted at the terminal.
A detailed discussion on genesis, determinant and algorithmic method of the harmonic distortion of Switched Capacitor integrator and Switched-Capacitor based second order Sigma-Delta modulator is presented. In many instances, people make harmonic distortion analysis of signal through expanding periodic signal into Fourier series or making Fourier transformation for non-periodic signal respectively. Actually, due to the complexity of transient response of Switched-Capacitor integrator, the output expression of second-order Sigma-Delta modulator loop filter is also not trivial, so we will be in great trouble if traditional method is employed when its harmonics are analyzed and calculated in such a way. A fact that is noteworthy is no matter how complicated the output response of the second integrator of the modulator is, its harmonic expression has the same functional form whether in the whole time domain or at the discrete time moments. From this we turn the harmonic analysis of the continuous-time transient response into another thing, namely computing the harmonic coefficients of the transient response at discrete time moments. The least square method is adopted in process of calculation. When developing the output expression of second-order Sigma-Delta modulator, the following point is clarified, that the harmonic distortion is dominated by the first Switched-Capacitor integrator, owing to the suppression resulted from the closed feedback of harmonic distortion of the second stage is much greater than the first stage. In addition, it is avoided that the harmonic distortion is once again brought into the feedback signal in calculation, through the way that first the additive harmonic error model is utilized to get the transfer function, second replaced by gain model in the form of power series. And by doing so, both the feasibility and simplicity of the analysis and mathematical derivation are enhanced effectively.
Aim: This study aimed to evaluate the benefits of Arnica montana on post-operative blood loss and seroma production in women undergoing unilateral total mastectomy by administering Arnica Montana 1000 Korsakovian dilution (1000 K). Materials and Methods: From 2012 to 2014, 53 women were randomly assigned to A. montana or placebo and were followed up for 5 days. The main end point was the reduction in blood and serum volumes collected in drainages. Secondary end points were duration of drainage, a self-evaluation of pain, and the presence of bruising or hematomas. Results: The per-protocol analysis revealed a lower mean volume of blood and serum collected in drainages with A. montana (-94.40 ml; 95% confidence interval [CI]: 22.48-211.28; P = 0.11). A regression model including treatment, volume collected in the drainage on the day of surgery, and patient weight showed a statistically significant difference in favor of A. montana (-106.28 ml; 95% CI: 9.45-203.11; P = 0.03). Volumes collected on the day of surgery and the following days were significantly lower with A. montana at days 2 (P = 0.033) and 3 (P = 0.0223). Secondary end points have not revealed significant differences. Conclusions: A. montana 1000 K could reduce post-operative blood and seroma collection in women undergoing unilateral total mastectomy. Larger studies are needed with different dilutions of A. montana to further validate these data.
Among recent high profile scientific debates was the proposal that life could exist with arsenic in place of phosphorous in its nucleic acids and other biomolecules. Soon after its initial publication, scientists across diverse disciplines began to question this extraordinary claim. Using the original article, its claims, its scientific support, and the ensuing counterarguments, a two-day, active learning classroom exercise was developed focusing on the presentation, evaluation, and discussion of scientific argumentation and discourse. In this culminating assignment of a first semester biochemistry course, undergraduate students analyze the scientific support from the original research articles and then present and discuss multiple scientific rebuttals in a lively, civil classroom debate. Through this assignment, students develop a sense of skepticism, especially for the original arsenic-based life claims, and learn to clearly articulate their counterarguments with scientific support and critical reasoning. With its direct integration into first-semester biochemistry curriculum and the excitement surrounding arsenic based life, this assignment provides a robust, simple, and stimulating framework for introducing scientific discourse and active learning into the undergraduate molecular science curriculum. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):40-45, 2017.
Artemisinin, a sesquiterpene lactone isolated from Artemisia annua L. (sweet wormwood), is extensively used in the treatment of malaria. In order to better understand the metabolism of terpenes in A. annua and the influence of terpene synthases on artemisinin yield, the expression pattern of a monoterpene alcohol dehydrogenase (ADH2) has been studied using transgenic plants expressing promoter-beta-glucuronidase (GUS) fusion. ADH2 played a major role in monoterpenoid biosynthesis including carveol, borneol, and artemisia ketone through in vitro biochemical analysis. In this study, the ADH2 promoter was cloned by the genome walking method. A number of putative cis-acting elements were predicted in promoter region, suggesting that the ADH2 is driven by a complex regulation mechanism. ADH2 gene was highly expressed in old leaves, whereas the artemisinin biosynthetic genes were mainly expressed in bud and young leaves. The expression of ADH2 gene increased quickly during leaf development, revealed by qRT-PCR. GUS expression analysis in different tissues of transgenic A. annua demonstrates that ADH2 expression is exclusively located to T-shaped trichome, not glandular secretory trichome. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 834-840, 2016
Two newly established canine histiocytic sarcoma (HS) cell lines, designated as PWC-HS01 and FCR-HS02, were obtained from brain and articular tumors, respectively. These 2 HS cell lines had phagocytic ability and modal chromosome aberrations. Although morphologic features of both HS cells were similar, immunocytochemical examinations revealed that the PWC-HS01 cell line expressed both dendritic cell (ie, S100, CD208, CD1, and CD4) and macrophage (ie, CD68, CD163, and CD204) markers. In contrast, the FCR-HS02 cell line was immunonegative for CD204 and CD68 but consistently positive for the dendritic cell markers. Moreover, reverse transcription polymerase chain reaction analyses confirmed histiocytic differentiation of both HS cell lines. These results suggest that HS from the central nervous system may have a tendency to be more undifferentiated compared with cases from other organs. In addition, the 2 newly established HS cell lines were also tumorigenic and metastatic in immunodeficient mice, supporting that these cell lines can be used as new tumor models for investigating canine histiocytic diseases.
shmiRs are pri-miRNA-based RNA interference triggers from which exogenous siRNAs are expressed in cells to silence target genes. These reagents are very promising tools in RNAi in vivo applications due to their good activity profile and lower toxicity than observed for other vector-based reagents such as shRNAs. In this study, using high-resolution northern blotting and small RNA sequencing, we investigated the precision with which RNases Drosha and Dicer process shmiRs. The fidelity of siRNA release from the commonly used pri-miRNA shuttles was found to depend on both the siRNA insert and the pri-miR scaffold. Then, we searched for specific factors that may affect the precision of siRNA release and found that both the structural features of shmiR hairpins and the nucleotide sequence at Drosha and Dicer processing sites contribute to cleavage site selection and cleavage precision. An analysis of multiple shRNA intermediates generated from several reagents revealed the complexity of shmiR processing by Drosha and demonstrated that Dicer selects substrates for further processing. Aside from providing new basic knowledge regarding the specificity of nucleases involved in miRNA biogenesis, our results facilitate the rational design of more efficient genetic reagents for RNAi technology. (C) 2016 Elsevier B.V. All rights reserved.
This paper presents the development of an artificial neural network (ANN)-based improved inductive signal conditioning circuit for pressure transducer with bellow as sensor. A bellow is an elastic-type mechanical pressure sensor. The deflection of the bellow due to applied pressure must be translated into an efficient electrical signal for continuous monitoring, wireless transmission, and digital readout. A ferromagnetic wire attached to the bellow as a part of an inductive coil arrangement, gets deflected due to applied pressure, thereby changing the self inductance of the coil. An op-amp inductive signal conditioning circuit (OISCC) is designed to produce voltage proportional to changes in self-inductance, but the OISCC voltage versus applied pressure exhibits a considerable nonlinearity error due to stray inductances and component drifts. The ANN modeling estimates and compensates the nonlinearity of OISCC. An embedded unit is used for implementation of ANN learning process. The pressure transducer with significant stability has exhibited high linearity and sensitivity of +/- 0.35% and 10 mH/psig, respectively, in the measuring range of 0-70 psig. The design and experimental aspects of the technique are reported.
One of the major challenges of developing and growing of parabolic trough solar thermal power plants (PTSTPPs) is enhancing the techno-economic performance. The goal of this study is to develop a unique artificial neural network (ANN) model that gives the best approach to predict the levelized cost of electricity (LCOE) of two different PTSTPPs integrated with thermal energy storage and fuel backup system; the first one is using thermic oil as primary heat transfer fluid in the solar field, while the other one is based on molten salt. By this way, the optimum designs of the two plants were determined in the LCOE analysis by using the obtained weights and biases of the best ANN topology. The techno-economic potentials of using Molten salt in comparison to thermic oil of the two optimized plants were investigated considering both hourly and annual performances. The results show that it is possible to get minimum values of LCOE of 8.3 and 7.0 cent$/kWh for oil and salt configurations, respectively. Moreover, because of the difference in dispatch of thermal energy system and solar field aperture area of the plants, the annual power generation and capacity factor of salt plant are much higher than those of oil plant with a difference of around 26%. (C) 2016 Elsevier Ltd. All rights reserved.
Background: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. Objective: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. Design, setting, and participants: Plasma samples were collected from 36 CRPC patients before they began second-line hormonal treatment. Exosomes were isolated and RNA extracted for analysis of AR-V7 by ddPCR. Outcome measurements and statistical analysis: The absolute target gene concentration as copies per milliliter (copies/ml) was determined by ddPCR. Statistical analyses were performed with SPSS software (IBM Corp., Armonk, NY, USA). Results and limitations: A total of 26 patients received abiraterone and 10 enzalutamide; 39% of patients were found to be AR-V7 positive (AR-V7(+)). Median progression-free survival was significantly longer in AR-V7 negative (AR-V7(-)) versus AR-V7(+) patients (20 vs 3 mo; p < 0.001). Overall survival was significantly shorter in AR-V7(+) participants at baseline compared with AR-V7(-) participants (8 mo vs not reached; p < 0.001). Conclusions: This study demonstrates that plasma-derived exosomal RNA is a reliable source of AR-V7 that can be detected sensitively by ddPCR assay. We also showed that resistance to hormonal therapy may be predicted by AR-V7, making it a clinically relevant biomarker. Patient summary: We report a first study on a method for androgen receptor splice variant 7 (AR-V7) detection in RNA extracted from cancer cell vesicles released in blood. Results confirmed the role of AR-V7 as a predictive biomarker of resistance to hormonal therapy. Our assay showed that vesicles are a reliable source of AR-V7 RNA and that the method is fast, highly sensitive, and affordable. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
The molecular mechanisms of the endogenous circadian clocks that allow most animals to adapt to environmental cycles have recently been uncovered. The draft genome of the ascidian, Ciona intestinalis, a model animal that is close to vertebrates, has been described. However, the C. intestinalis genome lacks the canonical clock genes such as Per, Bmal and Clock that are shared by vertebrates and insects. Here, we found the circadian rhythms at the physiological and molecular levels. The oxygen consumption rate was lower during the light phase and higher during the dark phase during a day, and the rhythm highly damped and continued under constant darkness. From the microarray analysis, the 396 spots (1.8% of the total; corresponding to 388 clones) were extracted as candidates for circadian expression. We confirmed the circadian expression of several candidate genes by northern blotting. Furthermore, three of four rhythmic expressed genes showed phase-shifts to prolonged light period. However, most of known clock genes did not oscillate. These data suggest that C. intestinalis have a unique molecular circadian clock and the daily environmental change is not such a strong effect for sea squirt in its evolution when compared to vertebrates and insects.
Ascorbate peroxidase (APX) is one of the key enzymes of the plant antioxidant system playing, along with catalase, a central role in hydrogen peroxide scavenging. An approach to further increase the knowledge about cytosolic APX gene organization can be achieved by isolating and characterisating new cDNAs, thus providing new insights about the physiological roles and regulation of these enzymes. A partial cDNA clone (corresponding to the 3' untranslated region), cytosolic ascorbate peroxidase-related, was isolated from potato sprouts by RT-PCR. Database analysis retrieved several expressed sequence tags (ESTs) coding potato cytosolic ascorbate peroxidase, that were used to infer the complete cDNA sequence. The deduced amino acid sequence revealed high homologies with other plant cytosolic ascorbate peroxidases, confirming the reliability of the virtual cDNA. Northern blot analysis revealed the existence of a single band related to the isolated cDNA and the southern blotting results allowed the elaboration of a possible gene organization.
Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta 1 (TGF-beta 1). The synthesis of type VII collagen was elevated by TGF-beta 1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1 beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.
Safety and reliability are major issues for the ASDEX Upgrade (AUG) pulsed power supply systems. To avoid long downtimes during an experimental campaign, fault-prone components have to be identified and treated early. This becomes even more important due to the AUG participation in the EUROfusion Medium Sized Tokamak (MST) program. Operating equipment which is up to 40 years old adds additional complications. This contribution describes one such example where a 35 year old flywheel generator at AUG was identified as fault-prone and pre-emptively upgraded with a new drive converter with integrated control. Most challenging was to adapt a modern converter, originally designed for wind turbines, toward a drive system for a flywheel-motor-generator system. To identify the layout of the controller and the control parameters, accurate modeling and comprehensive simulations were performed. This effort paid off during commissioning and measuring results verified the calculated design values. Finally, the system shows good performance during AUG plasma experiments. (C) 2015 Elsevier B.V. All rights reserved.
1. Host-parasitoid systems are characterized by a continuous development of new defence strategies in hosts and counter-defence mechanisms in parasitoids. This co-evolutionary arms race makes host-parasitoid systems excellent for understanding trade-offs in host use caused by evolutionary changes in host immune responses and parasitoid virulence. However, knowledge obtained from natural host-parasitoid systems on such trade-offs is still limited. 2. In this study, the aim was to examine trade-offs in parasitoid virulence in Asecodes parviclava (Hymenoptera: Eulophidae) when attacking three closely related beetles: Galerucella pusilla, Galerucella calmariensis and Galerucella tenella (Coleoptera: Chrysomelidae). A second aim was to examine whether geographic variation in parasitoid infectivity or host immune response could explain differences in parasitism rate between northern and southern sites. 3. More specifically, we wanted to examine whether the capacity to infect host larvae differed depending on the previous host species of the parasitoids and if such differences were connected to differences in the induction of host immune systems. This was achieved by combining controlled parasitism experiments with cytological studies of infected larvae. 4. Our results reveal that parasitism success in A. parviclava differs both depending on previous and current host species, with a higher virulence when attacking larvae of the same species as the previous host. Virulence was in general high for parasitoids from G. pusilla and low for parasitoids from G. calmariensis. At the same time, G. pusilla larvae had the strongest immune response and G. calmariensis the weakest. These observations were linked to changes in the larval hemocyte composition, showing changes in cell types important for the encapsulation process in individuals infected by more or less virulent parasitoids. 5. These findings suggest ongoing evolution in parasitoid virulence and host immune response, making the system a strong candidate for further studies on host race formation and speciation.
The article presents design of operational amplifier circuit in Austria Micro Systems, 350 nm SiGe BiCMOS technology, suitable for Chua's diodes construction. By connecting an external passive components it became the basis of Chua's circuit that can be used for example in communications and cryptography. The whole design is implemented in nanometer IC design kit from Mentor Graphics. The development kit allows to implement both pre-layout simulations but also close to the reality post-layout simulations, based on accurate models of technology processes which are available from the manufacturer of the integrated circuits in which they will be integrated. The results obtained are presented in this article.
Recurrent pneumonia with cavitation leading to pneumatoceles, secondary fungal infections, and hemoptysis are major causes of mortality and morbidity in patients with hyper-IgE syndrome. Prevention and aggressive treatment of pneumonia in these patients are essential to prevent further lung damage, but treatment may be delayed because the classic signs/symptoms of infection such as fever, chills, or rigors may be lacking. Early imaging to identify infection is essential for diagnosis and treatment. The mainstay of therapy is continuous, full-dose daily trimethoprim-sulfamethoxazole and commonly fungal coverage. Because hyper-IgE syndrome is a progressive disease, patients' condition may worsen despite compliance with prophylactic therapy. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Fungal specific CD154(+) T-cells have been described as a biomarker in invasive aspergillosis. The influence of sample storage on the detection of these cells was assessed. Six-hour delay prior to PBMC isolation is associated with an 18% decrease of cell viability and alterations of the cellular composition of the sample. This results in 87% reduction of CD154(+) A. fumigatus specific cells due to reduced assay sensitivity and increased background values in unstimulated samples. If prompt cell measurement is not feasible, isolated PBMCs can be frozen (at -20 degrees C and -80 degrees C) and processed later with comparable assay reliability (mean value fresh vs. thawing: 0.126, 0.133; Pearson-Coefficient: 0.962).
A mycelium-bound lipase from Aspergillus oryzae (AOL) exhibited excellent enantioselectivity for kinetic resolution of (RS)-1-phenylethanol ((RS)-1-PE) in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied, including type of acyl donor, solvent, molar ratio, temperature, enzyme amount, and substrate concentration. The optimum reaction conditions were found to be transesterification with vinyl acetate at 30 degrees C in methyl tert-butyl ether with a vinyl acetate: (RS)-1-PE molar ratio of 1: 1 and an enzyme concentration of 60 g/L. At the optimum reaction conditions, the conversion could reach above 46% with >99% enantiomeric excess of the product, (R)-1-phenylethyl acetate, when the substrate concentration was below 1.4 M. The enzyme displayed an excellent enantioselectivity with an E-value of >200 and a strong tolerance for high substrate concentration of up to 1.8 M. Those results indicated that AOL was a promising biocatalyst in the kinetic resolution of (RS)-1-PE. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Aims: The study was carried out to isolate and identify the spontaneously growing populations of bacteria and fungi on the surface of biologically recovered polyhydroxyalkanoate (PHA) copolymer, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)]. Methodology and results: Large-scale PHA biosynthesis was carried out using 300 L fermenter and a biological methodology developed in our laboratory was utilized for PHA recovery. Using standard microbiological and molecular biology techniques the naturally growing microbial populations on the surface of biologically recovered PHA were identified. Scanning electron microscopy (SEM) analysis showed that the identified bacterial (Bacillus cereus and Burkholderia cepacia) and fungal isolates (Aspergillus niger, Byssochlamys nivea, Penicillium citrinum and Penicillium griseofulvum) were able to grow on and degrade the P(3HB-co-3HHx) copolymer. Conclusion, significance and impact of study: This is the first report on biologically recovered PHA pellet addressing the occurrence of microorganisms that grew spontaneously on it during storage under laboratory conditions. Fungi appeared to be dominant over bacteria in their ability to colonize the biologically recovered PHA.
Background: Indoor air pollution caused by fungal contamination is suspected to have a public health impact. Monitoring of the composition of the indoor airborne fungal contaminants is therefore important. To avoid problems linked to culture-dependent protocols, molecular methods are increasingly being proposed as an alternative. Among these molecular methods, the polymerase chain reaction (PCR) and the real-time PCR are the most frequently used tools for indoor fungal detection. However, even if these tools have demonstrated their appropriate performance, some of them are not able to discriminate between species which are genetically close. A solution to this could be the use of a post-qPCR high resolution melting (HRM) analysis, which would allow the discrimination of these species based on the highly accurate determination of the difference in melting temperature of the obtained amplicon. In this study, we provide a proof-of-concept for this approach, using a dye adapted version of our previously developed qPCR SYBR (R) Green method to detect Aspergillus versicolor in indoor air, an important airborne fungus in terms of occurrence and cause of health problems. Despite the good performance observed for that qPCR method, no discrimination could previously be made between A. versicolor, Aspergillus creber and Aspergillus sydowii. Methods: In this study, we developed and evaluated an HRM assay for the discrimination between A. versicolor, Aspergillus creber and Aspergillus sydowii. Results: Using HRM analysis, the discrimination of the 3 Aspergillus species could be made. No false positive, nor false negatives were observed during the performance assessment including 20 strains of Aspergillus. The limit of detection was determined for each species i.e., 0.5 pg of gDNA for A. creber and A. sydowii, and 0.1 pg of gDNA for A. versicolor. The HRM analysis was also successfully tested on environmental samples. Conclusion: We reported the development of HRM tools for the discrimination of A. versicolor, A. creber and A. sydowii. However, this study could be considered as a study case demonstrating that HRM based on existing qPCR assays, allows a more accurate identification of indoor air contaminants. This contributes to an improved insight in the diversity of indoor airborne fungi and hence, eventually in the causal link with health problems.
BACKGROUND: The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. METHODS: A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. RESULTS: To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephinebiopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. CONCLUSIONS: The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. (C) 2016 American Cancer Society.
Numerous evidences indicate that aspirin usage causes a significant reduction in colorectal cancer. However, the molecular mechanisms about aspirin preventing colon cancer are largely unknown. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a most frequently used method to identify the target molecules regulated by certain compound. However, this method needs stable internal reference genes to analyze the expression change of the targets. In this study, the transcriptional stabilities of several traditional reference genes were evaluated in colon cancer cells treated with aspirin, and also, the suitable internal reference genes were screened by using a microarray and were further identified by using the geNorm and NormFinder softwares, and then were validated in more cell lines and xenografts. We have showed that three traditional internal reference genes, beta-actin, GAPDH and a-tubulin, are not suitable for studying gene transcription in colon cancer cells treated with aspirin, and we have identified and validated TMEM208 and PQLC2 as the ideal internal reference genes for detecting the molecular targets of aspirin in colon cancer in vitro and in vivo. This study reveals stable internal reference genes for studying the target genes of aspirin in colon cancer, which will contribute to identify the molecular mechanism behind aspirin preventing colon cancer.
The consideration of worker heterogeneity in assembly lines has received a fair amount of attention in the literature in the past decade. Most of this exploration uses as motivation the example of assembly lines in sheltered work centers for the disabled. Only recently has the community started looking at the situation faced in assembly lines in the general industrial park, when in the presence of worker heterogeneity. This step raises a number of questions around the best way to incorporate heterogeneous workers in the line, maximizing their integration while maintaining productivity levels. In this paper we propose the use of Miltenburg's regularity criterion and cycle time as metrics for integration of workers and productivity, respectively. We then define, model and develop heuristics for a line balancing problem with these two goals. Results obtained through an extensive set of computational experiments indicate that a good planning can obtain trade-off solutions that perform well in both objectives. (C) 2017 Elsevier Ltd. All rights reserved.
A thorough understanding of the molecular biosciences requires the ability to visualize and manipulate molecules in order to interpret results or to generate hypotheses. While many instructors in biochemistry and molecular biology use visual representations, few indicate that they explicitly teach visual literacy. One reason is the need for a list of core content and competencies to guide a more deliberate instruction in visual literacy. We offer here the second stage in the development of one such resource for biomolecular three-dimensional visual literacy. We present this work with the goal of building a community for online resource development and use. In the first stage, overarching themes were identified and submitted to the biosciences community for comment: atomic geometry; alternate renderings; construction/annotation; het group recognition; molecular dynamics; molecular interactions; monomer recognition; symmetry/asymmetry recognition; structure-function relationships; structural model skepticism; and topology and connectivity. Herein, the overarching themes have been expanded to include a 12th theme (macromolecular assemblies), 27 learning goals, and more than 200 corresponding objectives, many of which cut across multiple overarching themes. The learning goals and objectives offered here provide educators with a framework on which to map the use of molecular visualization in their classrooms. In addition, the framework may also be used by biochemistry and molecular biology educators to identify gaps in coverage and drive the creation of new activities to improve visual literacy. This work represents the first attempt, to our knowledge, to catalog a comprehensive list of explicit learning goals and objectives in visual literacy. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):69-75, 2017.
Parental sense of competence is one of the central dimensions targeted on psychosocial interventions aimed at supporting at-risk families. Researchers and practitioners need reliable instruments to assess the parental role adapted for these families. Although the parental sense of competence (PSOC) scale has been frequently used to assess this construct, there is still no adapted version for Portuguese parents. In this study, the reliability, validity and factor structure of the PSOC scale is examined with a clinical sample of 146 mothers from at-risk families receiving psychosocial interventions for family preservation from Child Protective Services. Results show that the Portuguese version of the PSOC measures three distinct constructs with acceptable psychometric properties: efficacy, dissatisfaction and controllability. As expected, the obtained factors were significantly and positively related to parenting alliance and family cohesion, and negatively associated with parenting stress. In sum, the proposed Portuguese version shows reliability and validity evidences to measure three relevant dimensions of parental self-evaluation, and it constitutes a cost- and time-effective instrument suited for at-risk mothers.
New Zealand kauri (Agathis australis) (D.Don) Lindl. is a large and long-lived tree species endemic to the species-rich forests of the north of the North Island. Agathis australis are culturally and ecologically significant, but little is known about their ecophysiology. In particular, environmental drivers of fluxes of carbon and water for A. australis trees have not been quantified. We measured leaf gas exchange to explore the effect of leaf age, tree size, foliar nitrogen concentration, photosynthetically active radiation (PAR) and vapour pressure deficit (D) on assimilation rates (A) and stomatal conductance (g(s)). We also measured carbon isotope discrimination of leaves and applied an optimal stomatal behaviour model. Both g(s) and A were highest for year one leaves (130mmolm(-2)s(-1) and 5molm(-2)s(-1), respectively) then declined with leaf age to < 80mmolm(-2)s(-1) and < 3molm(-2)s(-1), respectively, in 4-5-year-old leaves. Instantaneous water use efficiency (A/g(s)) was highly variable, but there was no leaf age-related pattern. Our diurnal results indicate that A. australis g(s) peaks early in the day (before 0900 h at 250mmolm(-2)s(-1)) and A is comparatively low, remaining below 9molm(-2)s(-1) throughout the day. Overall, water use efficiency is low based on intrinsic water use efficiency and the stomatal model. Isotopic analysis indicated moderate water use efficiency over the life of leaves compared to other temperate conifers. This information is valuable for modelling carbon and water fluxes of A. australis and for improving our understanding of the threat of summer droughts to these forest giants.
BackgroundHLA-E products, class Ib human leukocyte antigens, act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy. AimsTo evaluate HLA-E role in the establishment of a viable pregnancy. Materials & MethodsHLA-E was genotyped by sequence-based typing (SBT) and analyzed for specific polymorphisms, comparing couples who underwent assisted reproduction treatment (ART) and fertile control couples. ResultsThere was a significant difference in HLA-E allele and genotype distributions between ART couples and control couples. The allele HLA-E*01:03 was observed in 63.2% of ART men and in 35.1% of fertile men (P = 0.0032). ConclusionThese results suggest that HLA-E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.
Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections. Rather than investigating the immune pathways necessary to induce this rather unique state of tolerance toward the rapidly growing parasitic antigen load of the fetus, the field, instead, concentrated on irrelevant secondary immune phenomena (i.e., "immunological noise"). It, therefore, does not surprise that interesting recent research, offering new potential insights into maternal tolerance during pregnancy, was mostly published outside of the field of reproductive medicine. This research offers evidence for existence of inducible maternal tolerance pathways with the ability of improving maternal fecundity and, potentially, reducing such late pregnancy complications as premature labor and preeclampsia/eclampsia due to premature abatement of maternal tolerance. Increasing evidence also suggests that tolerance-inducing immune pathways are similar in successful pregnancy, successful organ transplantation and, likely also in the tolerance of "self" (i.e., prevention of autoimmunity). Identifying and isolating these pathways, therefore, may greatly benefit all three of these clinical areas, and research in reproductive immunology should be accordingly redirected.
Recent studies on the association between particular single nucleotide polymorphisms of serine-threonine kinase with no lysine (K) 4 gene (WNK4) and essential hypertension have yielded controversial results. Here, frequencies of Ala589Ser polymorphism within exon 8 of the WNK4 gene were assessed among 259 unrelated ethnic Chinese patients with essential hypertension and 235 strictly matched normotensive controls. All subjects were derived from a relatively isolated population identified in the Kerqin desert region in Zhangwu county of Liaoning, northeastern China, which features a dry climate and the people having a high dietary salt intake, in addition to a significantly higher prevalence (similar to 35%) of essential hypertension. Genotypes were verified with polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. Expression pattern and regulatory mechanisms of the WNK4 gene were also explored using Northern blotting and in vitro hormone stimulation assays. Strong associations between the Ala589Ser polymorphism and both raised systolic and diastolic blood pressures were identified. In addition to the kidneys, WNK4 gene expression was also found in many other organs. Several cis-acting elements had been discovered in the promoter region of the gene. As revealed by preliminary experiment, various hormones can down-regulate the expression of WNK4, among which glucocorticoid hormone seems to act in a dose-dependent manner. The WNK4 gene probably plays an important role in the pathogenesis of essential hypertension. As a missense mutation, the Ala589Ser polymorphism may bring changes to the enzyme's function(s), resulting in increased susceptibility to the disease.
Asthenozoospermia is an important cause of male infertility. The mutations in sperm mitochondrial DNA (mtDNA) result in either functionless or malfunctioning some proteins, subsequently affecting sperm motility leading to asthenozoospermia. The purpose of this study was to investigate sperm mtDNA 4,977-bp deletion in infertile men with low sperm motility/immotile spermatozoa compared to healthy subjects with high sperm motility. Semen samples of 256 asthenozoospermic infertiles and 200 controls from northern Iran were collected. After extraction of spermatozoa total DNA, Gap-polymerase chain reaction (Gap-PCR) was performed. The deletion was observed in 85.93% of patients with asthenozoospermia compared with 14% in controls [OR=37.5397, 95% confidence interval=12.937-108.9276, p<.0001]. It is concluded that there is a strong association between sperm mtDNA 4,977-bp deletion and asthenozoospermia-induced infertility in the population examined. Large-scale mtDNA deletions in spermatozoa may induce bioenergetic disorders. Nevertheless, to validate our results broader research may be needed.
BACKGROUND: Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment. OBJECTIVE: The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations. METHODS: Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physiciandiagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations. RESULTS: Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P =.580). Pharmacy-based records of metereddose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score. CONCLUSIONS: Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations. (C) 2016 American Academy of Allergy, Asthma & Immunology.
BACKGROUND: Severe uncontrolled asthma (SUA) is associated with increased asthma exacerbations. Whether high blood eosinophil counts are related to this burden is uncertain. OBJECTIVES: To determine the relationship of blood eosinophil counts to asthma exacerbations, utilization, and cost in patients with SUA. METHODS: Patients with persistent asthma (age >= 12 years) were identified administratively with SUA in phase I by evidencing (1) 2 or more asthma exacerbations; (2) 6 or more medium-or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or with long-acting beta(2)-agonist; and (3) 3 or more dispensed non-ICS controllers. Of the 541 patients with SUA invited to participate in the prospective phase II follow-up study, 261 (48.2%) had blood tests (index date) to determine eosinophil count and other atopic biomarkers. The relationship of blood eosinophil cutoff points to asthma exacerbations and direct costs 1 year after the index date were determined by multivariable regression. RESULTS: A blood eosinophil cutoff point of greater than or equal to 400 cells/mm(3) compared with less than 400 cells/mm(3), but not 150 cells/mm(3) or 300 cells/mm(3), was a risk factor in the outcome year in adjusted analyses for 2 or more asthma exacerbations (risk ratio, 1.55; 95% CI, 1.02-2.35; P = .04) and any asthma emergency department visit or hospitalization (risk ratio, 2.29; 95% CI, 1.16-4.55; P = .02), but not for rate of asthma exacerbations or incremental total direct asthma costs per patient ($ 202; 95% CI, -286 to 691). CONCLUSIONS: A high blood eosinophil count was an independent risk factor for 2 or more asthma exacerbations or any asthma emergency department visit or hospitalization, but not direct costs in patients with SUA, possibly constrained by limited power. (C) 2016 American Academy of Allergy, Asthma & Immunology
BACKGROUND: Severe bronchiolitis (ie, bronchiolitis requiring hospital admission) is thought to markedly increase asthma risk, with 30%-50% developing asthma by age 5 years. To date, studies of this association are small, and most are from outside the United States. OBJECTIVE: The objective of this study was to investigate the association between severe bronchiolitis and risk of asthma in a US birth cohort. METHODS: We studied a cohort nested within the Massachusetts General Hospital Obstetric Maternal Study (MOMS), a prospective cohort of pregnant women enrolled during 1998-2006. Children of mothers enrolled in MOMS were included in the analysis if they received care within our health system (n = 3653). Diagnoses and medications were extracted from the children's electronic health records; we also examined pregnancy and perinatal risk factors collected for the underlying pregnancy study. RESULTS: The birth cohort was 52% male, 49% white, and 105 infants (2.9%) had severe bronchiolitis. Overall, 421 children (11.5%) developed asthma by age 5 years. Among the children with severe bronchiolitis, 27.6% developed asthma by age 5 years. In multivariable logistic regression adjusting for 12 risk factors, severe bronchiolitis remained a strong risk factor for developing asthma by age 5 years (odds ratio 2.57; 95% confidence interval 1.61-4.09). Conclusions: In a large Boston birth cohort, the frequency of severe bronchiolitis and childhood asthma was similar to published data. Among children with severe bronchiolitis, the risk of developing asthma was lower than prior studies but still high (27.6%). This difference may be due to different study designs, populations, and outcome definitions studied. (C) 2016 American Academy of Allergy, Asthma & Immunology.
BACKGROUND: Mexican-born children living in the United States have a lower prevalence of asthma than other US children. Although children of Mexican descent near the Arizona (AZ)Sonora border are genetically similar, differences in environmental exposures might result in differences in asthma prevalence across this region. OBJECTIVE: The objective of this study was to determine if the prevalence of asthma and wheeze in these children varies across the AZ-Sonora border. METHODS: The International Study of Asthma and Allergy in Children written and video questionnaires were administered to 1753 adolescents from 5 middle schools: Tucson (school A), Nogales, AZ (schools B, C), and Nogales, Sonora, Mexico (schools D, E). The prevalence of asthma and symptoms was compared, with analyses in the AZ schools limited to selfidentified Mexican American students. RESULTS: Compared with the Sonoran reference school E, the adjusted odds ratio (OR) for asthma was significantly higher in US schools A (OR 4.89, 95% confidence interval [CI] 2.72-8.80), B (OR 3.47, 95% CI 1.88-6.42), and C (OR 4.12, 95% CI 1.789.60). The adjusted OR for wheeze in the past year was significantly higher in schools A (OR 2.19, 95% CI 1.20-4.01) and B (OR 2.67, 95% CI 1.42-5.01) on the written questionnaire and significantly higher in A (OR 2.13, 95% CI 1.22-3.75), B (OR 1.95, 95% CI 1.07-3.53), and Sonoran school D (OR 2.34, 95% CI 1.28-4.30) on the video questionnaire compared with school E. CONCLUSIONS: Asthma and wheeze prevalence differed significantly between schools and was higher in the United States. Environmental factors that may account for these differences could provide insight into mechanisms of protection from asthma. (C) 2016 American Academy of Allergy, Asthma & Immunology
BACKGROUND: Adding a long-acting beta(2)-agonist (LABA) to inhaled corticosteroids (ICS) using a fixed-dose combination (FDC) inhaler is the UK guideline recommendation for children aged more than 4 years with uncontrolled asthma. The evidence of benefit of adding an FDC inhaler over a separate LABA inhaler is limited. OBJECTIVE: The objective of this study was to compare the effectiveness of a LABA added as an FDC inhaler, and as a separate inhaler, in children with uncontrolled asthma. METHODS: Two UK primary care databases were used to create a matched cohort study with a 2-year follow-up period. We included children prescribed their first step-up from ICS monotherapy. Two cohorts were formed for children receiving an add-on LABA as an FDC inhaler, or a separate LABA inhaler. Matching variables and confounders were identified by comparing characteristics during a baseline year of follow-up. Outcomes were examined during the subsequent year. The primary outcome was an adjusted odds ratio for overall asthma control (defined as follows: no asthma-related hospital admission or emergency room visit, prescription for oral corticosteroids or antibiotic with evidence of respiratory consultation, and <= 2 puffs of short-acting bagonist daily). RESULTS: The final study consisted of 1330 children in each cohort (mean age 9 years; 59% male). In the separate ICSDLABA cohort, the odds of achieving overall asthma control were lower (adjusted odds ratio, 0.77 [95% confidence interval, 0.66-0.91]; P =.001) compared with the FDC cohort. CONCLUSION: The study demonstrates a small but significant benefit in achieving asthma control from an add-on LABA as an FDC, compared with a separate inhaler and this supports current guideline recommendations. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2-driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study. Objective To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics. Methods Measurements of FeNO (elevated = 25 ppb) and S-ECP (elevated = 20 ng/mL) were performed in 339 adult asthmatics. Asthma events (attacks and symptoms) were selfreported. Results Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently associated with asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8). Conclusions Simultaneously elevated FeNO and S-ECP levels were related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma to identify individuals at high risk of exacerbations. Clinical relevance FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.
BACKGROUND: Obesity and asthma are common health problems in the United States. OBJECTIVE: The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. METHODS: Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. RESULTS: A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. CONCLUSIONS: These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. (C) 2016 American Academy of Allergy, Asthma & Immunology
A large number of asthmatic patients, particularly females, present inadequate disease control. Depressive symptoms are reportedly common in asthma and have been related to poor disease control, but the mechanism of this association is still unclear. Poor quality sleep, frequently observed in asthmatics, is also a manifestation of depression and has been related to uncontrolled asthma. This study aimed to investigate the relationship between depressive symptoms, sleep quality, and asthma control. This was a cross-sectional study of 123 women with previous diagnosis of asthma from a reference center in Fortaleza, Brazil. Depressive symptoms were assessed by the Beck Depression Inventory (BDI); quality of sleep was evaluated by the Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness by the Epworth Sleepiness Scale (ESS), and asthma control by the Asthma Control Test (ACT). Inadequate asthma control (ACT5) in 99 (80.49 %), and excessive daytime sleepiness (ESS >= 10) in 34 (27.64 %). Depressive symptoms were associated with both poor quality sleep (R = 0.326) and inadequate asthma control (R = -0.299). Regression analysis showed that depressive symptoms and sleep quality were independent predictors of the level of asthma control. Asthma control in women is independently associated with depressive symptoms and quality of sleep, suggesting that these patients might benefit from simple measures to promote healthy sleep behavior and sleep hygiene and also that routine screening for depression can be relevant, particularly, in poorly controlled cases.
The health and economic burden of asthma in the United States is substantial. Asthma self-management education (AS-ME) and home-based interventions for asthma can improve asthma control and prevent asthma exacerbations, and interest in health care-public health collaboration regarding asthma is increasing. However, outpatient AS-ME and home-based asthma intervention programs are not widely available; economic sustainability is a common concern. Thus, we conducted a narrative review of existing literature regarding economic outcomes of outpatient AS-ME and home-based intervention programs for asthma in the United States. We identified 9 outpatient AS-ME programs and 17 home-based intervention programs with return on investment (ROI) data. Most programs were associated with a positive ROI; a few programs observed positive ROIs only among selected populations (eg, higher health care utilization). Interpretation of existing data is limited by heterogeneous ROI calculations. Nevertheless, the literature suggests promise for sustainable opportunities to expand access to outpatient AS-ME and home-based asthma intervention programs in the United States. More definitive knowledge about how to maximize program benefit and sustainability could be gained through more controlled studies of specific populations and increased uniformity in economic assessments. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
Asthma is a condition that has consistently demonstrated significant health outcome inequalities for minority populations. One approach used for care of patients with asthma is the incorporation of technology for behavioral modification, symptom monitoring, education, and/or treatment decision making. Whether such technological interventions can improve the care of black and inner-city patients is unknown. We reviewed all randomized controlled trial technological interventions from 2000 to 2015 performed in minority populations. A total of 16 articles met inclusion and exclusion criteria; all but 1 was performed in a childhood or adolescent age group. The interventions used MPEG audio layer-3 players, text messaging, computer/Web-based systems, video games, and interactive voice response. Many used tailored content and/or a specific behavior theory. Although the interventions were based on technology, most required additional special staffing. Subject user satisfaction was positive, and improvements were noted in asthma knowledge, medication adherence, asthma symptoms, and quality of life. Unfortunately, health care utilization (emergency department visits and/or hospitalizations) was typically not improved by the interventions. Although no single intervention modality was vastly superior, the computer-based interventions appeared to have the most positive results. In summary, technology-based interventions have a high level of user satisfaction among minority and urban/low-income individuals with asthma, and can improve asthma outcomes. Further large-scale studies are needed to assess whether such interventions can decrease health disparities in asthma. (C) 2016 American Academy of Allergy, Asthma & Immunology.
BACKGROUND: Home-based interventions to improve indoor air quality have demonstrated benefits for asthma morbidity, yet little is known about the effect of environmental interventions in the school setting. OBJECTIVE: We piloted the feasibility and effectiveness of a classroom-based air cleaner intervention to reduce particulate pollutants in classrooms of children with asthma. METHODS: In this pilot randomized controlled trial, we assessed the effect of air cleaners on indoor air particulate pollutant concentrations in 18 classrooms (9 control, 9 intervention) in 3 urban elementary schools. We enrolled 25 children with asthma (13 control, 12 intervention) aged 6 to 10 years. Classroom air pollutant measurements and spirometry were completed once before and twice after randomization. Asthma symptoms were surveyed every 3 months. RESULTS: Baseline classroom levels of fine particulate matter (particulate matter with diameter of <2.5 mu m [PM2.5]) and black carbon (BC) were 6.3 and 0.41 mu g/m(3), respectively. When comparing the intervention to the control group, classroom PM2.5 levels were reduced by 49% and 42% and BC levels were reduced by 58% and 55% in the first and second follow-up periods, respectively (P<.05 for all comparisons). When comparing the children randomized to intervention and control classrooms, there was a modest improvement in peak flow, but no significant changes in forced expiratory volume in 1 second (FEV1) and asthma symptoms. CONCLUSIONS: In this pilot study, a classroom-based air cleaner intervention led to significant reductions in PM2.5 and BC. Future large-scale studies should comprehensively evaluate the effect of school-based environmental interventions on pediatric asthma morbidity. (C) 2016 American Academy of Allergy, Asthma & Immunology
Compelling evidences point out a crucial role for extracellular nucleotides such as adenosine triphosphate (ATP) during inflammatory conditions. Once released into the extracellular space, ATP modulates migration, maturation and function of various inflammatory cells via activating of purinergic receptors of the P2Y- and P2X- family. P2RX4 is an ATP-guided ion channel expressed on structural cells such as alveolar epithelial and smooth muscle cells as well as inflammatory cells including macrophages, dendritic cells (DCs) and T cells. P2RX4 has been shown to interact with P2RX7 and promote NLRP3 inflammasome activation. Although P2RX7 has already been implicated in allergic asthma, the role of P2RX4 in airway inflammation has not been elucidated yet. Therefore, we used a selective pharmacological antagonist and genetic ablation to investigate the role of P2RX4 in an ovalbumin (OVA) driven model of allergen-induced airway inflammation (AAI). Both, P2RX4 antagonist 5-BDBD treatment and P2rx4 deficiency resulted in an alleviated broncho alveolar lavage fluid eosinophilia, peribronchial inflammation, Th2 cytokine production and bronchial hyperresponsiveness. Furthermore, P2rx4-deficient bone marrow derived DCs (BMDCs) showed a reduced IL-1 beta production in response to ATP accompanied by a decreased P2rx7 expression and attenuated Th2 priming capacity compared to wild type (WT) BMDCs in vitro. Moreover, mice adoptively transferred with P2rx4-deficient BMDCs exhibit a diminished AAI in vivo. In conclusion our data suggests that P2RX4-signaling contributes to AAI pathogenesis by regulating DC mediated Th2 cell priming via modulating IL-1 beta secretion and selective P2RX4-antagonists might be a new therapeutic option for allergic asthma.
To summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A total of 227 studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the Assess Systematic Reviews tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke, and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild-to-moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe respiratory syncytial virus infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies. (C) 2016 American Academy of Allergy, Asthma& Immunology.
Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the antitumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability. Real-time polymerase chain reaction and western blot were used to measure the messenger RNA and protein expression. Results showed that astragaloside IV treatment could suppress the proliferation of non-small cell lung cancer cells. In addition, combined treatment with astragaloside IV remarkably enhanced the chemosensitivity to gefitinib in three non-small cell lung cancer cell lines including NCI-H1299, HCC827, and A549. Furthermore, compared with gefitinib-treated cells, the messenger RNA expression of SIRT6 was obviously increased in non-small cell lung cancer cells treated with gefitinib combined with astragaloside IV. In addition, downregulation of SIRT6 was accomplished using small interference RNA technology. As a result, SIRT6 inhibition abolished the sensitization role of astragaloside IV in non-small cell lung cancer cells. Taken together, these data demonstrated that astragaloside IV sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that astragaloside IV may serve as potential therapeutic approach for lung cancer.
A retrospective chart review was completed of patients self-identified as lesbian, gay, or bisexual seen through a program for survivors of torture between June 9, 2009 and December 31, 2014 (n = 50). Almost all (98 %) experienced persecution due to their sexual orientation and 84 % were survivors of torture. The circumstances under which the disclosure of sexual orientation took place in the country of origin were often traumatic. In several, efforts were made to change their sexual orientation often through forced marriage. Those in same sex relationships had relationships often marred by tragedy. Women were more likely to be forced to move from place to place, experience rape/sexual assault and threats whereas men were more likely to be persecuted by people on the street. All presented with symptoms of depression and anxiety. Providers need to be attuned to the potential traumatic histories of those fleeing persecution due to sexual orientation, and the medical, social, psychological, and legal implications.
This paper explores the engagement in physical activity as a potential coping strategy for asylum seekers living in the Australian community without the right to work and with prolonged uncertainty, and benefits or barriers to undertaking such activity. Semi-structured in-depth interviews were held with 29 asylum seekers who had arrived to Australia by boat and were living in the community in the cities of Perth, Sydney or Melbourne in July-October 2013 after their release from immigration detention. The ratio of the numbers of men and women interviewed (23 men and 6 women) was comparable to the ratio of men and women who came by boat to Australia seeking asylum in 2012-2013. Nine participants reported that they participated in physical activity as a coping strategy. Seven other participants were so worried about their future and their families that they did not have the mental or physical energy to engage in physical activity. A further six wanted to participate in physical activity but faced a number of barriers to doing so. The seven remaining participants were either not asked about their physical activity engagement because they focused their discussion on other challenges or did not elaborate on why they were not engaging in physical activity. The findings suggest that physical activity, coupled with other coping strategies, are important for some asylum seekers in trying to manage the distress of being denied the right to work and living with prolonged uncertainty. In addition, these findings highlight the critical barrier that government policy plays in disabling engagement in physical activity, which further compounds social exclusion. This includes the lack of welfare support provided, which hinders people's financial ability to access activities and support in the community.
Construction of a random ssDNA sublibrary is an important step of the aptamer screening process. The available construction methods include asymmetric PCR, biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR amplification is a key step. The main drawback of PCR amplification is overamplification increasing nonspecific hybridization among different products and by-products, which may cause the loss of potential high-quality aptamers, inefficient screening, and even screening failure. Cycle number optimization in PCR amplification is the main way to avoid overamplification but does not fundamentally eliminate the nonspecific hybridization, and the decreased cycle number may lead to insufficient product amounts. Here, we developed a new method, "asymmetric emulsion PCR," which could overcome the shortcomings of conventional PCR. In asymmetric emulsion PCR, different templates were separated by emulsion particles, allowing single-molecule PCR, in which each template was separately amplified, and the nonspecific hybridization was avoided. Overamplification or formation of by-products was not observed. The method is so simple that direct amplification of 40 or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric emulsion PCR would improve the screening efficiency of systematic evolution of ligands by exponential enrichment. (C) 2015 The Authors. Biotechnology and Applied Biochemistry published by Wiley Periodicals, Inc. on behalf of the International Union of Biochemistry and Molecular Biology, Inc.
This paper presents a technique for reducing the input current ripple on multiphase power converters that provide multiple heterogeneous power supply rails, such as those present in portable electronics and computers. Through asymmetric interleaving of individual phases, the input current ripple can be reduced compared to conventional interleaving. The technique is derived based on an analytic description of the relevant current waveforms. Practical requirements of a digital control implementation of the proposed technique are analyzed, and its possible performance improvement is quantified through simulations and experimental results. With the proposed technique, close to a 3x reduction in input current ripple, compared to conventional methods, is demonstrated using an experimental prototype comprising a microcontroller that controls a multiphase 180 nm CMOS power management IC.
Optically pure t-butyl 6-cyano-(3R, 5R)-dihydroxyhexanoate ((R)-1b) is the key precursor for atorvastatin calcium, the most widely used cholesterol-lowering drug. In this work, a strain ZJB-09224 capable of asymmetrically reducing t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate (1a) to corresponding optically pure (R)-1b was successfully isolated from soil sample, identified belonging to Rhodotorula glutinis based on the morphology, physiological tests, and the 18S rDNA sequence analysis. It was found that heat treatment of cell suspension at 45 degrees C for 25 Min significantly improved R. glutinis ZJB-09224 stereoselectivity. The asymmetric bioreduction of 1a was most efficient at pH 7.5, 35 degrees C, 50 mM (15.0 g L-1) substrate concentration, 40.0 g DCW L-1 cell loading size, 0.54 M (60.0 g L-1) sodium lactate acting as co-substrate. Under these optimal conditions, 0.046 M (R)-1b was produced with de (diastereomeric excess) value of 99.2% after 40 H conversion. Moreover, R. glutinis ZJB-09224 has a broad substrate spectrum, making it a potential tool for some valuable chiral alcohol pharmaceutical intermediates synthesis. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 795-804, 2016
The traditional power control schemes for induction heating device mainly focus on the pulse frequency modulation (PFM) and the pulse density modulation. But they cannot solve the problems of power control, efficiency, and load-adaption well. This paper presents and analyzes the asymmetrical frequency modulation (AFM) control scheme used in the full-bridge series resonant inverter. With the proposed AFM control technique, the output power is controlled by two variables: the operation frequency and the division factor. Better efficiency performance can be achieved in the medium and low output power range when compared with PFM. The principles as well as the zero-voltage switching condition of the AFM are explained and the power losses of switches are analyzed. A control algorithm that schedules the three control modes of AFM is experimentally verified with a digital signal processor based induction heating prototype. The load-adaption, noise and thermal distribution problem of switches are also analyzed.
Antithymocyte globulin (ATG) is often included in the conditioning regimen to prevent graft vs. host disease in allogeneic hematopoietic stem cell (HSC) transplantation. However, because ATG contains antibodies targeting a wide range of antigens on human cells, its potential off-target effects remain a concern. Here, we explored this question in humanized mice that permit the analysis of human cell depletion in tissues. We showed that ATG binds to almost all lineages of human hematopoietic cells including HSCs, and accordingly it is capable of depleting almost all human hematopoietic cells. Interestingly, the efficacy of ATG was highly variable depending on the tissue of residence, with human cells in bone marrow significantly less susceptible than those in the blood and spleen. Recovery of multilineage human lymphohematopoietic reconstitution in humanized mice that received ATG 3 weeks after HSC transplantation indicates that ATG had a minimal effect on human HSCs that have settled in bone marrow niches. However, efficient human HSC depletion and engraftment failure were seen in mice receiving ATG at the time of transplantation. Our data indicate that the efficacy of ATG is tissue-dependent, and suggest a potential risk of impairing donor hematopoietic engraftment when ATG is used in preparative conditioning regimens.Cellular & Molecular Immunology (2017) published online 26 October 2015
Background: Autophagy is a bulk degradation pathway for long-lived proteins, protein aggregates, and damaged organelles. ULK1 protein kinase and Vps34 lipid kinase are two key autophagy regulators that are critical for autophagosome biogenesis. However, it isn't fully understood how ULK1 regulates Vps34, especially in the context of disease. Polyglutamine expansion in huntingtin (Htt) causes aberrant accumulation of the aggregated protein and disrupts various cellular pathways including autophagy, a lysosomal degradation pathway, underlying the pathogenesis of Huntington's disease (HD). Although autophagic clearance of Htt aggregates is under investigation as therapeutic strategy for HD, the precise mechanism of autophagy impairment remains poorly understood. Moreover, in-vivo assays of autophagy have been particularly challenging due to lack of reliable and robust molecular biomarkers. Method: We generated anti-phosphorylated ATG14 antibody to determine ATG14-mediated autophagy regulation; we employed Huntington's disease (HD) genetic cell models and animal models as well as autophagy reporter animal model to understand autophagy signaling and regulation in vivo. We applied biochemical analysis and molecular biology approaches to dissect the alteration of autophagy kinase activity and regulation. Results: Here, we demonstrate that ULK1 phosphorylates ATG14 at serine 29 in an mTOR-dependent manner. This phosphorylation critically regulates ATG14-Vps34 lipid kinase activity to control autophagy level. We also show that ATG14-associated Vps34 activity and ULK1-mediated phosphorylation of ATG14 and Beclin 1 are compromised in the Q175 mouse model of Huntington's disease. Finally, we show that ATG14 phosphorylation is decreased during general proteotoxic stress caused by proteasomal inhibition. This reduction of the specific phosphorylation of ATG14 and Beclin 1 is mediated, in part, by p62-induced sequestration of ULK1 to an insoluble cellular fraction. We show that increased ULK1 levels and phosphor-mimetic mutant ATG14 facilitate the clearance of polyQ mutant in cells. Conclusion: Our study identifies a new regulatory mechanism for ATG14-Vps34 kinase activity by ULK1, which can be used as valuable molecular markers for in-vivo autophagic activity as well as potential therapeutic target for the clearance of polyglutamine disease protein.
Remodeling of endothelial basement membrane is important in atherogenesis. Since little is known about the actual relationship between type IV collagen and matrix metalloprotease-2 (MMP-2) in endothelial cells (ECs) under shear stress by blood flow, we performed quantitative analysis for type IV collagen and MMP-2 in ECs under high shear stress. The mRNA of type IV collagen from ECs exposed to high shear stress (10 and 30 dyn/cm(2)) had a higher expression compared to ECs exposed to a static condition or low shear stress (3 dyn/cm(2)) (P < 0.01). (3)H-proline uptake analysis and fluorography revealed a remarkable increase of type IV collagen under high shear stress (P < 0.01). In contrast, zymography revealed that exposing to high shear stress, however similar positivity was leveled in the intracellular MMP-2 in the control and high shear stress-exposed ECs, reduced the secretion of MMP-2 in ECs. The results of Northern blotting, gelatin zymography and monitoring the intracellular trafficking of GFP-labeled MMP-2 revealed that MMP-2 secretion by ECs was completely suppressed by high shear stress, but the intracellular mRNA expression, protein synthesis, and transport of MMP-2 were not affected. In conclusion, we suggest that high shear stress up-regulates type IV collagen synthesis and down-regulates MMP-2 secretion in ECs, which plays an important role in remodeling of the endothelial basement membrane and may suppress atherogenesis.
Purpose of review ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition. Recent findings ACLY is a critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis. Human genetic variants have been associated with enhanced growth and survival of several cancers, and with attenuated plasma triglyceride responses to dietary fish oil. In mice, liver-specific Acly deficiency protects from hepatic steatosis and dyslipidemia, whereas adipose tissue-specific Acly deletion has no phenotype, supporting therapeutic inhibition of ACLY. A lipid-regulating compound, bempedoic acid, was discovered to potently inhibit ACLY, and in animal models, it prevents dyslipidemia and attenuates atherosclerosis. Phase 2 clinical trials revealed that bempedoic acid effectively lowers LDL-C as monotherapy, combined with ezetimibe, added to statin therapy and in statin-intolerant hypercholesterolemic patients. Summary The efficacy of bempedoic acid as an LDL-C-lowering agent has validated ACLY inhibition as a therapeutic strategy. Positive results of phase 3 patient studies, together with long-term cardiovascular disease outcome trials, are required to establish ACLY as a major new target in cardiovascular medicine.
Rationale: Forkhead box P3(+) T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. Objective: Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe(-/-) mice, and what effect Treg plasticity might have on the pathology of atherosclerosis. Methods and Results: We demonstrate that atherosclerosis promotes Treg plasticity, resulting in the reduction of CXCR3(+) Tregs and the accumulation of an intermediate Th1-like interferon (IFN)-gamma(+) CCR5(+) Treg subset (Th1/Tregs) within the aorta. Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice are dysfunctional in suppression assays. Using an adoptive transfer system and plasticity-prone Mir146a-/-Tregs, we demonstrate that elevated IFN gamma(+)Mir146a(-/-)Th1/Tregs are unable to adequately reduce atherosclerosis, arterial Th1, or macrophage content within Apoe(-/-) mice, in comparison to Mir146a(+/+) Tregs. Finally, via single-cell RNA-sequencing and real-time-polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional phenotype characterized by coexpression of Treg and Th1 lineage genes and a downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and Il10. In addition, an ingenuity pathway analysis further implicates IFN gamma, IFN alpha, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg plasticity. Conclusions: Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFN gamma(+) Th1/Tregs that may permit further arterial inflammation and atherogenesis.
Objectives: The aim of this study is to determine the relationship between atherosclerosis and periodontopathogenic microorganisms in chronic periodontitis patients following periodontal treatment. Materials and Methods: A total of 40 patients were included in the study. 20 of these patients diagnosed with atherosclerosis and chronic periodontitis formed the test group. The remaining 20 patients were systemically healthy patients diagnosed with chronic periodontitis and formed the control group. All patients had nonsurgical periodontal treatment. The periodontopathogenic microorganism levels were determined at baseline and at 6 months in microbial dental plaque samples and WBC, LDL, HDL, PLT, fibrinogen, creatinine and hs-CRP levels were determined by blood samples. Results: Statistically significant reduction has been achieved in clinical periodontal parameters following non-surgical periodontal treatment in test and control groups. Following periodontal treatment, WBC, LDL, PLT, fibrinogen, creatinine and hs-CRP levels significantly decreased and HDL levels significantly increased in both test and control groups. Similarly, the periodontopathogenic microorganism levels significantly decreased following periodontal treatment in the test and control groups. A statistically significant positive correlation has been determined between the periodontopathogenic microorganism levels and WBC, LDL, PLT, fibrinogen, creatinine, and hs-CRP levels in the test group. Conclusions: The association between hs-CRP, WBC, LDL, PLT, fibrinogen, creatinine, and the amount of periodontopathogenic microorganisms indicates the possibility that periodontal treatment could decrease the risk atherosclerosis. More studies must be conducted in order for these results to be supported.
Objective-UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. Approach and Results-Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4(+) forkhead box P3(+) regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell-depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4(+) forkhead box P3(+) regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. Conclusions-Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.
It is accepted that inflammation plays a critical role in the development of atherosclerosis; the pathogenesis is not clear. B-cell-produced interleukin (IL) 10 is an immune regulatory cytokine that can inhibit immune inflammation. This study tests a hypothesis that a psychological stress hormone, cortisol, suppresses IL-10 expression in peripheral B cells of patients with atherosclerosis. Peripheral blood samples were collected from patients with coronary artery atherosclerosis. B cells were isolated from the blood samples to be analyzed for the expression of IL-10 and micro RNA (miR) 98 by real-time polymerase chain reaction. We observed that the frequency of IL-10(+) B cell was less in patients with atherosclerosis than healthy controls. The serum cortisol levels were higher in the patients than that in healthy controls. Peripheral B-cell frequency was negatively correlated with the serum cortisol levels. Exposure of B cells to cortisol increased the expression of miR-98 in B cells. Cortisol also inhibited the expression of IL-10 in B cells, in which miR-98 played a critical role. Treating B cells from atherosclerosis patients with anti-miR-98 liposomes reversed the ability of expression of IL-10 in the cells. The expression of IL-10 is suppressed in peripheral B cells, which can be up regulated by anti-miR-98 liposomes.
Paroxysmal dyskinesias (PDs) are a group of hyperkinetic movement disorders characterised by circumscribed episodes of disturbed movement, superimposed on a background state in which such abnormality is absent. There is no loss of consciousness. Episodes can last seconds, minutes or hours, and the beginning and end of the movement disturbance are abrupt. Neurological examination is typically normal between episodes. PDs are associated with a broad spectrum of clinical presentations, encompassing various aetiologies. In humans, three main groups of PDs are distinguished, based on precipitating events rather than phenomenology: (1) paroxysmal kinesigenic dyskinesia (PKD); (2) paroxysmal nonkinesigenic dyskinesia (PNKD); and (3) paroxysmal exertion-induced dyskinesia (PED). In recent years, there has been an expansion of the spectrum of manifestations of PD due to the identification of genes associated with PD in humans (PRRT1, MR-1, SLC2A1 and KCNMAI) and dogs (BCAN and P1GN). The precise pathophysiological mechanism underlying the clinical manifestations of these reported mutations remains to be elucidated. Progress is also being made in the field of immunology, and links to gluten hypersensitivity in Border terriers with so-called canine epileptoid cramping syndrome (CECS) have been reported. This review aims to synthesise a classification scheme for veterinary PDs by reviewing human systems and applying them to veterinary examples. However, it is anticipated that genetic advancement will greatly aid in future stratification and therapy for PDs in dogs. Therefore, classification systems should be viewed as works in progress that should be modified as necessary. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
Large-scale atmospheric removal of greenhouse gases (GHGs) including methane, nitrous oxide and ozone depleting halocarbons could reduce global warming more quickly than atmospheric removal of CO2. Photo catalysis of methane oxidizes it to CO2, effectively reducing its global warming potential (GWP) by at least 90%. Nitrous oxide can be reduced to nitrogen and oxygen by photocatalysis; meanwhile halocarbons can be mineralized by red-ox photocatalytic reactions to acid halides and CO2. Photocatalysis avoids the need for capture and sequestration of these atmospheric components. Here review an unusual hybrid device combining photocatalysis with carbon-free electricity with no-intermittency based on the solar updraft chimney. Then we review experimental evidence regarding photocatalytic transformations of non-CO2 GHGs. We propose to combine Ti02-photocatalysis with solar chimney power plants (SCPPs) to cleanse the atmosphere of non-CO2 GHGs. Worldwide installation of 50,000 SCPPs, each of capacity 200 MW, would generate a cumulative 34 PWh of renewable electricity by 2050, taking into account construction time. These SCPPs equipped with photocatalyst would process 1 atmospheric volume each 14 16 years, reducing or stopping the atmospheric growth rate of the non-CO2 GHGs and progressively reducing their atmospheric concentrations. Removal of methane, as compared to other GHGs, has enhanced efficacy in reducing radiative forcing because it liberates more-OH radicals to accelerate the cleaning of the troposphere. The overall reduction in non-CO2 GHG concentration would help to limit global temperature rise. By physically linking greenhouse gas removal to renewable electricity generation, the hybrid concept would avoid the moral hazard associated with most other climate engineering proposals. (C) 2017 The Authors. Published by Elsevier Ltd.
Exposure to cold physical plasma has been proposed to be of therapeutical value in in oncology via the generation of a number of biologically relevant redox-active molecules. Cancer cells can be recognized and eliminated by cells of the immune system, and accordingly many tumors are populated with these cells, among them T helper cells (TH cells). These lymphocyte population is crucial for effector immune responses against tumor antigens, in response to immunogenic cell death in malignant cells. However, a number of TH populations exists, each having distinct phenotypical features. Using a cold atmospheric pressure argon plasma jet, its redox activity was tested in different TH cell subpopulations to better understand the immunological consequences of potential antitumor plasma treatments in vivo.
The Arabidopsis vacuolar Na+/H+ antiporter gene, AtNHX1, was introduced into soybean by Agrobacterium-mediated transformation. Four independent kanamycin resistant lines were obtained. The result of PCR, Southern blotting and Northern blotting analyses demonstrated that the AtNHX1 gene was successfully inserted into the soybean genome and stably expressed in these kanamycin resistant lines. The stability of AtNHX1 expression and salt resistance were evaluated in the soybean transformants for over 6 generations. Two independently derived transgenic lines with high expression level of AtNHX1 were selected, and propagated to generation T-5 in the absence of selection pressure. PCR and RT-PCR examinations revealed that AtNHX1 was highly expressed in all investigated transgenic T-5 progenies. Furthermore, all transgenic T-5 plants showed resistant to salt stress, same as those of homozygous T-2 plants. Taken together, our results indicated that constitutive expression of AtNHX1 enhanced salt tolerance in soybean for over 6 generations, suggesting a great potential use of AtNHX1 for improving salt tolerance in plants by genetic engineering.
The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed.
Atomic Layer Deposition (ALD) is an enabling technology which provides coating and material features with significant advantages compared to other existing techniques for depositing precise nanometer-thin two-dimensional (2D) nanostructures. It is a cyclic process which relies on sequential self-terminating reactions between gas phase precursor molecules and a solid surface. ALD is especially advantageous when the film quality or thickness is critical, offering ultra-high aspect ratios. ALD provides digital thickness control to the atomic level by depositing film one atomic layer at a time, as well as pinhole-free films even over a very large and complex areas. Digital control extends to sandwiches, hetero-structures, nano-laminates, metal oxides, graded index layers and doping, and it is perfect for conformal coating and challenging 2D electrodes for various functional devices. The technique's capabilities are presented on the example of ALD-developed ultra-thin 2D tungsten oxide (W0(3)) over the large area of standard 4" Si substrates. The discussed advantages of ALD enable and endorse the employment of this technique for the development of hetero-nanostructure 2D semiconductors with unique properties. (C) 2016 Elsevier B.V. All rights reserved.
Atopic dermatitis (AD) or eczema is the most common chronic inflammatory skin disease. It is a multifactorial disease with local and systemic immune changes. Current therapies focus on restoring the local skin barrier or inhibiting immune responses. In this issue of the European Journal of Immunology, Sehra et al. [Eur. J. Immunol. 2016. 46: 2609-2613] describe a mouse model with T-cell-specific expression of constitutively active Stat6 in Flaky tail mice, which have mutations in the Flg and Tmem79 genes. The authors describe that it is the combination of changes in the skin barrier proteins filaggrin and Tmem79, together with Th2 cytokine signaling in the constitutively active Stat6 transgene, that drives the immune-pathomechanism in AD. These results are consistent with human studies where it is demonstrated that diminished filaggrin expression in skin is a predisposing factor for AD, but is neither required nor sufficient for disease indicating that additional factors are required for disease development. The current mouse model by Sehra et al. could be instrumental in evaluation new therapeutic strategies for AD.
Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. We sought to assess efficacy and safety of ustekinumab in patients with moderate-to-severe AD. In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks, and last dose at 32 weeks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. The ustekinumab group achieved higher SCORAD50 responses at 12, 16 ( the primary endpoint) and 20 weeks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32 weeks in the initial ustekinumab group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4 weeks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-gamma, elafin/PI3, CXCL1 and CCL17; P<. 05). Epidermal responses (K16, terminal differentiation) showed faster (4 weeks) and long-term regulation (32 weeks) from baseline in the ustekinumab group. No severe adverse events were observed. Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound "placebo" effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD.
Introduction: The goal of replantation after dental avulsion is to maintain the tooth in its socket. Presence of vital periodontal ligament cells on the root surface of the replanted tooth and the immunologic status of the patient are factors that protect against root resorption. It is known that dental constituents play an active role in root resorption by inducing specific and non-specific immune responses; however, little information exists regarding the influence of the acquired immune response on replantation. Therefore, the aim of this study was to evaluate the 5-year outcome of replantation in non-atopic and atopic patients. Methods: Clinical and radiographic examinations were performed in 62 replanted teeth during a 5-year period. The evaluation of atopy was based on the patients' personal and family histories and skin prick test results. The X-2 and the Z tests were used to assess the association between atopy and the outcome of the replanted teeth (P < .05). Results: There were significant differences between the 1-year and 5-year outcomes of the replanted teeth (P < .05) and atopic and non-atopic patients who had their teeth extracted because of inflammatory or replacement root resorption after 5 years (P < .05). Conclusions: Being atopic may offer the advantage of loss of fewer teeth because of replacement resorption, whereas being non-atopic may create an advantage of loss of fewer teeth because of inflammatory root resorption during the first 5 years after trauma.
1. Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family, transports certain lipophilic drugs, such as digoxin. To investigate the roles of this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA library, named ABCA8a. 2. The deduced mouse ABCA8a protein is 66% identical with that of human ABCA8 and possesses features common to the ABC superfamily. It was found that ABCA8a was mainly expressed in the liver and heart, similar to human ABCA8. 3. We further evaluated the effect of acute digoxin (a substrate for ABCA8) intoxication on the mRNA expression of ABCA8 using northern blotting with a 3' non-coding region as a probe to avoid cross-hybridization with other ABCA genes. 4. Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but not in the heart and kidney. 5. Real-time quantitative polymerase chain reaction analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5, ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin did not affect ABCA8a mRNA expression in the liver. 6. The results suggest that ABCA8 may play a role in digoxin metabolism in the liver.
There is a large body of literature on attachment styles and personality traits. The purpose of this study was to compare two commonly used instruments of attachment that measure secure, fearful, dismissing, and preoccupied styles. Furthermore, we sought to determine which personality factors and facets were common on both of the attachment measures. Overall, 273 undergraduates completed a demographic measure, two attachment scales (RQ and RSQ), and the NEO-PI-R to measure personality. We found high concordance between the NEO-PI-R factors and facets that predicted RSQ and RQ attachment. On both measures of attachment, a secure style was associated with lower neuroticism and higher extraversion. Fearful attachment was consistently predicted by being female, having higher neuroticism (specifically depression) as well as lower extraversion and agreeableness (specifically trust). Individuals scoring higher on preoccupied attachment had higher neuroticism (specifically depression) and lower agreeableness. Finally, individuals scoring higher on dismissing attachment had lower trust. These results confirm Griffin and Bartholemew's(1994) conceptualization of attachment as falling on the dimensions of anxiety and avoidance. Individuals with higher anxiety had higher neuroticism and lower agreeableness and those with higher avoidance had lower levels of trust. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
The relationship between adolescents' communication with their significant others (mother, father, and best friend) and quality of life (KIDSCREEN) was investigated in 2262 Scottish adolescent pet owners. The variable attachment to pets was also tested and assessed as a mediator of this relationship. A positive relationship between adolescents' communication with their significant other (mother, father, and best friend) and quality of life decreased when controlling for attachment to dogs. In cat owners, a positive relationship between communication with a best friend and quality of life decreased when controlling for attachment to cats. In cat and dog owners, attachment to these pets predicted higher levels of quality of life. Higher attachment to dogs and cats was explained by good best friend (IV) and attachment to pets (DV) and best friends. Mediation effects of attachment to dogs and cats might be explained in terms of the caring activities associated with these types of pets.
The authors examined the association between maternal childhood abuse and the frequency of providing social support to mothers when the victim is an adult and investigated the mediating effects of internal working models (self-esteem, positive relations with others) and maladaptive coping. Using data from the National Survey of Midlife Development in the United States II, they analyzed a sample of 887 adult children using a structural equation modeling approach. The results showed that maternal childhood abuse was associated with providing less frequent emotional support to mothers, although the authors did not find significant mediating effects of internal working models and maladaptive coping in the association between child abuse and intergenerational support giving. The findings suggest implications for theory, practice, and policy to address specific concerns and possible challenges that adults with a history of childhood abuse may experience in the relationship with their mothers.
Much is unknown about adult attachment style formation. We investigate whether negative reinforcement schedules promote hallmark features of secure and anxious attachment styles in a shock threat support-seeking paradigm. Participants ostensibly asked for help from another participant seated in another room. Each time a shock threat signal appeared they were to press a button to indicate their need for help. The supporter could then stop the imminent shock. The reliability of the supporters was varied such that some supporters were consistent (continuous reinforcement) whereas others were inconsistent (variable ratio reinforcement). Results indicated that inconsistently responsive others, reinforcing on a variable ratio schedule, led to heightened approach-related attentional biases toward the supporter, measured by event-related potentials, increased positive attachment associations with the supporter, implicitly measured via a lexical decision task, and more negative explicit evaluations of the supporter.
Reder and Duncan's well-known studies of the 1990s on fatal child abuse drew attention to how parental scripts regarding their children could dangerously distort relationships in ways that were sometimes fatal to children. This article reports on a new system for assessing the meaning of the child to the parent', called the Meaning of the Child Interview (MotC). Parents are interviewed using the established Parent Development Interview, or equivalent, and the transcript of the interview is then analysed according to parental sensitivity and likely risk to the child. The MotC constructs were developed from those used in observed parent-child interaction (specifically, the CARE-Index) and the form of discourse analysis used in the Dynamic Maturational Model - Adult Attachment Interview, allowing a more systemic and inter-subjective understanding of parenting representations than often put forward. This article discusses the theoretical background to the MotC, gives a brief review of similar measures and then introduces the coding system and patterns of caregiving. The validity of the MotC is addressed elsewhere.
Objective: A social-cognitive perspective on posttraumatic stress disorder (PTSD) has been proposed and posits that impaired social cognition, rooted in attachment insecurity, plays a role in the development of PTSD. Support for the role of impaired social cognition in PTSD has been found in adults, but the social-cognitive perspective on PTSD has not been examined in adolescents. This study sought to explore differences in social cognition and PTSD on the basis of attachment security, and it examined social cognition as a mediator in the relation between attachment security and PTSD and with regard to PTSD symptom change during inpatient treatment. Method: We recruited 142 adolescents from an inpatient psychiatric hospital, where adolescents and their parents completed assessments at admission and discharge. Results: Adolescents with a secure attachment demonstrated better social-cognitive skills than did those with an insecure attachment. Social cognition mediated the relation between adolescents' maternal attachment representations and PTSD at admission across 3 self-and parent-report measures. Social cognition also mediated the relation between adolescents' maternal attachment representations at admission and PTSD treatment outcome. Conclusion: This study provides the 1st support for the application of Sharp, Fonagy, and Allen's (2012) social-cognitive perspective of PTSD to adolescents by showing a link between clinically significant symptoms of PTSD and attachment security through social-cognitive impairment. Findings indicate that improvement in PTSD during medium-stay inpatient treatment is partially driven by baseline attachment security and social-cognitive abilities, highlighting the potential of social-cognitive skills as important targets of clinical intervention among adolescents with PTSD.
There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-alpha between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-alpha and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-alpha between groups. Pearson correlations were used to study associations between IL-6, TNF-alpha, and CAR. There were no significant differences in serum IL-6 or TNF-alpha levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0386, p=0.020), TNF-alpha Cr=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between 1L-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-alpha, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-alpha and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies. (C) 2017 Elsevier Ltd. All rights reserved.
Two experiments were conducted to investigate the effects of coaction on saccadic and manual responses. Participants performed the experiments either in a solitary condition or in a group of coactors who performed the same tasks at the same time. In Experiment 1, participants completed a pro-and antisaccade task where they were required to make saccades towards (prosaccades) or away (antisaccades) from a peripheral visual stimulus. In Experiment 2, participants performed a visual discrimination task that required both making a saccade towards a peripheral stimulus and making a manual response in reaction to the stimulus's orientation. The results showed that performance of stimulus-driven responses was independent of the social context, while volitionally controlled responses were delayed by the presence of coactors. These findings are in line with studies assessing the effect of attentional load on saccadic control during dual-task paradigms. In particular, antisaccades - but not prosaccades - were influenced by the type of social context. Additionally, the number of coactors present in the group had a moderating effect on both saccadic and manual responses. The results support an attentional view of social influences.
Moving beyond the distinction between biological and social facts has proved challenging due to several basic methodological and ontological differences among scientific disciplines. The aim of this paper is to show how attention schema theory (hereafter AST), developed by Michael Graziano, provides a useful addition to existing integrative approaches that can be used to overcome impediments to interdisciplinary crossfertilization, such that the influence of a range of interconnected institutional, situational, biographical, psychological, neural and genetic variables can be considered simultaneously in a parsimonious way. The paper provides an overview of three basic methodological and ontological differences dividing scientists researching human nature and society. It then draws on AST and a selection of existing approaches in the interdisciplinary vein to demonstrate how to move beyond the reductionist tendencies of each discipline. In the view of AST, intrinsic brain processes and social and situational aspects are intricately intertwined and continuously influence each other in shaping specific attentional focuses. Social identities, biographical experiences, symbols, roles and subject positions contribute to directing attention to certain kinds of stimuli, details, or information, while at the same time, intrinsic predispositions make individuals inclined to attend to different types of information. By accounting for the brain basis of awareness as a subjective experience, AST can be used to clarify how social identities influence attention, and thus, the linkages between individual cognition and wider institutional structures. Finally, the paper considers the relationships between the cognitive and the institutional levels of analysis, and highlights the importance of the latter as a distinct level of analysis. In this way, the paper charts the multidirectional and interactive causal relationship between intrinsic brain processes, attention and conscious awareness, and how they relate to wider institutional structures and joint attentional interactions at higher levels of aggregation.
Despite a wealth of knowledge about the neural mechanisms behind emotional facial expression processing, little is known about how they relate to individual differences in social cognition abilities. We studied individual differences in the event-related potentials (ERPs) elicited by dynamic facial expressions. First, we assessed the latent structure of the ERPs, reflecting structural face processing in the N170, and the allocation of processing resources and reflexive attention to emotionally salient stimuli, in the early posterior negativity (EPN) and the late positive complex (LPC). Then we estimated brain-behavior relationships between the ERP factors and behavioral indicators of facial identity and emotion-processing abilities. Structural models revealed that the participants who formed faster structural representations of neutral faces (i.e., shorter N170 latencies) performed better at face perception (r = -.51) and memory (r = -.42). The N170 amplitude was not related to individual differences in face cognition or emotion processing. The latent EPN factor correlated with emotion perception (r = .47) and memory (r = .32), and also with face perception abilities (r = .41). Interestingly, the latent factor representing the difference in EPN amplitudes between the two neutral control conditions (chewing and blinking movements) also correlated with emotion perception (r = .51), highlighting the importance of tracking facial changes in the perception of emotional facial expressions. The LPC factor for negative expressions correlated with the memory for emotional facial expressions. The links revealed between the latency and strength of activations of brain systems and individual differences in processing socio-emotional information provide new insights into the brain mechanisms involved in social communication.
In heterosexual individuals, attention is automatically captured by physically attractive members of the opposite sex. Although helpful for selecting new mates, attention to attractive relationship alternatives can threaten satisfaction with and commitment to an existing romantic relationship. The current study tested the hypothesis that although a mating prime would increase selective attention to attractive opposite-sex targets (relative to less attractive targets) among single participants, this effect would be reduced among people already committed to a long-term romantic partner. Consistent with hypotheses, whereas single participants responded to a mating prime with greater attentional adhesion to physically attractive opposite-sex targets (relative to less attractive targets), participants in a committed romantic relationship showed no such effect. These findings extend previous research suggesting the presence of relationship maintenance mechanisms that operate at early stages of social cognition.
Fearful faces both capture our attention and hold it. However, little is known about the time-course for the capture and hold of spatial attention by fearful, and other emotional, faces. In three dot-probe studies we examined this time-course. Experiments 1 and 2 used fearful and neutral faces. In Experiment 1, dot-probe targets occurred 133, 266, and 532 ms post-face onset and in Experiment 2, dot-probe targets occurred 84, 168, 336, and 672 ms post-face onset. In Experiment 1, for both 133 and 266 ms conditions, reaction times were fastest for congruent trials and slowest for incongruent trials with reaction times for baseline trials falling between the two. The same pattern was found for the 84 and 168 ms conditions in Experiment 2. For the later time-points in both experiments there were no significant differences between conditions. To examine whether this time-course is unique to fearful faces, a third dot-probe experiment using time-points identical to Experiment 2 was conducted with happy and neutral faces. The results from Experiment 3 suggest that happy faces captured and held attention in the 168 and 336 ms conditions. Together, the results indicate that attention is captured and held by fearful faces at times earlier than approximately 300 ms, while happy faces also captured and held attention, but on a slightly different time-course from 168 to 336 ms.
Explicit tests of social cognition have revealed pervasive deficits in schizophrenia. Less is known of automatic social cognition in schizophrenia. We used a spatial orienting task to investigate automatic shifts of attention cued by another person's eye gaze in 29 patients and 28 controls. Central photographic images of a face with eyes shifted left or right, or looking straight ahead, preceded targets that appeared left or right of the cue. To examine automatic effects, cue direction was non-predictive of target location. Cue-target intervals were 100, 300, and 800 ms. In non-social control trials, arrows replaced eye-gaze cues. Both groups showed automatic attentional orienting indexed by faster reaction times (RTs) when arrows were congruent with target location across all cue-target intervals. Similar congruency effects were seen for eye-shift cues at 300 and 800 ms intervals, but patients showed significantly larger congruency effects at 800 ms, which were driven by delayed responses to incongruent target locations. At short 100-ms cue-target intervals, neither group showed faster RTs for congruent than for incongruent eyeshift cues, but patients were significantly slower to detect targets after direct-gaze cues. These findings conflict with previous studies using schematic line drawings of eye-shifts that have found automatic attentional orienting to be reduced in schizophrenia. Instead, our data indicate that patients display abnormalities in responding to gaze direction at various stages of gaze processing-reflected by a stronger preferential capture of attention by another person's direct eye contact at initial stages of gaze processing and difficulties disengaging from a gazed-at location once shared attention is established.
Attentional lapses are usually defined as temporary and often brief shifts of attention away from some primary task to unrelated internal information processing. This study addressed the incidence of attention lapses and differences in attentional functioning in 30 children with attention-deficit/hyperactivity disorder (ADHD), 26 healthy children, and 29 children with spina bifida myelomeningocele and hydrocephalus (SBH). Assessments were conducted using computerized tonic and phasic attention tests, the Symbol Digit Modalities Test (SDMT), and the Trail Making Test Form B (TMT-B). The group with SBH differed from normal controls on cognitive measures of attention and executive functions. The ADHD group obtained lower scores than the SBH group and healthy children. ANOVA results showed that there was an effect of shunt revisions and shunt-related infections on neuropsychological performance. Lapses of attention together with reaction time may thus represent important factors for the understanding of cognitive deficits in SBH.
Introduction: Previous studies have demonstrated that students with attention-deficit/hyperactivity disorder (ADHD) struggle particularly with grasping the implicit, inferential level of narratives that is crucial for story comprehension. However, these studies used offline tasks (i.e., after story presentation), used indirect measurements (e.g., identifying main ideas), and/or yielded inconclusive results using think-aloud techniques. Moreover, most studies were conducted with preschool or elementary school children with ADHD, using listening or televised story comprehension. In this study, we were interested in examining the spontaneous, immediate activation and/or suppression of forward-predictive inferences, backward-explanatory inferences, and inference-evoking textual information, as they occur online during reading comprehension by adolescents with ADHD. Method: Participants with and without ADHD read short narrative texts, each of which included a predictive sentence, a bridging sentence that referred back to the predictive sentence via actualization of the predicted event, and two intervening sentences positioned between the predictive and bridging sentences that introduced a temporary transition from the main (predictive) episode. Activation and suppression of inferential and/or textual information were assessed using naming times of word probes that were implied by the preceding text, explicitly mentioned in it, or neither when following control texts. In some cases, a true-false inferential or textual question followed the probe. Results: Naming facilitations were observed for the control but not for the ADHD group, in responding to inference probes that followed the predictive and bridging sentences, and to text probes that followed the predictive sentences. Participants with ADHD were accurate, albeit slower, than controls in answering the true-false questions. Conclusions: Adolescents with ADHD have difficulties in generating predictive and explanatory inferences and in retaining relevant textual information in working memory while reading, although they can answer questions after reading when texts are relatively short. These findings are discussed with regard to development of comprehension strategies for individuals with ADHD.
Introduction: Cannabis users are at higher risk for any mental disorder than the general population. However, there remains a shortage of research that examines the relationship between reluctance to seek mental health treatment and subsequent frequent cannabis use. This study evaluates whether negative attitudes toward mental health treatment (i.e. attitudinal barriers) predict a high frequency of cannabis use and whether using cannabis to cope with mental health symptoms (i.e., coping motives) explains this relationship. Methods: Participants were students at Washington State University (WSU) who received violations for illegal cannabis use or possession. Data were collected from participants 60 days after a mandated two-part course for cannabis harm reduction (n = 98). A cross-sectional path analysis was performed to assess whether coping motives mediated the relationship between attitudinal barriers to mental health treatment and frequency of cannabis use after controlling for mental health symptoms. Results: Coping motives fully mediated the relationship between negative attitudes toward treatment and frequency of use (indirect effect: (beta = 0.087, bootstrap CI: 0.016-0.541). The direction of results was confirmed by switching the mediator and criterion variable. The model fit well with the data (x(2) (2) = 0.367, p = 0.83, RMSEA = 0.00, CFI = 1, SRMR = 0.008). Conclusions: Reluctance to seek mental health treatment may be related to higher levels of cannabis use through coping motives. Addressing attitudes toward mental health treatment may be an alternative way to decrease frequency of use or possibly promote mental health treatment-seeking behaviors when needed. Further studies are needed to confirm the implications of this finding. Published by Elsevier Ltd.
This study aims to investigate the impacts of a digital learning module with guided peer feedback on students' domain-specific knowledge gain and their attitudinal change in the field of biotechnology and molecular life sciences. The extent to which the use of this module is appreciated by students is studied as well. A pre-test, post-test design was used with 203 students who were randomly assigned to groups of three. They were asked to work on the digital module with the aim of exploring various perspectives, and the pros and cons on the topic of Genetically Modified Organisms (GMOs). The results suggest that the module can be used to foster students' domain-specific knowledge gain and their attitudinal change. Furthermore, the module was evaluated positively in terms of students' motivation and satisfaction with the learning experiences. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):31-39, 2017.
High-valent Au(III) complexes have attracted much attention as catalysts in many reactions. Nevertheless Au(III) catalysts suffer from instability of the oxidized metal complexes during preparation and use. Herein, we demonstrated that Au(III) catalysts can be stabilized against reduction to metallic Au by modifying supported-ionic-liquid-phase-stabilized Au(III) catalyst with CuCl2. It was found that the that reduced Au could be re -oxidized in situ to Au3+ species by CuCl2 during the reaction and further stabilized by the electron transfer from Cu to these active species. When evaluated in the acetylene hydrochlorination reaction, the Au-Cu-IL/AC catalyst displayed an excellent specific activity with the turnover frequency (TOF) as high as 168.5 h(-1) and more than 99.8% selectivity fot the product, vinyl chloride (VCM). Furthermore, the Au-Cu-IL/AC catalyst demonstrated a stable catalytic performance with a negligible loss of C2H2 conversion after 500 h under typical industrial reaction conditions for acetylene hydrochlorination. Therefore, the findings of this work provide an efficient approach for designing stable high-valent metals for long-term operation, and also pave the way for the application of Au-Cu-IL/AC catalyst in industrial VCM production. (C) 2017 Elsevier B.V. All rights reserved.
A low-quiescent high-performance class-AB headphone amplifier is presented. The effect of the input-referred offset on the quiescent power of audio power amplifier (APA) that drives very small resistive load is described and analyzed. A digitally assisted offset calibration-based APA topology together with improved frequency compensation is proposed. This permits the use of low quiescent power and small compensation capacitance. Implemented in 65-nm CMOS technology, the amplifier occupies an area of 0.15 mm(2) and consumes 0.4 mW at +/- 1 V supplies. At the load of 16 Omega//200 pF, the gain-bandwidth product is 1.78 MHz using a total compensation capacitance of 8.5 pF. Other performance metrics are measured with -89-dB total harmonic distortion (THD+ N), 93.5-dB signal-to-noise ratio, 84-dB power supply rejection ratio (PSRR+), and 105-dB PSRR-@ 217 Hz. It can deliver a peak power of 35 mW (1.5 Vpp swing) to the above load, yielding the best figure-of-merit (FOM) = (peak load power/quiescent power) and the best FOM2 = [peak load power/quiescent power * (THD+ N)%] with respect to other reported representative works.
It is traditionally challenging to implement higher-order PWM closed-loop Class-D audio amplifiers using analog intensive techniques in deep-submicron, low voltage process technologies. This is primarily attributed to reduced power supply, degraded analog transistor characteristics, including short-channel effects, increased flicker noise, random telegraph noise, transistor reliability concerns and passive component performance. In this paper, we introduce a global closed-loop mixed-signal architecture incorporating digital control and integrate a fourth-order amplifier prototype in 55 nm CMOS. A systematic approach to analyze, design and compensate the feedback loop in the digital domain is also presented. The versatility of implementing the loop gain poles and zeros digitally attains high gain throughout the audio band and attenuates residual high frequency ripples around the loop, simultaneously accomplishing improvements in THD+ N and PSRR. The overall architecture is inherently amenable to implementation in deep-submicron and is therefore compatible with scaled CMOS. The measured prototype achieves a high 105 dBA SNR, 0.0031% THD+ N, 92 dB PSRR and 85% efficiency when supplying 1 W into emulated 8 speaker load. This performance is competitive with conventional designs using large feature size precision CMOS or specialized BCD technologies and reports the highest output power (1.5 W) for deep-submicron designs.
In this study a novel auditory version of the Single Category Implicit Association Test (SC-IAT-A) was developed to investigate (a) the valence of adults' associations to infant cries and laughs, (b) moderation of implicit associations by gender and empathy, and (c) the robustness of implicit associations controlling for auditory sensitivity. Eighty adults (50% females) were administered two SC-IAT-As, the Empathy Quotient, and the Weinstein Noise Sensitivity Scale. Adults showed positive implicit associations to infant laugh and negative ones to infant cry; only the implicit associations with the infant laugh were negatively related to empathy scores, and no gender differences were observed. Finally, implicit associations to infant cry were affected by noise sensitivity. The SC-IAT-A is useful to evaluate the valence of implicit reactions to infant auditory cues and could provide fresh insights into understanding processes that regulate the quality of adult-infant relationships.
Introduction. Plum cultivars exhibit differences in their fruit quality; however, very little is known about the changes in fruit growth and quality of plum cultivars maturing in different seasons. This study was conducted to contribute to a better understanding of the fruit growth and ripening behavior of Japanese plum (Prunus silicina Lindl.) varieties according to their maturing season. Materials and methods. Three Japanese plum cultivars were studied: early- ['Black Amber' (BA)], mid-['Amber Jewel' (AJ)] and late-season ['Angelino' (AG)] maturing. The increase in fruit weight and diameter was determined from days after full bloom (DAFB) to harvest, whilst changes in fruit pulp, skin and seed dry weights, fruit firmness, soluble solid contents (SSC), and titratable acidity (TA) were studied during days after stone hardening (DASH). Ethylene production, respiration rate, activities of 1-aminocyclopropane-1-carboxylic acid synthase (ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) enzymes, fruit firmness, fruit color, SSC, TA, ascorbic acid, total antioxidant and carotenoid contents were determined at alternate days during fruit ripening. Results and discussion. All plum cultivars exhibited three distinct phases of fruit growth and development in the DAFB. The AG fruit exhibited the longest duration of phase-III, about 64 days and 12 days more, as compared with BA and AJ fruits, respectively. Fruit skin dry weight (%) was higher for AG fruit, whilst, AJ and BA fruits exhibited the highest increase in seed and pulp dry weight (%) during DASH. The BA and AJ fruits showed climacteric fruit ripening with a sharp rise in ACS and ACO enzymes; whereas AG fruit showed suppressed climacteric ripening. During the fruit ripening period AG fruit remained more firm with higher SSC, and SCC: TA ratio as compared with BA and AJ fruits. The level of ascorbic acid (24.8 mg 100 g(-1)) was higher in AG fruit. Whilst, total carotenoids (0.66 mg 100 g(-1)) and total antioxidants (215 mu mol Trolox 100 g(-1)) were higher in AJ and BA fruit respectively. Conclusion. The physico-chemical changes during fruit ripening vary with cultivar and are associated with the level of endogenous ethylene production. Japanese plum cultivars exhibit varying levels of SSC, SSC: TA ratio, levels of individual and total antioxidants of their ripe fruits.
Although recent scholarship focuses on the increasing significance of processes of standardization in contemporary social life, much less attention has been given to how standardization impacts intimate life, and how intimate standards are made meaningful in interaction. This article draws from participant observation in online transgender groups to examine how the medical standardization of transsexuality, known as the wrong-body' model, impacts the way users understand and communicate their gendered self. I show how rather than simply adopting the wrong-body model, participants use its language and logic in ironic and playful ways that carve out spaces for ways of knowing the self that feel authentically their own. This case shows how intimate standards become part of the language of the self in ways that may be unexpected.
Across a broad range of design professions, there has been extensive research on design practices and considerable progress in creating new computer-based systems that support design work. Our research is focused on educational/instructional design for students' learning. In this sub-field, progress has been more limited. In particular, neither research nor systems development have paid much attention to the fact that design is becoming a more collaborative endeavor. This paper reports the latest research outcomes from R&D in the Educational Design Studio (EDS), a facility developed iteratively over four years to support and understand collaborative, real-time, co-present design work. The EDS serves to (i) enhance our scientific understanding of design processes and design cognition and (ii) provide insights into how designers' work can be improved through appropriate technological support. In the study presented here, we introduced a complex, multi-user, digital design tool into the existing ecology of tools and resources available in the EDS. We analysed the activity of four pairs of 'teacher-designers' during a design task. We identified different behaviors - in reconfiguring the task, the working methods and toolset usage. Our data provide new insights about the affordances of different digital and analogue design surfaces used in the Studio. (C) 2017 Elsevier Ltd. All rights reserved.
The aim of this study was to identify specific cognitive abilities that predict functional outcome in high-functioning adults with autism spectrum disorder (ASD), and to clarify the contribution of those abilities and their relationships. In total, 41 adults with ASD performed cognitive tasks in a broad range of neuro- and social cognitive domains, and information concerning functional outcomes was obtained. Regression analyses revealed that emotion perception and verbal generativity predicted adaptive functioning directly, and the former mediated between the other two. These findings provide the first evidence of a triadic relationship among neuro- and social cognition and functional outcome in this population. Our results suggest that psychosocial interventions targeting these cognitive abilities could benefit social adaptation in adults with ASD.
Background Cognitive differences, including deficits in self-awareness, are common in high-functioning individuals with autism spectrum disorder (ASD) and represent a fruitful target for intervention. The current project presents the preliminary research undertaken in the development of metacognitive training (MCT), an intervention designed to increase knowledge about personal strengths and challenges in adolescents with ASD.Method Two groups of 4 adolescents with ASD completed MCT, as well as measures to assess satisfaction and adverse effects. Visual inspection and thematic analysis were used to interpret the data.Results Overall, both participants and their parents rated MCT favourably; the youth most enjoyed the interactive activities, whereas parents appreciated the opportunity for socialising and psychoeducation. There were no systematic changes on quantitative measures of adverse effects (i.e. self-esteem or depression).Conclusion Although the results suggest further investigation of MCT may be warranted, certain modifications to the MCT protocol and research methodology are needed.
The present study aimed to examine the effects of a novel avatar interviewing aid during memory interviews with children with autism spectrum disorder (ASD). Thirty children were recruited for our study (Age: M = 7.60, SD = 0.68), half with ASD (13 boys; 2 girls) and the other half being neurotypical (13 boys; 2 girls). Children participated in a target event and were subsequently interviewed a week later by either an avatar interviewer or a human. The participants were also asked six misleading questions aimed to examine their suggestibility. Bayesian analysis showed some increase in memory performance for both groups of children interviewed by the avatar interviewer, and this effect exacerbated for children with ASD. These results showed encouraging implications for future applications.
The ability of individuals with Autism Spectrum Disorder (ASD) to process context has long been debated: According to the Weak Central Coherence theory, ASD is characterized by poor global processing, and consequentlypoor context processing. In contrast, the Social Cognition theory argues individuals with ASD will present difficulties only in social context processing. The complexity theory of autism suggests context processing in ASD will depend on task complexity. The current study examined this controversy through two priming tasks, one presenting human stimuli (facial expressions) and the other presenting non-human stimuli (animal faces). Both tasks presented visual targets, preceded by congruent, incongruent, or neutral auditory primes. Local and global processing were examined by presenting the visual targets in three spatial frequency conditions: High frequency, low frequency, and broadband. Tasks were administered to 16 adolescents with high functioning ASD and 16 matched typically developing adolescents. Reaction time and accuracy were measured for each task in each condition. Results indicated that individuals with ASD processed context for both human and non-human stimuli, except in one condition, in which human stimuli had to be processed globally (i.e., target presented in low frequency). The task demands presented in this condition, and the performance deficit shown in the ASD group as a result, could be understood in terms of cognitive overload. These findings provide support for the complexity theory of autism and extend it. Our results also demonstrate how associative priming could support intact context processing of human and non-human stimuli in individuals with ASD. Autism Res2017, 10: 520-530. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with atypical cortical maturation leading to a deficiency in social cognition and language. Numerous studies have attempted to classify ASD using brain measurements such as cortical thickness, surface area, or volume with promising results. However, the underpowered sample sizes of these studies limit external validity and generalizability at the population level. Large scale collaborations such as Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) or the Autism Brain Imaging Data Exchange (ABIDE) aim to bring together like-minded scientists to further improve investigations into brain disorders. To the best of our knowledge, this study represents the largest classification analysis for detection of ASD vs. healthy age and sex matched controls using cortical thickness brain parcellations and intracranial volume normalized surface area and subcortical volumes. We were able to increase classification accuracy overall from 56% to 60% and for females only by 6%. These novel findings using Evolving Partitions to Improve Connectomics (EPIC) underscore the importance of large-scale data-driven approaches and collaborations in the discovery of brain disorders.
Machine learning approaches have been widely used for the identification of neuropathology from neuroimaging data. However, these approaches require large samples and suffer from the challenges associated with multi-site, multi-protocol data. We propose a novel approach to address these challenges, and demonstrate its usefulness with the Autism Brain Imaging Data Exchange (ABIDE) database. We predict symptom severity based on cortical thickness measurements from 156 individuals with autism spectrum disorder (ASD) from four different sites. The proposed approach consists of two main stages: a domain adaptation stage using partial least squares regression to maximize the consistency of imaging data across sites; and a learning stage combining support vector regression for regional prediction of severity with elastic-net penalized linear regression for integrating regional predictions into a whole-brain severity prediction. The proposed method performed markedly better than simpler alternatives, better with multi-site than single-site data, and resulted in a considerably higher cross-validated correlation score than has previously been reported in the literature for multi-site data. This demonstration of the utility of the proposed approach for detecting structural brain abnormalities in ASD from the multi-site, multi-protocol ABIDE dataset indicates the potential of designing machine learning methods to meet the challenges of agglomerative data.
Social deficits are a core symptom of autism spectrum disorder; however, the perturbed neural mechanisms underpinning these deficits remain unclear. It has been suggested that social prediction errors-coding discrepancies between the predicted and actual outcome of another's decisions-might play a crucial role in processing social information. While the gyral surface of the anterior cingulate cortex signalled social prediction errors in typically developing individuals, this crucial social signal was altered in individuals with autism spectrum disorder. Importantly, the degree to which social prediction error signalling was aberrant correlated with diagnostic measures of social deficits. Effective connectivity analyses further revealed that, in typically developing individuals but not in autism spectrum disorder, the magnitude of social prediction errors was driven by input from the ventromedial prefrontal cortex. These data provide a novel insight into the neural substrates underlying autism spectrum disorder social symptom severity, and further research into the gyral surface of the anterior cingulate cortex and ventromedial prefrontal cortex could provide more targeted therapies to help ameliorate social deficits in autism spectrum disorder.
We tested social cognition abilities of adolescents with autism spectrum disorders (ASD) and neurotypically developed peers (NTD). A multi-faceted test-battery including facial emotion categorization (FEC), classical false belief tasks (FBT), and complex social cognition (SC), yielded significantly lower accuracy rates for FEC and complex SC tasks in ASD, but no significant differences in performance concerning FBT. A significant correlation between age and performance in a FEC task and in a complex task was found only in ASD. We propose that dynamic and/or fragmented FEC tasks can elicit deficits in implicit processing of facial emotion more efficiently. The difficulties of ASD in solving complex SC tasks can be ascribed to deficits in the acquisition and application of social schemata.
Objective Children with autism have sitting and on-task behavior problems in class. In this study, the effect of three alternative classroom-seating devices such as regular classroom chairs, therapy balls, and air cushions were examined on students' classroom behavior. Materials & Methods 15 students with autism participated in this A1-B-A2-C multiple treatments study from Mashhad's Tabasom School, Mashhad, Iran in 2014. Students' behaviors were video recorded in three phases: sitting on their common chairs during phase A, air-sit cushioned in phase B, and ball chairs in phase C. Sitting times and on-task behaviors were quantified by momentary time sampling and compared during different phases for important changes during 8 wk. Additionally, the Gilliam Autism Rating Scale-Second Edition test was used to examine stereotyped movements, social and communication skills of the students in the before and after research. Results Significant increases in in-seat behaviors in 86.7% (thirteen out of 15) of the students and on-task behaviors in 53.3% of the students (eight out of 15) when seated on therapy balls. Air cushions had no significant effects on in-seat/on-task behaviors. The results also showed significant decrease in stereotyped movement and increase in communication and social skills of these students. The teachers also preferred the use of the balls and/ or air-cushioned chairs for their students. Conclusion Therapy ball chairs facilitated in-seat behavior and decreased autism related behavior of the students with Autism Spectrum Disorder in class.
People with autism spectrum disorder (ASD) have difficulties in identifying another person by face and voice. This might contribute considerably to the development of social cognition and interaction difficulties. The characteristics of the voice recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral test battery to systematically investigate voice processing in high-functioning ASD (n=16) and typically developed pair-wise matched controls (n=16). The ASD group had particular difficulties with discriminating, learning, and recognizing unfamiliar voices, while recognizing famous voices was relatively intact. Tests on acoustic processing abilities showed that the ASD group had a specific deficit in vocal pitch perception that was dissociable from otherwise intact acoustic processing (i.e., musical pitch, musical, and vocal timbre perception). Our results allow a characterization of the voice recognition deficit in ASD: The findings indicate that in high-functioning ASD, the difficulty to recognize voices is particularly pronounced for learning novel voices and the recognition of unfamiliar peoples' voices. This pattern might be indicative of difficulties with integrating the acoustic characteristics of the voice into a coherent percepta function that has been previously associated with voice-selective regions in the posterior superior temporal sulcus/gyrus of the human brain. Autism Res2017, 10: 155-168. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Individuals with autism spectrum disorders (ASD) show significant impairments in social skills and theory of mind (ToM). The aim of this study was to evaluate ToM and social information processing abilities in 52 children with ASD compared to 55 typically developing (TD) children. A mediation analysis evaluated whether social information processing abilities can be mediated by ToM competences. In our results, children with autism showed a deficit in social skills and ToM components. The innovative results of our study applying mediation analysis demonstrate that ToM plays a key role in the development of social abilities, and the lack of ToM competences in children with autism impairs their competent social behavior.
Background: Responding to joint attention (RJA) is reduced in young children with ASD despite being vital to the early development of social communication. For this reason, RJA is a frequent target in early intervention programs. Clinical guidelines suggest that exaggerating facial expressions or gestural pointing may improve RJA in children with autism by clarifying the meaning of the gaze or gesture. In the current study, we investigate the effect of intensity of emotional expression on RJA in preschoolers with ASD. Method: Twenty-five preschoolers with ASD and 21 typically developing peers were administered a specifically designed eye-tracking task in which an actor directs attention to a moving object by looking at it with an expression that was either neutral, mildly surprised or intensely surprised. In a supplementary condition, gestural pointing was accompanied by a neutral gaze shift. Results: Commensurate with previous studies, children with ASD oriented less to the face of the actor and were less responsive to RJA when compared to their typically developing peers. However, children with autism differed in their response to RJA according to the different task conditions. They demonstrated more frequent responses to RJA when the actor's facial expression was either intense or supported by gestural pointing. Conclusions: We report initial evidence for the importance of clarifying content cues in order to help preschoolers with autism adhere to receptive joint attention (RJA) opportunities. Our findings inform knowledge about early treatment and attention to emotional expressions in autism and improve our understanding of how early interventions may work to increase RJA in young children with ASD. (C) 2016 Elsevier Ltd. All rights reserved.
Aim: Oxytocin presents an exciting potential to target the core symptoms of autism spectrum disorder (ASD) pharmacologically in an easily administered, cost-effective form with possibly minimal adverse effects. But, there are still major gaps in this area of research. This paper reviewed randomized controlled trials (RCTs) examining the effects of oxytocin administration on social cognition and restricted, repetitive behaviors in individuals with an ASD. Method: Electronic literature searches were conducted from PsycINFO, PubMed, Web of Knowledge, and EMBASE for RCTs published through June 2015. Results: 12 RCTs were included in this review. 7 out of the 11 studies that examined social cognition reported improvements. Additionally, one out of the 4 studies on restricted, repetitive behaviors, reported improvements following oxytocin administration. However, results from our meta-analyses suggest that oxytocin has no significant effect on these 2 domains. Conclusion: Previous evidence revealed mixed findings about the effects of oxytocin on ASD. Given the limited number of RCTs, our summary of findings on the effectiveness of oxytocin on ASD should still be considered tentative.
The purpose of this study was to examine the utility of the Systematic Observation of Red Flags as an observational level-two screening measure to detect risk for autism spectrum disorder in toddlers when used with a video-recorded administration of the Communication and Symbolic Behavior Scales. Psychometric properties of the Systematic Observation of Red Flags were examined in a sample of 247 toddlers of 16- to 24months old: 130 with autism spectrum disorder, 61 with developmental delays, and 56 typically developing. Individual items were examined for performance to create an algorithm with improved sensitivity and specificity, yielding a total Composite score and Domain scores for Social Communication and Restricted Repetitive Behaviors. Codes indicating clear symptom presence were collapsed to yield a count of the number of Red Flags for the overall scale and each symptom domain. Results indicated significant group differences with large effects for the Composite, both Domain scores, and Red Flags score, and good discrimination (area under the curve=0.84-0.87) between autism spectrum disorder and nonspectrum groups for the Composite, Social Communication Domain, and Social Communication Red Flags score. The Systematic Observation of Red Flags provides an observational screening measure for 16- to 24-month-olds with good discrimination, sensitivity, and specificity. A cutoff of 20 on the Composite is recommended to optimally detect autism spectrum disorder risk.
It has been recognized that individuals with autism spectrum disorder (ASD) show discrepancies between their abstract capacities to solve social cognition dilemmas and their ability to spontaneously decipher live social interactions. In the last 15 years, different paradigms have been designed to investigate how individuals with ASD grasp information when emerged in naturalistic or live social interactions. The present paper reviews three categories of such paradigms that focus on (1) verbal questionnaires and interviews while participants view a naturalistic social scenario, (2) eye tracking methods while participants view naturalistic settings, and (3) simulation of social interactions using virtual reality or robotics. This paper discusses the advantages and limitations of each paradigm and suggests a new concept for combining these paradigms.
Autism is characterised by difficulties in social functioning, notably in interactions with other people. Yet, most studies addressing social difficulties have used static images or, at best, videos of social stimuli, with no scope for real interaction. Here, we study one crucial aspect of social interactionsgaze behaviourin an interactive setting. First, typical individuals were shown videos of an experimenter and, by means of a deception procedure, were either led to believe that the experimenter was present via a live video-feed or was pre-recorded. Participants' eye movements revealed that when passively viewing an experimenter they believed to be live, they looked less at that person than when they believed the experimenter video was pre-recorded. Interestingly, this reduction in viewing behaviour in response to the believed live presence of the experimenter was absent in individuals high in autistic traits, suggesting a relative insensitivity to social presence alone. When participants were asked to actively engage in a real-time interaction with the experimenter, however, high autistic trait individuals looked significantly less at the experimenter relative to low autistic trait individuals. The results reinforce findings of atypical gaze behaviour in individuals high in autistic traits, but suggest that active engagement in a social interaction may be important in eliciting reduced looking. We propose that difficulties with the spatio-temporal dynamics associated with real social interactions rather than underlying difficulties processing the social stimulus itself may drive these effects. The results underline the importance of developing ecologically valid methods to investigate social cognition. Autism Res2017, 10: 359-368. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
To assess the impact of their child's symptoms of Autism Spectrum Disorder upon parents' anxiety and depression, 68 mothers of boys aged 10 to 15 years (M = 12.6 years, SD = 1.6 years) completed the ASD Behaviour Checklist, the GAD7 and the PHQ9 at a single setting. Results indicated that the boys' restricted and repetitive behaviours had the strongest relationship with their mothers' anxiety and depression, followed by communication difficulties, but the latter set of behaviours did not significantly add to the variance predicted by restricted and repetitive behaviours. Their sons' intense reactions to stressors was the most powerful ASD-related contributor to the anxiety and depression experienced by these mothers. Several suggestions for enhancing parental coping with this aspect of their child's ASD behavioural symptomatology are discussed.
Background: Although children with autism spectrum disorder (ASD) are more likely to be exposed to harsh parental discipline, research on this issue is scarce. In particular, few studies have examined the risk factors for harsh parental discipline in this population. We responded to this gap in the literature by testing multiple individual and environmental factors as potential predictors of parental psychological aggression and physical assault toward children with ASD. Guided by a developmental-ecological perspective, we hypothesized that harsh parental discipline would be shaped by the characteristics of the child (symptom severity), the parent (parenting stress), the family (economic pressure), and the broader context (discrimination in the community). Method: A total of 424 Hong Kong parents of children with ASD completed standardized questionnaires. The hypotheses were tested using bivariate correlation and multivariate regression analyses. Results: At the bivariate level, child symptom severity, parenting stress, family economic pressure, and experienced discrimination were positively associated with parental psychological aggression. Moreover, child symptom severity and parenting stress were positively associated with parental physical assault. At the multivariate level, parenting stress was significantly related to psychological aggression, while child symptom severity and parenting stress were significantly related to physical assault. Mediation analyses further demonstrated that psychological aggression partially mediated the effect of parenting stress on physical assault. Conclusions: Theoretically, our findings contributed to our understanding of the origin of harsh parenting practices toward children with ASD. Practically, our findings provided insights about ways to identify high-risk families and to develop effective child maltreatment intervention programs. (C) 2016 Elsevier Ltd. All rights reserved.
Electrophysiologic studies suggest that autism spectrum disorder is characterized by aberrant anatomic and functional neural circuitry. During normal brain development, pruning and synaptogenesis facilitate ongoing changes in both short- and long-range neural wiring. In developmental disorders such as autism, this process may be perturbed and lead to abnormal neural connectivity. Careful analysis of electrophysiologic connectivity patterns using EEG coherence may provide a way to probe the resulting differences in neurological function between people with and without autism. There is general consensus that electroencephalogram coherence patterns differ between individuals with and without autism spectrum disorders; however, the exact nature of the differences and their clinical significance remain unclear. Here we review recent literature comparing electroencephalogram coherence patterns between patients with autism spectrum disorders or at high risk for autism and their non-autistic or low-risk for autism peers.
Detecting where our partners direct their gaze is an important aspect of social interaction. An atypical gaze processing has been reported in autism. However, it remains controversial whether children and adults with autism spectrum disorder interpret indirect gaze direction with typical accuracy. This study investigated whether the detection of gaze direction toward an object is less accurate in autism spectrum disorder. Individuals with autism spectrum disorder (n=33) and intelligence quotients-matched and age-matched controls (n=38) were asked to watch a series of synthetic faces looking at objects, and decide which of two objects was looked at. The angle formed by the two possible targets and the face varied following an adaptive procedure, in order to determine individual thresholds. We found that gaze direction detection was less accurate in autism spectrum disorder than in control participants. Our results suggest that the precision of gaze following may be one of the altered processes underlying social interaction difficulties in autism spectrum disorder.
Interoceptive awareness is linked to emotional and social cognition, which are impaired in individuals with autism spectrum disorder (ASD). It is unknown how this ability is associated with age in either typical or atypical development. We used a standard test of interoceptive accuracy (IA) to investigate these questions in children and adults with and without ASD. Perceived number of heartbeats over 4 time intervals was compared with actual heart rate to determine IA. Effects of group, age, IQ, heart rate, and mental counting ability on accuracy were assessed using multiple regression. Post hoc correlations were performed to clarify significant interactions. Age was unrelated to IA in both groups when IQ >= 115. When IQ < 115, this relationship was positive in typical development and negative in ASD. These results suggest that cognitive ability moderates the effect of age on IA differently in autism and typical development.
Background: Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors. In studies of brain tissue, the age of the population is clearly a factor in interpreting study outcome, yet sex is rarely considered. To begin to address this issue, we extend our previously published microarray analyses to examine expression of small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), in ASD and in the control temporal cortex in males and females. Predicted miRNA targets were identified as well as the pathways they overpopulate. Findings: After considering age, sexual dimorphism in ASD sncRNA expression persists in the temporal cortex and in the patterning that distinguishes regions. Among the sexually dimorphic miRNAs are miR-219 and miR-338, which promote oligodendrocyte differentiation, miR-125, implicated in neuronal differentiation, and miR-488, implicated in anxiety. Putative miRNA targets are significantly over-represented in immune and nervous system pathways in both sexes, consistent with previous mRNA studies. Even for common pathways, the specific target mRNAs are often sexually dimorphic. For example, both male and female target genes significantly populate the Axonal Guidance Signaling pathway, yet less than a third of the targets are common to both sexes. Conclusions: Our findings of sexual dimorphism in sncRNA levels underscore the importance of considering sex, in addition to age, when interpreting molecular findings on ASD brain.
Autism Spectrum Disorder (ASD) has been associated with reduced orienting to social stimuli such as eyes, but the results are inconsistent. It is not known whether atypicalities in phasic alerting could play a role in putative altered social orienting in ASD. Here, we show that in unisensory (visual) trials, children with ASD are slower to orient to eyes (among distractors) than controls matched for age, sex, and nonverbal IQ. However, in another condition where a brief spatially nonpredictive sound was presented just before the visual targets, this group effect was reversed. Our results indicate that orienting to social versus nonsocial stimuli is differently modulated by phasic alerting mechanisms in young children with ASD. Autism Res2017, 10: 246-250. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
Background: Early research has documented that young children show an increased interest toward objects that are verbally labeled by an adult, compared to objects that are presented without a label. It is unclear whether the same phenomenon occurs in neurodevelopmental disorders affecting social development, such as autism spectrum disorder (ASD) and Williams syndrome (WS). Methods: The present study used a novel eye-tracking paradigm to determine whether hearing a verbal label increases the salience of novel objects in 35 preschoolers with ASD, 18 preschoolers with WS, and 20 typically developing peers. Results: We found that typically developing children and those with WS, but not those with ASD, spent significantly more time looking at objects that are verbally labeled by an adult, compared to objects that are presented without a label. Conclusions: In children without ASD, information accompanied by the speaker's verbal label is accorded a "special status," and it is more likely to be attended to. In contrast, children with ASD do not appear to attribute a special salience to labeled objects compared to non-labeled objects. This result is consistent with the notion that reduced responsivity to pedagogical cues hinders social learning in young children with ASD.
Background The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. Methods A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. Results The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate-to high-risk genotypes, with only 5 FDR with low-risk genotypes. Conclusions The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.
Objective: To evaluate the role of auto-antibodies in Chinese patients with primary and secondary infertility in routine clinical practice. Methods: We reviewed the medical records of infertile Chinese patients of either gender (>= 18 year old) who were failed to conceive after 12 months of regular sexual intercourse without the use of contraception, and visited at department of Gynaecology and Obstetrics, Renmin Hospital of Wuhan University, China between January 2004 to December 2014, and undergone auto-antibody estimation along with other routine antenatal screening tests. Immunological assay was performed using dot immuno-gold filtration assay. Positive case was compared among patients with primary and secondary infertility. Results: Our chart review study showed that the positive case of Anti-Sperm Antibody (ASAb) was significantly higher in female with primary than male (p<0.05). In female patients with primary infertility, all other auto-antibodies (anti-Endometrium Antibody (EMAb), Anti-Ovary Antibody (AOAb), Anti-Zona Pellucida Antibody (AZP)) and Anti-Cardiolipin Antibody (ACA) were significantly higher compared to patients with secondary infertility (p<0.05). Moreover, positive case of all auto-antibodies was significantly higher among female with primary fertility than secondary fertility and control groups. Conclusion: Our study results suggested the involvement of auto-antibodies related to reproduction system in development of primary infertility. Auto-antibodies related to reproduction were significantly higher in patients with primary infertility, this implicated involvement of auto-immunological factors in development of infertility.
Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.814.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls (p<0.0001). Fatigue in SLE was higher than a normal reference range (p<0.0001) and associated with lower MD (ss=-0.61, p=0.02), depression (ss=0.17, p=0.001), anxiety (ss=0.13, p=0.006) and higher body mass index (ss=0.10, p=0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration (p=0.003) and higher MD (p=0.03) and, in adjusted analysis, higher levels of IL-6 (ss=-0.15, p=0.02) but not with MD. Meta-analysis (10 studies, n=261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.
Objectives: Autoimmune pancreatitis (AIP) is a representative IgG4-related and inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis resulting from AIP, we focused on methylation abnormalities and KRAS mutations in AIP. Methods: Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP) samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct sequencing. Results: Hypermethylation events (>= 10%) were identified in NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases, respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct sequencing results for KRAS showed no single-point mutations in AIP. Conclusions: These are the first studies characterizing methylation abnormalities in AIP. AIP's inflammatory condition may be related to carcinogenesis. Further study will elucidate methylation abnormalities associated with carcinogenesis in AIP.
The process of curing a patient by removing his illness by extracting blood is a very old one. Many years ago, phlebotomy was practiced to cure illness. Now, this old process, placed on a rational basis with therapeutic apheresis (TA), is being followed in clinical practice. Therapeutic plasma exchange (TPE) with hollow fiber modules has been used in different severe diseases for more than 40 years. Based on many years of experience with the extracorporeal circulation in end-stage renal disease, the authors herein give an overview of TA in immunological diseases, especially in hematologic, autoimmune and dermatologic diseases. Updated information on immunology and molecular biology of different immunological diseases is discussed in relation to the rationale for apheresis therapy and its place in combination with other modern therapies. With the introduction of novel and effective biologic agents, TA is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved in recent years, due in part to very aggressive therapy schemes. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Applications Committee of the American Society for Apheresis are cited. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement.
Immune checkpoint inhibitors (ICI) represent a new revolutionary weapon in the armamentarium of anti-cancer therapies. The side effects of these new agents represent a new challenge for oncologists; they are usually unpredictable and sometimes life threatening, if not managed rapidly and adequately. The most frequent side effects are the dermatologic, but they are usually low grade side effects and consequently easily manageable. Rash, pruritus and vitiligo are the most frequent dermatologic side effects. We aimed in this review to describe first all the dermatologic side effects of ICI according to the subtype of ICI and combination therapies in the clinical trials, then to report all the rare case reports dermatologic side effects, and finally to present the management algorithm of these side effects.
Blood transcriptional profiles could serve as biomarkers of clinical changes in subjects at-risk for or diagnosed with diabetes. However, transcriptional variation over time is poorly understood due to the impracticality of frequent longitudinal phlebotomy in large patient cohorts. We have developed a novel transcriptome assessment method that could be applied to fingerstick blood samples self-collected by study volunteers. FifteenL of blood from a fingerstick yielded sufficient RNA to analyse >176 transcripts by high-throughput quantitative polymerase chain reaction (PCR). We enrolled 13 subjects with type 1 diabetes and 14 controls to perform weekly collections at home for a period of 6 months. Subjects returned an average of 24 of 26 total weekly samples, and transcript data were obtained successfully for >99% of samples returned. A high degree of correlation between fingerstick data and data from a standard 3 mL venipuncture sample was observed. Increases in interferon-stimulated gene expression were associated with self-reported respiratory infections, indicating that real-world transcriptional changes can be detected using this assay. In summary, we show that longitudinal monitoring of gene expression is feasible using ultra-low-volume blood samples self-collected by study participants at home, and can be used to monitor changes in gene expression frequently over extended periods.
The importance of T-cell receptor (TCR) repertoire diversity is highlighted in murine models of immunodeficiency and in many human pathologies. However, the true extent of TCR diversity and how this diversity varies in health and disease is poorly understood. In a previous issue of the European Journal of Immunology, Lossius et al. [Eur. J. Immunol. 2014. 44: 3439-3452] dissected the composition of the TCR repertoire in the context of multiple sclerosis (MS) using high-throughput sequencing of TCR-beta chains in cerebrospinal fluid samples and blood. The authors demonstrated that the TCR repertoire of the CSF was largely distinct from the blood and enriched in EBV-reactive CD8(+) T cells in MS patients. Studies of this kind have long been hindered by technical limitations and remain scarce in the literature. However, TCR sequencing methodologies are progressing apace and will undoubtedly shed light on the genetic basis of T-cell responses and the ontogeny of T-cell-mediated diseases, such as MS.
Objectives: Human cytomegalovirus (HCMV) infection induces production of CD13-specific autoantibodies, which may promote inflammation and tissue damage. HCMV infection has been suggested as a cause of biliary atresia (BA), but little is known of its role in other forms of neonatal cholestasis. We studied serum levels of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of different causes, including BA, and in mothers of healthy, term infants without cholestasis, as well as in healthy blood donors. Methods: Using fluorescence-activated cell sorting, we measured CD13-specific autoantibody levels in serum from the above-mentioned groups. In addition, the effect of serum from mothers of infants with neonatal cholestasis was tested on the differentiation of monocytes into macrophages. Results: CD13-specific autoantibodies were found in mothers of infants with neonatal cholestasis, but not in mothers of infants without cholestasis and healthy blood donors, and were associated with HCMV seropositivity. Sera from mothers of infants with all forms of neonatal cholestasis inhibited differentiation of monocytes into macrophages, but this was not dependent on CD13-specific autoantibodies. Conclusions: The significantly higher frequency of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of all forms compared with mothers of healthy infants without cholestasis suggests an association, but does not prove that they are pathogenic. The presence of CD13-specific autoantibodies does not correlate with HCMV IgG serostatus, suggesting a more complicated mechanism that possibly reflects active HCMV infection in these individuals. Further studies are needed to elucidate whether these autoantibodies contribute to the development of cholestasis or represent an epiphenomenon.
In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. (C) 2017 Elsevier B.V. All rights reserved.
Background: Systemic autoinflammatory diseases (SAIDs) represent a growing number of monogenic, polygenic or multifactorial disorders that are often difficult to diagnose. Case presentation: Here we report a patient who was initially erroneously diagnosed and treated for SAID. Symptoms consisted of recurrent fever, erythematous and/or blistering skin lesions, angioedema, susceptibility to bleeding, external ear infections and reversible anisocoria in the absence of laboratory evidence of systemic inflammation. After two and a half years of extensive diagnostic work-up and multiple empirical therapies, a final diagnosis of Munchausen by proxy syndrome (MBPS) was established. Conclusions: The diagnosis of SAID needs to be carefully reassessed if measurable systemic inflammation is missing, and MBPS should be included in the differential diagnosis.
The human microbiome consists of all microorganisms occupying the skin, mucous membranes and intestinal tract of the human body. The contact of the mucosal immune system with the human microbiome is a balanced interplay between defence mechanisms of the immune system and symbiotic or pathogenic microbial factors, such as microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome, the immune system is deranged to a chronic inflammatory state and autoantibodies are an important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome can lead to local mucosal inflammation and increased intestinal permeability. Proinflammatory lymphocytes and cytokines can spread to the systemic circulation and increase the risk of inflammation at distant anatomical sites, such as the joints or salivary glands. Increased intestinal permeability increases antigen exposure and the risk of autoantibody production. If the human microbiome indeed plays such a critical role in SADs, this finding holds a great promise for new therapeutic strategies, such as diet interventions and probiotics and prebiotics. This review provides a background on the human microbiome and mucosal immunity in the gut and oral cavity and gives a summary of the current knowledge on the microbiome-SADs connection.
The paper deals with a hardware solution for the study of low power active filter with Bode plotting. By using a DAQ card and an experimental platform it shows how LabVIEW graphical programming environment can be used for manual or automated testing and analysis of the first order active filter with operational amplifier (op-amp). The hardware platform can provide a template to build real op-amp circuits to better understand (together with a previous one paper for developing the software simulation and demonstrations) the op-amp filters principles. The main contribution for this paper refers to a software / hardware solution for obtaining a manual / automat Bode plotting. For plotting the frequency response curve of a filters, it is often necessary to measure the output signal over a range of input frequency. The hardware experiments allows a range of test voltages with variable frequency to be input and the filters response measured, displayed and analyzed. The frequency scan range, scan rate and number of test points can be selected from front panel controls. Another contribution is a practical tool for the analysis of the response filter to various input signals (sine / square / triangular wave) and calculating the filter gain depending on the amplitude measured in units of peak, peak to peak or roots mean square signal level.
In the present paper a novel automatic gain control pre-amplifier for hearing aid device is proposed and analyzed. The proposed design utilizes feedback and feed forward loop in order to control the gain of the device. Input and output thresholds have been accommodated to provide dual control. The weak input signal is amplified in three modes. High gain for low input and low gain for high input forms the basis of amplification. The measured average power dissipation of the complete pre-amplifier is 410 mu W with a dual power supply of +/- 0.7 V in 180 nm technology node. Frequency of operation is up to 20 kHz.
Mixed-signal integrated circuit design and simulation highly rely on behavioral models of circuit blocks. Such models are used for the validation of design specification, optimization of system topology, and behavioral synthesis using a description language, etc. However, automatic behavioral model generation is still in its early stages; in most scenarios designers are responsible for creating behavioral models manually, which is time-consuming and error prone. In this paper an automatic behavioral model generation method for switched-capacitor (SC) integrator is proposed. This technique is based on symbolic circuit modeling with approximation, by which parametric behavioral integrator model can be generated. Such parametric models can be used in circuit design subject to severe process variational. It is demonstrated that the automatically generated integrator models can accurately capture process variation effects on arbitrarily selected circuit elements; furthermore, they can be applied to behavioral simulation of SC Sigma-Delta modulators (SDMs) with acceptable accuracy and speedup. The generated models are compared to a recently proposed manually generated behavioral integrator model in several simulation settings.
Technology is rapidly changing the nature of service, customers' service frontline experiences, and customers' relationships with service providers. Based on the prediction that in the marketplace of 2025, technology (e. g., service-providing humanoid robots) will be melded into numerous service experiences, this article spotlights technology's ability to engage customers on a social level as a critical advancement of technology infusions. Specifically, it introduces the novel concept of automated social presence (ASP; i. e., the extent to which technology makes customers feel the presence of another social entity) to the services literature. The authors develop a typology that highlights different combinations of automated and human social presence in organizational frontlines and indicates literature gaps, thereby emphasizing avenues for future research. Moreover, the article presents a conceptual framework that focuses on (a) how the relationship between ASP and several key service and customer outcomes is mediated by social cognition and perceptions of psychological ownership as well as (b) three customer-related factors that moderate the relationship between ASP and social cognition and psychological ownership (i. e., a customer's relationship orientation, tendency to anthropomorphize, and technology readiness). Finally, propositions are presented that can be a catalyst for future work to enhance the understanding of how technology infusion, particularly service robots, influences customers' frontline experiences in the future.
Numerous epidemiological studies have demonstrated a close and bidirectional association between depression and cardiovascular disorders (CVD). This comorbidity places a significant burden on individuals and the healthcare system. Not surprisingly, in the last two decades preclinical research in the field of depression and CVD has rapidly progressed. Multiple studies have demonstrated that aspects of human depression/cardiovascular comorbidity can be modeled in rodents exposed to chronic stress paradigms and that a depressive-like syndrome can be induced in rodent models of CVD. This research has provided insights into neural, autonomic, humoral, immune and circulatory mechanisms linking cooccurring mood and CVD. Recent investigations have started to address gender and individual differences in the vulnerability to both disorders and have begun to explore the efficacy of novel pharmacological interventions for the treatment of these comorbid conditions. This review discusses relatively wellestablished findings and the latest discoveries from rodent models of depression and CVD, with the aim of providing an up-to-date reference which may guide future studies of the relationship between mood and cardiovascular disturbances. (C) 2016 Elsevier Ltd. All rights reserved.
Spinal cord injury (SCI) is a devastating event for individuals, who frequently develop motor and sensory impairment as well as autonomic dysfunction. Previous studies reported that autonomic activity plays a major role in social cognition and that difficulties in the ability to interpret social information are commonly observed in a variety of mental disorders, which in turn correlate with a poor autonomic nervous system (ANS) regulation. It is well established that subjects with SCI have an alteration in ANS regulation mechanisms. We hypothesized that subjects diagnosed with SCI, who are experiencing a period of adaptation and socio-labor insertion suffer alterations in an emotion recognition task, a component of social cognition, which correlate with poor ANS regulation. We evaluated ANS function by measuring the heart rate variability (HRV) in 18 healthy subjects and 10 subjects with SCI. A 5-min baseline HRV was compared to a task period while performing The reading the mind in the eyes test (RMET). We found that while both groups have similar general performance in the test, healthy subjects responded with greater certainty during the RMET. This level of certainty during the RMET was positively correlated with baseline HRV measures in this group. Also, the group of healthy subjects exhibited higher HRV at baseline than participants with SCI. Finally, the changes in HRV between baseline and task condition were significantly higher in healthy individuals than in SCI participants. Our results show that patients with SCI have low levels of autonomic regulation mechanisms which may promote social cognition problems during their reinsertion to daily life.
Filamentous plant pathogens deliver effector proteins to host cells to promote infection. The Phytophthora infestans RXLR-type effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and perturbs host-selective autophagy. However, the structural basis of this interaction remains unknown. Here, we define the crystal structure of PexRD54, which includes a modular architecture, including five tandem repeat domains, with the AIM sequence presented at the disordered C terminus. To determine the interface between PexRD54 and ATG8, we solved the crystal structure of potato ATG8CL in complex with a peptide comprising the effector's AIM sequence, and we established a model of the full-length PexRD54-ATG8CL complex using small angle x-ray scattering. Structure-informed deletion of the PexRD54 tandem domains reveals retention of ATG8CL binding in vitro and in planta. This study offers new insights into structure/function relationships of oomycete RXLR effectors and how these proteins engage with host cell targets to promote disease.
Edwin M. Southern is a professor emeritus at the University of Oxford. He is perhaps best known for development of the Southern blot (Dr. Southern was at the University of Edinburgh when he wrote his landmark paper). The Southern blot provided a scientific breakthrough by allowing scientists to detect a particular DNA sequence without first purifying it from the rest of the genome; the basic method involves the transfer of the DNA to a membrane, followed by detection with a specific probe. Although few people perform Southern blots as originally carried out by Southern, due in part to the more recent technique of the polymerase chain reaction, the basic concept continues to play an important role in molecular biology.
A new task force on postmortem imaging was established at the annual meeting of the European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The postmortem task force is separate from the child abuse task force as it covers all aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of the task force is the guidance and standardization of non-radiographic postmortem imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines the starting point of the task force, with a mission statement, outline of current experience, and short- and long-term goals.
A novel nonparametric system identification (SI) algorithm is described, focusing on PID-based control loops for buck converters with effective series resistance (ESR) in the output filter. Dithering amplification effects on the control path are exploited during the steady-state converter operation. The noise injected is used to stimulate the loop reaction and to identify the output filter configuration. Oversampling-dithering features of third-order Delta Sigma modulators are used to increase the DPWM resolution during the converter nominal operation and, moreover, as the core key to compute the SI algorithm. A modified structure of a noise shaper is used to handle the resolution of the SI algorithm over a range of the desired frequencies during the nonparametric identification. The SI algorithm comprises two steps: the first processing step extracts the resonant frequency, and the second extracts the ESR zero from the power spectrum density computation of the control feedback error. The SI method has been validated with different buck converter configurations, and has successfully been integrated and measured into a digitally controlled buck converters prototype for automotive safety application.
Lignocellulosic biomass gasification followed by the Fischer-Tropsch (Fe) synthesis is becoming a promising pathway to produce synthetic biofuels, having the potential of being coupled with combined-cycle strategies in order to coproduce electricity. In this work, the thermodynamic performance of this type of bioenergy system is evaluated through exergy analysis. A base-case process combining biomass gasification, FT synthesis and a combined cycle is defined. Furthermore, two alternative configurations modifying the base-case process are considered: (i) autothermal reforming (ATR) of a fraction of the FT tail gas to increase the fuel yield, and (ii) combustion of a fraction of the conditioned biosyngas to increase electricity production. The biomass conversion plants are simulated using Aspen Plus (R) to obtain the data required for the assessment. The indirect gasifier and the gas combustor are identified as the main sources of irreversibility within the three process configurations, with exergy destruction ratios of 21% and 5-7%, respectively. The gasification subsystem is found to contribute over 50% to the overall exergy destruction, showing 68% efficiency. The power generation subsystem also shows a high contribution to the overall exergy destruction (19-28%) due to high fuel consumption and the significant thermodynamic irreversibility of the cycle. Depending on the plant configuration, overall exergetic efficiencies of 24-27% are attained. The ATR case leads to a higher yield of biofuels, at the expense of lower electricity production. This configuration enhances the exergetic efficiency of the system and thus its thermodynamic performance, in contrast to the alternative configuration for increased power generation. (C) 2017 Elsevier Ltd. All rights reserved.
An auto-zero and chopper operational amplifier with a 4.5-60 V supply voltage range is realized, using a 0.18 mu m CMOS process augmented by 5 V CMOS and 60 V DMOS transistors. It achieves a maximum offset voltage drift of 0.02 mu V/degrees C, a minimum CMRR of 145 dB, a noise PSD of 6.8 nV/root Hz, and a 3.1 MHz unity gain bandwidth, while dissipating 840 mu A of current. Up-modulated chopper ripple is suppressed by auto-zeroing. Furthermore, glitches from the charge injection of the input switches are mitigated by employing six parallel input stages with 800 kHz interleaved clocks. This moves the majority of the glitch energy up to 4.8 MHz, while leaving little energy at 800 kHz. As a result, the requirements on an external low-pass glitch filter is relaxed, and a wider usable signal bandwidth can be obtained. Maximum input bias current due to charge injection mismatch is reduced from 1.5 nA to 150 pA by post production trimming with an on-chip charge mismatch compensation circuit.
Short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme involved in the oxidation of fatty acids and the catabolic pathway of valine and, to a lesser extent, isoleucine. Deficiency of this enzyme was recently shown to cause an early childhood Leigh syndrome phenotype. The few reported patients were compound heterozygotes for two missense or missense with truncating variants in ECHS1 that encodes SCEH. We describe two siblings with severe refractory lactic acidosis and death within the first 2 days of life. Following negative clinical whole-exome and whole-genome sequencing, we resorted to autozygome/exome analysis on research basis and identified a homozygous splice site mutation (c.88+5G>A) in the two cases. Analysis of cDNA confirmed complete replacement of the normal transcript with an aberrant transcript (r.88_89ins 88+1_88+11) predicting premature truncation of the protein [p.(Ala31Glufs*23)]. Furthermore, quantitative reverse transcriptase polymerase chain reaction (RTPCR) showed marked reduction in ECHS1, most likely nonsense-mediated decay (NMD)-mediated. This is the first report of homozygosity for a truncating mutation in ECHS1, which may explain the severe phenotype. Our report highlights the need to consider SCEH deficiency in patients with lethal neonatal lactic acidosis, and the potentially limited sensitivity of untargeted genomic sequencing towards non-canonical splicing mutations, which may explain at least some of the negative' cases on clinical exome/genome sequencing.
This review presents a broader approach to the implementation and study of runs of homozygosity (ROH) in animal populations, focusing on identifying and characterizing ROH and their practical implications. ROH are continuous homozygous segments that are common in individuals and populations. The ability of these homozygous segments to give insight into a population's genetic events makes them a useful tool that can provide information about the demographic evolution of a population over time. Furthermore, ROH provide useful information about the genetic relatedness among individuals, helping to minimize the inbreeding rate and also helping to expose deleterious variants in the genome. The frequency, size and distribution of ROH in the genome are influenced by factors such as natural and artificial selection, recombination, linkage disequilibrium, population structure, mutation rate and inbreeding level. Calculating the inbreeding coefficient from molecular information from ROH (F-ROH) is more accurate for estimating autozygosity and for detecting bothpast and more recent inbreeding effects than are estimates from pedigree data (F-PED). The better results of F-ROH suggest that F-ROH can be used to infer information about the history and inbreeding levels of a population in the absence of genealogical information. The selection of superior animals has produced large phenotypic changes and has reshaped the ROH patterns in various regions of the genome. Additionally, selection increases homozygosity around the target locus, and deleterious variants are seen to occur more frequently in ROH regions. Studies involving ROH are increasingly common and provide valuable information about how the genome's architecture can disclose a population's genetic background. By revealing the molecular changes in populations over time, genome-wide information is crucial to understanding antecedent genome architecture and, therefore, to maintaining diversity and fitness in endangered livestock breeds.
This paper introduces a new voltage regulator module (VRM) that merges a highly efficient switched-inductor converter as the main unit with a load-side switched-capacitor-based converter to assist during load transient events. The resulting hybrid-VRM exhibits improved dynamic performance for both loading and unloading transient events, while maintaining a compact design with reduced output capacitance and lower components stress. The hybrid controller that has been developed allows operation that is based on output voltage measurement alone, further reducing the circuit complexity. A power processing efficiency analysis that has been carried out shows efficiency improvement in favor of the hybrid-VRM when compared to time-optimal control under varying load conditions. The operation of the VRM is verified on a 20-W, 12V-to-1.5-V prototype with peak power conversion efficiency of 93%, demonstrating near-ideal transient recovery.
In some high-performance applications, an LC filter must be added to the auxiliary resonant snubber inverter (ARSI) to reduce the output current ripple. However, resonance occurs due to the additional LC filter, which makes the traditional closed-loop control not suitable to be used directly. Therefore, this paper presents a double-loop digital control based on the active damping method of capacitor current feedback to stabilize the system. Most of the studies on active damping methods are focused on the grid in consideration of zero resistance. However, the load resistance should not be neglected in the drive system. Therefore, the load resistance and digital control delays are considered in this paper. Moreover, an improved loading method is proposed to improve the duty ratio range. In order to verify the effectiveness of the controller, a prototype was developed. The simulation and experimental results demonstrate that soft-switching can be realized for the entire load range. The maximum duty ratio is improved by 0.01 by using the proposed loading method. The resonance can be eliminated by using the proposed control method.
We report the cloning of a glycoside hydrolase family (GHF) 9 gene of rice (Oryza sativa L. cv. Sasanishiki), OsCel9A, corresponding to the auxin-induced 51 kDa endo-1,4-beta-glucanase (EGase). This enzyme reveals a broad substrate specificity with respect to sugar backbones (glucose and xylose) in beta-1,4-glycans of type II cell wall. OsCel9A encodes a 640 amino acid polypeptide and is an ortholog of TomCel8, a tomato EGase containing a carbohydrate-binding module (CBM) 2 sequence at its C-terminus. The expression of four rice EGase genes including OsCel9A showed different patterns of organ specificity and responses to auxin. OsCel9A was preferentially expressed during the initiation of lateral roots or subcultured root calli, but was hardly expressed during auxin-induced coleoptile elongation or in seed calli, in contrast to OsCel9D, a KORRIGAN (KOR) homolog. In situ localization of OsCel9A transcripts demonstrated that its expression was specifically up-regulated in lateral root primordia (LRP). Northern blotting analysis showed the presence of a single product of OsCel9A. In contrast, both mass spectrometric analyses of peptide fragments from purified 51 kDa EGase proteins and immunogel blot analysis of EGase proteins in root extracts using two antibodies against internal peptide sequences of OsCel9A revealed that the entire CBM2 region was post-translationally truncated from the 67 kDa nascent protein to generate 51 kDa EGase isoforms. Analyses of auxin concentration and time course dependence of accumulation of two EGase isoforms suggested that the translation and post-translational CBM2 truncation of the OsCel9A gene may participate in lateral root development.
This paper proposes a digital phase leading filter current compensation (PLFCC) technique for a continuous conduction mode boost power factor correction to improve PF in high line voltage and light load conditions. The proposed technique provides a corrected average inductor current reference and utilizes an enhanced duty ratio feed-forward technique which can cancel the adverse effect of the phase leading currents caused by filter capacitors. Moreover, the proposed PLFCC technique also provides the switching dead-zone in nature so the switching loss can be reduced. Therefore, the proposed PLFCC can significantly improve power quality and can achieve a high efficiency in high line voltage and light load conditions. The principle and analysis of the proposed PLFCC are presented, and performance and feasibility are verified by experimental results from the universal input (90-260 V-AC) and 750 W-400 V output laboratory prototype.
This paper presents a shunt active power filter (APF) with division-summation (D-Sigma) digital control and based on a three-phase three-wire inverter configuration. The APF shapes source current by introducing one degree of freedom to compensate load harmonic currents. The adopted D-Sigma digital control approach can accommodate filter-inductance variation, reducing core size significantly, and it can derive control laws directly. An average power method is adopted in this paper for determining the fundamental current at the source side, which can readily be implemented without complex calculation, frame transformation, and extra filter. In the design and implementation, the inductances corresponding to various inductor currents were estimated at the startup and stored in the microcontroller for scheduling loop gain cycle by cycle, which can ensure the system stability. Measured results from a 5-kVA three-phase APF have confirmed the analysis and discussion of the APF.
There has been a growing demand of using multi-function inverters for grid-connected systems applied to nonconventional energy sources, such as solar, wind and so on. In addition to power quality conditioning, the inverter can also be used for bidirectional active power exchange with a three-phase four-wire grid. Therefore, the inverter acts as a multi-function compensator. The functions of the proposed inverter system include active power injection, rectification and active power filtering (APF) (including phase power balancing). This paper presents design and implementation of a three-leg split-capacitor shunt multi-function inverter with division-summation (D-Sigma) digital control. The adopted D-Sigma digital control can accommodate filter inductance variation, reducing core size significantly, and its control laws can be derived directly to cancel the variation effects of dc-bus voltage, switching period and filter inductance. An average power method is adopted in this paper for determining fundamental currents at the source side. In the design and implementation, the inductances corresponding to various inductor currents were estimated at the startup and stored in the microcontroller for scheduling loop gain cycle by cycle, which can insure system stability. Measured results from a three-phase four-wire inverter have confirmed the analysis and discussion.
The activity of lateral habenula (LHb) represents a substrate for the encoding of negative-valenced events. The exposure to aversive stimuli in naive mice is sufficient to trigger a reduction in GABA(B)-mediated signaling in the LHb. This is ultimately instrumental for the hyperactivity of LHb neurons and for the establishment of depressive-like phenotypes. However, the mechanisms responsible for the induction of this aversion-driven plasticity are missing. Using ex-vivo patch-clamp recordings in slices, here we show that exposing mice to a series of inescapable footshocks (FsE) rapidly reduces baclofen-mediated GABA(B) currents in the LHb. This plasticity of GABA(B) signaling requires the activation of the dopamine and stress pathways. Indeed, the systemic administration of dopamine and glucocorticoids receptor antagonists prevents the FsE-induced reduction of GABA(B) currents in the LHb. To test whether the recruitment of these receptors occurs within the LHb, we exposed slices from control mice to either dopamine or corticosterone. Both manipulations failed to alter the amplitudes of baclofen-mediated GABA(B) currents. Altogether, these data suggest that dopamine and stress signaling are necessary for the induction of FsE-evoked GABA(B) plasticity in the LHb. However, the activation of these specific receptors may occur in structures different than the LHb, suggesting a circuit-based mechanism for this form of plasticity. These findings provide mechanistic insights on aversion-driven plasticity within the LHb.
Previous observational research suggests that stretching is contagious in budgerigars (Melopsittacus undulatus). Here we report the first experimental evidence of this response through a reanalysis of a previous experiment testing for contagious yawning in this species. Using a repeated measures design, 16 birds were tested as pairs alongside familiar and unfamiliar conspecifics with and without visual barriers. Our results show that stretching behavior was temporally clustered only when the birds could see one another, corroborating previous observational findings supporting contagion. Additionally, for the first time, we show an ingroup bias in this response. That is, while the overall frequency of stretching did not significantly differ as a function of conspecific familiarity, contagious stretching was only present when cage mates were paired together. These findings are discussed in relation to recent research studying social cognition in this species.
Background: We developed a new oligonucleotide microarray comprising 16 identical subarrays for simultaneous rapid detection of avian viruses: avian influenza virus (AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and infectious bursal disease virus (IBDV) in single-and mixed-virus infections. The objective of the study was to develop an oligonucleotide microarray for rapid diagnosis of avian diseases that would be used in the course of mass analysis for routine epidemiological surveillance owing to its ability to test one specimen for several infections. Methods and results: The paper describes the technique for rapid and simultaneous diagnosis of avian diseases such as avian influenza, Newcastle disease, infectious bronchitis and infectious bursal disease with use of oligonucleotide microarray, conditions for hybridization of fluorescent-labelled viral cDNA on the microarray and its specificity tested with use of AIV, NDV, IBV, IBDV strains as well as biomaterials from poultry. Sensitivity and specificity of the developed microarray was evaluated with use of 122 specimens of biological material: 44 cloacal swabs from sick birds and 78 tissue specimens from dead wild and domestic birds, as well as with use of 15 AIV, NDV, IBV and IBDV strains, different in their origin, epidemiological and biological characteristics (RIBSP Microbial Collection). This microarray demonstrates high diagnostic sensitivity (99.16% within 95% CI limits 97.36-100%) and specificity (100%). Specificity of the developed technique was confirmed by direct sequencing of NP and M (AIV), VP2 (IBDV), S1 (IBV), NP (NDV) gene fragments. Conclusion: Diagnostic effectiveness of the developed DNA microarray is 99.18% and therefore it can be used in mass survey for specific detection of AIV, NDV, IBV and IBDV circulating in the region in the course of epidemiological surveillance. Rather simple method for rapid diagnosis of avian viral diseases that several times shortens duration of assay versus classical diagnostic methods is proposed.
BackgroundIn Bangladesh, nomadic duck flocks are groups of domestic ducks reared for egg production that are moved to access feeding sites beyond their owners' village boundaries and are housed overnight in portable enclosures in scavenging areas. The objectives of this study were to measure the prevalence of influenza A virus RNA and H5-specific antibodies in nomadic ducks and to characterize nomadic duck raising practices in northeastern Bangladesh. MethodsWe tested duck egg yolk specimens by competitive ELISA to detect antibodies against avian influenza A (H5) and environmental fecal samples by real-time reverse-transcription polymerase chain reaction (rRT-PCR) to detect influenza A virus RNA and H5 subtype. ResultsThe median age of the ducks was 24months (range: 8-36months) and the median flock size was 300 ducks (range: 105-1100). Of 1860 egg yolk samples, 556 (30%, 95% confidence interval (CI): 28-32) were positive for antibodies against H5 and 58 flocks (94%) had at least one egg with H5-specific antibodies. Of 496 fecal samples, 121 (24%, 95% CI: 22-29) had detectable influenza A RNA. Thirty-three flocks (53%) had at least one fecal sample positive for influenza A RNA. ConclusionsNomadic ducks in Bangladesh are commonly infected with avian influenza A (H5) virus and may serve as a bridging host for transmission of avian influenza A (H5) virus or other avian influenza A viruses subtypes between wild waterfowl, backyard poultry, and humans in Bangladesh.
Magellanic penguins (Spheniscus magellanicus) are native to Argentina, Chile and the Falkland Islands. Magellanic penguins are highly susceptible to blood parasites such as the mosquito-borne Plasmodium spp., which have been documented causing high morbidity and mortality in zoos and rehabilitation centres. However, to date no blood parasites have been detected in wild Magellanic penguins, and it is not clear whether this is reflective of their true absence or is instead related to an insufficiency in sampling effort or a failure of the diagnostic methods. We examined blood smears of 284 Magellanic penguins from the Argentinean coast and tested their blood samples with nested polymerase chain reaction tests targeting Haemoproteus, Plasmodium, Leucocytozoon and Babesia. No blood parasites were detected. Analysing the sampling effort of previous studies and the climatogeography of the region, we found there is strong basis to conclude that haemosporidians do not infect wild Magellanic penguins on the Argentinean coast. However, at present it is not possible to determine whether such parasites occur on the Chilean coast and at the Falkland Islands. Furthermore, it is troubling that the northward distribution expansion of Magellanic penguins and the poleward distribution shift of vectors may lead to novel opportunities for the transmission of blood parasites.
Problem. - Neurobiology, adorned with the most recent discoveries of the molecular biology, the genetics and the cognitive sciences, is present everywhere: In the report of the man with his body, with his intellectual faculties, with his perception of others and himself. Our social conducts, morality and our affects would be governed by neuronal substrata. Are things so simple? Methodology. - To try to answer this question, the author is going to use the opposition "to explain" and "understand", in a long-standing and often passionate debate which concerns the epistemology and the ontology, two modalities to be inflexible. Different thus of methods: In the mind of Dilthey, we explain the nature (submitted to the principle of the causality) but we understand the psychic life (which sends back to the sphere of the sense). Results. - If the debate to explain and understand is further and far from being simple, the author adduces to draw from it some conclusions by questioning the speech of the promising of a reductionist neurobiology which believe to explain everything including all our actions in the name of the neurobiological reason: (1) if this is the case, we would be slaves of a history which already has its fate: The neurobiological-shaped man is neurobiological, (2) this speech is based on the mechanism of the tautology, that is it goes round in circles, teaches us absolutely nothing, (3) if the same neurobiologist asserts the opposite, why while reporting me what I say, I have no precise and localizable perception of my consciousness? (4) if the consciousness has no appropriate place or, to say it differently, if there is no intellectual topic appropriate to the consciousness, then what takes place in me will remain forever untranslatable and will be condemned to the silence. To go out of one, exist thus, I need the immediate and permanent help of an other one (or of contradiction), (5) if this process is purely an event of the brain then all our actions, all our gestures, in brief all that it is allowed us to live has to take place as it takes place, (6) finally to assert it brings us nothing more because the explanation always leaves something aside: the phenomenon of the life in which he is imperceptible. The example of the alcoholic is significant: if a change of the intellectual mechanisms is responsible of his alcohol addiction, why the alcoholic, by wanting to drink "how everybody", makes as if written history beforehand was of not much importance? If the alcoholic began thinking of his own cerebral dysfunction while he lives, his life would have no shape. Indeed, if he receives the message and knows the felling about which it is a question. Indeed, if he receives the message and knows the feeling about which it is a question, he cannot, by force of circumstance, feel what his brain passes on to him: he does not witness what appears in its brain. On the other and he witnesses the world in which he lives but also on his condition of mortal. So, without objects to be cultivated, that is without the world of the presence which is the one of the existence and not the understanding, the neurobiological explanation of his alcohol addiction will concern a knowledge but will ignore any life. It means that there is well a gap to live and theorize and that the alcoholic is not reduced to a cerebral dysfunction: he is in the life of relation, that is it is capable of taking up himself by using its real-life experience. The psychopathology implications are going to show themselves here of a very big importance: any reduction comes to truncate the understanding of the man sick coach in reality we constantly have to deal with the "global and complete" man, with the anthropology of the human fate. Conclusion. - If the science brings us news discovered in this domain, it has to keep always in mind that the life remains imperceptible and deeply moving. Without this existential event which allows us "to live", the air will become unbreathable in our more and more technical-scientific world: it would like being sentenced to asphyxiation. (C) 2016 Elsevier Masson SAS. All rights reserved.
In recent years, transportation electrification has emerged as a trend to support energy efficiency and CO2 emissions reduction targets. The true success, however, of this trend depends on the successful integration of electric transportation modes into the infrastructure systems that support them. Left unmanaged, plug-in electric vehicles may suffer from delays due to charging or cause destabilizing charging loads on the electrical grid. Online electric vehicles have emerged to remediate the need for stationary charging and its effects. While many works have sought to mitigate these effects with advanced control functionality, such as coordinated charging, vehicle-to-grid stabilization, and charging queue management, few works have assessed these impacts as a holistic transportation-electricity nexus. This paper develops a hybrid dynamic system model for transportation electrification. It also includes next generation traffic simulation concepts of multimodality and multiagency. Such a model can be used by electrified transportation fleet operators to not just assess but also improve their operations and control. The hybrid dynamic system model is composed of a marked Petri-net model superimposed on the continuous time kinematic and electrical state evolution. The model is demonstrated on an illustrative example of moderate size and functional heterogeneity.
Aluminum-doped zinc oxide (AZO) has attained intensive attention as being a very good transparent conducting oxide for photovoltaic applications. In this work, AZO films have been deposited on glass substrate by radio frequency (RF) magnetron sputtering. The influences of substrate temperatures on morphological, structural, optical and electrical properties of AZO films were systematically investigated. The results indicate that all AZO films have the hexagonal structure with c-axis preferred orientation. Morphological and electrical measurements have revealed that the substrate temperatures have strong influence on the microstructure, optical and electrical properties of AZO films. The AZO film is highly transparent from ultraviolet up to near infrared range with highest average transparency exceeding 83%. The minimum resistivity is as low as 6.1 x 10(-4) Omega cm. The carrier concentration and mobility are as high as 3.357 x 10(20) cm(-3) and 30.48 cm(2)/Vs, respectively. Finally, the performances of the AZO film are evaluated by its practical application in Cu(ln(1-x)Ga(x))Se-2 (CIGS) photovoltaic device as a transparent electrode. Benefited from its highly transparent and conductive feature, the most efficient device reveals an efficiency of 7.8% with a short-circuit current density of 28.99 mA/cm(2), an open-circuit voltage of 430 mV, and a fill factor of 62.44 under standard conditions. (C) 2017 Elsevier B.V. All rights reserved.
The present study examines the molecular mechanism underlying in vitro-induced resistance to FLC (fluconazole), KTC (ketaonazole), MCZ (miconazole) and CHX (cycloheximide) in AS (azole-susceptible) strains of Candicia albicans when exposed to CaCDR1/CaCDR2 inducers like FPZ (fluphenazine) and steroids [PRG (progesterone) and beta-EST (beta-oestradiol)]. By employing spot and checkerboard titre assays, we provide evidence of an in vitro-induced antagonism between tested drugs and inducers, which was accompanied with a concomitant increase in CaCDR1 and CaCDR2 transcript levels. Notably, unlike AS isolates, parental WT (wild-type) and Delta cdr2 null strains, Delta cdrl as well as Delta cdr1/Delta cdr2 nulls, when challenged with the inducers could not display antagonism. Our results validated by Northern blotting, reporter gene transcription and TRO (transcription run on) assays show that in vitro-induced antagonism between tested drugs and inducer in AS isolates was mainly due to a transient and reversible transcriptional activation of CaCDR1. Notwithstanding our earlier observation that consistent high transcript levels of CaCDR1 in clinical AR (azole-resistant) isolates were maintained due to the combination of its transcriptional activation and enhanced mRNA stability via elongated poly(A) tails, this study shows that transient and reversible transcriptional activation of CaCDR1 was the major determinant of induced antagonism in AS isolates. The distinct strategies between sustained (in AR isolates) and transiently induced resistance mechanisms (in AS isolates) adopted by Candida should become useful in improving therapeutic approaches.
Testicular maturation arrest is characterized by interruption of germ cell development and differentiation. Genetic factors play important role in the causation of human disease, including male infertility. The objective was to study copy number variations in testicular maturation arrest using single nucleotide polymorphism (SNP) microarray technique. Conventional cytogenetics, targeted fluorescence insitu hybridization (FISH) and sequence-tagged site (STS) polymerase chain reaction (PCR) were used to confirm some of the SNP microarray findings. SNP microarray on 68 cases of testicular maturation arrest detected copy number variations (CNVs) mostly on sex chromosomes involving pseudoautosomal regions (PAR) 1, 2 and 3 as well as azoospermic factors (AZFs) besides three cases of chromosomal abnormalities (two Klinefelter syndromes and one case of dicentric Y). The AZF deletion was observed in 14 (20.6%) cases and the AZFc gain was observed in 6 (8.8%) cases. PAR 1 and 2 CNVs was observed in 5 (7.3%) cases. PAR 3 CNVs was detected in 19 cases and 2 controls. The TSPY2 gene gain (within PAR 3 CNVs) was observed in 16 cases and 1 control. CNV containing autosomal genes possibly associated with male infertility in this study was SPATA31A2-A5 (9p12) in five cases. In this study, SNP microarray identified possible underlying aetiology in 55.9% (38/68) cases besides identifying minimal critical region of AZFc deletion as 0.51mb (Y:24356128-24873665) involving TTY5, RBMY2FP, RBMY1F, RBMY1J, TTY6 and PRY genes. SNP microarray seems superior, sensitive, specific as well as cost-effective method and has potential to be the first tier investigations to explore underlying genomic factors of testicular maturation arrest. The present study is an attempt to find out probable genomic factors with idiopathic testicular maturation arrest.
Properly regulated immunity requires precise integration of activating and inhibitory signals. As for other lymphocytes, B cells express an antigen-specific activating receptor, the B-cell antigen receptor (BCR), and inhibitory receptors (e.g. Fc gamma RIIb) that exercise checkpoint control on B-cell activation. Moreover, following BCR engagement, CD19 recruits proteins that amplify BCR signaling, while CD22 initiates a negative feedback loop by recruiting proteins that inhibit BCR signaling. Initial BCR signaling is mediated by protein tyrosine kinases and lipid kinases; inhibitory receptors directly antagonize the actions of these enzymes by recruiting protein tyrosine phosphatases and lipid phosphatases and positioning them close to actively signaling BCRs. Previously it was thought that inhibitory receptors such as Fc gamma RIIb and CD22 were essential for bringing these phosphatases near the BCR. In this issue of the European Journal of Immunology, Manno et al. show that a tripartite inhibitory module consisting of the adaptor proteins Dok-3 and Grb2 and the lipid phosphatase SHIP1 binds directly to activated BCRs and limits the Ca2+ mobilization that is required for B lymphocyte activation. This reveals that the BCR can be both an activating and inhibitory receptor, one that activates signaling enzymes while initiating a negative feedback loop that prevents excessive signaling.
Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV.
Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors. Here, we review recent advances in the understanding of the role of cell populations and soluble components of the innate immune system in cancer, with a focus on complement, the adapter molecule Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells.
Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpGmeasures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naive and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.
Osteopontin (OPN) is a protein, generally considered to play a pro-tumorigenic role, whereas several reports have demonstrated the anti-tumorigenic function of OPN during tumor development. These opposing anti-and pro-tumorigenic functions are not fully understood. Here, we report that host-derived OPN plays an anti-tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in Rag2(-/-) mice suggests that OPN is dispensable in the adaptive immune response. We found that host-derived OPN enhanced infiltration of natural killer (NK) cells into TRAMP tumors. The requirement of OPN in NK cell migration towards TRAMP cells was confirmed by an ex vivo cell migration assay. In contrast to TRAMP cells, in vivo B16 tumor development was not inhibited by OPN, and B16 tumors did not show OPN-mediated cell recruitment. It is possible that low levels of chemokine expression by B16 cells do not allow OPN to enhance immune cell recruitment. In addition to demonstrating the anti-tumorigenic role of OPN in TRAMP tumor development, this study also suggests that the contribution of OPN to tumor development depends on the type of tumor as well as the source and isoform of OPN.
Design and implementation of a low cost grid-connected 5kVA solar photovoltaic (PV) system is proposed in this paper. Since the inverter is a major component of the PV system, the B4 inverter used in this paper reduces the total cost of the PV system. In order to eliminate the massive transformer, the PV system is connected to the grid through IGBT switches. In addition to injection of active power into the grid, the B4 inverter can compensate reactive power and reduce harmonics of the nonlinear loads. A TMS320F28335 DSP processor is used for effective control of the B4 inverter. Various features of this processor enable the implementation of the necessary control algorithms. As a first step, the PV system is simulated and evaluated in Matlab/Simulink. In the second step, hardware circuits are designed and implemented based on the simulation results. The operation of the PV system has been evaluated under balanced, unbalanced, linear and nonlinear loads which proves its accuracy and efficiency.
B7-homolog 4 (B7-H4), one of the costimulatory molecules of the B7 family, has been reported to be widely expressed in multiple types of cancer tissues, and to be important in tumor progression and poor prognosis. However, the role of B7-H4 in esophageal precancerous lesions has not been elucidated yet. In the present study, a model of esophageal squamous cell carcinogenesis was established in 208 C57BL/6 mice by 4-nitroquinoline-1-oxide (4NQO) drinking water of mice, and the changes in the expression of B7-H4 during the whole pathological process were investigated. Hematoxylin and eosin staining results demonstrated that the pathological stage was exacerbated with the increase in time of 4NQO-mediated carcinogenesis induction, and the pathological features were similar to those observed in humans. Immunohistochemistry results revealed that B7-H4 expression was upregulated and positively correlated with pathological stage (P < 0.0001) as well as with infiltration of cluster of differentiation (CD) 11b(+) macrophage cells (P=0.0002). In addition, B7-H4 messenger RNA expression increased in the esophagi of model mice compared with that of control mice, which was positively associated with the gene expression of interleukin (IL)-6 and signal transducer and activator of transcription 3 (STAT3), according to the results of reverse transcription-quantitative polymerase chain reaction analysis. Similarly, B7-H4 protein expression was upregulated in the esophageal tissues of model mice in comparison with that of control mice, and was positively associated with IL-6 expression and STAT3 phosphorylation. In conclusion, the present data suggested that B7-H4 expression increased during esophageal squamous cell carcinogenesis in mice in association with IL-6/STAT3 signaling pathway activation.
Background: Babesiosis is a socioeconomically important tick- borne disease of animals (including humans) caused by haemoprotozoan parasites. The severity of babesiosis relates to host and parasite factors, particularly virulence/pathogenicity. Although Babesia bovis is a particularly pathogenic species of cattle, there are species of Babesia of ruminants that have limited pathogenicity. For instance, the operational taxonomic unit Babesia sp. Xinjiang (abbreviated here as Bx) of sheep from China is substantially less virulent/pathogenic than B. bovis is in cattle. Although the reason for this distinctiveness is presently unknown, it is possible that Bx has a reduced ability to adhere to cells or evade/suppress immune responses, which might relate to particular proteins, such as the variant erythrocyte surface antigens (VESAs). Results: We sequenced and annotated the 8.4 Mb nuclear draft genome of Bx and compared it with those of B. bovis and B. bigemina by synteny analysis; we also investigated the genetic relationship of Bx with selected Babesia species and related apicomplexans for which genomic datasets are available, and explored the VESA complement in Bx. Conclusions: The availability of the Bx genome now provides unique opportunities to elucidate aspects of the molecular biology, biochemistry and physiology of Bx, and to explore the reason(s) for its limited virulence and/or apparent ability to evade immune attack by the host animal. Moreover, the present genomic resource and an in vitro culture system for Bx raises the prospect of establishing a functional genomic platform to explore essential genes as new intervention targets against babesiosis.
The apicoplast (ap) is a unique, non-photosynthetic organelle found in most apicomplexan parasites. Due to the essential roles that this organelle has, it has been widely considered as target for drugs against diseases caused by apicomplexans. Exploring the ap genomes of such parasites would provide a better understanding of their systematics and their basic molecular biology for therapeutics. However, there is limited information available on the ap genomes of apicomplexan parasites. In the present study, the ap genomes of two operational taxonomic units of Babesia (known as Babesia sp. Lintan [Bl] and Babesia sp. Xinjiang [Bx]) from sheep were sequenced, assembled and annotated using a massive parallel sequencing based approach. Then, the gene content and gene order in these ap genomes (similar to 30.7 kb in size) were defined and compared, and the genetic differences were assessed. In addition, a phylogenetic analysis of ap genomic data sets was carried out to assess the relationships of these taxonomic units with other apicomplexan parasites for which complete ap genomic data sets were publicly available. The results showed that the ap genomes of Bl and Bx encode 59 and 57 genes, respectively, including 2 ribosomal RNA genes, 25 transfer RNA genes and 30-32 protein-encoding genes, being similar in content to those of Babesia bovis and B. orientalis. Ap gene regions that might serve as markers for future epidemiological and population genetic studies of Babesia species were identified. Using sequence data for a subset of six protein-encoding genes, a close relationship of Bl and Bx with Babesia bovis from cattle and B. orientalis from water buffalo was inferred. Although the focus of the present study was on Babesia, we propose that the present sequencing-bioinformatic approach should be applicable to organellar genomes of a wide range of apicomplexans of veterinary importance. (C) 2016 Elsevier B.V. All rights reserved.
Baby factories are new systematic abuse structures that are promoting infant trafficking, neo-slavery and the exploitation of young women with unwanted pregnancies in Nigeria. Since this practice was first described in 2006, it has been growing rather than abating. This paper reviews the scientific literature, along with media reports, and critiques this phenomenon from a children's rights' perspective. Children born into baby factories are denied various civil rights. They also suffer abuse in the baby factories and as a consequence of being born in such places. This abuse can be classified into immediate and long term. Immediate abuse includes inadequate care and its repercussions, denial of birth registration, illegal adoption and murder. Long-term or delayed abuse that they may be exposed to includes health-related consequences, neglect, death, child labour, prostitution and other sexual abuse, organ trafficking and recruitment as child soldiers. Various factors are thought to drive the baby factory phenomenon which include poverty, high infertility rates and the profitability of local and inter-country adoptions. Programmes directed at addressing the root cause of the problem are needed in order to eliminate infant trafficking. Also, clear laws that delineate inter-country adoption and infant trafficking need to be enacted. Most importantly, baby factories need to be recognised as child trafficking routes. Copyright (c) 2015 John Wiley & Sons, Ltd.
Baby factories and baby harvesting are relatively new terms that involve breeding, trafficking, and abuse of infants and their biological mothers. Since it was first described in a United Nations Educational, Scientific and Cultural Organization report in Nigeria in 2006, several more baby factories have been discovered over the years. Infertile women are noted to be major patrons of these baby factories due to the stigmatization of childless couples in Southern Nigeria and issues around cultural acceptability of surrogacy and adoption. These practices have contributed to the growth in the industry which results in physical, psychological, and sexual violence to the victims. Tackling baby factories will involve a multifaceted approach that includes advocacy and enacting of legislation barring baby factories and infant trafficking and harsh consequences for their patrons. Also, programs to educate young girls on preventing unwanted pregnancies are needed. Methods of improving awareness and acceptability of adoption and surrogacy and reducing the administrative and legal bottlenecks associated with these options for infertile couples should be explored to diminish the importance of baby factories.
Clostridium haemolyticum causes bacillary hemoglobinuria (BH), an infectious and usually fatal disease that occurs mostly in cattle, which is clinically characterized by jaundice, hemoglobinuria, and anemia. The trematode Fasciola hepatica has been commonly reported as the main predisposing factor that triggers this condition. The authors evaluated 20 naturally occurring cases of bovine BH to characterize the pathology and pathogenesis of the disease. Grossly, the most consistent finding was a large, frequently single focus of necrosis surrounded by a red to purple halo, observed most frequently on the parietal surface of the right and left hepatic lobes. Other findings were jaundice, dark-brown discoloration of kidneys, and red urine in the urinary bladder. Microscopically, characteristic lesions were locally extensive, necrotizing hepatitis with thrombosis and numerous intralesional Gram-positive rod-shaped bacteria, and acute renal tubular necrosis. By immunohistochemistry, many hepatocytes outside the necrotic focus in the liver were positive for activated caspase 3, suggesting that those cells were undergoing apoptosis. Ultrastructural evaluation revealed hepatocyte necrosis, hemolysis, and clumps of vegetative and sporulating bacilli within the liver. Polymerase chain reaction for the C. haemolyticum beta toxin gene was positive in randomly selected liver samples. No gross or microscopic lesions indicative of fascioliasis were detected in the liver of any animal, suggesting that other yet undetermined predisposing factors were associated with these cases of BH.
Deeper understanding of plant-endophyte interactions under abiotic stress would provide new insights into phytoprotection and phytoremediation enhancement. Many studies have investigated the positive role of plant-endophyte interactions in providing protection to the plant against pollutant stress through auxin (indole-3-acetic acid (IAA)) production. However, little is known about the impact of endophytic colonization patterns on plant stress response in relation to reactive oxygen species (ROS) and IAA levels. Moreover, the possible effect of pollutant phase on plant stress response is poorly understood. Here, we elucidated the impact of endophytic colonization patterns on plant stress response under airborne formaldehyde compared to formaldehyde-contaminated soil. ROS, tryptophan and IAA levels in the roots and shoots of endophyte-inoculated and non-inoculated plants in the presence and absence of formaldehyde were measured. Strain-specific quantitative polymerase chain reaction (qPCR) was used to investigate dynamics of endophyte colonization. Under the initial exposure to airborne formaldehyde, non-inoculated plants accumulated more tryptophan in the shoots (compared to the roots) to synthesize IAA. However, endophyte-inoculated plants behaved differently as they synthesized and accumulated more tryptophan in the roots and, hence, higher levels of IM accumulation and exudation within roots which might act as a signaling molecule to selectively recruit B. cereus ERBP. Under continuous airborne formaldehyde stress, higher levels of ROS accumulation in the shoots pushed the plant to synthesize more tryptophan and IAA in the shoots (compared to the roots). Higher levels of IAA in the shoots might act as the potent driving force to relocalize B. cereus ERBP from roots to the shoots. In contrast, under formaldehyde-contaminated soil, B. cereus ERBP colonized root tissues without moving to the shoots since there was a sharp increase in ROS, tryptophan and IAA levels of the roots without any significant increase in the shoots. Pollutant phase affected endophytic colonization patterns and plant stress responses differently. (C) 2017 Elsevier Masson SAS. All rights reserved.
To isolate and identify DNA-binding protein(s) with affinity for the mobile chromosomal repeat element bcr1 in Bacillus cereus group bacteria. A biotinylated bcr1 element was immobilized to streptavidin-coated magnetic beads and used to pull out a 20 kDa DNA-binding protein from a whole cell protein extract of B. cereus ATCC 14579. The protein was identified as the product of ORF 2 encoded by the bacteriophage-related autonomously replicating linear genetic element pBClin15 carried by the strain. DNA binding was not bcr1-specific. By Northern blotting ORF 2 was co-transcribed with ORF 1, and also in certain instances with ORF 3 by transcriptional readthrough of the terminator located between ORF 2 and ORF 3. ORF 2 from pBClin15 encodes a DNA-binding protein. ORF 2 is co-transcribed with its upstream gene ORF 1, and in a subset of the transcripts also with the downstream gene ORF 3 through alternative transcription termination. The B. cereus group contains bacterial species of medical and economic importance. Bacteriophages or phage-encoded proteins from these bacteria have been suggested as potential therapeutic agents. Understanding the biology of bacteriophage-related genetic elements through functional characterization of their genes is of high relevance.
Effects of reactive oxygen species (ROS) on cell growth and poly(-glutamic acid) (-PGA) synthesis were studied by adding hydrogen peroxide to a medium of Bacillus subtilis NX-2. After optimizing the addition concentration and time of H2O2, a maximum concentration of 33.9g/L -PGA was obtained by adding 100 mu M H2O2 to the medium after 24H. This concentration was 20.6% higher than that of the control. The addition of diphenyleneiodonium chloride (ROS inhibitor) can interdict the effect of H2O2-induced ROS. Transcriptional levels of the cofactors and relevant genes were also determined under ROS stress to illustrate the possible metabolic mechanism contributing to the improve -PGA production. The transcriptional levels of genes belonging to the tricarboxylic acid cycle and electron transfer chain system were significantly increased by ROS, which decreased the NADH/NAD(+) ratio and increased the ATP levels, thereby providing more reducing power and energy for -PGA biosynthesis. The enhanced -PGA synthetic genes also directly promoted the formation of -PGA. This study was the first to use the ROS control strategy for -PGA fermentation and provided valuable information on the possible mechanism by which ROS regulated -PGA biosynthesis in B. subtilis NX-2. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Many food and feed additives result from fermentation of genetically modified (GM) microorganisms. For vitamin B2 (riboflavin), GM Bacillus subtilis production strains have been developed and are often used. The presence of neither the GM strain nor its recombinant DNA is allowed for fermentation products placed on the EU market as food or feed additive. A vitamin B2 product (80% feed grade) imported from China was analysed. Viable B. subtilis cells were identified and DNAs of two bacterial isolates (LHL and LGL) were subjected to three whole genome sequencing (WGS) runs with different devices (MiSeq, 454 or HiSeq system). WGS data revealed the integration of a chloramphenicol resistance gene, the deletion of the endogenous riboflavin (rib) operon and presence of four putative plasmids harbouring rib operons. Event- and construct-specific real-time PCR methods for detection of the GM strain and its putative plasmids in food and feed products have been developed. (C) 2017 The Authors. Published by Elsevier Ltd.
To explore the influence of the direct repeat sequence (DRS) in Bacillus chitinase genes on heterogonous expression in Escherichia coli, we cloned and sequenced the entire open reading frame (ORF) and upstream sequences of the chitinase B (chiB) and chitinase MY75 (chiMY75) from Bacillus thuringiensis and Bacillus licheniformis. A pair of 8-bp DRS was found upstream of each chi gene. Chi ORFs with a series of truncated DRS were cloned and transformed into E. coli XL-Blue. The activity of the transformants without the DRS were significantly higher in chitinase assays than transformants containing the DRS. SOS-PAGE showed that part and full deletion of the DRS increased chi gene expression by approximately 1.7 and 3.8-fold, respectively. Northern blotting revealed deletion of the DRS regions increased chiB and chiMY75 mRNA expression. Specific binding of DNA-binding factors in the E. coli cell lyaste was observed to both the chiB and chiMY75 promoter regions and DRS elements. This is the first investigation to demonstrate that heterologous expression of Bacillus chi genes in E. coli is negatively regulated by their upstream DRS regions, which act as cis-acting elements. (C) 2012 Elsevier Inc. All rights reserved.
In recent years, model predictive control (MPC) has been successfully used for the control of power electronics converters with different topologies and for different applications. MPC offers many advantages over more traditional control techniques such as the ability to avoid cascaded control loops, easy inclusion of constraint, and fast transient response. On the other hand, the controller computational burden increases exponentially with the system complexity and may result in an unfeasible realization on modern digital control boards. This paper proposes a novel distributed MPC (DMPC), which is able to achieve the same performance of the classical MPC while reducing the computational requirements of its implementation. The proposed control approach is tested on a ac/ac converter in a back-to-back configuration used for power flow management. Simulation results are provided and validated through experimental testing in several operating conditions.
This work presents a fully FPGA based deadbeat-like predictive control scheme for back-to-back converter PMSG wind turbine systems with space vector modulator (SVM). A deadbeat-like predictive torque/current controller is used to control the machine side converter, while a deadbeat power control method in alpha beta frame is used to control the grid side converter. Both sides achieve nice steady state performances requiring few tuning efforts. Both the machine and grid side predictive controllers are realized on a commercial-off-the-shelf FPGA based platform. By using a single-cycle-timed-loop (SCTL) technique, the whole computation time is quite short (less than 4 mu s), which makes the calculation time compensation not required. The effectiveness of the presented method is verified through experimental data.
The use of power converters has considerably grown up, in part, because refined control strategies have been recently proposed, including nonlinear schemes such as predictive control. This approach is used in this work considering a variable grid frequency environment in order to get an appropriate response for a wide ac mains frequency range. Indeed, in order to achieve appropriate, both dynamic and static, responses for all operating frequencies, the number of samples per period is kept constant and independent of the ac mains frequency. This allows a fixed resolution of the sensed voltages and/or currents, which is preferable if high-performance digital control schemes are required. However, imposing a constant number of samples per period requires a variable sampling time in systems that feature variable ac mains frequency. On the other hand, predictive control has been developed and well documented just for a constant sampling frequency. This work presents how to extend the predictive control algorithms for variable sampling time allowing high-performance waveforms and wider ac mains frequency range. Simulated and experimental results show the feasibility of the proposed control strategy which corroborates the mathematical and model analysis.
This paper presents a three-phase back-to-back transformerless inverter for online uninterruptible power supply applications. The inverter consists of a three-phase three-wire input rectifier stage and a three-phase four-wire output inverter stage with their ground wires tied together. Both of the two stages are with sinusoidal pulse width modulation based division-summation (D-Sigma) digital control. The input stage controls the power flow between utility grid and dc link, regulates the dc-link voltage, and fulfills power factor correction. While the output stage tracks three-phase ac reference voltages. The proposed control laws derived based on the D-Sigma digital approach take into account the effects of dc-link voltage fluctuation, grid-voltage distortion, and inductance variation due to different current levels. Thus, distortion of input current and output voltage, and filter inductor core size can be reduced significantly. Moreover, circulating current through their common ground can be suppressed effectively. Simulated and experimental results from a three-phase back-to-back transformerless inverter have confirmed the analysis and discussion of the proposed control approach.
The aim of this study was to evaluate the occurrence of Toxoplasma gondii in backyard pigs destined for human consumption in Pernambuco state, Brazil. Blood and tissue samples (liver, heart, brain, lung and diaphragm) were collected from 224 pigs from legal slaughterhouses and tested for T. gondii infection. Antibodies to T. gondii were found in the sera of 37.9% (85/224) by using the immunofluorescence antibody test (cut-off -1: 64). Tissue samples from seropositive pigs were bioassayed in mice. Tissue samples from seropositive pigs and from mice of the bioassay were submitted to histopathology, immunohistochemistry, polymerase chain reaction (PCR) and sequencing; 14.1% of pig tissue samples and 27.7% of bioassayed mouse samples were positive for T. gondii DNA, but all pig and mouse tissues were negative in histopathology analysis and immunochemistry. By using a risk assessment questionnaire, there was significant difference (p< 0.001) in seroprevalence of 21.2% (reproducer) and 3.1% (finishing pig). These data serve as indicative of the sanitary conditions and risk of T. gondii infection for backyard pigs. Preventive measures must be implemented by health services to avoid toxoplasmosis human cases due to ingestion of pig meat.
Waterborne diseases have emerged as global health problems and their rapid and sensitive detection in environmental water samples is of great importance. Bacterial identification and enumeration in water samples is significant as it helps to maintain safe drinking water for public consumption. Culture-based methods are laborious, time-consuming, and yield false-positive results, whereas viable but nonculturable (VBNCs) microorganisms cannot be recovered. Hence, numerous methods have been developed for rapid detection and quantification of waterborne pathogenic bacteria in water. These rapid methods can be classified into nucleic acid-based, immunology-based, and biosensor-based detection methods. This review summarizes the principle and current state of rapid methods for the monitoring and detection of waterborne bacterial pathogens. Rapid methods outlined are polymerase chain reaction (PCR), digital droplet PCR, real-time PCR, multiplex PCR, DNA microarray, Next-generation sequencing (pyrosequencing, Illumina technology and genomics), and fluorescence in situ hybridization that are categorized as nucleic acid-based methods. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are classified into immunology-based methods. Optical, electrochemical, and mass-based biosensors are grouped into biosensor-based methods. Overall, these methods are sensitive, specific, time-effective, and important in prevention and diagnosis of waterborne bacterial diseases.
A repetitive sequence-based (rep)-polymerase chain reaction (PCR) and inter-simple sequence repeat (ISSR)-PCR were used to molecular type Pseudomonas syringae pv. syringae (PSS) strains isolated from barley and wheat plants with bacterial black node symptoms grown in 22 different locations and six different seed-production districts in Japan. Eighteen genomic fingerprinting (GF) genotypes were obtained from the combined results of BOX-, REP-, and GTG(5)-PCR, indicating that the PSS population in Japan has high genetic diversity. The result based on logistic regression indicated that the population of GF genotype A was significantly related to a seed-producing district and that the epidemic of PSS strains in fields originated mainly from seed infection. This study will be applicable to future studies of the molecular epidemiology of bacterial plant diseases that have multiple infection routes.
The objective of this study was to assess the effect of dietary probiotics on rumen fermentation and the bacterial community in dairy calves. Twelve Holstein calves were randomly allocated to three treatments: a basal diet, the basal diet supplemented with Lactobacillus plantarum GF103 (LB) or basal diet supplemented with a mixture of Lactobacillus plantarum GF103 and Bacillus subtilis B27 (LBS). A milk replacer was fed to calves from 8days of age. A starter and alfalfa hay was offered ad libitum from 21 and 28days of age, respectively, and the orts were weighted daily. The ruminal fluid was sampled at 56 and 83days of age to determine the rumen fermentation characteristics. The bacterial community was analyzed by denaturing gradient gel electrophoresis (DGGE) and the number of certain bacteria was quantified by real-time polymerase chain reaction. The ratio of total dry matter intake to average body wieght was higher in the control (P<0.05). The DGGE fingerprint of the 16S ribosomal RNA gene was affected by the blended probiotics at 83days of age. The number of Ruminococcus albus was lower in the LB and LBS treatment (P<0.05). Oral administration of the probiotics affected the rumen bacterial community and the numbers of cellulolytic bacteria decreased.
To determine the effect of oxytetracycline on the anaerobic biological treatment of livestock wastewater, we studied the removal efficiency of chemical oxygen demand (determined by K2Cr2O7, CODCr), methane production, and bacterial diversity under the stress of different concentrations of oxytetracycline. Results indicated that the removal of COD and the yield of methane were inhibited by oxytetracycline. With an increase in oxytetracycline concentration, methane production decreased from 392 to 207mL (the control group was 448 mL) and COD removal efficiency fell from 92% to 84% (the control group was 94%). Results of PCRDGGE (polymerase chain reaction and denaturing gradient gel electrophoresis) indicated that, with an increase in oxytetracycline concentration, the richness values of the bacterial community fell from 0.86 to 0.45 (the control group was 1). In addition, oxytetracycline reduced COD removal efficiency, methane production, and bacterial diversity in livestock wastewater. Results presented in this study provide important information about bacterial diversity in livestock wastewater treated using oxytetracycline.
Watermelon (Citrullus lanatus) is an important crop of the Cucurbitaceae family in fruit production worldwide. During its production, bacterial fruit blotch (BFB) caused by Acidovorax citrulli (Acidovorax avenae subsp. citrulli) is an important limiting factor on the volume and value of crops. This pathogen is known as a seed-borne pathogen, and the infested seeds can be a primary source of inoculum. Hence, a rapid and sensitive method for detecting A. citrulli on seeds would be an important tool in the management of BFB. In this study, we sought to develop a method to detect A. citrulli bacterial cells based on a TaqMan probe-based insulated isothermal PCR (TiiPCR) assay. Firstly, the specific primers and probe were designed based on a specific DNA fragment from the genome of A. citrulli. Then, PCR amplification was performed with the plasmid DNA to adjust the components of the PCR reagents, such as the concentrations of primers, magnesium chloride, and Taq DNA polymerase. Results revealed that 10 copies of plasmid DNA were detectable within the modified reagents by TiiPCR. Moreover, 10 bacterial cells in each reaction tube were detectable at a 100 % detection rate in this condition with a fluorescent signal intensification over 1.8. Based on these results, we concluded that a specific, rapid, and sensitive method based on TiiPCR had been successfully developed to detect bacterial cells of A. citrulli.
The targeting of bacterial type III secretion systems (T3SSs), which are critical virulence factors in most Gram-negative pathogens, is regarded as an alternative strategy for the development of novel anti-microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc) are two of the most important bacterial pathogens on rice, which cause leaf blight and leaf streak diseases, respectively. To identify potential anti-virulence drugs against these two pathogens, we screened a library of plant phenolic compounds and derivatives for their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the promoter activity of a harpin gene, hpa1. These inhibitors were further tested for their impact on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results showed that pretreatment of Xoo with TS006 (o-coumaric acid, OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without affecting bacterial growth or survival. In addition, Cya translocation assays demonstrated that the translocation of two T3 effectors was suppressed by the four inhibitors. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that mRNA levels of representative genes in the hrp (hypersensitive response and pathogenicity) cluster, as well as the regulatory genes hrpG and hrpX, were reduced by treatment with the four inhibitors, suggesting that expression of the Xoo T3SS was suppressed. The expression of other virulence factors was not suppressed, which indicated possible T3SS-specific inhibition. Finally, we demonstrated that these inhibitors reduced the disease symptoms of Xoo and Xoc on the rice cultivar (Oryza sativa) IR24 to varying extents.
Objective. -To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Methods. -Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Results. -Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (ELI). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). Conclusion. -The screening and treatment of BV during pregnancy in asymptomatic low-risk population is not recommended in the prevention of the risk of spontaneous preterm delivery (grade A): In the population at high risk with the only notion of antecedent of premature delivery, screening and treatment of the BY is not recommended (grade C). (C) 2016 Elsevier Mason SAS.
In 2016, the British Journal of Biomedical Science published 36 reports outlining specific advances in each of the various disciplines within biomedical science. These were one review, 25 original articles, 9 'In Brief' reports and one letter to the Editor. Of these, the majority were in blood science (5 in biochemistry, 7 in haematology and 2 in immunology) and infection science (8 in microbiology, 2 in virology) with a smaller number in cellular sciences (6 in cellular pathology and 2 in cytopathology). Three reports considered both biochemistry and immunology, while another reported an advance in the identification of chromosomal abnormalities. The present report will summarise key aspects of these publications that are of greatest relevance to laboratory scientists.
The Dutch microbiologist/biochemist Albert Jan Kluyver (1888-1956) was an early proponent of the idea of biochemical unity, and how that concept might be demonstrated through the careful study of microbial life. The fundamental relatedness of living systems is an obvious correlate of the theory of evolution, and modern attempts to construct phylogenetic schemes support this relatedness through comparison of genomes. The approach of Kluyver and his scientific descendants predated the tools of modern molecular biology by decades. Kluyver himself is poorly recognized today, yet his influence at the time was profound. Through lens of today however, it has been argued that the focus by Kluyver and others to create taxonomic and phylogenetic schemes using morphology and biochemistry distorted and hindered progress of the discipline of microbiology, because of a perception that the older approaches focused too much on a reductionist worldview. This essay argues that in contrast the careful characterization of fundamental microbial metabolism and physiology by Kluyver made many of the advances of the latter part of the twentieth century possible, by offering a framework which in many respects anticipated our current view of phylogeny, and by directly and indirectly training a generation of scientists who became leaders in the explosive growth of biotechnology.
In this article we compare the efficacy of different pharmacological agents ( ranitidine, and omeprazole) to support phage transit from stomach to distal portions of the gastrointestinal tract in rats. We show that a temporal modification of environment in the animal stomach may protect Twort-like therapeutic antistaphylococcal phage A5/80 ( from bacteriophage collection of the Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland) from the inactivation by gastric juice effectively enough to enable a significant fraction of orally administered A5/80 to pass to the intestine. Interestingly, we found that yogurt may be a relatively strong in enhancing phage transit. Given the immunomodulating activities of phages our data may suggest that phages and yogurt can act synergistically in mediating their probiotic activities and enhancing the effectiveness of oral phage therapy. We also demonstrate that orally applied phages of similar size, morphology, and sensitivity to acidic environment may differ in their translocation into the bloodstream. This was evident in mice in which a therapeutic staphylococcal phage A5/80 reached the blood upon oral administration combined with antacid agent whilst T4 phage was not detected even when applied in 103 times higher dose. Our findings also suggest that phage penetration from digestive tract to the blood may be species-specific.
The Poisson distribution played a key role in experiments that had a historic role in the development of molecular biology. In particular, the interpretation and design of experiments elucidating the actions of bacteriophages and their host bacteria during the infection process were based on the parameters of the Poisson distribution. I briefly review three of the most important of these experiments and offer suggestions on the use of the Poisson distribution in statistical calculations in biology laboratory exercises reflecting the use of the Poisson distribution in current biological investigations.
His-Asn-His (HNH) proteins are a very common family of small nucleic acid-binding proteins that are generally associated with endonuclease activity and are found in all kingdoms of life. Although HNH endonucleases from mesophiles have been widely investigated, the biochemical functions of HNH endonucleases from thermophilic bacteriophages remain unknown. Here, we characterized the biochemical properties of a thermostable HNH endonuclease from deep-sea thermophilic bacteriophage GVE2. The recombinant GVE2 HNH endonuclease exhibited non-specific cleavage activity at high temperature. The optimal temperature of the GVE2 HNH endonuclease for cleaving DNA was 60-65 A degrees C, and the enzyme retained its DNA cleavage activity even after heating at 100 A degrees C for 30 min, suggesting the enzyme is a thermostable endonuclease. The GVE2 HNH endonuclease cleaved DNA over a wide pH spectrum, ranging from 5.5 to 9.0, and the optimal pH for the enzyme activity was 8.0-9.0. Furthermore, the GVE2 HNH endonuclease activity was dependent on a divalent metal ion. While the enzyme is inactive in the presence of Cu2+, the GVE2 HNH endonuclease displayed cleavage activity of varied efficiency with Mn2+, Mg2+, Ca2+, Fe2+, Co2+, Zn2+, and Ni2+. The GVE2 HNH endonuclease activity was inhibited by NaCl. This study provides the basis for determining the role of this endonuclease in life cycle of the bacteriophage GVE2 and suggests the potential application of the enzyme in molecular biology and biotechnology.
Bacteriophages represent a simple viral model of basic research with many possibilities for practical application. Due to their ability to infect and kill bacteria, their potential in the treatment of bacterial infection has been examined since their discovery. With advances in molecular biology and gene engineering, the phage application spectrum has been expanded to various medical and biotechnological fields. The construction of bacteriophages with an extended host range or longer viability in the mammalian bloodstream enhances their potential as an alternative to conventional antibiotic treatment. Insertion of active depolymerase genes to their genomes can enforce the biofilm disposal. They can also be engineered to transfer various compounds to the eukaryotic organisms and the bacterial culture, applicable for the vaccine, drug or gene delivery. Phage recombinant lytic enzymes can be applied as enzybiotics in medicine as well as in biotechnology for pathogen detection or programmed cell death in bacterial expression strains. Besides, modified bacteriophages with high specificity can be applied as bioprobes in detection tools to estimate the presence of pathogens in food industry, or utilized in the control of food-borne pathogens as part of the constructed phage-based biosorbents.
Secretory immunoglobulin A (SIgA) antibody-secreting cells (ASCs) are the major effector cells of mucosal immunity, and immunoglobulin G (IgG) ASCs are also associated with mucosal immunity. This study aimed to explore the distribution of these 2 ASC populations in the palatine tonsils of Bactrian camels of different ages. Eighteen Bactrian camels were divided into the following three age groups: pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). SIgA and IgG ASCs within different sites of the palatine tonsils were observed through histological and immunohistochemical techniques, and their densities were analyzed using statistical methods. The results from all age groups showed that both the SIgA and IgG ASCs were primarily distributed in the subepithelial compartments of the reticulated crypt epithelium and secondarily distributed in the subepithelial compartments of the stratified surface squamous epithelium, with a few ASCs located in the extrafollicular region. Their densities in these three areas were significantly decreased in turn (P<0.05). However, the densities of SIgA ASCs were significantly higher than IgG ASCs in the same regions (P<0.05), and the densities of both ASC populations decreased with age. The results confirmed that Bactrian camel palatine tonsils are the primary mucosal immune organ producing SIgA ASCs, and the subepithelial compartment of the reticulated crypt epithelium is the primary region for the colonization and functional activity of SIgA and IgG ASCs.
In the present study, we reveal for the first time that the Bactrocera oleae chorion peroxidase (bPxd) participates essentially in B. oleaechorion formation and clearly represents the homologous member of Drosophila melanogaster chorion peroxidase (Pxd). Comparative sequence analysis disclosed that the bPxd cDNA semi-central region,which encodes for the putative catalytic domain of the enzyme, exhibits great homology (98%) with its Pxd counterpart. Thus, it is very likely that bPxd is highly responsible for the chorion hardening process, through protein cross-linking mediated by the formation of di- and tri-tyrosine bonds. Distinct molecular weight bPxd RNA transcripts were detected in Northern blotting analysis of total RNA extracts of adult flies (2.9 and 1.7 kb) and ovaries (2.2 kb). The ovarian-specific bPxd RNA transcript is selectively expressed in the follicle cell layer during the late stages of oogenesis 12-14, as revealed by in situ hybridization. Moreover, reverse transcription reactions confirmed the stage-specific developmental regulation of the bPxd gene, which is maximally expressed during stage 13. Western blotting with the rabbit anti-rAePO polyclonal antibody revealed three immunoreactive bands of 76, 66 and 54 kDa in crude protein extracts from adult flies, while in larva and purified chorion preparations, a unique 54 kDa band was clearly detected. Immunolocalization experiments revealed that bPxd peroxidase constitutes an essential structural chorionic component, being abundantly localized in all the successive chorionic layers and vitelline membrane as well.
The genus Potexvirus is one of the eight genera belonging to the family Alphaflexiviridae according to the Virus Taxonomy 2015 released by International Committee on Taxonomy of Viruses (www. ictvonline. org/index. asp). Currently, the genus contains 35 known species including many agricultural important viruses, e.g., Potato virus X (PVX). Members of this genus are characterized by flexuous, filamentous virions of 13 nm in diameter and 470-580 nm in length. A potexvirus has a monopartite positive-strand RNA genome, encoding five open-reading frames (ORFs), with a cap structure at the 5 0 end and a poly(A) tail at the 3 0 end. Besides PVX, Bamboo mosaic virus (BaMV) is another potexvirus that has received intensive attention due to the wealth of knowledge on the molecular biology of the virus. In this review, we discuss the enzymatic activities associated with each of the functional domains of the BaMV replication protein, a 155kDa polypeptide encoded by ORF1. The unique cap formation mechanism, which may be conserved across the alphavirus superfamily, is particularly addressed. The recently identified interactions between the replication protein and the plant host factors are also described.
We constructed a SSH (suppression subtractive hybridization) library based on two populations (Rs-C and Rs-P) of Radopholus similis from different host plants and exhibiting differences in pathogenicity on Musa paradisiaca and Anthurium andraeanum plants. In order to screen the clones with significant expression differences from the SSH library, a total of 2,400 clones was randomly selected and reverse northern blotting was performed on them. Out of the 2,400 clones, 89 clones showed significant expression differences. Out of sequencing these 89 clones, distinct sequences from 87 clones were obtained. Aligning the 87 distinct sequences against the non-redundant nucleotide database (nr) in NCBI, we found that five sequences were highly conserved with Rs-eng-1b. Two of five sequences with lengths of 467 base pairs (bp) (GW395922) and 742 bp (GW395923) were further employed to perform 5' RACE-PCR and 3' RACE-PCR, respectively. Subsequently, the complete length of Rs-eng-1b (EU414839) was obtained (1,427 bp). Our qPCR result showed that expression of Rs-eng-1b in the population Rs-C with high pathogenicity on host plants was approximately 2.7 times as much as the expression of Rs-eng-1b in the population Rs-P with low pathogenicity on host plants. Furthermore, the gene Rs-eng-1b from the Rs-C population also showed expression differences amongst four different development stages. The order of Rs-eng-1b relative expression abundance from high to low was females, juveniles, males, and eggs. We further used RNAi to test whether Rs-eng-1b of Rs-C population was responsible for pathogenicity which was the first RNAi work about Rs-eng-1b. The RNAi results showed that Rs-eng-1b expression had a positive correlation to pathogenicity of the population. The longer the RNAi treatment, the less pathogenic the nematode population was. Non-endogenous gfp dsRNA had no significant influence on the expression of Rs-eng-1b and pathogenicity of R. similis Rs-C population. In conclusion, all our evidence indicated Rs-eng-1b might be a crucial pathogenicity-related gene in R. similis.
Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is among the most destructive diseases of banana (Musa spp.). Because no credible control measures are available, development of resistant cultivars through genetic engineering is the only option. We investigated whether intron hairpin RNA (ihpRNA)-mediated expression of small interfering RNAs (siRNAs) targeted against vital fungal genes (velvet and Fusarium transcription factor 1) in transgenic banana could achieve effective resistance against Foc. Partial sequences of these two genes were assembled as ihpRNAs in suitable binary vectors (ihpRNA-VEL and ihpRNA-FTF1) and transformed into embryogenic cell suspensions of banana cv. Rasthali by Agrobacterium-mediated genetic transformation. Eleven transformed lines derived from ihpRNA-VEL and twelve lines derived from ihpRNA-FTF1 were found to be free of external and internal symptoms of Foc after 6-week-long greenhouse bioassays. The five selected transgenic lines for each construct continued to resist Foc at 8 months postinoculation. Presence of specific siRNAs derived from the two ihpRNAs in transgenic banana plants was confirmed by Northern blotting and Illumina sequencing of small RNAs derived from the transgenic banana plants. The present study represents an important effort in proving that host-induced post-transcriptional ihpRNA-mediated gene silencing of vital fungal genes can confer efficient resistance against debilitating pathogens in crop plants.
A low-voltage bandgap reference implemented in 0.18 mu m CMOS process is designed. The bandgap reference circuit is optimized by adjusting the ratio of the resistors, and reducing the working voltage of operational amplifier. It achieves the performance of a temperature coefficient of 25 ppm/degrees C in the range of 0 similar to 100 degrees C which works under the voltage of 0.8V. The simulated power supply rejection ratio is 46.3dB @1Hz and the line regulation is 1.5mV/V in the range from 0.8V to 1.8V.
This article designed a bandgap voltage reference source with a low temperature drift, high power supply rejection ratio for the TCXO chips, and design the sensitive reaction of thermal protection circuit is used to protect TCXO chips. The structure of self-biased current source and differential operational amplifier is used in the bandgap reference, And the over temperature protection circuit controlled oscillator on or off by a NPN transistor to detection the circuit current. The simulation results show that the range of the voltage output is not more than 0.78 mV when the temperature changes at -40 to 125, The power supply rejection ratio in the circuit is as high as 95dB; the oscillator is turned off When the temperature is greater than 150 degrees, and it's restart when the temperature is less than 130 degrees, and it turn off needs less than 0.071 S, restart needs less than 0.064 S. The circuit can provide a stable reference and good temperature protection effect, which has great practical value for the TCXO chip.
This paper presents a new curvature-compensated CMOS bandgap reference topology with a high power supply reject ratio (PSRR). A dual-differential input amplifier (DDIA) is used to generate a complementary to absolute temperature voltage. This voltage and the DDIA are then used to fine-tune its curvature compensation. Experimental characterization of the bandgap reference circuit implemented on a 0.5 A mu m CMOS process yielded a bandgap reference voltage with a temperature coefficient (TC) of 4.1 ppm/A degrees C across the temperature range of -40 to 125 A degrees C. A PSRR of 82 dB was also realized with a high output load current driving ability without the use of an external buffer amplifier.
This paper proposes a new CMOS based Bandgap voltage reference generator (BGR) circuit by using polysilicon resistors in 32nm CMOS technology. This reference generator uses a three stage operational amplifier for improved performance over previously proposed BGR circuits. The proposed design is simulated in Synopsys HSPICE simulator. This circuit produces an output reference voltage of 0.725V at the room temperature (25 degrees C) for the supply voltage of 1.8V. Analysis shows that, a very low temperature coefficient (TC) of 13ppm/degrees C is obtained in the output reference voltage for the temperature range of-40 degrees C to 100 degrees C. Using poly-silicon resistor the area is reduced, without losing too much control over current consumption.
This paper presents a novel low power bandgap reference circuit, the bandgap reference adopts half a period working mechanism. The operational amplifier doesn't work during the switched capacitor network sampling. And the operational amplifier works after the charge balanced. The bandgap reference runs discontinuously. The design implements in standard 0.18um CMOS process. The simulation result shows that, the circuit consumes 19.8 uAat 3.3V. The noise of the circuit in low frequency achieves 3.9 mu V/root Hz and the temperature coefficient is 21 ppm/degrees C.
Grid voltage feedforward is extensively used for controlling grid-connected converters. However, the conventional voltage feedforward control reduces the stability margins of the converter connected to a high-impedance grid. The effect mechanism of voltage feedforward on the grid-connected converter control under high-inductive conditions of the grid impedance is clearly explained in this study using the equivalent transformations of control block diagrams. Results show that the delay produced by the digital control is the root cause of this effect. An improved voltage feedforward strategy, in which a bandpass filter (BPF) is introduced into the feedforward path, is proposed to strengthen the converter's robust stability against grid impedance variations. The selection method of the BPF's bandwidth is also provided considering the tradeoff between the response speed to the grid voltage sag and the system's robust stability. The converter can work stably over a wide range of the grid impedance through the proposed approach. Simulation and experimental results fully verify the effectiveness of the BPF-based voltage feedforward strategy.
In this paper a DVCC based operational amplifier has been proposed. A pole has been introduced in transfer characteristic of DVCC by an integrated capacitor. The op amp is composed of an on chip DVCC, one integrated NMOS resistor, a capacitor and a CMOS voltage follower. The bandwidth of DVCC op amp can be adjusted by voltage tuning of the resistor. Conventional voltage mode operational amplifiers suffer from introduction of second pole at high frequencies, thus rendering the circuits suitable for low frequency applications only. The proposed DVCC op amp has large signal bandwidth and can operate for wide range of frequencies. A bandpass filter has been tested using the reported op amp in PSPICE and theoretical analysis has been presented.
A low component sensitivity band-pass filter has been proposed. The filter has only one operational amplifier as active component and three resistors and one grounded capacitor as passive components. Two resistors provide the positive feedback and one resistor is used for independent tuning of Q factor. The capacitor is grounded which is an advantage in integrated technology. The circuit uses the pole frequency of the operational amplifier for its working and can be operated at high frequency range. PSpice simulations have been presented to verify theoretical analysis.
This paper presents the design and characterization of a fully-differential intermediate frequency (IF) filter based on an operational transconductance amplifier (OTA) with 6th order Butterworth bandpass characteristic. The designed 2-stage BiCMOS OTA can be treated as an operational amplifier (OPAmp) together with its output resistance. The combination exhibits an open-loop voltage gain of 75 dB and high gainbandwidth product (GBP) of 5.8 GHz, while stability is achieved with a worst case phase margin (PM) of 54 degrees from a low bias-current of only 520 mu A. The multiple-feedback filter (MFB) elements for the target Butterworth frequency response are determined with circuit analysis based on an ideal OTA transfer function. The filter center frequency is set to 60 MHz, whereby a measured -3 dB-bandwidth of 15.5MHz is achieved. To enable the operation within an on-time of 200 ns the filter is able to settle at +/- 1 dB of its steady state amplitude in less than 115 ns. The filter was fabricated in the IHP 130nm BiCMOS technology and requires a current of only 1.6mA from a 2.5V-supply including all bias circuits.
Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in traditional Chinese medicine, is widely distributed in South China, especially in Fujian. Recent studies about B. cusia mainly focus on its chemical composition and pharmacological effects, but further analysis of the plant's gene functions and expression is required to better understand the synthesis of its effective compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful method for gene expression analysis. It is necessary to select a suitable reference gene for expression normalization to ensure the accuracy of RT-qPCR results. Ten candidate reference genes were selected from the transcriptome datasets of B. cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. By employing different algorithms, such as geNorm, NormFinder, and BestKeeper, which are complementary approaches based on different statistical procedures, 18S rRNA was found to be the most stable gene under UV irradiation and hormonal stimuli, whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different plant organs. This novel study aimed to screen for suitable reference genes and corresponding primer pairs specifically designed for gene expression studies in B. cusia, in particular for RT-qPCR analyses.
This study had the aim to identify and relat the occurrence of billfish larvae and eggs in the Southeastern coast of Brazil. During the summer in two seasons (2012/2013 and 2013/2014) 74 surface trawls were done using an ichthyoplankton net off the coast of Vitoria-ES, Rio de Janeiro-RJ and Ilhabela-SP and 391 fish larvae were collected. The identification of the billfish larvae was done by molecular biology using the DNA barcode (COI gene). During the 2012/2013 season, five sailfish and two white marlin larvae were identified and in the 2013/2014 season, two sailfishes, two white marlin larvae and two swordfish eggs were identified. The occurrence of billfish larvae shall be further studied, so that inferences about the area and period of spawning and development of early life stages of these fish can be made more accurately.
This article has three aims. First, it reacts to the doubts expressed recently about the possibility of making generalizations about Catholicism after the Council of Trent. Second, it discusses the different uses of the term "Catholic Reformation" and proposes a definition that involves a movement toward the universalization of divine love. And third, it also discusses the success of confessionalization in some parts of Europe and the reasons why it was not a top-down process. The emphasis on disciplining endeavors in the analysis of the history of confessionalization misses the integrative character of various devotional practices in Baroque Europe and fails to pay sufficient attention to the religious constraints affecting political actors.
Functional genomic screening of the rat enamel organ (EO) has led to the identification of a number of secreted proteins expressed during the maturation stage of amelogenesis, including amelotin (AMTN) and odontogenic ameloblast-associated (ODAM). In this study, we characterise the gene, protein and pattern of expression of a related protein called secretory calcium-binding phosphoprotein-proline-glutamine-rich 1 (SCPPPQ1). The Scpppq1 gene resides within the secretory calcium-binding phosphoprotein (Scpp) cluster. SCPPPQ1 is a highly conserved, 75-residue, secreted protein rich in proline, leucine, glutamine and phenylalanine. In silico data mining has revealed no correlation to any known sequences. Northern blotting of various rat tissues suggests that the expression of Scpppq1 is restricted to tooth and associated tissues. Immunohistochemical analyses show that the protein is expressed during the late maturation stage of amelogenesis and in the junctional epithelium where it localises to an atypical basal lamina at the cell-tooth interface. This discrete localisation suggests that SCPPPQ1, together with AMTN and ODAM, participates in structuring the basal lamina and in mediating attachment of epithelia cells to mineralised tooth surfaces.
High metabolic activity and low levels of antioxidant enzymes make neurons particularly prone to damage by reactive oxygen species. Thus, repair of oxidative DNA damage is essential for normal brain function. Base excision repair is the major pathway for repair of oxidative DNA damage, and is initiated by DNA glycosylases recognizing and removing the damaged base. In mammalian cells at least five different DNA glycosylases with overlapping substrate specificity, NEIL1, NEIL2, NEIL3, OGG1 and NTH1, remove oxidative DNA base lesions. Here we report mRNA expression and distribution of these five DNA glycosylases in human and rodent brains using in situ hybridization and Northern blotting supported by glycosylase activity assays. NEIL1, NEIL2, OGG1 and NTH1 showed widespread expression at all ages. in situ hybridization studies in mouse brain showed that expression of mNeil1 increased with age. In newborn mouse brain, mNeil3 revealed a discrete expression pattern in brain regions known to harbour stem cell populations, i.e., the subventricular zone, the rostral migratory stream, and the hilar region of the hippocampal formation. Expression of mNeil3 decreased with age, and in old mice brains could be detected only in layer V of neocortex. MNth1 was constitutively expressed during lifespan. in Northern blots, mOgg1 expression showed a transient decrease followed by an increase after 8 weeks of age. Assays for faPy DNA glycosylase activity revealed increased activity level with age in all brain regions analyzed.
Currently there is no effective approach for monitoring early -cell loss during islet graft rejection following human islet transplantation (HIT). Due to ethical and technical constraints, it is difficult to directly study biomarkers of islet destruction in humans. Here, we established a humanized mouse model with induced human -cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of ALT-treated mice had perigraft lymphocyte infiltration, fewer insulin(+) cells, and increased -cell apoptosis. Islet-specific miR-375 was used to validate our model, and expression of miR-375 was significantly decreased in the grafts and increased in the circulation of ALT-treated mice before hyperglycemia. A NanoString expression assay was further used to profile 800 human miRNAs in the human islet grafts, and the results were validated using quantitative real-time polymerase chain reaction. We found that miR-4454 and miR-199a-5p were decreased in the human islet grafts following ALT and increased in the circulation prior to hyperglycemia. These data demonstrate that our in vivo model of induced human -cell destruction is a robust method for identifying and characterizing circulating biomarkers, and suggest that miR-4454 and miR-199a-5p can serve as novel biomarkers associated with early human -cell loss following HIT.
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded exvivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3 signaling domain (CAR) and one lacking an intracellular signaling domain (CAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or CAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and CAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.
Basic fibroblast growth factor (bFGF) regulates pluripotent marker expression and cellular differentiation in various cell types. However, the mechanism by which bFGF regulates REX1 expression in stem cells, isolated from human exfoliated deciduous teeth (SHEDs) remains unclear. The aim of the present study was to investigate the regulation of REX1 expression by bFGF in SHEDs. SHEDs were isolated and characterized. Their mRNA and protein expression levels were determined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In some experiments, chemical inhibitors were added to the culture medium to impede specific signaling pathways. Cells isolated from human exfoliated deciduous tooth dental pulp tissue expressed mesenchymal stem cell surface markers (CD44, CD73, CD90, and CD105). These cells differentiated into osteogenic and adipogenic lineages, when appropriately induced. Treating SHEDs with bFGF induced REX1 mRNA expression and this effect was attenuated by pretreatment with FGFR or Akt inhibitors. Cycloheximide pretreatment also inhibited the bFGF-induced REX1 expression, implying the involvement of intermediate molecule(s). Further, the addition of an IL-6 neutralizing antibody attenuated the bFGF-induced REX1 expression by SHEDs. In conclusion, bFGF enhanced REX1 expression by SHEDs via the FGFR and Akt signaling pathways. Moreover, IL-6 participated in the bFGF-induced REX1 expression in SHEDs. (C) 2016 Wiley Periodicals, Inc.
Rationale, aims and objectivesThe purpose of medical education is to produce competent and capable professional practitioners who can combine the art and science of medicine. Moreover, this process must prepare individuals to practise in a field in which knowledge is increasing and the contexts in which that knowledge is applied are changing in unpredictable ways. The basic sciences' are important in the training of a physician. The goal of basic science training is to learn it in a way that the material can be applied in practice. Much effort has been expended to integrate basic science and clinical training, while adding many other topics to the medical curriculum. This effort has been challenging. The aims of the paper are (1) to propose a unifying conceptual framework that facilitates knowledge integration among all levels of living systems from cell to society and (2) illustrate the organizing principles with two examples of the framework in action - cybernetic systems (with feedback) and distributed robustness. MethodsLiterature related to hierarchical and holarchical frameworks was reviewed. ResultsAn organizing framework derived from living systems theory and spanning the range from molecular biology to health systems management was developed. The application of cybernetic systems to three levels (regulation of pancreatic beta cell production of insulin, physician adjustment of medication for glycaemic control and development and action of performance measures for diabetes care) was illustrated. Similarly distributed robustness was illustrated by the DNA damage response system and principles underlying patient safety. ConclusionsEach of the illustrated organizing principles offers a means to facilitate the weaving of basic science and clinical medicine throughout the course of study. The use of such an approach may promote systems thinking, which is a core competency for effective and capable medical practice.
The feruloyl esterase (FAE) gene EST1 from the basidiomycete Pleurotus sapidus was heterologously expressed in Escherichia coli and Pichia pastoris. Catalytically active recombinant Est1 was secreted using P. pastoris as a host. For expression in P. pastoris, the expression vector pPIC9K was applied. The EST1 gene was cloned with an N-terminal a-mating factor pre-pro sequence and expressed under the control of a methanol inducible alcohol oxidase 1 promotor. Est1 was purified to homogeneity using ion exchange and hydrophobic interaction chromatography. The recombinant Est1 showed optima at pH 5.0 and 50 degrees C, and released ferulic acid from saccharide esters and from the natural substrate destarched wheat bran. Substrate specificity profile and descriptor-based analysis demonstrated unique properties, showing that Est1 did not fit into the current FAE classification model. Transferuloylation synthesis of feruloyl-saccharide esters was proven for mono- and disaccharides. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 852-862, 2016
Large collections of data in studies on cancer such as leukaemia provoke the necessity of applying tailored analysis algorithms to ensure supreme information extraction. In this work, a custom-fit pipeline is demonstrated for thorough investigation of the voluminous MILE gene expression data set. Three analyses are accomplished, each for gaining a deeper understanding of the processes underlying leukaemia types and subtypes. First, the main disease groups are tested for differential expression against the healthy control as in a standard case-control study. Here, the basic knowledge on molecular mechanisms is confirmed quantitatively and by literature references. Second, pairwise comparison testing is performed for juxtaposing the main leukaemia types among each other. In this case by means of the Dice coefficient similarity measure the general relations are pointed out. Moreover, lists of candidate main leukaemia group biomarkers are proposed. Finally, with this approach being successful, the third analysis provides insight into all of the studied subtypes, followed by the emergence of four leukaemia subtype biomarkers. In addition, the class enhanced DEG signature obtained on the basis of novel pipeline processing leads to significantly better classification power of multi-class data classifiers. The developed methodology consisting of batch effect adjustment, adaptive noise and feature filtration coupled with adequate statistical testing and biomarker definition proves to be an effective approach towards knowledge discovery in high-throughput molecular biology experiments.
The aim of this study is to optimize the production of optically pure D (-) lactic acid (DLA) employing a cost-effective production medium. Based on the designed biomass approach, Sporolactobacillus inulinus NBRC 13595 was found to exhibit high DLA titer (19.0 g L-1) and optical purity (99.6%). A cost-effective medium was constituted using Palmyra palm jaggery (PJ) from Borassus flabellifer and whey protein hydrolysate (WPH) as carbon and nitrogen sources, respectively. Plackett-Burman design indicated that PJ, WPH, and MnSO4 as significant variables influence DLA production. A rotatable central composite design and response surface methodology were used to optimize the PJ and WPH concentrations. A maximum DLA titer (170.14 g L-1) was predicted for 222.24 g L-1 of PJ and 11.99 g L-1 of WPH, respectively. Fermentation experimental results exhibited a maximum DLA titer (189.0 +/- 8.53 g L-1) and productivity (5.25 +/- 0.24 g L-1 H-1), which is the highest ever reported for DLA production from a renewable feedstock in the batch process. The present investigation substantiates that the potential application of economically viable raw feedstocks (PJ and WPH) for enhanced DLA production, which is attributed to 2.5-fold reduction in DLA production cost compared with conventional medium. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Selection on floral traits in hermaphroditic plants is determined by both male and female reproductive success. However, predictions regarding floral trait and mating system evolution are often based solely on female fitness. Selection viamale fitness has the potential to affect the outcomes of floral evolution. In this study, we used paternity analysis to assess individual selfing rates and selection on floral traits via male and female fitness in an experimental population of Clarkia xantiana where pollen limitation of seed set was strong. We detected selection through both female and male fitness with reinforcing or noninterfering patterns of selection through the two sex functions. For female fitness, selection favored reduced herkogamy and protandry, traits that promote increased autonomous selfing. For male fitness, selection on petal area was disruptive, with higher trait values conferring greater pollinator attraction and outcross siring success and smaller trait values leading to higher selfed siring success. Combining both female and male fitness, selection on petal area and protandry was disruptive because intermediate phenotypes were less successful as both males and females. Finally, functional relationships among male and female fertility components indicated that selfing resulted in seed discounting and pollen discounting. Under these functional relationships, the evolutionarily stable selfing rate can be intermediate or predominantly selfing or outcrossing, depending on the segregating load of deleterious mutations.
This report describes the case of a 10-month-old infant, who was delivered to our hospital by the emergency physician intubated and in an unclear unconscious state. The father reported that the child had fallen from the couch to the ground. The consulted ophthalmologist reported venous stasis in both eyes including intraretinal and preretinal bleeding in all four quadrants, a diffuse vitreous hemorrhage in the right eye and temporal retinal wrinkling in both eyes. Based on these particular clinical findings a shaken baby syndrome was suspected. This report demonstrates the importance of recognizing and correctly interpreting the typical ophthalmological signs of physical child abuse in order to detect and prevent further mistreatment of children; moreover, the increasing importance of photographic documentation and histological work-up of the findings for forensic reasons are emphasized.
The objective of this study was to examine factors facilitating and constraining the identification and management of intimate partner violence (IPV) at an emergency department (ED). Semi-structured interviews were conducted with 18 ED employees of a university hospital in the Netherlands. All interviews were audiotaped, transcribed verbatim, and analyzed by using qualitative content analysis in Atlas. ti. Constraining factors were lack of knowledge, awareness, and resources at the ED. ED employees felt many barriers to bringing up IPV. Facilitating factors were good cooperation among staff, the involvement of one team member in producing an IPV protocol, having received training on child abuse, and private consulting rooms. The ED setting and the ED employees' task perception and attitude contained both constraining and facilitating factors: ED employees saw it as their task and responsibility to help IPV victims, but their priorities were to secure a high turnover and treat acute physical problems. Although ED employees expressed openness and willingness to help, they also took the view that victims had a considerable responsibility of their own in disclosing and managing IPV, which led to ambivalent feelings. In conclusion, ED employees faced tensions in IPV identification and management caused by lack of awareness, knowledge and resources, conflicting priorities at the ED, and ambivalent feelings. Improvements can be made by supporting ED employees with guidelines in the form of a protocol and with training that also addresses the tensions ED employees face.
In the United States, the judicial system response to violence between intimate partners, or intimate partner violence (IPV), typically mandates that adjudicated perpetrators complete a batterer intervention program (BIP). The social science data has found that these programs, on the whole, are only minimally effective in reducing rates of IPV. The authors examined the social science literature on the characteristics and efficacy of BIPs. More than 400 studies were considered, including a sweeping, recently conducted survey of BIP directors across the United States and Canada. Results of this review indicate that the limitations of BIPs are due, in large part, to the limitations of current state standards regulating these programs and, furthermore, that these standards are not grounded in the body of empirical research evidence or best practices. The authors, all of whom have considerable expertise in the area of domestic violence perpetrator treatment, conducted an exhaustive investigation of the following key intervention areas: overall effectiveness of BIPs; length of treatment/length of group sessions; number of group participants and number of facilitators; group format and curriculum; assessment protocol and instruments; victim contact; modality of treatment; differential treatment; working with female perpetrators; working with perpetrators in racial and ethnic minority groups; working with lesbian, gay, bisexual, and transgender (LGBT) perpetrators; perpetrator treatment and practitioner-client relationships; and required practitioner education and training. Recommendations for evidence-based national BIP standards were made based on findings from this review.
Treatment of perpetrators is tried and tested albeit little researched for the prevention of recidivism in domestic violence in Germany. This study investigated the evidence of batterer programs on the risk of domestic violence recidivism and the risk of child maltreatment reported by fathers on 161 perpetrators of domestic violence. Based on the indicators for a high risk for reassault that were confirmed in international longitudinal studies, a risk inventory for domestic violence was developed and implemented in three German program sites. A shortened German version of the Child Abuse Potential Inventory and the Interpersonal- Reactivity- Index were used for perpetrators' self report. The study showed that the child abuse potential of program dropouts was significantly higher compared to program completers at baseline (n = 92). Longitudinal results showed significant improvements with moderate effect sizes in all risk indicators assessed by specialists (n = 78) and battered women (n = 44). Perpetrators' self report on cognitive empathy improved too (n = 62). However, selfreported risk of child maltreatment did not change (n = 46). No evidence of selective questioning of victims was found. A classification of the results as well as the implications for the treatment of perpetrators and research on recidivism in Germany are discussed.
The deployment of renewable energy technologies, such as solar photovoltaics and wind turbines, poses challenges in terms of electricity grid stability due to the intermittent nature of such energy sources, which creates a need for innovative storage solutions. We demonstrate a metal hydride-based hybrid electrochemical system that enables a solid-oxide fuel cell to operate in both fuel cell mode and battery mode, allowing for un-interrupted electricity generation. In the fuel cell mode, the device acts as a conventional fuel cell and converts the chemical energy stored in fuels into electrical energy. In the battery mode, the metal hydride near the anode releases hydrogen and quickly responds to fuel supply interruption or power demand surges. The concept demonstrated here is a promising way to provide a robust and economical solution for balancing power supply and demand for the electrical grid of the future.
This paper introduces a module-integrated distributed battery energy storage and management system without the need for additional battery equalizers and centralized converter interface. This is achieved by integrating power electronics onto battery cells as an integrated module. Compared with the conventional centralized battery system, the modular design brings several advantages such as reduced power rating and voltage stress of power electronics, no extra equalizers or centralized converters, active thermal distribution control ability, enhanced safety and reliability, etc. The battery system can now be built by simply attaching integrated modules together. The integrated module is implemented by a synchronous bidirectional dc/dc converter with digital control techniques. The design considerations and control strategy of the system are discussed. A prototype is built that the power electronics are integrated onto the battery cell. Experimental results of a three-module system verified that the module-integrated distributed system provides satisfied functional performance without extra equalizers, centralized charger, or bidirectional dc/dc converter.
The battery energy storage systems (BESSs) have been increasingly installed in the power system, especially with the growing penetration rate of the renewable energy sources. However, it is difficult for BESSs to be profitable due to high capital costs. In order to boost the economic value of BESSs, this paper proposes a hierarchical energy management system (HiEMS) to aggregate multiple BESSs, and to achieve multimarket business operations. The proposed HiEMS optimizes the multimarket bids considering a realistic BESS performance model, and coordinates the BESSs and manages their state of charge values, according to their price penalties based on dynamically generated annualized cost. By taking part in the energy market and regulation market at the same time, the cost-performance index (CPI) of the BESS aggregation is greatly improved. The impact of photovoltaic generation on system performance and CPI is also studied.
Battery energy storage (BES) plays an important role in the integration of intermittent renewable power and distributed generation. The price arbitrage is a major source of energy storage income. In China, the electricity price is tightly regulated by the government. It's interesting to find out whether the BES is economic viability in such a special electricity market, and what's the optimal response of the grid (or regulator) when facing the arbitrage activities of BES. This research starts with a price arbitrage model to evaluate the feasibility of energy storage in China's electricity market, which can be used to determine the optimal investment scale and operation mode of energy storage. A quantitative assessment is also implemented to discuss the influence when factors change. Following this, an optimal pricing strategy for grid is established. The results reveal that the storage investment can realize positive profit in some districts where the price gap between peak/off-peak periods is high. Appropriate subsidies can be quantitatively described by sensitivity analysis. In terms of social welfare, the energy storage can be deployed on a large-scale at a low social cost under a suitable price mechanism. (C) 2017 Elsevier Ltd. All rights reserved.
This paper proposes a supervisory power management system (PMS) for a grid interactive microgrid with a hybrid energy storage system. The key feature of the proposed PMS is reduced number of sensors required to implement the PMS. The PMS considers renewable power variation, grid availability, electricity pricing, and changes in local loads. It can detect the operating mode of system without measuring load currents and powers. A single-phase voltage source converter (VSC) transfers real power between dc grid and utility grid besides offering ancillary services such as harmonic mitigation, reactive power support, and unity power factor at the point of common coupling (PCC). In the proposed system, a better dc-link voltage regulation is achieved and the usage of supercapacitors reduces the current stress on the battery. The PMS also addresses extreme operating conditions such as load shedding, off-maximum power point tracking operation of photovoltaic, elimination of critical oscillation of hybrid energy storage systems power, islanded operation, and resynchronization with grid. The performance of the proposed PMS is verified by digital simulation and experimental studies.
In order to reduce the stress on fuel cell based hybrid source fed electric drive system the controller design is made through active current sharing (ACS) technique. The effectiveness of the proposed ACS technique is tested on a dc drive system fed from fuel cell and battery energy sources which enables both load current sharing and source power management. High efficiency and reliability of the hybrid system can be achieved by proper energy conversion and management of power to meet the load demand in terms of required voltage and current. To overcome the slow dynamics feature of FC, a battery bank of adequate power capacity has to be incorporated as FC voltage drops heavily during fast load demand. The controller allows fuel cell to operate in normal load region and draw the excess power from battery. In order to demonstrate the performance of the drive using ACS control strategy different modes of operation of the hybrid source with the static and dynamic behavior of the control system is verified through simulation and experimental results. This control scheme is implemented digitally in LabVIEW with PCI 6251 DAQ I/O interface card. The efficacy of the controller performance is demonstrated in system changing condition supplemented by experimental validation. (C) 2016 Elsevier Ltd. All rights reserved.
Herein, we present a fully integrated electronic product code (EPC) Gen-2 compatible battery-assisted passive (BAP) radio-frequency identification sensor tag integrated circuit (IC) with efficient power management. The key components of the tag IC include an adaptive radio-frequency (RF) energy harvester, a battery access controller (BAC), a storage capacitor charger, and a power-gated sensor block. External RF energy is efficiently harvested using dynamically controlled rectifying stages and a threshold-compensation technique. The BAC tightly controls the power path, cutting off leakage current from the battery. The power-gated sensor block supports multiplexed sensing operations in a power efficient manner. The sensor interface includes a chopper amplifier, a programmable gain amplifier, multiplexers, and an 8-bit ADC. For sensing data logging, custom designed nonvolatile memory is employed via one-time programmable memory. The digital control block is based on an EPCglobal Gen-2 standard that is modified to support the sensing operation. The tag chip was fabricated in a 1-poly 6-metal standard 0.18-mu m standard CMOS process. The tag IC consumes 1 mu A for leakage and active operation (0.1% duty), and the estimated lifespan of the BAP tag IC is about 0.2 year/mA.h.
Suppose that, to assess the joint distribution of a random vector (X-1,...,X-n), one selects the kernels Q(1),...,Q(n) with Q(1) to be regarded as a possible conditional distribution for X-i, given (X, : j not equal i);,Q(n) are compatible if there exists a joint distribution for (X-1,...,X-n) with conditionals Q(1),...,Q(n). Similarly, are improperly compatible if they can be obtained, according to the usual rule, with an improper distribution in place of a probability distribution. In this paper, compatibility and improper compatibility of Q(1),...,Q(n) are characterized under some assumptions on their functional form. The characterization applies, in particular, if each Q(i) belongs to a one parameter exponential family. Special attention is paid to Gaussian conditional autoregressive models. (C) 2017 Elsevier B.V. All rights reserved.
Efficient performance modeling is an extremely important task for yield analysis and design optimization of analog circuits. In this paper, a novel regression modeling method based on hierarchical shrinkage priors is proposed to construct hybrid performance models with both high accuracy and low computational cost. In particular, the user-defined model templates derived from design equations and the general-purpose orthogonal polynomials are combined together to set up a hybrid dictionary. Next, in order to avoid over-shrinking large model coefficients, a novel regression method based on hierarchical shrinkage priors and variational Bayesian inference is adopted for model fitting. A rail-to-rail operational amplifier example demonstrates that the proposed method achieves up to 40% error reduction over other state-of-the-art approaches without increasing the modeling cost.
We routinely observe others' choices and use them to guide our own. Whose choices influence us more, and why? Prior work has focused on the effect of perceived similarity between two individuals (self and others), such as the degree of overlap in past choices or explicitly recognizable group affiliations. In the real world, however, any dyadic relationship is part of a more complex social structure involving multiple social groups that are not directly observable. Here we suggest that human learners go beyond dyadic similarities in choice behaviors or explicit group memberships; they infer the structure of social influence by grouping individuals (including themselves) based on choices, and they use these groups to decide whose choices to follow. We propose a computational model that formalizes this idea, and we test the model predictions in a series of behavioral experiments. In Experiment 1, we reproduce a well-established finding that people's choices are more likely to be influenced by someone whose past choices are more similar to their own past choices, as predicted by our model as well as dyadic similarity models. In Experiments 2-5, we test a set of unique predictions of our model by looking at cases where the degree of choice overlap between individuals is equated, but their choices indicate a latent group structure. We then apply our model to prior empirical results on infants' understanding of others' preferences, presenting an alternative account of developmental changes. Finally, we discuss how our model relates to classical findings in the social influence literature and the theoretical implications of our model. Taken together, our findings demonstrate that structure learning is a powerful framework for explaining the influence of social information on decision making in a variety of contexts.
In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine Immunol 24: e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16) describe a dual-purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures to SIV to become infected relative to nonimmunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4(+) T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses, and increased susceptibility to human immunodeficiency virus (HIV).
Objective. Conventional, multi-channel scalp electroencephalography (EEG) allows the identification of the attended speaker in concurrent-listening ('cocktail party') scenarios. This implies that EEG might provide valuable information to complement hearing aids with some form of EEG and to install a level of neuro-feedback. Approach. To investigate whether a listener's attentional focus can be detected from single-channel hearing-aid-compatible EEG configurations, we recorded EEG from three electrodes inside the ear canal ('in-Ear-EEG') and additionally from 64 electrodes on the scalp. In two different, concurrent listening tasks, participants (n = 7) were fitted with individualized in-Ear-EEG pieces and were either asked to attend to one of two dichotically-presented, concurrent tone streams or to one of two diotically-presented, concurrent audiobooks. A forward encoding model was trained to predict the EEG response at single EEG channels. Main results. Each individual participants' attentional focus could be detected from single-channel EEG response recorded from short-distance configurations consisting only of a single in-Ear-EEG electrode and an adjacent scalp-EEG electrode. The differences in neural responses to attended and ignored stimuli were consistent in morphology (i.e. polarity and latency of components) across subjects. Significance. In sum, our findings show that the EEG response from a single-channel, hearing-aid-compatible configuration provides valuable information to identify a listener's focus of attention.
In current brain computer interfacing (BCI) system is used for many applications. This technology also used for capturing brain signals in the form of EEG. This technique have intensive applications in non-invasive technique of signal capturing, Due to its temporal resolution, low set-up cost, easy portability compared to all other techniques. In the EEG technique, as we are dealing with very low frequency signals, these signals have plagued with various noise and interferences, so there is an urge for designing and implementing an accurate and stabilized system for acquiring these low frequency signals. This paper is aiming for VLSI design and testing of EEG acquisition system to acquire brain signals. Initially the low power and high gain generalized operational amplifier is designed. Later a suitable filter is designed to eliminate the noise signals produced in low frequency operations, in order to capture EEG signals. The generalized amplifier design of this system consists of differential amplifier followed with voltage follower circuit. The above circuit is designed using the Cadence tool which facilitates the capturing of transient response and generation of virtual layouts. Each and every blocks of the system is designed and tested individually, for each blocks virtual layouts are generated. And the transient response of the system which contains EEG signals with different voltage levels and frequencies are captured.
Embryo implantation is a complex initial step in establishment of a successful pregnancy. Many mRNAs have been shown to be differentially expressed in the rat uterus during embryo implantation. However, the expression profiles of microRNAs (miRNAs), a key post-transcriptional regulator of gene expression, in the rat uterus between the pre-receptive and receptive phases are still unknown. Here, an miRNA microarray was used to examine differential expression of miRNAs in the rat uterus between the pre-receptive and receptive phases. Twenty-eight miRNAs were up-regulated and 29 miRNAs were down-regulated at least twofold during the receptive phase in rat uterus; these results were confirmed by Northern blotting. miR-29a was only highly expressed in rat uterus during the implantation period, and activation of delayed implantation and artificial decidualization enhanced the miR-29a level. Further investigation revealed that both the pro-apoptotic factor genes Bak1 and Bmf and the anti-apoptotic factor gene Bcl-w are targets of miR-29a. There was weak binding between miR-29a and the 3 UTR of the anti-apoptotic factor gene Mcl1. Over-expression of miR-29a inhibited the late apoptosis of endometrial stromal cells, which may be due to the stronger binding capacity between miR-29a and the 3 UTR of pro-apoptotic factors than that between miR-29a and the 3 UTR of anti-apoptotic factors. Collectively, miR-29a plays an important role during embryo implantation by regulating both pro-apoptotic and anti-apoptotic factors. miR-29a may predominantly bind pro-apoptotic factors, leading to inhibition of cell apoptosis.
Sequential measurement of BCR-ABL1 mRNA levels by reverse transcription quantitative polymerase chain reaction (RT-qPCR) is embedded in the management of patients with chronic myeloid leukaemia (CML), and has played an important role in the remarkable improvement in patient outcomes seen in this disease. As a provider of external quality assessment (EQA) in this area, UK NEQAS for Leucocyte Immunophenotyping (UKNEQAS LI) has a unique perspective on the changing face of BCR-ABL1 testing in CML. To assess the impact of technical standardisation and the development of the International Scale (IS) upon the accuracy of BCR-ABL1 testing, we reviewed EQA trial data from 2007 to 2015. Comparison of participant results identified considerable variability at both high and low levels of disease, including therapeutically important decision points; however, results converted to the IS showed less variability compared to unconverted data sets. We also found that different methods of converting to the IS produce consistently different median results within UKNEQAS LI IS data sets. This data suggests that whilst the development of the IS has improved the comparability of results between centres, there is still the need for further improvement in the processes of converting raw results to the IS in order to fully realise the benefits of molecular monitoring of CML.
What is known and objectiveThe role of CYP3A5 in drug metabolism has been receiving attention because CYP3A5 may be more involved in the metabolism of CYP3A substrates in vivo than previously thought. The polymorphism of transporters, such as P-gp (P-glycoprotein) and breast cancer-related protein (BCRP), influences the metabolism of these substrates, and felodipine is a substrate of P-gp. The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodipine in healthy Chinese subjects. MethodsA single dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentration of felodipine was measured by using LC/MS/MS. We detected the SNPs of cytochromes P450 enzymes and transporters, which play vital roles in drug metabolism and have a high frequency of mutation in Chinese population. Results and discussionThe area under the plasma concentration-time curve (AUC) within the time points 0 to 72 h (AUC((0-72))) after felodipine administration was significantly higher in subjects possessing the BCRP421AA alleles than in those with the BCRP421 CC or CA genotype (P = 0034). The subjects with CYP3A5*3/*3 (n = 27) had higher felodipine exposure than CYP3A5*1/*3 (n = 15) (P = 0035). What is new and conclusionThis study showed that the genetic polymorphisms of CYP3A5*3 and BCRPC421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype x gender (P= 0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Va166Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. (C) 2017 Elsevier Ltd. All rights reserved.
Aims Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis. Methods and results BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyper-reactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype in WT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Conclusion Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.
A number of measures to increase the quality of data recorded with an improved Balzers Eldigraph KD-G2 gas-phase electron diffractometer are discussed. The beam-stop has been decoupled from the sector enabling us recording the current of the primary beam and scattered electrons during the experiment. Different beam-stops were tested for use in the present setup. Modifications of the nozzle tip of an earlier described medium temperature nozzle are reported. The measures lead to reduced exposure times and reduced amount of sample necessary for complete data collection.
Bearingless permanent magnet synchronous motors (BPMSMs) have been received more and more attention during the past few decades. To realize the high-performance control for rotation and levitation, we will first need to obtain the accurate suspension force model of a BPMSM. In this work, different from conventional suspension force models, a modeling scheme for the suspension force of a BPMSM is presented by taking into account rotor eccentricity with the Maxwell stress tensor modeling scheme. The theoretical value of a suspension force model is compared by the two-dimensional finite element (FE) analysis, and calculation results reveal that the theoretical value closely agree with the FE computed one. Furthermore, the digital control system is devised by taking advantage of TMS320F2812, and a test platform for experiments is then set up. In accordance with the corresponding findings of the experiments, the rotor stabilization with magnetic levitation can be achieved. The results lay a theoretical and experimental foundation for further study of the BPMSM.
Recently, bearingless switched reluctance motor (BLSRM) has been received more and more attention. To realize the stable levitation and rotation, the corresponding suspending force and torque should be controlled. In this paper, different from the conventional bearingless SRM control, one independent control scheme for levitation force and torque is presented. In the control, a complex control algorithm based on a lookup table is not needed. Torque control is separated from radial force control, and each channel of radial force is independently controlled. Therefore, the control is very simple to be implemented. First, based on the brief introduction of the BLSRM structure and operating principle, the mathematical relationship of levitation force with respect to current and displacement is derived. Furthermore, the rotor dynamics model, in which levitation force in four degrees of freedom is considered, is established. Based on the given analysis, the digital control system, which includes torque and suspending force, is designed by means of TMS320F28335, and an experimental platform is established. According to the experimental results, the proposed BLSRM can be steadily levitated in the static and rotating conditions.
Power electronic converters are single input multiple output (SIMO) systems in frequency domain. In distributed power system (DPS), one converter's switching frequency ripples are another converter's perturbations, and beat frequency components are generated due to their SIMO characteristics. As the control loops of power converters always take high gains in low-frequency regions if the beat frequency components are relatively low, they may be magnified and presented as oscillations, which will introduce system instability. This paper proposes a matrix-based multifrequency output impedance model to describe the SIMO characteristics of power converters and to analyze the stability of DPS. The buck converter is specifically illustrated as demonstration. The proposed model indicates that the variation of switching frequency, as well as those traditionally discussed parameters of control loops and passive components, could also change output impedance characteristics and introduce system instability. In DPS, the beat frequency oscillation that traditional models fail to explain could be accurately predicted by the proposed model. In addition, based on the proposed model, the switching frequencies for power converters can be optimized to improve the stability of power electronic-based systems. Simulation and experimental results validate the accuracy and the effectiveness of the proposed method.
Current ambitions to limit climate change to no more than 1.5 degrees C-2 degrees C by the end of the 21st century rely heavily on the availability of negative emissions technologies (NETs)-bioenergy with CO2 capture and storage (BECCS) and direct air capture in particular. In this context, these NETs are providing a specific service by removing CO2 from the atmosphere, and therefore investors would expect an appropriate risk-adjusted rate of return, varying as a function of the quantity of public money involved. Uniquely, BECCS facilities have the possibility to generate both low carbon power and remove CO2 from the atmosphere, but in an energy system characterised by high penetration of intermittent renewable energy such as wind and solar power plants, the dispatch load factor of such BECCS facilities may be small relative to their capacity. This has the potential to significantly under utilise these assets for their primary purpose of removing CO2 from the atmosphere. In this study, we present a techno-economic environmental evaluation of BECCS plants with a range of operating efficiencies, considering their full-and part-load operation relative to a national-scale annual CO2 removal target. We find that in all cases, a lower capital cost, lower efficiency BECCS plant is superior to a higher cost, higher efficiency facility from both environmental and economic perspectives. We show that it may be preferable to operate the BECCS facility in base-load fashion, constantly removing CO2 from the atmosphere and dispatching electricity on an as-needed basis. We show that the use of this 'spare capacity' to produce hydrogen for, e.g. injection to a natural gas system for the provision of low carbon heating can add to the overall environmental and economic benefit of such a system. The only point where this hypothesis appears to break down is where the CO2 emissions associated with the biomass supply chain are sufficiently large so as to eliminate the service of CO2 removal.
Introduction: Depressive symptoms are common in patients assessed by neuropsychologists, and these symptoms can have an effect on cognitive functioning. Discrepancies between patient- and informant-reported depressive symptoms have been found in some diagnostic groups, raising concerns as to the value of assessing depressive symptoms via self-report alone. This study aimed to examine the relationship between these discrepancies and cognitive functioning in a heterogeneous outpatient neuropsychological sample. Method: Sixty-two patients with a variety of diagnoses (e.g., stroke, mild cognitive impairment) completed a measure of depressive symptoms and a battery of neuropsychological tests. Informants also rated the patients' depressive symptoms and completed a measure of the patients' functional abilities. Results: Patient and informant reports of depressive symptoms were moderately correlated; larger differences between patient- and informant-reported symptoms were associated with poorer verbal learning and memory and greater functional impairments. Conclusions: The moderate level of agreement found for depressive symptoms is consistent with past studies using specific neuropsychological patient groups and other studies in both clinical and non-clinical populations. These results highlight the utility of collecting informant reports of depressive symptoms in neuropsychological evaluations.
Aim: The aim of this study was to determine Nigerian parents' views about the causes and treatment of childhood enuresis. Methods: Parents of children aged 5-17 years were individually interviewed in an urban community in Nigeria using a pretested questionnaire. Their responses about the causes and treatment of enuresis were grouped under common themes. Results: We included 448 respondents in the study: 75.5% were mothers, 44.2% had at least one child with enuresis and only 1.3% had spoken to a doctor about it. Enuresis was thought to be due to playing too much and drinking too much fluid at night by 69.7% and 21.2% of the respondents, respectively. The two most common treatment methods that parents were aware of for enuresis were waking to void (23.7%) and urinating on hot charcoal (20.8%). The most common methods that parents actually employed included waking to void (49.0%), punishing the child (36.9%) and doing nothing (28.8%). Conclusion: Most of the respondents believed that playing too much and drinking or eating too much were responsible for childhood enuresis. Parents rarely discussed childhood enuresis with their doctors and some of the self-help measures that were employed may be harmful and could constitute child abuse.
A full-length Beet black scorch virus (BBSV) cDNA clone (pUBF52) was constructed by RT-PCR. The clone contains an upstream T7 RNA polymerase promoter designed for in vitro transcription of infectious RNAs from the linearized plasmid that faithfully represent the viral cDNA. Leaves of Chenopodium amaranticolor inoculated with in vitro transcripts developed the same symptoms and disease phenotype as the wild type virus. The presence of BBSV RNA and coat protein in the leaves was confirmed respectively by Northern blotting and Western blotting. Comparisons of specific immunoreactions between the expression product of the BBSV p24 gene in E. coli and antiserum against purified BBSV virions demonstrated that the p24 gene encodes the coat protein. Based on the sequence of the pUBF52 cDNA, a frame-shift mutant and two deletion mutants were generated. One of the deletions encompasses the entire CP ORF and the other truncates 174 amino acids from the central region of the protein. Transcripts derived from the frame-shift CP mutant, which terminates the CP after the first 23 amino acids, elicited the same symptom phenotype and levels of RNA accumulation as the wild type virus, but the leaves infected with the CP deletion mutants exhibited greatly reduced RNA accumulation. In addition, leaves inoculated with in vitro transcripts of the mutant in which the entire CP gene was deleted had lower local lesions than wild type virus transcripts. Two expression vectors, pBGFP and pBGUS, were constructed by fusing the GFP and GUS genes to the 23 N-terminal amino acids of the CP gene, respectively. Leaves infected with in vitro transcripts of pBGFP and pBGUS exhibited expression of GFP and GUS proteins as assessed by laser confocal microscopy and histochemical staining, respectively. The high levels of expression of the GFP and GUS proteins provide tools that can be used for studies of replication and movement of the virus, and indicate that BBSV has considerable biotechnology potential as a plant virus expression vehicle.
Co-infection of none-coding satellite RNAs (sat-RNAs) usually inhibits replication and attenuates disease symptoms of helper viruses. However, we find that the sat-RNA of Beet black scorch virus (BBSV) and low temperature (18 degrees C) additively enhance the systemic infection of BBSV in Nicotiana benthamiana. Northern blotting hybridization revealed a relatively reduced accumulation of BBSV-derived small interfering RNAs (siRNAs) in presence of sat-RNA as compared to that of BBSV alone. Cloning and sequencing of total small RNAs showed that more than 50% of the total small RNAs sequenced from BBSV-infected plants were BBSV-siRNAs, whereas the abundance of sat-siRNAs were higher than BBSV-siRNAs in the sat-RNA co-infected plants, indicating that the sat-RNA occupies most of the silencing components and possibly relieves the RNA silencing-mediated defense against BBSV. Interestingly, the 5' termini of siRNAs derived from BBSV and sat-RNA were dominated by Uridines (U) and Adenines (A), respectively. Besides, the infection of BBSV alone and with sat-RNA induce down-regulation of miR168 and miR403, respectively, which leads to high accumulation of their targets, Argonaute 1 (AGO1) and AGO2. Our work reveals the profiles of siRNAs of BBSV and sat-RNA and provides an additional clue to investigate the complicated interaction between the helper virus and sat-RNA
This study examines whether the delivery of three components, (a) exercise training, (b) behavior management skill building, and (c) dementia-related education, in an evidence-based program are differentially associated with changes in outcomes for individuals with dementia (IWDs) after 3 months. Data come from 508 IWDs participating in the community replication of the evidence-based Reducing Disability in Alzheimer's Disease program. Regression results indicate that after 3 months, more exercise sessions are associated with improvements in physical functioning, mobility, minutes exercising, and symptoms of depression; more dementia education sessions are related to fewer restricted activity days; and more behavior management sessions are related to more symptoms of depression. As resource-strapped agencies look to best serve participants, further analysis and consideration is needed to determine the ideal balance of program efficacy, feasibility, and resources, as well as program benefits for IWDs and caregivers.
Depression is associated with decreased engagement in behavioural activities. A wide range of activities can be promoted by simulating them via mental imagery. Mental imagery of positive events could thus provide a route to increasing adaptive behaviour in depression. The current study tested whether repeated engagement in positive mental imagery led to increases in behavioural activation in participants with depression, using data from a randomized controlled trial (Blackwell et al. in Clin Psychol Sci 3(1):91-111, 2015. doi:10.1177/2167702614560746). Participants (N = 150) were randomized to a 4-week positive imagery intervention or an active non-imagery control condition, completed via the internet. Behavioural activation was assessed five times up to 6 months follow-up using the Behavioural Activation for Depression Scale (BADS). While BADS scores increased over time in both groups, there was an initial greater increase in the imagery condition. Investigating mental imagery simulation of positive activities as a means to promote behavioural activation in depression could provide a fruitful line of enquiry for future research.
We propose a simulation-based analog equivalence boundary search methodology for high level Simulink models and their low level HSpice counterparts. The equivalence of high and low level designs is determined by comparing a set of predefined performance parameters measured during the simulation of both models. Our methodology investigates the search space to obtain boundary of input parameters, where both models have equivalent performance parameters. We build an optimization problem, where the error percentage between the performance parameters of both models being less than a specified threshold is defined as success criteria. In this problem, input parameters are determined by utilizing evolutionary computation. At the end of the optimization, the border of equivalence for the models is found for input parameters satisfying the success criteria. We demonstrate the validity of our approach on three designs, an inverter, an operational amplifier, and a buck converter, where our approach proves to be an efficient tool in finding an equivalence boundary of analog circuits and models. (C) 2016 Elsevier B.V. All rights reserved.
Symbolically generated network functions for an analog integrated circuit are complicated in general. For this reason a variety of simplification methods have been proposed in the literature. In this work a novel topology-based symbolic simplification method is proposed, which is capable of generating a simplified symbolic network function together with a simplified small-signal circuit. The technique is developed by applying the recently proposed graph-pair decision diagram (GPDD) algorithm that generates a symbolic network function stored in a binary decision diagram (BDD). Two types of element elimination can directly be operated on such a GPDD data structure. The performance variation by eliminating each symbol from the original circuit is assessed by the means of two monitored response metrics (dc gain and phase margin). After sorting the performance loss, those circuit elements with less performance loss are eliminated, resulting in a reduced GPDD which is automatically a simplified network function. A simplified small-signal circuit is available simultaneously after reduction. Applications to two operational amplifier examples confirm the effectiveness of the proposed methodology.
A model of the operational amplifier based on VHDL-AMS is proposed. According to needs of simulating the total ionizing dose (TED) radiation effect, parameters of operational amplifier are taken into account when the performance is specified. The operational amplifier model used for the TID radiation effect simulation is completed after verifying each modeled parameter. And a parameter for describing the external environment is introduced to make the model combined with TID. Finally, an example is used to illustrate the TID effect on the operational amplifier of MC14573, proving the validity of the model.
Introduction. Behavioral changes often occur after moderate-to-severe traumatic brain injury (TBI) and can lead to poor health, psychosocial functioning, and quality of life. Challenges in evaluating these behaviors often result from the complexity and variability in the way they are conceptualized and defined. We propose and test a conceptual model that is specific to behavioral symptoms after TBI, to serve as a basis for better assessment and treatment. We hypothesized that clusters of individuals, with unique emotional, cognitive, and behavioral characteristics, would emerge that would illustrate this conceptual model. Methods. We conducted model-based cluster analyses in two cohorts, 6-months post-injury (n=79) and >6months post-injury (n=62), of adults with moderate-to-severe TBI to explore the face validity of our conceptual model by evaluating how participants clustered with regard to emotional (Patient Health Questionnaire 9, Positive and Negative Affect Schedule), cognitive (neuropsychological test battery), and frontal behavioral (Frontal Systems Behavior Scale) symptoms. Results. In each cohort, unique clusters of participants emerged that differed significantly with regard to emotional state, cognition, and behavior (ps6months) demonstrated a more complex pattern of symptoms; the most severe behavioral symptoms occurred in the context of severe emotional symptoms, even in the absence of cognitive impairment. However, problematic behavioral symptoms were also present in the context of severe cognitive impairment, even in the absence of emotional symptoms. Conclusions. Emotional, cognitive, and behavioral characteristics were represented as expected, based on the proposed conceptual model of behavior. This conceptual model provides the basis for evaluating behavioral changes after moderate-to-severe TBI and identifying modifiable targets and relevant subpopulations for behavioral intervention, with the goal of improved evidence-based personalized medicine for this population.
Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally-with a slight predilection for the right-in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.
Aims: To conduct a pilot trial to test the feasibility of a guided self-help intervention for chronic orofacial pain. Methods: A pilot randomized controlled trial was conducted to compare the intervention with usual treatment. A total of 37 patients with chronic orofacial pain were randomized into either the intervention group (n = 19) or the usual treatment (control) group (n = 18). Validated outcome measures were used to measure the potential effectiveness of the intervention over a number of domains: physical and mental functioning (Short Form 36 [SF-36]); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); pain intensity and interference with life (Brief Pain Inventory [BPI]); disability (Manchester Orofacial Pain Disability Scale [MOPDS]); and illness behavior (Revised Illness Perceptions Questionnaire [IPQr]). Bootstrap confidence intervals were computed for the treatment effect (ES) posttreatment and at 3 months follow-up and adjusted for baseline values of the outcome measure by using analysis of covariance. Results: At posttreatment and the 3-month follow-up, 11 participants in the intervention group and 7 in the control group failed to complete outcome measures. The intervention was acceptable and could be feasibly delivered face to face or over the telephone. Although the pilot trial was not powered to draw conclusions about the effectiveness, it showed significant (P <.05) effects of the intervention on physical and mental functioning and treatment control. Conclusion: The self-help intervention was acceptable to patients and allowed them to better understand and self-manage chronic orofacial pain. It showed potential effectiveness on outcome domains related to functioning and illness perception. Further research is needed to understand the cost effectiveness of the intervention for chronic orofacial pain.
Imagination pushes humanity well beyond its natural biological capacities. An approach of co-evolution, between molecular biology and behaviour, is thus required to explain these combined processes. Technological performances define spiritual conquests and formulas whose sole function is cultural. Humanity operates according to intentional social modes defined by the group, but these immediately become conditions for their own evolution. These choices are the motor for the history of humanity, and thus humanity can itself choose its own path. Anatomic modernisation is only a distant reflection of bipedalism, but freeing the hands leads to the development of abstract thought. The relationship between anatomy and awareness allows infinite variations in the harmonious adaptation to nature, animals and other societies. In Europe, humanity arrived in abrupt bursts because it was the result of external evolution, continuous and distant, dispersed across Asia. By its unceasing audacity, humanity combats biological determinism, imposing "moral" rules, or imperatives. The balance between biology and culture is reflected in the rules for sharing food: the biological life itself is coded by social sharing. These systems take on ternary values as soon as they include animal behaviours. Built shelters integrate societies with the cosmos because they delimit cultural spaces within natural chaos. Mastery of cognitive mechanisms gives humanity an entirely new responsibility, that of being able to define its destiny. Our united disciplines are transformed into ethical requirements. (C) 2016 Published by Elsevier Masson SAS on behalf of Academie des sciences.
Faces play an integral role in day-to-day functioning, particularly for social interactions where dynamic and rapid processing of information is vital. Analysis of faces allows an individual to ascertain a wide range of information including deciphering mood and identity, with these assessments directing an individual's subsequent response and behaviours. The prominent social and emotional deficits observed in frontotemporal dementia (FTD), a youngeronset dementia syndrome, may in part reflect a breakdown of the face processing network. Different subtypes of FTD present with divergent patterns of atrophy, although damage is predominantly confined to the frontal and temporal lobes. Specific predictions regarding the role of frontal and temporal regions in face processing have been proposed in the model outlined by Haxby et al. Trends in Cognitive Sciences, 4(6), 223-233 (2000). This model presents a parsimonious method by which to understand face processing in FTD while concurrently allowing assessment of the predictive value and applicability of such a model. By applying the Haxby model to the existing FTD literature, this review presents both direct and indirect evidence of a breakdown in key elements of the face processing network. The type and degree of breakdown appears to differ as a function of FTD subtype and associated brain atrophy. The evidence presented in this review and its relationship with predictions of the Haxby model provides impetus and direction for future research investigating face processing in FTD.
Transforming Growth Factor (TGF)-beta inhibitors have been in development for decades with the outmost results of being promising candidates. From the latest clinical results at the 2016 ASCO meeting converging evidences suggest that we have moved from promising to effective drug nominees.
Beliefs about the unacceptability of experiencing and expressing emotions have been found to be related to worse outcomes in people with persistent physical symptoms. The current study tested mediation models regarding emotional suppression, beliefs about emotions, support-seeking and global impact in fibromyalgia. One hundred eighty-two participants took part in an online questionnaire testing potential mechanisms of this relationship using mediation analysis. The model tested emotional suppression and affective distress as serial mediators of the relationship between beliefs about emotions and global impact. In parallel paths, two forms of support-seeking were tested (personal/emotional and symptom-related support-seeking) as mediators. Emotional suppression and affective distress significantly serially mediated the relationship between beliefs about emotions and global impact. Neither support-seeking variable significantly mediated this relationship. Results indicate a potential mechanism through which beliefs about emotions and global impact might relate which might provide a theoretical basis for future research on treatments for fibromyalgia.
The prostate is composed mainly of epithelial and stromal cells, whose dynamic interaction is vital to a broad array of cellular processes, including proliferation, differentiation, growth, and apoptosis. To understand intercellular communication in the development and progression of prostatic diseases, we examined gene expression in tissues from five patients diagnosed with benign prostatic hyperplasia (BPH). Fibroblasts and epithelial cells derived from these tissues were grown in a primary co-culture system that retains many characteristics of the intact human prostate. The mRNA levels of expressed genes as assessed by differential-display reverse transcription-PCR revealed that 110 genes were differentially expressed in co-cultured fibroblasts and epithelial cells, compared with expression in separately cultured cells. Eighty-four of these were confirmed by reverse Northern blotting, and 68 were successfully sequenced. Of the sequenced genes, 43 were differentially expressed in epithelial cells (37 upregulated, 6 downregulated), and 25 were differentially expressed in fibroblasts (6 upregulated, 19 downregulated) in co-cultures versus separate cultures. Semi-quantitative RT-PCR analysis of 12 genes with known functions showed that five of these were differentially expressed in co-cultured cells. Human kallikrein gene 7 (KLK7) was markedly upregulated in co-cultured compared with separately cultured epithelial cells (P<0.001), whereas S100 calcium binding protein All, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, cyclin I, and latexin were significantly downregulated in co-cultured fibroblasts (P<0.05). Quantitative real-time RT-PCR and Western blot analysis confirmed KLK7 up-regulation at both the mRNA and protein levels, respectively. Thus, epithelial-stromal cell interaction and communication are likely to be important in BPH. Epithelial cells and fibroblasts may interplay coordinately or collaboratively to influence cellular growth and death through dynamically differential gene expression in response to physiological and pathophysiological changes.
All clinically-used antipsychotics display similar affinity for both D-2 (D2R) and D-3 (D3R) receptors, and they likewise act as 5-HT2A receptor antagonists. They provide therapeutic benefit for positive symptoms, but no marked or consistent improvement in neurocognitive, social cognitive or negative symptoms. Since blockade of D-3 and 5-HT6 (5-HT6R) receptors enhances neurocognition and social cognition, and potentially improves negative symptoms, a promising approach for improved treatment for schizophrenia would be to develop drugs that preferentially act at D3R versus D2R and likewise recognize 5-HT6R. Starting from the high affinity 5-HT6R ligands I and II, we identified compounds 11a and 14b that behave as 5-HT6R ligands with significant selectivity for D3R over D2R. (C) 2016 Elsevier Ltd. All rights reserved.
Selective inhibitors of histone deacetylase 6 (HDAC6) are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Herein, the synthesis of ten new benzohydroxamic acids, constructed by employing the tetrahydrobenzothiazepine core as a privileged pharmacophoric unit, is described. This is the first report on the synthesis and isolation of octahydrodibenzothiazepines and octahydro-6H-benzocycloheptathiazepines, which were then used to develop a new class of HDAC6 inhibitors. Evaluations of their HDAC-inhibiting activity resulted in the identification of cis-N-(4-hydroxycarbamoyl-benzyl)-1,2,3,4,4a, 5,11,11a-octahydrodibenzo[b, e] [1,4]thiazepine-10,10-dioxide and cis-N-(4-hydroxycarbamoyl-benzyl)-7-trifluoromethyl-1,2,3,4,4a, 5,11,11a-octahydrodibenzo[b,e][1,4]thiazepine-10,10-dioxide as highly potent and selective HDAC6 inhibitors with activity in the low nanomolar range, which also show excellent selectivity on the enzymatic and cellular levels. Furthermore, four promising inhibitors were subjected to an Ames fluctuation assay, which revealed no mutagenic effects associated with these structures.
Berberine is traditionally used to treat gastrointestinal (GI) motility disorders. The interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal tract, which are responsible for the production of gut movements. The present study aimed to investigate the effects of berberine on pacemaker potentials (PPs) in cultured ICC clusters from the mouse small intestine, and sought to identify the receptors involved and the underlying mechanisms of action. All experiments were performed on cultured ICCs, and a whole-cell patch-clamp configuration was used to record PPs from ICC clusters (current clamp mode). Under current clamp mode, berberine was shown to decrease the amplitude and frequency of PPs. However, these effects were suppressed by treatment with glibenclamide, a specific ATP-sensitive K+ channel blocker. Nor-binaltorphimine dihydrochloride (a kappa opioid receptor antagonist) did not suppress berberine-induced PP inhibition, whereas ICI 174,864 (a delta opioid receptor antagonist) and CTOP (a mu opioid receptor antagonist) did suppress the inhibitory effects of berberine. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or with KT-5720 (a protein kinase A inhibitor) did not suppress the effects of berberine; however, pretreatment with 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (a guanylate cyclase inhibitor) or KT-5823 [a protein kinase G (PKG) inhibitor] did. In addition, berberine stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. These observations indicate that berberine may inhibit the pacemaker activity of ICC clusters via ATP-sensitive K+ channels and the cGMP-PKG-dependent pathway by stimulating mu and delta opioid receptors. Therefore, berberine may provide a basis for the development of novel agents for the treatment of GI motility dysfunction.
Psychological adaptation following homicide loss can prove more challenging for grievers than other types of losses. Although social support can be beneficial in bereavement, research is mixed in terms of identifying whether it serves as a buffer to distress following traumatic loss. In particular, studies have not parsed out specific domains of social support that best predict positive bereavement outcomes. Recruiting a sample of 47 African Americans bereaved by homicide, we examined six types of social support along with the griever's perceived need for or satisfaction with each and analyzed them in relation to depression, anxiety, complicated grief, and posttraumatic stress disorder outcomes. Results of multivariate analyses revealed that the griever's level of satisfaction with physical assistance at the initial assessment best predicted lower levels of depression, anxiety, and posttraumatic stress disorder levels 6 months later, while less need for physical assistance predicted lower complicated grief at follow-up. Clinical implications and suggestions for future research are discussed.
Mental health issues have been increasingly recognized as public health problems globally. Their burden is projected to increase over the next several decades. Additional therapies for mental problems are in urgent need worldwide due to the limitations and costs of existing healthcare approaches. Essential oil aromatherapy can provide a cost-effective and safe treatment for many mental problems. This pilot study observed the effects of bergamot essential oil inhalation on mental health and well-being, as measured by the Positive and Negative Affect Scale, in a mental-health treatment center located in Utah, USA. Fifty-seven eligible participants (50 women, age range: 23-70years) were included for analysis. Fifteen minutes of bergamot essential oil exposure improved participants' positive feelings compared with the control group (17% higher). Unexpectedly, more participants participated in experimental periods rather than control periods, suggesting even brief exposure to essential oil aroma may make people more willing to enroll in clinical trials. This study provides preliminary evidence of the efficacy and safety of bergamot essential oil inhalation on mental well-being in a mental health treatment center, suggesting that bergamot essential oil aromatherapy can be an effective adjunct treatment to improve individuals' mental health and well-being. (c) 2017 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of beta 2 ->1-fructans on immunity via microbiota-dependent and-independent effects. To this end, conventional or germ-free mice received short-or long-chain beta 2 ->1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that beta 2 ->1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the beta 2 ->1-fructans type polymer. Both short-and long-chain beta 2 ->1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain beta 2 ->1-fructans increased regulatory T cells and CD11b(-)CD103(-)dendritic cells (DCs) in the MLN. A common feature after short-and long-chain beta 2 ->1-fructan treatment was enhanced 2-alpha-L-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short-and long-chain beta 2 ->1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the beta 2 ->1-fructans. Short-chain beta 2 ->1-fructan induced lower CD80 expression by CD11b(-)CD103(-) DCs in PPs, whereas long-chain beta 2 ->1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of beta 2 ->1-fructans and is partially microbiota independent.
Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients. In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal. We used 3 interferons that are commercially available for MS therapy, namely Avonex (Biogen Idec Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens. BAbs reacting with Rebif were found in 24.4% to 55% of patients, depending on the units of their expression. The levels of anti-ebif antibodies remained high in 8 patients and in 4 patients they dropped significantly. Strong correlations were obtained in all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-anti-Avonex) and the existence of cross-reactivity in the formation of antibodies against all the tested formulations of interferon beta was confirmed. The levels of BAbs remain significant in the clinical context, and their assessment is the first choice screening; however, methods of BAbs evaluation can be crucial for further decisions. More studies are needed to confirm our results; specifically it would be of interest to evaluate methods of neutralizing antibodies identification, as we only assessed the binding antibodies. Nevertheless, our results support the concept that in interferon nonresponders, that are positive for binding antibodies, switching the therapy to alternative disease-modifying agent (for example glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to another interferon formulation will probably be of no benefit.
Plant beta-1, 3-glucanases are involved in plant defense and in development. Very little data are available on the expression of rice glucanases both in developmental tissues and under various stresses. In this study, we cloned and characterized twenty-seven rice beta-1, 3-glucanases (OsGlu) from at total of 71 putative glucanases. The OsGlu genes were obtained by PCR from a cDNA library and were classified into seven groups (Group I to VII) according to their DNA or amino acid sequence homology. Analysis of the expression of the twenty-seven OsGlu genes by Northern blotting revealed that they were differentially expressed in different developmental tissues as Well as in response to plant hormones, biotic stress, high salt etc. OsGlu11 and 27 in Group IV were clearly expressed only in stem and leaf and were also induced strongly by SA (5 mM), ABA (200 mu M), and M. grisea. OsGlu1, 10, 11, and 14 were induced earlier and to higher levels in incompatible M. grisea interaction than in compatible one. Taken together, our findings suggest that the twenty-seven rice OsGlu gene products play diverse roles not only in plant defense but also in hormonal responses and in development.
Backgound: beta-Carotene exhibits biological activity as provitamin A. Key step in vitamin A formation is the cleavage of beta-carotene to retinal by an enzyme designated as beta-carotene 15,15'-monooxygenase (BCM). Recently, it is reported that expression of BCM gene in the intestine is under feedback regulation by retinoic acid (RA). However, the regulation of BCM gene expression in various other tissues is still unknown. Aim of the study: In the present study, we identified the full-length cDNA encoding the rat BCM gene and investigated the regulation of its expression in several tissues by RA in the presence of vitamin A deficiency. Methods: We cloned the full-length cDNA encoding BCM gene from a rat intestinal cDNA library by hybridization screening. The BCM gene expression was examined using Northern blotting and reverse transcription-PCR analysis. We also investigated whether BCM gene expression was regulated by retinoids in several tissues of vitamin A-deficient rats. Results: Sequence analysis of this clone revealed an open reading frame of 1,701 bases encoding a protein of 566 amino acids. The predicted polypeptide showed 94%, 81%, and 66% identity with mouse, human, and chicken BCM, respectively. Rat BCM mRNA was highly expressed in the intestine and liver, while there was weak expression in the testes, kidneys, and lungs. Immunoblotting revealed that rat BCM is a 64-kDa protein. BCM gene expression was increased in the small intestine by vitamin A deficiency compared with that in rats on a control diet, while this upregulation was suppressed by all-trans RA (ATRA) or 9-cis RA (9-cis RA). BCM gene expression in the lungs and testes was also suppressed by ATRA or 9-cis RA in rats with vitamin A deficiency. However, hepatic BCM gene expression was only decreased by ATRA and renal expression was not affected by either retinoid. As the small intestine is the major site of beta-carotene conversion, intestinal BCM gene expression may be more tightly regulated. Conclusion: These data suggest that BCM gene expression in several tissues may be down-regulated by RA at the level of conversion of beta-carotene to retinal. To prevent an excess of retinol, homeostasis may occur at the level of conversion of beta-carotene to retinal in several tissues.
To efficiently express a gene of interest in transgenic plants, the choice of promoter is a crucial factor as it directly affects the expression of the transgene that will yield the desired phenotype. The Arabidopsis beta-carotene hydroxylase 1 gene (AtBch1) shows constitutive and ubiquitous expression and was thus selected as one of best candidates for constitutive promoter analysis by both in silico northern blotting and semi-quantitative RT-PCR analysis. To investigate AtBch1 promoter activity, the 1,981-bp 5'-upstream region of this gene was fused with beta-glucuronidase (GUS) and transformed into Arabidopsis. Through the molecular characterization of transgenic leaf tissues, the AtBch1 promoter generated strong activity that drives 1.8- and 2-fold higher GUS expression than the cauliflower mosaic virus 35S (35S) promoter at the transcriptional and translational levels, respectively. Furthermore, the GUS enzyme activity driven by the AtBch1 promoter was 2.8-fold higher than that produced by the 35S promoter. By histochemical GUS staining, the ubiquitous expression of the AtBch1 promoter was observed in all tissues of Arabidopsis. Semi-quantitative RT-PCR analysis with different tissues further showed that this promoter serves as a strong constitutive driver of transgene expression in dicot plants.
This work was conducted to prepare beta-caryophyllene-hydroxypropyl-beta-cyclodextrin inclusion complex (HP beta CD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HP beta CD/BCP was prepared, optimized, characterized, and evaluated. HP\CD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HP beta CD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HP beta CD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HP beta CD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HP beta CD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HP beta CD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HP beta CD/BCP in the therapy of vascular dementia in the future.
A novel type of pH-responsive star polymer based on beta-cyclodextrin (beta-CD) was synthesized and further covalently conjugated with enzyme. The impact of its self-assembly behavior on enzyme activity was investigated. In our design, azide containing the polymer (N-3)(7)-beta-CD-(PtBA)(14) was synthesized via atom transfer radical polymerization of tert-butyl acrylate using (N-3)(7)-beta CD-(Br)(14) as the multifunctional initiator. The final product (N-3)(7)-beta-CD-(PAA)(14) was obtained via hydrolysis and covalently conjugating pectinase onto pH-responsive polyacrylic acid (PAA) arms. PAA can change its conformation with the self-assembly by altered pH, leading its nanostructure into micellar nanoparticles in aqueous solution and further affecting the activity of immobilized pectinase. The results were proved by fluorescence spectroscopy and dynamic light scattering. This system proves that the activity of immobilized enzyme can be tailored predictably, and this pH-responsive polymer holds great potential for controllable delivery of enzymes. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Aims: We investigated the mechanism(s) by which valsartan, a selective antagonist of angiotensin subtype 1 (AT(1)) receptor, decreased plasma glucose in streptozotocin (STZ)-induced diabetic rats. Methods: The plasma glucose concentration was assessed by the glucose oxidase method. The concentration of beta-endorphin in plasma or medium incubating adrenal medulla was measured using an enzyme-linked immunosorbent assay. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis, while the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. Results: A single intravenous injection of valsartan dose-dependently increased plasma beta-endorphin-like immunoreactivity (BER) in parallel with the lowering of plasma glucose concentration in STZ-induced diabetic rats. Naloxone and naloxonazine inhibited the plasma glucose-lowering action of valsartan at doses sufficient to block opioid mu-receptors. In contrast to its action in wild-type diabetic mice, valsartan failed to modify plasma glucose in opioid mu-receptor knockout diabetic mice. Bilateral adrenalectomy in STZ-induced diabetic rats eliminated both the plasma glucose-lowering action and the plasma BER-elevating action of valsartan. In the isolated adrenal medulla of STZ-induced diabetic rats, angiotensin II (Ang II) or valsartan did not affect spontaneous BER secretion. Activation of cholinergic receptors by 1.0 mu mol/l acetylcholine (ACh) enhanced BER secretion from the isolated adrenal medulla of STZ-induced diabetic rats, but not in the presence of 1.0 nmol/l Ang II, while valsartan reversed this inhibition by Ang II in a concentration-dependent manner. Treatment of STZ-induced diabetic rats with valsartan (0.2 mg/kg) three times daily for 3 days resulted in an increase in gene expression of GLUT4 in soleus muscle and impeded the reduction of elevated mRNA or protein level of hepatic PEPCK. Both of these effects were blocked by opioid mu-receptor antagonist. Conclusions: The results suggest that blockade of AT(1) receptor by valsartan may enhance the adrenal beta-endorphin secretion induced by ACh, activating the opioid mu-receptors to increase glucose utilization and/or to decrease hepatic gluconeogenesis, resulting in the reduction of plasma glucose in STZ-induced diabetic rats.
Endonuclease cleavage is the rate-limiting step in the decay of nonsense-containing human beta-globin mRNA in erythroid cells. The 5'-truncated intermediates thus generated are polyadenylated and more stable than the parent mRNA. Northern blotting is commonly used to measure the decay rate of full-length mRNA, and S1 nuclease protection is used to assay the fate of decay intermediates. We have adapted the more sensitive and facile MBRACE assay (Lasham et al., Nucleic Acids Res 38: e19, 2010) to quantitatively monitor the decay process by detecting full-length beta-globin and its decay intermediates.
Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine widely used for improving sports performance. Although limp is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HM beta treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results: Chronic HM beta treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions: The data presented herein extend the body of evidence on the potential role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HM beta supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.
Although large numbers of long noncoding RNAs (IncRNAs) expressed in the mammalian nervous system have been detected, their functions and mechanisms of regulation remain to be fully clarified. It has been reported that the IncRNA antisense transcript for beta-secretase-1 (BACE1-AS) is elevated in Alzheimer's disease (AD) and drives the rapid feed-forward regulation of p-secretase, suggesting that it is critical in AD development. In the present study, the senile plaque (SP) AD SH-SY5Y cell model was established using the synthetic amyloid beta-protein (A beta) 1-42 in vitro. Using this model, the potential of siRNA-mediated silencing of IncRNA BACE1-AS expression to attenuate the ability of beta-secretase-1 (BACE1) to cleave amyloid precursor protein (APP) and to reduce the production of A beta(1-42) oligomers was investigated. MTT assays demonstrated that exogenous A beta(1-42) suppressed SH-SY5Y cell proliferation and induced APP-related factor expression and SP formation: Furthermore, quantitative polymerase chain reaction and western blot analysis revealed that the mRNA and protein expression of A beta(1-42) and A beta(1-40) was significantly increased in the AD model group, with a marked decrease in Ki-67 expression at day six. RNase protection assays (RPA) and northern blotting analysis confirmed that exogenous A beta(1-42) not only promoted the expression of the APP-cleaving enzyme BACE1, but also induced IncRNA BACE1-AS expression. Furthermore, IncRNA BACE1-AS formed RNA duplexes and increased the stability of BACE1 mRNA. Downregulation of IncRNA BACE1-AS expression in SH-SY5Y cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to cleave APP and delayed the induction of SP formation in the SP AD SH-SY5Y cell model.
Recently, we discovered that beta-thujaplicin (BT) induces metallothionein (MT) expression in mouse ker- atinocytes, both in vivo and in vitro. However, the molecular mechanisms by which BT exerts its biological effects have not been elucidated. The purpose of this study is to explore the signal transduction pathway involved in the MT mRNA induction by BT. Using a HaCaT keratinocyte cell line, Northern blotting was performed for analyzing the human MT-IIA mRNA expression levels in combination with BT and a number of protein kinase (PK) in hibitors including H7, HA1004 and a PKC-specific inhibitor chelerythrin. CAT assays with the MT-IIA gene promorter-CAT construct were conducted for examining the transcriptional regulation by BT of MT. A free radical scavenger N-acetylcysteine (NAC) was used for analyzing a role of oxidative stress for the MT gene induction by BT. BT increased MT-IIA gene transcript levels and CAT activity in a dose-dependent fashion in HaCaT cells. The increase in MT-IIA mRNA levels and CAT activity were completely suppressed by H7 but not by HA1004. In addition, chelerythrin prevented BT-inducible MT-IIA promoter activation. Furthermore, NAC suppressed BT4 inducible MT-IIA promoter activation. These results demonstrate that BT is a potent activator of the MT-IIA gene promoter and that PKC activation and reactive oxygen species are implicated in BT-inducible MT-IIA gene expression. BT may be a useful tool for dissecting the signal transduction pathway mediating MT-IIA promoter activation.
BackgroundRetinoblastoma is the most common malignant cancer of the eye in children. Although metastatic retinoblastoma is rare, cure rates for this advanced disease remain below 50%. High-level polo-like kinase 1 expression in retinoblastomas has previously been shown to be correlated with adverse outcome parameters. Polo-like kinase 1 is a serine/threonine kinase involved in cell cycle regulation at the G2/M transition. Polo-like kinase 1 inhibition has been demonstrated to have anti-tumour effects in preclinical models of several paediatric tumours. Here, we assessed its efficacy against retinoblastoma cell lines. MethodsExpression of polo-like kinase 1 was determined in a panel of retinoblastoma cell lines by polymerase chain reaction and western blot analysis. We analysed viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT assay), proliferation (5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay), cell cycle progression (propidium iodid staining) and apoptosis (cell death enzyme-linked immunosorbent assay) in three retinoblastoma cell lines after treatment with two adenosine triphosphate-competitive polo-like kinase 1 inhibitors, BI6727 or GSK461364. Activation of polo-like kinase 1 downstream signalling components including TP53 were assessed. ResultsTreatment of retinoblastoma cells with either BI6727 or GSK461364 reduced cell viability and proliferative capacity and induced both cell cycle arrest and apoptosis. Polo-like kinase 1 inhibition also induced the p53 signalling pathway. Analysis of key players in cell cycle control revealed that low nanomolar concentrations of either polo-like kinase 1 inhibitor upregulated cyclin B1 and increased activated cyclin-dependent kinase 1 (phosphorylated at Y15) in retinoblastoma cell lines. ConclusionsThese preclinical data indicate that polo-like kinase 1 inhibitors could be useful as components in rationally designed chemotherapy protocols to treat patients with metastasized retinoblastoma in early phase clinical trials.
The paper aims to determine the day-ahead market bidding strategies for retailers with flexible demands to maximize the short-term profit. It proposes a short-term planning framework to forecast the load under dynamic tariffs and construct biding curves. Stochastic programming is applied to manage the uncertainties of spot price, regulating price, consumption behaviors, and responsiveness to dynamic tariffs. A case study based on data from Sweden is carried out. It demonstrates that a real-time selling price can affect the aggregate load of a residential consumer group and lead to load shift toward low-price periods. The optimal bidding curves for specific trading periods are illustrated. Through comparing the bidding strategies under different risk factors, the case study shows that a risk-averse retailer tends to adopt the strategies with larger imbalances. The benefit lies in the reduction of low-profit risk. However, the aversion to risk can only be kept in a certain level. A larger imbalance may lead to a quick reduction of profit in all scenarios.
This paper presents a new approach for determining the day-ahead bidding strategies of a large-scale hybrid electric energy company. The company has both energy generation and energy retailing businesses in a competitive electricity market. Demand response programs are also considered in the retail side of the company in order to hedge the risk of participation in wholesale market. This paper introduces a max-min bilevel mathematical programming with equilibrium constraint model for offering a strategy that manages the risk of uncertain forecasted rivals' bids by robust optimization. The max-min bilevel model is converted to its equivalent single-level optimization using Karush-Kuhn-Tucker optimality conditions. The duality theory is utilized to find the equivalent ordinary maximization model of the max-min problem. Strong duality theory and big M method are also used to linearize the final model of offering strategy. Applicability of the proposed approach is shown by implementing it on the IEEE 118-bus test system.
This paper presents a novel interleaved high-conversion-ratio bidirectional dc-dc converter based on switched capacitors and coupled inductors. Series-connected switched capacitor and inductor cells were used to increase the voltage conversion ratio, reduce voltage stresses on power switches, realize soft-charging/discharging of switched capacitors, and achieve autocurrent-sharing in parallel inductors. The interleaved structure combined with switched capacitors was adopted to reduce current ripple at the side having lower voltage, thus enabling applications that require high power levels. In this paper, we first review the status of high-voltage-ratio bidirectional dc-dc converters. Then, the evolution of the proposed extensible topologies and the steady-state operating principle under the inductor current continuous conduction mode is presented. Finally, the performance and features such as voltage gain, voltage and current stress, and the autocurrent-sharing mechanism that are realized by switched capacitors are verified; the optimal design of coupled-inductors, switched-capacitors, and the chip size of switches are given. A specific design of the driving circuit that facilitates actual applications is described. A 1-kW prototype converter, employing a hybrid configuration of SiC and Si MOSFETs, was constructed to verify the theoretical analysis, and achieved an optimal compromise between conversion efficiency and low cost.
The two-stage 48 V-12 V-1.8 V voltage regulator module (VRM) structure is gaining more and more attention in high-end server applications. The LLC converter is the preferred choice for the first conversion stage because it provides the isolated 12-V output efficiently, which is then converted to 1.8 V by the multi-phase Buck converter. Since the CPU works in sleep-mode most of the time, the light-load efficiency is very important for energy saving. This paper proposes to change the primary side of the LLC converter from the full-bridge (FB) configuration into the half-bridge (HB) configuration dynamically in the light-load condition, so that the output of the LLC dc transformer (DCX) can be changed from 12 to 6 V. This will increase the overall light-load efficiency significantly due to the reduced core loss of the LLC DCX and the reduced switching loss of the multiphase Buck converter. To achieve a fast transition of the bus voltage between 12 and 6 V, the capacitance for the intermediate bus is properly selected and the optimal trajectory control for transition between the FB configuration and HB configuration is proposed. A high-efficiency high-density 48-12 /6 V LLC DCX is designed, and experiments on the two-stage VRM demonstrate that there is a fast transient response and a more than 10% light-load efficiency improvement.
This paper proposes a bidirectional three-level LLC resonant converter with a new pulse width and amplitude modulation control method. With different control signals, it has three different operation modes with different voltage gains. Therefore, it can achieve wide voltage gain range by switching among these three modes, which is attractive for energy storage system applications needing wide voltage variation. The proposed topology operates with constant switching frequency, which is easy to implement with digital control, and it can achieve soft switching for all the switches and diodes in the circuit as a conventional LLC resonant converter. The performance of the proposed converter is validated by the experimental results from a 1-kW prototype with 20 A maximum output current.
Bifenthrin (BF) is a chiral pesticide with two enantiomers. In this work, its stereoselective degradation was investigated in plants and domesticated active sludge. Considering that the degradation to pesticides of plants was effected by external conditions, hence, nanometer materials (gothite) were added into soil to explore the effect of sorption on enantioselectivity in degradation of BF. The microbial community that was responsible for BF-biodegrading in active sludge was studied by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE). In plant researches, chiral difference was discovered in the degradation of pesticides that onions resulted in. The existence of gothite in soil not only reduced the amount of BF that plants uptake from the environment, but it also enlarged the chiral difference during the process, indicating that the absorption of gothite to pesticides had enantioselectivity, which may be generated by that adsorption site where BF combined with gothite located in the chiral center of the pesticide. In studies of sludge, BF can be effectively degraded and decline of both isomers followed first-order kinetics. However, there was no obvious stereoselective degradation in domesticated sludge. The analysis of DGGE revealed that active sludge maintained the rich microbial community in the whole process (H >3). The H index increased in the early domestication, which may because BF had no direct toxicity to the bacteria. The bacteria were able to degrade the small dose of the pesticide and absorbed it as nutrition. The sequence results demonstrated that the variety of bacteria grew, instead of Acidobacteria, Betaproteobacteria, Sphingobacteriia and Alphaproteobacteria, Flavobacteria also appearing in sludge after domestication.
The paper reviews the circuitry of differential stages (DSs) based on the elements of radiation-hardened bipolar and field effect analog gate-array master chip "AGAMC-1.3" (OJSC "Integral", Minsk city, Belarus). It suggests architectures of op amps (OAs) realized on the base of BJTs-JFETs. Their feature lies in the absence of classical reference current source setting a steady-state behavior of the input transistors. It increases the radiation stability. The parameters of experimental circuit of OA of this class IC-3, oriented for the use in sensor systems of demanding application, are given.
The architectures of the operational amplifiers (OA), implemented on the basis on bipolar and field (JFET) transistors, are offered. Their feature - the use of transistors operating on different physical principles, precision in the input circuits of differential stages (DS). This allows you to set a static DS mode due to the choice of the geometric dimensions of field-effect transistors and to exclude from structure of the classical sources of the reference current. The circuit engineering and the basic circuits of inclusion of the differential difference operational amplifiers (DDA), based on the analog gate-array master chip AGAMC (OJSC "Integral", Minsk) with low offset voltages, are provided. Parameters and topology of the experimental chip of OA of this class (IC-3) oriented on use in the sensor systems of responsible application are given.
Efficiency in a light load dc-dc converter is improved by reducing the switching frequency with the load current. Further, a bifrequency operation (BFO) using pulse train (PT) control can achieve spread spectrum. Using discrete-time models, this paper shows that a stable periodic BFO is generally not achievable in existing PT control methods. Thereafter, a unified multimode digital control technique is proposed, in which a voltage-mode digital pulse-width-modulator (DPWM) is used to control a predefined periodic BFO. Beside the fixed-frequency DPWM, an extra multiplexer is considered for real-time configuration to: 1) bifrequency pulse frequency modulation; 2) PT control; or 3) pulse regulation control; or 4) pulse skipping control with smooth transition. Analysis and design methods are discussed to ensure periodic BFO and to customize the power spectrum with predictable ripple parameters. A buck converter prototype is made, and the proposed control is implemented using an FPGA device.
In order to find new insect resistance genes, four homologous cDNAs, hta-a, hta-b, hta-c and hta-d with lengths of 775, 718, 784 and 752 bp, respectively (GenBank accession numbers AF477031-AF477034), were isolated from a tuber cDNA expression library of Helianthus tuberosus L. Sequence analysis revealed that all four cDNAs contain an open reading frame of 444 bp, coding a polypeptide of 147 amino acid residues, and that the sequences of the cDNAs are very similar to those of the mannose-binding agglutinin genes of the jacalin-related family. In hemagglutination reactions and hapten inhibition assays, affinity-purified HTA (Helianthus tuberosus agglutinin) from induced Escherichia coli BL21(DE3) expressing GST-HTA shows hemagglutination ability and a higher carbohydrate-binding ability for mannose than other tested sugars. Trypsin inhibitory activity was detected in the crude extracts of induced E. coli BL21(DE3) expressing HTA, and was further verified by trypsin inhibitory activity staining on native polyacrylamide gel. The mechanism of interaction between HTA and trypsin was studied by molecular modeling. We found that plenty of hydrogen bonds and electrostatic interactions can be formed between the supposed binding sites of HTA-b and the active site of trypsin, and that a stable HTA/trypsin complex can be formed. The results above imply that HTA might be a bifunctional protein with carbohydrate-binding activity and trypsin inhibitory activity. Moreover, Northern blotting analysis demonstrated that hta is predominantly expressed in tubers of H. tuberosus, very weakly expressed in stems, but not expressed at all in other tissues. Southern blotting analysis indicated that hta is encoded by a multi-gene family. The insect resistance traits have been described in another paper.
DC distribution power systems are vulnerable to instability because of the destabilizing effect of converter-controlled constant power loads (CPLs) and input filters. Standard stability analysis tools based on averaging linearization techniques can be used only when the switching frequency of the converter is significantly higher than the cutoff frequency of the filter. However, dc distribution systems with a reduced size filter, and consequently a high cutoff frequency, are common in transportation applications. Conventional methods fail to detect instabilities in the system because they do not take into account the switching effect. To overcome this drawback, this paper proposes a discrete-time method to analyze the stability of dc distribution systems. This model is applied here to a dc power system with a CPL. The switching effects and the nonlinearities of the system model are taken into account with a simple discretization approach. The proposed method is able to predict the dynamic properties of the system, such as slow-scale and fast-scale instabilities. An active stabilizer is also included in the system model in order to extend the stability margin of the system. Finally, these observations are validated experimentally on a laboratory test bench.
We report a five-component autonomous chaotic oscillator of jerky type, hitherto the simplest of its kind, using only one operational amplifier. The key component of the circuit is a junction field-effect transistor operating in its triode region, which provides a nonlinear resistor of antisymmetrical current-voltage characteristic, emulating a Colpitts-like chaotic circuit. We describe the experimental results illustrating the dynamical behavior of the circuit. In addition, we report numerical simulations of a model of the circuit which display good agreement with our measurements.
Smart meters play vital roles in the aspects of the management and operation of smart grids such as demand response, energy efficiency improvement, and electricity pricing. Massive amounts of data are being collected owing to the popularity of smart meters. Two main issues should be addressed in this context. One is the communication and storage of big data from smart meters at reduced cost. The other is the effective extraction of useful information from this massive dataset. In this paper, the K-SVD sparse representation technique, which includes two phases (dictionary learning and sparse coding), is used to decompose load profiles into linear combinations of several partial usage patterns (PUPs), which allows the smart meter data to be compressed and hidden electricity consumption patterns to be extracted. Then, a linear support vector machine (SVM) based method is used to classify the load profiles into two groups, residential customers and small and medium-sized enterprises (SMEs), based on the extracted patterns. Comprehensive comparisons with the results of k-means clustering, the discrete wavelet transform (DWT), principal component analysis (PCA), and piecewise aggregate approximation (PAA) are conducted on real datasets in Ireland. The results show that our proposed technique outperforms these methods in both compression ratio and classification accuracy.
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.
Disease has an effect on crop yields, causing significant losses. As the worldwide demand for agricultural products increases, there is a need to pursue the development of new methods to protect crops from disease. One mechanism of plant protection is through the activation of the plant immune system. By exogenous application, 'plant activator molecules' with elicitor properties can be used to activate the plant immune system. These defence-inducing molecules represent a powerful and often environmentally friendly tool to fight pathogens. We show that the secondary bile acid deoxycholic acid (DCA) induces defence in Arabidopsis and reduces the proliferation of two bacterial phytopathogens: Erwinia amylovora and Pseudomonas syringae pv. tomato. We describe the global defence response triggered by this new plant activator in Arabidopsis at the transcriptional level. Several induced genes were selected for further analysis by quantitative reverse transcription-polymerase chain reaction. We describe the kinetics of their induction and show that abiotic stress, such as moderate drought or nitrogen limitation, does not impede DCA induction of defence. Finally, we investigate the role in the activation of defence by this bile acid of the salicylic acid biosynthesis gene SID2, of the receptor-like kinase family genes WAK1-3 and of the NADPH oxidase-encoding RbohD gene. Altogether, we show that DCA constitutes a promising molecule for plant protection which can induce complementary lines of defence, such as callose deposition, reactive oxygen species accumulation and the jasmonic acid and salicylic acid signalling pathways.
Accumulation of hydrophobic bile acids in the liver contributes to cholestatic liver injury. Inflammation induced by excessive bile acids is believed to play a crucial role, however, the mechanisms of bile acids triggered inflammatory response remain unclear. Recent studies have highlighted the effect of NLRP3 inflammasome in mediating liver inflammation and fibrosis. In this study, we for the first time showed that chenodeoxycholic acid (CDCA), the major hydrophobic primary bile acid involved in cholestatic liver injury, could dose-dependently induce NLRP3 inflammasome activation and secretion of pro-inflammatory cytokine-IL-1 beta in macrophages by promoting ROS production and K+ efflux. Mechanistically, CDCA triggered ROS formation in part through TGR5/EGFR downstream signaling, including protein kinase B, extracellular regulated protein kinases and c-Jun N-terminal kinase pathways. Meanwhile, CDCA also induced ATP release from macrophages which subsequently causes K+ efflux via P2X7 receptor. Furthermore, in vivo inhibition of NLRP3 inflammasome with caspase-1 inhibitor dramatically decreased mature IL-1 beta level of liver tissue and ameliorated liver fibrosis in bile duct ligation (BDL) mouse model. In conclusion, excessive CDCA may represent an endogenous danger signal to activate NLRP3 inflammasome and initiate liver inflammation during cholestasis. Our finding offers a mechanistic basis to ameliorate cholestatic liver fibrosis by targeting inflammasome activation.
Worldwide natural gas consumption has increased significantly, especially for power generation in electricity systems with the gas-to-power (G2P) process of natural gas fired units. Supply for both natural gas and electricity systems should be dispatched economically and simultaneously due to their firm interconnection. This paper proposes a security-constrained bi-level economic dispatch (ED) model for integrated natural gas and electricity systems considering wind power and power-to-gas (P2G) process. The upper level is formulated as an ED optimization model for electricity system, while the lower level is an optimal allocation problem for natural gas system. Natural gas system is modeled in detail. In addition, the security constraints and coupling constraints for the integrated energy systems are considered. The objective function is to minimize the total production cost of electricity and natural gas. The lower model is converted and added into the upper model as Karush-Kuhn-Tucher (KKT) optimality conditions, thus the bi-level optimization model is transformed into a mix-integer linear programming (MILP) formulation. Numerical case studies on the PJM-5bus system integrated with a seven-node gas system and IEEE 118-bus system integrated with a modified Belgian high-calorific gas system demonstrate the effectiveness of the proposed bi-level ED model. (C) 2016 Elsevier Ltd. All rights reserved.
This paper describes a variable output voltage, multi-phase switched capacitor step-up DC-DC converter with a digital voltage regulation scheme, implemented in CMOS VLSI technology. The number of conversion ratios generated using n flying capacitors is of the order of 2(n). A scheme for selection of switch is presented. Expressions for equivalent series resistance (Req), conduction, switching power loss and efficiency are obtained and compared with the cadence spectre simulation results. The step-up open loop converter circuit for one of the gain is described and analysed by varying the switching frequency. An open loop converter efficiency of about 78% is achieved with 4% bottom plate parasitic capacitance for a load current of 1 mA and input voltage of 0.6 V at 4 MHz of switching frequency for a gain of 4/3. The voltage regulation scheme for a desired output voltage is designed with a digital control circuit using inherent capacitive DAC which can interpolate through various gain configuration for n = 2 flying capacitor and is simulated in Cadence Analog-Mixed Signal Flow using 180nm CMOS technology. The layout design using MIM cap has been done and back annotation results are presented.
Destination memory refers to the ability to remember to whom a piece of information was previously transmitted. Our paper assessed this ability in schizophrenia. Twenty-five patients with schizophrenia and 25 control participants told proverbs (e.g., "send a thief to catch a thief") to pictures of celebrities (e.g., Elvis Presley). Afterward, participants had to indicate to which celebrity they had previously said the proverbs. Participants also completed a binding task in which they were required to associate letters with their corresponding context (i.e., location). Analysis revealed worse destination memory and binding in patients with schizophrenia than in controls. In both populations, destination memory was significantly correlated with performances on the binding task. Our findings suggest difficulty in the ability to attribute information to its appropriate destination in schizophrenia. This difficulty may be related to compromise in binding separate cues together to form a coherent representation of an event in memory.
Background: A 12-month, open-label extension study assessed the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating disorder (BED). Methods: Adults (aged 18-55 y) with BED who completed 1 of 3 antecedent studies were enrolled in a 52-week, open-label extension study (dose optimization, 4 weeks [initial titration dose, 30-mg LDX; target doses, 50-or 70-mg LDX]; dose maintenance, 48 weeks). Safety evaluations included the occurrence of treatment-emergent adverse events (TEAEs), vital sign and weight assessments, and Columbia-Suicide Severity Rating Scale responses. Results: Of the 604 enrolled participants, 599 (521 women and 78 men) comprised the safety analysis set, and 369 completed the study. Mean (SD) LDX exposure was 284.3 (118.84) days; cumulative LDX exposure duration was 12 months or longer in 344 participants (57.4%). A total of 506 participants (84.5%) reported TEAEs (TEAEs leading to treatment discontinuation, 54 [9.0%]; severe TEAEs, 42 [7.0%]; serious TEAEs, 17 [2.8%]). Treatment-emergent adverse events reported in greater than or equal to 10% of participants were dry mouth (27.2%), headache (13.2%), insomnia (12.4%), and upper respiratory tract infection (11.4%). Mean (SD) changes from antecedent study baseline in systolic and diastolic blood pressure, pulse, and weight at week 52/early termination (n = 597) were 2.19 (11.043) and 1.77 (7.848) mm Hg, 6.58 (10.572) beats per minute, and -7.04 (7.534) kg, respectively. On the Columbia-Suicide Severity Rating Scale, there were 2 positive responses for any active suicidal ideations; there were no positive responses for suicidal behavior or completed suicides. Conclusions: In this 12-month, open-label, extension study, the long-term safety and tolerability of LDX in adults with BED were generally consistent with its established profile for attention-deficit/hyperactivity disorder.
ObjectiveThis study aims to evaluate the theory of mind ability in a sample of obese patients with and without binge eating disorder (BED) and to explore the correlations between emotional and clinical assessments. MethodsOverall, 20 non-BED, 16 under-threshold BED and 22 BED obese patients completed a battery of tests assessing social cognition and eating disorder psychopathology. ResultsBinge eating disorder, non-BED and under-threshold-BED obese patients showed similar ability to recognise others' emotions, but BED obese patients exhibited a deficit in recognising their own emotions as demonstrated by more impaired levels of alexithymia and interoceptive awareness and were more depressed. High positive correlations were evident between binging, depression, interoceptive awareness and alexithymia. ConclusionsBinge eating disorder patients have a comparable ability to understand others' emotions but a more impaired capacity to understand and code their own emotions compared with non-BED obese patients. This impairment is highly correlated with depression. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
This study presents a bioacoustic sensor system developed for early detection of the recovery of bowel activity after abdominal surgery and to perform analysis on bowel sounds. Different than other studies, in order to be able to attenuate noise, two capacitive microphones oriented in opposite directions are used. Bowel sounds are typically observed at a frequency between 100 Hz and 1500 Hz and amplitude between 0 and 20mV. The signal strength is boosted 48 times with an amplifying circuit. The second microphone is used to observe environmental noise such as examination room noise. Both signals are digitized using an ADC (NI DAQ Data Acquisition USB 6009). Finally, we developed a software that can extract spectral properties of the signal and present the results in real time.
Reclamation of wastewater (WW) for irrigation, after treatment represents a challenge that could alleviate pressure on water resources and address the increasing demand for agriculture. However, the risks to human health must be assessed, particularly those related to human enteric viruses that resist standard treatments in most wastewater treatment plants (WWTP). The risks associated with exposure to viral bioaerosols near WWTP and near agricultural plots irrigated with WW are poorly documented. The objectives of this study were to 1) better characterize human enteric viruses found in bioaerosols near a "standardWWTP" and over fields irrigated with treated WW and 2) propose a numeric model to assess the health risk to populations located close to the irrigated areas, with particular attention to norovirus, which is responsible for most viral gastroenteritis in France. Water and air samples were collected at various locations in the largest French WW-irrigated site near Clermont-Ferrand, at the WWTP entrance and after treatment, in the air above activated sludge basins, and above fields irrigated with WW. Various enteric viruses were found in the water samples collected both before and after treatment. Norovirus was the most abundant with >10e4 genome copies/l (GC/L) before treatment and similar to 10e3 GC/L after treatment. Low quantities (= 3 m/s) and a constant emission rate of 8e3 GC/m(3)/s. This probability decreases by 3 log when the distance to the emission source is doubled. This information can aid development of safe water reuse policies in terms of local setback distance and wind conditions for wastewater reuse. (C) 2017 Elsevier B.V. All rights reserved.
Synergistic effects of multiple plant secondary metabolites on upper trophic levels constitute an underexplored but potentially widespread component of coevolution and ecological interactions. Examples of plant secondary metabolites acting synergistically as insect deterrents are not common, and many studies focus on the pharmaceutical applications of natural products, where activity is serendipitous and not an evolved response. This review summarizes some systems that are ideal for testing synergistic plant defenses and utilizes a focused meta-analysis to examine studies that have tested effects of multiple compounds on insects. Due to a dearth of ecological synergy studies, one of the few patterns for synergy that we are able to report from the meta-analysis is that phytochemical mixtures have a larger overall effect on generalist herbivores than specialist herbivores. We recommend a focus on synergy in chemical ecology programs and suggest future hypothesis tests and methods. These approaches are not focused on techniques in molecular biology to examine mechanisms at the cellular level, rather we recommend uncovering the existence of synergy first, by combining the best methods in organic synthesis, isolation, chemical ecology, bioassays, and quantitative analyses. Data generated by our recommended methods should provide rigorous tests of important hypotheses on how intraclass and interclass compounds act synergistically to deter insects, disrupt the immune response, and ultimately contribute to diversification. Further synergy research should also contribute to determining if antiherbivore synergy is widespread among plant secondary metabolites, which would be consistent with the hypothesis that synergistic defenses are a key attribute of the evolved diverse chemical mixtures found in plants.
The l-alanine dehydrogenase of Bacillus subtilis (BasAlaDH), which is strictly dependent on NADH as redox cofactor, efficiently catalyzes the reductive amination of pyruvate to l-alanine using ammonia as amino group donor. To enable application of BasAlaDH as regenerating enzyme in coupled reactions with NADPH-dependent alcohol dehydrogenases, we alterated its cofactor specificity from NADH to NADPH via protein engineering. By introducing two amino acid exchanges, D196A and L197R, high catalytic efficiency for NADPH was achieved, with k(cat)/K-M=54.1 mu M(-1)Min(-1) (K-M=32 +/- 3 mu M; k(cat)=1,730 +/- 39Min(-1)), almost the same as the wild-type enzyme for NADH (k(cat)/K-M=59.9 mu M(-1)Min(-1); K-M=14 +/- 2 mu M; k(cat)=838 +/- 21Min(-1)). Conversely, recognition of NADH was much diminished in the mutated enzyme (k(cat)/K-M=3 mu M(-1)Min(-1)). BasAlaDH(D196A/L197R) was applied in a coupled oxidation/transamination reaction of the chiral dicyclic dialcohol isosorbide to its diamines, catalyzed by Ralstonia sp. alcohol dehydrogenase and Paracoccus denitrificans -aminotransferase, thus allowing recycling of the two cosubstrates NADP(+) and l-Ala. An excellent cofactor regeneration with recycling factors of 33 for NADP(+) and 13 for l-Ala was observed with the engineered BasAlaDH in a small-scale biocatalysis experiment. This opens a biocatalytic route to novel building blocks for industrial high-performance polymers. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Chromatin immunoprecipitation (ChIP) is an indispensable tool in the fields of epigenetics and gene regulation that isolates specific protein-DNA interactions. ChIP coupled to high throughput sequencing (ChIP-seq) is commonly used to determine the genomic location of proteins that interact with chromatin. However, ChIP-seq is hampered by relatively low mapping resolution of several hundred base pairs and high background signal. The ChIP-exo method is a refined version of ChIP-seq that substantially improves upon both resolution and noise. The key distinction of the ChIP-exo methodology is the incorporation of lambda exonuclease digestion in the library preparation workflow to effectively footprint the left and right 5 ' DNA borders of the protein-DNA crosslink site. The ChIP-exo libraries are then subjected to high throughput sequencing. The resulting data can be leveraged to provide unique and ultra-high resolution insights into the functional organization of the genome. Here, we describe the ChIP-exo method that we have optimized and streamlined for mammalian systems and next-generation sequencing-by-synthesis platform.
N-6-Methyladenosine (m(6)A) modifications of RNA are diverse and ubiquitous amongst eukaryotes. They occur in mRNA, rRNA, tRNA, and microRNA. Recent studies have revealed that these reversible RNA modifications affect RNA splicing, translation, degradation, and localization. Multiple physiological processes, like circadian rhythms, stem cell pluripotency, fibrosis, triglyceride metabolism, and obesity are also controlled by m(6)A modifications. Immunoprecipitation/sequencing, mass spectrometry, and modified northern blotting are some of the methods commonly employed to measure m(6)A modifications. Herein, we present a northeastern blotting technique for measuring m6A modifications. The current protocol provides good size separation of RNA, better accommodation and standardization for various experimental designs, and clear delineation of m(6)A modifications in various sources of RNA. While m(6)A modifications are known to have a crucial impact on human physiology relating to circadian rhythms and obesity, their roles in other (patho) physiological states are unclear. Therefore, investigations on m6A modifications have immense possibility to provide key insights into molecular physiology.
Considerable effort has recently been directed toward the implementation of molecular bioassays on digital-microfluidic biochips (DMFBs). However, today's solutions suffer from the drawback that multiple sample pathways are not supported and on-chip reconfigurable devices are not efficiently exploited. As a result, impractical manual intervention is needed to process protocols for gene-expression analysis. To overcome this problem, we first describe our benchtop experimental studies to understand gene-expression analysis and its relationship to the biochip design specification. We then introduce an integrated framework for quantitative gene-expression analysis using DMFBs. The proposed framework includes: 1) a spatial-reconfiguration technique that incorporates resource-sharing specifications into the synthesis flow; 2) an interactive firmware that collects and analyzes sensor data based on quantitative polymerase chain reaction; and 3) a real-time resource-allocation scheme that responds promptly to decisions about the protocol flow received from the firmware layer. This framework is combined with cyberphysical integration to develop the first design-automation framework for quantitative gene expression. Simulation results show that our adaptive framework efficiently utilizes on-chip resources to reduce time-to-result without sacrificing the chip's lifetime.
Various grafts or combination of bone substitute materials have been used in sinus lift procedures. Currently, ongoing developments in several disciplines, from molecular biology and chemistry to computer science and engineering, have contributed to the understanding of biological processes leading to bone healing after the use of bone substitute materials (BSBs) and therefore of the behavior of BSBs. The understanding of the properties of each graft enables individual treatment concepts and therefore allows shift from a simple replacement material to the modern concept of an individually created composite biomaterial. Indeed, the choice of the best BSB still remains crucial for success in maxillary sinus augmentation procedures. The present article provides an overview of most of the materials currently available for sinus lift, with a specific focus on their histological, molecular, cellular and pharmaceutical aspects.
Biochemical analysis of biological substances found at a crime scene is an important aspect of forensic investigations, where the objective is to determine the identification of crime victims and suspects/persons-of-interest. One particular biochemistry/molecular biology-based area of interest in forensic analysis is forensic serology; this area focuses on the complex task of gathering information regarding the type, age, ethnicity, and/or gender of the sample originator from the biological fluids (blood, saliva, etc.) found at a crime scene. In this review, we cover various studies involving biocomputing techniques used for the analysis of biological samples namely blood - in different forensic applications. The studies covered include the differentiation of gender and ethnicity using a biocomputing system that produces a binary result, as well as the determination of blood spot age. Each of the applications showcased in this review produces sometimes ambiguous results that would normally pose major problems for a study, however, the addition of biocomputing logic provides an extra level of certainty and clarity. We hope to convey the advantages of utilizing biocomputing methods in various forms of forensic analysis.
Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.
In recent years, there has been increasing concern over public health threat presented by introduction of petroleum hydrocarbon pollutants in environment due to anthropogenic activities to a greater extent and natural processes to some extent. Many countries all over the world are currently facing severe problem due to these pollutants as they are one of the persistent organic pollutants (POPs). Remediation of polluted sites by biodegradation is a viable option as conventional physico-chemical methods for remediation seems technically as well as economically challenging. Biodegradation is non-invasive and could be cost-effective in removal of petroleum hydrocarbon pollutants. It is considered as ultimate mechanism for pollutants removal. Immobilized microbial cells give advantage over free microbial cells to improve the survival and retention of the bioremediation agents in polluted sites. However, current biodegradation approaches suffer from a number of limitations, which include pollutant characteristics, poor capabilities of microbial communities in the field, lesser bioavailability of pollutants, growth conditions, etc. Understanding the factors affecting microbial degradation is of great research interest in present scenario. This review selectively examines and provides a critical view on bioavailability of the substrates, microorganisms in petroleum hydrocarbon pollutants degradation and the molecular techniques for their characterization, degradation mechanisms under aerobic and anaerobic conditions, commercially available bioremediation agents and factors affecting biodegradation of these pollutants. Role of genetically modified organisms and biodegradation of petroleum hydrocarbon pollutants by immobilized will also be discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Microbiological deterioration was observed on a historic collection of retouched glass plate negatives. The collection came from a burnt manor house that belonged to the Brandys family before World War Ilnd. The photographs were taken at the end of 19th century. The collection consists of 35 glass plate negatives, 4 of which were examined for possible presence of microorganisms. The current state of the negatives indicated that the collection may have been flooded. Initially, the viability of the microorganisms on the plates was examined using luminescence adenosine phosphate assay. The fungi were isolated and identified with molecular biology methods as Trichoderma longibrachiatum, Hypocrea Aspergillus versicolor, Penicillium sp. As the historic negatives were covered with a protective varnish layer, the impact of the isolated fungi on test negative plates covered with dammar and sandarac varnishes, and on a gelatine image layer were examined. The most effective in degradation of gelatine emulsion was T. longibrachiatum. All of the investigated microorganisms quickly decomposed silver image in gelatine layer not covered with varnish in opposite to slower decomposition of silver image in gelatine layer covered with sandarac and dammar varnishes. UV-induced luminescence observation confirmed that the microorganisms quickly decomposed gelatin layer not covered with varnish. The cracking of varnish was the result of fungal activity within gelatin, however, some fungi also attacked the varnish itself. (C) 2016 Elsevier Ltd. All rights reserved.
The present study deals with the exposure of four different mortar formulations in the headspace of two distinct sewer networks prone to biodeterioration phenomenon due to the presence of hydrogen sulphide. Cylindrical specimens composed of two cements, ordinary Portland cement ( OPC) and calcium aluminate cement ( CAC), with or without a substitution of 75 % of cement by blast furnace slag ( BFS) were prepared and exposed. During the exposure, the evolution of cement materials was monitored. After 4 years exposure, OPC materials without BFS are deeply deteriorated at high speed. Best performances have been observed with CAC mortars correlated to their higher content in aluminium ion ( Al3+). The rank of durability observed on site is OPC < OPC+BFS<CAC+BFS<CAC. Molecular biology analysis revealed that microbial diversity is varying according to binder type as well as during the exposure duration.
Humans have drastically altered the abundance of animals in marine ecosystems via exploitation. Reduced abundance can destabilize food webs, leading to cascading indirect effects that dramatically reorganize community structure and shift ecosystem function. However, the additional implications of these top-down changes for biogeochemical cycles via consumer-mediated nutrient dynamics (CND) are often overlooked in marine systems, particularly in coastal areas. Here, we review research that underscores the importance of this bottom-up control at local, regional, and global scales in coastal marine ecosystems, and the potential implications of anthropogenic change to fundamentally alter these processes. We focus attention on the two primary ways consumers affect nutrient dynamics, with emphasis on implications for the nutrient capacity of ecosystems: (1) the storage and retention of nutrients in biomass, and (2) the supply of nutrients via excretion and egestion. Nutrient storage in consumer biomass may be especially important in many marine ecosystems because consumers, as opposed to producers, often dominate organismal biomass. As for nutrient supply, we emphasize how consumers enhance primary production through both press and pulse dynamics. Looking forward, we explore the importance of CDN for improving theory (e.g., ecological stoichiometry, metabolic theory, and biodiversity-ecosystem function relationships), all in the context of global environmental change. Increasing research focus on CND will likely transform our perspectives on how consumers affect the functioning of marine ecosystems.
Plant virus ecology mainly focuses upon populations and their interactions with host plants within environment. The subject includes interesting insights as many factors which affect the virus behavior, population, virus-vector interactions, biodiversity and host plants genotypes are involved in it. Moreover the achievements in the field of molecular ecology by application of recent molecular biology techniques are included which enhance the strength in understanding the economically important virus populations, growth and their world wide spread. Virus infection results direct and indirect effect on insect vectors by evolution of changes in their life cycles, health and interacting behaviors that support their spread. Similarly, the description of the recent information about how plant viruses disseminate towards the important agro-ecological zones in naturally managed vegetations and which factors play important role in ecological aspects are also included in this review. The modern era of science and technology requires a better understanding about movement of viruses in both directions which has become a highly important issue to levitate such kinds of aspects thus making plant virus ecology an exciting research discipline in future.
In the biorefinery context, thermochemical processes have attracted a significant attention in recent years. Such processes generally consist of three main steps: pretreatment, thermochemical treatment, and post-treatment. In these developing processes, drying and feeding of biomass feedstock remain a significant and costly challenge. The moisture content of biomass feedstock must be decreased to an economic level at pretreatment step otherwise it has to have a detrimental effect on the process efficiency and quality of products. This work addresses the drying of biomass feedstock using novel but practical technology, called biodrying. It is a green technology that offers an opportunity for biomass drying without using an external heat source or fossil fuels, since drying energy is generated through exothermic microbial activity in the biomass that enhances the drying rate. This paper focuses on technoeconomic assessment of continuous biodrying technology integrated to gasification-based biorefinery and investigates the conditions that make such novel technology viable in conjunction with gasification process. Fixed capital investment and operating cost of different biodrying scenarios were estimated as M$4.3-21 and M$0.85/y-3.6/y, respectively, and potential benefits (sludge landfilling cost, energy savings, and carbon credit) from integration of the continuous biodrying system in gasification process implemented in pulp and paper mill were calculated, and ultimately economic performances of the scenarios were assessed. Furthermore, the viable biodrying conditions were specified as 4-day residence time and the major viability risk was found to be bound moisture of biomass.
Bioelectrochemical systems (BESs) may be used to upgrade anaerobic digester biogas by directly converting CO2 to CH4. The objective of this study was to evaluate gas (N-2, CO2, CH4, and H-2) and carbon transport within a methanogenic BES. Four BES configurations were evaluated: abiotic anode with abiotic cathode (AAn-ACa), bioanode with abiotic cathode (BAn-ACa), abiotic anode with biocathode (AAn-BCa), and bioanode with biocathode (BAn-BCa). Transport of N-2, a gas commonly used for flushing anoxic systems, out of the anode headspace ranged from 3.7 to 6.2L/d-atm-m(2), normalized to the proton exchange membrane (PEM) surface area and net driving pressure (NDP). CO2 was transported from the cathode to the anode headspace at rates from 3.7 to 5.4L/d-atm-m(2). The flux of H-2 from cathode to anode headspace was 48% greater when the system had a biocathode (AAn-BCa) than when H-2 was produced at an abiotic cathode (BAn-ACa), even though the abiotic cathode headspace had 75% more H-2 than the AAn-BCa biocathode at the end of 1 day. A 7-day carbon balance of a batch-fed BAn-BCa BES showed transient microbial carbon storage and a net transport of carbon from anode to cathode. After a 7-day batch incubation, the CH4 production in the biocathode was 27% greater on a molar basis than the initial CO2 supplied to the biocathode headspace, indicating conversion of CO2 produced in the anode. This research expands the current understanding of methanogenic BES operation, which may be used in improving the assessment of BES performance and/or in the development of alternative BES designs and mathematical models. Biotechnol. Bioeng. 2017;114: 961-969. (C) 2016 Wiley Periodicals, Inc.
In this work, the performance of dual-chamber microbial fuel cells (MFCs) constructed either with commonly used Nafion (R) proton exchange membrane or supported ionic liquid membranes (SILMs) was assessed. The behavior of MFCs was followed and analyzed by taking the polarization curves and besides, their efficiency was characterized by measuring the electricity generation using various substrates such as acetate and glucose. By using the SILMs containing either [C(6)mirn][PF6] or [Bmiml[NTf2] ionic liquids, the energy production of these MFCs from glucose was comparable to that obtained with the MFC employing polymeric Nafion (R) and the same substrate. Furthermore, the MFC operated with [Bmim] [NTf2]-based SILM demonstrated higher energy yield in case of low acetate loading (80.1 J g(-1) CODin m(-2) h(-1)) than the one with the polymeric Nafion N115 (59 J g(-1) CODin m(-2) h(-1)). Significant difference was observed between the two SILM-MFCs, however, the characteristics of the system was similar based on the cell polarization measurements. The results suggest that membrane-engineering applying ionic liquids can be an interesting subject field for bioelectrochemical system research. (C) 2017 Elsevier Ltd. All rights reserved.
Bio-electrochemical systems (BESs) are the microbial systems which are employed to produce electricity directly from organic wastes along with some valuable chemicals production such as medium chain fatty acids; acetate, butyrate and alcohols. In this review, recent updates about value-added chemicals production concomitantly with the production of gaseous fuels like hydrogen and methane which are considered as cleaner for the environment have been addressed. Additionally, the bottlenecks associated with the conversion rates, lower yields and other aspects have been mentioned. In spite of its infant stage development, this would be the future trend of energy, biochemicals and electricity production in greener and cleaner pathway with the win-win situation of organic waste remediation. Henceforth, this review intends to summarise and foster the progress made in the BESs and discusses its challenges and outlook on future research advances. (C) 2017 Elsevier Ltd. All rights reserved.
Limiting global warming to well below 2 degrees C requires the transformation of the global energy system at a scale unprecedented since the industrial revolution. To meet this 2 degrees C goal, 87% of integrated assessment models opt for using bioenergy with carbon capture and storage (BECCS). Without BECCS, the models predict that the goal will be either unachievable or substantially more costly to meet. While the modeling literature is extensive, studies of how key climate policy actors perceive and prioritize BECCS are sparse. This article provides a unique intercontinental mapping of the prioritization of BECCS for the long term transition of the electricity supply sector. Based on survey responses from 711 UN climate change conference delegates, the article reports the low prioritization of BECCS relative to alternative technologies, indicating an urgent need for studies of the sociopolitical preconditions for large-scale BECCS deployment.
Exposure to air pollution claimed the lives of about seven million people worldwide in 2010, largely from combustion of solid biomass fuels. Bioenergy is an alternative renewable source which can mitigate a climate change. Little is known about the human health and ecosystem effects of bioenergy, mainly in the electricity sector. This research applied a life cycle assessment approach to examine the human health and ecosystem effects of four bioenergy pathways: direct combustion of wood biomass, direct combustion of forest residue, direct combustion of pellets, and biomass integrated gasification and combined cycle (BIGCC). All pathways showed some variability of impacts; therefore, no single bioenergy pathway was the best absolute option. With the exception of the slightly higher human health impact, BIGCC has the least impact for all impact categories. However, all bioenergy systems implied lower ecosystem impact but higher human health impact as compared to climate change impact. Electricity generation from wood-biomass would improve the environmental sustainability of Alberta's electricity grid system because it reduces the human health and ecosystem impacts, as compared to the existing electricity production mix of the province. (C) 2017 Elsevier Ltd. All rights reserved.
Coal-fired power plants produce nearly 40% of the electricity in the United States, contributing more than three-quarters of all carbon dioxide emissions from the electricity sector. While many European coal-fired power plants have been transitioning to wood pellets to abate carbon dioxide emissions, such a changeover has not occurred in the United States electricity sector. This analysis examines the environmental implications of co-firing coal and wood pellets in the Southeastern United States, where the vast majority of wood pellet exports to Europe originate. Utilizing primary data from existing wood pellet manufacturers, a life cycle inventory is presented that characterizes the full cradle-to-grave environmental performance of co-firing coal and wood pellets for electricity generation. Furthermore, the avoided life cycle emissions related to shipping wood pellets to Europe are calculated. Life cycle assessment modeling scenarios for co-firing wood pellets in existing coal-fired power plants within the Southeastern United States result in reductions in eight of nine impact categories. The results presented here indicate that co-firing with wood pellets could be a viable interim solution for the aging fleet of coal-fired power plants within the Southeastern United States, particularly if stricter emission regulations and renewable portfolio standards are implemented. (C) 2017 Published by Elsevier Ltd.
Substrate nanotopography has been shown to be a potent modulator of cell phenotype and function. To dissect nanotopography modulation of cell behavior, a large area of nanopatterned substrate is desirable so that enough cells can be cultured on the nanotopography for subsequent biochemical and molecular biology analyses. However, current nanofabrication techniques have limitations to generate highly defined nanopatterns over a large area. Herein, we present a method to expand nanopatterned substrates from a small, highly defined nanopattern to a large area using stitch technique. The method combines multiple techniques, involving soft lithography to replicate poly(dimethylsiloxane) (PDMS) molds from a well-defined mold, stitch technique to assemble multiple PDMS molds to a single large mold, and nanoimprinting to generate a master mold on polystyrene (PS) substrates. With the PS master mold, we produce PDMS working substrates and demonstrate nanotopographical modulation of cell spreading. This method provides a simple, affordable yet versatile avenue to generate well-defined nanopatterns over large areas, and is potentially extended to create micro-/nanoscale devices with hybrid components.
Biofouling is a pervasive challenge in industrial and medical settings with enormous economic and health impacts. Use of quorum-quenching phages is a potential solution in either combating the biofilm or inhibiting biofilm formation when an engineered phage is designed for a specific bacterial system. In the event of a real-life application of synthetic phage, it is necessary to consider the effect of environmental conditions on the synthetic phage. This study focused on both (1) stability of phage lysate under different types of carbon sources and (2) competition of the engineered phage in comparison to a wild-type (wt) phage. Optimal results were found (in plaque forming units [PFUs]) with glucose as a carbon source and were kept stable for almost 30 days. Results suggested that competition happens before 4h. After that time, polymerase chain reaction results from PFU samples showed an increase in T7aiiA, which indicates that these conditions favored the phage replication of the engineered phage over the wt at 27h in a monoculture system. When both stability and competition were combined, the mix of phages showed a trend similar to T7aiiA only primarily after 8 days.
Biofuels have transitioned from a technology expected to deliver numerous benefits to a highly contested socio-technical solution. Initial hopes about their potential to mitigate climate change and to deliver energy security benefits and rural development, particularly in the Global South, have unravelled in the face of numerous controversies. In recognition of the negative externalities associated with biofuels, the European Union developed sustainability criteria which are enforced by certification schemes. This paper draws on the literature on stewardship to analyse the outcomes of these schemes in two countries: the UK and Guatemala. It explores two key issues: first, how has European Union biofuels policy shaped biofuel industries in the UK and Guatemala? And second, what are the implications for sustainable land stewardship? By drawing attention to the outcomes of European demand for biofuels, we raise questions about the ability of European policy to drive sustainable land practices in these two cases. The paper concludes that, rather than promoting stewardship, the current governance framework effectively rubberstamps existing agricultural systems and serves to further embed existing inequalities.
The present research study presents the optimization of Solid Oxide Fuel Cell (SOFC) power plants directly fed by biogas. By considering energy and exergy balances for such a system, a detailed thermodynamic model (THERMAS) was designed and implemented. A specific SOFC-based system was selected as case study, equipped with three heat exchangers (preheaters), a reformer, a SOFC-stack system and an afterburner. The use of the simulation tool THERMAS give us the opportunity to investigate all the appropriate parameters that affect system's efficiency based on exergy analysis while incorporating a detailed parametric analysis regarding the whole system. The optimization process relies on the difference between the energy and exergy efficiency by considering an innovative Optimization Factor (OPF) for each simulated system, which is dynamically affected by operational parameters, such as fuel composition, extension of chemical reactions and temperatures. It is found that the use of a pure fuels seems to be meaningless without optimization. (C) 2017 Elsevier Ltd. All rights reserved.
Herein a techno-economic assessment was performed on an energy-crop-based biogas plant coupled with a greenhouse for utilizing thermal energy produced by cogeneration. Seven energy crops were evaluated: triticale, maize, alfalfa, sunflower, clover, barley and wheat. According to the evaluation, triticale was the most competitive energy crop under selected climate conditions for northern Greece. Although maize displays higher biomass yield and biogas potential than the drought-resistant crop triticale, it has high irrigation demand that contributes significantly to total production costs. For a triticale-based biogas production to become economically feasible, agricultural arable area larger than 500 ha, or biogas plant size larger than 1000 kW(el), is required. However, with public funding, biogas production becomes feasible at smaller area (>250 ha) or biogas plant size (>500 kW(el)). The inclusion of a greenhouse into the design of the biogas plant contributes positively to the economic viability of the entire system. Under this scenario, greenhouse financial income accounts for about 17-18% of total income. Results of a sensitivity analysis suggest that the selection of an appropriate energy crop for biogas production should be based principally on both digestibility (specific methane yield) and biomass yield per hectare, these factors being more critical than biomass production costs.
Many recent studies have reported that microRNA (miRNA) biogenesis and function are related to the molecular mechanisms of various clinical diseases. Several methods, including northern blotting and DNA chip analyses, are capable of assessing miRNA-production patterns in cells. However, the development of repetitive monitoring of the miRNA-production profile in a noninvasive manner is demanded for the application of miRNAs to human medicine. Here, we describe a noninvasive system for monitoring miRNA biogenesis, from the stage of primary transcripts to that of mature miRNA regulation. We review the optical methods that have been developed to image miRNA production at each step of the miRNA-processing pathway in living subjects. We propose that an optical miRNA-imaging strategy, based on molecular imaging, can be used as an miRNA imaging detector to monitor various miRNAs, by using different reporters, simultaneously, for high-throughput screening, and will provide potential application for the diagnosis and therapeutics of multiple diseases.
Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.
Tripterygium wilfordii Hook. F. is one of the most valuable medicinal plants because it contains a large variety of active terpenoid compounds, including triptolide, celastrol, and wilforlide. All of the pharmacologically active secondary metabolites are synthesized from the 2-C-methyl-D-erythritol 4-phosphate and mevalonate pathway in the isoprenoid biosynthetic system. The key step in this pathway is the isomerization of dimethylallyl diphosphate and isopentenyl diphosphate, which is catalyzed by isopentenyl diphosphate isomerase (IPI). In the present study, a full-length cDNA encoding IPI (designate as TwIPI, GenBank accession no. KT279355) was cloned from a suspension of cultured cells from T. wilfordii. The full-length cDNA of TwIPI was 1,564 bp and encoded a polypeptide of 288 amino acids. The bioinformatics analysis showed that the deduced TwIPI sequence contained the TNTCCSHPL and WGEHELDY motif. The transcription level of the TwIPI in the suspension cells increased almost fivefold after treatment with methyl jasmonate as an elicitor. A functional color assay in Escherichia coli indicated that TwIPI could promote the accumulation of lycopene and encoded a functional protein. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 863-869, 2016
It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions (He-4) and the same dose of low-LET radiation (gamma rays). In expression profiles, a wide transcriptional response to desiccation stress that much exceeded the amount of up-regulated transcripts to irradiation exposure was observed. An extensive group of coincidently up-regulated overlapped transcripts in response to desiccation and ionizing radiation was found. Among this, overlapped set of transcripts was indicated anhydrobiosis-related genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock proteins. The most overexpressed group was that of protein-L-isoaspartate/D-aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins, were the most represented. Performed functional analysis showed strongly enriched gene ontology terms associated with protein methylation. In addition, active processes of DNA repair were detected. We assume that the cross-tolerance of the sleeping chironomid to both desiccation and irradiation exposure comes from a complex mechanism of adaptation to anhydrobiosis.
Background: Hepatitis B virus (HBV) DNA sequence data from thousands of samples are present in the public sequence databases. No publicly available, up-to-date, multiple sequence alignments, containing full-length and subgenomic fragments per genotype, are available. Such alignments are useful in many analysis applications, including data-mining and phylogenetic analyses. Results: By issuing a query, all HBV sequence data from the GenBank public database was downloaded (67,893 sequences). Full-length and subgenomic sequences, which were genotyped by the submitters (30,852 sequences), were placed into a multiple sequence alignment, for each genotype (genotype A: 5868 sequences, B: 4630, C: 7820, D: 8300, E: 2043, F: 985, G: 189, H: 108, I: 23), according to the results of offline BLAST searches against a custom reference library of full-length sequences. Further curation was performed to improve the alignment. Conclusions: The algorithm described in this paper generates, for each of the nine HBV genotypes, multiple sequence alignments, which contain full-length and subgenomic fragments. The alignments can be updated as new sequences become available in the online public sequence databases. The alignments are available at http://hvdr.bioinf.wits.ac.za/alignments.
Human multipotent mesenchymal stromal cells (hMSCs) possess the ability to differentiate into osteoblasts, and they can be utilized as a source for bone regenerative therapy. Osteoinductive pretreatment, which induces the osteoblastic differentiation of hMSCs in vitro, has been widely used for bone tissue engineering prior to cell transplantation. However, the molecular basis of osteoblastic differentiation induced by osteoinductive medium (OIM) is still unknown. Therefore, we used a next-generation sequencer to investigate the changes in gene expression during the osteoblastic differentiation of hMSCs. The hMSCs used in this study possessed both multipotency and self-renewal ability. Whole-transcriptome analysis revealed that the expression of zinc finger and BTB domain containing 16 (ZBTB16) was significantly increased during the osteoblastogenesis of hMSCs. ZBTB16 mRNA and protein expression was enhanced by culturing the hMSCs with OIM. Small interfering RNA (siRNA)-mediated gene silencing of ZBTB16 decreased the activity of alkaline phosphatase (ALP); the expression of osteogenic genes, such as osteocalcin (OCN) and bone sialoprotein (BSP), and the mineralized nodule formation induced by OIM. siRNA-mediated gene silencing of Osterix (Osx), which is known as an essential regulator of osteoblastic differentiation, markedly downregulated the expression of ZBTB16. In addition, chromatin immunoprecipitation (ChIP) assays showed that Osx associated with the ZBTB16 promoter region containing the GC-rich canonical Sp1 sequence, which is the specific Osx binding site. These findings suggest that ZBTB16 acts as a downstream transcriptional regulator of Osx and can be useful as a late marker of osteoblastic differentiation. J. Cell. Biochem. 117: 2423-2434, 2016. (c) 2016 Wiley Periodicals, Inc.
Recent developments in single-cell transcriptomics have opened new opportunities for studying dynamic processes in immunology in a high throughput and unbiased manner. Starting from a mixture of cells in different stages of a developmental process, unsupervised trajectory inference algorithms aim to automatically reconstruct the underlying developmental path that cells are following. In this review, we break down the strategies used by this novel class of methods, and organize their components into a common framework, highlighting several practical advantages and disadvantages of the individual methods. We also give an overview of new insights these methods have already provided regarding the wiring and gene regulation of cell differentiation. As the trajectory inference field is still in its infancy, we propose several future developments that will ultimately lead to a global and data-driven way of studying immune cell differentiation.
Bioinformatics field has now solidly settled itself as a control in molecular biology and incorporates an extensive variety of branches of knowledge from structural biology, genomics to gene expression studies. Bioinformatics is the application of computer technology to the management of biological information. Genomic signal processing (GSP) techniques have been connected most all around in bioinformatics and will keep on assuming an essential part in the investigation of biomedical issues. GSP refers to using the digital signal processing (DSP) methods for genomic data (e.g. DNA sequences) analysis. Recently, applications of GSP in bioinformatics have obtained great consideration such as identification of DNA protein coding regions, identification of reading frames, cancer detection and others. Cancer is one of the most dangerous diseases that the world faces and has raised the death rate in recent years, it is known medically as malignant neoplasm, so detection of it at the early stage can yield a promising approach to determine and take actions to treat with this risk. GSP is a method which can be used to detect the cancerous cells that are often caused due to genetic abnormality. This systematic review discusses some of the GSP applications in bioinformatics generally. The GSP techniques, used for cancer detection especially, are presented to collect the recent results and what has been reached at this point to be a new subject of research.
The tertiary structure of the proteins determines their functions. Therefore, the predicting of protein's tertiary structure, based on the primary amino acid sequence from long time, is the most important and challenging subject in biochemistry, molecular biology, and biophysics. One of the most popular protein structure prediction methods, called Hydrophobic-Polar (HP) model, is based on the observation that in polar environment hydrophobic amino acids are in the core of the molecule-in contact between them and more polar amino acids are in contact with the polar environment. In this study, we present a new mixed integer programming formulation, exact algorithm, and two heuristic algorithms to solve the protein folding problem stated as a combinatorial optimization problem in a simple cubic lattice. The results from computational runs on a set of benchmarks are favorably compared to known algorithms for solving the 3D lattice HP model as genetic algorithms, ant colony optimization algorithm, and Monte Carlo algorithm.
The chances of raising crop productivity to enhance global food security would be greatly improved if we had a complete understanding of all the biological mechanisms that underpinned traits such as crop yield, disease resistance or nutrient and water use efficiency. With more crop genomes emerging all the time, we are nearer having the basic information, at the gene-level, to begin assembling crop gene catalogues and using data from other plant species to understand how the genes function and how their interactions govern crop development and physiology. Unfortunately, the task of creating such a complete knowledge base of gene functions, interaction networks and trait biology is technically challenging because the relevant data are dispersed in myriad databases in a variety of data formats with variable quality and coverage. In this paper we present a general approach for building genomescale knowledge networks that provide a unified representation of heterogeneous but interconnected datasets to enable effective knowledge mining and gene discovery. We describe the datasets and outline the methods, work flows and tools that we have developed for creating and visualising these networks for the major crop species, wheat and barley. We present the global characteristics of such knowledge networks and with an example linking a seed size phenotype to a barley WRKY transcription factor orthologous to TTG2 from Arabidopsis, we illustrate the value of integrated data in biological knowledge discovery. The software we have developed (www.ondex.org) and the knowledge resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source and provide a first step towards systematic and evidence-based gene discovery in order to facilitate crop improvement. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.
Hepatocellular carcinoma is the major form of primary liver cancer, which is the second and sixth leading cause of cancer-related death in men and women, respectively. Extensive research indicates that Wnt/beta-catenin signaling pathway, which plays a pivotal role in growth, development, and differentiation of hepatocellular carcinoma, is one of the major signaling pathways that is dysregulated in hepatocellular carcinoma. Cyclin D1 is a proto-oncogene and is one of the major regulators of Wnt signaling pathway, and its overexpression has been detected in various types of cancers including hepatocellular carcinoma. Using several validated bioinformatic databases, we predicted that the microRNAs are capable of targeting 3'-untranslated region of Cyclin D1 messenger RNA. According to the results, miR-20a was selected as the highest ranking microRNA targeting Cyclin D1 messenger RNA. Luciferase assay was recruited to confirm bioinformatic prediction results. Cyclin D1 expression was first assessed by quantitative real-time polymerase chain reaction in HepG2 cell line. Afterward, HepG2 cells were transduced by lentiviruses containing miR-20a. Then, the expression of miR-20a and Cyclin D1 was evaluated. The results of luciferase assay demonstrated targeting of 3'-untranslated region of Cyclin D1 messenger RNA by miR-20a. Furthermore, 238-fold decline in Cyclin D1 expression was observed after lentiviral induction of miR-20a in HepG2 cells. The results highlighted a considerable effect of miRNA-20a induction on the down-regulation of Cyclin D1 gene. Our results suggest that miR-20a can be used as a novel candidate for therapeutic purposes and a biomarker for hepatocellular carcinoma diagnosis.
Eucheuma denticulatum, an economically and industrially important red alga, is a valuable marine resource. Although microRNAs (miRNAs) play an essential role in gene post-transcriptional regulation, no research has been conducted to identify and characterize miRNAs in E. denticulatum. In this study, we identified 134 miRNAs (133 conserved miRNAs and one novel miRNA) from 2,997,135 small-RNA reads by high-throughput sequencing combined with bioinformatics analysis. BLAST searching against miRBase uncovered 126 potential miRNA families. A conservation and diversity analysis of predicted miRNA families in different plant species was performed by comparative alignment and homology searching. A total of 4 and 13 randomly selected miRNAs were respectively validated by northern blotting and stem-loop reverse transcription PCR, thereby demonstrating the reliability of the miRNA sequencing data. Altogether, 871 potential target genes were predicted using psRobot and TargetFinder. Target genes classification and enrichment were conducted based on Gene Ontology analysis. The functions of target gene products and associated metabolic pathways were predicted by Kyoto Encyclopedia of Genes and Genomes pathway analysis. A Cytoscape network was constructed to explore the interrelationships of miRNAs, miRNA-target genes and target genes. A large number of miRNAs with diverse target genes will play important roles for further understanding some essential biological processes in E. denticulatum. The uncovered information can serve as an important reference for the protection and utilization of this unique red alga in the future.
Sclerospora graminicola (Sacc.) Schroet., an oomycete pathogen of Pennisetum glaucum (L.) R. Br. infects the meristematic tissues of young seedlings. The motile zoospores from the sporangia encyst, germinate and penetrate the plant tissue. Resistance to the invading pathogen is governed by the specific recognition of conserved pathogen-associated proteins or elicitors. In the present study, a zoospore protein was isolated and purified to homogeneity by a combination of size exclusion and high-performance liquid chromatography ( HPLC). The crude fractionated protein was able to elicit an array of defence responses in resistant and susceptible cells of pearl millet. Treatment of cultured cells of pearl millet with partially purified elicitor protein resulted in a rapid loss of cell viability in the resistant cells and the percentage of cell death was higher in the resistant than in the susceptible cells. Cultures of resistant cells showed a sharp increase in the extra cellular pH compared with susceptible cells when treated with the crude elicitor. Increased oxidative burst was also recorded in the cells treated with the crude elicitor. The purified elicitor showed unique properties. The purified protein was acidic with a pI of 5.6 as revealed by isoelectric focusing (IEF) and matrix-assisted laser desorption ionisation (MALDI) analysis showed that the elicitor had a molecular mass of 7040 daltons. The primary structure determined by N-terminal Edman degradation and searches with BLAST did not reveal similarities to any known plant pathogenic or oomycete elicitor. Higher activities of the important defence-related enzymes phenylalanine ammonia lyase ( PAL) and peroxidase in the resistant cell cultures than in the susceptible cell cultures treated with the purified elicitor were clearly evident. Studies of gene expression by northern blotting with heterologus peroxidase, PAL and oxalate oxidase probes showed that the mRNA transcripts were strongly up-regulated in resistant cell cultures within 30 min of elicitor treatment. The purified elicitor also demonstrated a very strong concentration-dependent sterol binding. The purified elicitor protein belongs to a class of low molecular weight oomycete elicitors with sterol carrier properties. The identified low molecular weight protein elicitor displays unique properties that can be exploited for synthesis of novel molecules for eco-friendly crop protection.
Whereas significant advances have been made in understanding how exposure to early adversity gets under the skin of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy-two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self-reported prenatal maternal depression and higher mother-infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development.
The fast growth of the human population forces us to produce more food, but higher crop production also leads to the fast spread of diseases. Plant pathology deploys a wide range of methods that do not provide an adequate solution to all disease losses. In the case of viroids, therapeutic means of control are not available; therefore control strategies are more focused on the development of reliable detection methods to quickly exclude the infected plant material. Although viroids are the smallest and simplest plant pathogens, their identification and detection is not straightforward. Each viroid-host combination is specific, and for reliable identification, all steps from sampling to final detection must be performed accurately. In this review, several methods for viroid detection in various host plants are discussed, including their advantages and disadvantages. Even though relatively new molecular methods enable fast and sensitive detection of viroids, a combination of different methods gives the most reliable identification. Techniques based on nucleic acids may be the future for viroid detection but they still cannot replace biological indexing, which is usually essential in epidemiological and aetiological studies.
The definition of biological individuality is one of the most discussed topics in philosophy of biology, but current debate has focused almost exclusively on evolution-based accounts. Moreover, several participants in this debate consider the notions of a biological individual and an organism as equivalent. In this paper, I show that the debates would be considerably enriched and clarified if philosophers took into account two elements. First, physiological fields are crucial for the understanding of biological individuality. Second, the category of biological individuals should be divided into two subcategories: physiological individuals and evolutionary individuals, which suggests that the notions of organism and biological individual should not be used interchangeably. I suggest that the combination of an evolutionary and a physiological perspective will enable biologists and philosophers to supply an account of biological individuality that will be both more comprehensive and more in accordance with scientific practices.
Salivary biomarkers could be helpful to characterize breast cancer. Therefore, this review was performed to evaluate the capability of salivary biological markers in the diagnosis and monitoring of breast cancer. Studies were eligible for inclusion if they assessed the potential diagnostic value or other discriminatory properties of biological markers in saliva of patients with breast cancer. The search was performed in six electronic databases (Cochrane, LILACS, PubMed, Science Direct, Scopus, Web of Science). In addition the biomarkers were classified according to their potential clinical application. We identified 567 pertinent studies, of which 13 met the inclusion criteria. Combined biomarker approaches demonstrated better ability to predict breast cancer patients than individual biomarkers. As single biomarlcer, namely proline, reported great capacity in both early and late stage breast cancer diagnosis. Taurine showed interesting capability to identify early breast cancer individuals. Furthermore, valine also demonstrated excellent diagnostic test accuracy for advanced stages of breast cancer. Only seven studies reported sensitivity and specificity (Zhang et al., 2010; Streckfus et al., 2000a; Brooks et al., 2008; Cheng et al., 2015; Bigler et al., 2002; Zhong et al., 2016; Streckfus, 2009), which varied considerably from 50% to 100%, and from 51% to 97%, respectively. In general, salivary biomarkers identified advanced stages of breast cancer better than early stages. There is currently limited evidence to confirm the putative implementation of salivary biomarkers as diagnostic tools for breast cancer. However, current review provides new research directions. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Background and Aim: In our previous study, we demonstrated that four microRNAs (miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non-invasive diagnostic biomarkers for gastric cancer (GC). Methods: We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan-Meier curves and log-rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis. Results: The median of miRNA expression in paraffin-embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down-regulation of miR-26a and miR-148a was significantly associated with shorter OS of GC patients either in the test set (miR-26a: P=0.009; miR-148a: P=0.005) or the validation set (miR-26a: P=0.011; miR-148a: P=0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR-26a and miR-148a were independent prognostic factors for predicting OS of patients with GC (miR-26a: HR=0.76, 95% CI=0.61-0.94; miR-148a: HR=0.73, 95% CI=0.58-0.91). Furthermore, elevated expression of miR-26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC-803 cells compared with negative control groups (P<0.05). Conclusion: These findings supported miR-26a and miR-148a could serve as potential prognostic biomarkers for GC.
Power to gas (P2G) may be used to store curtailed electricity whilst converting the energy vector to gas. To be economically viable these systems require cheap electricity and a cheap concentrated source of CO2. Biogas produced from anaerobic digestion typically comprises of 60% methane and 40% CO2. The P2G system substitutes for the conventional upgrading system by using hydrogen (derived from surplus wind electricity) to react with CO2 and increases the methane output. The potential CO2 production from biogas in Ireland associated with typical wet substrates is assessed as more than 4 times greater than that required by the potential level of H-2 from curtailed electricity. Wind energy curtailment in 2020 in Ireland is assessed conservatively at 2175GW(e)h/a. Thus P2G is limited by levels of curtailment of electricity rather than biogas systems. It is shown that 1 GW(e)h of electricity used to produce H-2 for upgrading biogas in a P2G system can affect a savings of 97 tonnes CO2. The cost of hydrogen is assessed at (sic)0.96/m(3) renewable methane when the price of electricity is (sic)c5/kW(e)h. This leads to a cost of compressed renewable gas from grass of (sic)1.8/m(3). This drops to (sic)1.1/m(3) when electricity is purchased at (sic)c0.2/1cW(e)h. (C) 2016 Elsevier Ltd. All rights reserved.
The beamline BL19U2 is located in the Shanghai Synchrotron Radiation Facility (SSRF) and is its first beamline dedicated to biological material small-angle X-ray scattering (BioSAXS). The electrons come from an undulator which can provide high brilliance for the BL19U2 end stations. A double flat silicon crystal (111) monochromator is used in BL19U2, with a tunable monochromatic photon energy ranging from 7 to 15 keV. To meet the rapidly growing demands of crystallographers, biochemists and structural biologists, the BioSAXS beamline allows manual and automatic sample loading/unloading. A Pilatus 1M detector (Dectris) is employed for data collection, characterized by a high dynamic range and a short readout time. The highly automated data processing pipeline SASFLOW was integrated into BL19U2, with help from the BioSAXS group of the European Molecular Biology Laboratory (EMBL, Hamburg), which provides a user-friendly interface for data processing. The BL19U2 beamline was officially opened to users in March 2015. To date, feedback from users has been positive and the number of experimental proposals at BL19U2 is increasing. A description of the new BioSAXS beamline and the setup characteristics is given, together with examples of data obtained.
Biologics, both monoclonal antibodies (mAbs) and fusion proteins, have revolutionized the practice of medicine. This year marks the 30th anniversary of the Food and Drug Administration approval of the first mAb for human use. In this review, we examine the biotechnological breakthroughs that spurred the explosive development of the biopharmaceutical mAb industry, as well as how critical lessons learned about human immunology informed the development of improved biologics. We also discuss the most common mechanisms of action of currently approved biologics and the indications for which they have been approved to date. (C) 2016 Elsevier Inc. All rights reserved.
Background: Distinguishing recipient cells from donor ligament cells is difficult in the early graft-healing phase after anterior cruciate ligament (ACL) reconstruction. The ability to track the distribution and differentiation of recipient cells using genetically engineered transgenic (Tg) animals would have significant clinical and research effects on graft healing after ACL reconstruction. Hypothesis: Kusabira-Orange Tg pigs may allow the tracking of recipient cells infiltrating the graft after ACL reconstruction. The repopulation of recipient cells within the graft would be apparent even in the early graft-healing phase when necrotic donor cells are still present. Study Design: Descriptive laboratory study. Methods: In 17 genetically engineered Tg pigs, which carried the red fluorescent protein Kusabira-Orange, ACL reconstruction was performed on the right knee using a digital flexor tendon harvested from wild-type pigs. Tissue samples harvested at different time points were subjected to histological, immunohistochemical, and electron microscopic analyses. Results: At 3 weeks postoperatively, recipient cells expressing red fluorescence embraced the graft and were infiltrating the central part of the graft. These cells with oval nuclei gradually infiltrated the gap of collagen fibers, losing their regular orientation. At 6 weeks, cellularity within the graft had doubled to match that of the native ACL, while acellular necrotic regions still existed centrally. Ubiquitous cellular distributions resembling the native ACL were observed at 24 weeks. Electron microscopic analysis showed that the mean collagen fibril diameter and density gradually decreased over 24 weeks. Conclusion: Genetically engineered pigs carrying the Kusabira-Orange gene were useful animal models for analyzing intrinsic and extrinsic cellular dynamics during the course of graft healing after ACL reconstruction. Cellular repopulation by recipient cells occurred in the very early stage, and the cellular distribution within the graft resembled that in the native ACL by 24 weeks, but the reconstructed graft had not restored the ultrastructure of the native ACL by that stage. Clinical Relevance: In allograft ACL reconstruction in a pig model, cellular repopulation was completed by 24 weeks after surgery, but the collagen matrix had not resumed the ultrastructure of the native ACL. Surgeons should be aware that risks may remain with returning to sports activities at 24 weeks after surgery.
Food poisoning by Staphylococcus aureus is a result of ingestion of Staphylococcal enterotoxins (SEs) produced by this bacterium and is a major source of foodborne illness. Staphylococcal enterotoxin D (SED) is one of the predominant enterotoxins recovered in Staphylococcal food poisoning incidences, including a recent outbreak in Guam affecting 300 children. Current immunology methods for SED detection cannot distinguish between the biologically active form of the toxin, which poses a threat, from the inactive form, which poses no threat. In vivo bioassays that measure emetic activity in kitten and monkeys have been used, but these methods rely upon expensive procedures using live animals and raising ethical concerns. A rapid (5 h) quantitative bioluminescence assay, using a genetically engineered T-cell Jurkat cell line expressing luciferase under regulation of nuclear factor of activated T cells response elements, in combination with the lymphoblastoid B-cell line Raji for antigen presentation, was developed. In this assay, the detection limit of biologically active SED is 100 ng/mL, which is 10 times more sensitive than the splenocyte proliferation assay, and 105 times more sensitive than monkey or kitten bioassay. Pasteurization or repeated freeze-thaw cycles had no effect on SED activity, but reduction in SED activity was shown with heat treatment at 100 degrees C for 5 min. It was also shown that milk exhibits a protective effect on SED. This bioluminescence assay may also be used to rapidly evaluate antibodies to SED for potential therapeutic application as a measurement of neutralizing biological effects of SED.
Background: Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment. Objective: To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations. Design, setting, and participants: Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n = 216, Cx n = 27) and plasma samples (NMIBC n = 39, Cx n = 27) from patients harbouring mutations were subsequently screened using ddPCR assays. Outcome measurements and statistical analysis: Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied. Results and limitations: In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p = 0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p = 0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study. Conclusions: Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer. Patient summary: Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
OBJECTIVE The incidence of posttraumatic ventriculomegaly (PTV) and shunt-dependent hydrocephalus after nonaccidental head trauma (NAHT) is unknown. In the present study, the authors assessed the timing of PTV development, the relationship between PTV and decompressive craniectomy (DC), and whether PTV necessitated placement of a permanent shunt. Also, NAHT/PTV cases were categorized into a temporal profile of delay in admission and evaluated for association with outcomes at discharge. METHODS The authors retrospectively reviewed the cases of patients diagnosed with NAHT throughout a 10-year period. Cases in which sequential CT scans had been obtained (n = 28) were evaluated for Evans' index to determine the earliest time ventricular dilation was observed. Discharge outcomes were assessed using the King's Outcome Scale for Childhood Head Injury score. RESULTS Thirty-nine percent (11 of 28) of the patients developed PTV. A low admission Glasgow Coma Scale (GCS) score predicted early PTV presentation (within1 week). A majority of PTV/NAHT patients presented with a subdural hematoma (both convexity and interhemispheric) and ischemic stroke, but subarachnoid hemorrhage was significantly associated with PTV/NAHT (p = 0.011). Of 6 patients undergoing a DC for intractable intracranial pressure, 4 (67%) developed PTV (p = 0.0366). These patients tended to present with lower GCS scores and develop ventriculomegaly early. Only 2 patients developed hydrocephalus requiring shunt placement. CONCLUSIONS PTV presents early after NAHT, particularly after a DC has been performed. However, the authors found that only a few PTV/NAHT patients developed shunt-dependent hydrocephalus.
Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC.
Introduction: Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.
Flexible multi-generation systems (FMGs) consist of integrated and flexibly operated facilities that provide multiple links between the different sectors of the energy system. The present study treated the design optimization of a conceptual FMG which integrated a methanol-producing biorefinery with an existing combined heat and power (CHP) unit and industrial energy utility supply in the Danish city of Horsens. The objective was to optimize economic performance and minimize total CO2 emission of the FMG while it was required to meet the local district heating demand plus the thermal utility demand of the butchery. The design optimization considered: Selection, dimensioning, location and integration of processes; operation optimization with respect to both hourly variations in Operating conditions over the year as well as expected long term energy system development; and uncertainty analysis considering both investment costs and operating conditions. Applying a previously developed FMG design methodology, scalable models of the considered processes were developed and the system design was optimized with respect to hourly operation over the period 2015-2035. The optimal design with respect to both economic and environmental performance involved a maximum-sized biorefinery located next to local industry rather than in connection with the existing CHP unit. As the local industry energy demands were limited when compared to the biorefinery dimensions considered, process integration synergies were found to be marginal when compared to the economic and environmental impact of the biorefinery for the present case. Assessing the impact of uncertainties on the estimated FMG performances, the net present value (NPV) of the optimal design was estimated to vary within the range 252.5-1471.6 ME in response to changes of 25% in investment costs and methanol price, and considering two different electricity price scenarios. In addition, a change in the interest rate from 5% to 20% was found to reduce the lower bound of the NPV to 181.3 ME for reference operating conditions. The results suggest that the applied interest rate and operating conditions, in particular the methanol price, would have a much higher impact on the economic performance of the designs than corresponding uncertainties in investment costs. In addition, the study outcomes emphasize the importance of including systematic uncertainty analysis in the design optimization of FMG concepts. (C) 2016 Elsevier Ltd. All rights reserved.
This paper first reviews the potential causality from biomass energy to CO2 emissions and economic development within relevant literature. Later, the paper examines statistically the impacts of biomass energy consumption on CO2 emissions and GDP in the US. To this end, paper observes environmental and economic implications of biomass fuel usage throughout energy literature and launches asymmetric causality test to confirm/disconfirm the literature output. The findings of the tests indicate that biomass energy consumption per capita mitigates CO2 emissions per capita and increases GDP per capita. Eventually, upon its output, this research asserts that biomass energy consumption can be an efficient policy tool for environmentally sustainable development in the US, and, that, hence, biomass production technologies and biomass consumption need to be promoted in other countries as well as in the US. On the other hand, analyses underline the fact that policy makers should consider as well some potential constraints of biomass energy usage such as land use constraints and carbon leakage from biomass production. Therefore, although this paper explores the remedial impact of biomass on environment and growth, one may suggest also that further possible works consider the effects of biomass sources in detail to minimize the some worsening influence of biomass usage on climate change.
The quality and composition of biomass as used in Portugal's thermal power plants is highly variable. The biomass consists mainly of residual forest biomass derived from forestry operations and wood waste from industrial processes, in particular paper and pulp industry. Its quality and composition is influenced by the presence of moisture and inert fragments, the latter being incorporated during collection or as a consequence of adherence to the biomass prior to collection. This variability presents difficulties for the thermal power plants; besides being an additional operational cost, the presence of large amounts of water and inerts in biomass used as a fuel, can result in problems related to the instability of the combustion and the accumulation of ash or rock that have to be removed and discarded. The objective of this paper is to review the main parameters that influence the quality of biomass, while analysing the current state-of-the-art power generation from the biomass sector in Portugal, as a new contribution to earlier studies.
Biomass is the most widely used renewable energy source in the world today. It is used mostly in solid form and, to a lesser extent, in the form of liquid fuels and gas. The utilization of biomass for energy production has increased at only a modest rate in modern times. Biomass is the major source of energy in rural Turkey. Biomass is used to meet a variety of energy needs, including generating electricity, heating homes, fueling vehicles and providing process heat for industrial facilities. Biomass potential includes wood, animal and plant wastes. Among the biomass energy sources, fuel wood seems to be the most interesting because its share of the total energy production of Turkey is high at 14%. The total biomass energy potential of Turkey is about 33 million tons of oil equivalents (Mtoe). The amount of usable biomass potential of Turkey is approximately 17 Mtoe. The electrical production potential from usable bioenergy sources are 73 MW in 2010 and corporate income and represent more than 280,000 jobs. This study shows that there is important biomass energy potential for climate change mitigation and energy sustainability in Turkey. (C) 2017 Elsevier Ltd. All rights reserved.
Three-dimensional (3D) carbon materials derived from waste biomass have been attracted increasing attention in catalysis and materials science because of their great potential of catalyst supports with respect to multi-functionality, unique structures, high surface area, and low cost. Here, we present a facile and efficient way for preparing 3D heterogeneous catalysts based on vertical MnO2 wires deposited on hemp-derived 3D porous carbon. The 3D porous carbon materials are fabricated by carbonization and activation processes using hemp (Cannabis Sttiva L). These 3D porous carbon materials are employed as catalyst supports for direct deposition of vertical MnO2 wires using a one-step hydrothermal method. The XRD and XPS results reveal the crystalline structure of alpha-MnO2 wires. The resultant composites are further employed as a catalyst for glycolysis of poly(ethylene terephthalate) (PET) with high conversion yield of 98%, which is expected to be expressly profitable for plastics recycling industry. (C) 2017 Elsevier B.V. All rights reserved.
Greenhouse gas emissions in the transport sector can significantly be reduced by replacing fossil based fuels with green alternatives. Various alternative fuel concepts have been developed differing in used sustainable feedstock, synthesis technology and final fuel characteristics. Whether these fuels can succeed in the market will depend on the fuel net production costs, the expected cost reduction potentials and the political intention to mitigate climate change. Results of previous studies for the techno-economic assessment of alternative fuels are difficult to compare due to significant differences in the applied methodology, level of detail and key assumptions in terms of economic factors and market prices. In this work, a standardized methodology for techno-economic analysis of fuel production processes is presented and exemplarily applied on sustainable fuels from Fischer-Tropsch (FT) synthesis. The methodology was adapted from a best practice approach from chemical industry and consists of three main steps: (A) literature survey on feasible production designs, (B) flowsheet simulation and (C) techno-economic assessment with the in-house software tool TEPET (Techno-Economic Process Evaluation Tool). It is shown that the standardized approach enables qualitative and quantitative statements regarding the technical and economic feasibility of fuel synthesis concepts including the identification of the appropriate fuel production concept due to predefined framework conditions. Results from the case study on green FT fuels reveal that Biomass-to-Liquid (BtL) concepts have lowest production costs at high electricity costs, whereas the Power-to-Liquid (PtL) and Power and Biomass-to-Liquid (PBtL) concepts are superior at low electricity prices. Fuel production costs in the range of 1.2 and 2.8 (sic)(2014)/1 were estimated. (C) 2016 Elsevier Ltd. All rights reserved.
Controversy exists regardingwhether violent shaking is harmful to infants in the absence of impact. In this study, our objective was to characterize the biomechanical response of the infant head during shaking through use of an instrumented anthropomorphic test device (commonly referred to as a "crash test dummy'' or surrogate) representing a human infant and having improved biofidelity. A series of tests were conducted to simulate violent shaking of an infant surrogate. The Aprica 2.5 infant surrogate represented a 5th percentile Japanese newborn. A 50th percentile Japanese adult male was recruited to shake the infant surrogate in the sagittal plane. Triaxial linear accelerometers positioned at the center of mass and apex of the head recorded accelerations during shaking. Five shaking test series, each 3-4 sec in duration, were conducted. Outcome measures derived from accelerometer recordings were examined for trends. Head/neck kinematics were characterized during shaking events; mean peak neck flexion was 1.98 radians (113 degrees) and mean peak neck extension was 2.16 radians (123 degrees). The maximum angular acceleration across all test series was 13,260 radians/sec 2 (during chin-to-chest contact). Peak angular velocity was 105.7 radians/sec (during chin-to-chest contact). Acceleration pulse durations ranged from 72.1 to 168.2ms. Using an infant surrogate with improved biofidelity, we found higher angular acceleration and higher angular velocity than previously reported during infant surrogate shaking experiments. Findings highlight the importance of surrogate biofidelity when investigating shaking.
This brief presents a submicrowatt, offset-free, and implantable system for a biomedical capacitive sensor. The system is powered by a 13.56-MHz radio frequency signal and performs sensor signal amplification, analog-to-digital conversion, and load-shift keying uplink data transmission within 640 mu s. An ultralow-power capacitance-to-digital converter (CDC) is designed by replacing a power-hungry operational amplifier with a subthreshold inverter in a switched-capacitor amplifier (SC-amp). A fast-response-gain compensation method is employed to reduce the gain error of the SC-amp while achieving high energy efficiency for the CDC. To eliminate the offset, a two-step autocalibration is applied. The application-specific integrated circuit is implemented in the Taiwan Semiconductor Manufacturing Company 90-nm complementary metal-oxide-semiconductor technology, and the whole system achieves an 8.02 effective number of bits with 9-bit linearity while consuming only 5.5 mu W.
Background: The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. Results: In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. Conclusions: A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl. obolibrary. org/obo/ dron. owl. A smaller version without NDCs is available at: http://purl. obolibrary. org/obo/dron/dron-lite. owl
In the present paper, an operational amplifier (Op-Amp) topology that achieves high-gain and low- power dissipation is designed and analyzed. The design uses a current mirror with a class-A output stage having capacitive Miller compensation. The low power operational amplifier is the main active power consuming block. The proposed Op-Amp operates at +/- 0.75V supply voltage and consumes a total power of 1.83mW with the gain >= 90dB. The proposed design has been implemented using Tanner EDA Tools for 90nm CMOS technology node.
Finger vein recognition has drawn increasing attention from biometrics community due to its security and convenience. In this paper, a novel discriminative binary codes (DBC) learning method is proposed for finger vein recognition. First of all, subject relation graph is built to capture correlations among subjects. Based on the relation graph, binary templates are transformed to describe vein characteristics of subjects. To ensure that templates are discriminative and representative, graph transform is formulated into an optimization problem, in which the distance between templates from different subjects is maximized and templates provide maximum information about subjects. At last, supervised information for training instances is provided by the obtained binary templates, and SVMs are trained as the code learner for each bit. Compared with existing binary codes for finger vein recognition, DBC are more discriminative and shorter. In addition, they are generated with considering the relationships among subjects which may be useful to improve performance. Experimental results on PolyU database and MLA database demonstrate the effectiveness and efficiency of DBC for finger vein recognition and retrieval.
Calcium carbonate skeletal tissues in metazoans comprise a small quantity of occluded organic macromolecules, mostly proteins and polysaccharides that constitute the skeletal matrix. Because its functions in modulating the biomineralization process are well known, the skeletal matrix has been extensively studied, successively via classical biochemical approaches, via molecular biology and, in recent years, via transcriptomics and proteomics. The optimistic view that the deposition of calcium carbonate minerals requires a limited number of macromolecules has been challenged, in the last decade, by high throughput approaches. Such approaches have made possible the rapid identification of large sets of mineral-associated proteins, i.e., 'skeletal repertoires' or 'skeletomes', in several calcifying animal models, ranging from sponges to echinoderms. One of the consequences of this expanding set of data is that a simple definition of the skeletal matrix is no longer possible. This increase in available data, however, makes it easier to compare skeletal repertoires, shedding light on the fundamental evolutionary mechanisms affecting matrix components. (C) 2016 Elsevier Inc. All rights reserved.
In this paper a detailed mathematical and physical model is presented in order to calculate the impedance of a tooth. The proposed model is based in an op-amp balanced Wien bridge oscillator and a voltage divider. From the amplitude of the signal and the phase shift we can calculate the resistance and the capacitance of a tooth.
The discovery of the importance of kinase activity and its relationship to the emergence and proliferation of cancer cells, due to changes in normal physiology, opened a remarkable pathway for the treatment of chronic myelogenous leukemia through intense search of drug candidates. Six Abl kinase inhibitors have received the US FDA approval as chronic myelogenous leukemia treatment, and continuous efforts in obtaining new, more effective and selective molecules are being carried out. Herein we discuss the mechanisms of Abl inhibition, structural features and ligand/protein interactions that are important for the design of new Abl kinase inhibitors. This review provides a broad overview of binding mode predictions, through molecular docking, which can be an approach to discover novel Abl kinase inhibitors.
Sialic acid sugars that terminate cell-surface glycans form the ligands for the sialic acid binding immunoglobulin-like lectin (Siglec) family, which are immunomodulatory receptors expressed by immune cells. Interactions between sialic acid and Siglecs regulate the immune system, and aberrations contribute to pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between living cells are difficult to study owing to a lack of specific tools. Here, we report a glycoengineering approach to remodel the sialic acids of living cells and their binding to Siglecs. Using bioorthogonal chemistry, a library of cells with more than sixty different sialic acid modifications was generated that showed dramatically increased binding toward the different Siglec family members. Rational design reduced cross-reactivity and led to the discovery of three selective Siglec-5/14 ligands. Furthermore, glyco-engineered cells carrying sialic acid ligands for Siglec-3 dampened the activation of Siglec-3(+) monocytic cells through the NF-kappa B and IRF pathways.
AimsThe aim of this study was to develop and evaluate a real-time PCR technology for microbiological control methods to examine individualized cell therapeutics, an emerging class of pharmaceutical formulations. Methods and ResultsOligonucleotide primers and hybridization probe for bacterial detection targeting the 16SrRNA gene were adapted based on Nadkarni etal. [Microbiology148 (2002) 257]. For detection of yeast and moulds, primers and probe were designed from conserved sequences of the 18SrRNA gene in this study. The real-time PCR assays were tested on genomic DNA of Escherichia coli and Candida albicans to assess efficiency and linear dynamic range. After successful establishment of robust real-time PCRs, applicability of the assays was evaluated by extracting microbial target DNA from cell-based preparations. Different commercial DNA extraction methods were compared identifying the MagNA Pure DNA Isolation Kit III as the method of choice. Sensitivity was examined for different strains and a detection limit of 10(2)-10(3) CFU per ml in a sample containing similar to 10(6) mammalian cells per ml was achieved. ConclusionsThis study reports the successful establishment of two qualitative real-time PCR assays, enabling in general the broad-range detection of microbial contaminants in a cell-based sample matrix. Significance and Impact of the StudyIndividualized cell therapeutics tend to have a short shelf life. Due to lengthy incubation periods, compendial testing according to current pharmacopoeial guidelines may not be applicable. We report a suitable alternative method upon which future microbiological quality control methods for such products could be based on. However, to implement valid rapid microbiological testing methods using real-time PCR technology, further challenges need to be addressed.
During embryogenesis, the spherical inner cell mass (ICM) proliferates in the confined environment of a blastocyst. Embryonic stem cells (ESCs) are derived from the ICM, and mimicking embryogenesis in vitro, mouse ESCs (mESCs) are often cultured in hanging droplets. This promotes the formation of a spheroid as the cells sediment and aggregate owing to increased physical confinement and cell-cell interactions. In contrast, mESCs form two-dimensional monolayers on flat substrates and it remains unclear if the difference in organization is owing to a lack of physical confinement or increased cell-substrate versus cell-cell interactions. Employing microfabricated substrates, we demonstrate that a single geometric degree of physical confinement on a surface can also initiate spherogenesis. Experiment and computation reveal that a balance between cell-cell and cell-substrate interactions finely controls the morphology and organization of mESC aggregates. Physical confinement is thus an important regulatory cue in the three-dimensional organization and morphogenesis of developing cells.
Context: Hypericum perforatum L., commonly known as St. John's wort, is practised as an alternative medicine against depression. Conversely, its remedial efficacy is indulged by various adverse effects that are recuperated in formulating nanoscaled commercial capsules encased by the biopolymer chitosan. A potential application of nanoencapsulation with regards to polymer enhances a slow controlled release of the targeted drug to achieve the desired delay until the right stimulus is obtained. Aims: To value synthesizing biopolymeric nanocomposites encapsulating St. John's wort commercial capsules substantiating it with a study of animal model of depression to endorse the effect of nanocapsulated drug as an effective brain drug. Methods The nanoparticulated suspension was prepared by ionic gelation technique and characterized to attest its antidepressant activity by in vivo studies. Results: The drug binding efficiency was endorsed by FT-IR studies and the nanoparticles were characterized by an average particle size of 211.4 nm with a positive zeta potential of 45.9 mV. The animal despair studies on depression induced mice models displayed a significant difference in the immobility time during force swimming and tail suspension test. The commercial capsules were administed orally (p.o., 50 and 100 mg/kg). The animal despair studies were substantiated with affirmative biochemical assessments like SOD, CAT, GP(x), GSH and LPO and compared with control groups. Conclusions: The outcomes of this work manifest the calibre of St. John's wort nanocomposites in a lower dosage that can alleviate depression and reduce side effects.
Building blocks made from renewable sources attract increasing attention for the design of new polymer systems. Recently, in this particular context, cellulose nanocrystals (CNCs) have gained great interest in both academic research and industry, mainly on account of their ability to reinforce range of polymer matrices and afford nanocomposites with attractive mechanical properties. The limited thermal stability of conventionally produced cellulose nanocrystals (CNCs) has, however, so far limited the range of polymers that could be used as basis for melt-processed CNC nanocomposites. We herein show that a commercially accessible nanocrystal source, a particular grade of microcrystalline cellulose (MCC), can easily be converted into thermally stable CNCs by ultrasonication in phosphoric acid. A scalable melt-mixing process was used to produce nanocomposites of these CNCs with a thermoplastic polyurethane (TPU) elastomer. A significant improvement of the room temperature storage modulus from 40 MPa (neat polymer) to 120 MPa (10% w/w CNC) was observed. The introduction of CNCs not only increased the stiffness of the polymer matrix, but also improved the shape memory properties of the nanocomposite. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45033.
In this paper, a new low power, low noise operational amplifier dedicated to implantable biomedical applications is introduced. The amplifier is designed to minimize input referred noise and power consnmption. To rednce inpnt thermal noise, we use the EKV Model to set the bias currents of the transistors. To rednce the flicker noise, PMOS inpnt transistors with large gate areas and operating in weak inversion are used. The noise rednction techniqne of switched biasing is then applied, which involves switching the transistor periodically between accnmnlation (cntoff) and inversion region. This helps to fnrther reduce the flicker noise of the transistors. The use of switched biasing allows ns to rednce the inpnt noise, withont having to increase the current and thus allows us to avoid the problem of trading power with noise. Using this techniqne, we are able to achieve an extremely low input noise of 2.89/mu V-rms in the desired bandwidth, at a small snpply cnrrent of 4.8/mu A. The additional circuitry required for switched biasing consumes minimal power, and the average power consnmption of the amplifier is 15.174/mu W, which makes it ideal for implantable applications. The gain of the amplifier is 76.2dB in the required frequency range, with a phase margin of 74 degrees and a CMRR greater than 120dB at all frequencies. The circuit is designed using the TSMC 0.18/mu m process, in the Analog Design Environment of Cadence Virtuoso. The performance of the circuit is studied at all process corners, namely TT, FF, SS, SF and FS. The simulations are carried out at 36.9 degrees C, the normal human body temperature.
Industrialization of mammalian cell culture has been achieved by integrating knowledge from several applying core concepts of chemical engineering, cellular and molecular biology, and biochemistry. Modeling has been applied to biological and physical processes to gain additional insights into such processes. This article covers modeling of the bioreactor and metabolic processes as it applies to bioprocess. Hydrodynamics of a bioreactor is briefly described while additional focus is given to gas-liquid mass transfer. Biological modeling is presented in the order of increasing complexity. First steady state models are presented followed by dynamic models, cybernetic models, and finally bioreactor integrated models. The closing discussion summarizes challenges of implementation of model-based approaches in the biopharmaceutical industry. (c) 2016 American Institute of Chemical Engineers AIChE J, 63: 398-408, 2017
Recombinant consensus interferon (CIFN) is a therapeutic protein with molecular weight of 19.5kDa having broad spectrum antiviral activity. Recombinant human CIFN (rhCIFN) has previously been expressed in Escherichia coli using isopropyl--d-thiogalactopyranoside (IPTG), a non-metabolizable and expensive compound, as inducer. For economical and commercial-scale recombinant protein production, it is greatly needed to increase the product yield in a limited time frame to reduce the processing cost. To reduce the cost of production of rhCIFN in E. coli, induction was accomplished by using lactose instead of IPTG. Lactose induction (14g/L) in shake flask experiment resulted in higher yield as compared with 1mM IPTG. Finally, with single-step purification on DEAE sepharose, 150mg/L of >98% pure rhCIFN was achieved. In the present study, an attempt was made to develop a low cost process for producing quality product with high purity. Methods devised may be helpful for pilot-scale production of recombinant proteins at low cost. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
We analyzed 115 iliac crest bone marrow biopsy specimens from 101 patients with metastatic castration resistant prostate cancer, divided into a test (n = 57) and a validation (n = 58) set. We developed a score based on computed tomography Hounsfield units and lactate dehydrogenase levels, which were associated with a positive biopsy result. The score can be used to select patients for whom a bone marrow biopsy will provide tissue for molecular characterization. Background: The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of clinical and imaging criteria could maximize tissue acquisition from bone marrow biopsies (BMBs). We aimed to develop a score for the selection of patients undergoing BMB. Materials and Methods: A total of 115 BMBs were performed in 101 patients: 57 were included in a derivation set and 58 were used as the validation set. The clinical and laboratory data and prebiopsy computed tomography parameters (Hounsfield units [HUs]) were determined. A score for the prediction of biopsy positivity was developed from logistic regression analysis of the derivation set and tested in the validation set. Results: Of the 115 biopsy specimens, 75 (62.5%) were positive; 35 (61.4%) in the test set and 40 (69%) in the validation set. On univariable analysis, hemoglobin (P = .019), lactate dehydrogenase (P = .003), prostate specific antigen (P = .005), and mean HUs (P = .004) were selected. A score based on the LDH level (>= 225 IU/L) and mean HUs (>= 125) was developed in multivariate analysis and was associated with BMB positivity in the validation set (odds ratio, 5.1; 95% confidence interval, 1.9%-13.4%; P = .001). The area under the curve of the score was 0.79 in the test set and 0.77 in the validation set. Conclusion: BMB of the iliac crest is a feasible technique for obtaining tumor tissue for genomic analysis in patients with castration-resistant prostate cancer metastatic to the bone. A signature based on the mean HUs and LDH level can predict a positive yield with acceptable internal validity. Prospective studies of independent cohorts are needed to establish the external validity of the score. (C) 2016 The Author(s). Published by Elsevier Inc.
Background: Driven by a range of sustainability challenges, e.g. climate change, resource depletion and expanding populations, a circular bioeconomy is emerging and expected to evolve progressively in the coming decades. South Africa along with other BRICS countries (Brazil, Russia, India and China) represents the emerging bioeconomy and contributes significantly to global sugar market. In our research, South Africa is used as a case study to demonstrate the sustainable design for the future biorefineries annexed to existing sugar industry. Detailed techno-economic evaluation and Life Cycle Assessment (LCA) were applied to model alternative routes for converting sugarcane residues (bagasse and trash) to selected biofuel and/or biochemicals (ethanol, ethanol and lactic acid, ethanol and furfural, butanol, methanol and Fischer-Tropsch synthesis, with co-production of surplus electricity) in an energy self-sufficient biorefinery system. Results: Economic assessment indicated that methanol synthesis with an internal rate of return (IRR) of 16.7% and ethanol-lactic acid co-production (20.5%) met the minimum investment criteria of 15%, while the latter had the lowest sensitivity to market price amongst all the scenarios. LCA results demonstrated that sugarcane cultivation was the most significant contributor to environmental impacts in all of the scenarios, other than the furfural production scenario in which a key step, a biphasic process with tetrahydrofuran solvent, had the most significant contribution. Conclusion: Overall, the thermochemical routes presented environmental advantages over biochemical pathways on most of the impact categories, except for acidification and eutrophication. Of the investigated scenarios, furfural production delivered the inferior environmental performance, while methanol production performed best due to its low reagent consumption. The combined techno-economic and environmental assessments identified the performance- limiting steps in the 2G biorefinery design for sugarcane industry and highlighted the technology development opportunities under circular bioeconomy context.
Bioremediation plays an important role in oil spill management and bio-electrochemical treatment systems are supposed to represent a new technology for both effective remediation and energy recovery. Diesel removal rate increased by four times in microbial fuel cells (MFCs) since the electrode served as an electron acceptor, and high power density (29.05 W m(-3)) at current density 72.38 A m(-3) was achieved using diesel (v/v 1%) as the sole substrate. As revealed by Scanning electron microscope images, carbon fibres in the anode electrode were covered with biofilm and the bacterial colloids which build the link between carbon fibres and enhance electron transmission. Trace metabolites produced during the anaerobic biodegradation were identified by gas chromatography-mass spectrometry. These metabolites may act as emulsifying agents that benefit oil dispersion and play a vital role in bioremediation of oil spills in field applications. (C) 2017 Elsevier Ltd. All rights reserved.
Here, we aimed our attention at the synthesis of carbon dots (C-dots) with the ability to interact with DNA to suggest an approach for the detection of DNA damage. Primarily, C-dots modified with amine moieties were synthesized using the one-step microwave pyrolysis of citric acid in the presence of diethylenetriamine. The C-dots showed strong photoluminescence with a quantum yield of 4%. In addition, the C-dots (2.8 +/- 0.8 nm) possessed a good colloidal stability and exhibited a positive surface charge (zeta=36 mV) at a neutral pH. An interaction study of the C-dots and the DNA fragment of lambda bacteriophage was performed, and the DNA binding resulted in changes to the photoluminescent and absorption properties of the C-dots. A binding of the C-dots to DNA was also observed as a change to DNA electrophoretic mobility and a decreased ability to intercalate ethidium bromide (EtBr). Moreover, the Forster (or fluorescence) resonance energy transfer (FRET) between the C-dots and EtBr was studied, in which the C-dots serve as an excitation energy donor and the EtBr serves as an acceptor. When DNA was damaged using ultraviolet (UV) radiation (lambda=254 nm) and hydroxyl radicals, the intensity of the emitted photoluminescence at 612 nm significantly decreased. The concept was proved on analysis of the genomic DNA from PC-3 cells and DNA isolated from melanoma tissues.
This paper presents a low-power, low-noise CMOS instrumentation amplifier intended for use in wireless bio-potential monitoring system. It employs a capacitively-coupled topology to achieve high power efficiency. In order to depress the noise, chopper-stabilized technique is used and a transconductance-boost technique is introduced in low-noise amplifier (LNA). All MOS transistors implemented in LNA are biased in subthreshold region with a supply voltage of 0.5 V to reduce the power consumption. Moreover, a DC-servo loop (DSL) is implemented to realize a high-pass corner for electrode offset cancellation. Implemented in a 0.18 mu m CMOS process, the front-end circuit occupies 0.48 mm(2) and draws 1.5 mu A. The capacitively-coupled chopper-stabilized instrumentation amplifier (CCIA) draws 800 nA and its input-referred noise is 3.5 mu V-rms integrated from 0.5 to 1 kHz, which results in a NEF of 3.8 and a PEF of 7.2 respectively. The whole circuit achieves 98 dB CMRR and 73 dB PSRR. The total input-referred noise of the front-end instrumentation amplifier including the DSL is 4.3 mu V-rms integrated from 0.5 to 1 kHz. (C) 2016 Elsevier Ltd. All rights reserved.
Foodborne pathogens have been a cause of a large number of diseases worldwide and more so in developing countries. This has a major economic impact. It is important to contain them, and to do so, early detection is very crucial. Detection and diagnostics relied on culture-based methods to begin with and have developed in the recent past parallel to the developments towards immunological methods such as enzyme-linked immunosorbent assays (ELISA) and molecular biology-based methods such as polymerase chain reaction (PCR). The aim has always been to find a rapid, sensitive, specific and costeffective method. Ranging from culturing of microbes to the futuristic biosensor technology, the methods have had this common goal. This review summarizes the recent trends and brings together methods that have been developed over the years.
Unwanted immune responses to therapeutic proteins can severely impact their safety and efficacy. Studies show that the presence of trace amounts of host cells and process-related impurities that stimulate pattern recognition receptors (PRR) can cause local inflammation and enhance product immunogenicity. Here we used purified PRR agonists as model impurities to assess the minimal level of individual innate immune response modulating impurities (IIRMIs) that could activate a local immune response. We show that levels of endotoxin as low as 10 pg (0.01 EU), 1 ng for polyinosinic: polycytidylic acid (PolyI: C), 100 ng for synthetic diacylated liopprotein, thiazoloquinolone compound, or muramyl dipeptide, 1 mg for flagellin or b-glucan, or 5 mg for CpG-oligodeoxynucleotide increased expression of genes linked to innate immune activation and inflammatory processes in the skin of rhesusmacaques. Furthermore, spiking studies using rasburicase as a model therapeutic showed that the levels of PRR agonists that induced detectable gene upregulation in the skin were associated with increased immunogenicity for rasburicase. This study underscores the need for testing multiple IIRMIs in biologics, strengthening the connection between the local mRNA induction in skin, innate immune activation, and antibody development in primates, and provides an indication of the levels of IIRMI in therapeutic products that could impact product immunogenicity. Published by Elsevier Inc. on behalf of the American Pharmacists Association.
In the nearly 20 years since Rabinow's 1996 "Artificiality and Enlightenment: From Sociobiology to Biosociality," scholarly attention to biosociality and related concepts such as biological citizenship have expanded Foucault's theories of biopolitics, updating them-as it were-for the 21st century. In this commentary, I explicate these "new biopolitical theories" and propose a schema for operationalizing them for deductive analyses in ethnographic research. I illustrate the way this schema may be applied with examples from an ethnographic study on autism in Italy. In doing so, I provide a model of new biopolitical theory that can be used in future projects in a variety of research settings and put scholarship on biosocialities and biological citizenships in more explicit conversation with each other. Such robust conversation will further scholarly understanding of biopolitics in general and of the local particularity of biologies, biomedicines, and politics that affect them.
Innovations in novel enzyme discoveries impact upon a wide range of industries for which biocatalysis and biotransformations represent a great challenge, i. e., food industry, polymers and chemical industry. Key tools and technologies, such as bioinformatics tools to guide mutant library design, molecular biology tools to create mutants library, microfluidics/microplates, parallel miniscale bioreactors and mass spectrometry technologies to create high-throughput screening methods and experimental design tools for screening and optimization, allow to evolve the discovery, development and implementation of enzymes and whole cells in (bio) processes. These technological innovations are also accompanied by the development and implementation of clean and sustainable integrated processes to meet the growing needs of chemical, pharmaceutical, environmental and biorefinery industries. This review gives an overview of the benefits of highthroughput screening approach from the discovery and engineering of biocatalysts to cell culture for optimizing their production in integrated processes and their extraction/ purification.
Biocatalysis is a fundamental concept in biotechnology. The topic integrates knowledge of several disciplines; therefore, it was included in the course " design and optimization of biological systems" which is offered in the biochemistry curricula. We selected the ciliate tetrahymena as an example of a eukaryotic system with potential for the biotransformation of sterol metabolites of industrial interest; in particular, we focused on the conversion of cholesterol to provitamin D-3. The students work with wild type and recombinant strains and learn how sterol pathways could be modified to obtain diverse sterol moieties. During the course the students identify and measure the concentration of sterols. They also search for related genes by bioinformatic analysis. Additionally, the students compare biotransformation rates, growing the ciliate in plate and in a bioreactor. Finally, they use fluorescence microscopy to localize an enzyme involved in biotransformation. The last day each team makes an oral presentation, explaining the results obtained and responds to a series of key questions posed by the teachers, which determine the final mark. In our experience, this course enables undergraduate students to become acquainted with the principles of biocatalysis as well as with standard and modern techniques, through a simple and robust laboratory exercise, using a biological system for the conversion of valuable pharmaceutical moieties. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2): 105- 114, 2017.
This study questions the presumed relation between formal schooling and scientific literacy about biotechnologies. Comparing science and nonscience majors ' knowledge of and attitudes toward biotechnological applications, conclusions are drawn if their formal learnings improve pupils ' understandings of and attitudes toward biotechnology applications. Sample of the study consists of 403 undergraduate and graduate students, 198 nonscience, and 205 science majors. The Biotechnology Knowledge Questionnaire and the Biotechnology Attitude Questionnaire were administered. Descriptive statistics ( mean and percentages), t test, and correlations were used to examine the participants ' knowledge of biotechnology and attitudes toward biotechnological applications and differences as regards their majors. Although the science majors had higher knowledge and attitude scores than the nonscience majors, it is not possible to say that they have sufficient knowledge of biotechnologies. Besides, the participants ' attitudes toward biotechnological applications were not considerably related to their knowledge of biotechnology. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45( 2): 115- 125, 2017.
This study evaluated the effect of an aluminosilicate mineral additive-Biotite V (BV) on growth performance, the immunological and adrenal responses in weaned pigs after Escherichia coli lipopolysaccharide (LPS) challenge. Thirty-two crossbred weaned pigs were used in this 2x2 factorial experiment, with dietary treatment (basal diet with or without 0.45% BV supplementation) and LPS challenge (challenged or not challenged) as two main factors. On day 14 and 21, pigs were injected intraperitoneally with either 100 mu g/kg body weight of LPS or an equivalent amount of sterile saline. Blood samples were collected 3 h after the first challenge followed by total and differential leukocyte counts and analysis of plasma tumor necrosis factor-alpha (TNF-alpha), prostaglandin E-2 (PGE(2)), cortisol, insulin, and biochemical parameters. Body weight and feed intake were measured weekly throughout the 4-week experiment. The results showed that both LPS challenges reduced average daily gain (ADG) (P < 0.05) and increased feed/gain (P < 0.001), and BV decreased feed/gain (P < 0.05) of immunology challenged pigs. The LPS challengexdiet interactions were observed for ADG (P < 0.05) and feed/gain (P < 0.05) during both challenge. LPS challenge reduced the number of white blood cells, lymphocytes, monocytes, and neutrophils (P < 0.05). LPS challengexdiet interaction was observed for plasma TNF-alpha (P < 0.05) concentration, showing decreased plasma TNF-alpha response to LPS challenged in pigs receiving BV. But no LPS challenge x diet interaction was observed for plasma cortisol or PGE(2). There was a diet effect for plasma insulin (P < 0.05) and glucose (P < 0.05), showing increased plasma insulin and decreased glucose with BV supplementation, but no LPS challengexdiet interaction was observed. We conclude that BV improved the weight gain and feed efficiency of weaned pigs during an immunological challenge by suppressing the proinflammatory cytokine release.
The synergistic effect between displacement damage dose (DDD) and analog transient radiation effects on electronics (ATREE) in an operational amplifier (LM124) (opamp) from three different manufacturers is investigated. Pulsed X-ray experiments have highlighted ATREE sensitivity on devices significantly more important following exposure to fission neutrons than for unirradiated devices. A previously developed simulation tool is used to model ATREE responses taking into account the electrical parameters degradation due to displacement damage phenomenon. A good agreement is observed between model outputs and experimental ATREE results.
The influence of external circuit designs on ASET shapes in a high speed current feedback amplifier (CFA) (AD844) is investigated by means of the pulsed laser single event effect (PLSEE) simulation technique. Changes of the feedback resistors modify circuit's electrical parameters such as closed-loop gain and bandwidth, affecting amplifier stability and so ASET shapes. Qualitative explanations based on general electronic rules and feedback theories enable the understanding of a CFA operation establishing a correlation between the evolution of external feedback resistor values and ASET parameters. TID effects on the ASET sensitivity in AD844 CFA are also investigated in this work highlighting different behaviors according to the impacted bipolar transistor in the integrated circuit.
The propagation of Analog Single Event Transients (ASETs) to multiple outputs of Bipolar Junction Transistor (BJTs) Integrated Circuits (ICs) is reported for the first time. The results demonstrate that ASETs can appear at several outputs of a BJT amplifier or comparator as a result of a single ion or single laser pulse strike at a single physical location on the chip of a large-scale integrated BJT analog circuit. This is independent of interconnect cross-talk or charge-sharing effects. Laser experiments, together with SPICE simulations and analysis of the ASET's propagation in the s-domain are used to explain how multiple-output transients (MOTs) are generated and propagate in the device. This study demonstrates that both the charge collection associated with an ASET and the ASET's shape, commonly used to characterize the propagation of SETs in devices and systems, are unable to explain quantitatively how MOTs propagate through an integrated analog circuit. The analysis methodology adopted here involves combining the Fourier transform of the propagating signal and the current-source transfer function in the s-domain. This approach reveals the mechanisms involved in the transient signal propagation from its point of generation to one or more outputs without the signal following a continuous interconnect path.
Objective: To examine emotion processing in euthymic bipolar patients (EBP) compared to healthy controls. In addition, to determine whether or not there is an association between emotion processing and psychosocial functioning. Material and methods: A sample of 60 EBP and 60 healthy controls matched for age, gender, education level, and premorbid intelligence were studied. All subjects were assessed using the MATRICS Consensus Cognitive Battery (MCCB) and two additional executive function measures: the Trail Making Test-Part B and the Stroop Test. Emotion processing was examined using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Psychosocial functioning was assessed using the Functional Assessment Short Test (FAST). Results: Euthymic bipolar patients obtained lower scores than controls in all MSCEIT measures except for the using emotions branch. Likewise, EBP obtained a worse performance than healthy controls in all neurocognitive domains. Correlation between MSCEIT strategic area measures and FAST total score was found (r = -0.311; P < 0.016). Regression analysis showed that residual depressive symptomatology explains a 9.1% of the variance in functional outcome. MSCEIT strategic area score explained an additional 8.6%. Neurocognition did not increase the percentage of the variance explained by emotion processing. Conclusions: Euthymic bipolar patients exhibit deficits in emotion processing. Emotion processing is associated with social functioning in these patients.
Background: Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. Methods/ design: This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-SaloveyCaruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. Discussion: The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma
Objectives: Emotional processing abnormalities have been implicated in bipolar disorder (BD) but studies are typically small and uncontrolled. Here, facial expression recognition was explored in a large and naturalistically recruited cohort of BD patients. Methods: 271 patients with BD completed the facial expression recognition task. The effects of current medication together with the influence of current mood state and diagnostic subtype were assessed whilst controlling for the effects of demographic variables. Results: Patients who were currently receiving treatment with lithium demonstrated significantly poorer accuracy in recognising angry faces, an effect that held in a monotherapy sub-analysis comparing those participants on lithium only and those who were medication-free. Accuracy in recognising angry faces was also lower amongst participants currently taking dopamine antagonists (antipsychotics). Higher levels of current depressive symptoms were linked to poorer accuracy at identifying happy faces. Conclusion: Use of lithium and possibly dopamine antagonists may be associated with reduced processing of anger cues in BD. Findings support the existence of mood-congruent negative biases associated with depressive symptoms in BD. Observational cohort studies provide opportunities to explore the substantial effects of demographic, psychometric and clinical variables on cognitive performance and emotional processing.
In patients with major depressive disorder or bipolar disorder, abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate and gamma-aminobutyric acid have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic-dose ketamine has led to a collection of studies that have examined neurochemical (e.g., glutamatergic and gamma-aminobutyric acidergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation.
Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors.
Background: Bipolar disorder is a common chronic illness characterized by high levels of morbidity and all-cause mortality. Lithium is one of the gold standard mood stabilizer treatments, but the identification of good, partial and non-responders in clinical settings is inconsistent. Methods: We used an established rating scale (the Alda scale) to classify the degree of lithium response (good response, partial response, non-response) in a large, multicentre clinically representative sample of well-characterized cases of bipolar disorders I and II. Next, we examined previously reported clinical predictors of response to determine which factors significantly differentiated between the three response groups. Results: Of 754 cases, 300 received lithium, for at least 6months, as a treatment for bipolar disorder (40%). Of these cases, 17% were classified as good response, 52% as partial response and 31% as non-response. Lifetime history of mixed episodes (p=0.017) and alcohol use disorders (p=0.015) both occurred in >20% of partial response and non-response groups but <10% of good response cases. Family history of bipolar disorder I was of borderline statistical significance, being more frequent in the good response group (38%) compared with the non-response group (18%). There was a trend (p=0.06) for bipolar disorder II to be associated with non-response. Conclusions: Only three factors previously identified as predictors of lithium response significantly differentiated the response groups identified in our sample. Interestingly, these factors have all been found to co-occur more often than expected by chance, and it can be hypothesized that they may represent a shared underlying factor or dimension. Further prospective studies of predictors and the performance of the Alda scale are recommended.
Background: The relationship between Toxoplasma gondii infection and the development of bipolar disorder (BD) has long been investigated, yet to date it is still poorly understood and documented. The aim of this review is to derive a summary estimate of the strength of the association between infection with T. gondii and BD from the available published studies. Methods: A systematic review was performed using PubMed, LILACS, PsycINFO, and Embase databases. Studies which included a proportion of seropositive BD patients and controls were further examined in a meta analysis. Results: One hundred eighteen citations were initially retrieved. Thirteen studies were included in our systematic review. Eight out of these thirteen studies were included in our meta-analysis. Statistical analyses showed that T. gondii infection is associated with with BD (OR=1.26). Limitations: Small sample size was the major limitation among the studies that carried out serological analyses. In addition, the available studies did not have enough information on disease status/severity or type of bipolar disorder. Also, it was not possible to analyze pregnancy status or perinatal infection. Future studies addressing the aforementioned topics are clearly needed. Conclusions: Despite heterogeneous results, patients with BD are more likely to be infected by T. gondii than controls. Early T. gondii infection might predispose the development of BD. T.gondii infection is becoming clinically relevant in psychiatric disorders and future mechanistic studies are required to elucidate the underlying pathophysiological mechanisms.
Sleep disruptions represent a core feature of bipolar disorders and have been widely studied through the use of actigraphy, which is an objective measure of motor activity and sleep. Finding objective outcomes, which reliably measure sleep in bipolar disorders, is essential in developing better therapies and improving follow-up monitoring strategies. Our aim is to understand the role of actigraphy as an objective measure of sleep in bipolar disorder. We undertook a systematic review and meta-analysis on studies using actigraphy to detect changes in activity and sleep patterns in bipolar patients versus healthy controls. The primary outcome measures were the analyses of 'activity mean' and 'sleep duration'. As secondary outcomes we analysed 'sleep onset latency', 'sleep efficiency', and 'time awake after sleep onset'. Thirteen studies comprising 821 subjects met quality criteria for inclusion. The results show a decrease in activity mean and an altered pattern of sleep in bipolar patients. Further analyses suggest that the results might be generalized to a bipolar condition which underlies manic and depressed episodes as well as euthymic phases. This study highlights the role of actigraphy as an important objective tool for the ambulatory monitoring of sleep and activity in bipolar disorders. (C) 2016 Elsevier Ltd. All rights reserved.
Background. The different patterns of Emotional Intelligence (EI) deficits in schizophrenia and bipolar I disorder are are not yet well understood. This study compares EI levels among these groups and highlights the potential impact of non-social cognition on EI. Method. Fifty-eight schizophrenia and 60 bipolar outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score. Results. Compared to bipolar subjects, schizophrenia patients showed significantly lower levels in both EI and nonsocial cognition. After adjustment for the BACS composite score, the difference in EI was lost. The mediation analysis revealed that differences between schizophrenia and bipolar patients in strategic EI are almost fully attributable to the mediating effect of non-social cognition. Conclusions. Our findings suggest that in both schizophrenia and bipolar patients EI is strongly influenced by nonsocial cognitive functioning. This has to be taken into account when interpreting MSCEIT data in comparative studies in serious mental illness and emphasizes the importance of cognitive remediation.
The degradation of LM124J operational amplifier under the gamma-irradiation is studied for different dose rates and temperatures during irradiation. The results show that degradation of studied devices due to total ionizing dose effects continues to increase significantly, if the dose rate decreases below 0.01 rad(Si)/s, that is not typical for the most of bipolar devices. It can complicate the use of criteria of enhanced low dose rate sensitivity (ELDRS), which are defined by existing standards for radiation tests. The paper shows how to take into account such effects during radiation testing considering ELDRS.
Objective: Bipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where BR+BD not equal LR), resilience (HR not equal BD+LR), or illness (BD not equal HR+LR). Method: During functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth. Results: We found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporoparietal junction). Conclusion: If replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk.
Urban habitats are described as having an overall negative influence on many fitness-related traits in several bird species, but a vital function such as immunity remains poorly studied. The immune response is strongly linked to individual condition, which partly depends on resource availability and the parasitic context that often differ between urban and natural habitats. A difference between the immunity of populations dwelling in urban areas and populations from more natural habitats can, therefore, be hypothesized. We conducted a 2-year experimental study on great tits (Parus major) in urban and forest areas. We stimulated the constitutive immunity of nestlings and assessed both the inflammatory response by measuring the plasma levels of haptoglobin, an inflammatory marker, and its activation cost through the loss of body mass. In addition, we checked the nestlings for ectoparasites and assessed haemosporidian prevalence in adults. Nestlings from urban sites produced relatively less haptoglobin and lost more body mass than those from forest sites, which suggests that the activation of constitutive immunity is more costly for birds living in urban sites than for those living in the forest. We detected no ectoparasite in birds in both habitats. However, urban adults showed lower haemosporidian prevalence than forest ones, suggesting a reduced exposure to these parasites and their vectors in towns. Overall, our study provides evidence for an immune difference between urban and forest populations. Because immunity is crucial for organism fitness, it is of prime interest to identify causes and processes at the origin of this difference.
Introducing an animal into a new location could be hazardous in the form of disease transmission, especially with respect to infections that are often overlooked. Such introduced infectious agents, including parasitic ones, then pose potential danger to the native animal population. Within the conservation program, the European bison was introduced into many European countries. However, this largest European herbivore was recognized as a new host for an invasive parasitic nematode, Ashworthius sidemi, in Poland in 1998. Since then, the prevalence of this non-native parasite in Poland has increased not only in bison but also in other wild ruminants. In 2011 five European bison individuals were transported from Poland to the Czech Republic. In the current study, we examined the gastrointestinal tracts of two European bison and two red deer culled in the Z. idlov game reserve. A. sidemi was identified in all investigated animals using both morphological and molecular methods; infection intensity was higher in bison than in deer. Our findings represent the first record of this invasive parasite in European bison at the Czech territory. The results of this study indicate changes in epidemiological patterns of Ashworthius infections in the climatic condition of Central Europe as well as the need to verify the reliability of ashworthiosis intravital diagnostics. One can expect A. sidemi to spread gradually in the Czech Republic and colonize other native ruminant hosts.
In the present study, sediment was spiked with bisphenol A (BPA) solution to explore the interaction between indigenous bacterial communities and BPA biodegradation in sediment. Results showed that BPA could be adsorbed to the sediment and then biodegraded rapidly. Biodegradation efficiency of BPA in treatments with 10 and 50 mg/L BPA reached 64.3 and 61.8% on the first day, respectively. Quantitative polymerase chain reaction and denaturing gradient gel electrophoresis analysis indicated that BPA affected the densities, species, and diversities of bacteria significantly. The response of bacterial community to BPA favored BPA biodegradation by promoting the growth of BPA-reducing bacteria and inhibiting other competitors. According to the results of sequencing, Pseudomonas and Sphingomonas played vital roles in the degradation of BPA. They presented over 73% of the original bacterial community, and both of them were promoted by BPA comparing with controls. Laccase and polyphenol oxidase contributed to the degradation of BPA and metabolic intermediates, respectively. This paper illustrates the rapid biodegradation of BPA induced by the response of indigenous bacterial communities to the BPA stress, which will improve the understandings of BPA degradation in sediment.
Aberrant expression of EPH receptors and their ligands, ephrins, has been reported in a large variety of human cancers, including epithelial cancers from the colon and ovary. Due to the recently reported decrease or loss of EPHBs expression in colorectal carcinomas and the abundance of CpG sites in their promoters, we analyzed the promoter methylation status of three members of the EPHB family, EPHB2, EPHB3 and EPHB4, in a series of 22 colon cancer cell lines, as well as in four ovarian cancer cell lines and 56 ovarian tumor samples. The promoters of the three receptor genes were unmethylated in the vast majority of samples as assessed by methylation-specific polymerase chain reaction (MSP). These results were confirmed by direct bisulphite sequencing. Furthermore, from RT-PCR analyzes and Northern blotting, EPHB2 showed only small variation in RNA expression across ovarian cancer cell lines and clinical samples. We conclude that promoter hypermethylation of EPHB2, EPHB3 and EPHB4 is not a common event in colon and ovarian cancers and therefore plays no major role in these tumors.
Children represent a population at risk, because of their short size, their naivety and their attraction to animals. The face and hands are the most specific locations in young children. Wounds are often multiple. In more than half the cases, the child knows the animal, which are dogs and cats by frequency argument. The bite episode occurs mostly when the child is alone with the pet without direct supervision, while playing or stroking the animal. As in all bites, pediatric lesions are infectious, functional and aesthetic emergencies, but the goal of this work was primarily to make a point on principles of surgical management of animal bites in children, highlighting pediatric specificities. Animal bites require psychological, anesthetic and surgical treatment, adapted to the child, in a specialized structure. Hospitalization and general anesthesia are more frequent in children. Any suspicion of mistreatment (and/or abuse) should lead to the child's hospitalization, even if wounds do not justify monitoring in a surgical environment. Emergency surgery is essential to limit functional and aesthetic consequences. The healing capacities of the child and the frequent lack of co-morbidity allow a conservative surgical treatment with suture, repositioning skin flaps and controlled healing in the first place. Immobilization, drainage, and antibiotics will complete the surgery. The healing process, however, leads to a specific management during scar remodeling phase and growth. Psychological care of the child and parents should not be forgotten, and has to start at the same time as surgical treatment at in acute phase. (C) 2016 Elsevier Masson SAS. All rights reserved.
BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods. Serum antibodies against this polyomavirus were revealed using immunological techniques, which, however, cross-react with other polyomaviruses such as JC (JCPyV) and Simian Virus 40. These non-specific data indicate the need of novel immunological methods and new investigations to check in a specific manner, BKPyV spread in humans. To this aim, mimotopes from BKPyV structural capsid protein 1 (VP1) were employed for specific immunological reactions to IgG antibodies of human serum samples. An indirect enzyme-linked immunosorbent assay with synthetic peptides mimicking immunogenic epitopes of BKPyV VP1 was set up and employed to test sera of healthy adult subjects. Data from this innovative immunological assay indicate that serum antibodies against BKPyV VP1 mimotopes are detectable in healthy subjects ranging from 18 to 90 years old. The overall prevalence of serum samples that reacted to BKPyV VP1 mimotopes was 72%. The strong points from this investigation are the novelty of the immunological method, its simplicity of the approach, and the specificity of BKPyV antibody reaction to VP1 mimotopes.
Infections and malignancies are the expected complications of immunosuppressive therapy, which non-specifically impairs cellular and humoral immune responses in renal transplant recipients. Infections were usually frequent and severe during the early post-transplant period (first year). Recent diagnostic methods (molecular biology) and availability of new antivirals, antifungal and. antibiotic drugs made rapid diagnosis and systematic preventive strategies much easier and this resulted in a significant reduction of infections and infectious death in this population. However, new infectious agents like BK polyomavirus, hepatitis E virus, parvovirus (as well as Chigunkunya, West Nile and others in particular areas) were recently recognized as responsible of aggressive infections in the immunocompromised host. Malignancies are also common after transplantation, due to the intensity and duration of immunosuppression. Skin cancers and lymphoproliferative disorders are the most common and are undoubtedly caused by viral infections, but incidence of non-skin cancers is also increased. After reduction of immunosuppression, treatment is similar to non-transplant patients: Results are usually poor and cancer is now the third cause of death in transplant recipients. Due to their anti-proliferative and anti-tumoral properties, incidence of de novo cancer significantly decreased in patients receiving mTor inhibitors as maintenance immunosuppression; furthermore, in patients already diagnosed with Kaposi sarcoma or recurrent skin cancers, introduction of mTor was associated with stabilisation and/or regression of malignant lesions. (C) 2016 Association Societe de nephrologie. Published by Elsevier Masson SAS. All rights reserved.
Objective: The purpose of the present, prospective, cohort study was to monitor urine cytology samples from recipients of renal transplants to search for the occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to correlate the existence of these cells with molecular detection of polyomavirus BK (BKV) DNA in urine. Material and methods: This study included patients who underwent renal transplantation. Patients had their urine tested quarterly, during the first year post-transplantation, for the presence of decoy cells and degenerated cells, as well as by quantitative determination of BKV load in the urine and plasma. Results: Three hundred and sixty-one examinations were performed on 101 patients within 12 months of attendance. Urine cytology results were: 198 (54.9%) negative and 60 (16.6%) positive for the presence of viral cytopathic effects depending on the presence of BKV infection, 72 (19.9%) positive for the manifestation of degenerated cells and 31 (8.6%) unsatisfactory for analysis. There was a subtle tendency towards the presence of degenerated inclusion-bearing cells in cases in which the virus was detected in voided urine. However, the presence of degenerated cells exhibited a tendency to BKV positivity in months 3, 6 and 9 and, exclusively in month 12, this trend was statistically significant. Conclusions: There were not enough strong morphological and staining elements to state the origin of the degenerated cells or to describe the nature of the infection (viral or bacterial), given that these cells were undergoing an apoptotic process in post renal transplant patients.
Background. Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have not been previously associated with Trichinella nativa infection. Methods. Patient interviews and medical chart reviews were conducted on 10 men who became ill following consumption of a common source of black bear meat. Trichinella serology on patient sera as well as polymerase chain reaction (PCR) and larval identification of the meat samples was conducted. Results. All 10 exposed individuals developed an acute illness clinically compatible with trichinellosis, characterized by fever, abdominal pain, and diarrhea, along with eosinophilia ranging from 0.9 x 10(9)/L to 6.1 x 10(9)/L. Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-elevation myocardial infarction and sinus venous tract thrombosis occurred as a complication of trichinellosis in 2 patients. Acute serology was nonreactive in all patients, though convalescent serology was reactive in 6 of 8 (75%) patients for whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and was corroborated by microscopic larval identification. Conclusions. We report a 100% attack rate of T. nativa from bear meat among those who were exposed, and demonstrate that this species can cause serious thrombotic complications of trichinellosis in humans. Education of hunters and the public regarding the importance of proper preparation of wild game prior to ingestion is warranted.
Black rot, caused by Xanthomonas campestris pv. campestris (Pammel) Dowson (Xcc), is one of the most damaging diseases of cauliflower and other crucifers. In order to investigate the molecular resistance mechanisms and to find the genes related to black rot resistance in cauliflower, a suppression subtractive hybridization (SSH) cDNA library was constructed using resistant line C712 and its susceptible near-isogenic line C731 as tester and driver, respectively. A total of 280 clones were obtained from the library by reverse northern blotting. Sequencing analysis and homology searching showed that these clones represent 202 unique sequences. The library included many defense/disease-resistant related genes, such as plant defensin gene PDF1.2, lipid transfer protein, thioredoxin h. Gene expression profiles of 12 genes corresponding to different functional categories were monitored by real-time RT-PCR. The results showed that the expression induction of these genes in the susceptible line C712 in response to Xcc was quicker and more intense, while in C731 the reaction was delayed and limited. Our results imply that these up-regulated genes might be involved in cauliflower responses against Xcc infection. Information obtained from this study could be used to understand the molecular mechanisms of disease response in cauliflower under Xcc stress.
Instrumental test of black tea samples instead of human panel test is attracting massive attention recently. This study focused on an investigation of the feasibility for estimation of the color sensory quality of black tea samples using the VIS-NIR spectroscopy technique, comparing the performances of models based on the spectra and color information. In model calibration, the variables were first selected by genetic algorithm (GA); then the nonlinear back propagation-artificial neural network (BPANN) models were established based on the optimal variables. In comparison with the other models, GA-BPANN models from spectra data information showed the best performance, with the correlation coefficient of 0.8935, and the root mean square error of 0392 in the prediction set. In addition, models based on the spectra information provided better performance than that based on the color parameters. Therefore, the VIS-NIR spectroscopy technique is a promising tool for rapid and accurate evaluation of the sensory quality of black tea samples. (C) 2017 Elsevier B.V. All rights reserved.
Possible altered gene expression patterns in bladder tumour carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles. Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28 weeks. Equal numbers of control rats were given tap water without BBN. After treatment, the rat bladders were excised for RNA extraction and histopathological examinations. Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia. The atlas glass rat microarray was used, which included oligonucleotides of 1081 rat genes. Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting. Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs, and these included fly proto-oncogene, Lipocortin 2, COX IV, COX V a, and cathepsin D. Also, 15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1, TNFr1, APOA1 and VHL. The results of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles. The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.
To date, molecular evidence studies for bladder cancer, using the microarray technology, are focusing on the transitional cell carcinoma, however, similar fingerprinting studies have rarely been performed on the other molecular phenotypes of bladder cancer, squamous cell carcinoma (SCC). This study was conducted to monitor the gene expression profiles for bilharzial-related SCC of the bladder to be able to compare its data with transitional cell carcinoma microarray data. A total of 17 paired bilharzial urinary bladder SCC specimens and their corresponding normal urothelium were analyzed using the complementary deoxyribonucleic acid microarray hybridization approach to study the molecular basis of the development of SCC of the urinary bladder. Validation of the microarray results was performed using the Northern blotting technique. After supervised analysis of the microarray data, there was at least a 3-fold difference in the expression between SCC of the bladder and normal urothelium in 82 genes. A total of 38 genes were up-regulated in SCC of the bladder, including matrix degradation-related genes, growth factors, different oncogenes, and immunology related genes. Conversely, 44 genes were down-regulated in SCC of the bladder, including integrins, laminins, cadherins, nonmetastatic cell 1 (NM23) and apoptosis-related genes. Our findings can explain the aggressive behavior of SCC of the bladder. Such gene profiling studies will add to our understanding of the mechanisms of carcinogenesis, and may also improve our ability to diagnose and treat bladder cancer. (c) 2007 Elsevier Inc. All rights reserved.
Objective. - Comment the new WHO histological classification of tumors of the urinary system and male genital organs 2016 and expose the state of art about urothelial carcinogenesis and molecular modifications of bladder cancer, with the consequences on the treatments. Material and method. - A systematic review of the literature search was performed from the data base PubMed, focused on the following keywords: "bladder cancer", "molecular", "subtypes". Results. - The new WHO histological classification of tumors of the urinary system 2016 confirm the importance of pathology in determining the care of patients, especially the grade, the histological type and the infiltration, while taking into account the difficulties. In 2014, the Cancer Genome Atlas reported genetic modifications of bladder cancer. Recently, several studies explored molecular anomalies of bladder cancer and elaborated molecular classifications, analyzing their predictive value. According to the groups, different molecular subtype had been defined: Urobasal A, Urobasal B, genomically unstable, infiltrated, squamous cell carcinoma-like and p53-like luminal bladder cancers. This latter subgroup seems to be chemoresistant. Conclusions. - The molecular biology and classifications allow a better understanding of bladder cancer and could complete in near future histological data to improve patient management. (C) 2016 Elsevier Masson SAS. All rights reserved.
Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.
We sought to identify and validate a novel urinary autophagy transcript signature in patients with bladder cancer and evaluate its clinical utility. We performed an initial screening for seven autophagy transcript-based panel (autophagy-related protein 12 (ATG12); WD repeat domain, phosphoinositide interacting 2 (WIPI2); FYVE and coiled-coil domain-containing protein 1 (FYCO1); microtubule-associated protein light chain (MAPLC3); RB1-inducible coiled-coil 1 (RB1CC1); tachylectin-II-like beta-propeller domain 1 (TECPR1); and Unc-51-like kinase (ULK1)) that was identified based on bioinformatics analysis followed by SYBR Green-based polymerase chain reaction array validation in paired tissue and urine samples. Afterward, we evaluated the expression of differentially expressed autophagy transcripts in an independent validation set with reverse transcription quantitative real-time polymerase chain reaction in urine sediments of 140 patients with bladder cancer, 68 patients with benign urological lesions, and 74 healthy controls (age and sex matched). The expression levels of ATG12, FYCO1, TECPR1, and ULK1 in paired bladder tissue and urine samples were significantly lower in bladder cancer than in control group (p < 0.001). In the validation set, the receiver-operating characteristic curve analyses demonstrated that each urinary autophagy transcripts showed high sensitivity and specificity for distinguishing bladder cancer from non-bladder cancer patients (ATG12, 75.4% and 86.1%; FYCO1, 87% and 75.7%; ULK1, 85.5% and 75.6%; and TECPR1, 90% and 81.9%). We document and validate a novel autophagy transcript signature for human bladder cancer diagnosis: bilharzial and non-bilharzial types.
Background: Bladder cancer is a leading cause of morbidity and mortality. Despite recent advances in understanding its molecular biology, the 5-year survival for muscle-invasive disease (muscle-invasive bladder cancer [MIBC]) remains approximately 50%. Although neoadjuvant chemotherapy (NAC) offers an established 5% absolute survival benefit at 5 years, only the 40% of patients with a major tumor response appear to benefit. There remains, therefore, a critical unmet need for predictive markers to determine which patients are best managed with NAC, as well as for novel targeted therapies to overcome resistance to NAC. Methods: The NAC paradigm offers the optimal clinical context for developing precision therapy for MIBC. Abundant tissue is available for analysis before NAC in all patients and after NAC in patients with residual MIBC. Technologic advances have enabled next-generation sequencing and gene expression microarray analysis of routinely collected and even archived tissue specimens. These technologies provide a foundation for the identification of markers of chemoresistance and for the development of rational cotargeting strategies. Results: Modern computational methods allow for some measure of target validation, which can be enhanced by the use of patient-derived primary xenografts (PDX). These PDX can be established at the time of radical cystectomy after NAC if there is residual MIBC. By the time a patient recurs clinically, candidate drugs targeting specific molecular changes in the patient tumor and corresponding PDX would have been tested in the PDX model, and only the most efficacious drug(s) would be administered to the patient. Liquid biopsies in the form of circulating tumor DNA and circulating tumor cells allow noninvasive longitudinal monitoring of the molecular landscape of an advanced tumor as it is being treated with successive courses of systemic therapy. Conclusions: These tools combined form the foundation of an evidence-based precision oncology strategy for MIBC. (C) 2016 Elsevier Inc. All rights reserved
Objective: This study examined symptom reporting related to the 10th Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria for postconcussional syndrome (PCS) in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) Veterans. Our aims were to: (a) examine relationships among PCS symptoms by identifying potential subscales of the British Columbia Postconcussion Symptom Inventory (BC-PSI); and (b) examine group differences in BC-PSI items and subscales in Veterans with and without blast exposure, mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD). Method: Our sample included Veterans with blast-related mTBI history (n=47), with blast exposure but no mTBI history (n=20), and without blast exposure (n=23). Overall, 37 Veterans had PTSD, and 53 did not. We conducted an exploratory factor analysis (EFA) of the BC-PSI followed by multivariate analysis of variance to examine differences in BC-PSI subscale scores by blast exposure, mTBI history, and PTSD. Results: BC-PSI factors were interpreted as cognitive, vestibular, affective, anger, and somatic. Items and factor scores were highest for Veterans with blast exposure plus mTBI, and lowest for controls. Vestibular, affective, and somatic factors were significantly higher for Veterans with blast exposure plus mTBI than for controls, but not significantly different for those with blast exposure but no mTBI. These results remained significant when PTSD symptom severity was included as a covariate. Cognitive, anger, and somatic subscales were significantly higher for Veterans with PTSD, though there was no interaction effect of PTSD and mTBI or blast history. Conclusions: EFA-derived subscales of the BC-PSI differentiated Veterans based on blast exposure, mTBI history, and PTSD.
The extraction of molten iron and slag in the liquid phase from the lower part of a blast furnace (hearth) is usually accomplished according to operational experience and involves a high degree of uncertainty, mainly because the liquid level cannot be directly measured. This study presents a methodology for obtaining multistep models to forecast the hearth liquid level by measuring a voltage generated on the blast furnace shell, which is strongly correlated with the hearth liquid level. The results show that this electrical signal is a nonstationary and nonlinear time-series that, after appropriate treatment, can be represented by a time-delay neural network (TDNN) model. Some comparisons are made with linear time-series models represented by an autoregressive moving average model and a seasonal autoregressive integrated moving average model, and the results indicate that the TDNN model provides better forecasting performance up to one hour ahead. Note to Practitioners-This work was motivated by the need for better knowledge regarding the liquid level in a blast furnace hearth because this information affects the strategy of the opening and closing of tapholes in the blast furnace and, consequently, the production control and operational quality. Due to the difficulties of measuring the liquid level in the hearth directly, a system was installed that uses a voltage generated in the hearth shell as a liquid-level sensor in the hearth. In this study, the analysis and treatment of this signal is performed by achieving a stationary, nonlinear signal strongly correlated with the level of molten iron and slag inside the blast furnace hearth. A mathematical model that represents this signal was developed and implemented online in the blast furnace digital control system to enable forecasting of the liquid level up to one hour ahead. This computational tool aids operators and engineers in deciding in advance the instants to open or close the tapholes, thereby increasing safety and financial gains.
The aims of this study were to observe the effects of vacuum sealing drainage (VSD) with three different negative pressures on the wound healing rate, macrophage count and the expression of hyaluronic acid (HA) as well as its receptor CD44 in seawater-immersed blast-injury wounds (SIBIW) and to determine the optimal negative pressure value. In a minipig SIBIW model, different suction pressures and routine dressing were applied. Histological and immunohistochemical comparisons as well as molecular biology methods were performed to compare the wound healing conditions, macrophage count and the levels of HA and CD44. The wound healing rate of the VSD group was significantly higher than that of the control group, with the -120 mmHg group exhibiting the best effects. The macrophage count of the VSD group was higher than that of the control group. The HA level fluctuation was higher in the VSD group, with the -120 mmHg and the -180 mmHg groups showing the most significant fluctuation (P < 005). CD44 was expressed in the full-thickness wound-limbic tissues and was higher in the treatment group than that in the control group, with the -120 mmHg group having the most obvious expression. VSD significantly improved the healing ability and increased the macrophage count and the HA content. It also promoted CD44 expression. -120 mmHg is the optimal negative pressure value.
Blastocystis, a genetically diverse intestinal parasite with controversial pathogenic potential, has increasingly been incriminated for diarrheal illness in immunocompromised individuals including colorectal cancer (CRC) patients. The aim of the current study was to assess the possible association between Blastocystis infection and CRC condition in Makkah, Saudi Arabia (KSA). Methods: Stool samples were collected from 80 non-cancer (NC) and 138 cancer subjects including 74 CRC patients and 64 patients with other cancers outside gastrointestinal tract (COGT). Molecularly confirmed Blastocystis isolates were genetically grouped and subtyped using multiplex polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and sequence-tagged site primers-based PCR (PCR-STS), respectively. Results: Blastocystis hominis were confirmed in 29.7, 25 and 15% among CRC, COGT and NC patients, respectively. Obtained Blastocystis isolates were initially categorized into 2 groups (A and C), which were subsequently subtyped into 3 different subtypes; subtype-I (38%), subtype-II (44%) and subtype-V (22%). Interestingly, subtype-I was the most predominantly detected subtype (54.5%) among CRC patients with a significant association risk (COR 7.548; 95% CI: 1.629-34.987; P = 0.004). Conclusion: To the best of our knowledge, the current study is the first to provide genetic insights on the prevalence of Blastocystis hominis among CRC patients in Makkah, KSA. Moreover, the study suggests for a possible association between subtype-I of Blastocystis hominis and CRC, which could indicate a potential influence of Blastocystis on CRC condition. Further studies are required to confirm this association risk and to investigate the possible underlying mechanism of postulated carcinogenic influence of Blastocystis hominis subtype-I.
Purpose of review In the last nine decades, large advances have been made toward the characterization of the pathogenic basis and clinical management of von Willebrand disease (VWD), the most prevalent inherited bleeding disorder. Pathological variations at the von Willebrand factor (VWF) locus present as a range of both quantitative and qualitative abnormalities that make up the complex clinical spectrum of VWD. This review describes the current understanding of the pathobiological basis of VWD. Recent findings The molecular basis of type 2 (qualitative abnormalities) and type 3 VWD (total quantitative deficiency) have been well characterized in recent decades. However, knowledge of type 1 VWD (partial quantitative deficiency) remains incomplete because of the allelic and locus heterogeneity of this trait, and is complicated by genetic variability at the VWF gene, interactions between the VWF gene and the environment, and the involvement of external modifying loci. Recent genome wide association studies and linkage analyses have sought to identify additional genes that modify the type 1 VWD phenotype. Summary Understanding the pathogenic basis of VWD will facilitate the development of novel treatment regimens for this disorder, and improve the ability to provide complementary molecular diagnostics for type 1 VWD.
The objective was to investigate a family from Argentina. The proposita was a 51-year-old woman who had a moderate bleeding tendency. Some of her children showed a mild bleeding tendency. Her mother and the husband were asymptomatic. Clotting, immunological and molecular biology techniques were used. Partial thromboplastin, prothrombin, Russell Viper venom-clotting times were moderately prolonged in the proposita, whereas they were slightly prolonged in the children and in her mother. Factor X (FX) activity was about 2-3% of normal in all assay systems. FX antigen was less than 5%. Other clotting factors and platelet were normal. Genetic analysis showed a compound heterozygosis: combination of a 'new' mutation (Gln138Arg) with an already known mutation (Glu350Lys). The children had intermediate FX levels (35-63% of normal) and were carriers of one of the two mutations present in the proposita. This is the first observation of a FX deficiency in Argentina. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
According to the Huaxi Group 2# blind inclined shaft hoisting machine adopts TKD-A control system in speed control performance is poor, the control circuit is complex, high noise, stability and low reliability, this paper proposes a SCR-D system to replace the original scheme of reforming the electric control system. The paper introduces the structure and working principle of SCR-D system, shows the main equipment selection of the main circuit, and gives the system installation and adjustment. The result shows, the reformed electric control system has characteristics of perfect protection, control with high precision, good energy saving effect. It achieved the expected goal.
Clavibacter michiganensis ssp. michiganensis (Cmm) causes substantial economic losses in tomato production worldwide. The disease symptoms observed in plants infected systemically by Cmm are wilting and canker on the stem, whereas blister-like spots develop in locally infected leaves. A wide repertoire of serine proteases and cell wall-degrading enzymes has been implicated in the development of wilt and canker symptoms. However, virulence factors involved in the formation of blister-like spots, which play an important role in Cmm secondary spread in tomato nurseries, are largely unknown. Here, we demonstrate that Cmm virulence factors play different roles during blister formation relative to wilting. Inoculation with a green fluorescent protein (GFP)-labelled Cmm382 indicates that penetration occurs mainly through trichomes. When spray inoculated on tomato leaves, the wild-type Cmm382 and Cmm100 (lacking plasmids pCM1 and pCM2) strains form blister-like spots on leaves, whereas Cmm27 (lacking the chp/tomA pathogenicity island) is non-pathogenic, indicating that plasmid-borne genes, which have a crucial role in wilting, are not required for blister formation. Conversely, mutations in chromosomal genes encoding serine proteases (chpC and sbtA), cell wall-degrading enzymes (pgaA and endX/Y), a transcriptional regulator (vatr2), a putative perforin (perF) and a putative sortase (srtA) significantly affect disease incidence and the severity of blister formation. The transcript levels of these genes, as measured by quantitative reverse transcription-polymerase chain reaction, showed that, during blister formation, they are expressed early at 8-16 h after inoculation, whereas, during wilting, they are expressed after 24-72 h or expressed at low levels. Plant gene expression studies suggest that chpC is involved in the suppression of host defence.
DNA nanotechnology enables the synthesis of nanometer-sized objects that can be site-specifically functionalized with a large variety of materials. For these reasons, DNA-based devices such as DNA origami are being considered for applications in molecular biology and nanomedicine. However, many DNA structures need a higher ionic strength than that of common cell culture buffers or bodily fluids to maintain their integrity and can be degraded quickly by nucleases. To overcome these deficiencies, we coated several different DNA origami structures with a cationic poly(ethylene glycol)-polylysine block copolymer, which electrostatically covered the DNA nanostructures to form DNA origami polyplex micelles (DOPMs). This straightforward, cost-effective, and robust route to protect DNA-based structures could therefore enable applications in biology and nanomedicine where unprotected DNA origami would be degraded.
Canine brucellosis caused by Brucella canis is a neglected zoonosis worldwide and is a leading cause of reproductive failure in dogs, often causing substantial economic losses in breeding kennels. This study aimed to investigate the occurrence of B.canis infection in dogs of commercial breeding kennels located in SAo Paulo State, Brazil. A total of 753 dogs (183 males and 570 females) from 38 commercial kennels were clinically examined, and blood samples were collected for brucellosis diagnosis through blood culture. The association between clinical manifestations suggestive of brucellosis and positive results through blood culture was determined. Of the 753 dogs tested, 166 (22.0%) had at least one clinical sign suggestive of brucellosis and 158 (20.9%) had positive blood cultures. Seventy-two dogs had positive blood culture and had at least one clinical sign suggestive of brucellosis, while 91 dogs showed at least one clinical manifestation suggestive of brucellosis although blood culture was negative. Of the 38 kennels, 16 (42.1%) had at least one positive dog. The prevalence of infection in each kennel varied from 3.8% to 62.6%. Abortion/stillbirth, failure to conceive and enlargement of lymph nodes were significantly associated with brucellosis in female. No association of clinical signs and positive results in blood culture was observed in males. None of the kennels has been carrying out programmes to control brucellosis, and the sale of infected dogs was considered a common practice yielding risks to the public health, in view of the zoonotic potential of the infection.
Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2-4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection.
Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies have tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by ischemia and ischemia-reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca2+, an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC on skeletal muscle physiology and immunology, the present paper aims to illustrate the potential protective effects of IPC on EIMD by discussing possible underlying mechanisms. (C) 2016 Elsevier Ltd. All rights reserved.
Objective-Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. Approach and Results-Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.112.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1 +/- 3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1-dependent pathway. Incubation of SLE-activated platelets with an interleukin-1-neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. Conclusions-Platelet activity measurements and subsequent interleukin-1-dependent activation of the endothelium are increased in subjects with SLE. Platelet-endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE.
We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell-specific CNP knockout and vascular smooth muscle cell-specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell-specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell-specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell-specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell-specific GC-B knockout mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from vascular smooth muscle cell-specific GC-B knockout mice. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B. Online Data Supplement
Ehrlichiosis in lung transplant (LT) recipients is associated with severe outcomes. Ehrlichia ewingii is a less frequent cause of symptomatic ehrlichiosis, characterized by cytoplasmic inclusions (morulae) within circulating neutrophils. We report a case of E.ewingii infection in an LT recipient diagnosed promptly by blood smear exam and confirmed with molecular studies.
The social isolation rearing of young adult rats is a model of psychosocial stress and provides a nonpharmacological tool to study alterations reminiscent of symptoms seen in psychosis. We have previously demonstrated that social isolation in rats leads to increased oxidative stress and to cerebral NOX2 elevations. Here, we investigated early alterations in mRNA expression leading to increased NOX2 in the brain. Rats were exposed to a short period of social isolation (1 week) and real-time polymerase chain reaction (PCR) for mRNA expression of genes involved in blood-brain barrier (BBB) formation and integrity (ORLs, Vof 21 and Vof 16, Leng8, Vnr1, and Trank 1 genes) was performed. Real-time PCR experiments, immunohistochemistry, and Western blotting analysis showed an increased expression of these genes and related proteins in isolated rats with respect to control animals. The expression of specific markers of BBB integrity, such as matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), occludin 1, and plasmalemmal vesicle associated protein-1 (PV-1), was also significantly altered after 1 week of social isolation. BBB permeability, evaluated by quantification of Evans blue dye extravasation, as well as interstitial fluid, was significantly increased in rats isolated for 1 week with respect to controls. Isolation-induced BBB disruption was also accompanied by a significant increase of Interleukin 6 (IL-6) expression. Conversely, no differences in NOX2 levels were detected at this time point. Our study demonstrates that BBB disruption precedes NOX2 elevations in the brain. These results provide new insights in the interplay of mechanisms linking psychosocial stress to early oxidative stress in the brain, disruption of the BBB, and the development of mental disorders.
Since the lacZ alpha-based blue/white screening system was introduced to molecular biology, several different visual reporter systems were developed and used for various purposes in Escherichia coli. A common limit to the existent visual reporter systems is that an extracellular chromogenic substrate has to be added for the visible pigment production. In this study, we developed a new blue/white screening system based on a non-ribosomal peptide synthetase encoded by idgS from Streptomyces and a phosphopantetheinyl transferase encoded by sfp from Bacillus. When IdgS is activated from an apo-form to a holo-form via a posttranslational modification catalyzed by Sfp, it can synthesize a blue pigment indigoidine using L-glutamine, the amino acid abundant in cells, as a substrate. The new blue/white screening system contains a recipient E. coli strain with an optimized idgS gene cassette and a cloning vector harboring an sfp gene with an in-frame insertion of a multiple cloning site close to its N-terminal. We demonstrated that the IdgS/Sfp-based blue/white screening system is a powerful alternative to the lacZ alpha-based screening system, which does not require any external substrate addition.
Bluetongue is a non-contagious, haemorrhagic, Culicoides-borne disease of ruminants. The causative agent, bluetongue virus (BTV), is a member of the Orbivirus genus of the Reoviridae family. So far, 26 BTV serotypes have been identified worldwide. The global distribution of bluetongue has been expanding, and rapid detection of BTV, preferably in the field, is critical for timely implementation of animal movement restrictions and vector control measures. To date, many laboratory-based, molecular assays for detection of BTV have been developed. These methods require the samples to be shipped to a central laboratory with sophisticated instruments and highly skilled technicians to perform the assays, conduct analyses and interpret the results. Here, we report the development and evaluation of a rapid, portable, user-friendly, pan-BTV reverse transcription-insulated isothermal polymerase chain reaction (RT-iiPCR) assay that can potentially be used in low-resource field conditions. The total length of the assay was < 60 min, and at the end of the assay, the results were automatically displayed as `+' or '_' without the need for data interpretation. The RT-iiPCR assay detected 36 BTV isolates and two in vitro transcribed RNA samples representing all 26 BTV serotypes. The assay did not cross-react with other animal viruses tested, including two closely related orbiviruses. The analytical sensitivity of the assay was as low as nine copies of in vitro transcribed double-stranded BTV RNA. Analysis of BTVinfected whole blood samples showed that the BTV RT-iiPCR assay was as sensitive as real-time RT-PCR. The assay can potentially be used for rapid screening of animals for BTV in routine diagnostics and for monitoring bluetongue outbreaks both in ruminants and in Culicoides vectors in the field and in the laboratory.
Small intestinal injury is seldom described in the context of child abuse. Signs and symptoms are subtle, often leading to delays in diagnosis. We describe a 3-year-old boy initially admitted with severe blunt abdominal trauma from physical child abuse. He was successfully managed nonoperatively. The child was then hospitalized several times for nonspecific abdominal symptoms until diagnostic laparoscopy discovered a jejunal stricture with a proximal jejuno-jejunal fistula. Symptoms fully resolved after resection. Delayed presentation of small intestinal injury should remain on the differential diagnosis in the evaluation of persistent abdominal symptoms in a child with a prior history of physical abuse, even if imaging studies do not reveal specific abnormalities.
Background. Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. Method. We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). Results. While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z=-2.33, p=0.02) and at trend level in healthy controls (Z=-1.87, p=0.06). Conclusions. These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.
We previously reported that higher education protects against executive dysfunction related to higher body mass index (BMI) in younger, but not older, adults. We now extend the previous analyses to verbal and nonverbal memory. Fifty-nine healthy, dementia-free community-dwelling adults ranging in age from 18 to 81years completed the Hopkins Verbal Learning Test - Revised (HVLT-R) and the Brief Visuospatial Memory Test - Revised (BVMT-R). Self-reported years of education served as a proxy for cognitive reserve. We found that more highly educated individuals maintained their BVMT-R immediate recall performance across the range of BMI, but in less educated individuals, higher BMI was associated with worse performance. Our findings suggest that education may play a protective role against BMI-related nonverbal learning deficits, similar to previous reports for verbal memory and executive functioning. Results highlight the importance of considering educational background when determining the risk for BMI-related cognitive impairment in clinical settings.
NS3 protease plays a vital role in the replication of the hepatitis C virus (HCV). BMS-605339 is a novel linear tetra-peptide alpha-ketoamide inhibitor of NS3 protease and shows specificity for HCV NS3 protease genotype 1a and genotype 1b. Mutation at the key site 168 of the HCV NS3 protease can induce resistance to BMS-605339, which greatly affects the antiviral therapy efficacy to hepatitis C. In the present study, we employed molecular dynamics simulations, free energy calculations, and free energy decomposition to explore the drug resistance mechanism of BMS-605339 due to the three representative mutations D168C/Y/V. The free energy decomposition analysis indicates that the decrease in the binding affinity is mainly attributed to the decrease in both van der Waals and electrostatic interactions. After detailed analysis of our calculated results, we observed that the break of the salt bridge between residues 155 and 168 caused by the mutations D168C/Y/V is the original reason for the decrease in the binding ability between BMS-605339 and the mutant NS3 proteases. The obtained results will reveal the drug resistance mechanism between BMS-605339 and the mutant NS3 proteases, and provide valuable clue for designing novel and more potent drugs to HCV NS3 protease. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
The Kruppel-associated box (KRAB)-containing zinc finger proteins (ZFPs) comprise the largest family of zinc finger transcription factors that function as transcriptional repressors. In the study of glial cell line-derived neurotrophic factor (GDNF)-RET signaling, we have identified bone marrow zinc finger 3 (BMZF3), encoding a KRAB-ZFP, as a GDNF-inducible gene by differential display analysis. The expression of BMZF3 transcripts in the human neuroblastoma cell line TGW increased I h after GDNF stimulation, as determined by Northern blotting and quantitative reverse-transcriptase polymerase chain reaction. The BMZF3 possesses transcriptional repressor activity in the KRAB domain. BMZF3 interacts with a co-repressor protein, KRAB-associated protein I (KAP-1), through the KRAB domain and siRNA-mediated knockdown of KAP-1 abolished the transcriptional repressor activity of BMZF3, indicating that KAP-1 is necessary for BMZF3 function. Furthermore, siRNA-mediated silencing of BMZF3 inhibited cell proliferation. These findings suggest that BMZF3 is a transcriptional repressor induced by GDNF that plays a role in cell proliferation. (c) 2007 Elsevier Inc. All rights reserved.
We present a generalization of the Bode integral formula for discrete-time linear periodic systems. It is shown that similar to the classical Bode integral formula, the sensitivity integral for a discrete-time linear periodic system depends only on the open-loop dynamics of the system; in particular, on the open-loop characteristic multipliers outside the unit circle in the complex plane. The integral is derived by using an asymptotic eigenvalue distribution theorem for block Toeplitz matrices, which does not require the open loop system to be stable or the disturbance to be Gaussian. The result is demonstrated through application to a class of multi-rate sampled data systems with commensurate rates.
Bodily knowledge has attracted significant attention within the humanities and other related fields over the last two decades. Although theoretical discussion on bodily knowledge in the context of physical education has been active over the past 10 years, these discussions lack clear conceptual analyses of bodily knowledge. Using a phenomenological approach, the purpose of this paper is to clarify the notion of bodily knowledge, furthering epistemological discussions of the topic within reflective, embodied practices. Instead of seeing bodily knowledge inherently connected to the acquisition of motor skills or improving physical fitness, we will discuss physical training as a reflective, embodied process that can turn sensuous information about the moving body into knowledge. Using outdoor running as an example, we describe the process of forming bodily knowledge, which includes: (1) the exploring and identifying of movement qualities, (2) developing capabilities of registering changes in the body and (3) directing and modifying one's own training processes based on bodily findings. Contextualizing this epistemological discussion with adults' recreational physical activity, this paper argues that bodily knowledge can cultivate individuals to trust their own body awareness and embodied responses to take more responsibility for their own physical exercise. When biomedical knowledge of the body in sport sciences tends to shrink the body to physiological attributes, such as muscle mass and fat percentage, our analysis stresses the agency of the lived body as a source of knowledge in physical activity.
The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and cognitive deficits concerning mental flexibility and inhibitory control efficiency. The present study aims at replicating and extending these observations. We compared cognitive control performance of normal weight (BMI= 25) university students on a task tapping either inhibitory control (Experiment 1) or interference control (Experiment 2). Experiment 1 replicated previous findings that found less efficient inhibitory control in overweight individuals. Experiment 2 complemented these findings by showing that cognitive control impairments associated with high BMI also extend to the ability to resolve stimulus-induced response conflict and to engage in conflict-driven control adaptation. The present results are consistent with and extend previous literature showing that high BMI in young, otherwise healthy individuals is associated with less efficient cognitive control functioning. (C) 2017 Elsevier Ltd. All rights reserved.
This study investigated the association between child maltreatment and body mass index (BMI) using data from four waves (wave 2 in 2011 through 5 in 2014) of the Korean Children & Youth PanelSurvey collected by the South Korean National Youth Policy Institute. We employed a latent growth curve modeling approach to estimate an unobserved latent trajectory and to test the longitudinal effects of child abuse and neglect on BMI. Our results indicate that child abuse is significantly associated with BMI and children who report higher levels of abuse tend to have higher rates of increase in their BMI. This study addresses a gap in the literature by demonstrating that a parent's maltreatment of their child has a long-term effect on the rate of change in their BMI over time.
The aim of this study was to explore the significant predictors associated with electroconvulsive therapy (ECT) outcome for patients with major depressive disorder. Major depressive disorder inpatients (N=130) requiring ECT were recruited from a major psychiatric center in South Taiwan. ECT was generally performed for a maximum of 12 sessions. Symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S) before ECT, after every three ECT sessions, and after the last ECT. The generalized estimating equations method was used to analyze the influence of potential variables over time on the HAMD-17 and CGI-S, respectively. Fourteen patients not completing the first three sessions of ECT were excluded. The remaining 116 patients were included in the analysis. Patients with treatment-resistant depression, longer duration of the current depressive episode, and higher levels of pain were more likely to have less symptom reduction after acute treatment with ECT, irrespective of how the depressive symptoms were rated using HAMD-17 or CGI-S. To improve efficacy, earlier application of ECT and pain control should be considered during an acute course of ECT. Other clinical predictors related to ECT outcome require further investigation in future studies.
The majority of human neuroscience research has focussed on understanding functional organisation within segregated patches of cortex. The ventral visual stream has been associated with the detection of physical features such as faces and body parts, whereas the theory-of-mind network has been associated with making inferences about mental states and underlying character, such as whether someone is friendly, selfish, or generous. To date, however, it is largely unknown how such distinct processing components integrate neural signals. Using functional magnetic resonance imaging and connectivity analyses, we investigated the contribution of functional integration to social perception. During scanning, participants observed bodies that had previously been associated with trait-based or neutral information. Additionally, we independently localised the body perception and theory-of-mind networks. We demonstrate that when observing someone who cues the recall of stored social knowledge compared to non-social knowledge, a node in the ventral visual stream (extrastriate body area) shows greater coupling with part of the theory-of-mind network (temporal pole). These results show that functional connections provide an interface between perceptual and inferential processing components, thus providing neurobiological evidence that supports the view that understanding the visual environment involves interplay between conceptual knowledge and perceptual processing.
For young birds in a nest, body size may have implications for other aspects of development such as telomere length and immune function. However, it is possible to predict associations in either direction. On the one hand, there may be trade-offs between growth and telomere maintenance, and growth and investment in immune function, suggesting there will be negative correlations. On the other hand, relatively larger individuals might be advantaged in competition with their nest-mates, allowing them to garner more resources overall, leading to positive correlations. We studied development over the nestling period in 34 nests of wild European starlings, Sturnus vulgaris. Intrabrood competition is typically more intense in larger broods. Hence, we predicted that body size should become an increasingly positive predictor of telomere length and immune functioning as brood size increases. In partial support of our prediction, there were significant interactions between brood size and body size in predicting both erythrocyte telomere length change and plasma levels of the cytokine interleukin-6. The associations between body size and these outcomes went from negative in the smallest broods to positive in the largest. A further immune marker, high-sensitivity C-reactive protein, showed no systematic patterning with body size or brood size. Our results confirm that the size to which a nestling grows is important for telomere dynamics and the development of the immune system, but the phenotypic associations are moderated by the competitive context.
Background: Small non-coding RNAs (ncRNAs) are important regulators of gene expression in eukaryotes. Previously, only microRNAs (miRNAs) and piRNAs have been identified in the silkworm, Bombyx mori. Furthermore, only ncRNAs (50-500nt) of intermediate size have been systematically identified in the silkworm. Results: Here, we performed a systematic identification and analysis of small RNAs (18-50nt) associated with the Bombyx mori argonaute2 (BmAgo2) protein. Using RIP-seq, we identified various types of small ncRNAs associated with BmAGO2. These ncRNAs showed a multimodal length distribution, with three peaks at similar to 20nt, similar to 27nt and similar to 33nt, which included tRNA-, transposable element (TE)-, rRNA-, snoRNA-and snRNA-derived small RNAs as well as miRNAs and piRNAs. The tRNA-derived fragments (tRFs) were found at an extremely high abundance and accounted for 69.90% of the BmAgo2-associated small RNAs. Northern blotting confirmed that many tRFs were expressed or up-regulated only in the BmNPV-infected cells, implying that the tRFs play a prominent role by binding to BmAgo2 during BmNPV infection. Additional evidence suggested that there are potential cleavage sites on the D, anti-codon and T psi C loops of the tRNAs. TE-derived small RNAs and piRNAs also accounted for a significant proportion of the BmAgo2-associated small RNAs, suggesting that BmAgo2 could be involved in the maintenance of genome stability by suppressing the activities of transposons guided by these small RNAs. Finally, Northern blotting was also used to confirm the Bombyx 5.8 s rRNA-derived small RNAs, demonstrating that various novel small RNAs exist in the silkworm. Conclusions: Using an RIP-seq method in combination with Northern blotting, we identified various types of small RNAs associated with the BmAgo2 protein, including tRNA-, TE-, rRNA-, snoRNA-and snRNA-derived small RNAs as well as miRNAs and piRNAs. Our findings provide new clues for future functional studies of the role of small RNAs in insect development and evolution.
The larval pigment pattern in the silkworm, Bombyx mori, is formed by melanin, ommochromes and pteridines. During development all these pigments are synthesized autonomously, and possibly also with mutual interaction between them, to yield unique pigment patterns. In order to find the key trigger for such pigment pattern formation, developmental changes in pteridine biosynthesis were studied using the quail mutant (q/q), which has darker larval marks formed by melanin and an abundance of ommochromes in the integument. In the current study, emphasis has been placed on the analysis of GTP-cyclohydrolase I (GTP-CH I), which is a key enzyme for the biosynthesis of pteridines, during the development of the silkworm. Results of Northern blotting showed that in the quail mutant strong signals of GTP-CH I mRNA appeared around each period of ecdysis, while no such signals appeared in the background strain (+q/q) used. Also, both GTP-CH I activities and pteridine content were higher in the quail mutant compared with the background strain. These results strongly suggest that pteridine biosynthesis is closely linked to the formation of melanin and ommochromes. It is also suggested here that in the silkworm a recessive gene (q) may be involved in the regulation of its pigment pattern formation.
Transforming growth factor (TGF)-beta are strongly associated with osteoblast differentiation. Mechanical stress including compressive force (CF) also involve in osteoblast differentiation via the alteration of the expression of bone-specific transcription factors, namely Runx2 and Osterix. However, the role of TGF-beta s in mediating the effects of CF on osteoblasts remains unclear. In the present study, we examined the effects of CF on the expression of TGF-beta 1, TGF-beta 2, TGF-beta type 1 and 2 receptor (T beta r1 and T beta r2), and Runx2 and Osterix in osteoblasts: We also investigated the effects of CF on the phosphorylation of Smad2, Smad3 and p38; which were located on the downstream of T beta rs. Effect of T beta r inhibitor (LY2109761) on expression of Runx2 and Osterix, and phosphorylation of Smad2, Smad3 and p38 were additionally examined Cultured MC3T3-E1 osteoblast-like cells were subjected, or not, to continuous CF (1.0 g/ cm(2) or 2.0 g/cm(2)) for 1-9 h. TGF-beta 1, TGF-beta 2, T beta r1, T beta r2, Runx2 and Osterix expression were measured by real-time polymerase chain reaction and Western blot analysis. Phosphorylation levels of Smad2, Smad3 and p38 were determined by Western blot analysis. The mRNA and protein expression of TGF-beta 1 and TGF-beta 2 were significantly increased by 1.0 g/cm(2), but not 2.0 g/cm(2), CF for 3-6 h, relative to control cells; T beta r1 and T beta r2 expression were unaffected by either CF condition. The 1.0 g/cm(2) CF also increased the phosphorylation of Smad2, Smad3 and p38 and the expression of Runx2 and Osterix, and these increases were attenuated by pretreatment with LY2109761. The present findings indicate that 1.0 g/cm(2) CF can induce bone-specific transcription factors via autocrine action of CF-induced TGF-beta signaling in osteoblasts.
Chimerism associated with placental sharing in marmosets has been traditionally analysed using conventional chromosome staining on metaphase spreads or polymerase chain reaction. However, the former technique requires the presence of proliferating cells, whereas the latter may be associated with possible blood cell contamination. Therefore, we aimed to develop a single-cell analysis technique for sexing marmoset cells. We applied fluorescent in situ hybridisation (FISH) to cell nuclei using differentially labelled X and Y chromosome-specific probes. Herein we present the validation of this method in metaphase cells from a marmoset lymphoblastoid cell line, as well as application of the method for evaluation of cross-sex chimerism in interphase blood lymphocytes and haematopoietic bone marrow cells from marmosets of same- and mixed-sex litters. The results show conclusively that haematopoietic cells of bone marrow and leucocytes from blood are cross-sex chimeric when the litter is mixed sex. In addition, single samples of liver and spleen cell suspensions from one individual were tested. Cross-sex chimerism was observed in the spleen but not in liver cells. We conclude that FISH is the method of choice to identify cross-sex chimerism, especially when combined with morphological identification of nuclei of different cell types, which will allow a targeted tissue-specific analysis.
Background Diamond-Blackfan anemia and Shwachman-Diamond syndrome are inherited bone marrow failure syndromes linked to defects in ribosome synthesis. The purpose of this study was to determine whether yeast models for Diamond-Blackfan anemia and Shwachman-Diamond syndrome differed in the mechanism by which ribosome synthesis was affected. Design and Methods Northern blotting, pulse-chase analysis, and polysome profiling were used to study ribosome synthesis in yeast models. Localization of 60S ribosomal subunits was assessed using RPL25eGFP. Results Relative to wild-type controls, each disease model showed defects in 60S subunit maturation, but with distinct underlying mechanisms. In the model of Diamond-Blackfan anemia, 60S subunit maturation was disrupted at a relatively early stage with abortive complexes subject to rapid degradation. 5S ribosomal RNA, unlike other large subunit ribosomal RNA in this model, accumulated as an extra-ribosomal species. In contrast, subunit maturation in the Shwachman-Diamond syndrome model was affected at a later step, giving rise to relatively stable pre-60S particles with associated 5S ribosomal RNA retained in the nucleus. Conclusions These differences between the yeast Diamond-Blackfan anemia and Shwactiman-Diamond syndrome models have implications for signaling mechanisms linking abortive ribosome. assembly to cell fate decisions and may contribute to the divergent clinical presentations of Diamond-Blackfan anemia and Shwachman-Diamond syndrome.
Background: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent cells with a high constitutive level of autophagy and low expression of CD99. Under certain conditions, MSCs may develop tumorigenic properties. However, these transformation-induced conditions are largely unknown. Recently, we have identified an association between Hsp70, a main participant in cellular stress response and tumorigenesis, and CD99. Preliminary observations had revealed upregulation of both proteins in stressed long-term cultured MSCs. And so we hypothesized that CD99 is implicated in stress-induced mechanisms of cellular transformation in MSCs. Hence, we investigated the effects of prolonged stress on MSCs and the role of CD99 and autophagy in their survival. Methods: Human telomerase reverse transcriptase (hTERT) overexpressing immortalized MSCs and primary bone marrow stromal cells were used to investigate the influence of long-term serum deprivation and hypoxia on growth and differentiation of MSCs. Cell proliferation and apoptosis were evaluated using flow cytometry, differentiation capabilities of MSCs were assessed by immunohistochemical staining followed by microscopic examination. CD99, Hsp70 expression were analyzed using flow cytometry, western blotting, and reverse transcriptase polymerase chain reaction. Autophagy was explored with specific inhibitors using cell morphology examination and western blotting. Results: Chronic stress factors are able to change the morphology of MSCs and to inhibit spontaneous differentiation into adipocyte lineage. Furthermore, CD99 elevation and downregulation of p53 and p21 accompanied defective autophagy, which is usually associated with tumor formation. We found that inhibition of autophagy by chloroquine promoted cell detachment and modulated CD99 expression level whereas incorporation of CD99 recombinant protein into the cells suppressed autophagy. Conclusions: Obtained results provide a model for chronic stress-induced transformation of MSCs via CD99 and may therefore be highly relevant to mesenchymal tumorigenesis.
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34(+) cells: NSG, NSG-3GS, hSCF-Tg-NSG, and hSIRP alpha-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen, and liver was evaluated by flow cytometry 12 weeks after transplant. The highest levels of human engraftment were observed in the liver, spleen, and bone marrow, whereas peripheral blood cell chimerism was notably less. The highest levels of tissue engraftment were in hSCF-Tg-NSG mice, but NSG mice exhibited the highest blood leukocyte engraftment. hSCF-Tg-NSG mice also exhibited the highest levels of CD133(+)CD34(++) stem cells. hSIRPa-DKO engrafted poorly and exhibited poor breeding. Myelopoiesis was greatest in NSG-3GS mice, followed by hSCF-Tg-NSG and NSG mice, whereas B cell engraftment exhibited the opposite pattern. Engraftment of CD3(+) T cells, CD3(+)CD161(+)T cells, and CD3(-)CD56(+) NK cells was greatest in NSG-3GS mice. Mast cell engraftment was highest in hSCF-Tg-NSG mice, but was also elevated in spleen and livers of NSG-3GS mice. Basophils were most abundant in NSG-3GS mice. Overall, hSCF-Tg-NSG mice are the best recipient mice for studies requiring high levels of human hematopoiesis, stem cell engraftment, and an intermediate level of myelopoiesis, whereas NSG and NSG-3GS mice offer select advantages in the engraftment of certain blood cell lineages.
Aim: To test the hypothesis that genistein stimulates the osteoblastic differentiation through the p38 mitogen activated protein kinase (MAPK)-core-binding factor 1 (Cbfa1) pathway. Methods: The activation of p38 MAPK was detected by Western blotting. Alkaline phosphatase (ALP) activity and calcium deposition were assessed for osteoblastic differentiation of bone marrow-derived mesenchymal stem cell (BMSC) cultures. The expression of Cbfa1 was analyzed at both the mRNA and protein levels. The activity of Cbfa1 was detected by electrophoretic mobility shift assay. Bone sialoprotein (BSP), ALP, osteocalcin (OC), and osteopontin (OPN) gene transcription were also evaluated by either RT-PCR or Northern blotting. Results: Genistein (0.01-1 mu mol/L) dose dependently led to the rapid and sustained activation of the p38 MAPK pathway in mouse BMSC cultures. Treatment with genistein (1 mu mol/L) resulted in increased ALP activity and calcium deposition of BMSC cultures as a function of time. Genistein also enhanced Cbfa1 DNA binding activity and promoted the expressions of Cbfa1 itself as well as several Cbfa1-regulated genes, including ALP, BSP, OC, and OPN. Concurrent treatment with p38 MAPK inhibitor (SB203580) diminished the genistein-induced osteoblastic maturation and p38 MAPK-Cbfa1 activation in mouse BMSC cultures. Conclusion: These results indicated that genistein could stimulate the osteoblastic differentiation of BMSC cultures through the p38 MAPK-Cbfa1 pathway.
Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy. Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-nai " ve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription-polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation. Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non-AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient. Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients. (C) 2016 European Association of Urology. Published by Elsevier B. V.
Bone morphogenetic protein-2 (BMP-2) participates significantly in vascular development and pathophysiological processes. Angiotensin II (AngII) has been demonstrated to be critical in the initiation and progression of atherosclerosis. However, the effects of AngII on BMP-2 expression and of probucol on the AngII-induced BMP-2 expression in human umbilical vein endothelial cells (HUVECs) are unknown. The aim of our study was to investigate these effects. HUVECs were cultured and stimulated with various agents. The total superoxide dismutase (SOD) activity and the concentrations of malondialdehyde (MDA) and BMP-2 were measured by standard methods. Northern blotting was used to detect the expression of BMP-2 mRNA. The activation of NF-kappa B in the HUVECs was also determined. The AngII treatment significantly increased BMP-2 expression levels and activated NF-kappa B. These effects were suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or probucol. Furthermore, the increased levels of MDA in the conditioned medium and the decrease in the total SOD activity caused by the AngII treatment were reversed by treatment with probucol or PDTC. Probucol downregulated the AngII-nduced BMP-2 expression. These effects of probucol may be mediated by the inhibition of NF-kappa B activation.
Alveolar bone resorption caused by trauma or periodontal diseases has represented a challenge for both dental clinicians and researchers. In this study, we evaluate the osteogenic potential of human gingival fibroblasts (HGFs) through a direct transdifferentiation from HGFs to functional osteoblasts via epigenetic modification and osteogenic signaling with bone morphogenetic protein 2 (BMP2) in vitro and in vivo. HGF treatment with 5-aza-2'-deoxycytidine (5-aza-dC) induced demethylation in the hypermethylated CpG islands of the osteogenic lineage marker genes RUNX2 and ALP, and subsequent BMP2 treatment successfully drove the fibroblasts to the osteoblasts' lineage. Cell morphological changes viewed under microscopy and alkaline phosphatase (ALP) and alizarin red S (ARS) staining confirmed the osteoblastic change mediated by epigenetic modification as did real-time polymerase chain reaction (PCR), methylation-specific PCR (MSP), and chromatin immunoprecipitation (ChIP) assay, which demonstrated the altered methylation patterns in the RUNX2 and ALP promoter regions and their effect on gene expression. Furthermore, micro-computed tomography (CT) analysis of in vivo mouse cell transplantation experiments showed high-density signal in the epigenetically modified HGF group; in addition, a significant amount of bone formation was observed in the transplanted material using hematoxylin and eosin (H&E) staining as well. Collectively, our results indicate that epigenetic modification permits the direct programming of HGFs into functional osteoblasts, suggesting that this approach might open a novel therapeutic avenue in alveolar bone regeneration.
Objective: The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification (HO). Background: HO is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is upregulated during incidents of trauma, thereby coincident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation. Methods: Mice underwent hindlimb Achilles' tendon transection and dorsal burn injury (burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Results: Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% vs 0.8%, P < 0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% vs 3.3%, P < 0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2-/CD45-/CD90-/BP1-) were also significantly decreased after lymph node excision (10.2% vs 0.5%, P < 0.05). A significant decrease was noted in the volume of de novo HOpresent within the soft tissues (0.12 mm(3) vs 0.02 mm(3)). Conclusion: These findings suggest that lymphatic vessels are intimately linked with the de novo formation bone within soft tissues following trauma, and their presence may facilitate bone formation.
Growth recovery lines, also known as growth arrest lines, are transverse radiodense metaphyseal bands that develop due to a temporary arrest of endochondral ossification caused by local or systemic insults. To determine if growth recovery lines are more common in infants at high risk versus low risk for abuse. Reports of American College of Radiology compliant skeletal surveys (1999-2013) were reviewed with clinical records. Infants at low risk for abuse had a skull fracture without significant intracranial injury, history of a fall and clinical determination of low risk (child protection team/social work assessment). Infants at high risk had significant intracranial injury, retinal hemorrhages, other skeletal injuries and clinical determination of high risk. There were 52 low-risk infants (mean: 4.7 months, range: 0.4-12 months) and 21 high-risk infants (mean: 4.2 months, range: 0.8-9.1 months). Two blinded radiologists independently evaluated the skeletal survey radiographs of the knees/lower legs for the presence of at least one growth recovery line. When growth recovery lines are scored as probably present or definitely present, their prevalence in the low-risk group was 38% (standard deviation [SD] = 8%; reader 1 = 17/52, reader 2 = 23/52) vs. 71% (SD = 7%; reader 1 = 16/21, reader 2 = 14/21) in the high-risk group (P < 0.001; odds ratio 4.0, 95% CI: 1.7-9.5). Growth recovery lines are encountered at a significantly higher rate in infants at high risk vs. low risk for abuse. This suggests that abused infants are prone to a temporary disturbance in endochondral ossification as a result of episodic physiological stresses.
Determining individual health status is of great importance for a better understanding of life history trade-offs between growth, reproduction, and maintenance. However, existing immunological methods are invasive and therefore not suitable for investigating health status in wild populations. Thus, there is an urgent need for non-invasive methods to assess the immune status of animals. Neopterin is involved in the cell-mediated pathway of the immune response (Th1-type), secreted during the activation of monocytes and macrophages. We investigated if urinary neopterin could serve as a biomarker of health status in bonobos and chimpanzees. First, we performed a chemical validation of a commercial neopterin enzyme immune assay (EIA) for bonobo and chimpanzee urine. We then examined if urinary neopterin levels in bonobos increase during the acute period of respiratory infections. We found that neopterin levels can be reliably measured in urine of the two species with a commercial EIA. Stability experiments revealed considerable changes in urinary neopterin levels in relation to multiple freezethaw cycles and extended exposure to room temperature. Exposure to sunlight led to a degradation of urinary neopterin, whereas sample storage up to two years did not affect urinary neopterin levels. There was no detectable diurnal variation in neopterin levels, and levels remained very stable across several days in healthy individuals. While urinary neopterin levels were independent of sex, nonadult individuals had higher urinary neopterin levels than adults. Most importantly, there was a significant increase in urinary neopterin levels during a period of respiratory infection. Our results demonstrate that regular urine sample collection would allow for the monitoring of individual health status and disease progression with minimal disturbance of the subjects. In combination with behavioral, life history, and endocrinological parameters, the method can be used to investigate questions related to immunocompetence handicaps or life history trade-offs.
Conventionally, a high accuracy operational amplifier (OPA)-based current sensor is used for sensing current message under a full load range, which increases the cost characteristic. Instead of a high accuracy OPA-based current sensor, this paper describes using a switching inductor quasi-V-2 hysteretic control boost dc-dc regulator with a proposed current-sensing technique named emulated-ramp feedback (ERF), which can improve transfer efficiency under a full load range. Two control systems are presented in this paper. The first system, a hysteretic voltage control switching boost converter with ERF, achieves the hysteretic voltage control in a boost regulator and lowers the cost characteristic without using compensator. The second system, a quasi-V-2 hysteretic voltage control switching boost converter with ERF, demonstrates the compatibility of ERF technique in rippled-based control boost converters. The regulator was implemented with TSMC 0.25-mu m HV CMOS process. Experimental results show the second system can work under the specification of 5-12V with a 0 to 300-mA load range. Additionally, this system attained a recovery time is 27/95 mu s for step-up/step-down in a 100 to 300-mA continuous conduction mode load current, and a peak efficiency of 92.1% with a chip area of only 1.014mm(2). Copyright (c) 2016 John Wiley & Sons, Ltd.
Monte Carlo (MC) techniques are widely applied to check a design on its robustness and for estimating the production yield of integrated circuits. Using standard random MC and the sample yield for estimation, a very large number of samples is required for accurate verification, especially if a high yield is desired. This can make MC extremely time consuming, but if the data follows a normal Gaussian distribution a much faster yield prediction is possible by using the well-known C-PK method. We extended this specification-distance-based scheme for the far more difficult general non-normal case by three different means, ending up in a new generalized process capability index named C-GPK. First, we apply parametric modeling only to the specification-sided distribution part. This way any difficulties in distribution parts that actually have little yield impact do not degrade the model fit anymore. Second, to improve the parametric model we introduce a new tail parameter t. Third, to allow modeling of difficult asymmetrical, multimodal or flat distributions we also introduce a new reference location parameter instead of using the mean. An advantage of improving MC this way is that-in opposite to many other MC enhancements (like importance sampling)-the performance of the C-GPK is not negatively impacted by design complexity. We described the formulation of the C-GPK and derived confidence intervals using an advanced bootstrap scheme. We verified the performance against the sample yield and C-PK for a representative set of distributions, including real production data and MC data from the design of a CMOS operational amplifier and other circuits.
ObjectivesBorderline personality disorder (BPD) is characterized by emotional instability, interpersonal dysfunction, and other features that typically develop before a background of insecure attachment and traumatic experiences. Dialectical behaviour therapy (DBT) has proven highly effective in reducing self-harm and improving emotion regulation, whereby problems concerning social cognition, which are also characteristic of BPD, may need additional approaches such as mentalization-based treatment (MBT). MethodsHere, we examined, in a pilot study, the effectiveness of MBT given adjunct to DBT, compared to DBT alone, in an inpatient sample with BPD, whereby mentalization was measured using a novel cartoon-based task. ResultsBoth treatments were highly effective in reducing symptom severity. The combination of DBT and MBT was superior in reducing fearful attachment and in improving affective mentalizing. ConclusionsMentalization-based treatment in combination with DBT may improve certain aspects of social cognitive skills and attachment security, as compared to DBT alone, although the exact mechanisms that led to these changes need to be studied further. Practitioner points Clinical implications Dialectical behaviour therapy (DBT) can usefully be combined with mentalization-based treatment (MBT). The combination of DBT and MBT reduces self-harm more than DBT alone. DBT plus MBT may lead to a reduction in fearful attachment and improvement of affective mentalizing. Short-term combinations of evidence-based borderline treatments may enrich psychiatric inpatient care. Therefore, such approaches deserve further research. Limitations The treatment condition was therapeutically more intense than the control condition. The study lacked a follow-up assessment. The impact of comorbid conditions on treatment response was not taken into account. Adherence to the manualized approach was not measured.
Borderline personality disorder (BPD) has been shown to be a valid and reliable diagnosis in adolescents and associated with a decrease in both general and social functioning. With evidence linking BPD in adolescents to poor prognosis, it is important to develop a better understanding of factors and mechanisms contributing to the development of BPD. This could potentially enhance our knowledge and facilitate the design of novel treatment programs and interventions for this group. In this paper, we outline a theoretical model of BPD in adolescents linking the original mentalization-based theory of BPD, with recent extensions of the theory that focuses on hypermentalizing and epistemic trust. We then provide clinical case vignettes to illustrate this extended theoretical model of BPD. Furthermore, we suggest a treatment approach to BPD in adolescents that focuses on the reduction of hypermentalizing and epistemic mistrust. We conclude with an integration of theory and practice in the final section of the paper and make recommendations for future work in this area.
Impairments in interpersonal relationships are a core feature of borderline personality disorder (BPD). Social cognition dysfunction, like false recognition of others' emotions and intentions, may lead to emotional disturbances, self-injury, and impulsive aggression behaviors in patients with BPD. This study explored the extent to which social cognition, including emotional recognition and theory of mind (ToM), can predict the ability of social awareness in patients with BPD. Emotion recognition tasks (matching emotional facial expressions to prosody), verbal and nonverbal theory of mind tasks, and the awareness of social inference test were assessed. Results of a stepwise multiple regression showed that the quality of the early parent-child relationship, anger prosody recognition, and ToM were significantly related to the ability to be aware of social interactions in the patients with BPD.
Canine respiratory diseases are commonly seen in dogs along with co -infections with multiple respiratory pathogens, including viruses and bacteria. Virus infections in even vaccinated dogs were also reported. The clinical signs caused by different respiratory etiological agents are similar, which makes differential diagnosis imperative. An oligonucleotide microarray system was developed in this study. The wild type and vaccine strains of canine distemper virus (CDV), influenza virus, canine herpesvirus (CHV), Bordetella bronchiseptica and Mycoplasma cynos were detected and differentiated simultaneously on a microarray chip. The detection limit is 10, 10, 100, 50 and 50 copy numbers for CDV, influenza virus, CHV, B. bronchiseptica and M. cynos, respectively. The clinical test results of nasal swab samples showed that the microarray had remarkably better efficacy than the multiplex PCR-agarose gel method. The positive detection rate of microarray and agarose gel was 59.0% (n=33) and 41.1% (n =23) among the 56 samples, respectively. CDV vaccine strain and pathogen co -infections were further demonstrated by the microarray but not by the multiplex PCR-agarose gel. The oligonucleotide microarray provides a highly efficient diagnosis alternative that could be applied to clinical usage, greatly assisting in disease therapy and control. (C) 2017 Elsevier B.V. All rights reserved.
Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B.burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B.burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B.burgdorferi infection. Thus, obesity and B.burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.
Tick-borne borreliae include Lyme disease and relapsing fever agents, and they are transmitted primarily by ixodid (hard) and argasid (soft) tick vectors, respectively. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering vertebrate host skin is with local antigen-presenting cells, regardless of whether the tick-associated Borrelia sp. is pathogenic. In this study, we performed a basic comparison of cytokine responses in THP-1-derived macrophages after exposure to selected borreliae, including a nonpathogen. By using THP-1 cells, differentiated to macrophages, we eliminated variations in host response and reduced the system to an in vitro model to evaluate the extent to which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi (B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides (LPS) (activated) or media (no treatment) controls. Intracellular and secreted interferon (IFN)-gamma, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured using flow cytometric and Luminex-based assays, respectively, at 6, 24, and 48 h postexposure time points. Using a general linear model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no treatment) had a significant effect on secreted TNF-alpha only. Time point had a significant effect on intracellular IFN-gamma, TNF-alpha and IL-6. However, we did not see significant differences in selected cytokines among Borrelia spp. treatments. Thus, in this model, we were unable to distinguish pathogenic from nonpathogenic borreliae using the limited array of selected cytokines. While unique immune profiles may be detectable in an in vitro model and may reveal predictors for pathogenicity in borreliae of unknown pathogenicity, a larger panel of cytokines would be desirable to test.
The translationally controlled tumor protein (TCTP) is an important component of the target of rapamycin (TOR) signaling pathway, the major regulator of cell growth in animals and fungi. Despite its relevance, knowledge on plant TCTP homologs is still limited. In the present study, the full-length BoTCTP cDNA was isolated from a cabbage (Brassica oleracea L.) cDNA library. The BoTCTP cDNA encodes a polypeptide of 168 amino acids and shared the highly conserved GTPase binding surface in all of the species analyzed. Northern blotting analysis showed that BoTCTP was specifically expressed in the root and stem. Furthermore, the expression of BoTCTP could be obviously enhanced by stress stimuli, including high temperature and salt stresses, while no significant changes in the BoTCTP expression were observed under ABA stress. Functional analysis of BoTCTP was performed by the silencing of BoTCTP using RNA interference (RNAi) and the BoTCTP RNAi plants exhibited reduced vegetative growth rate and decreased tolerance of the cold, high temperature, and salt stresses. The reported results clearly suggest that the BoTCTP gene is involved in the regulation of both growth and stress response in cabbage.
Introduction: Botulinum toxin (BT) is used in many medical specialties to treat muscle hyperactivity, exocrine gland hyperactivity and pain disorders. BT drugs consist of botulinum neurotoxin (BNT), complexing proteins (CP) and excipients. Antibodies can be formed against BNT and CP. When they are formed against BNT (BTAB) they can block BT's therapeutic efficacy thus producing antibody induced therapy failure (ABTF).Areas covered: BT applied and BTAB are in a functional balance within the body. ABTF is rare, but influences the treatment algorithms of BT therapy considerably. ABTF risk factors include BT doses given, interinjection intervals, booster injections and immunological quality of the BT drug. Testing for BTAB and interpretation of ABTF is complicated. As management of ABTF is frustrating, prevention of ABTF is of major importance. Improved antigenicity of new BT drugs may improve treatment algorithms of BT therapy, substandard antigenicity may very likely be their end.Expert commentary: Concern about ABTF has influenced the treatment algorithms of BT therapy considerably. Better understanding of ABTF may improve them and, thus, the outcome of BT therapy. New BT drugs may have further improved antigenicity, especially when their CP are removed. They may, however, fail because of antigenicity problems.
Conventional phase leading input current (PLIC) compensation techniques have focused on a continuous conduction mode (CCM) boost power factor corrector (PFC). In precedent studies, the causes of the PLIC have been investigated by analyzing the current control loop and the input impedance of a boost PFC. However, in a boundary conduction mode (BCM) boost PFC, the current flowing through the input filter capacitor becomes a main cause due to its large ripple current. Despite that, there has not been any effort to compensate the current in the input filter capacitor (IFC) in a BCM boost PFC. In this paper, a new digital control method is proposed to compensate PLIC in a BCM boost PFC, by minimizing the effect of the IFC. The proposed method uses only the derivative of the input voltage, without any additional component. Also, the proposed method improves the displacement factor, but does not affect the distortion factor, resulting in a high power quality in the entire input and output conditions. The derivation of the proposed method is presented based on time-domain analysis, and the effectiveness of the proposed method is experimentally verified with a 60-Hz, 90-230 V-rms input and 395-V/0.5-A output prototype.
This paper presents a novel predictive digital control method for boundary conduction mode PFC converters without the need for detecting the inductor current. In the proposed method, the inductor current is predicted by analytical equations instead of being detected by a sensing-resistor. The predicted zero-crossing point of the inductor current is determined by the values of the input voltage, output voltage and predicted inductor current. Importantly, the prediction of zero-crossing point is achieved in just a single switching cycle. Therefore, the errors in predictive calculation caused by parameter variations can be compensated. The prediction of the zero-crossing point with the proposed method has been shown to have good accuracy. The proposed method also shows high stability towards variations in both the inductance and output power. Experimental results demonstrate the effectiveness of the proposed predictive digital control method for PFC converters.
In boost converters and other indirect energy transfer topologies, transient-oriented controllers are designed to facilitate a dynamic response that may range from minimum time up to minimum output voltage deviation. Since analytical definitions for these control laws can become quite complex, a large-signal stability verification is not immediate. This paper explores the existence of stability of indirect energy transfer converters that are controlled by either boundary or hybrid controllers and introduces a new simplified procedure for examination of large-signal stability of a given converter and load type using a graphical-analytical approach. The stability analysis and examination method are demonstrated on a boost converter loaded by resistive load and constant current load. The stability conditions are verified using a 30 W 3.3-to-12 V boost converter prototype, controlled by a programmable-deviation controller and time-optimal controller, verifying their large-signal stability.
This article explores socially withdrawn young Finnish people on an Internet forum who identify with the Japanese hikikomori phenomenon. We aim to overcome the dualism between sociology and psychology found in earlier research by referring to Pierre Bourdieu, who provides insights into how individual choices are constructed in accordance with wider social settings. We focus on the individual level and everyday choices, but we suggest that psychological factors (anxiety, depression) can be seen as properties of social relations rather than as individual states of mind, as young adults have unequal access to valued resources. We scrutinise young people's specific reasoning related to the social and psychological factors and contingent life events that influence their choice to withdraw. An experience of inadequacy, a feeling of failure and a lack of self-efficacy are common experiences in the data. This indicates that young adults who identify with the hikikomori phenomenon find external society demanding and consider themselves lacking resources such as education, social networks or the personality type that they see as valued in society and as essential to survival'. They also feel that they cannot control their life events, which may mean that they receive little help in their everyday lives.
We have previously shown that there is high Na(+)/Ca(2+) exchange (NCX) activity in bovine adrenal chromaffin cells. In this study, by monitoring the [Ca(2+)](i) change in single cells and in a population of chromaffin cells, when the reverse mode of exchanger activity has been initiated, we have shown that the NCX activity is enhanced by K(+). The K(+)-enhanced activity accounted for a significant proportion of the Na(+)-dependent Ca(2+) uptake activity in the chromaffin cells. The results support the hypothesis that both NCX and Na(+)/Ca(2+)-K(+) exchanger (NCKX) are co-present in chromaffin cells. The expression of NCKX in chromaffin cells was further confirmed using PCR and northern blotting. In addition to the plasma membrane, the exchanger activity, measured by Na(+)-dependent (45)Ca(2+) uptake, was also present in membrane isolated from the chromaffin granules enriched fraction and the mitochondria enriched fraction. The results support that both NCX and NCKX are present in bovine chromaffin cells and that the regulation of [Ca(2+)](i) is probably more efficient with the participation of NCKX.
Background: In this study we evaluated the RespoCheck Mycoplasma triplex real-time PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.) dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory disease (BRD). Primers and probes of the RespoCheck Mycoplasma triplex real-time PCR are based on the V3/V4 region of the 16S rRNA gene of the three Mycoplasma species. Results: The analytical sensitivity of the RespoCheck triplex real-time PCR was, as determined by spiking experiments of the Mycoplasma strains in Phosphate Buffered Saline, 300 colony forming units (cfu)/mL for M. dispar, and 30 cfu/mL for M. bovis or M. bovirhinis. The analytical sensitivity of the RespoCheck Mycoplasma triplex real-time PCRwas, as determined on purified DNA, 10 fg DNA per assay for M. dispar and 100 fg fo rM. bovis and M. bovirhinis. The analytical specificity of the RespoCheck Mycoplasma triplex real-time PCR was, as determined by testing Mycoplasmas strains (n = 17) and other bacterial strains (n = 107), 100, 98.2 and 99.1% for M. bovis, M. dispar and M. bovirhinis respectively. The RespoCheck Mycoplasma triplex real-time PCR was compared with the PCR/DGGE analysis for M. bovis, M. dispar and M. bovirhinis respectively by testing 44 BALF samples from calves. Conclusion: In conclusion, the RespoCheck PCR assay can be a valuable tool for timely and accurate detection of three Mycoplasma species associated with in bovine respiratory disease.
Background: Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract. The objective of this study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung and lymph node tissue samples harvested from fatal BRD cases and clinically healthy animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue samples were collected from calves diagnosed as BRD cases by veterinary laboratory pathologists and from clinically healthy calves. NGS 16S amplicon libraries, targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology (QIIME) was used to determine operational taxonomic units (OTUs) which corresponded to the 16S rRNA gene sequences. Results: Leptotrichiaceae, Mycoplasma, Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae, Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative abundances in post-mortem lung samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances in post-mortem lymph node samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Two Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-enriched shotgun sequences. Conclusions: The microbiomes of the cranial lung lobe and mediastinal lymph node from calves which died from BRD and from clinically healthy H-F calves have been characterised. Contigs corresponding to the abundant Leptotrichiaceae OTU were sequenced and found not to be identical to any known bacterial genus. This suggests that we have identified a novel bacterial species associated with BRD.
Extrafetal tissues are a noncontroversial and inexhaustible source of mesenchymal stem cells that can be harvested noninvasively at low cost. In the veterinary field, as in man, stem cells derived from extrafetal tissues express plasticity, reduced immunogenicity, and have high anti-inflammatory potential making them promising candidates for treatment of many diseases. Umbilical cord mesenchymal cells have been isolated and characterized in different species and have recently been investigated as potential candidates in regenerative medicine. In this study, cells derived from bovine Wharton jelly (WJ) were isolated for the first time by enzymatic methods, frozen/thawed, cultivated for at least 10 passages, and characterized. Wharton jelly-derived cells readily attached to plastic culture dishes displaying typical fibroblast-like morphology and, although their proliferative capacity decreased to the seventh passage, these cells showed a mean doubling time of 34.55 +/- 6.33 hours and a mean frequency of one colony-forming unit fibroblast like for every 221.68 plated cells. The results of molecular biology studies and flow cytometry analyses revealed that WJ-derived cells showed the typical antigen profile of mesenchymal stem cells and were positive for CD29, CD44, CD105, CD166, Oct-4, and c-Myc. They were negative for CD34 and CD14. Remarkably, WJ-derived cells showed differentiation ability. After culture in induced media, WJ-derived cells were able to differentiate into osteogenic, adipogenic, chondrogenic, and neurogenic lines as shown by positive staining and expression of specific markers. On polymerase chain reaction analysis, these cells were negative for MHC-II and positive for MHC-I, thus reinforcing the role of extrafetal tissue as an allogenic source for bovine cell-based therapies. These results provide evidence that bovine WJ-derived cells may have the potential to differentiate to repair damaged tissues and reinforce the importance of extrafetal tissues as stem cell sources in veterinary regenerative medicine. A more detailed evaluation of their immunologic properties is necessary to better understand their potential role in cellular therapy. (C) 2016 Elsevier Inc. All rights reserved.
Objective: Skeletal dysplasia with bowing long bones is a rare group of multiple characterized congenital anomalies. Materials and Methods: We introduce a simple, practical diagnostic flowchart that may be helpful in identifying the appropriate pathway of obstetrical management. Results: Herein, we describe four fetal cases of bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests, distinctive X-ray features, and chondral growth plate histology. The first case was a typical campomelic dysplasia resulting from a de novo mutation in the SOX9 gene. The second fetus was affected by osteogenesis imperfecta Type II carrying a mutation in the COLA1 gene. The third case was a rare presentation of campomelic dysplasia, Cumming type, in which SOX9 examination was normal. Subsequently, a femoral hypoplasia unusual fades syndrome is also discussed. Conclusion: Targeted molecular tests and genetic counseling are required for supplementing ultrasound imaging in order to diagnose the correct skeletal disorders. Copyright (C) 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
OBJECTIVE: To define the increased mRNA expression of Bpifb1, a member of the bactericidal/permeability-increasing protein family, in parotid acinar cells from non-obese diabetic (NOD) mice, an animal model for Sjogren's syndrome. MATERIALS AND METHODS: Parotid acinar cells were prepared from female NOD (NOD/ShiJcl) mice with or without diabetes, as well as from control (C57BL/6JJcl) mice. Total RNA and homogenate were prepared from the parotid acinar cells. Embryonic cDNA from a Mouse MTC (TM) Panel I kit was used. The expression of Bpifb1 was determined by cDNA microarray analysis, RT-PCR, real-time PCR, northern blotting and in situ hybridization. RESULTS: The expression of Bpifb1 mRNA was high in parotid acinar cells from diabetic and non-diabetic NOD mice at 5-50 weeks of age. Acinar cells in the C57BL/6 mice had a low expression of Bpifb1 mRNA at an age >8 weeks, but had a relatively high expression in the foetus and infantile stages. CONCLUSIONS: Bpifb1 mRNA is upregulated in parotid acinar cells in NOD mice, but its expression is not related to the onset of diabetes. These findings suggest that high expression levels of Bpifb1 might predict disease traits before the onset of autoimmunity.
Previous studies have demonstrated that targeting bradykinin receptors is a promising strategy to counteract the cognitive impairment related with aging and Alzheimer's disease (AD). The hippocampus is critical for cognition, and abnormalities in this brain region are linked to the decline in mental ability. Nevertheless, the impact of bradykinin signaling on hippocampal function is unknown. Therefore, we sought to determine the role of hippocampal bradykinin receptors B1R and B2R on the cognitive decline of middle-aged rats. Twelve-month-old rats exhibited impaired ability to acquire and retrieve spatial information in the Morris water maze task. A single intra-hippocampal injection of the selective B1R antagonist des-Arg(9)-[Leu(8)]-bradykinin (DALBK, 3 nmol), but not the selective B2R antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-BK (Hoe 140, 3 nmol), reversed the spatial learning and memory deficits on these animals. However, both drugs did not affect the cognitive function in 3-month-old rats, suggesting absence of nootropic properties. Molecular biology analysis revealed an up-regulation of B1R expression in the hippocampal CA1 sub-region and in the pre-frontal cortex of 12-month-old rats, whereas no changes in the B2R expression were observed in middle-aged rats. These findings provide new evidence that inappropriate hippocampal B1R expression and activation exert a critical role on the spatial learning and memory deficits in middle-aged rats. Therefore, selective B1R antagonists, especially orally active non-peptide antagonists, may represent drugs of potential interest to counteract the age-related cognitive decline. (C) 2016 Elsevier B.V. All rights reserved.
OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor (BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.
Aim: Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. Materials & methods: We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. Results: The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). Conclusion: In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.
BackgroundThe role of BRAF mutations in cancerogenesis has been demonstrated in several solid tumor types. However, in salivary gland tumors, this genetic alteration is very uncommon, and its role still remains unclear. Thus, the aim of this study was to analyze BRAF V600E (VE1) protein expression with BRAF mutation status in codon 600, in malignant and benign salivary gland tumors. MethodsStudies were performed on archived formalin-fixed paraffin-embedded tissue sections derived from 95 patients who underwent surgery for tumors of the salivary gland. Immunohistochemical staining (IHC) on tissue microarray slides was performed for evaluation of BRAF V600E (VE1) protein expression, and the automatic molecular diagnostics platform was used for the evaluation of mutations in codon 600 of BRAF gene. ResultsIHC cytoplasmic expression of BRAF V600E (VE1) protein was found in two of 95 cases: one case of adenocarcinoma NOS (one of three; 33%) and one case of carcinoma ex pleomorphic adenoma (one of five; 20%). Although, in IHC studies, nuclear BRAF V600E (VE1) protein expression was found in 14 (15%) of the analyzed cases: nine of 28 (32%) cases of pleomorphic adenoma, three of five (60%) cases of ductal carcinoma, one of nine (11%) case of mucoepidermoid carcinoma, and in one of five (20%) case of carcinoma ex pleomorphic adenoma. All cases were negative for polymerase chain reaction PCR-based analyses of BRAF mutations in codon 600. ConclusionsIn studied salivary gland cancers, no PCR-based prove mutations of BRAF V600 were detected. Further molecular analyses are necessary to rapid molecular arrays for the identification of specific mutations, optimal for individualized targeted therapies.
To examine molecular events in hippocampus associated with aging and acupuncture effect, we employed cDNA arrays providing data of 588 genes to define transcriptional patterns. Male 8-month-old SAMP 10 and its homologous SAMR1 were selected and randomly divided into four groups: RI control group (Rc), P10 control group (PC), P10 acupuncture group (Pa) and PIO non-acupoint group (Pn). The points consisted Shanzhong (CV17), Zhongwan (CV12), Qihai (CV6), Zusanli (ST36) and Xuehai (SPIO). In Pa, we found that points stimuli could completely or partly reverse some genes expression profiles in hippocampus with aging. Simultaneously, some genes not related with brain aging were affected by acupuncture as well. Meanwhile, non-acupoint had some effect on aging-unrelated genes expression and little or negative effect on aging-related genes. We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1. In conclusion, acupuncture Could be a potential intervention to retard molecular events with aging in mammals. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
As the most fascinating, complex, and dynamic part of our organism, the human brain is shaped by many interacting factors that not only are of neurobiological (including sex hormones) and environmental origin but are also sociocultural in their very nature (such as social roles). Gender is one of these factors. Most neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders are characterized by impairments in visual social cognition (primarily body language reading and face perception) and a skewed sex ratio: females and males are affected differently in terms of clinical picture, prevalence, and severity. Is the social brain sex specific? This is still an open question. For a long time and for many reasons, sex differences have been overlooked or entirely ignored in neuroscience and biomedical research: there is a paucity of neuroimaging work examining sex differences in the social brain. However, the pattern of experimental behavioral data in both healthy, typically developing individuals and patients with deficient social cognition is beyond simple interpretation: contrary to popular wisdom, females are not always more proficient in understanding social signals, and their social abilities may be particularly affected by disease. Clarification of how neurobiological sex and sociocultural gender affect the social brain would provide novel insights into understanding gender-specific vulnerability to neuropsychiatric disorders. This interaction is far beyond simplicity. Although sex differences represent a rather delicate topic, underestimation or exaggeration of possible effects retards progress in the field. (C) 2016 Wiley Periodicals, Inc.
Objective. Brain-computer interfaces (BCIs) can help patients who have lost control over most muscles but are still conscious and able to communicate or interact with the environment. One of the most popular types of BCI is the P300-based BCI. With this BCI, users are asked to count the number of appearances of target stimuli in an experiment. To date, the majority of visual P300-based BCI systems developed have used the same character or picture as the target for every stimulus presentation, which can bore users. Consequently, users attention may decrease or be negatively affected by adjacent stimuli. Approach. In this study, a new stimulus is presented to increase user concentration. Honeycomb-shaped figures with 1-3 red dots were used as stimuli. The number and the positions of the red dots in the honeycomb-shaped figure were randomly changed during BCI control. The user was asked to count the number of the dots presented in each flash instead of the number of times they flashed. To assess the performance of this new stimulus, another honeycomb-shaped stimulus, without red dots, was used as a control condition. Main results. The results showed that the honeycomb-shaped stimuli with red dots obtained significantly higher classification accuracies and information transfer rates (p < 0.05) compared to the honeycomb-shaped stimulus without red dots. Significance. The results indicate that this proposed method can be a promising approach to improve the performance of the BCI system and can be an efficient method in daily application.
Social cognition refers to the ability to use social cues to infer the meaning and intentions behind the behaviour of others in order to respond in a socially adaptive manner. It is increasingly recognised that disorders of social cognition, including problems with emotion perception, theory of mind, conversational inference, morality judgements, decision making and social inhibition, characterise many developmental and psychiatric disorders and are highly relevant to many with acquired brain injuries or diseases, especially the frontotemporal dementias. This review provides an introduction and overview of the papers in this special edition on social cognition and places these in the context of other recent research. In doing so, several current issues in the clinical management of social cognition are delineated. Given that social cognition seems to be a sensitive predictor of psychosocial function, the assessment of social cognition is seen by many clinicians to be important although which profession is responsible is yet to be resolved. Issues in how social cognition are assessed are discussed, including the importance of context to social cognition, its interactive nature and the need to recognise influences such as family upbringing, gender and emotional state on social cognitive performance. There also needs to be development of tests that address all aspects of social cognition, including decision making and inhibition. Finally, this review discusses intervention research. Interventions are especially well developed in relation to schizophrenia, and less well developed in brain injury. These appear to be generally effective although treatments for emotional self-awareness are yet to be developed.
Confronted with brain metastases (BM), pathologists aim to rule out a primary central nervous system (CNS) tumor and to identify or verify the primary tumor site to guide the clinician to specific therapies. Apart from morphological features, ancillary immunohistochemical analysis is the most effective tool for characterizing a metastatic neoplasm of unknown origin. A limited array of antibodies is used, taking into account relevant clinical information and the known brain tropism of lung cancer, breast cancer and melanoma. Recently, targeted therapies have enriched the therapeutic arsenal, in particular for patients with non-small cell lung cancer or melanoma and for patients carrying molecular anomalies. These therapies can lead to a substantial tumor response, brain metastases included, which justifies rapid determination of a molecular profile. To combine different tools and provide timely results, good tumor sample management and careful attention at the pre-analytical phase are critical. Appropriate strategies for molecular and immunohistochemical analysis are needed to identify theranostic markers. This article aims to review the anatomopathological diagnostic approach for BM in the age of targeted therapies.
Background: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients' outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743-43.881], p = 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078-0.699], p = 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240-41.012], p = 0.028), but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM.
Brain single-photon emission computerized tomography (SPECT), in particular, with perfusion agents or with neuroreceptor imaging radiopharmaceuticals, is rapidly becoming a clinical tool in many neurologic and psychiatric conditions. This imaging modality has been used for diagnosis, prognosis assessment, evaluation of response to therapy, risk stratification, detection of benign vs. malignant viable tissue, and the choice of medical or surgical therapy. We will present our institutional experience in this area, formatting a pictorial review of brain perfusion SPECT on more than 20 types of different neurologic and psychiatric diseases, such as dementia, epilepsy, cerebral palsy, head injury, brain tumor, herpes encephalitis, hypoxic brain damage, vacuities, depression, carbon monoxide (CO) poisoning, and cocaine abuse. This is a demanding procedure as far as the need for trained and experienced physicians and personnel as well as advanced equipment are concerned. However, extraordinary useful clinical information achieved by this technology outweighs the existing challenge. More routine use of this procedure which is unfortunately underutilized in many countries including ours should be encouraged.
Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II.
Basic helix-loop-helix PAS domain proteins form a growing family of transcription factors. These proteins are involved in the process of adaptation to cellular stresses and environmental factors such as a change in oxygen concentration. We describe the identification and characterization of a recently cloned PAS domain protein termed Npas4 in ischemic rat brain. Using gene expression profiling following middle cerebral artery occlusion, we showed that the Npas4 mRNA is differentially expressed in ischemic tissue. The full-length gene was cloned from rat brain and its spatial and temporal expression characterized with in situ hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in the brain and is highly up-regulated in ischemic tissues following both focal and global cerebral ischemic insults. Immunohistochemistry revealed a strong expression in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a protein of similar to 100 kDa. In brain samples, however, in addition to the 100 kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the 100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for activation and/or deactivation of this protein in response to ischemic brain injury.
Although, overwhelmingly, behavior is similar in males and females, and, correspondingly, the brains are similar, sex differences permeate both brain and behavioral measures, and these differences have been the focus of increasing scrutiny by neuroscientists. This Review describes milestones from more than 3 decades of research in brain and behavior. This research was necessarily bound by available methodology, and we began with indirect behavioral indicators of brain function such as handedness. We proceeded to the use of neuropsychological batteries and then to structural and functional neuroimaging that provided the foundations of a cognitive neuroscience-based computerized neurocognitive battery. Sex differences were apparent and consistent in neurocognitive measures, with females performing better on memory and social cognition tasks and males on spatial processing and motor speed. Sex differences were also prominent in all major brain parameters, including higher rates of cerebral blood flow, higher percentage of gray matter tissue, and higher interhemispheric connectivity in females, compared with higher percentage of white matter and greater intrahemispheric connectivity as well as higher glucose metabolism in limbic regions in males. Many of these differences are present in childhood, but they become more prominent with adolescence, perhaps linked to puberty. Overall, they indicate complementarity between the sexes that would result in greater adaptive diversity. (C) 2016 Wiley Periodicals, Inc.
One-third of cancer patients undergoing chemotherapy treatment often display symptoms of depression leading to poor adherence and decreased quality of life. Thus, this study aimed to investigate the possible protective effect of nebivolol against cisplatin-associated depressive symptoms in adult male rats. Nebivolol is a highly cardioselective -adrenergic receptor blocker that possesses endothelium-dependent vasodilator properties and antioxidant capacities. Animals were allocated into four groups. Group one was given aqueous solution of carboxymethyl cellulose and served as control, group two was given nebivolol (10mg/kg p.o., daily), group three was given cisplatin (2mg/kg i.p. once per week) for 10 consecutive weeks and group four was treated with cisplatin concomitantly with nebivolol as per above schedule. Cisplatin-treated rats showed an increase in both depressive-like behaviors in open-field and forced swimming tests. In addition, histopathological examination revealed cortical encephalomalacia along with hippocampal neuronal degeneration and kidney dysfunction. In parallel, cisplatin administration prominently reduced GABA and elevated glutamate levels in the cortical and hippocampal tissues. Furthermore, it resulted in a significant decline in cortical and hippocampal brain-derived neurotrophic factor and nitric oxide contents concomitantly with a marked decrease in endothelial- and an increase in inducible-nitric oxide synthase genes expression. On the other hand, treatment with nebivolol effectively mitigated the aforementioned cisplatin-associated behavioral, biochemical, and histopathological alterations without changing its antitumor activity as evidenced by sulforhodamine B cell survival assay. Taken together, our results suggest that nebivolol may offer a promising approach for alleviating depressive symptoms associated with the use of cisplatin.
Background: Preclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS. Methods: Behavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions. Results: Using unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory-and salience-related regions, and with a history of early life trauma. Conclusions: The results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.
(R)ecent advances in deep brain stimulators and brain -machine interfaces have greatly expanded the possibilities of neuroprosthetics and neuromodulation. Together with advances in neuroengineering, nanotechnology, molecular biology and material sciences, it is now possible to address fundamental questions in neuroscience in new, more powerful ways. It is now possible to apply these new technologies in ways that range from augmenting and restoring function to neuromodulation modalities that treat neuropsychiatric disorders. Recent developments in neuromodulation methods offer significant advantages and potential clinical benefits for a variety of disorders. Here we describe the current state of the art in neuromodulation methods, and some advances in brain -machine interfaces, describing the advantages and limitations of the clinical applications of each method. The future applications of these new methods and how they will shape the future of psychiatry and medicine, along with safety and ethical implications, are also discussed. (c) 2017 Elsevier Inc. All rights reserved.
Introduction. - Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children. In this study the authors present their experience with frameless robotic-guided biopsy of DIPG in a pediatric population. Patients and methods. - Retrospective study on a series of five consecutive pediatric patients harboring DIPG treated over a 4-year period. All patients underwent frameless robotic-guided biopsy via a transcerebellar approach. Results. - Among the 5 patients studied 3 were male and 2 female with a median age of 8.6 years [range 5 to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56 minutes (range 45 to 67 minutes). No new postoperative neurological deficits were recorded. Histological diagnosis was achieved in all cases as follows: two anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma (grade III). Conclusion. - Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis. (C) 2016 Elsevier Masson SAS. All rights reserved.
Diffuse intrinsic pontine glioma (DIPG) is a malignant brain tumor of childhood that carries an extremely poor prognosis. There are similar to 200-300 new cases diagnosed each year, [1, 2] and little progress has been made in changing the prognosis and outcome of the tumor since it was first documented in the literature in 1926 [3]. The median overall survival is 8-11 months [4], with an overall survival rate of 30% at 1 year, and less than 10% at 2 years [4]. This review will provide background information on DIPGs, a historical look at the trends in caring for DIPG, and current trends in diagnosis and treatment. By changing the way we care for these terminal tumors, we can work towards having a better understanding of the underlying molecular biology, and attempt to develop better chemotherapeutic tools to combat the disease.
We study the energy dispatch of power distribution networks (PDNs) coupled with urban transportation networks. The electricity demand at each charging/swapping facility is influenced by the arrival rates and charging requests of electric vehicles, which further depends on the spatial distribution of traffic flows over the entire transportation system. We consider the impact of the road congestion on route choices of vehicles from a system-level perspective. The traffic flow pattern in steady state is characterized by the Wardrop user equilibrium. We consider the PDN load perturbation caused by the traffic demand uncertainty, and propose a robust dispatch method that maintains the feasibility of an alternating current power flow constraints. By applying the convex relaxation to nonlinear branch power flow equations, the proposed model yields a two-stage robust convex optimization problem with an implicit uncertainty set. Moreover, a decomposition framework is proposed, in which the first phase determines the uncertainty set of electricity demand by solving two traffic assignment problems associated with the extreme scenarios, and the second phase solves a two-stage robust second-order cone program following a delayed constraint generation framework. Several issues regarding the scalability and conservatism are elaborated. Case studies corroborate the applicability and efficiency of the proposed method.
Three genes, gnd, pgl, and fbp, relevant to the pentose phosphate pathway (PPP) were overexpressed in Corynebacterium glutamicum IWJ001, leading to increase of L-isoleucine production. The transcriptional levels of gnd, pgl, and fbp significantly increased in IWJ001/pDXW-8-gnd-fbp-pgl. Compared with the control strain IWJ001/pDXW-8, intracellular NADPH/NADP(+) ratios in IWJ001/pDXW-8-gnd and IWJ001/pDXW-8-gnd-fbp cells grown for 36 H increased threefold and fourfold, respectively, indicating that overexpression of gnd and fbp redirected the carbon flux to PPP. Intracellular NADPH/NADP(+) ratio in IWJ001/pDXW-8-gnd-fbp-pgl grown for 36 H was similar to IWJ001/pDXW-8, suggesting that the NADPH produced by PPP could be quickly consumed for L-isoleucine production. 10.9 and 28.96 g/L of L-isoleucine was produced in IWJ001/pDXW-8-gnd-fbp-pgl in shake flask cultivation and fed-batch fermentation, respectively. In addition, IWJ001/pDXW-8-gnd-fbp-pgl grew fast, its dry cell weight reached 49 g/L after 48 H, whereas the start strain IWJ001/pDXW-8 reached only 40 g/L. After 96 H fermentation, L-isoleucine yield on glucose in IWJ001/pDXW-8-gnd-fbp-pgl reached 0.138 g/g. The results demonstrate that carbon flux redirection to PPP is an efficient approach to enhance L-isoleucine production in C. glutamicum. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 877-885, 2016
Background: During embryogenesis, tight regulation of retinoic acid (RA) availability is fundamental for normal development. In parallel to RA synthesis, a negative feedback loop controlled by RA catabolizing enzymes of the cytochrome P450 subfamily 26 (CYP26) is crucial. In vertebrates, the functions of the three CYP26 enzymes (CYP26A1, CYP26B1, and CYP26C1) have been well characterized. By contrast, outside vertebrates, little is known about CYP26 complements and their biological roles. In an effort to characterize the evolutionary diversification of RA catabolism, we studied the CYP26 genes of the cephalochordate amphioxus (Branchiostoma lanceolatum), a basal chordate with a vertebrate-like genome that has not undergone the massive, large-scale duplications of vertebrates. Results: In the present study, we found that amphioxus also possess three CYP26 genes (CYP26-1, CYP26-2, and CYP26-3) that are clustered in the genome and originated by lineage-specific duplication. The amphioxus CYP26 cluster thus represents a useful model to assess adaptive evolutionary changes of the RA signaling system following gene duplication. The characterization of amphioxus CYP26 expression, function, and regulation by RA signaling demonstrated that, despite the independent origins of CYP26 duplicates in amphioxus and vertebrates, they convergently assume two main roles during development: RA-dependent patterning and protection against fluctuations of RA levels. Our analysis suggested that in amphioxus RA-dependent patterning is sustained by CYP26-2, while RA homeostasis is mediated by CYP26-1 and CYP26-3. Furthermore, comparisons of the regulatory regions of CYP26 genes of different bilaterian animals indicated that a CYP26-driven negative feedback system was present in the last common ancestor of deuterostomes, but not in that of bilaterians. Conclusions: Altogether, this work reveals the evolutionary origins of the RA-dependent regulation of CYP26 genes and highlights convergent functions for CYP26 enzymes that originated by independent duplication events, hence establishing a novel selective mechanism for the genomic retention of gene duplicates.
BACKGROUND: Glutamine synthetase (GS; EC 6.3.1.2) is a key enzyme of nitrogen (N) assimilation, catalysing the synthesis of glutamine from ammonium and glutamate. Plants have two types of GS isoenzyme that are localised in different compartments: one in the cytosol (GS1) and the other in the chloroplast (G52). GS1 is the major form of GS in plant roots and directly converts ammonium taken up by plant roots to glutamine. RESULTS: The GS1 gene cDNA of non-heading Chinese cabbage (Brassica campestris ssp. chinensis Makino) cultivar 'Suzhouqing' was isolated by RT-PCR (real-time polymerase chain reaction) and (5'/3')-RACE (rapid amplification of cDNA ends) techniques. It was classified as GS1 by sequence alignment and motif search and named B. campestris ssp. chinensis Makino GS1 (BcGS1). Subcellular localisation analysis showed that BcGS1 was distributed in the cytoplasm of cells. BcGS1 was expressed in all parts, but mainly in the roots, which was verified by northern blotting analysis. Additionally, its expression was influenced by the N source concentration. CONCLUSION: These results suggest that BcGS1 is a novel member of the GS family in plants. BcGS1 was significantly related to N assimilation in non-heading Chinese cabbage, demonstrating that this gene plays an important role in plant growth and development. (C) 2010 Society of Chemical Industry
FLOWERING LOCUS C (FLC), which encodes a MADS-box domain protein, is a flowering repressor involved in the key position of Arabidopsis (Arabidopsis thaliana) flowering network. In Brassica species, several FLC homologues are involved in flowering time like Arabidopsis FLC. Here, we report the analysis of splicing variation in BrpFLC1 and the expression of BrpFLC homologues associated with early flowering of Purple Flowering Stalk (Brassica campestris L. ssp. chinensis L. var. purpurea Bailey). It was indicated that a splice site mutation happened in intron 6 with G to A at the 5' splice site. Three alternative splicing patterns of BrpFLC1, including the entire exon 6 excluded and 24 bp or 87 bp of intron 6 retained, were identified in Purple Flowering Stalk. But there was only one normal splicing pattern in Pakchoi (Brassica campestris ssp. chinensis var. communis). Northern blotting and semi-quantitative RT-PCR revealed that the expression levels of the three FLC homologues in Purple Flowering Stalk were lower than that in Pakchoi. However, the expression levels of downstream genes, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and FLOWERING LOCUS T (FT), were higher in Purple Flowering Stalk. These results suggest that a natural splicing site mutation in BrpFLC1 gene and repressed expression of all BrpFLC genes contribute significantly to flowering time variation in Purple Flowering Stalk.
The polygalacturonase (PG) gene family has been found to be enriched in pollen of several species; however, little is currently known about the function of the PG gene in pollen development. To investigate the exact role that the PG gene has played in pollen development and about this family in general, one putative PG gene, Brassica campestris Male Fertility 9 (BcMF9), was isolated from Chinese cabbage (Brassica campestris ssp. chinensis, syn. B. rapa ssp. chinensis) and characterized. RT-PCR, northern blotting and in situ hybridization were used to analyse the expression pattern of BcMF9, and antisense RNA technology was applied to study the function of this gene. BcMF9 is expressed in particular in the tapetum and microspore during the late stages of pollen development. Antisense RNA transgenic plants that displayed decreased expression of BcMF9 showed pollen morphological defects that resulted in reduced pollen germination efficiency. Transmission electron microscopy revealed that the homogeneous pectic exintine layer of pollen facing the exterior was over-developed and predominantly occupied the intine, reversing the normal proportional distribution of the internal endintine layer and the external exintine in transgenic pollen. Inhibition of BcMF9 also resulted in break-up of the previously formed tectum and baculae from the beginning of the binucleate stage, as a result of premature degradation of tapetum. Several lines of evidence, including patterns of BcMF9 expression and phenotypic defects, suggest a sporophytic role in exine patterning, and a gametophytic mode of action of BcMF9 in intine formation. BcMF9 might act as a co-ordinator in the late stages of tapetum degeneration, and subsequently in the regulation of wall material secretion and, in turn, exine formation. BcMF9 might also play a role in intine formation, possibly via regulation of the dynamic metabolism of pectin.
Based on the significant differences in the resistance to Sclerotinia sclerotiorum between two Brassica napus cultivars, ZhongR888 and Zhongyou821, near isogenic lines (NILs) were established. The resistance differences between Zhongyou821 and BC5 progeny (the fifth generation from a cross between Zhongyou821 and ZhongR888 with Zhongyou821 as successive backcross parent) was displayed by cDNA-AFLP and differential transcripts-derived fragments (TDFs). The full-length cDNA of 1,707 bp with 1,323 bp open reading frame (ORF, open box), named Rsk was identified by RT-RACE from the resistance related fragment 40-2 in Zhongyou821. It encoded a protein of 440 amino acid residues, which contained a putative extracellular domain, a transmembrane domain, and an intracellular domain. Analysis of the deduced amino acid sequence of Rsk revealed that it had high homology to Arabidopsis thaliana kinase involved in protein binding, and had a conserved region of LRR-RI, indicating it might be a member of leucine-rich repeats, ribonuclease inhibitor-like subfamily. DNA sequences of 1,685 bp and 1,703 bp without an intron were also identified from Zhongyou821 and BC5, respectively. Expression analysis showed that Rsk might play a role in disease resistance pathways.
Oilseeds of the plant family Brassicaceae are important for providing both lipid and protein contents to human nutrition. Cruciferins (12S globulins) are seed storage proteins, which are getting attention due to their allergenic and pathogenicity related nature. This study describes the purification and characterization of a trimeric (similar to 190 kDa) cruciferin protein from the seeds of Brassica nigra (L). Cruciferin was first partially purified by ammonium sulfate precipitation (30% saturation constant) and further purified by size exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82% sequence homology with cruciferin from Arabidopsis thaliana. The 50-55 kDa monomeric cruciferin produced multiple bands of two major molecular weight ranges (a-polypeptides of 28-32 kDa and (beta-polypeptides of 17-20 kDa) under reduced conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further separation of the bands into their isoforms with major pI ranges between 5.7 and 8.0 (a-poly peptides) and 5.5-8.5 (beta-polypeptides). The Dynamic Light Scattering (DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of 5.8 +/- 0.1 nm confirming the trimeric nature of the protein. The Circular Dichroism (CD) spectra showed both a-helices and beta-sheets in the native conformation of the trimeric protein. The pure cruciferin protein (40 mg/m1) was successfully crystallized; however, the crystals diffracted only to low resolution data (8 A). Small-angle x-ray scattering (SAXS) was applied to gain insights into the three-dimensional structure in solution. SAXS showed that the radius of gyration is 4.24 +/- 0.25 nm and confirmed the nearly globular shape. The SAXS based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins (PDB ID: 3KGL) of B. napus which further confirmed a highly similar molecular weight and globular shape indicating a conserved trimerization of B. nigra cruciferin. The comparison of the scattering patterns of both proteins showed a minimized x(2)-value of 1.337 confirming a similar molecular structure. This is the first report describing the purification and characterization of a cruciferin protein from seeds of B. nigra. (C) 2017 Elsevier B.V. All rights reserved.
The species Brassica rapa includes various vegetable crops. Production of these vegetable crops is usually impaired by heat stress. Some microRNAs (miRNAs) in Arabidopsis have been considered to mediate gene silencing in plant response to abiotic stress. However, it remains unknown whether or what miRNAs play a role in heat resistance of B. rapa. To identify genomewide conserved and novel miRNAs that are responsive to heat stress in B. rapa, we defined temperature thresholds of non-heading Chinese cabbage (B. rapa ssp. chinensis) and constructed small RNA libraries from the seedlings that had been exposed to high temperature (46 degrees C) for 1 h. By deep sequencing and data analysis, we selected a series of conserved and novel miRNAs that responded to heat stress. In total, Chinese cabbage shares at least 35 conserved miRNA families with Arabidopsis thaliana. Among them, five miRNA families were responsive to heat stress. Northern hybridization and real-time PCR showed that the conserved miRNAs bra-miR398a and bra-miR398b were heat-inhibitive and guided heat response of their target gene, BracCSD1; and bra-miR156h and bra-miR156g were heat-induced and its putative target BracSPL2 was down-regulated. According to the criteria of miRNA and miRNA* that form a duplex, 21 novel miRNAs belonging to 19 miRNA families were predicted. Of these, four were identified to be heat-responsive by Northern blotting and/or expression analysis of the putative targets. The two novel miRNAs bra-miR1885b.3 and bra-miR5718 negatively regulated their putative target genes. 5'-Rapid amplification of cDNA ends PCR indicated that three novel miRNAs cleaved the transcripts of their target genes where their precursors may have evolved from. These results broaden our perspective on the important role of miRNA in plant responses to heat.
Recent advances in our understanding of the molecular biology of epithelial ovarian cancer have led to the development of a number of targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this therapeutic approach. Importantly, companion homologous recombination deficiency scores are being developed to help guide the selection of patients most likely to gain clinical benefit from PARP inhibition. Olaparib, the first and most extensively investigated PARP inhibitor, is now licensed in Europe for maintenance treatment of patients with platinum-sensitive relapsed BRCA-mutated (germ-line or somatic) high-grade serous ovarian cancer who have responded to platinum-based chemotherapy. In the United States, olaparib is licensed for treatment of patients with germline BRCA-mutated ovarian cancer who have received 3 or more lines of chemotherapy. There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. This review will focus on the current evidence for PARP inhibitors in ovarian cancer and discuss ongoing clinical trials and future research directions in this rapidly evolving area.
Germline BRCA2 mutations are the first known cause of inherited (familial) pancreatic ductal adenocarcinoma (PDAC). This tumor is the third most frequent cancer in carriers of germline BRCA2 mutations, as it occurs in around 10% of BRCA2 families. PDAC is known as one of the most highly lethal cancers, mainly because of its chemoresistance and frequently late diagnosis. Based on recent developments in molecular biology, a subgroup of BRCA2-associated PDAC has been created, allowing screening, early surgical treatment and personalized systemic treatment. BRCA2 germline mutation carriers who have >= 1 first-degree relative, or >= 2 blood relatives with PDAC, should undergo screening and regular follow-up based on magnetic resonance imaging and endoscopic ultrasound. The goal of screening is to detect early invasive PDAC and advanced precancerous lesions suitable for a stepwise surgical complete (R0) resection. Increasing evidence on the molecular role of the BRCA2 protein in the homologous recombination of DNA damages suggest that BRCA2-related PDAC are sensitive to agents causing DNA cross-linking damage, such as platinum salts, and treatments targeting rescue DNA repair pathways, such as poly(ADP-ribose) polymerase inhibitors that are currently under investigation.
Aims: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that locates characteristically to the midline of the head and neck, and mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare, and we report a case series of seven cases. Methods and results: We searched for cases in files of different hospitals as well as a thorough search of the English language literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, fluorescence in-situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three previously published cases, and in this series add four cases of our own. Conclusions: NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness among pathologists is warranted. NMC has characteristic morphological features, and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is emphasized further by new promising treatment strategies.
Irinotecan is a natural alkaloid agent widely used in cancer therapy. High-mobility group protein B1 as a non-histone chromosomal protein plays a fundamental role in gene expression and inflammation. In this study, the effect of irinotecan on high-mobility group protein B1 and MMP9 content, gene expression, cell cycle, and cell growth in human breast cancer cells (MCF-7) was investigated. The cells were exposed to various concentrations of irinotecan and the viability determined by trypan blue exclusion and 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazolium bromide assays. High-mobility group B proteins were extracted from the control and drug-treated cells and analyzed by immunoblot. High-mobility group protein B1 and MMP9 messenger RNA expression was studied by reverse transcription polymerase chain reaction. The results demonstrated reduction of cell viability upon increasing irinotecan concentration, up-regulated high-mobility group protein B1 gene expression, and down-regulated MMP9 mRNA. Although the content of high-mobility group protein B1 was decreased in chromatin extract upon drug action, no high-mobility group protein B1 release to extracellular space was detected by immunoblot analysis. Irinotecan decreased H3K9 acetylation and increased poly ADP-ribose polymerase fragmentation to 89 kDa and anion superoxide production suggesting induction of apoptosis in these cells. Propidium iodide staining of the cells 24 h after the drug treatment revealed arrest of the cells in S-phase. From the results, it is concluded that overexpression of high-mobility group protein B1 in the presence of irinotecan precedes breast cancer cells into apoptosis and in this response the binding of irinotecan to chromatin or high-mobility group protein B1 may condense/aggregate chromatin, preventing high-mobility group protein B1 release from chromatin.
Neoadjuvant chemotherapy, that is, the administration of chemotherapy before surgery, has been commonly used for locally advanced breast cancer to improve the surgical outcomes and increase the opportunity for breast-conserving therapy. Women with breast cancer often receive an anthracycline-based regimen as the neoadjuvant chemotherapy, which is associated with a high risk of emesis. Despite the development of novel antiemetics, chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as a major adverse effect, affecting the quality of life of the patients. However, the factors predicting CINV in women with breast cancer undergoing neoadjuvant chemotherapy remain unclear. In this single-institution, prospective, observational study conducted at an outpatient cancer centre in the Republic of Korea from November 2013 to March 2016, we analysed women with breast cancer who planned to be treated with neoadjuvant chemotherapy before surgery. Candidate factors associated with CINV were assessed before neoadjuvant chemotherapy using the Munich Chronotype Questionnaire, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. CINV was assessed after chemotherapy by using the Multinational Association of Supportive Care in Cancer Antiemesis Tool. Of a total of 143 participants, 7 patients were lost to follow-up and 2 patients were excluded due to changes in their treatment plan; thus, 134 patients were finally included in the analyses. Overall, 48.5% of the participants experienced CINV, with delayed CINV prevalence (42.5%) being more common than acute (39.6%). In the univariate analyses, overall CINV was significantly associated with late chronotypes (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.37-8.87; p = 0.009), a history of nausea/vomiting (OR, 2.19; 95% CI, 1.10-4.37; p = 0.026) and anxiety (OR, 2.25; 95% CI, 1.05-4.81; p = 0.036). In the multivariate analyses, late chronotypes (OR, 3.53; 95% CI, 1.27-9.79; p = 0.015) and a history of nausea/vomiting (OR, 2.83; 95% CI, 1.31-6.13; p = 0.008) remained significantly associated with CINV. In conclusion, in women with breast cancer undergoing neoadjuvant chemotherapy before surgery, late chronotypes were found to have an increased risk of CINV; these data suggest that clinicians need to assess and consider the chronotype in the management of CINV.
The present study tested the supposition that greater levels of couple identity (or we-ness) increase a woman's coping self-efficacy in relation to breast cancer, which, in turn, predicts better psychosocial adjustment. Women (N = 112) in committed relationships completed surveys assessing their levels of couple identity, cancer coping self-efficacy, and aspects of their psychosocial adjustment (specifically, depression, anxiety and functional well-being) during one of their outpatient visits to the cancer centre. As predicted, the more women identified with their relationships, the lower their levels of depression and anxiety were and the greater their functional well-being was. This relationship was mediated by coping self-efficacy: greater identification with one's relationship predicted greater confidence in one's ability to cope, which, in turn, predicted better adjustment. The role intimate relationships play in women's adjustment to breast cancer, as well as directions for further research, are discussed.
Background: High levels of distress are expected shortly after the diagnosis breast cancer. The Distress Thermometer (DT) is commonly used to screen for distress, using a cutoff score of 4 or 5; however, this score might not be appropriate for detecting distress in women with recently diagnosed breast cancer. Objectives: The aims of this study were to establish the optimal DT cutoff score for detecting high distress shortly after breast cancer diagnosis and to correlate this score with the reported problems. Methods: We selected for this study Dutch women who completed the DT and the Hospital Anxiety and Depression Scale within 1 month after breast cancer diagnosis. Receiver operating characteristic analysis of DT scores was performed, with the Hospital Anxiety and Depression Scale being used as the criterion standard for the level of distress. The sensitivity, specificity, positive predictive value, and negative predictive value of each DT score were calculated. Results: In total, 181 women participated in the study. The optimal DT cutoff score for detecting distress was 7 with a sensitivity of 0.73, specificity of 0.84, positive predictive value of 69%, and negative predictive value of 87%. Emotional problems were the most frequently reported concerns. Conclusion: We consider a cutoff score of 7, shortly after breast cancer is diagnosed, optimal to identify those women with high distress and therefore at risk of chronic distress. Implications for Practice: The findings are clinically important because they can enable healthcare professionals to direct their time and resources to those most in need of their assistance.
Treatment strategies in oncology are nowadays largely based on the "target therapy model", which allows to personalize the cure of each patient depending on distinctive host and disease features. As a general concept "targeted drugs" are effective only when the tumor exhibits the "target", which in breast cancer pathology may correspond to the expression of estrogen receptors and/or of HER2. These biomarkers are evaluated on breast cancer tissues by companion diagnostic tests, however, evidence suggests that the first step in breast cancer predictive pathology is still represented by morphology. For instance, histological types, such as tubular and cribriform carcinomas, define patients who may not need any treatments other than surgical excision. Neoadjuvant studies have shown that patients affected by lobular carcinomas are not likely to have any beneficial effects from chemotherapy. The second step in prediction is represented by immunophenotyping. If the immunohistochemical evaluation of four markers (estrogen and progesterone receptors, HER2 and Ki67) remains the best practice for breast cancer predictive pathology, molecular pathology has certainly reshaped the way we approach breast cancer diagnosis. The aim of this review is to discuss current knowledge in predictive pathology for the management of breast cancer patients, focusing on the benefits and drawbacks of traditional tools and of novel improvements of molecular biology.
Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens. What's new? Breast cancer incidence is rising rapidly throughout Africa, but few epidemiologic or molecular studies have been undertaken there. Best practices for study design are yet to be established. In this study, the authors discuss factors such as recruitment, data collection and biological sample collection. They found that the prevalence of various risk factors differed but the magnitudes of associations were similar to those observed elsewhere. These methods and results indicate that successful studies in Africa are possible, despite many challenges.
Background: Breast cancer is the most common type of cancer among females. Genetic polymorphisms might have a role in carcinogenesis. The aim of this study was to determine whether C to T base substitution within TaqI Vitamin D receptor (VDR) gene (rs731236) in exon 9 was a risk factor among patients with breast cancer. Methods: Peripheral blood was drawn from 122 Jordanian breast cancer patients and 100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months (from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification of serum 25-hydroxy Vitamin D (25[OH] D) level was determined by competitive immunoassay Elecsys. Results: Genotypic frequencies for TaqI TT, Tt, and tt genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for control, respectively. Vitamin D serum level was significantly lower in the breast cancer patients (8.1 +/- 0.3 ng/ml) compared to the control group (21.2 +/- 0.6 ng/ml; P = 0.001). This study showed an inverse association between 25(OH) D serum level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI], 10.06-51.29). Conclusions: An inverse association was found between 25(OH)D serum level and breast cancer risk. Statistical difference was also found between different VDR TaqI genotypes and circulating levels of 25(OH) D among Jordanian females with breast cancer.
Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues. A total of 51 subjects were studied, in which the frequency of promoter methylation in cancerous tissue was 37.25% as against 11% in the normal tissues (p = 0.001). The hypermethylated status of the gene was significantly associated with the loss of the protein expression (r = -0.449, p = 0.001, odds ratio = 7.42, 95% confidence interval = 2.05-26.92). Furthermore, when compared with the clinical parameters, the significant association was found between the promoter hypermethylation and lymph node metastasis (p = 0.001), tumor stage (p = 0.039), tumor grade (p = 0.028), estrogen receptor status (p = 0.018), and progesterone receptor status (p = 0.046). Our study is the first of its kind in Kashmiri population, which indicates that GSTP1 shows aberrant methylation pattern in the breast cancer with the consequent loss in the protein expression. Furthermore, it also shows that the gene polymorphism (Ile105Val) at codon 105 is not related to the promoter methylation and two are the independent events in breast cancer development.
Keratins are fibrous proteins. Hair keratins constitute hard structures such as the hair and nails, and cytokeratins have been used as markers of breast carcinoma. However, the expression and function of full-size hair keratin genes have not been previously demonstrated in breast cancer. We investigated the expression of the hair keratin, KRT81, and its function in human breast cancer and normal mammary epithelial cells. Western blotting showed full size 55-kDa KRT81 expression in the human breast cancer cell lines, MCF7, SKBR3 and MDA-MB-231, normal human mammary epithelial cells (HMEC), and non-neoplastic cells (MCF10A). Reverse transcription-polymerase chain reaction revealed that the full size KRT81, including its 5' region is expressed in breast cells. Immunohistochemical and immunofluorescence analyses showed that KRT81 was located in the cytoplasm. To investigate the function of KRT81, we knocked down KRT81 by siRNA in MCF10A cells. Microarray analysis revealed that the expression of genes related to invasion such as matrix metallopeptidase (MMP)9 was decreased. In KRT81-knockdown MDA-MB231 cells, zymography revealed a decrease in MMP9 activity, while scratch and invasion assays revealed that KRT81-knockdown decreased cell migration and invasion abilities. This is the first study showing that full size KRT81 is expressed in normal breast epithelial cells and breast cancer cells. Moreover, our results indicate that KRT81 contributes to the migration and invasion of breast cancer cells.
Breast cancer is a disease of unknown etiology; however, the major risk factors are genetic alterations. Studies have demonstrated an association between insulinlike growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two polymorphic variants of the IGF-1 gene are highlighted in association with breast cancer, rs6220 and rs7136446, although controversy exists as to this relationship. The current study included 137 women (68 breast cancer cases and 69 controls without breast cancer) who had 3 ml of peripheral blood drawn for the study of genomic DNA extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. The CC genotype (rs7136446) was present in 4 women (5.9%) from the case group and in 2 (3.0%) women from the control group (p = 0.67), while the GG genotype (rs6220) occurred in 8 (11.5%) women from the case group and in 5 (7.2%) women from the control group (p = 0.75). No statistically significant difference was observed between the CC genotype of variant rs7136446 in premenopausal case and control women (p = 0.31), thus as there was also no significant difference between case and control postmenopausal women (p = 1.00). Concerning the GG genotype of rs6220, it occurred in 6 (14.2%) premenopausal case and 4 (8%) control women (p = 0.71) and no difference was found in postmenopausal women (p = 1.00). In the current study, IGF-1 gene polymorphism of SNP variants rs6220 and rs7136446 had no statistically significant association with breast cancer, both in premenopausal and postmenopausal women.
Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.
Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy.
Studies have demonstrated low expression of miR-145 associated with cell proliferation and migration in a wide variety of tumors. Here, we studied the expression of miR-145 in relation to the occurrence and development of breast cancer. Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-145 expression by quantitative real-time polymerase chain reaction (qRT-PCR). We also transfected breast cancer cells with hsa-miR-145 mimics, hsa-miR-145 inhibitor, mimics negative control (mimics NC) or inhibitor negative control (inhibitor NC). Cell proliferation was analyzed by colony formation assays and methyl thiazolyl tetrazolium assays. Cell proliferation in breast cancer cells was decreased after overexpression of miR-145 and increased following miR-145 suppression. Cell migration and invasion were assessed using Transwell and wound healing assays, respectively, and were also decreased after overexpression of miR-145 and increased after miR-145 suppression in breast cancer cells. Finally, western blot assays showed that over expression of miR-145 inhibited expression of transforming growth factor-beta 1 (TGF-beta 1). Collectively, these data suggest that miR-145 may inhibit TGF-beta 1 protein expression which may in turn contribute to tumor formation.
We here report identification and characterization of Required for Cell Differentiation I homolog (RQCD1) as a potential therapeutic target for breast cancer. Gene-expression profiling analysis of breast cancer cells, semi-quantitative RT-PCR, Northern blotting and Western blotting confirmed RQCD1 to be frequently up-regulated in breast cancer specimens and breast cancer cell lines. On the other hand, its expression was very weak or hardly detectable in normal human tissues except testis, indicating this molecule to be a novel cancer-testis antigen. Treatment of breast cancer cell lines with siRNA targeting RQCD1 drastically suppressed cell proliferation. Concordantly, introduction of exogenous RQCD1 into HEK293 cells significantly enhanced cell growth, implying RQCD1 to have an oncogenic activity. Co-immunoprecipitation experiments and immunocytochemical staining revealed an interaction of RQCD1 protein with Grb10 interacting GYF protein I (GIGYF1) and 2 (GIGYF2) proteins, involved in regulation of Akt activation, in breast cancer cells. Interestingly, knockdown of either of RQCD1, GIGYF1 or GIGYF2 resulted in significant reduction of the phosphorylation of Akt at Ser 473 in breast cancer cell lines. Our findings suggest that RQCD1 is a potential molecular target for treatment of breast cancer.
Background: Elevation of fatty acid synthase (FAS) in human cancers is often associated with increased tumor aggression. The basic genetic mechanisms leading to increased enzyme content in cancer cells were investigated using cell lines derived from human metastatic breast carcinomas (T47D, Zr75 and SKBr3) and normal human breast epithelium (184A1). Materials and Methods: Western analysis, Northern blotting, [2-C-14]malonyl-CoA incorporation assays, nuclear run-off transcription assays, mRNA decay assays, and poly(A) tail assays were used to measure and compare transcription rates of the FAS gene among the four cell lines. Results: By Western analysis, FAS levels in T47D were 2.6 times lower than ZR75 and SK-Br3, but 6.7 times greater than non-neoplastic 184A1 cells. FAS mRNA levels and specific activity correlated with protein content. In contrast, relative rates of FAS gene transcription were significantly higher in non-neoplastic 184A1 cells than T47D, ZR75 and SKBr3. Stability of message was investigated to explain this discrepancy. The half-life of FAS mRNA in 184A1 cells was 5.6 h, or 4-5-fold less than ZR75 and SKBr3. Poly(A) tail assays showed that FAS mRNA species from 184A1 cells tended to be longer than those of breast cancer cell lines (500-1500 nt versus 500-800 nt, respectively). Conclusion: Breast cancer cell lines contained significantly more FAS enzyme, message and activity than nonneoplastic 184A1 cells. Yet, 184A1 cells exhibited higher rates of FAS gene activation. The discrepancy is explained by faster decay of FAS message in 184A1 cells, suggesting that stabilization of FAS mRNA plays a major role in overexpression of the protein in breast cancer. Increased stability could not be explained simply by degree of polyadenylation. Therefore, some other mechanism (s) must be responsible for conferring stability to FAS RNA species in breast cancer cells.
Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2 alpha (TOP2 alpha) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2 alpha genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2 alpha gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2 alpha and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2 alpha were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2 alpha amplification and over expression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.
Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase (COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants (N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.
Breast cancer is the second most common cause of mortality in women; therefore, the identification of novel putative markers is required to improve its diagnosis and prognosis. Selenium is known to protect mammary epithelial cells from oxidative DNA damage, and to inhibit the initiation phase of carcinogenesis by stimulating DNA repair and apoptosis regulation. Consequently, the present study has focused attention on the selenoprotein family and their involvement in breast cancer. The present study performed a global analysis of the seleno-transcriptome expression in human breast cancer MCF-7 and MDA-MB231 cell lines compared with healthy breast MCF-10A cells using reverse transcription-quantitative polymerase chain reaction. The present data revealed the presence of differently expressed genes in MCF-7 and MDA-MB231 cells compared with MCF-10A cells: Four downregulated [glutathione peroxidase (GPX) 1, GPX4, GPX5 and GPX7] and three upregulated (deiodinase iodothyronine, type II, GPX2 and GPX3) genes. Additionally, interactomic investigation were performed by the present study to evaluate the association between the downregulated and upregulated genes, and to identify putative HUB nodes, which represent the centers of association between the genes that are capable of direct control over the gene networks. Network analysis revealed that all differentially regulated genes, with the exception of selenoprotein T, are implicated in the same network that presents three HUB nodes interconnected to the selenoprotein mRNAs, including TP53, estrogen receptor 1 and catenin-beta 1 (CTNNB1). Overall, these data demonstrated for the first time, a profile of seleno-mRNAs specific for human breast cells, indicating that these genes alter their expression on the basis of the ER-positivity or negativity of breast cancer cells.
It has recently become apparent that it is possible to characterize productively recombined, T-cell receptor (TcR) gene segments in tumor exome files, which presumably include representations of the DNA of other cells in the microenvironment. Similar characterizations have been done for TcR recombinations in tumor specimen RNASeq files. While exome files have been used to characterize immunoglobulin gene segment recombinations for tumors closely related to B-cells, immunoglobulin recombinations have yet to be characterized for putative microenvironment cells for solid tumors. Here we report a novel scripted algorithm that detects productive and unproductive immunoglobulin recombinations in both B-cell related tumor exome files and in solid tumor exome files, with the most important result being the relatively high level B-cell infiltrate in breast cancer. This analysis has the potential of streamlining and dramatically augmenting the knowledge base regarding B-cell infiltrates into solid tumors; and leading to antibody reagents directed against tumor antigens and tissue resident, infectious pathogens.
Purpose This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis. Materials and Methods DNMT1 rs2228611, DNMT3A rs1550117, DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC). Results Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation -induced fibrosis (GG vs. M; hazard ratio, 0.26; 95% confidence interval [Cl], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% Cl, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710). Conclusion DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.
Aim: Aim of the present study is to evaluate the risk of residual neoplastic foci, in patients treated with breast conservative surgery, based on duct carcinoma in situ (DCIS) grading. Materials and methods: The study is based on a retrospective analysis of 419 resection specimens relative to 161 patients. All these patients underwent surgical re-excision when the first specimen had shown one or more margins involved by DCIS. Margins were oriented and the side of margin involved was recorded. Clonal analysis, using the mitochondrial DNA (mtDNA) technique, was obtained in selected cases. Results: Residual neoplastic foci were found in 145 out of 419 (34.6%) re-excised specimens. Specifically, residual foci of DCIS grade 2 and 3 were found more frequently in the margin facing the nipple (33.3% and 51.6%, respectively). On the contrary foci of DCIS grade 1 did not show any specific distribution. Clonal mt DNA analysis evidenced that DCIS grade 3 foci present in the re-excision specimens were genetically similar to the tumor removed in the first specimen, while DCIS grade 1 foci were not clonally related each other. Conclusions: The present data further confirm that DCIS grade 3 is characterized by a circumscribed neoplastic process extending along the large ducts probably of a single mammary lobe. On the contrary DCIS grade 1 is characterized by multiple independent neoplastic foci,, dispersed through several lobes indicating a field where multiple independent foci of cancer harbor. (C) 2016 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
The sialidase gene from Brevibacterium casei was cloned in pET28a and overexpressed as a histidine-tagged protein in Escherichia coli BL21(DE3). The histidine-tagged sialidase protein was purified and characterized from the crude cell extracts of isopropyl-beta-D-thiogalactopyranoside-induced cells using Ni-NTA agarose chromatography. SDS-PAGE using the purified sialidase indicated a single band at 116 kDa. This sialidase showed maximum activity at a pH of 5.5 and temperature of 37 degrees C. The kinetic parameters K-m and V-max for the artificial substrate 2'-(4-methylumbelliferyl)-alpha-D-N-acetyl-neuraminic acid sodium salt hydrate were 1.69 x 10(-3) mM and 244 mmol.Min(-1)center dot mg(-1), respectively. The sialidase may catalyze the hydrolysis of terminal sialic acids linked by the alpha-(2,3) and alpha-(2,8) linkage of polysialogangliosides, but it does not act on monosialotetrahexosylganglioside (GM1), which offers it a great potential for commercially producing GM1 from polysialogangliosides. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
This paper presents a scheme to improve the line current distortion of power factor corrector (PFC) topology at the zero crossing point using a predictive control algorithm in both the continuous conduction mode (CCM) and discontinuous conduction mode (DCM). The line current in single-phase PFC topology is distorted at the zero crossing point of the input AC voltage because of the characteristic of the general proportional integral (PI) current controller. This distortion degrades the line current quality, such as the total harmonic distortion (THD) and the power factor (PF). Given the optimal duty cycle calculated by estimating the next state current in both the CCM and DCM, the proposed predictive control algorithm has a fast dynamic response and accuracy unlike the conventional PI current control method. These advantages of the proposed algorithm lower the line current distortion of PFC topology. The proposed method is verified through PSIM simulations and experimental results with 1.5 kW bridgeless PFC (BLPFC) topology.
The present paper summarizes the results of some numerical calculations carried out on the basis of a recent wide experimental research. The calculations are performed on axisymmetric specimens weakened by V notches consisting of a large bulk of different shapes. The specimens are subjected to multiaxial fracture loading (tension + torsion). Stress and strain fields in the whole specimens are evaluated herein by using the finite element method (FEM). Special attention is paid to the changing distribution of stresses induced by loading and notch shape. By taking advantage of the numerical calculations carried out in the present investigation, a new non-local fracture criterion for notched specimens under multiaxial loading is proposed and successfully employed and compared with some data taken from the recent literature. (C) 2017 Published by Elsevier Ltd.
AimsThe aim of this study was to investigate potential molecular mechanisms associated with loss of BRM expression in poorly differentiated clear cell renal cell carcinoma (ccRCC). Methods and resultsNineteen previously selected BRM-negative RCC tissues were examined by DNA sequencing, fluorescence in-situ hybridization (FISH) and methylation-specific polymerase chain reaction (PCR) of the BRM gene. BRM mutation was identified in 78.9% (15 of 19) cases, chromosome 9 monosomy or BRM deletion in 43.8% (seven of 16) and BRM promoter region cytosine-phosphate-guanine (CpG) methylation in 42.8% (six of 14). These results indicated that 89.5% (17 of 19) of the cases harboured at least one type of BRM genetic alteration, with two or more types of alteration in 47.4% (nine of 19). Such alterations were found rarely in adjacent non-neoplastic tissues and low-grade areas of composite tumours. ConclusionsBRM gene mutation, chromosome 9 monosomy or BRM deletion and CpG methylation contribute collectively to the loss of BRM expression in ccRCC. This work focusing on composite tumours indicated that BRM abnormality occurred during tumour progression.
Multifunction RF systems which can operate with different RF functions like radar, communication and electronic warfare offer a variety of benefits beyond the well-known AESA (Active Electronically Steerable Antenna) features. To reach a sufficient technology maturity to start product development a series of challenges most stemming from the large required operation bandwidth have to be resolved. Dual-polarised low-loss apertures with array grids designed for a grating lobe and scan blindness free 60 conical Field of View (FoV) at the highest operational frequency have to be considered. The active components of the AESA and especially the T/R-M are required to be power efficient over the whole multifunction bandwidth and they shall be miniaturised to fit the array grid. RF functions like high speed datalink require linear high power amplification with low harmonics generation and interference suppression in receive is essential in order to maintain performance. Enablers for such broadband AESA are the GaN technology for T/R-M front-end components and SiCe BiCMOS technology for core chip and digital control of the T/R-M. The paper shows the state-of-the-art technology in Europe for multifunction RF Systems.
Multifunction RF systems which can operate with different RF functions like radar, communication and electronic warfare offer a variety of benefits beyond the well-known AESA (Active Electronically Steerable Antenna) features. To reach a sufficient technology maturity to start product development a series of challenges most stemming from the large required operation bandwidth have to be resolved. Dual-polarised low-loss apertures with array grids designed for a grating lobe and scan blindness free 60 conical Field of View (FoV) at the highest operational frequency have to be considered. The active components of the AESA and especially the T/R-M are required to be power efficient over the whole multifunction bandwidth and they shall be miniaturised to fit the array grid. RF functions like high speed datalink require linear high power amplification with low harmonics generation and interference suppression in receive is essential in order to maintain performance. Enablers for such broadband AESA are the GaN technology for T/R-M front-end components and SiGe BiCMOS technology for core chip and digital control of the T/R-M. The paper shows the state-of-the-art technology in Europe for multifunction RF Systems.
Ventilator-associated pneumonia (VAP) is the most common infection in critically ill patients. Initial antibiotic therapy is often broad spectrum, which promotes antibiotic resistance so new techniques are under investigation to obtain early microbiological identification and quantification. This trial compares the performance of a new real-time quantitative molecular-based method with conventional culture in patients with suspected VAP. Patients with suspected VAP who were ventilated for at least 48 h were eligible. An endotracheal aspirate (ETA) and a bronchoalveolar lavage (BAL) were performed at each suspected VAP episode. Both samples were analysed by conventional culture and molecular analysis. For the latter, bacterial DNA was extracted from each sample and real-time PCR were run. In all, 120 patients were finally included; 76% (91) were men; median age was 65 years, and clinical pulmonary infection score was >= 6 for 73.5% (86) of patients. A total of 120 BAL and 103 ETA could be processed and culture results above the agreed threshold were obtained for 75.0% (90/120) of BAL and 60.2% (62/103) of ETA. The main isolated bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae. Performancewas 89.2% (83.2% e93.6%) sensitivity and 97.1% (96.1% e97.9%) specificity for BAL samples and 71.8% (61.0% e81.0%) sensitivity and 96.6% (95.4% e97.5%) specificity for ETA samples when the molecular biology method was compared with conventional culture method (chosen as reference standard). This new molecular method can provide reliable quantitative microbiological data and is highly specific with good sensitivity for common pathogens involved in VAP. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP)-1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM)-16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT. (C) 2016 Elsevier Ltd. All rights reserved.
We quantitatively examined the transcript levels of ten fatty acid-binding protein (FABP) isoforms in the brown adipose tissue (BAT) of rats kept at room temperature and of rats exposed to the cold by Northern blotting using the synthesized RNA of each isoform as an external standard. FABP3-5 were expressed in BAT of both rats maintained at room temperature and those exposed to the cold. FABP4 was the most abundantly expressed isoform, but its transcript level was not significantly affected by cold exposure. FABP3 was slightly expressed in the BAT of rats maintained at room temperature and its transcript level was elevated ten fold by cold exposure. FABP5 was also elevated four fold by cold exposure but the amount of its mRNA in BAT was negligible.
Brown spiders are venomous arthropods that use their venom for predation and defense. In humans, bites of these animals provoke injuries including dermonecrosis with gravitational spread of lesions, hematological abnormalities and impaired renal function. The signs and symptoms observed following a brown spider bite are called loxoscelism. Brown spider venom is a complex mixture of toxins enriched in low molecular mass proteins (4-40 kDa). Characterization of the venom confirmed the presence of three highly expressed protein classes: phospholipases D, metalloproteases (astacins) and insecticidal peptides (knottins). Recently, toxins with low levels of expression have also been found in Loxosceles venom, such as serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like toxins and histamine-releasing factors. The toxin belonging to the phospholipase-D family (also known as the dermonecrotic toxin) is the most studied class of brown spider toxins. This class of toxins single-handedly can induce inflammatory response, dermonecrosis, hemolysis, thrombocytopenia and renal failure. The functional role of the hyaluronidase toxin as a spreading factor in loxoscelism has also been demonstrated. However, the biological characterization of other toxins remains unclear and the mechanism by which Loxosceles toxins exert their noxious effects is yet to be fully elucidated. The aim of this review is to provide an insight into brown spider venom toxins and toxicology, including a description of historical data already available in the literature. In this review article, the identification processes of novel Loxosceles toxins by molecular biology and proteomic approaches, their biological characterization and structural description based on x-ray crystallography and putative biotechnological uses are described along with the future perspectives in this field.
Brownian motion with adaptive drift has attracted much attention in prognostics because its first hitting time is highly relevant to remaining useful life prediction and it follows the inverse Gaussian distribution. Besides linear degradation modeling, nonlinear-drifted Brownian motion has been developed to model nonlinear degradation. Moreover, the first hitting time distribution of the nonlinear-drifted Brownian motion has been approximated by time-space transformation. In the previous studies, the drift coefficient is the only hidden state used in state space modeling of the nonlinear-drifted Brownian motion. Besides the drift coefficient, parameters of a nonlinear function used in the nonlinear-drifted Brownian motion should be treated as additional hidden states of state space modeling to make the nonlinear-drifted Brownian motion more flexible. In this paper, a prognostic method based on nonlinear-drifted Brownian motion with multiple hidden states is proposed and then it is applied to predict remaining useful life of rechargeable batteries. 26 sets of rechargeable battery degradation samples are analyzed to validate the effectiveness of the proposed prognostic method. Moreover, some comparisons with a standard particle filter based prognostic method, a spherical cubature particle filter based prognostic method and two classic Bayesian prognostic methods are conducted to highlight the superiority of the proposed prognostic method. Results show that the proposed prognostic method has lower average prediction errors than the particle filter based prognostic methods and the classic Bayesian prognostic methods for battery remaining useful life prediction. (C) 2017 Elsevier Ltd. All rights reserved.
The cDNA encoding brain protein 44-like (Brp44l) was identified from the brain and spinal cord cDNA library of Gekko japonicus. It contains a 324 bp open reading frame corresponding to a deduced protein of 107 amino acids. The molecular weight of the BRP44L protein is 12.2664 kDa and its theoretical pI is 9.67. At amino acid level, the BRP44L from gecko shares 85-89% similarity with those from other species. Northern blotting showed that Brp44l was ubiquitously expressed in the major organs of Gekko japonicus including brain, spinal cord, heart, lung, liver, and kidney, suggesting a fundamental biological role of this gene. In situ hybridization (ISH) revealed that positive hybridization signals were present in gray matter of spinal cord. The change of Brp44l expression in spinal cord after tail amputation was examined by reverse transcription polymerase chain reaction (RT-PCR). The expression level of this gene increased in the spinal cord after tail amputation, and reached the highest value at 1 week after tail amputation, which indicated that the expression level of Brp44l might be associated with the process of spinal cord injury and regeneration.
We evaluated the capacity of the Brucella sp. eryC gene as a diagnostic marker for brucellosis by quantitative real-time PCR. eryC gene encodes the enzyme d-erythrulose-1-phosphate dehydrogenase that plays an important role in the erythritol metabolism and is related with the Brucella survival in the intracellular environment of the macrophage. The assay includes an internal amplification control (IAC) in order to avoid false negative results. It was 100% specific, with an analytical sensitivity of 1 genome equivalent (GE) in 43% of the reactions, being the quantification highly linear (R (2) >0.9953) and efficient (PCR efficiency >0.8820) over a 6-log dynamic range, down to 10 GE. Finally, the applicability of this assay was evaluated with artificially contaminated biological matrices implicated in the transmission of this bacterium such as sheep raw milk and pig blood. The eryC-IAC real-time PCR assay allowed detection of as few as ten Brucella cells per 25 ml of sheep raw milk or per 1 ml of pig blood. In conclusion, we present an alternative for the detection of Brucella genus and therefore facilitate the establishment of preventive and prophylactic measures in food and farm environments.
The genus Brucella causes significant economic losses due to infertility, abortion, stillbirth or weak calves, and neonatal mortality in livestock. Brucellosis is still a zoonosis of public health importance worldwide. The study was aimed to optimize and evaluate PCR assays used for the diagnosis of Brucella infections. For this aim, several primers and PCR protocols were performed and compared with Brucella cultures and biological material inoculated with Brucella. In PCR assays, genus- or species-specific oligonucleotide primers derived from 16S rRNA sequences (F4/R2, Ba148/928, IS711, BruP6-P7) and OMPs (JPF/JPR, 31ter/sd) of Brucella were used. All primers except for BruP6-P7 detected the DNA from reference Brucella strains and field isolates. In spiked blood, milk, and semen samples, F4-R2 primer-oriented PCR assays detected minimal numbers of Brucella. In spiked serum and fetal stomach content, Ba148/928 primer-oriented PCR assays detected minimal numbers of Brucella. Field samples collected from sheep and cattle were examined by bacteriological methods and optimized PCR assays. Overall, sensitivity of PCR assays was found superior to conventional bacteriological isolation. Brucella DNA was detected in 35.1, 1.1, 24.8, 5.0, and 8.0% of aborted fetus, blood, milk, semen, and serum samples by PCR assays, respectively. In conclusion, PCR assay in optimized conditions was found to be valuable in sensitive and specific detection of Brucella infections of animals.
Careful examination of the skin and soft tissues is a routine part of the forensic autopsy to identify and characterise traumatic lesions. Three cases are reported where benign vascular lesions presented as bruises. In case 1, a 44-year-old man with a history of epilepsy was found dead on the floor. Dissection of the neck revealed a haemorrhagic area 15mmx1.5mm, deep to the left thyrohyoid muscle. In case 2, an 87-year-old man was found dead with a plastic bag over his head attached to an opened cylinder of nitrogen gas. On the mucosal surface of his upper lip, there was an apparent 5mm blue/purple bruise. In case 3, examination of the back of a 16-month-old girl revealed an apparent 15mm bruise. Histological examination of all three lesions revealed benign vascular lesions. In the absence of microscopy, these lesions would have been considered traumatic in origin, raising the possibility of inflicted trauma.
Bruxism (BRX) is a condition of great interest for researchers and clinicians in dental and medical areas. BRX has two circadian manifestations; it can occur during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, WB). However, it can be suffered together. Recent investigations suggest that central nervous system neurotransmitters and their genes could be involved in the genesis of BRX. Serotonin is responsible for the circadian rhythm, maintaining arousal, regulating stress response, muscle tone and breathing. Thus, serotonin could be associated with BRX pathogenesis. The aim of this work was to evaluate the frequency of genetic polymorphisms in the genes HTR1A (rs6295), HTR2A (rs1923884, rs4941573, rs6313, rs2770304), HTR2C (rs17260565) and SLC6A4 (rs63749047) in subjects undergoing BRX treatment. Patients included were classified according to their diagnosis in awake bruxism (61 patients), sleep bruxism (26 patients) and both (43 patients). The control group included 59 healthy patients with no signs of BRX. Data showed significant differences in allelic frequencies for the HTR2A rs2770304 polymorphism, where the C allele was associated with increased risk of SB (odds ratio = 213, 95% confidence interval: 108-421, P = 003). Our results suggest that polymorphisms in serotonergic pathways are involved in sleep bruxism. Further research is needed to clarify and increase the current understanding of BRX physiopathology.
Background: Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle. Methods: A chloroform extract derived from a bulk of botanically well-characterized pulverized B. pinnata leaves was separated using column chromatography with step-gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells. Results: Results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552 mu g/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50: 50) and showed IC50 at 91 mu g/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. Conclusions: Our study therefore demonstrates presence of anticancer and anti-HPV an activity in B. pinnata leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.
The eco-toxicological effects of Bacillus thuringiensis (Bt) maize on earthworm life-history traits were widely studied and the results were controversial, while their effects on earthworm bacterial community have been rarely studied. Here, effects of two hybrids of Bt maize [5422Bt1 (event Bt11) and 5422CBCL (MON810)] straw return on Eisenia fetida bacterial community were investigated by the terminal restriction fragment length polymorphism (T-RFLP) and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) combing with DNA sequencing, compared to near-isogenic non-Bt maize (5422). Bt maize straw return had significant effects on soil nutrients, especially for available nitrogen (N). The significant differences were shown in soil bacterial community between Bt and non-Bt maize treatments on the 75th and 90th d, which was closely correlated with soil available N, P and K rather than CrylAb protein. There was no statistically significant difference in the bacterial community of earthworm gut contents between Bt and non-Bt maize treatments. The significant differences in the bacterial community of earthworm casts were found among three maize varieties treatments, which were closely correlated with CrylAb protein and N levels. The differentiated bacterial species in earthworm casts mainly belonged to Proteobacteria, including Brevundimonas, Caulobacter, Pseudomonas, Stenotrophomonas, Methylobacterium, Asticcacaulis and Achromobacter etc., which were associated with the mineralization, metabolic process and degradation of plants residues. Therefore, Bt maize straw return caused changes in the bacterial community of E. fetida casts, which was possibly caused by the direct (CrylAb protein) and non-expected effects (N levels) of Bt maize straw. (C) 2017 Elsevier Ltd. All rights reserved.
In digitally controlled circuits for power electronic circuits, sampling data are important because the digital control circuit is operated on the basis of these data. If the sampled values have been affected by switching noise from the power circuit, the control stability of the circuit would be disturbed. This paper proposes a noiseless sampling method that can sample a value without being affected by the switching noise. The synchronous sampling method may be affected by the switching noise depending on the duty ratio of the circuit. The noiseless sampling method does not obtain data immediately after turn-on and turn-off switching. The control circuit can avoid the switching noise by using noiseless sampling, which leads to a disturbance in the control circuit and enhances the robustness of the circuit when applying the multisampling method. Experimental results are presented to verify that the current control of the proposed sampling method is not disturbed by the switching noise even in the absence of a noise filter.
This paper presents the design of a digital control strategy for a dc-dc type Buck converter used as an efficient lead acid battery charger in isolated electric, photovoltaic systems. The strategy is designed to be implemented in a digital signal processor (DSP). The control acts depending on the state of charge of the batteries by regulating the drive duty cycle with the proper combination of incremental conductance MPPT technique and precise control of the battery current according to three charging stages, providing a joint solution which on one hand maximizes the production of solar energy available in the PV array, and on the other ensures a long battery lifetime, both aspects, which are generally investigated independently in technical literature, are treated simultaneously in our approach. The work explains in detail the converter modeling, the project of the compensator, as well as the development of MPPT used. Validation simulations are done via Matlab and experimental results from a prototype low power TMS320F2812 using a DSP from Texas Instruments, are provided and discussed, which show satisfactory performance of the proposed control system. (C) 2016 Elsevier Ltd. All rights reserved.
Implantable devices like artificial cardiac pacemakers are generally used to control irregular pulses of heart. For 10-year usage, high accuracy supply voltage is essential with the unavoidable aging of the power system to achieve near-natural beat rhythm. A Self-Calibration DC-DC Buck converter (SC-Buck) is proposed to achieve high output voltage accuracy by eliminating offset caused by mismatch of process, voltage and temperature (PVT). Furthermore, the discontinuity which affects transient performance in conventional offset cancellation is also overcome. Large area occupation, which is required to decrease mismatch in conventional operational amplifier, can be largely decreased according to Monte Carlo analysis. Without trimming process, the proposed SC-Buck technique achieves high accuracy for long-term usage (years) and low cost. The test chip fabricated in UMC 28nm CMOS process proves the output voltage accuracy of 97% since the mismatch of error amplifier can be suppressed from 122% to 1%.
A new hysteresis window method is proposed as a solution for avoiding the operational dead zone that exists at the transition between buck and boost operating modes in all noninverting buck-boost converters. In addition, this method also eliminates the discontinuities in the converter's steady-state output voltage transfer characteristic, which is a function of the duty cycle. The converter's output voltage function is surjective and, therefore, smooth mode transitions are achieved. The negative effects of operating within the dead zone are shown by the presence of subharmonics in the output voltage, increased output voltage ripple, poor regulation, and the instability of the converter during the transition between buck and boost operating modes. The dead-zone avoidance technique proposed in this paper eliminates all these issues while at the same time ensures highly efficient operation of the converter. An additional advantage of the technique is its simplicity, which allows for implementation into low-cost digital signal controllers, as well as into analog control circuits. The advantageous features of the proposed approach were evaluated on the basis of comparisons with three other dead-zone avoidance approaches and the initial case, which does not utilize any dead-zone avoidance technique. All the experiments were carried out on a purpose-built prototype of a noninverting buck-boost converter with magnetically coupled inductors.
To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells. The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRNA and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively. The bufalin was effective to inhibit proliferation of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%+/- 2.1% to 87.2%+/- 5.4% with an half maximal inhibit concentration (IC50) of 0.046 mu mol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The proliferation index of cell cycle decreased from 76.4%+/- 1.9% to 49.7%+/- 1.3%. The expression levels of WT1 mRNA and its protein reduced gradually with increasing doses of bufalin, meanwhile, the methylation status of WT1 gene changed from unmethylated into partially or totally methylated. While, the expression levels of DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-dependent manner. Bufalin can not only significantly inhibit the proliferation of HEL cells and arrest cell cycle at G(0)/G(1) phase, but also induce cellular apoptosis and down-regulate the expression level of WT1. Our results provide the evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1 methylation status which is related to the up-regulation of DNMT3a and DNMT3b proteins in erythroid leukemic HEL cells.
Information security and customers' privacy in smart grid are significant concerns. Existing security and privacy preserving schemes consider that the consumption reports for electricity consumption aggregation and billing purposes are sent periodically. These periodic messages increase the computation and communication burden on restricted-capabilities smart meters. In this paper, we propose a lightweight security and privacy preserving scheme that is based on forecasting the electricity demand for a cluster of houses in the same residential area; it limits the cluster's connection with electricity utility only when the cluster needs to adjust its total demand. The scheme efficiently satisfies the security and privacy requirements in customer-side networks, i.e., communication between customers and power utility. At the same time, it significantly reduces the communication and computation overhead. Moreover, the proposed scheme utilizes NTRU cryptosystem to further reduce the computation complexity.
Building-integrated photovoltaic (BIPV) windows provide the benefits of generating electricity, reducing building cooling and heating energy consumption, and efficiently utilizing daylight simultaneously. In this paper, the overall energy performance of a PV double skin facade (PV-DSF) and a PV insulating glass unit (PV-IGU) is studied through comparative experiments on a test rig in Hong Kong. The PV-DSF means ventilated PV-DSF by default, if not special mentioned. It is found that the average solar heat gain coefficients (SHGCs) of the PV-DSF and the PV-IGU are 0.152 and 0.238, while the U-values are 2.535 W/m(2) K and 2.281 W/m(2) K. The results indicate that the PV-DSF has better performance than PV-IGU in reducing solar heat gains, while it has worse performance regarding thermal insulation. With a lower PV module temperature, the energy conversion efficiency of PV-DSF is 1.8% better than PV-IGU. Simulation models for the PV-DSF and the PV-IGU are developed and validated against experimental data. Using the validated models, the overall energy performances of PV-DSF and PV-IGU in five different climates of China are investigated. The results show that the average energy saving potential of the PV-DSF and the PV-IGU are 28.4% and 30%, respectively, compared to the commonly used insulating glass window in five different climates. On average, the performance of PV-IGU was 2% better performance than the ventilated PV-DSF in the five representative cities. However, if an appropriate ventilation control scheme was adopted, PV-DSF can have a much better performance than the PV-IGU. The models developed in this study can be used for selecting suitable PV windows in the design process, and the results achieved can be used as a guideline for utilizing PV windows in different climates. (C) 2017 Elsevier Ltd. All rights reserved.
Understanding the energy demand of cities is a challenge especially in countries such as Brazil where the lack of building energy consumption benchmarks makes it hard to decide upon interventions in the building stock, as neither the existing nor the attainable energy performance are known. Aiming to overcome these difficulties this study develops a framework to estimate the Energy Use Intensity (EUI) baseline of an existing building stock category based on the investigation of land use regulations, a land tax database and field surveys. These offer a starting point to estimate current energy consumption and promising interventions without having to study specific buildings in depth. A case study of the high-rise commercial building stock took place in the city of Belo Horizonte, Brazil. Three representative typologies were identified. For each of these, archetype energy models were created in order to assess EUI. The analysis of the EUI baselines highlights differences between archetypes, explaining the impact of technical choices on the overall electricity consumption and indicating a growing tendency of energy consumption for forthcoming buildings. The archetype analysis also provides knowledge to identify the most promising energy savings potential and thus to support further energy policies in the city. (C) 2017 Elsevier B.V. All rights reserved.
This study provides understanding of the influence of outside temperature on intuitional buildings in an urban landscape. We derive heating and cooling degree days for each of the buildings by identifying an appropriate choice of balance point temperatures and perform multiple linear regression seasonally to characterize the temperature-electricity use relations. Our study reveals considerable differences in temperature-electricity relationships based on building use and characteristics. In addition to outside temperature, the weekday effect has large influences on electricity consumption of buildings. Summer months have greater influence of outside temperature on electricity consumption followed by transition months and winter as an increase in one cooling degree day (CDD) increases daily electricity consumption by 0.124 kW/m2 whereas during winter, one heating degree day (HDD) increases daily electricity consumption by 0.025 kW/m2 and by 0.099 kW/m2 during transition months. We apply two kinds of models to project electricity demand for projected temperature profiles in 2030. Both cases strongly suggest higher electricity demand not just in summer months but also during transition periods in spring and fall. Overall, electricity demand increases by 0.95% under a low emission scenario (RCP 4.5) and 2.03% under a high emission scenario (RCP 8.5), which is likely to put immense pressure on the United States electric grid system and an overall increase in the energy cost by 2030. (C) 2017 Elsevier B.V. All rights reserved.
This study aims to conduct the nonlinearity analysis of the shading effect on the technical-economic performance of the building-integrated photovoltaic blind (BIPB), which is designed as a preliminary study to evaluate the feasibility of the BIPB before its implementation. First, in terms of the technical performance of the BIPB, the shading effect due to the blind's slat in the BIPB can have a nonlinear effect on the amount of electricity generation per unit area (AEGunit) from the BIPB. Particularly, as the width of the PV panel increases, the AEG(unit) from the BIPB tends to decrease. Second, in terms of the economic performance of the BIPB, the feasibility of the BIPB depends on the type of investment values. Specifically, as' the width of the PV panel increases, the NPV25 (net present value at year 25) tends to increase; however, the SIR25 (saving-to-investment ratio at year 25) tends to decrease. That is, while the NPV25 is determined to be highest at US$82,869 when the width of the PV panel is 50 mm, the SIR25 is determined to be highest at 2.90 times when the width of the PV panel is 10 mm. The main findings of this study can be used to clearly define the design specifications of the BIPB before its implementation, which ensure to meet the client expectations on various objectives, such as technical performance (e.g., the AEG(unit) from the BIPB) and economic performance (e.g., NPV25 and SIR25). (C) 2016 Elsevier Ltd. All rights reserved.
Electricity generators of varying capacities are popularly utilized in Nigeria as alternative source of power owing to the unreliability of electricity supply through the national grid. This study evaluated the impact of emissions from generating sets on air quality and human health in selected areas of Abeokuta city, Nigeria. The levels of particulates (PM1, PM3), carbon monoxide, carbon dioxide, sulphur oxides, nitrogen oxides, nitrogen dioxide, hydrogen sulphide and methane were monitored using portable samplers. Copies of questionnaire were administered to generator operators and nearby residents so as to collect additional information. The capacities of sampled generators ranged from 1 to 25 kVA. The range of mean concentrations of PM1 (4.7-219.2 mu g/m(3)), PM3 (7.8-251.6 mu g/m(3)), carbon dioxide (4.5-10.9%), methane (0.0-1.2 ppm), carbon monoxide (141.1-4167.0 ppm), NOx (4.0-85.7 ppm), methane (2.3-31.0 ppm), sulphur oxides (3.5-65.6 ppm) and hydrogen sulphide (0.0-0.7 ppm) was highest at generator sites. The distance of sample sites to generator locations accounted for 14-66% variation of pollutants levels. Ailments frequently suffered by the exposed residents included nasal congestion (66%), cough (33%), headache (24%) and fever (12%). A national policy on appropriate use of electricity generator is urgently needed in Nigeria.
Improvement in noise performance and transconductance using positive feedback approach in bulk driven operational amplifier is proposed in this paper. Downscaling of CMOS technology has compelled the supply voltage to reduce, which in turn demands the reduction in threshold voltage. To overcome the barrier of threshold, bulk driven technique is a good non-conventional approach because it require no modification in the existing structure of MOSFET. The limitation with bulk driven approach is that the transconductance of operational amplifier get reduced almost three to four times. Thanks to loop of positive feedback. The resulting transconductance is boosted to a higher value; thus, increasing the voltage gain and decreasing the input referred noise. So, concept of positive feedback is used in the design of low voltage (LV) low Power (LP) building blocks of operational amplifier using standard CMOS technology. Though amplifier is designed for power supply of 1V, it is also capable to operate at supply of less than 1V. The simulation is carried out using Mentorgraphics tools of 180 nm technology.
A simple realization of a 0.5V bulk-driven voltage follower/direct current (DC) level shifter designed in a 0.18 mu m CMOS technology is presented in the paper. The circuit is characterized by large input and output voltage swings and a DC voltage gain close to unity. The DC voltage shift between input and output terminals can be regulated in a certain interval around zero, by means of biasing current sinks. An application of the proposed voltage follower circuit for realization of a low-voltage class AB output stage has also been described in the paper. Finally, the operational amplifier exploiting the proposed output stage has been presented and evaluated in detail. Copyright (c) 2014 John Wiley & Sons, Ltd.
The effective transconductance (G(m)) of a bulk-driven operational amplifier opamp) can significantly vary with the input common-mode voltage. This variation of G(m) complicates frequency compensation and creates harmonic distortion. Thus, this brief presents a G(m)-stabilizing technique to reduce the variation of G(m) across the input common-mode range (ICMR). The idea is to use a variable positive feedback structure to adaptively control G(m) to the input common-mode voltage. A low-voltage bulk-driven opamp with the proposed G(m)-stabilizing technique has been implemented in a 0.18-mu m n-well CMOS process. The opamp consumes 261 mu W from a 900-mV supply voltage. The variation of G(m) is reduced from 132% to 25% across the rail-to-rail ICMR. The measured dc gain is 76.8 dB and the unity-gain bandwidth is 7.11 MHz when the opamp is loaded with 17 pF parallel to 1 M Omega.
A new solution for an ultra-low-voltage, low-power, bulk-driven operational amplifier is presented in the paper. The amplifier is based on a new input stage, exploiting the concept of partial positive feedback. As compared with prior work, the proposed input stage offers improvement of all basic performance metrics, including such important parameters as input-referred noise and offset voltage. In order to improve the DC voltage gain of the overall op-amp, a novel solution for an ultra-low-voltage, high-input-resistance common-mode amplifier has also been proposed. Simulated performance of the overall operational amplifier for a 50 nm CMOS process and supply voltage of 0.4 V shows power dissipation of 24 W, the open-loop voltage gain of 60dB, and the gain-bandwidth product of 2.18 MHz for 20 pF load capacitance.
This paper presents a 0.25-V supplied bulk-driven symmetrical OTA implemented in 130-nm CMOS process. By operating in weak inversion, and using a distributed layout approach, the OTA can benefit from the voltage reduction and high linearity enabled by halo-implanted transistors. The proposed circuit consumes only 10-nW, features a low transconductance of 22-nS, and a total harmonic distortion of 0.53 % for a 100-mV(pp) input voltage, thus making it suitable for low-frequency and low-power -C applications.
A design solution for bulk-driven tunable transconductor capable of working under extremely low supply/consumption with rail-to-rail input common-mode range is presented in this work. The proposed transconductor topology consists of six bulk-driven CMOS inverters, and it uses a very simple biasing circuit for the transconductance tuning. The design robustness was verified for 0.5 and 0.25 V power supplies offering the advantages of the current-controlled input transconductance. For 0.5 V power supply, the proposed transconductor has 0.075-10.2 transconductance tuning range, input-referred intercept point IP3 = 1.81 V, and 4.62 MHz bandwidth for 3 current consumption. The design robustness of the tunable transconductor was verified by means of computer simulation using triple-well 0.18 CMOS process.
In this paper by using Gm-C compensation technique, an ultra-low-power two-stage operational transconductance amplifier (OTA) with full rail-to-rail input/output swing is presented. The proposed configuration consists of composite transistors, improved bulk-driven folded cascode (FC) structure, feed-forward compensation path and high-speed current mirrors. In comparison with the typical FC, the proposed input stage structure has the benefit of transconductance enhancement with the same power consumption without adversely affecting the noise and offset performance. The presented OTA is simulated in 0.18 mu m CMOS technology and the simulation results confirm the theoretical analyses. The proposed amplifier exhibits a DC gain enhancement of 9.5 dB as well as 100 % improvement in gain-bandwidth compared to the conventional FC input stage structure. Finally, the amplifier consumes 400 nW @ 0.6 V supply voltage which makes it suitable for ultra-low-power applications.
The characterization and quantitative analyses of the key transcription factors for spermiogenesis are necessary in the identification of causal factors for the production of the seemingly normal sperm with dysfunctions in Japanese Black bulls and further elucidation of whole aspect of molecular mechanisms for spermiogenesis in livestock. The objective of this study was to obtain the information regarding the characterization and individual changes of an activator cAMP-responsive element modulator (CREM), which is necessary to the normal progress of spermiogenesis and is required for the transcriptional activity of genes coding essential factors for the sperm fertilization ability in rodents, using testes from 21 Japanese Black bulls with the ability to produce sperm indicating the normal motility and morphology. The bull CREM Tay (one of activator variants) was detected in testes more strongly than livers by reverse transcription-polymerase chain reaction and Northern blotting. This variant was localized in the nuclei of spermatids as shown by indirect immunofluorescence with the homemade mouse antiserum. The motility and morphology of the cauda epididymal sperm from 16 Japanese Black bulls were examined before the quantitative analyses of testicular activator CREM to confirm the ability to produce sperm with normal motility and morphology in these males. The percentages of the motile sperm, those of the sperm with the normal acrosomes, and those of morphologically normal sperm were 60.0% to 90.0%, 88.0% to 100%, and 83.0% to 97.9%, respectively. The quantitative analyses with real-time polymerase chain reaction using the testicular RNA from the same bulls revealed that the relative expression levels of activator CREM variants in testes varied significantly among these bulls in the range from 0.56 to 1.64 (P < 0.05). These results are consistent with the suggestions that CREM Tay are involved in the spermiogenesis in the testes of Japanese Black bulls and that the expression levels of the activator CREM variant mRNAs in the testes are varied significantly among individual bulls that have the ability to produce sperm with the normal motility and morphology. (c) 2014 Elsevier Inc. All rights reserved.
This retrospective investigation examined the association among childhood bullying victimization, multiple forms of victimization, and psychological functioning in a college sample. Four hundred-and-eighty-two undergraduate students participated in the study (M = 19.98 years, SD = 1.82). The sample included 65 % women. For race/ethnicity, 66.4 % were European-American (N = 320), 16.8 % African-American (N = 81). For grade level, 21.6 % were freshmen (N = 104), followed by 38.2 % sophomores (N = 184), 16.2 % juniors (N = 78), and 23.4 % seniors (N = 113). Participants completed a survey packet of measures assessing childhood bullying victimization experiences and current levels of psychological functioning. Findings indicated that bullying victimization significantly predicted greater levels of depression, anxiety, and post-traumatic stress (PTS) after controlling for other childhood victimization experiences. PTS symptoms were predicted by exposure to community violence and child abuse with bullying victimization was found to be the strongest predictor. College-level practitioners need to assess for a wide range of childhood victimization experiences, including bullying victimization.
BACKGROUND: Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over-or underestimate the impact of diseases on an individual's QoL. OBJECTIVE: The objective of this study was to develop and validate a questionnaire to measure specific-health-related QoL for adults with CVID (CVID_QoL). METHODS: The 32-item content of the CVID_QoL questionnaire was developed using focus groups and individual patient interviews. Validation studies included 118 adults with CVID who completed Short Form-36, Saint George Respiratory Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a single session. Principal component and factor analysis solutions identified 3 scores to be similar in number and content for each solution. Validation of 3 factor scores was performed by construct validity. Reproducibility, reliability, convergent validity, and discriminant validity were evaluated. Matrices consisting of correlations between the 32 items in the CVID_QOL were calculated. RESULTS: Factor analysis identified 3 dimensions: emotional functioning (EF), relational functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n = 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity correlating with conceptually similar dimensions of other study scales. Acute and relapsing infections had a significant impact on EF and RF. CONCLUSIONS: This study provides evidence of the reliability and construct validity of the CVID_QoL to identify QoL issues in patients with CVID that may not be addressed by generic instruments. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC- ND license.
Since communal violence erupted in Myanmar's Rakhine State in 2012 between Buddhist and Muslim communities, the plight of the Rohingya Muslims has received much media attention both inside and outside of the country. Rarely, however, do we get critical analyses of how such reporting is constructed. Research on communal conflict and journalism tends to focus on the how-to of conflict-sensitive reporting and the dangers of employing local fixers and interpreters whose influence is seen to reduce the objectivity of news, rather than on the actual news gathering strategies used in specific conflicts. Based on personal observations of a freelance reporter in Myanmar, and interviews with journalists and fixers working in the country, this article analyses the news production processes in reporting on the conflict. The article maps out the various actors involved in the production of news, such as foreign and local journalists, local producers (the fixers) and interpreters, and the various challenges and limitations they face. These challenges function to perpetuate a familiar set of reporting routines and us vs them or binary narratives, with consequences for the de-escalation or perpetuation of the conflict.
Plastic encapsulated microcircuits (PEMs) have been used tremendously in commercial and industrial fields due to their cost, weight, availability and performance advantages. However, the inherent structures and materials of PEMs introduce high risks of failures and limit their use in high reliability field. Screening test for package-level plays an important part in improving reliability of PEMs by eliminating marginal components and early time failures. Failure analysis of the microcircuits failed in screening test contributes to find out failure mechanisms and helps improve design for package reliability. However, during screening test, after screening out failed components, failure analysis is not conducted to figure out the root cause of failure and does not contribute to the conclusion of the screening test or to the advice for design. In this paper, dynamic burn-in of screening test on plastic encapsulated components is presented. An integrated circuit OPA134UA (single operational amplifier) fails in the electrical test after 24hrs. Failure analysis is carried out on the failed components to discover the root causes. It turns out that OPA134UA fails because of the delamination between the mold compound/die pad interface. The result of failure analysis proves that thermal mismatch in PEMs causes delamination, which suggests that other components also have delamination and that the design for packaging reliability require lower difference of coefficients of thermal expansion (CTE) of different materials in PEMs.
Curious eroded depressions, most resembling an eye shedding an elongate tear, are found in gently sloping, intertidal, carbonate-rich arenite outcropping on the sea coast near Lakes Entrance, Victoria, southeast Australia. The depressions, known locally as Tears of the Virgin, are evidently formed by multiple generations of a barnacle, Chthamalus antennatus Darwin, 1854 in association with cyanobacteria. While the round part of a depression offers the barnacle a modicum of protection from impacts during high tides, it is also partially inhabited by cyanobacteria, which extend into and tend to fill the elongate tear. As such, this appears to be the first case of mutualism between a higher invertebrate and cyanobacteria, with the cyanobacteria reducing the barnacle's risk of desiccation while receiving metabolic wastes from it during low tides. It is also the first record of a balanomorph barnacle eroding calcareous arenite beneath its shell, the net effect of which would be expected to reduce its adhesion to the substrate. However, the siliceous residue, resulting from the barnacle's dissolution of the more than 80% of the calcite-rich sedimentary rock, is sequestered in delicate folds on the inside of the shell wall as it grows. A brief review of cirripedes capable of excavation includes the first photographic documentation of excavation of a mollusc shell by a verrucomorph.
The digital low dropout regulator (D-LDO) has drawn significant attention recently for its low-voltage operation and process scalability. However, the tradeoff between current efficiency and transient response speed has limited its applications. In this brief, a coarse-fine-tuning technique with burst-mode operation is proposed to the D-LDO. Once the voltage undershoot/overshoot is detected, the coarse tuning quickly finds out the coarse control word in which the load current should be located, with large power MOS strength and high sampling frequency for a fixed time. Then, the fine-tuning, with reduced power MOS strength and sampling frequency, regulates the D-LDO to the desired output voltage and takes over the steady-state operation for high accuracy and current efficiency. The proposed D-LDO is verified in a 65-nm CMOS process with a 0.01-mm(2) active area. The measured voltage undershoot and overshoot are 55 and 47 mV, respectively, with load steps of 2 to 100 mA with a 20-ns edge time. The quiescent current is 82 mu A, with a 0.43-ps figure of merit achieved. Moreover, the reference tracking speed is 1.5 V/mu s.
This paper presents a new driving method for a sulfur plasma lamp in low-power applications. The newly developed magnetron power supply (MPS) is a series-resonance type with a full-bridge topology controlled by the phase shift to track the beam current of the magnetron. To drive the sulfur plasma lamp optimally, the MPS should: 1) provide peak power above a discharge condition to excite the sulfur plasma lamp, and 2) allow average power control of the light dimmer while satisfying condition 1. The newly developed driving method uses the burst mode, which enables both peak and average power controls to satisfy these conditions. Furthermore, a magnetizing current offset balancer is developed; it guarantees zero-voltage switching of all field-effect transistors, although the MPS operates in the burst mode. Thus, the proposed method provides easy lighting and relighting under optimized conditions with high efficiency. The power of the MPS delivered by the proposed method reached 1.6 kW with variable average power of 200 similar to 400 W by adjusting burst-on time proportionally. Experimental results proved the feasibility of the proposed driving method.
Objective: Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence microbial translocation and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. Design: A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants. The effect of exogenously added butyrate on gut T-cell activation and HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model. Methods: Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo isolated lamina propria mononuclear cells were infected with C-C chemokine receptor type 5-tropic HIV-1Bal, cultured with enteric gram-negative bacteria and a range of butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels measured. Results: Relative abundance of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-uninfected individuals. In HIV-1-infected study participants, R. intestinalis relative abundance inversely correlated with systemic indicators of microbial translocation, immune activation, and vascular inflammation. Exogenous butyrate suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation and HIV-1 infection levels in vitro. Conclusion: Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
The paradigmatic system of societal abuse occurs in totalitarian state systems. The relational systems of subjugation that maintain such states of terror must, of necessity, destroy any authentic civic space in which individuals can flourish. Similar dynamics characterize child abuse within families. Survival requires the use of varied strategies, the most extreme of which are dissociative in nature, and that result in marked distortions of developmental trajectories across all psychological domains. Such dynamics are mirrored in dissociative systems that, in the absence of intervention, perpetuate the trauma of non-recognition by subjugation and self-objectification, or by omnipotent denial of others' subjectivity. All abusive systems are facilitated by bystanders, whose awareness of what is disavowed is always partial, resulting in a state of knowing and not-knowing. As dynamics shift, bystanders may behave like victimspassive, helpless, frightened and frozen, or like perpetratorstaking vicarious and voyeuristic pleasure in abuse or actively aiding and abetting the abusers.
Background: The Clostridium difficile rate in symptomatic patients represents both those with C difficile infection (CDI) and those with colonization. To predict the extent of CDI overdiagnosis, we compared the asymptomatic colonization rate to the symptomatic positivity rate in hospitalized patients using nucleic acid testing. Methods: Between July 2014 and April 2015, formed stool samples were collected from asymptomatic patients after admission to 3 hospital wards at the Stanford Hospital. Stool samples from symptomatic patients with suspected CDI in the same wards were collected for testing per provider order. The GeneXpert C. difficile tcdB polymerase chain reaction (PCR) assay (Cepheid, Sunnyvale, CA, USA) was performed on all stool samples and PCR cycle threshold was used as a measure of genomic equivalents. Chart review was performed to obtain clinical history and medication exposure. Results: We found an asymptomatic C. difficile carriage rate of 11.8% (43/365) (95% confidence interval [CI], 8.515.1%) and a positivity rate in symptomatic patients of 15.4% (54/351) (95% CI, 11.6-19.2%; P = 0.19). The median PCR cycle thresholds was not significantly different between asymptomatic carriers and symptomatic positives (29.5 versus 27.3; P = 0.07). Among asymptomatic patients, 11.6% (5/43) of carriers and 8.4% (27/322; P = 0.56) of noncarriers subsequently became symptomatic CDI suspects within the same hospitalization. Single and multivariate analysis did not identify any demographic or clinical factors as being significantly associated with C difficile carriage. Conclusions: Asymptomatic C difficile carriage rate was similar to symptomatic positivity rate. This suggests the majority of PCR-positive results in symptomatic patients are likely due to C. difficile colonization. Disease specific biomarkers are needed to accurately diagnose patients with C difficile disease. (C) 2017 Elsevier Inc. All rights reserved.
ScopeNaturally occurring isothiocyanates (ITCs) have been investigated for their chemopreventive actions. However, limited studies have determined the potential for regulation of hepatic glutathione S-transferase A2 (GSTA2) by arylalkyl or alkyl ITCs. Methods and resultsThe present study was designed to investigate the effects of ITCs on GSTA2 expression and upstream signaling analyzed by Northern blotting, RT-PCR, immunoblotting, and promoter-luciferase assay. A single dose of ethyl isothiocyanate and phenethyl isothiocyanate (PEITC) enhanced GSTA2 mRNA levels in rats. The three consecutive injections of arylalkyl ITCs resulted in the gene induction. PEITC was the most potent and sustained inducer of GSTA2 in vivo. PEITC induced GSTA2 mRNA and protein expression in H4IIE cells. PEITC increased the levels of nuclear factor erythroid 2 related factor 2 and CCAAT/enhancer binding protein (C/EBP). The cells transfected with a pGL-ARE or pGL-C/EBP-deleted promoter construct failed to increase GSTA2 promoter activity by PEITC. These effects of PEITC were downstream of multiple cellular signaling, including phosphoinositide 3-kinase (PI3K), c-jun N-terminal kinase (JNK), and/or protein kinase A (PKA). ConclusionThese results demonstrated that PEITC is the most efficacious of the arylalkyl ITCs for the induction of GSTA2 in vivo and in vitro, and that transactivation of C/EBP and nuclear factor erythroid 2 related factor 2 downstream of multiple signaling pathways is involved in this induction.
In this study, we report the identification and characterization of a novel C2H2 zinc finger protein, ZNF552, from a human embryonic heart cDNA library. ZNF552 is composed of three exons and two introns and maps to chromosome 19q13.43. The cDNA of ZNF552 is 2.3 kb, encoding 407 amino acids with an amino-terminal KRAB domain and seven carboxyl-terminal C2H2 zinc finger motifs in the nucleus and cytoplasm. Northern blotting analysis indicated that a 2.3 kb transcript specific for ZNF552 was expressed in liver, lung, spleen, testis and kidney, especially with a higher level in the lung and testis in human adult tissues. Reporter gene assays showed that ZNF552 was a transcriptional repressor, and overexpression of ZNF552 in the COS-7 cells inhibited the transcriptional activities of AP-1 and SRE, which could be relieved through RNAi analysis. Deletion studies showed that the KRAB domain of ZNF552 may be involved in this inhibition. [BMB reports 2010; 43(3): 193-198]
The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT). We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation. CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p165 ng/mL hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p < 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002]. In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.
This review summarizes biogenesis, composition, intracellular transport, and possible functions of trichocysts. Trichocyst release by Paramecium is the fastest dense core-secretory vesicle exocytosis known. This is enabled by the crystalline nature of the trichocyst "body" whose matrix proteins (tmp), upon contact with extracellular Ca2+, undergo explosive recrystallization that propagates cooperatively throughout the organelle. Membrane fusion during stimulated trichocyst exocytosis involves Ca2+ mobilization from alveolar sacs and tightly coupled store-operated Ca2+-influx, initiated by activation of ryanodine receptor-like Ca2+-release channels. Particularly, aminoethyldextran perfectly mimics a physiological function of trichocysts, i.e. defense against predators, by vigorous, local trichocyst discharge. The tmp's contained in the main "body" of a trichocyst are arranged in a defined pattern, resulting in crossstriation, whose period expands upon expulsion. The second part of a trichocyst, the "tip", contains secretory lectins which diffuse upon discharge. Repulsion from predators may not be the only function of trichocysts. We consider ciliary reversal accompanying stimulated trichocyst exocytosis (also in mutants devoid of depolarization-activated Ca2+ channels) a second, automatically superimposed defense mechanism. A third defensive mechanism may be effectuated by the secretory lectins of the trichocyst tip; they may inhibit toxicyst exocytosis in Dileptus by crosslinking surface proteins (an effect mimicked in Paramecium by antibodies against cell surface components). Some of the proteins, body and tip, are glycosylated as visualized by binding of exogenous lectins. This reflects the biogenetic pathway, from the endoplasmic reticulum via the Golgi apparatus, which is also supported by details from molecular biology. There are fragile links connecting the matrix of a trichocyst with its membrane; these may signal the filling state, full or empty, before and after tmp release upon exocytosis, respectively. This is supported by experimentally produced " frustrated exocytosis", i.e. membrane fusion without contents release, followed by membrane resealing and entry in a new cycle of reattachment for stimulated exocytosis. There are some more puzzles to be solved: Considering the absence of any detectable Ca2+ and of acidity in the organelle, what causes the striking effects of silencing the genes of some specific Ca2+-release channels and of subunits of the H+-ATPase? What determines the inherent polarity of a trichocyst? What precisely causes the inability of trichocyst mutants to dock at the cell membrane? Many details now call for further experimental work to unravel more secrets about these fascinating organelles.
This study aimed to evaluate the recovery of structurally intact human norovirus (NoV) during Kimchi fermentation at varying temperatures. Lactic acid bacteria (LAB), pH, and acidity during storage and fermentation were also measured to assess the correlation between NoV reduction and microbial or physicochemical property alterations. LAB number, NoV G titer, pH, acidity, and the ability of NoV GII.4 to persist in Kimchi stored at 4 degrees C and 10 degrees C (survivability) as determined using nano magnetic beads conjugated with poly(methyl vinyl ether-maleic anhydride) combined with quantitative real-time reverse transcription-polymerase chain reaction amplification were investigated up to 28 days post inoculation. NoV was detected in all test samples after 28 days although the NoV recovery quantity was reduced to 1.31 (4 degrees C) and 1.66 (10 degrees C ) login genomic copies/reaction. The time required to reduce the amount of virus by 2.57 logic, (t(d)) on survival plots of NoV determined using a modified Weibull model was 2445 days at 4 degrees C and 138 days at 10 degrees C. These results indicate that NoV from food preparation or processing is able to persistently survive in Kimchi. Therefore, preventing NoV transmission is important for protecting Kimchi against NoV contamination. (C) 2016 Elsevier Ltd. All rights reserved.
An attributional life cycle assessment (LCA) was conducted to provide a comprehensive picture of the environmental burdens associated with cacao production and primary processing in the Philippines. The analysis considered the entire system, from agricultural operations in the field until storage of the dried beans, required to produce and process 1 ton of dried cacao beans. The inputs include fertilizer, pesticides, diesel, electricity and biodegradable plastics while the outputs include the dried beans, emissions of lambda-cyhalothrin, mancozeb, CO2, SO2, CH4, N2O, NO and CO, and solid wastes. The following impacts were found to be associated with the production of 1 ton dried cacao beans-0.163 kg 1,4-DB-eq. (human toxicity), 0.180 kg 1,4-DB-eq. (terrestrial ecotoxicity), 0.796 kg SO2 eq. (atmospheric acidification) and 629.93 kg CO2 eq. (climate change). Transportation, harvesting, pest management, and nutrient management contributed the most to the environmental impact categories considered in the study. As such, it is suggested that improvement measures be focused on the reduction of fossil fuel consumption and judicious application of fertilizers and pesticides to minimize the adverse environmental impacts of cacao production and primary processing. The amount of harmful emissions released and the impact scores of cacao production and primary processing are generally low. This may be an indication of the cleaner production and eco-efficiency of the system. The results of this LCA study serves as a feedback mechanism that will assist the Philippine cacao industry in identifying the options for improving the environmental management of its production and primary processing system.
Brazil, the Cadastro Ambiental Rural (CAR) is currently being implemented. This policy aims to geo-reference all properties and promote monitoring of, and compliance with, natural vegetation conservation requirements. Scholarly efforts and policy attention have so far concentrated on possible environmental impacts hereof, while the attention devoted to how the CAR might affect farmers' livelihoods has been limited. In this paper, we evaluate potential livelihood impacts of the CAR and programs that facilitate CAR registration. We do so by developing a conceptual framework and using evidence from semi-structured interviews with key stakeholders including farmers, governments, and funding agencies. We find that while the CAR and programs facilitating CAR do not have explicit livelihood impact goals, they nonetheless affect livelihoods, both positively and negatively, depending on the initial amount of natural vegetation on farmers' properties, farmers' access to credit and infrastructure, and changing market conditions. We argue that environmental interventions and policies need to consider potential livelihood impacts, especially if the policy intervention area has high poverty rates. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
Objective: To examine a possible association between maternal-request caesarean section (CS) and two intrapsychic psychoanalytic personality variables: object relations (OR) and unconscious defences.Background: While maternal-request CS is a growing phenomenon, studies are lacking regarding personality variables that may be associated with it.Methods: A cross-sectional questionnaire was conducted in one delivery ward. During 2009, 59 primigravida, healthy women were recruited; 28 who had requested and delivered by CS without an obstetrical indication and 31 who opted for a spontaneous vaginal delivery. Due to missing data for some measures, only 27 participants were analysed in each group. All women completed the fear of childbirth (FOC) questionnaire, and the object relations (SCORS) and unconscious defences (DMM) measures of the Thematic Apperception Test (TAT), as well as questionnaires assessing background variables. Multivariate analysis of variance (MANOVA) and a logistic hierarchical multiple regression were performed.Results: Preliminary MANOVA showed significant differences between groups in age, FOC and use of the defence mechanism projection. Hence, these variables entered as predictors of maternal-request CS to a logistic hierarchical multiple regression model. The model was found to have a good fit [(2)((4)) = 38.19, p<0.001]. Age, FOC and projection defence were found to be significant factors associated with maternal-request CS.Conclusion: Maternal-request CS was found to be strongly associated with age and FOC. Except for unconscious defence of projection, intrapsychic variables were not found to be associated with maternal-request CS. Possible implications are discussed.
There are numerous reports on intronic miRNAs from plants, most of which are involved in the regulation of unrelated genes. Some of the target genes are antagonistic to the host genes. Intronic miRNAs in animal systems, however, are known to have synergistic effects. This article is the first to report a similar regulatory effect of a miRNA originating from an intron in plants. NMT genes involved in caffeine biosynthesis were silenced to obtain transformants with reduced caffeine. Transcript analysis revealed the accumulation of transcripts for a related NMT gene (CaMTL1) in transformants bearing either antisense or RNAi constructs. The altered expression was assumed to relate to the silencing of the NMT genes. Bioinformatics analysis of the genes involved in biosynthesis revealed the presence of an intronic miRNA originating from the intron of the theobromine synthase gene targeting CaMTL1. The putative miRNA was cloned and sequenced. Modified 5'-RLM-RACE mapping of the cleavage site and subsequent Northern blotting experimentally demonstrated the presence and activity of such a miRNA in Coffee canephora. This novel regulatory mechanism previously unreported in plants will shed more light onto the evolution of multigene families and the role of introns in this process. (c) 2013 Elsevier B.V. All rights reserved.
Background: Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this biomarker a promising candidate to be used clinically in different laboratories. However, implementation of the method in routine practice requires analytical robustness and comparable results across laboratories. Therefore, a protocol originally established at the Institute of Immunology, Heidelberg was verified at the Institute of Laboratory Medicine, Klinikum Stuttgart, and a comparison study was conducted between the 2 laboratories. Methods: For the analytical verification, whole blood samples of healthy individuals were incubated with tacrolimus in vitro. Linearity, imprecision, and limit of quantification, as well as sample stability, were investigated. For interlaboratory comparison, samples of patients under cyclosporine A therapy were analyzed in Heidelberg and then reanalyzed in Stuttgart within 24 hours. Results: Tacrolimus (6.25-50 mcg/L) decreased the expression of NFAT-regulated genes in vitro dose dependently (15%-89%). Within-and between-assay coefficient of variations (n = 6 each) were <17%. The limit of quantification was,200 cDNA copies for each of the interleukin-2, interferon-g, and granulocyte-macrophage colony-stimulating factor genes. Samples were stable for 24 hours. Interlaboratory comparison using patient samples correlated well (r = 0.951) but showed an inconsistent bias depending on the magnitude of residual gene expression. Conclusions: The assay can be set up with a satisfactory analytical performance in a routine molecular biological laboratory and shows comparable results between laboratories. The reproducibility of the NFAT-regulated gene expression assay across laboratories can facilitate the implementation of this assay for pharmacodynamic routine monitoring of calcineurin inhibitors in different centers.
Hormonal responses to acute stress rely on the rapid induction of corticotropinreleasing hormone (CRH) production in the mammalian hypothalamus, with subsequent instructive steps culminating in corticosterone release at the periphery. Hypothalamic CRH neurons in the paraventricular nucleus of the hypothalamus are therefore considered as 'stress neurons'. However, significant morphological and functional diversity among neurons that can transiently produce CRH in other hypothalamic nuclei has been proposed, particularly as histochemical and molecular biology evidence associates CRH to both GABA and glutamate neurotransmission. Here, we review recent advances through single-cell RNA sequencing and circuit mapping to suggest that CRH production reflects a state switch in hypothalamic neurons and thus confers functional competence rather than being an identity mark of phenotypically segregated neurons. We show that CRH mRNA transcripts can therefore be seen in GABAergic, glutamatergic and dopaminergic neuronal contingents in the hypothalamus. We then distinguish 'stress neurons' of the paraventricular nucleus that constitutively express secretagogin, a Ca2+ sensor critical for the stimulus-driven assembly of the molecular machinery underpinning the fast regulated exocytosis of CRH at the median eminence. Cumulatively, we infer that CRH neurons are functionally and molecularly more diverse than previously thought.
Voltage-gated calcium (Ca-v) channels serve dual roles in the cell, where they can both depolarize the membrane potential for electrical excitability, and activate transient cytoplasmic Ca2+ signals. In animals, Ca-v channels play crucial roles including driving muscle contraction (excitation-contraction coupling), gene expression (excitation transcriptioncoupling), pre-synaptic and neuroendocrine exocytosis (excitation-secretion coupling), regulation of flagellar/ciliary beating, and regulation of cellular excitability, either directly or through modulation of other Ca2+-sensitive ion channels. In recent years, genome sequencing has provided significant insights into the molecular evolution of Ca-v channels. Furthermore, expanded gene datasets have permitted improved inference of the species phylogeny at the base of Metazoa, providing clearer insights into the evolution of complex animal traits which involve Ca-v channels, including the nervous system. For the various types of metazoan Ca-v channels, key properties that determine their cellular contribution include: Ion selectivity, pore gating, and, importantly, cytoplasmic protein-protein interactions that direct sub-cellular localization and functional complexing. It is unclear when these defining features, many of which are essential for nervous system function, evolved. In this review, we highlight some experimental observations that implicate Ca-v channels in the physiology and behavior of the most early-diverging animals from the phyla Cnidaria, Placozoa, Porifera, and Ctenophora. Given our limited understanding of the molecular biology of Ca-v channels in these basal animal lineages, we infer insights from better-studied vertebrate and invertebrate animals. We also highlight some apparently conserved cellular functions of Ca-v channels, which might have emerged very early on during metazoan evolution, or perhaps predated it.
The ipomoelin gene (IPO) was identified to be a wound-inducible gene from Ipomoea batatas, and its expression was stimulated by methyl jasmonate (MeJA) and hydrogen peroxide. IPO protein was also characterized as a defence-related protein, and it is also a carbohydrate-binding protein. In this study, the expression of IPO was used as a molecular probe to study the effects of Ca2+ on the signal transduction of ethylene. A confocal microscope monitored the Ca2+ within cells, and Northern blotting examined IPO expression. The presence of Ca2+ channel blocker, including diltiazem, neomycin or ruthenium red, abolished the increase of cytosolic Ca2+, and reduced the IPO expression in the cells induced by ethylene. Furthermore, both Ca2+ influxes and IPO expression stimulated by ethylene were prohibited in the presence of 10 mM ethylene glycol-bis(2-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA). These results indicated that Ca2+ influxes into the cytosol induced by ethylene are from both apoplast and organelles, and are required for activating IPO expression. However, in the presence of 1 mM EGTA, ethylene can still stimulate IPO expression, but mechanical wounding failed to do it. Therefore, Ca2+ channels in the plasma membrane induced by ethylene have higher affinity to Ca2+ than that stimulated by wounding. Moreover, the addition of A23187, an ionophore, raised cytosolic Ca2+, but was unable to stimulate IPO expression. These findings showed that IPO induction did not solely depend on Ca2+, and Ca2+ elevation in cytosol is necessary but not sufficient for IPO expression. The application of PD98059, a mitogen-activated protein kinase kinase (MAPKK) inhibitor, did not prevent Ca2+ from increasing in the cytosol induced by ethylene, but inhibited the IPO expression stimulated by staurosporine (STA), a protein kinase inhibitor. Conclusively, elevation of cytosolic Ca2+ by ethylene may stimulate protein phosphatase and MAPKK, which finally activates IPO expression.
A low energy- noise switched-capacitor (SC) sensor interface for resistive bridge sensor is presented. The SC amplifier achieves low-power metric with two operating modes using operation-phase-dependent biasing and compensation scheme in the op-amp design. This novel op-amp works in high-bandwidth high-power mode to sample the bridge signal for 13 mu s twice and in low-bandwidth low-power mode for 474 mu s over 500 mu s measurement interval. To further reduce the power of the SC amplifier in system level, a SC level-shift design is adopted. Regarding offset calibration, a capacitor divider based trimming scheme is implemented to generate the mid-point DC output voltage under the constraint of the feedback capacitor size. Implemented in 65 nm CMOS, the SC interface together with the regulator, voltage reference and trimming circuit occupies an area of 0.358 mm(2). For the first test setup utilizing Half Wheatstone Bridge, the proposed SC amplifier consumes 12.3 mu W at 1 V regulated supply with a 2 kHz system clock. The measured Signal-to-Noise Ratio (SNR) of SC circuit is 55.6 dB. In the second test setup using a commercial sensor with 0.092 mV/kPa sensitivity, the interface has demonstrated the sensing function with sensitivity of 3.52 mV/kPa. Finally, compared to the representative prior-arts, this work has achieved the best energy-noise figure-of-merit at identical fractional resistance change.
Food restriction affects the activation of the immune system although the metabolic cost associated with mounting such a response has rarely been examined except in model animals. Wild animals are constantly exposed to variations in the availability of food resources and they need to balance their energy budget to fight against pathogens. We examined the effect of food restriction in the fish eating Myotis (Myotis vivesi), a species of bat that experiences periods in which foraging is limited due to ambient conditions. We tested the hypothesis that acute food restriction (similar to 65% restriction for 1 night) would reduce the caloric response to lipopolysaccharidae (LPS) injection compared to bats fed ad libitum. We also measured a proxy for body temperature (T-skin) and expected reduced fever development when food intake was limited. Bats on the restricted diet had similar resting metabolic rate, total caloric cost and Tskin after the LPS challenge than when fed ad libitum. However, there was a delay in the metabolic and pyrogenic responses when bats were on the restricted diet. The effect of acute food restriction in delaying the hyperthermia development in fish eating Myotis might be of importance for its capacity to fight pathogens. Similar to other bats, the fish eating Myotis can fast for several consecutive days by entering torpor and future work is warranted to understand the effect of long periods of food restriction on bat immune response. (C) 2016 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.
Calprotectin is composed of two proteins, S100A8 and S100A9, which are S100 family members, and is detected in gingival crevicular fluid and gingival tissue with inflammation. The release and production of calprotectin are regulated by lipopolysaccharides of periodontopathic bacteria and cytokines. Emotional or psychological stress, a risk factor of periodontal disease, is transmitted by stress modulators including norepinephrine and cortisol. The aim of the present study was to investigate the effect of stress on calprotectin expression using norepinephrine and cortisol. U-937 cells, a human monocytic cell line, were incubated with norepinephrine in the presence or absence of beta- or alpha-adrenergic receptor antagonists, or with cortisol. The expression of S100A8/S100A9 mRNAs was examined by northern blotting and the amount of calprotectin was measured by enzyme-linked immunosorbent assay (ELISA). The DNA binding activity of C/EBP alpha (CCAAT enhancing binding protein), a transcription factor, was examined by electrophoretic mobility shift assay. Norepinephrine stimulated the expression of S100A8/S100A9 mRNAs via beta-adrenergic receptors in U-937 cells and significantly increased calprotectin production to about 3.6-fold that of the control. However, cortisol had no effect on calprotectin expression at the mRNA and protein levels. Norepinephrine elevated C/EBP alpha DNA binding activity, but cortisol did not increase the activity. Norepinephrine, a stress modulator, stimulated calprotectin expression in human monocytic cells. Calprotectin expression may be regulated by stress in addition to inflammatory factors.
Calprotectin is an antimicrobial complex composed of the S100A8 and S100A9 protein family subunits. Contributing to innate immunity, calprotectin expression is increased by interleukin-1 alpha (IL-1 alpha), which modulates keratinocyte differentiation. Keratinocyte growth factor (KGF) is produced by mesenchymal cells and has a mitogenic activity for epithelial cells. In this study, we investigated the effect of KGF on calprotectin expression in keratinocytes and modulation by IL-1 alpha. Human keratinocytes were cultured with KGF in the presence or absence of a KGF receptor (KGFR) inhibitor or mitogen-activated protein kinase (MAPK) inhibitors. Calprotectin (S100A8/S100A9) expression was determined by northern blotting and enzyme-linked immunosorbent assay, respectively, whereas MAPK phosphorylation was analyzed by western blot analysis. KGF significantly decreased the expression of S100A8/S100A9-specific mRNAs and calprotectin protein. In the presence of KGF, KGFR inhibitor or extracellular-regulated kinase inhibitor restored KGF-downregulated expression of S100A8/S100A9. KGF increased IL-1 alpha expression in keratinocytes, whereas IL-1 alpha increased KGF expression in fibroblasts. Cocultured fibroblast and keratinocytes showed lower S100A8/S100A9 mRNA expression than keratinocytes alone in the presence or absence of IL-1 alpha or KGF. These results suggest that fibroblast-derived KGF reduces or restricts calprotectin expression in keratinocytes, which supports our hypothesis that calprotectin expression in keratinocytes is modulated by factors associated with epithelial mesenchymal interactions. Immunology and Cell Biology (2010) 88, 328-333; doi: 10.1038/icb.2009.104; published online 12 January 2010
Background: The rapid increase of extended-spectrum beta-lactamase (ESBL) producing bacteria are a potential health hazard. Development of antimicrobial resistance in animal pathogens has serious implications for human health, especially when such strains could be transmitted to human. In this study, the antimicrobial resistance due to ESBL producing Pseudomonas aeruginosa in the camel meat was investigated. Methods: In this study meat samples from 200 healthy camels at two major abattoirs in Egypt (Cairo and Giza) were collected. Following culture on cetrimide agar, suspected P. aeruginosa colonies were confirmed with a Vitek 2 system (bioMe'rieux). P. aeruginosa isolates were phenotypically identified as ESBL by double disk synergy test. Additionally antimicrobial susceptibility testing of ESBL producing P. aeruginosa isolates were done against 11 antimicrobial drugs and carried out by disk diffusion method. The ESBL genotypes were determined by polymerase chain reaction according to the presence of the bla(PFR-1), bla(CTX-M), bla(SHV), and bla(TFM). Results: Pseudomonas aeruginosa was isolated from 45 camel meat sample (22.5%). The total percentage of ESBL producing P. aeruginosa was 45% (21/45) from camel meat isolates. Antibiogram results revealed the highest resistance was for c, ceftriaxone and rifampicin followed by cefepime and aztreonam. The prevalence rates of beta-lactamase genes were recorded (bla(PER-1) 28.5%, bla(CTX-M) 38%, bla(SHV) 33.3% and bla(TEM) 23.8%). Conclusions: This study illustrates the presence of high rates of ESBL-P. aeruginosa in camels that represents an increasing alarming for the risk of transmission to human and opens the door for current and future antibiotics therapy failure. Livestock associated ESBL-P. aeruginosa is a growing disaster, therefore, attention has to be fully given to livestock associated ESBL-bacteria which try to find its way to human beings.
The major aim of made tea identification is to identify the variety and provenance of the tea plant. The present experiment used 113 tea plants [Camellia sinensis (L.) O. Kuntze] housed at the Tea Research and Extension Substation, from which 113 internal transcribed spacer 2 (ITS2) fragments, 104 trnL intron, and 98 trnL-trnF intergenic sequence region DNA sequences were successfully sequenced. The similarity of the ITS2 nucleotide sequences between tea plants housed at the Tea Research and Extension Substation was 0.379-0.994. In this polymerase chain reaction-amplified noncoding region, no varieties possessed identical sequences. Compared with the trnL intron and trnL-trnF intergenic sequence fragments of chloroplast cpDNA, the proportion of ITS2 nucleotide sequence variation was large and is more suitable for establishing a DNA barcode database to identify tea plant varieties. After establishing the database, 30 imported teas and 35 domestic made teas were used in this model system to explore the feasibility of using ITS2 sequences to identify the varieties and provenances of made teas. A phylogenetic tree was constructed using ITS2 sequences with the unweighted pair group method with arithmetic mean, which indicated that the same variety of tea plant is likely to be successfully categorized into one cluster, but contamination from other tea plants was also detected. This result provides molecular evidence that the similarity between important tea varieties in Taiwan remains high. Wesuggest a direct, wide collection of made tea and original samples of tea plants to establish an ITS2 sequence molecular barcode identification database to identify the varieties and provenances of tea plants. The DNA barcode comparison method can satisfy the need for a rapid, low-cost, frontline differentiation of the large amount of made teas from Taiwan and abroad, and can provide molecular evidence of their varieties and provenances. Copyright (C) 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.
In higher plants, P450s participate in the biosynthesis of many important secondary metabolites. Here we reported for the first time the isolation of a new cytochrome P450 cDNA that expressed in a stem-specific manner from Camptotheca acuminata (designated as CaSS), a native medicinal plant species in China, using RACE-PCR. The full-length cDNA of CaSS was 1735 bp long containing a 1530 bp open reading frame (ORF) encoding a polypeptide of 509 amino acids. Bioinformatic analysis revealed that CASS contained a heme-binding domain PFGXGRRXCX and showed homology to other plant cytochrome P450 monooxygenases and hydroxylases. Southern blotting analysis revealed that there was only one copy of the CaSS present in the genome of Camptotheca acuminata. Northern blotting analysis revealed that CaSS expressed, in a tissue-specific manner, highly in stem and lowly in root, leaf and flower. Our study suggests that CaSS is likely to be involved in the phenylpropanoid pathway.
The aim of this study was to reveal the molecular mechanism involved in multidrug resistance and virulence of Campylobacter jejuni isolated from broiler chickens. The virulence of six multidrug resistant C. jejuni was determined by in vitro and in vivo methods. The de novo whole genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the multidrug resistance and virulence of a selected isolate (C. jejuni 1655). The comparative genomic analyses revealed a large number of single nucleotide polymorphisms, deletions, rearrangements, and inversions in C. jejuni 1655 compared to reference C. jejuni genomes. The co-emergence of Thr-86-1Ie mutation in gyrA gene, A2075G mutation in 23S rRNA gene, tetO, aphA and aadE genes and pTet plasmid in C. jejuni 1655 contributed its multidrug resistance to fluoroquinolones, macrolides, tetracycline, and aminoglycosides. The combination of multiple virulence genes may work together to confer the relative higher virulence in C. jejuni 1655. The co-existence of mobile gene elements (e.g., pTet) and CRISPR-Cas system in C. jejuni 1655 may play an important role in the gene transfer and immune defense. The present study provides basic information of phenotypic and genomic features of C. jejuni 1655, a strain recently isolated from a chicken displaying multidrug resistance and relatively high level of virulence.
Background: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis. Methods: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set from 2000 to 2015. All types of journal documents, excluding errata, were considered. Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented. The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals. Results: A total of 5522 documents were retrieved with median (Q1-Q3) citations of 9 (2-23) and h-index of 113. Annual number of publications showed a fluctuating increase. The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each. The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half of the top ten productive countries were European. France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration. Approximately half (50.1%) of retrieved articles were published in journals under the subject area of "immunology/microbiology". Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis. There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones. Conclusions: There was a clear increase in number of publications on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is highly recommended. International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.
Objective: To increase the level of awareness that Ehlers-Danlos/hypermobility syndrome (EDS) and vitamin D deficiency are associated with infantile fragility fractures and radiologic features that may be mistakenly reported to be caused by non-accidental trauma due to Child Abuse and Neglect (CAN). Patients and Methods: We constructed a case series, the largest to date, of infants with EDS who were vitamin D sufficient, insufficient and deficient and infants without EDS but with documented vitamin D deficiency and radiologic evidence of rickets who presented with multiple fractures originally diagnosed as being non-accidental and caused by child abuse. These infants were referred to the outpatient Bone Health Care Clinic at Boston University Medical Campus over a 6-year (2010-2015) period. We also present 6 index cases in which the court concluded that there was no convincing evidence of child abuse and the infants were returned to their parents. Institutional Review Board (IRB) approval was obtained. Results: We present 72 cases of infants with multiple fractures diagnosed to be caused by non-accidental trauma. All infants were younger than one year of age. Among them, 93%(67) had clinical evidence of EDS and/or a family history with a confirmed clinical diagnosis of at least one parent having EDS and the other 7%(5) without evidence of EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common fractures noted at diagnosis were ribs and extremity fractures (including classic metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH) D] were reported in 48 infants (18.0 +/- 8.5 ng/ml) and in 30 mothers (21.3 +/- 11.7 ng/ml). Sixty-three percent (27) of the EDS infants who had their serum 25(OH) D measured were vitamin D deficient 25(OH) D30 ng/ml. The mean serum level for infants with vitamin D deficiency/rickets was (10.2 +/- 3.0 ng/ml) Conclusion: EDS, OI/EDS and vitamin D deficiency/infantile rickets are associated with fragility fractures in infants that can be misinterpreted as caused by non-accidental trauma due to child abuse.
This article uses an intersectionality lens to explore how experiences of race, gender, sexuality, class and their intersections are associated with depression and unmet need for mental healthcare in a population of 704 women and transgender/gender liminal people from Ontario, Canada. A survey collecting demographic information, information about mental health and use of mental healthcare services, and data for the Everyday Discrimination Scale and the PHQ-9 Questionnaire for Depression was completed by 704 people via Internet or pen-and-paper between June 2011 and June 2012. Bivariate and regression analyses were conducted to assess group differences in depression and discrimination experiences, and predictors of depression and unmet need for mental healthcare services. Analyses revealed that race, gender, class and sexuality all corresponded to significant differences in exposure to discrimination, experiences of depression and unmet needs for mental healthcare. Use of interaction terms to model intersecting identities and exclusion contributed to explained variance in both outcome variables. Everyday discrimination was the strongest predictor of both depression and unmet need for mental healthcare. The results suggest lower income and intersections of race with other marginalised identities are associated with more depression and unmet need for mental healthcare; however, discrimination is the factor that contributes the most to those vulnerabilities. Future research can build on intersectionality theory by foregrounding the role of structural inequities and discrimination in promoting poor mental health and barriers to healthcare.
Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.
Measuring cell proliferation can be performed by a number of different methods, each with varying levels of sensitivity, reproducibility and compatibility with high-throughput formatting. This protocol describes the use of three different methods for measuring cell proliferation in vitro including conventional hemocytometer counting chamber, a luminescence-based assay that utilizes the change in the metabolic activity of viable cells as a measure of the relative number of cells, and a multi-mode cell imager that measures cell number using a counting algorithm. Each method presents its own advantages and disadvantages for the measurement of cell proliferation, including time, cost and high-throughput compatibility. This protocol demonstrates that each method could accurately measure cell proliferation over time, and was sensitive to detect growth at differing cellular densities. Additionally, measurement of cell proliferation using a cell imager was able to provide further information such as morphology, confluence and allowed for a continual monitoring of cell proliferation over time. In conclusion, each method is capable of measuring cell proliferation, but the chosen method is user-dependent.
Molecular imaging agents have the ability to non-invasively visualize, characterize, and quantify the molecular biology of disease. Recent advances in nuclear probe development, particularly in PET radiotracers, have generated many new imaging agents with precise molecular targets. With such specificity, PET probes may be utilized as biomarkers to objectively interrogate and evaluate pathology. Whereas the current indications for PET imaging are predominately confined to staging and restaging of malignancy, the utility of PET greatly expands when utilized as a biomarker, the topic of this review. As an imaging biomarker, PET may be used to (1) measure target expression to select subsets of patients who would most benefit from targeted therapy; (2) measure early treatment response to predict therapeutic efficacy; and (3) relate tumor response to survival. This review will discuss the application of radiotracers to targeted cancer therapy. Particular attention is given to new radiotracers evaluated in recently completed clinical trials and those with current or potential clinical utility. The diverse roles of PET in clinical trails for drug development are also examined. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
In order to study the impact of nucleus accumbens-1 (NAC1) expression on survival in cancer cell and the molecular mechanism involved. NAC1 has been observed to be up-regulated in human cancer, and to play an important role in progression and recurrence of ovarian cancer. In this study, we investigated the regulatory role of NAC1 in glycolysis and the effect of the NAC1-mediated glycolysis on cancer cell survival. Cell biology, molecular biology, and pharmacology approaches and methods were used in this study. We demonstrated: 1) NAC1 is a critical regulator of cancer cell survival under hypoxic condition. Silencing of NAC1 leads to increase in the cleaved caspase-3 and cleaved PARP, and a decline in cell viability and colony formation when the cells were subjected to hypoxia; 2) NAC1 is a novel regulator of glycolysis. Depletion of NAC1 leads to an increase in the concentration of glucose in the culture medium, a decrease in the level of intercellular lactate; 3) NAC1 enhances the stability and protein level of HIF-1 alpha. Under hypoxia, NAC1 promotes cancer cell survival and glycolysis through strengthening the stability of HIF-1 alpha.
Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.
Myeloid-derived suppressor cells (MDSCs) cause paraneoplastic leukemoid reactions and facilitate tumor cell metastasis. However, the interaction of MDSCs with tumor cells in live tissue has not been adequately visualized. To accomplish this task, we developed an intravital imaging protocol to observe metastasized tumor cells in mouse lungs. For visualization of the activation of MDSCs, bone marrow cells derived from transgenic mice expressing a Forster resonance energy transfer biosensor for ERK were implanted into host mice. Under a two-photon excitation microscope, numerous polymorphonuclear cells (PMNs) were found to infiltrate the lungs of tumor-bearing mice in which 4T1 mammary tumor cells were implanted into the footpads. By Forster resonance energy transfer imaging, we found ERK activation in PMNs around the 4T1 tumor emboli in the lungs. Because antibody array analysis implied the involvement of osteopontin (OPN) in the metastasis of 4T1 cells, we further analyzed the effect of OPN knockdown. The OPN knockdown in 4T1 cells did not affect the cell growth, but markedly suppressed lung metastasis of 4T1 cells and ERK activation in PMNs in the lung. Intravenous injection of recombinant OPN restored the lung metastasis of OPN-deficient 4T1 cells, suggesting that OPN functioned in a paracrine manner. It has been reported that ERK activation of neutrophils causes NETosis and that PMNs promote metastasis of tumor cells by NETosis. In agreement with previous reports, the NETosis inhibitor DNase I inhibited lung metastasis of 4T1 cells. These observations suggest that OPN promotes metastasis of 4T1 cells by activating PMNs and inducing NETosis.
The lymph node (LN) is an important immune system in which a number of antigen-presenting cells are present that induce rapid immune responses to foreign antigens. While a great number of macrophages exist in lymph nodes, recent studies using animal models have shown that lymph node sinus macrophages are associated with the induction of anti-tumor immunity, playing a significant role in host immune responses against tumor cells. In colorectal tumor, malignant melanoma, and endometrial tumor, it was shown that a high density of CD169-positive macrophages in the LN sinus was a predictive factor for better clinical prognosis. The observations that the density of CD169-positive macrophages in the LN sinus was positively associated with the density of infiltrating T or NK cells in tumor tissues, indicates the significance of CD169-positive macrophages in anti-tumor immune reactions of tumor patients. Moreover, antigen delivery targeting LN macrophages is also considered to be promising approach for vaccination. In this article, we have summarized the significance of CD169-positive LN macrophages in anti-tumor immunity.
Objective: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC. Methods: Upregulation of natural killer group 2D (NKG2D) ligands (retinoic acid early inducible 1 [RAE-1], mouse; major histocompatibility complex class I polypeptide-related sequence A [MIC-A], human) were evaluated by FACS. VPA concentrations that did not reduce tumor volume were calculated to avoid VPA cytotoxicity in a C3H mouse model of HCC. CIK cells were generated from mouse splenocytes using interferon gamma, a CD3 monoclonal antibody, and interleukin 2. The potential synergistic effect of CIK cells combined with VPA was evaluated in the mouse model and tissue pathology was investigated. Results: After 40h of incubation with VPA, RAE-1 and MIC-A expression were increased in 4 HCC cell lines compared with that in control (2.3-fold in MH-134, 2.4-fold in Huh-7, 3.7-fold in SNU-761, and 6.5-fold in SNU-475). The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10mg/kg/day. CIK cells were well generated from C3H mouse splenocytes. After 7d of treatment with CIK cells plus VPA, a synergistic effect was observed on relative tumor volume in the mouse model of HCC. While the relative tumor volume in untreated control mice increased to 11.25, that in the combination treatment group increased to only 5.20 (P = 0.047). Conclusions: The VPA-induced increase in NKG2D ligands expression significantly enhanced the effects of CIK cell therapy in a mouse model of HCC.
The progressive growth and spread of tumour cells in the form of metastases requires an interaction of healthy host cells, such as endothelial cells, fibroblasts, and other cells of mesenchymal origin with immune cells taking part in innate and adaptive responses within the tumour lesion and entire body. The host cells interact with tumour cells to create a dynamic tumour microenvironment, in which healthy cells can both positively and negatively influence the growth and spread of the tumour. The balance of cellular homeostasis and the effect of substances they secrete on the tumour microenvironment determine whether the tumour has a tendency to grow or disappear, and whether the cells remain within the lesion or are capable of metastasis to other regions of the body. Intercellular interactions also determine the tumour's susceptibility to radiation or other types of cancer treatment. They may also be a rational explanation for differences in treatment outcomes, in which some metastases regress and others progress in response to the same treatment method.
Hanahan and Weinberg described six distinct biological properties of cancer cells that enable tumor growth and metastasis. These properties were referred to as the traditional hallmarks of cancer. Recent discoveries further elucidated hallmarks including evasion of immune destruction by tumor cells that disrupt anticancer response pathways. This review discusses cancer immunology and new treatment strategies aimed at restoration of antitumor immune responses.
Introduction: Regulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods: Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results: DTX specifically depleted Treg in a transient, dose-dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor-peptide vaccination. Conclusions: BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor-specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.
The crosstalk between NK cells and M1 macrophages has a vital role in the protection against infections and tumor development. However, macrophages in the tumor resemble an M2 phenotype, and, at present, their effect on NK cells is less clear. This study investigated whether tumor-associated macrophages (TAMs) have a role in altering NK cell function and phenotype using in vitro cocultures of murine NK cells with peritoneal or bone marrow-derived, M2-polarized macrophages or TAMs isolated from spontaneous mouse breast tumors. We report here that both peritoneal and bone marrow-derived M2 macrophages, as well as TAMs, substantially inhibit NK cell activation and concordant cytotoxicity against tumor cells. The mechanism for this inhibition was found to require contact between the respective cell types. Both M2 macrophages and TAMs are producers of the immunosuppressive cytokine TGF-beta. The inhibition of TGF-beta restored the cytotoxicity of NK cells in contact with M2 macrophages, implicating TGF-beta in the mechanism for NK cell inhibition. In addition to affecting NK cell function, TAMs also induced a CD27(low)CD11b(high)-exhausted NK cell phenotype, which corresponds with the reduced activation and cytotoxicity observed. This study reveals a novel implication of TAMs in the tumor-associated inhibition of NK cell function by demonstrating their capacity to directly alter NK cell cytotoxicity and phenotype in a contact-dependent mechanism involving TGF-beta. These findings identify the interaction between NK cells and TAMs as a prospective therapeutic target to enhance NK cell effector function for effective NK cell cancer therapies.
The field of immune-oncology is rapidly progressing with new data being generated across all research areas of this field. The American Association for Cancer Research (AACR)'s Tumor Immunology and Immunotherapy meeting, the sixth in this series, provides a forum for researchers from academia and industry, as well as clinicians, to present their work to a global audience to enhance the understanding of the immune response to cancer and to focus on how this response can be used for disease treatment and prevention.
Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.
Background: Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment. Objective: The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age-and gender-matched healthy controls with occasional tiredness (n = 25). Methods: Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance. Results: Survivors of HCT reported increased physical (P <.001), mental (P <.001), and overall (P <.001) fatigue as well as increased anxiety (P <.05) and depression (P <.01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P <.001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-! (P <.001) and interleukin-6 (P <.05) levels were significantly higher in HCT survivors. Conclusions: Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-alpha and interleukin-6 levels may be important biomarkers. Implications for Practice: This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.
Many Siglecs function as inhibitory receptors on innate and adaptive immune cells and may contribute to the attenuation of immune responses to tumors. Siglec 9 on neutrophils and Siglec 7 on NK cells are prominent examples of inhibitory Siglecs that can potentially dampen anti-tumor immunity. CD169 is a Siglec that may function as an adhesion molecule and a facilitator of the recognition and internalization of sialic acid decorated apoptotic bodies and exosomes derived from tumors. It can potentially contribute to both the attenuation as well as the facilitation of anti-tumor immunity. Siglecs have been best studied in the tumor context in animal models of cancer. Modulators of Siglec function are likely to be developed and investigated clinically in a cancer context over the next few years.
Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors. Nevertheless, potent inhibitors for most H3K36 KMTases have not yet been developed, underlining the challenges associated with this target class. As we now have strong evidence linking H3K36 KMTases to cancer, drug development efforts are predicted to yield novel compounds in the near future.
Background: Adults, 65 years or older, are the most common age group diagnosed with cancer. However, little is known about their beliefs (representations) regarding treatment-related symptoms or how they make decisions to manage those symptoms at home. Objective: The aim of this study is to explore symptom representation of treatment-related symptoms in older adults with cancer. Methods: A total of 100 older adults in treatment for cancer completed a standardized measure of symptom representation. Demographic and other patient variables were also collected. Analysis of variance, t tests, and Pearson correlations were used for analysis. Results: Fatigue was both the most common and most noted symptom; however, several most noted symptoms were not common. Overall, older adults believed symptoms were caused by either their cancer or treatment and were unsure if symptoms would last a long time. They were able to recognize symptom consequences but were unsure about their ability to control symptoms. Adults who reported more comorbid illnesses and a higher number of symptoms believed that treatment-related symptoms had higher consequences. Conclusions: Findings suggest that older adults experience symptom-related consequences but question the impact that their actions will have on symptom severity. This may contribute to older adult's lack of active symptom self-management. Implications for Practice: Patient education strategies need to address these representations and new interventions may need to be developed to reinforce symptom consequences and empower older adults to self-manage symptoms.
Herein we report the synthesis and activity of an enzyme-directed immunostimulant with immune cell activation mediated by -galactosidase, either exogenously added, or on B16 melanoma cells. Covalent attachment of a -galactopyranoside to an imidazoquinoline immunostimulant at a position critical for activity resulted in a pro-immunostimulant that could be selectively converted by -galactosidase into an active immunostimulant. The pro-immunostimulant exhibited -galactosidase-directed immune cell activation as measured by NF-B transcription in RAW-Blue macrophages or cytokine production (TNF, IL-6, IL-12) in JAWSII monocytes. Conversion of the pro-immunostimulant into an active immunostimulant was also found to occur using -galactosidase-enriched B16 melanoma cells. In co-culture experiments with either immune cell line, -galactosidase-enriched B16 cells effected activation of bystander immune cells.
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions. Cancer state is not optimized for the whole organism. The discovery of crucial players in cancer, together with their developmental and physiological roles, in turn, suggests the existence of a hierarchical structure within molecular biology systems. Such a structure enables a decision network to be constructed from experimental knowledge. By examining the nonlinear stochastic dynamics of the network, robust states corresponding to normal physiological and abnormal pathological phenotypes, including cancer, emerge naturally. The nonlinear dynamical model of the network leads to a more encompassing understanding than the prevailing linear-additive thinking in cancer research. So far, this theory has been applied to prostate, hepatocellular, gastric cancers and acute promyelocytic leukemia with initial success. It may offer an example of carrying physics inquiring spirit beyond its traditional domain: while quantitative approaches can address individual cases, however there must be general rules/laws to be discovered in biology and medicine.
Patients with cancer often experience a high symptom burden prior to the start of treatment. As disease and treatment-related neurotoxicities appear to be additive, targeting disease-related symptoms may attenuate overall symptom burden for cancer patients and improve the tolerability of treatment. It has been hypothesized that disease-related symptoms are a consequence of tumor-induced inflammation. We tested this hypothesis using a syngeneic heterotopic murine model of human papilloma virus (HPV)related head and neck cancer. This model has the advantage of being mildly aggressive and not causing cachexia or weight loss. We previously showed that this tumor leads to increased IL-6, IL-1 beta, and TNF-alpha expression in the liver and increased 1L-1 beta expression in the brain. The current study confirmed these features and demonstrated that the tumor itself exhibits high inflammatory cytokine expression (e.g., IL-6, IL-1 beta, and TNF-alpha) compared to healthy tissue. While there is a clear relationship between cytokine levels and behavioral deficits in this model, the behavioral changes are surprisingly mild. Therefore, we sought to confirm the relationship between behavior and inflammation by amplifying the effect using a low dose of lipopolysaccharide (LPS, 0.1 mg/kg). In tumor-bearing mice LPS induced deficits in nest building, tail suspension, and locomotor activity approximately 24 h after LPS. However, these mice did not display an exacerbation of LPS-induced weight loss, anorexia, or anhedonia. Further, while heightened serum IL-6 was observed there was minimal priming of liver or brain cytokine expression. Next we sought to inhibit tumor-induced burrowing deficits by reducing inflammation using minocycline. Minocycline (similar to 50 mg/kg/day in drinking water) was able to attenuate tumor-induced inflammation and burrowing deficits. These data provide evidence in favor of an inflammatory-like mechanism for the behavioral alterations associated with tumor growth in a syngeneic murine model of HPV-related head and neck cancer. However, the inflammatory state and behavioral changes induced by this tumor clearly differ from other forms of inflammation-induced sickness behavior. (C) 2017 Elsevier Ltd. All rights reserved.
Cancer is a serious hazard to human health all around the world; however, many current therapies remain toxic and poor. In view of the understanding of immunology and tumor biology, cancer immunotherapy with minimal toxicity has been regarded as a promising strategy for cancer treatment because of immune surveillance. Unfortunately, the efficacy of immunotherapy was impeded and resisted due to the tumor immune evasion mechanism. Hence, targeted cancer immunotherapy has been proposed to tackle the tumor immune suppression and complexity of malignant tumor cells. Nanotechnology-based immunotherapy has improved the limitations and enhanced the therapeutic efficiency of traditional immunotherapy. This review illustrates the recent progresses in immunotherapy based on nanotechnology, and reveals that nanodevices could be utilized for active and passive cancer immunotherapy.
The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
The purpose of this study is to evaluate if locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures among terminally ill cancer patients at the time of palliative care consult. Multi-site analysis of patients with advanced cancer being seen as new patients in a Palliative and Supportive Care outpatient clinic. Patients completed the following surveys: locus of control (LOC) scale, Functional Assessment of Chronic Illness Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital Anxiety Depression Scale (HADS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of age, gender, race, partnership status, education, and months since diagnosis as potential confounders. This study enrolled 100 patients. After adjusting for site, race, and partnership status, higher levels of LOC chance predicted decreased QOL (FACT-G) (p < 0.01). Higher levels of LOC chance also correlated with increased depression and anxiety (p < 0.01) and decreased meaning/peace and faith (p < 0.01). Additionally, higher levels of LOC chance predicted decreased hope (HHI) (p < 0.001). Terminally ill cancer patients with a high LOC chance may be at risk for decreased physical and mental well-being at the end of life. Efforts should be made to identify these patients and design interventions to increase their feeling of control over the situation in order to improve physical and mental well-being at the end of life.
Metal complexes have been the subject of numerous investigations in oncology but, despite the plethora of newly synthesized compounds, their precise mechanisms of action remain generally unknown or, for the best, incompletely determined. The continuous development of efficient and sensitive techniques in analytical chemistry and molecular biology gives scientists new tools to gather information on how metal complexes can be effective toward cancer. This review focuses on recent findings about the anticancer mechanism of action of metal complexes and how the ligands can be used to tune their pharmacological and physicochemical properties.
microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical clustering was able to distinguish tumor from normal pancreas, pancreatitis and cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including microRNAs previously reported as differentially expressed in other human cancers (miR-155, miR21, miR-221 and miR-222) as well as those not previously reported in cancer (miR-376a and miR-301). Most of the top aberrantly expressed miRNAs displayed increased expression in the tumor. Expression of the active, mature microRNA was validated using a real-time PCR assay to quantify the mature microRNA and Northern blotting. Reverse transcription in situ PCR showed that three of the top differentially expressed miRNAs (miR-221, -376a and -301) were localized to tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA expression may offer new clues to pancreatic tumorigenesis and may provide diagnostic biomarkers for pancreatic adenocarcinoma. (c) 2006 Wiley-Liss, Inc.
Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in cancer survivors and decrease quality of life; however, the impact of the co-occurrence of these conditions has garnered little attention. This study investigated differences between obese and non-obese cancer survivors with CIPN and predictors of symptom burden and pain. Patients with CIPN were administered the MD Anderson Symptom Inventory and a modified version of pain descriptors from the McGill Pain Inventory. Independent t tests assessed group differences between obese and non-obese survivors, and linear regression analyses explored predictors of patient outcomes. Results indicated a significant difference in symptom severity scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08) patients (t(37.86) = -2.49, p = .02). Significant differences were also found for a total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus non-obese (M = 2.42, SD = 2.69) participants (t(74) = -2.53, p = .01). Obesity was a significant predictor of symptom severity and total pain descriptors endorsed. Other significant predictors included age and months since treatment. Cancer survivors with CIPN and co-occurring obesity may be more at risk for decreased quality of life through increased symptom severity and pain compared to non-obese survivors. This paper identified risk factors, including obesity, age, and months since treatment, that can be clinically identified for monitoring distress in CIPN patients. Future research should focus on the longitudinal relationship between obesity and CIPN, and robust interventions to address the multifaceted issues faced by cancer survivors.
BackgroundUDP-glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17) encodes for an enzyme that modifies carcinogens, C19 steroids, xenobiotics, and anticancer chemotherapeutic agents by glucuronidation. Pediatric cancers are much more sensitive to anticancer agents than adult cancers. The aim of this study was therefore to examine the effects of UGT2B17 deletion polymorphism on prognosis in pediatric cancer. MethodsA total of 145 DNA samples were collected from children with malignant disease. UGT2B17 copy number variant was determined on polymerase chain reaction. Survival analysis was carried out to analyze the effects of UGT2B17 deletion on relapse-free rate in lymphoblastic and non-lymphoblastic malignancy. ResultsUGT2B17 was deleted in 64% of children with lymphoblastic malignancy, but in 83% of children with non-lymphoblastic malignancy. Moreover, in non-lymphoblastic malignancy, children without UGT2B17 deletion polymorphism had significantly higher relapse rates than those with the deletion polymorphism (HR, 16.1; 95%CI: 1.67-154; P = 0.016), which remained significant after adjustment for age, sex, underlying disease, advanced stage, and adverse events (HR, 22.4; 95%CI: 1.10-454; P = 0.043). There was a significant interaction between UGT2B17 deletion and non-lymphoblastic malignancy. In the early subgroup, that is, stages 1-3 or standard/intermediate risk, children without UGT2B17 deletion polymorphism had a higher relapse rate than children with more advanced disease (log-rank test: P = 0.0004). ConclusionsUGT2B17 deletion polymorphism may improve the relapse-free rate in children with non-lymphoblastic malignancy.
Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make PM a reality today through the use of massive amounts of genetic, 'omics', clinical, environmental, and lifestyle data. With cancer being one of the most prominent public health threats in developed countries, both the research community and governments have been investing significant time, money, and efforts in precision cancer medicine (PCM). Although PCM research is extremely promising, a number of hurdles still remain on the road to an optimal integration of standardized and evidence-based use of PCM in healthcare systems. Indeed, PCM raises a number of technical, organizational, ethical, legal, social, and economic challenges that have to be taken into account in the development of an appropriate health policy framework. Here, we highlight some of the more salient issues regarding the standards needed for integration of PCM into healthcare systems, and we identify fields where more research is needed before policy can be implemented. Key challenges include, but are not limited to, the creation of new standards for the collection, analysis, and sharing of samples and data from cancer patients, and the creation of new clinical trial designs with renewed endpoints. We believe that these issues need to be addressed as a matter of priority by public health policymakers in the coming years for a better integration of PCM into healthcare.
Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions. (C) 2017 Elsevier B.V. All rights reserved.
Background: Fatigue is one of the most debilitating adverse effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy. Objective: We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue 1 year following treatment completion in men with nonmetastatic prostate cancer (NM-PC). Methods: A sample of 34 men with nonmetastatic prostate cancer scheduled to receive EBRT were followed up at baseline (T1), midpoint of EBRT (T2), and 1 year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer TherapyYFatigue was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits. Results: Significant correlations were observed between levels of interleukin 2 (IL-3), IL-8, IL-9, IL-10, IL-16, interferon + Yinduced protein 10, interferon alpha 2, interferon +, and stromal cell-derived factor 1 alpha at T2 with worsening of fatigue from T1 to T3. Conclusions: Immunological changes prior to chronic fatigue development may reflect the long-term response to radiation therapyYinduced damage. Implications for Practice: Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk of developing chronic fatigue after cancer treatment. This information will also aid in patient education, as well as symptom management.
In this paper, cotton seed oil deodorizer distillate (CSODD), was recovered to obtain fatty acid sterol ester (FASE), which is one of the biological activated substances added as human therapeutic to lower cholesterol. Esterification reactions were carried out using Candida rugosa lipase as a catalyst, and the conversion of phytosterol was optimized using response surface methodology. The highest conversion (90.8 +/- 0.4%) was reached at 0.84 wt% enzyme load, 1: 25 solvent/CSODD mass ratio, and 44.2 degrees C after 12 H reaction. A kinetic model based on the reaction rate equation was developed to describe the reaction process. The activation energy of the reaction was calculated to be 56.9 kJ/mol and the derived kinetic parameters provided indispensable basics for further study. The optimization and kinetic research of synthesizing FASE from deodorizer distillate provided necessary information for the industrial applications in the near future. Experimental results showed that the proposed process is a promising alternative to recycle sterol esters from vegetable oil deodorizer distillates in a mild, efficient, and environmental friendly method. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
In the absence of steroid receptors and any known mechanism of gene regulation by steroid hormones in Candida albicans, we did a genome-wide analysis of C. albicans cells treated with progesterone using Eurogentec cDNA microarrays to find the complete repertoire of steroid responsive genes. Northern blotting analysis was employed to validate the genes that were differentially regulated by progesterone in the microarray experiments. A total of 99 genes were found to be significantly regulated by progesterone, among them 60 were up-regulated and 39 were down-regulated. It was observed that progesterone considerably enhanced the expression of multi-drug resistance (MDR) genes belonging to ATP Binding Cassette (CDR1 and CDR2) super-family of multidrug transporters, suggesting a possible relationship between steroid stress and MDR genes. Several genes associated with hyphal induction and the establishment of pathogenesis were also found up-regulated. In silico search for various transcription factor (TF) binding sites in the promoter of the affected genes revealed that EFG1, CPH1, NRG1, TUP1, MIG1 and AP-1 regulated genes are responsive to progesterone. The stress responsive elements (STRE; AG(4) or C4T) were also found in the promoters of several responsive genes. Our data sheds new light on the regulation of gene expression in C. albicans by human steroids, and its correlation with drug resistance, virulence, morphogenesis and general stress response. A comparison with drug induced stress response has also been discussed.
In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung lobes. The neuraminidase gene sequence from the influenza virus isolated obtained from this dog had 98% homology to the strain circulating in the Chicago area.
Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite.
Canine parvovirus type 2 (CPV-2) comprises three antigenic subtypes (2a, 2b and 2c) that have been reported in many countries. These subtypes cause serious disease in dogs with characteristic gastroenteritis signs. Little information has been documented in Africa about the genetic characterization of CPV-2. The aim of this study was to detect and to characterize the CPV-2 subtypes circulating in dogs admitted to Veterinary Clinics from two cities of Mozambique, Maputo and Matola, in 2010. A total of 40 field fecal samples were collected and tested for CPV-2 by polymerase chain reaction assay. The partial length VP2 gene of the positive samples were sequenced and genetically analyzed. Twenty-six (65%) fecal samples were positive for CPV-2. The restriction fragment length polymorphism analysis was also performed from positive samples and did not reveal the presence of CPV-2c subtype. The results of the sequencing revealed the presence of CPV-2a (n = 9) and CPV-2b (n = 17). No CPV-2 and CPV-2c were detected. Sequence analysis comparison showed nucleotide identities of 99.6-100% among our CPV-2 isolates. Amino acid analysis showed predicted amino acid changes. Phylogenetically, all of the CPV-2a strains isolated formed a cluster together with South African and Nigerian isolates. Most of Mozambican CPV-2b isolates also tended to cluster together with South African isolates; however, four were more closely related to French strain and one isolates to the American strain. The present study was the first to characterize the CPV-2 circulating in the Mozambican dog population.
Aims: Recent evidence indicates that the defective ability to clear apoptotic cells by macrophages (efferocytosis) and the resultant apoptotic cells accumulation in atherosclerotic plaques play an important role during the progression of unstable plaques. The cannabinoid type 2 receptor (CB2), has recently been emerging as a new target to reduce vulnerability and promote stability of plaques, however, the underlying mechanisms have not been studied in detail. In the present study, we investigated whether selective activation of CB2 improves efferocytosis of macrophages. Main methods: RAW264.7 macrophage line and primary-isolated peritoneal lavage macrophages from C57bI/6J mice were cultured. The efferocytosis of macrophages was analyzed by using flow cytometry or confocal microscopy; and the possible mechanisms involved in regulation of efferocytosis were also explored by using molecular biology methods. Key findings: We found that JWH-133 and HU-308, selective agonists of CB2 receptor, concentration-dependently increased the phagocytosis of apoptotic cells in normal-cultured and oxidative low density lipoprotein (OxLDL) - loaded RAW264.7 and primary macrophages. JWH-133 and HU-308 also up-regulated expressions of tyrosine kinase family phagocytic receptors MerTK, Tyro3 and Axl, reduced levels of TNF-alpha and reactive oxygen species (ROS) induced by OxLDL, and inhibited activation of RhoA GTPase. Significance: The selective activation of CB2 improves efferosytosis of normal-cultured and OxLDL-loaded macrophages, which might provide a novel mechanism on how CB2 activation reduces vulnerability and promotes stability of atherosclerotic plaques. (C) 2016 Elsevier Inc All rights reserved.
Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post-partum. Participants (n= 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision-making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch-A-Sketch co-operation task. Mediation analyses showed that OXTR rs2254298 A-carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision-making task (estimate= 0.115, P < 0.005), while OXTR rs2254298 A-carriers had both direct and indirect effects on physically controlling parenting, also mediated through enhanced performance on decision-making (estimate=-0.059, P0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post-partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy.
A novel weak capacitance measurement system is proposed to measure the gas-solid two-phase flows. The system is mainly consist of capacitance sensor, Micro-programmed Control Unit (MCU), Direct Digital Synthesizer (DDS), operational amplifier, analogue multiplier and low-pass filter. Since the stray capacitance is much larger than the variation of measured capacitance, the stray capacitance should be eliminate by the measurement system. The experimental results show that the system meets the application requirement, and has good linearity, high measurement accuracy and stray-immune. The result of the percentage error is about 0.6% and the non-linear error is less than 1.5%. The sampling rate which is related to the frequency of the signal generator and the MCU clock can reach 500 kps.
In this work, capacitance multiplier is designed by using negative current feedback operational amplifier. The proposed circuit has low sensitivity to temperature variations. The simulation results are obtained by PSPICE simulations verify the theoretical analysis between 100KHz-6MHz.
Phase-sensitive detection circuit tests signals according to the correlation of the reference signal and the input signal. The noise is eliminated by the independence between the reference signal and the noise signal. The sensitivity of the detector is improved significantly by the suppression of the noise. In this work, a phase-sensitive detection circuit is designed for seismometer, which possesses the characteristics of low-input noise, variable-output gain and high sensitivity. The feasibility of this phase-sensitive detection circuit is verified by the Multisim and the signal-to-noise ratio is satisfactory.
Vapor detection using highly sensitive miniaturized resonant sensors is of great interest for many applications, including consumer, industrial, and environmental applications. An operational-amplifier-based multichannel oscillator that interfaces with a 50-MHz capacitive micromachined ultrasonic transducer array is presented for chemical sensing applications. The circuit was implemented in a 0.18-mu m CMOS technology to reduce power consumption, number of wires, and active area per channel. The presented integrated circuit also addresses the potential-frequency-locking problem between channels by allowing the open-loop gain to be adjustable off-chip. The feasibility of the developed oscillator for the chemical sensing application is demonstrated. Two channels that were operated simultaneously achieved excellent volume sensitivities of 8.5 x 10(-4)%/Hz and 3.9 x 10(-4)%/Hz, respectively, to relative humidity in N-2.
This paper presents a capacitive sensing system, addressing the issue of collision avoidance in partially modelled or unknown robot-assisted industrial environment by means of object distance measurement, motion tracking, and surface profile detection. The sensor consists of a mesh of multiple electrodes, a digital control module, a capacitance to digital converter, and a data processing module. The mesh is composed of 16 metal squares organized to form a 4x4 capacitor matrix. The electrode connections within the matrix can be reconfigured at run time by the digital control logic to provide multiple sense functionalities. Statistical regression models are applied to derive the distance and track the motion. A machine learning algorithm (Support Vector Machine, SVM) is applied to measured data to classify surface profiles. The fabricated sensing system has the ability of detecting objects at distances up to 20 cm from the sensor, and shows accuracy over 90% in profile recognition.
This brief presents an ultra-low-power low-noise chopped capacitively coupled instrumentation amplifier (CCIA) that is suitable for neural recording applications. An active high-pass filter is embedded in the ripple reduction loop (RRL) to suppress the residual noise and relax the capacitor size. Multiple chopping is employed to further reduce the residual output ripple due to the RRL offsets. A dc servo loop (DSL) using a 14-nA pseudofeedback amplifier is proposed to achieve a subhertz high-pass corner while using only a 15-pF on-chip capacitor. The complete CCIA is implemented in a standard 0.18-mu m CMOS process. It occupies an area of 0.23 mm(2) (including the DSL) and consumes 1.7 mu A froma 1.25-V supply, achieving a noise efficiency factor of 2.9 that compares favorably with the state of the art.
Optimal sizing of residential photovoltaic (PV) generation and energy storage (ES) systems is a timely issue since government polices aggressively promote installing renewable energy sources in many countries, and small-sized PV and ES systems have been recently developed for easy use in residential areas. We in this paper investigate the problem of finding the optimal capacities of PV and ES systems in the context of home load management in smart grids. Unlike existing studies on optimal sizing of PV and ES that have been treated as a part of designing hybrid energy systems or polygeneration systems that are stand-alone or connected to the grid with a fixed energy price, our model explicitly considers the varying electricity price that is a result of individual load management of the customers in the market. The problem we have is formulated by a D-day capacity planning problem, the goal of which is to minimize the overall expense paid by each customer for the planning period. The overall expense is the sum of expenses to buy electricity and to install PV and ES during D days. Since each customer wants to minimize his/her own monetary expense, their objectives look conflicting, and we first regard the problem as a multi-objective optimization problem. Additionally, we secondly formulate the problem as a D-day noncooperative game between customers, which can be solved in a distributed manner and, thus, is better fit to the pricing practice in smart grids. In order to have a converging result of the best-response game, we use the so-called proximal point algorithm. With numerical investigation, we find Pareto-efficient trajectories of the problem, and the converged game-theoretic solution is shown to be mostly worse than the Pareto-efficient solutions.
Capripoxviruses (CaPVs), consisting of Sheeppox virus (SPV), Goatpox virus (GPV), and Lumpy skin disease virus (LSDV) species, cause economically significant diseases in sheep, goats, and cattle, respectively. Quantitative real-time polymerase chain reaction (qPCR) assays are routinely used for rapid detection of CaPVs in surveillance and outbreak management programs. We further modified and optimized 2 previously published CaPV qPCR assays, referred to as the Balinsky and Bowden assays, by changing commercial PCR reagents used in the tests. The modified assays displayed 100% analytical specificity and showed no apparent changes in analytical sensitivities for detection of CaPVs compared with the original assays. Diagnostic sensitivities, assessed using 50 clinical reference samples from experimentally infected sheep, goats, and cattle, improved from 82% to 92% for the modified Balinsky assay and from 58% to 82% for the modified Bowden assay. The modified qPCR assays were multiplexed for detection of beta-actin as an indicator for potential false-negative results. The multiplex modified qPCR assays exhibited the same diagnostic sensitivities as the singleplex assays suggesting their utility in the detection of CaPVs.
Lentivirus-mediated transduction of autologous T cells with a chimeric antigen receptor (CAR) to confer a desired epitope specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance antitumor immunity have been less specific and less effective. These have included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes, recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells with tumor antigens. Unlike any of those methods, the engineering of CAR T cells combine specific monoclonal antibody gene sequences to confer epitope specificity and other T-cell receptor and activation domains to create a self-contained single vector approach to produce a very specific antitumor response, as is seen with CD19-directed CAR T cells used to treat CD19-expressing B-cell malignancies. Recent success with these therapies is the culmination of a long step-wise iterative process of improvement in the design of CAR vectors. This review aims to summarize this long series of advances in the development of effective CAR vector since their initial development in the 1990s, and to describe emerging approaches to design that promise to enhance and widen the human gene therapy relevance of CAR T-cell therapy in the future.
Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-2), has affected the commercial production of the goldfish Carassius auratus and gibelio carp Carassius auratus gibelio. High water temperature treatments are reported to reduce the mortality rate of infected goldfish and elicit immunity in the survivors. To define the mechanism by which this intervention induces resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related to both species and has been used in fish immunology, may represent a promising model species. In this study, we investigated the susceptibility of clonal ginbuna strains to CyHV-2 and the effect of high water temperature treatment on infected ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25 degrees C caused 100% mortality in ginbuna strains, which was accompanied by histopathological changes typical of HVHN. Both infected ginbuna S3n strain and goldfish, exposed to high temperature for 6 days [shifting from 25 degrees C (permissive) to 34 degrees C (non-permissive)], showed reduced mortalities after the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction of immunity. It was concluded that ginbuna showed a similar susceptibility and disease development in CyHV-2 infection compared to goldfish, suggesting that ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.
Background: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. Methods: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. Results: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. Conclusion: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.
The objective of this study was to reveal the molecular mechanism involved in carbapenem resistance and virulence of a K2 Klebsiella pneumoniae clinical isolate 24835. The virulence of the strain was determined by in vitro and in vivo methods. The de novo whole-genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the carbapenem resistance and virulence of K. pneumoniae 24835. Strain 24835 was highly resistant to carbapenems and belonged to ST14, exhibited hypermucoviscous and unique K2-aerobactin-kfu-rmpA positive phenotype. As the only carbapenemase gene in strain 24835, bla(NDM -5) was located on a 46-kb IncX3 self-transmissible plasmid, which is a very close relation of pNDM-MGR194 from India. Genetic context of blaNDM 5 in strain 24835 was closely related to those on IncX3 plasmids in various Enterobacteriaceae species in China. The combination of multiple virulence genes may work together to confer the relative higher virulence in K. pneumoniae 24835. Significantly increased resistance to serum killing and mice mortality were found in the virulent New Delhi metallo-beta -lactamase ( NDM)-producing K. pneumoniae strain compared to the other NDM-producing K. pneumoniae strain. Our study provides basic information of phenotypic and genomic features of K. pneumoniae 24835, a strain displaying carbapenem resistance and relatively high level of virulence. These findings are concerning for the potential of NDM-like genes to disseminate among virulent K. pneumoniae isolates.
Background: Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. Methods: A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR) assay was performed to determine the genotype. Results: Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74%) were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%); blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4%) showed positive detection of New Delhi metallo-beta-lactamase 1 (NDM-1) gene (bla(NDM1)). Conclusion: The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.
The physicochemical properties of anode material are important for the electron transfer of anode bacteria and electricity generation of microbial fuel cells (MFCs). In this work, carbon cloth anode was pretreated with isopropanol, hydrogen peroxide (H2O2) and sodium hypochlorite (NaOCl) in order to reduce the anode functional groups. The influence of functional groups on the electrochemical properties of carbon cloth anode and power generation of MFCs was investigated. The anode pretreatments removed the surface sizing layer of carbon cloth and substantially reduced the contents of C-O and pyridinic/pyrrolic N groups on the anode. Electrochemical impedance spectroscopy and cyclic voltammetry analyses of the biofilm-matured anodes revealed an enhanced electrochemical electron transfer property because of the anode pretreatments. As compared with the untreated control (612 +/- 6mWm(-2)), the maximum power density of an acetate-fed single-chamber MFC was increased by 26% (773 +/- 5mWm(-2)) with the isopropanol treated anode. Additional treatment with H2O2 and NaOCl further increased the maximum power output to 844 +/- 5mWm(-2) and 831 +/- 4 mWm(-2). A nearly inverse liner relationship was observed between the contents of C-O and pyridinic/pyrrolic N groups on anodes and the anodic exchange current density and the power output of MFCs, indicating an adverse effect of these functional groups on the electricity production of anodes. Results from this study will further our understanding on the microbial interaction with carbon-based electrodes and provide an important guidance for the modification of anode materials for MFCs in future studies. Copyright (c) 2016 John Wiley & Sons, Ltd.
China is currently the world's largest emitter of carbon dioxide. Considered as a large agricultural country, carbon emission in China's agriculture sector keeps on growing rapidly. It is, therefore, of great importance to investigate the driving forces of carbon dioxide emissions in this sector. The traditional regression estimation can only get "average" and "global" parameter estimates; it excludes the "local" parameter estimates which vary across space in some spatial systems. Geographically weighted regression embeds the latitude and longitude of the sample data into the regression parameters, and uses the local weighted least squares method to estimate the parameters point-by-point. To reveal the nonstationary spatial effects of driving forces, geographically weighted regression model is employed in this paper. The results show that economic growth is positively correlated with emissions, with the impact in the western region being less than that in the central and eastern regions. Urbanization is positively related to emissions but produces opposite effects pattern. Energy intensity is also correlated with emissions, with a decreasing trend from the eastern region to the central and western regions. Therefore, policymakers should take full account of the spatial nonstationarity of driving forces in designing emission reduction policies.
As the world's fastest growing major economy and home to nearly one-fifth of the worlds population, India a vibrant democracy is in the midst of a profound transformation and rapid urbanization. Urbanization improves the quality of life of people while promoting economic growth; however it also increases energy consumption and is capable of generating an energy crisis. Urbanization has a significant impact on Carbon Dioxide (CO,) emissions as well. This paper empirically investigates the temporal, dynamic and causal relationships between urbanization, energy consumption and emissions. The study also aims to understand the urbanization process in India, in terms of the level and tempo of urbanization and the urban growth morphology, by utilizing the census data of 1901-2011. The rise in energy consumption and resulting emissions in the context of rapid urbanization is also reviewed. To address these problems the study recommends a series of measures and a set of strategies that include energy intensity and emission intensity reduction measures through continuous monitoring, information feedback systems, introduction of industrial energy quota management, incentives for energy efficient facilities, shutting down of inefficient facilities, and setting up of smart residential buildings. Reduction of distribution and transmission losses by investing in smart grids is also highly recommended.
Power-to-X concepts promise a reduction of greenhouse gas emissions simultaneously guaranteeing a safe energy supply even at high share of renewable power generation, thus becoming a cornerstone of a sustainable energy system. Power-to-syngas, that is, the electro-chemical conversion of steam and carbon dioxide with the use of renewably generated electricity to syngas for the production of synfuels and high-value chemicals, offers an efficient technology to couple different energy-intense sectors, such as "traffic and transportation" and "chemical industry". Syngas produced by co-electrolysis can thus be regarded as a key-enabling step for a transition of the energy system, which offers additionally features of CO2-valorization and closed carbon cycles. Here, we discuss advantages and current limitations of low-and high-temperature co-electrolysis. Advances in both fundamental understanding of the basic reaction schemes and stable high-performance materials are essential to further promote co-electrolysis.
Climate models predict increased frequency and intensity of storm events, but it is unclear how extreme precipitation events influence the dynamics of soil fluxes for multiple greenhouse gases (GHGs). Intact soil mesocosms (0-10 cm depth) from a temperate forested watershed in the piedmont region of Maryland [two upland forest soils, and two hydric soils (i.e., wetland, creek bank)] were exposed to experimental water pulses with periods of drying, forcing soils towards extreme wet conditions under controlled temperature. Automated measurements (hourly resolution) of soil CO2, CH4, and N2O fluxes were coupled with porewater chemistry analyses (i.e., pH, Eh, Fe, S, NO3 (-)), and polymerase chain reaction-denaturing gradient gel electrophoresis to characterize changes in microbial community structure. Automated measurements quantified unexpected increases in emissions up to 245% for CO2 (Wetland), >23,000% for CH4 (Creek), and >110,000% for N2O (Forest Soils) following pulse events. The Creek soil produced the highest soil CO2 emissions, the Wetland soil produced the highest CH4 emissions, and the Forest soils produced the highest N2O emissions during the experiment. Using carbon dioxide equivalencies of the three GHGs, we determined the Creek soil contributed the most to a 20-year global warming potential (GWP; 30.3%). Forest soils contributed the most to the 100-year GWP (up to 53.7%) as a result of large N2O emissions. These results provide insights on the influence of extreme wet conditions on porewater chemistry and factors controlling soil GHGs fluxes. Finally, this study addresses the need to test biogeochemical thresholds and responses of ecosystem functions to climate extremes.
Luminescent carbon nanodots (CDots) have attracted much attention, but their luminescence is usually quenched in solid state. Efficient green or yellow emissive CDot-based phosphors are scarce. In this work, green emissive CDot@NaCl composite phosphors were fabricated through a convenient, low cost and eco-friendly way by embedding green emissive CDots (g-CDot) in NaCl crystals. With the protection of NaCl host, the g-CDot@NaCl composite phosphors exhibit good photostability, significant resistance to organic solvents, and improved photoluminescence quantum yields up to 25%. White light-emitting diodes with tunable color temperatures (3944-5478 K) and CIE coordinates have been realized based on the g-CDot@NaCl composite phosphors. (C) 2017 Elsevier Inc. All rights reserved.
In this study a pseudo comprehensive carbon footprint model for fossil fuel power plants is presented. Parameters which their effects are considered in this study include: plant type, fuel type, fuel transmission type, internal consumption of the plant, degradation, site ambient condition, transmission and distribution losses. Investigating internal consumption, degradation and site ambient condition effect on carbon footprint assessment of fossil fuel power plant is the specific feature of the proposed model. To evaluate the model, a sensitivity analysis is performed under different scenarios covering all possible choices for investigated parameters. The results show that carbon footprint of fossil fuel electrical energy that is produced, transmitted and distributed, varies from 321 g CO(2)eq/kWh to 980 g CO2 equivalent /kWh. Carbon footprint of combined cycle with natural gas as main fuel is the minimum carbon footprint. Other factors can also cause indicative variation. Fuel type causes a variation of 28%. Ambient condition may change the result up to 13%. Transmission makes the carbon footprint larger by 4%. Internal consumption and degradation influence the result by 2 and 2.5%, respectively. Therefore, to minimize the carbon footprint of fossil fuel electricity, it is recommended to construct natural gas ignited combined cycles in low lands where the temperature is low and relative humidity is high. And the internal consumption is as least as possible and the maintenance and overhaul is as regular as possible.
This paper presents an enhancement of a previous Conventional Carbon Nanotube Field Effect Transistor (C-CNTFET) compact model proposed by Raychowdhury et al. This improvement consists in three new extensions to the previous work: first, by adding adequate electronic noise sources to the C-CNTFET modelling the electronic noise at the source and drain access regions; i.e., thermal noise and the electronic noise in the device channel; i.e., flicker and shot noise, second by adopting a simple and a fast analytical calculating approach that models the Schottky barrier (SB) at the source and drain metal access and the semiconducting carbon nanotube (CNT) interface by including adequate noise sources, and finally by proposing a generic compact model that is suitable for circuit simulation purpose. In order to validate the proposed SB-CNTFET compact model, electrical simulation results are compared with literature reported experimental results. Good agreement is observed over a large range of the device biases. For the SB assessment, an operational amplifier (Op Amp) circuit has been designed and simulated using the SB-CNTFET compact model. A significant degradation on the Op Amp's performances is observed for large SB. As SB proprieties is associated with the CNT geometry; i.e., diameter, and to prevent circuit's performances degradation, an optimization work has been carried out to provide the circuit design community with the suitable CNT diameters that should be made.
This paper presents a computationally efficient Raychowdhury compact model for the Schottky barrier (SB) carbon nanotube field-effect transistor (CNTFET). In order to achieve an accurate compact model, shot noise sources is added. Then, for the assessment of the SB on circuit performances, an operational amplifier (Op-Amp) is designed using the SB-CNTFET compact model, and results are compared with a conventional CNTFET.
Carbonaceous stationary phases have gained much attention for their peculiar selectivity and robustness. Herein we report the fabrication and application of a graphene-coated polymeric stationary phase for anion exchange chromatography. The graphene-coated particles were fabricated by a facile evaporation reduction method. These hydrophilic particles were proven appropriate substrates for grafting of hyperbranched condensation polymers (HBCPs) to make pellicular anion exchangers. The new phase was characterized by zeta potentials, Fourier transform infrared spectroscopy, thermogravimetry and scanning electron microscope. Frontal displacement chromatography showed that the capacities of the anion exchangers were tuned by both graphene amount and HBCPs layer count. The chromatographic performance of graphene-coated anion exchangers was demonstrated with separation of inorganic anions, organic acids, carbohydrates and amino acids. Good reproducibility was obtained by consecutive injections, indicating high chemical stability of the coating. (C) 2017 Published by Elsevier B.V.
The innate immune system, which includes toll-like receptor (TLR) signaling, plays an important role in inflammation and oncogenesis. Although TLR common adaptor myeloid differentiation factor 88 (MyD88) is known to have multiple effects on carcinogenesis, the role of MyD88 in hepatocarcinogenesis remains unknown. In this study, MyD88 expression was examined in 105 samples of human hepatocellular carcinoma (HCC) tissue by immunohistochemistry, Western blot, and quantitative reverse-transcriptase polymerase chain reaction methods. The relationships between MyD88 expression and clinical and pathological parameters were analyzed. The results showed that attenuated expression of MyD88 in HCC tissue tumor cells was significantly related to hepatitis B virus infection, large tumor size, positive vascular invasion, and intrahepatic metastasis (P<0.05). Western blot analysis of MyD88 protein in nine normal livers and 28 HCCs showed gender disparity (P<0.01, P<0.05), and attenuated expression in cirrhotic livers (P<0.05). Low expression of MyD88 mRNA was evident in HCCs with vascular invasion (P<0.01). In contrast to previous reports, these results suggest that attenuated expression of MyD88 in HCC is associated with tumor progression.
Background: Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. Material/Methods: The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. Results: The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05). Conclusions: Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.
Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the growth, invasion and metastasis of tumor cells. However, to date little is known about the oncogenic mechanisms of CAFs. This study aimed to identify the microenvironmental factors involved in tumor development and progression directed by CAFs in liver metastases. Tissue samples collected from 20 patients with colorectal liver metastases were used in this study. Histological and morphological characterization of the samples was performed using hybridization and immunohistological assays. The m RNA expression of a-smooth muscle actin (alpha-SMA) was measured by northern blotting. The expression of plasminogen activator inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA). As a result, co-expression of Thy-1 (CD90) and alpha-SMA was identified in CAFs, while normal liver samples were negative for alpha-SMA and Thy-1. Compared with epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the expression of alpha-SMA increased significantly following transforming growth factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF) caused a significant suppression of alpha-SMA expression (P<0.05). PAI-1 expression was significantly lower in unstimulated fibroblasts compared to TGF-1-treated fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher in CAFs from the patient samples compared with the healthy controls. Taken together, our findings suggest that CAFs may be important in migration, matrix degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the activation of PAI-1 transcription in CAFs.
The opportunity to distinguish an accurate set of genes associated with multigenic diseases such as cardiomyopathies or cardiac arrhythmias was very limited before the genomic era. Numerous methods of measuring RNA abundance exist, including northern blotting, multiplex polymerase chain reaction (PCR), and quantitative real-time reverse transcriptase-PCR. However, these techniques might be used to assess the expression levels of only 10-50 genes at time. Today, DNA microarrays provide us with opportunity to simultaneously analyze tens of thousands of genes, giving a remarkable possibility to investigate the genomic contribution to cardiovascular diseases. A particular tissue at any stage of health or disease may be used to generate a genomic profile. Microarray techniques are already used in infectious diseases, oncology, and pharmacology to facilitate clinicians, risk-stratify patients, as well as to predict and assess therapeutic responses to drugs. In this paper, we describe recent advances in the use of various types of microarray technique in the diagnosis of arrhythmogenic heart disease. We also highlight other strategies and methods of differential gene typing comparing with pros and cons of microarray analysis.
Background: An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days to 3 months of induction. ATP sensitive potassium (K-ATP) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac K-ATP channels in diabetic disorders. Methods: Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of K-ATP channels. K-ATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of K-ATP channels by Western blot and Northern blot analysis. Results: The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of K-ATP channel. Two subunits of cardiac K-ATP channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K-ATP in these diabetic rats. Conclusions: Both mRNA and protein expression of cardiac K-ATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some K-ATP channel drugs.
The morbidity and mortality of heart failure with preserved left ventricular ejection fraction (HFpEF) were similar to those of systolic heart failure, but the pathogenesis of HFpEF remains poorly understood. It was demonstrated that, in systolic heart failure, microRNA-21 (miR-21) could inhibit the apoptosis of cardiac fibroblasts, leading to cardiac hypertrophy and myocardial fibrosis, but the role of miR-21 in HFpEF remains unknown. By employing cell culture technique, rat myocardiocytes and cardiac fibroblasts were obtained. The expression of miR-21 in the two cell types under different conditions was compared and we found that the miR-21 expression was significantly higher in cardiac fibroblasts than in myocardiocytes. We established a rat HFpEF model and harvested the tissues of cardiac apex for pathological examination, Northern blotting and so forth. We found that miR-21 expression was significantly higher in model rats than in sham-operated rats, and the model rats developed the cardiac atrophy and cardiac fibrosis. After injection of miR-21 antagonist, the the cardiac atrophy and cardiac fibrosis were conspicuously ameliorated. Both in vivo and in vitro, inhibition of miR-21 expression resulted in reduced Bcl-2 expression while over-expression of miR-21 led to elevation of Bcl-2 expression. Our study suggested that miR-21 promoted the development of HFpEF by up-regulating the expression of anti-apoptotic gene Bcl-2 and thereby suppressing the apoptosis of cardiac fibrosis.
Growing evidence suggests that microRNAs (miRNAs) play key roles in cardiac hypertrophy. To measure the expression of endogenous miRNAs is very conducive to understanding the importance of miRNAs in cardiac hypertrophy. However, current methods to monitor endogenous miRNA levels, such as Northern blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and microarrays cannot provide real-time information on miRNA biogenesis in vivo. We constructed a miRNA reporter imaging system to monitor miR-22 expression in isoproterenol-induced cardiac hypertrophy repetitively and noninvasively. There were three copies of the antisense of miR-22 (3xPT_miR-22) cloned into the 3' untranslated region (UTR) of the Gaussia luciferase (Gluc) reporter genes under the control of the cytomegalovirus (CMV) promoter in this miRNA reporter system (CMV/Gluc/3xPT_miR-22). CMV/firefly luciferase (Fluc) was used as a positive control for imaging of miR-22 expression. Meanwhile, quantifications of miR-22 in cardiomyocyte hypertrophy and in mouse cardiac hypertrophy induced by isoproterenol stimulation were measured by qRT-PCR. Furthermore, we used this miRNA reporter imaging system to appraise the antihypertrophic effect of antagomir-22 in vitro and in vivo. The bioluminescence signals of the CMV/Gluc/3xPT_miR-22 were gradually decreased with prolongation of isoproterenol intervention in vitro and in vivo. Overexpression of miR-22 was observed in cardiac hypertrophy, and markedly administration of antagomir-22 could reverse the upregulation of miR-22 and its prohypertrophic effects. Furthermore, knockdown of miR-22 by antagomir-22 could markedly reverse the repressed Gluc activities in vitro and in vivo. However, the Fluc activity of CMV/Fluc was not affected with isoproterenol treatment. This study elucidates the feasibility of using our constructed miRNA reporter imaging system to monitor the location and magnitude of expression levels of miR-22 in cardiac hypertrophy in vitro and in vivo.
Rationale: Direct reprogramming of cardiac fibroblasts to cardiomyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of 4 microRNAs (miR-1, miR-133, miR-208, and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here, we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism. Methods and Results: Using a quantitative polymerase chain reaction array, we found that histone methyltransferases and demethylases that regulate the trimethylation of H3K27 (H3K27me3), an epigenetic modification that marks transcriptional repression, were changed in miR combo-treated fibroblasts. Accordingly, global H3K27me3 levels were downregulated by miR combo treatment. In particular, the promoter region of cardiac transcription factors showed decreased H3K27me3 as revealed by chromatin immunoprecipitation coupled with quantitative polymerase chain reaction. Inhibition of H3K27 methyltransferases or of the PRC2 (Polycomb Repressive Complex 2) by pharmaceutical inhibition or siRNA reduced the levels of H3K27me3 and induced cardiogenic markers at the RNA and protein level, similarly to miR combo treatment. In contrast, knockdown of the H3K27 demethylases Kdm6A and Kdm6B restored the levels of H3K27me3 and blocked the induction of cardiac gene expression in miR combo-treated fibroblasts. Conclusions: In summary, we demonstrated that removal of the repressive mark H3K27me3 is essential for the induction of cardiac reprogramming by miR combo. Our data not only highlight the importance of regulating the epigenetic landscape during cell fate conversion but also provide a framework to improve this technique.
Optogenetics is a technique exploded in the last 10 years, which revolutionized several areas of biological research. The brightest side of this technology is the use of light to modulate non-invasively, with high spatial resolution and millisecond time scale, excitable cells genetically modified to express light-sensitive microbial ion channels (opsins). Neuroscience has first benefited from such fascinating strategy, in intact organisms. By shining light to specific neuronal subpopulations, optogenetics allowed unearth the mechanisms involved in cell-to-cell communication within the context of intact organs, such as the brain, formed by complex neuronal circuits. More recently, scientists looked at optogenetics as a tool to answer some of the questions, remained in the dark, of cardiovascular physiology. In this review, we focus on the application of optogenetics in the study of the heart, a complex multicellular organ, homing different populations of excitable cells, spatially and functionally interconnected. Moving from the first proof-of-principle works, published in 2010, to the present time, we discuss the in vitro and in vivo applications of optogenetics for the study of electrophysiology of the different cardiac cell types, and for the dissection of cellular mechanisms underlying arrhythmias. We also present how molecular biology and technology foster the evolution of cardiac optogenetics, with the aim to further our understanding of fundamental questions in cardiac physiology and pathology. Finally, we confer about the therapeutic potential of such biotechnological strategy for the treatment of heart rhythm disturbances (e.g. cardiac pacing, cardioversion). (C) 2016 Elsevier Inc. All rights reserved.
Objective: The aim of this study was to examine physical and heart rhythm management device malfunction complications after participating in a cardiac rehabilitation program intervention compared with usual care. Method: This study was a clinical trial of 100 patients. After randomization, intervention group patients received 8 cardiac rehabilitation program sessions for 8 weeks and follow-up phone calls. Each session consisted of exercise training, education, and psychological interventions. Data were collected at 3 points in both groups-baseline and 8 and 12 weeks after the first day of the intervention-using a researcher-designed case report form. Data were analyzed using descriptive and nonparametric tests. Results: Of the participants, 59% were men, and the sample was aged 40 to 60 years. At the 8- to 12-week follow-up, there were less physical complications among the cardiac rehabilitation group (P < .001) and no between-group differences in complications related to device malfunction. By heart rhythm device type, cardiac rehabilitation had the greatest efficacy in reducing physical complications in patients with cardioverter/defibrillators. Conclusions: Cardiac rehabilitation reduced physical complications in patients with cardiac rhythm management devices, especially in patients with cardioverter/defibrillators. Cardiac clinical nurse specialists should recommend rehabilitation programs as part of postimplantation rhythm device treatment to decrease the risk of physical complications.
Implantable cardiac pacemakers play a vital role in extending the lives of patients with cardiovascular diseases. The technique of wireless power transfer (WPT) via magnetic coupling resonance (MCR) makes it possible to wirelessly and uninterruptedly supply electricity for pacemakers from external. However, the eddy current in the metallic pacemaker shell seriously impacts the electric energy receiving by receiving coils, making the WPT system operate at low efficiency. To decrease eddy current effect and increase WPT efficiency, the precise implant position of receiving coils is theoretically and experimentally investigated in this paper. The electromagnetic model of pacemaker WPT system is built and the analytical solution of induced voltage across receiving coils is derived, which is verified by experiments. Accordingly, the minimum distance between the receiving coil and the pacemaker shell is reversely calculated for enough induced voltage. Experimental results show that supplied by a power source of 5.66 V/300 kHz, the pacemaker charging system successfully charged Lithium-ion battery from 3.98 (80% residual capacity) to 4.2 V within 30 min by a 0.15 mm thickness receiving coil implanted into 4 mm subcutaneously. On the safety of charging system, electromagnetic and thermal simulation results show that the maximum SAR and temperature rise in tissues are 36.8 W/kg and 0.66. degrees C, respectively. The results provide a theoretical and practical support for design of a wireless charging system.
Objective: To establish the transgenic mouse of cTnT(R141W) gene to make an animal model of dilated cardiomyopathy. Methods: A transgenic plasmid was constructed by inserting the cTnT(R141W) gene driven by the alpha-MHC promoter. The expression level of the gene was determined with Northern blotting. Pathologic changes were observed by light microscopy and transmission electronic microscopy and analyzed with echocardiography. The localization of the mutant human cTnT protein was detected by immunohistochemistry. The hypertrophy markers were analyzed by RT-PCR. Results: Transgenic mice carrying the cTnT(R141W) mutation were established. The cTnT(R141W) was expressed by 1.5- to 2.0-fold that of the endogenous cTnT gene and was showed to assemble in the sarcomere. The transgenic heart exhibited a thinner ventricular wall and an enlarged ventricular chamber. Interstitial fibrosis and the elongated and lysed myofrils were also observed in the transgenic heart tissue. The function on EF%, FS% and movement of the ventricular wall was significantly decreased. The immature death occurred after 4 months of age and the immature death rate was 11.1% before 8 months of age in the cTnT(R141W) mice. The increased NPPB, ACTA1 and decreased ATP2A2 were detected in the transgenic heart. Conclusions: The expression of mutant cTnT(R141W) in the mouse heart caused ventricular chamber enlargement, systolic dysfunction, myocardial hypertrophy, and interstitial fibrosis, suggesting that the cTnT(R141W) gene is a causal factor for DCM and that the cTnT(R141W) transgenic mouse is a useful animal model for the study of human DCM. (C) 2008 Published by Elsevier Ireland Ltd.
Rationale: Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well-established, the molecular events that inhibit or repress cardiac hypertrophy are less known. Objective: To identify and investigate novel regulators that modulate cardiac hypertrophy. Methods and Results: Here, we report the identification, characterization, and functional examination of a novel cardiac Isl1-interacting protein (CIP). CIP was identified from a bioinformatic search for novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear protein without recognizable motifs. Northern blotting, in situ hybridization, and reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes of developing and adult hearts. Yeast two-hybrid screening identified Isl1, a LIM/homeodomain transcription factor essential for the specification of cardiac progenitor cells in the second heart field, as a cofactor of CIP. CIP directly interacted with Isl1, and we mapped the domains of these two proteins, which mediate their interaction. We show that CIP represses the transcriptional activity of Isl1 in the activation of the myocyte enhancer factor 2C. The expression of CIP was dramatically reduced in hypertrophic cardiomyocytes. Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy. Conclusions: Our studies therefore identify CIP as a novel regulator of cardiac hypertrophy. (Circ Res. 2012; 110: 818-830.)
Endothelin, a vasoconstrictor peptide, plays important roles not only in the mammalian circulatory system but also in non-mammalian systems, such as the gill lamellar vascular network with complex structural characteristics. Here, we show that (i) the contraction of pillar cells that delimit the lamellar vasculature is controlled by endothelin through the type A endothelin receptor (ETA) linked to the intracellular calcium signaling system and (ii) ETA receptor is also highly expressed on fugu erythrocytes, a hitherto unexpected finding. Database mining revealed the presence of five endothelin receptor (ETR) sequences in the fugu genome. By Northern blotting, cDNA cloning, and fura-2 monitoring, the branchial ETR subtype was shown to be ETA able to induce a Ca2+ transit. Immunohistochemistry revealed its pillar cell and erythrocyte localization. These results suggest an endothelin/ETA-Mediated coordinated regulation of the pillar cell shape and erythrocyte membrane flexibility. (c) 2007 Elsevier Inc. All rights reserved.
Endomyocardial biopsy (EMB) has been established in parallel with the development of percutaneous catheter technology for the diagnosis of cardiac diseases. It was developed in the early 1960 s in Japan by Drs. Konno, Sakakibara and Sekiguchi of Tokyo Women's Medical University. EMB is a valuable and useful, but invasive, modality for making a definite diagnosis in diseases such as myocarditis and secondary cardiomyopathies, which are often difficult to diagnose by imaging modality alone. In the field of heart transplantation, the histology of EMB helps monitor rejection to allografts. In cases of chronic heart failure, fibrosis and degeneration of cardiomyocytes are very important findings of heart remodeling. Recently, molecular biology technology has been applied to EMB specimens to get more detailed information. However, we must also recognize that EMB is an invasive examination that should not be performed without skillful cardiac catheterization experience to avoid complications. In this review as a message from pathologists, we present key cardiac histopathology using EMB, in a way that allows one to imagine whole cardiac pathological conditions. We also describe the current role of EMB and its significance in order to encourage young cardiologists to perform EMB to see another world of pathology.
Objective: In flammation may contribute to an increased risk of cardiovascular disease (CVD) in HIV-1 infection. MicroRNAs (miRNAs) are involved in the regulation of inflammation. In treated HIV-1-infected individuals, we aimed to identify differentially expressed miRNAs with known roles in inflammation and CVD risk and to investigate associations between these and systemic inflammation. Methods: In a screening cohort including 14 HIV-1-infected individuals and 9 uninfected controls, microarray profiling was performed using peripheral blood mononuclear cells (PBMCs). Differentially regulated miRNAs previously related to inflammation and CVD were validated using real-time quantitative reverse-transcription polymerase chain reaction in 26 HIV-1-infected individuals and 20 uninfected controls. Validated miRNAs were measured in PBMCs, CD4+ and CD8+ T cells. Interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, lipopolysaccharide (LPS), cytomegalovirus immunoglobulin G, lipids, and fasting glucose were measured, and associations with validated miRNAs were assessed with multiple linear regression analysis. Results: Upregulation of miR-210, miR-7, and miR-331 was found in PBMCs from HIV-1-infected individuals when compared with those from uninfected controls (P, 0.005). In contrast, miR-210 and miR-331 were downregulated in CD8(+) T cells. In multivariate analysis, miR-210 in CD8(+) T cells was negatively associated with LPS (P = 0.023) and triglycerides (P = 0.003) but positively associated with tumor necrosis factor-alpha (P = 0.004). MiR-7 in PBMC was positively associated with interleukin-6 (P = 0.025) and fasting glucose (P = 0.005), whereas miR-331 was negatively associated with LPS (P = 0.006). In PBMCs from HIV-1-infected individuals with low cytomegalovirus immunoglobulin G, miR-7, miR-29a, miR-221, and miR-222 were downregulated. Conclusion: In 2 independent cohorts, miR-210, miR-7, and miR-331 were differentially regulated in treated HIV-1-infected individuals and associated with markers of systemic inflammation.
Background and Purpose There is increasing interest in extracellular RNAs (ex-RNAs), with numerous reports of associations between selected microRNAs (miRNAs) and a variety of cardiovascular disease phenotypes. Previous studies of ex-RNAs in relation to risk for cardiovascular disease have investigated small numbers of patients and assayed only candidate miRNAs. No human studies have investigated links between novel ex-RNAs and stroke. Methods We conducted unbiased next-generation sequencing using plasma from 40 participants of the FHS (Framingham Heart Study; Offspring Cohort Exam 8) followed by high-throughput polymerase chain reaction of 471 ex-RNAs. The reverse transcription quantitative polymerase chain reaction included 331 of the most abundant miRNAs, 43 small nucleolar RNAs, and 97 piwi-interacting RNAs in 2763 additional FHS participants and explored the relations of ex-RNAs and prevalent (n=63) and incident (n=51) stroke and coronary heart disease (prevalent=286, incident=69). Results After adjustment for multiple cardiovascular disease risk factors, 7 ex-RNAs were associated with stroke prevalence or incidence; there were no ex-RNA associated with prevalent or incident coronary heart disease. Statistically significant ex-RNA associations with stroke were specific, with no overlap between prevalent and incident events. Conclusions This is the largest study of ex-RNAs in relation to stroke using an unbiased approach in an observational cohort and the first large study to examine human small noncoding RNAs beyond miRNAs. These results demonstrate that when studied in a large observational cohort, extracellular miRNAs are associated with stroke risk
We investigated the physicochemical properties (size, shape, elemental composition, and endotoxin) of size resolved particulate matter (PM) collected from the indoor and corridor environments of classrooms. A comparative hazard profiling of these PM was conducted using human microvascular endothelial cells (HMVEC). Oxidative stress-dependent cytotoxicity responses were assessed using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and high content screening (HCS), and disruption of monolayer cell integrity was assessed using fluorescence microscopy and transwell assay. Scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDX) analysis showed differences in the morphology and elemental composition of PM of different sizes and origins. While the total mass of PM collected from indoor environment was lower in comparison with those collected from the corridor, the endotoxin content was substantially higher in indoor PM (e.g., ninefold higher endotoxin level in indoor PM8.1-20). The ability to induce oxidative stress-mediated cytotoxicity and leakiness in cell monolayer were higher for indoor PM compared to those collected from the corridor. In conclusion, this comparative analysis suggested that indoor PM is relatively more hazardous to the endothelial system possibly because of higher endotoxin content.
Objectives. - The link parent-child is central in the construction of the young subject. This link can be put in distress when the adult suffers from psychiatric disorders and become toxic. This article proposes a reflection on the impacts of adult's serious psychological troubles on the child and a discussion about the existing tension between psychiatric care for the parent and the measures of help and protection towards the child. Method. - To try to define all the elements of answer, the authors lean on their experience in a multidisciplinary team compound of social workers, psychologists, a jurist and doctors (pediatrician and child psychiatrist) asked for 30 years to realize the diagnostic and therapeutic care of situations of ill-treatments of children and teenagers. We met different situations involving parents and children within the framework of our process of multidisciplinary evaluation. We also base ourselves on a work of network, discussing with our colleagues in charge of the therapeutic support of the adult patients. Results. - The processes of evaluation between the looks of the professionals close to the child and those who meet the parents in their adult's suffering allowed to seize all the relevance to go out of an simplistic reading to understand the ins and outs which led to ill treatment. Discussion. - In spite, of the concern of the respect for every protagonist concerned in a holistic understanding of his course of life, we are confronted with the limits of our mission, on one hand, and what bases the therapeutic link on the other hand. It is so, for example, that the question of the shared professional secretly represents a stumbling block which can affect the process of evaluation and support in his purpose. Conclusion. - The clinical experience and the theoretical reflections confirm the interest of a complex multidisciplinary work, integrating the contributions of the visions of the professional asked to estimate and to accompany, on one hand, the child, and on the other hand, the parent. (C) 2016 Elsevier Masson SAS. All rights reserved.
Anxiety is common among postpartum women and can have adverse effects on mother's and child's somatic and psychological health if left untreated. In the UK, nurses or midwifes with a specialisation in community public health nursing, also called health visitors (HVs), work with families who have children younger than 5 years of age and are therefore in a key position to identify and support women with postpartum mental health issues. Until recently, postpartum mental health support provided by HVs mainly focused on identifying and managing depression, but the updated clinical guidance by the National Institute for Health and Care Excellence also includes guidance regarding screening and psychological interventions for perinatal anxiety. This study therefore aimed to explore HVs' experiences of supporting women with postpartum anxiety and their views on currently available care. Using a qualitative approach, in-depth semi-structured interviews were conducted with 13 HVs from the UK between May and October 2015. Participants were interviewed in person at their workplace or on the phone/Skype. Using thematic analysis, four main themes emerged: identification and screening issues; importance of training; service usage; and status of current service provision. Women with postpartum anxiety were commonly encountered by HVs in their clinical practice and described as often heavily using their or other related healthcare services, which puts additional strain on HVs' already heavy workload. Issues with identifying and screening for postpartum anxiety were raised and the current lack of perinatal mental health training for HVs was highlighted. In addition, HVs described a current lack of good perinatal mental health services in general and specifically for anxiety. The study highlights the need for HV perinatal mental health training in general and postpartum anxiety specifically, as well as better coverage of specialist mental health services and the need for development of interventions targeted at postpartum anxiety.
The objectives of this study were to describe illness representations in dementia caregiving and examine the relationship between illness perceptions and carers' sense of coherence. Illness perceptions were assessed by the Brief Illness Perception Questionnaire. We measured sense of coherence, symptoms of anxiety and depression and carer burden. Regression analyses indicated that after controlling for demographic factors, burden and psychological distress in carers, illness coherence and emotional responses to the disease independently contributed towards explaining variance in carers' sense of coherence. Results provide support for the usefulness of the self-regulation model in understanding dementia caregiving.
Considerable research has examined infants' understanding and evaluations of social agents, but two questions remain unanswered: First, do infants organize observed social relations into larger structures, inferring the relationship between two social beings based on their relations to a third party? Second, how do infants reason about a type of social relation prominent in all societies: the caregiving relation between parents and their babies? In a series of experiments using animated events, we ask whether 15- to 18-month-old infants infer that two babies who were comforted by the same adult, or two adults who comforted the same baby, will affiliate with one another. We find that infants make both of these inferences, but they make no comparable inferences when presented with the same visible events with voices that specify a peer context, in which one adult responds to another laughing adult. Thus, infants are sensitive to at least one aspect of caregiving and organize relations between infants and adults into larger social structures. (C) 2016 Elsevier B.V. All rights reserved.
In this paper, we use a car-following model to study each electric vehicle's trip cost and the total trip cost allowing late arrival. The numerical result show that the electricity cost has great effects on each commuter's trip cost and the total trip costs and that these effects are dependent on each commuter's time headway at the origin, but the electricity cost has no prominent impacts on the minimum value of total trip cost under each commuter's different time headway at the origin. (C) 2017 Elsevier B.V. All rights reserved.
While the US Food and Drug Administration has not approved the use of 3% papain gel in the United States, the authors feel this study adds to the literature regarding its use. Introduction. The aim of this study was to evaluate the effect of 3% papain gel on wounds in mice. Materials and Methods. Thirty healthy C57BL mice (25-30 g) aged 10 weeks were randomly divided into 2 groups: mice treated with 3% papain gel and mice treated with placebo gel. Skin incisions were performed with a 6-mm metallic punch with a cutting blade edge. On days 3 and 7 after creating the lesion, the mice were euthanized and lesion samples were collected. The lesion samples were processed and sectioned into 3 fragments of skin to be stained with 3 types of dye: hematoxylin and eosin, Picrosirius red, and Weigert. In addition, immunohistochemical analysis (alpha-SM actin and Ki67) followed by real-time polymerase chain reaction (PCR) protocol was performed on the samples. Results. On gross examination, the 3% papain-treated group took less time to heal the wounds compared with the control. On day 7, microscopic examination showed the 3% papain-treated group had lower numbers of inflammatory cells, increased neovascularization, and improved organization of collagen and elastic fibers. Using PCR analysis, the 3% papain-treated group showed a significant increase in transforming growth factor beta and interleukin-6 expression compared with the control (P < .05). Conclusion. Due to a reduced local inflammatory response, increased angiogenesis, and improved organization of collagen deposition, these findings demonstrate 3% papain gel can improve cutaneous wound healing in mice.
CarNAC3 contains 285 amino acids and a conserved NAC domain. NAC genes, including NAM, ATAF1, ATAF2, and CUC2, are members of one of the largest transcription factor families in plants. CarNAC3, a member of the NAP group, plays an important role in plant development and responses to abiotic stresses. In this study, CarNAC3 was transformed into hybrid poplar plants (Populus deltoides x P. euramericana 'Nanlin895') using Agrobacterium tumefaciens. PCR analysis confirmed integration of the introduced T-DNA into the target genome. Reverse transcription PCR confirmed the transformation, and Southern and northern blotting verified the transgene copy number and gene expression, respectively. Fourteen lines of positive transformants were transplanted into a greenhouse to verify their drought and salt tolerances. Under normal conditions, transgenic poplar plants were shorter than the wild-type, but under drought and salt stresses, they maintained their normal rooting and stem growth rates, while those of the wild-type plants were suppressed. Under stress conditions, CarNAC3 expression caused increases in proline and photosynthetic pigment levels and in antioxidant enzyme activities. Furthermore, the expression of CarNAC3 lowered malondialdehyde concentrations compared with the wild-type control. Overall, our results indicated that the CarNAC3 transgene enhanced drought and salt tolerance in transgenic poplar plants.
Phase noise correction is crucial to exploit full advantage of orthogonal frequency-division multiplexing (OFDM) in modern high-data-rate communications. OFDM channel estimation with simultaneous phase noise compensation has therefore drawn much attention and stimulated continuing efforts. Existing methods, however, either have not taken into account the fundamental properties of phase noise or are only able to provide estimates of limited applicability owing to considerable computational complexity. In this paper, we have reformulated the joint phase noise and channel estimation problem in the time domain as opposed to existing frequency-domain approaches, which enables us to develop much more efficient algorithms using the majorization-minimization technique. In addition, we propose two methods based on dimensionality reduction and regularization, respectively, that can adapt to various phase noise levels and signal-to-noise ratio and achieve much lower estimation errors than the benchmarks without incurring much additional computational cost. Several numerical examples with phase noise generated by free-running oscillators or phase-locked loops demonstrate that our proposed algorithms outperform existing methods with respect to both computational efficiency and mean squared error within a large range of SNRs.
Adoptive transfer of antigen-specific T cells has been adapted by investigators for treatment of cancer. This technology is becoming popular in the aspects of cell in vitro preparation and T cell proliferation. In addition, it also does well in enhancing immunity effect and reducing cytotoxicity. A major advantage for this adoptive T-cell therapy (ACT) is its ability to efficiently endow patient's T cells with reactivity for tumor antigens through stable or regulated introduction of genes that encode high affinity tumor-targeting T-cell receptors (TCRs) or synthetic chimeric antigen receptors (CARs). To overcome issues of immune tolerance which limit the endogenous adaptive immune response to tumor-associated antigens (TAAs), robust systems for genetic modification and characterization of T cells that express the chimeric antigen receptors (CARs) for redirecting their specificity have been produced. More and more cases have indicated that the CAR-T cells are excellent in cancer treatment. However, they still have many limitations in the treatment of solid malignancies. In addition, the toxicity of CARs T cells is also a serious problem in the CAR therapy as well. At present, the CAR therapy has been developed through four generations. This review thus focuses on the opportunities and challenges facing the CAR-T cells.
The design, construction, and experimental evaluation of a cascade thermoacoustic engine are presented in this paper. The system was designed and built under the constraint of an inexpensive device to meet the energy needs of the people based in remote and rural areas. From the cost and straightforward system point of view, the air at atmospheric pressure was applied as a working fluid, and the main resonator tubes were then constructed of conventional polyvinyl chloride (PVC) pipes. Such device consists of one standing-wave unit and one traveling-wave unit connected in series. This topology is preferred because the traveling-wave unit provides an efficient energy conversion, and a straight-line series configuration is easy to build and allows no Gedeon streaming. The system was designed to operate at a low frequency of about 57 Hz. The measured results were in a reasonably good agreement with the predicted results. So far, this system can deliver up to 61W of acoustic power, which was about 17% of the Carnot efficiency. In the further step, the proposed device will be applied as the prime mover for driving the thermoacoustic refrigerator.
Leakage current reduction of the single-phase transformerless cascaded H-bridge PV inverter is investigated in this paper. The high-frequency common-mode loop model of a typical single-phase cascaded H-bridge PV system is established. Based on the model, the main factors that affect the leakage current are discussed. The reason why the typical single-phase cascaded H-bridge inverter fails to reduce the leakage current is explained. In order to solve the problem, a cascaded topology based on the H5 inverter is presented, along with a new modulation strategy, which can ensure that the stray capacitor voltage is free of high-frequency components. In this way, the leakage current can be effectively reduced. Finally, a prototype with TMS320F28335DSP+XC3S400FPGA digital control is built. The performance tests of cascaded H-bridge and the proposed topologies are carried out. The experimental results verify the effectiveness of the proposed solution.
This paper proposes a modified cascaded multilevel grid-connected inverter (MCM-GCI) suitable for photovoltaic grid-connected generation system, which considers wide operation range, low grid current total harmonics distortion (THD), and high European efficiency. In the proposed topology, a bidirectional power switch is added to the standard single-phase cascaded multilevel inverter (CMI) to implement the transformation between CMI mode and H-bridge inverter (HBI) mode. An online topology transformation approach of the MCM-GCI is proposed to guarantee the topology modes transformed safely and smoothly. The proposed MCM-GCI operates in CMI mode when the PV arrays' output voltage and power are low, and transforms into HBI mode when the PV arrays' output voltage and power are high. Experimental results of five-level MCM-GCI are represented to validate the feasibility of the proposed topology and it is also compared with other three classic grid-connected inverters to highlight its advantages. Furthermore, more structures based on hybrid CMI, which possess the topology transformation ability, are shown to further improve the generation range and obtain a higher efficiency of the system.
Background: Colorectal cancer (CRC) is one of the most common cancers. As in other cancer locations, the involvement of human papillomaviruses (HPV) has been suggested but remains highly debated with wide differences among reported prevalence of HPV infection in CRCs. Aim: To determine the actual prevalence of high risk HPV16 and 18 in a large case-control study. Methods: CRC specimens were used for analysis of both tumor and distant healthy tissue. As a nonmalignant control group, samples from sigmoid diverticulosis resections were studied. Detection of HPV16 and HPV18 DNA was performed using a real time polymerase chain reaction (qPCR). Ten percent of tumor samples were also randomly subjected to a complete HPV genotyping using the INNO-LiPA technique. Results: 467 samples were analyzed: 217 tumor samples from 210 CRCs, 210 distant healthy tissue samples, and 40 sigmoid samples. HPV18 DNA was never amplified and HPV16 was amplified only three times in tumor tissues with viral loads under or at the limit of quantification. New extraction from the same tumor blocks for these samples revealed no HPV with qPCR and INNO-Lipa assays. Conclusion: With adequate procedures and reliable techniques, no HPV was detected in the largest case-control study so far, bringing more evidence on the absence of involvement of HPV in CRCs. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely. Genetic variability affecting the host response may also influence the susceptibility to MPP. Several studies have investigated the association between single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however, the results were inconsistent. Here, we investigated the association of 5 functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del), IL-6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715 subjects (415 cases, 300 controls) by using tetra-primer allele-specific polymerase chain reaction (PCR) and Sanger sequencing. The gene-gene interactions were analyzed using the Multifactor Dimensionality Reduction and cumulative genetic risk score approaches. Our results showed that 3 SNPs of ACE rs4340, IL-6 rs1800795, and NOS3 rs1799983 were significantly associated with the risks of MPP, while no differences were observed in genotype frequencies of GSTM1 (Ins/del) and CYP1A1 rs2606345 between both groups. The combinations of ACE rs4340D/NOS3 rs1799983T/CYP1A1 rs2606345G and ACE rs4340D/NOS3 rs1799983T contribute to the genetic susceptibility of MPP in Chinese children.
BACKGROUNDCurrent research on the gastrointestinal digestion of milk-casein strongly suggests the existence of novel bioactive peptides with antiviral activities that are attributable to their immunostimulatory effects. In the present study, we investigated the antiviral activity of casein peptides rich in phosphate groups, such as casein phosphopeptide (CPP-III). RESULTSWe prepared two types of CPP with different phosphorylation levels to clarify the role of the phosphate group. Further phosphorylation of CPP-III was conducted by dry heating with sodium pyrophosphate, whereas dephosphorylation was performed enzymatically using alkaline phosphatase and alkaline treatment. Feline calicivirus (FCV) strain F9, a typical norovirus surrogate, and Crandell Rees feline kidney cells were used as the target virus and host cells, respectively. Antiviral activity was determined based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and quantitative polymerase chain reaction quantification of antiviral cytokine mRNA expression. Higher cell viability was observed in the host cells treated with phosphorylated CPP-III, and a significant up-regulation of type 1 interferon expression was induced compared to that treated with native CPP-III. However, dephosphorylation of CPP-III resulted in a decrease in the anti-FCV effect. CONCLUSIONThe CPP effect was enhanced by the introduction of additional phosphates and conversely weakened by their elimination. Therefore, CPP-III phosphorylation represents an emerging approach for the production of food-grade antiviral agents. (c) 2016 Society of Chemical Industry
Caspian horse, a rare horse breed found in 1965 by Louise Firouz in northern Iran, is a small horse which is reported to be in danger of extinction in its original homeland. There seems to be a great need to prevent extinction of this valuable horse. In this study, 51 fibroblast cell lines from Caspian horse ear marginal tissue were successfully established by sampling 60 horses using primary explant technique. Cells were authenticated and growth curve was plotted. According to results obtained, population doubling time (PDT) was calculated 23 +/- 0.5 h for all cell lines. Multiplex polymerase chain reaction (multiplex PCR) revealed that cell lines had no cross-contamination with other species. Bacteria, fungi, and mycoplasma contamination were checked using standard methods such as PCR, direct culture, and Hoechst staining. In addition to providing a valuable source for genomic, postgenomic, and somatic cloning researches, the established cell lines would preserve Caspian horse genetic resources. It will also create an accessible database for researchers.
Although millions of cats live among humans worldwide the scientific community knows relatively little about cat behavior and cognition. Olfaction is an important perceptual sense for many members of Carnivora, however the role of chemical signals in cat social relationships is not fully understood. Research indicates chemical signals play an important role in many areas of cat behavior including mother offspring and conspecific interactions and exploration of their environment. Chemical cues appear to play a role in stress and anxiety reduction, allowing cats to feel secure in their environment. A better understanding of cat chemical signals, especially as it relates to within and between species communication, may lead to an increase in cat wellbeing as humans can utilize this knowledge in applied settings. Therefore, the purpose of this review is to investigate how cats process and use chemical signals in social contexts and identify ways this information can be applied to address cat behavioral issues, such as inappropriate litter box and scratching behavior, and improve cat welfare, including species-appropriate ways of reinforcing the human-cat bond. (C) 2016 Elsevier B.V. All rights reserved.
Abiotic stresses, such as drought, high salinity, and cold/freezing, lead plants to produce excess reactive oxygen species. Catalase, a unique hydrogen peroxide-scavenging enzyme, plays a very important role in plants. To characterize the catalase involved in plant response to abiotic stresses, we constructed a cDNA library from 4 degrees C-treated Festuca arundinacea Schreb seedlings and isolated a catalase gene from this library. The cDNA (FaCat1, 1 735 bp) contained an open reading frame of 1 479 bp. BLAST analysis indicated that the deduced amino acid sequence showed 96% identity with that from wheat TaCat1 and 87% identity with that from maize ZmCat2. Northern blotting analysis showed an obvious increase of FaCat1 transcripts in leaves in contrast with roots. Time-course analysis of the expression of FaCat1 in F. arundinacea leaves showed that FaCat1 expression was upregulated in cold- and salt-stressed leaves, with the FaCat1 transcripts accumulating mostly at 4 or 2 h after cold or salt stress, respectively. No significant changes in FaCat1 transcription were observed in dried leaves and inhibition of FaCat1 transcription was found in abscisic acid (ABA)-treated leaves, indicating that the FaCat1 gene is differentially expressed during cold, high salt, drought, and ABA treatment in F. arundinacea leaves.
OBJECTIVE: To examine the association of pain catastrophizing to pain experience and a history of childhood sexual abuse in women with chronic pelvic pain (CPP) of gynecologic origin. STUDY DESIGN: Cross-sectional study of women with CPP (N=273) attending a tertiary care obstetrics and gynecology pain clinic. Subjects completed standardized questionnaires to assess pain intensity, pain interference with daily activity, pain catastrophizing, severity of depressive symptoms, and a history of childhood sexual abuse. RESULTS: Correlational analysis indicated, that pain catastrophizing, pain intensity, pain interference and depression scores all shared significant association. Multiple regression analysis indicated that, after controlling for the influence of depressive symptoms on both pain intensity and pain interference, pain catastrophizing significantly predicted both pain outcome measures. After controlling for pain catastrophizing, depressive symptoms were found to significantly influence pain interference but not pain intensity. Of the abuse measures, only women who reported major sexual abuse in childhood were found to endorse more severe pain catastrophizing. CONCLUSION: Pain catastrophizing appears to be an important variable in understanding the pain experience of women with chronic pelvic pain. More over, the presence of a history of major sexual abuse in childhood may be an additional risk factor for pain catastrophizing in this population, contributing to further pain morbidity.
Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules are reduced on dendritic cells from CatG deficient mice compared to their wild type counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism for CatG to facilitate intercellular communication between infiltrating cells and the respective target cell. Subsequently, our findings highlight the pivotal role of CatG as a checkpoint protease which might force target cells to display their intracellular MHC I: antigen repertoire.
This brief comment explores the significance of a number of current lawsuits brought against Catholic Church leaders in Ballarat, Victoria, Australia, in the context of enduring failures of justice for Australian victims of Catholic clerical child sexual abuse. It examines the obstacles to criminal and civil justice that have prevented Church superiors from being held to account for child sexual abuse perpetrated in Catholic institutions, and explains the responsibility of Australian governments, courts and the Catholic Church to further justice for survivors(1) in this context.
Cationic copolymer emulsions of St, BA, AA, and GMA were successfully synthesized via semi-continuous emulsion polymerization. The properties of synthesized cationic emulsions were characterized by monomer conversion and solid content, differential scanning calorimeter, particle size and distribution, zeta potential, and centrifugal stability. The film performance of the cationic emulsions formed on cotton fiber surface was observed by scanning electricity microscopy. The influence of cationic emulsions on the color data, K/S values and rubbing fastness of dyed cotton fabrics was also investigated. The results show that P (St-BA-AAGMA) emulsion had larger particle size and higher zeta potential than P (St-BA-AA) emulsion. When the films were formed at room temperature, P (St-BA-AA-GMA) emulsion film had better performance than P (St-BA-AA) emulsion film. The addition of GMA monomers improved the film performance. P (St-BA-AA-GMA) emulsion films formed at 120 degrees C after acetic acid solution treatment had the best water resistance. Dyed cotton fabrics pretreated with P (St-BA-AA-GMA) emulsion had better pigment dyeing performance than those pretreated with P (St-BA-AA) emulsion. It demonstrates that the addition of GMA monomers further improved the effect of pigment dyeing for cotton fabrics with cationic emulsions as binders. With the increase of P (St-BA-AA-GMA) concentration, the color performance of dye fabrics improved while the rubbing fastness decreased a little. But, the handle and fastness still meets the use standards for consumers. (C) 2017 Wiley Periodicals, Inc.
The control of Rhipicephalus microplus is essential to prevent cattle discomfort and economic losses. However, increased resistance and acaricides inefficiency lead producers to adopt strategies that could result in the accumulation of chemical residues in meat and milk with possibilities of poisoning in animals and people. This scenario demonstrates the necessity of research into the identification of novel, effective and environmentally safe therapeutic options for cattle tick control. The objectives of this study were to develop and assess the efficacy of R. microplus biotherapic and of 5% eugenol for the control of R. microplus in artificially infested calves. Eighteen male 6-month-old Holstein calves were divided into three groups of six animals. In Group 1, the animals did not receive medication (control group); in Group 2, the animals received 1 mL of R. microplus biotherapic at dilution 6CH (centesimal Hahnemannian), orally administered twice daily. And in Group 3, they received a single application of eugenol 5% in the pour-on formulation. The median efficacy for biotherapy and eugenol 5% was respectively 10.13 and 13.97%; however, upon analyzing reproductive efficiency, it is noteworthy that the biotherapic had 45.86% efficiency and was superior to the action of eugenol (12.03%) after 37 days of treatment. The ultrastructural study provided information about the effects of R. microplus biotherapic on the ovaries of engorged females and showed disorganization in the deposition of the oocyte exochorion. The results suggest hatchability inhibition of larvae, interference in R. microplus reproduction and future possibilities for eco-friendly control of R. microplus with biotherapic 6CH.
A full-length cDNA of an immunogenic protein was cloned from a cDNA library of the local Egyptian cattle tick Boophilus annulatus. Antibodies raised against B. annulatus larval proteins were used to screen a cDNA expression library. A 936 bp cloned fragment was sequenced and showed an open reading frame of 516 bp encoding a protein of 171 amino acids. Comparison of the deduced amino acid sequence with protein data bank revealed that the sequence is related to a sequence isolated from the hard tick Haemaphysalis qinghaiensis (Hq05). Southern blot analysis of B. annulatus genomic DNA showed that the cloned cDNA hybridized to double bands per restriction digest, suggesting that the cloned cDNA is a double copy gene. Amino acid analysis of the cloned gene revealed the presence of two casein kinase 11 phosphorylation sites in the N-terminal domain suggesting that this molecule may be involved in the signal transduction or gene expression pathways. RT-PCR and northern blotting revealed the presence of two isoforms of the Ba05 gene in salivary glands and in the 3-day-old eggs. The cloned gene without the signal peptide, was expressed in Escherichia coli under T7 promotor of pET-30b vector, and purified under denaturation conditions. The purified protein appeared as a single band on 12% SDS-PAGE with a molecular weight around 22.8 kDa including the histidine tag of the vector. Antibodies raised against the purified molecule were used to detect the B. annulatus homologue to the Hq05 gene in whole tick, larvae and gut protein extracts. Immunoblotting revealed the presence of this molecule Ba05 only in whole tick and larval protein extracts and not in the gut protein extract. Using the same antibodies, homologues to the Ba05 gene were detected in other tick species as Hyalomma dromedarii and Rhipicephalus sp. but not in Ornithodoros moubata. (c) 2007 Elsevier B.V. All rights reserved.
The objective of this study was to assess the immune and stress responsiveness of cows identified as extremely high and low feed conversion efficiency phenotypes. The study utilised 16 Holstein-Friesian cows in their third to fourth lactation, and identified as having either extremely high (n = 8) or extremely low (n = 8) feed conversion efficiency. A commercial vaccine was used to induce measurable antibody-and cell-mediated adaptive immune responses and assess general immune responsiveness. Stress responsiveness was assessed by measuring changes in plasma cortisol concentrations in response to yarding and handling. No significant differences in antibody-or cell-mediated immune responsiveness were observed between the extreme high and low feed conversion efficiency phenotypes (P = 0.343 and 0.546, respectively). However, results suggested that plasma cortisol concentrations trended higher in the low feed conversion efficiency phenotype cows than their high feed conversion efficiency counterparts (P = 0.079) 48 h post-yarding and handling. A significant negative correlation was observed between antibody-mediated immune responsiveness and stress responsiveness (r = -0.44, P = 0.043) but not with cell-mediated immune responsiveness (r = 0.135, P = 0.309). This study provides preliminary evidence that cows selected for feed conversion efficiency may have improved stress-coping abilities and immune responsiveness.
The association between transportation and the occurrence of the bovine respiratory disease complex (BRDC) has long been recognised. Many hypotheses regarding this association have been declared through the past decades, and it is agreed upon by most researchers that the multiple stressors that calves experience during transportation result in an overall immunosuppression that allows the respiratory tract to be invaded by numerous opportunistic pathogens. Furthermore, the innate immune cells, neutrophils, may be trapped in a paradox whereby their crucial defence and pathogen-killing activities are counteracted by excessive inflammation and tissue damage that may exacerbate disease, including the BRDC. Neutrophilia in response to glucocorticoids has been attributed to an influx of immature neutrophils newly released from the bone marrow, a decrease in neutrophil margination along endothelial walls, and a decrease in neutrophil apoptosis. Several of these explanations have been confirmed by altered expression of genes and proteins important for neutrophil margination and apoptosis.
The genetically dystonic rat (SD-dt:JFL) is an autosomal recessive model of generalized dystonia. Without cerebellectomy, the dt rat dies prior to Postnatal Day 40. The dt locus was mapped to a 4.2 Mb region on Chr 7q11 and candidate genes were screened with semi-quantitative RT-PCR. Then, Southern blotting and genomic DNA sequencing identified the Y-long terminal repeat portion of an intracisternal A particle element inserted into Intron I of Atcay, the gene which encodes caytaxin. Northern and Western blotting and quantitative real-time RT-PCR defined the Atcay allele in dt rats (Atcay(dt)) as hypomorphic. To establish a framework for functional studies of caytaxin, the developmental expression of rat Atcay transcript was analyzed with Northern blotting, relative quantitative multiplex real-time RT-PCR (QRT-PCR) and in situ hybridization. With a multiple tissue Northern blot, three Atcay transcripts were identified in brain but none were present in heart, spleen, lung, liver, muscle, kidney or testis. With a multiple time-point Northern blot, the same three transcripts were present in cerebellum at Embryonic Day (E15), Postnatal Day 1 (P1), P7, P14, P36 and 8 months. During early development (E15 to P14), the relative proportion of the smallest transcript was increased. QRT-PCR was performed with total RNA from cerebral cortex, striatum, thalamus, hippocampus and cerebellum. Transcript levels peaked at P7 in hippocampus, increased linearly from PI to P36 in cerebellum, and showed minimal developmental regulation in cerebral cortex. Radioactive in situ hybridization localized Atcay transcript to seemingly all neuronal populations in brain. In cerebellum, Atcay transcript was present in the molecular, Purkinje and granular layers; transcript density in the molecular layer peaked at P14. In the background of previous biochemical, behavioral and electrophysiological studies in the dt rat, our data are compatible with a vital role for caytaxin in the development and neurophysiology of cerebellar cortex. (c) 2005 Elsevier B.V. All rights reserved.
Background: The psychological literature suggests that therapist perfectionism is common and potentially detrimental to client recovery. Little is known about the relationship between therapist perfectionism and client outcomes. Aims: This study aimed to measure perfectionism in High Intensity Cognitive Behavioural therapists, and establish any relationships between dimensions of therapist perfectionism, client outcomes and drop-out rates in treatment. Method: Thirty-six therapists took part in the study; levels of perfectionism were measured using a self-report questionnaire and these were analysed in relation to the clinical outcomes from a sample of their clients. Results: The results indicated that therapist perfectionism may be less common than previously suggested. Overall, a number of significant negative associations were observed between aspects of therapist perfectionism (e.g. having high standards for others), treatment efficacy and client retention in treatment. Conclusions: Therapist perfectionism is associated with CBT treatment outcomes; tentative recommendations for therapists managing their own schema as part of their clinical practice have been made, although further investigation is required.
Background: Eotaxin/CCL11 plays an important role in asthma. It acts through the chemokine receptor CCR3 expressed on hematopoietic and nonhematopoietic cells in the lung. Objective: To determine whether eotaxin/CCL11 modulates lung and bronchial fibroblast properties and thereby might contribute to airway remodeling. Methods: CCR3 expression was characterized on a lung fibroblast line (MRC-5; flow cytometry, fluorescent microscopy, RT-PCR, and Northern blotting), on primary bronchial fibroblasts (flow cytometry), and on fibroblasts in human lung tissue (confocal laser microscopy). The effects of eotaxin/CCL11 on lung fibroblast migration (Boyden chamber), proliferation (tritiated thymidine incorporation), a-smooth muscle actin expression (ELISA), 3-dimensional collagen gel contraction (floating gel), pro-alpha 1(I) collagen mRNA (Northern blotting), total collagen synthesis (tritiated proline incorporation), matrix metalloproteinase activity (gelatin zymography), and TGF-beta(1) release (ELISA) were evaluated. The contribution of eotaxin/CCL11/CCR3 binding on lung fibroblasts was also investigated by neutralizing experiments. Results: CCR3 is constitutively expressed in cultured lung and primary bronchial fibroblasts and colocalizes with specific surface markers for human fibroblasts in lung tissue. Eotaxin/CCL11 selectively modulates fibroblast activities by increasing their proliferation, matrix metalloproteinase 2 activity, and collagen synthesis but not their differentiation into myofibroblasts, contractility in collagen gel, or TGF-beta(1) release. Eotaxin/CCL11 enhances migration of lung fibroblasts in response to nonspecific chemoattractants, and this effect is completely inhibited by anti-CCR3-neutralizing antibodies. Conclusion: These data demonstrate that eotaxin/CCL11 has a direct and selective profibrogenic effect on lung and bronchial fibroblasts, providing a novel mechanism whereby eotaxin/CCL11 can participate in airway remodeling in asthma.
Background and Objectives: Calprotectin, a heterodimer of S100A8 and S100A9 with antimicrobial properties, is expressed in gingival keratinocytes and plays an important role in innate immunity. Because calprotectin expression is localized in the spinous cell layer of the gingival epithelium, we hypothesized that the expression of calprotectin in keratinocytes is related to the differentiation stage. The aim of the present study was to investigate the relationship between calprotectin expression and keratinocyte differentiation using some factors that regulated its differentiation. Material and Methods: Normal human gingival keratinocytes were isolated from gingival tissues obtained at the extraction of wisdom teeth, and were cultured in serum-free keratinocyte medium supplemented with interleukin-1 alpha or calcium, which promote keratinocyte differentiation, and transforming frowth factor-beta (TGF-beta) or retinoic acid, which suppress its differentiation. The expression of S100A8/A9 mRNA and the production of calprotectin in normal human gingival keratinocytes were examined by northern blotting and enzyme-linked immunosorbent assay, respectively. The expression of cytokeratin 14, involucrin and filaggrin (marker proteins of keratinocyte differentiation) was investigated by immunohistochemical staining, and the DNA-binding activity of CCAAT/enhancer binding protein alpha (C/EBP alpha), a transcription factor, was examined by electrophoretic mobility shift assay. Results: The expression of S100A8/A9 mRNA and the production of calprotectin were increased by interleukin-1 alpha and calcium, but decreased by TGF-beta. RA inhibited the expression of S100A8/A9 and keratinocyte differentiation, which were induced by interleukin-1 alpha. C/EBP alpha DNA-binding activity in normal human gingival keratinocytes was enhanced by interleukin-1 alpha and calcium, but suppressed by TGF-beta. Conclusion: The present study suggests that calprotectin expression is related to keratinocyte differentiation and that C/EBP alpha is a regulator of calprotectin expression in keratinocytes.
DREB transcription factors usually play important regulatory roles in the responses of plants to abiotic stress. In this study, a novel SlDREB1 transcription factor from tomato was isolated by yeast-one-hybrid system. Bioinformatics analysis showed that the SlDREB1 is a single copy gene with typical AP2 conserved domain, and located on the #6 chromosome of the tomato genome. The SlDREB1 protein was confirmed to be localized to the cell nucleus. To profile the physiological and molecular responses of the SlDREB1 gene to drought stress, we transferred the SlDREB1 gene into the Arabidopsis plants, and functionally characterized the SlDREB1 gene by molecular detection in vitro and drought stress experiments. The data showed that accumulation of the SlDREB1 mRNA in the roots of the tomato was higher than that in the shoots, and strongly induced by drought, salt or exogenous abscisic acid. Both transcriptional activation and gel mobility shift assay indicated that the SlDREB1 protein exhibited specific mechanism recognizing the CCGAC motif in the promoters of the stress-resistant genes in the transgenic Arabidopsis. The data exhibited that the transgenic Arabidopsis revealed obvious up-regulations in accumulations of the SlDREB1 and ERD15 mRNA in response to drought stress. Physiological measurements demonstrated that the transgenic Arabidopsis overexpressing the SlDREB1 gene remarkably increased accumulation of osmolytes, such as soluble sugar and free proline, but reduced the contents of malondialdehyde in the leaves, suggesting that overexpression of the SlDREB1 gene in the transgenic Arabidopsis plays crucial regulatory roles in maintaining the balance of osmotic potentials and alleviating physiological damage in response to drought stress. Northern blotting also provided evidence that the tomato SlDREB1 apparently up-regulated the expressions of the drought-resistant ERD15 gene through a transcriptional activation pathway recognizing the CCGAC motifs, such as the NNCCGACNN element in the promoter of the ERD15 instead of limiting to the specific DRE element in the promoter of the RD29A, and led to an enhanced tolerance of the transgenic Arabidopsis to drought stress.
Objective: Understanding how treatments work is a goal of psychotherapy research, however the strength of relationships between therapy processes and outcomes is inconsistent. DeRubeis, Cohen, et al. (2014) proposed that process-outcome relationships are moderated by patient characteristics. These "patient response patterns" (PRPs) indicate individuals' responsiveness to the active ingredients of treatment. Given the same quality of therapy, one individual may receive more benefit than another depending on their PRP. The "prognosis moderation hypothesis" states that PRPs can be defined by pretreatment prognostic indicators. Medium prognosis groups ("pliant-like") will have stronger process-outcome relationships than good ("easy-like") or poor ("challenging-like") groups. Method: N = 190 individuals received unguided computerized CBT. They were 58% women, aged 44.7 years. Engagement with the cCBT program was the process variable. PRPs were defined by predicted scores from a prognostic regression model. Outcomes were BDI scores at 3, 6, and 12 months. "Easy-like," "pliant-like" and "challenging-like" groups were created and the engagement-outcome relationship was assessed as a function of group. Results: Engagement-outcome correlations by PRP were: easy-like, r = -.27 (p < 05); pliant-like, r = -.36 (p < .01); and challenging-like, r = .05 (p = .70). The pliant-like group was found to be the only moderator of the engagement-outcome relationship. Results were similar at 6 months but faded at 12. Conclusions: The engagement-outcome relationship varied as a function of prognosis, providing support for the prognosis moderation hypothesis. The "pliant-like" group appeared most sensitive to treatment procedures. Future research is needed to refine the methods for identifying PRPs.
The immense work presented in this paper is a high frequency sinusoidal oscillator using positive second generation current controlled conveyor (CCCII+) with minimum passive components. CCCII is implemented using single Current Feedback Operational Amplifier (CFOA) and single Operational Trans-conductance Amplifier (OTA). The frequency (time period) of CCCII is tuned to a maximum of 4 MHz using external bias current. The performance of the proposed circuit is practically verified using ICs AD844 (CFOA) and LM 13700 (OTA) and its results are incIuded. The topology is suitable for monolithic IC fabrication.
Combined cooling, heating and power (CCHP) system plays a significant role in efficient usage of energy in field of small scale power system for application ranging from residence to utilities. In the paper, a new CCHP system is proposed which consists of a power generation unit (PGU), an absorption chiller, a storage tank and a ground source heat pump (GSHP) to substitute conventional electric chiller and auxiliary boiler to supply the deficient cooling or heating load. In the study, three basic load following strategies: following electric load (FEL), following thermal load (FTL) and following hybrid load (FHL) are employed to analyze the annual total cost (ATC), operational cost (COST), carbon dioxide emissions (CDE) and primary energy consumption (PEC) based on a case study of a regional energy system in Sino-Singapore eco-city. For the evaluated case, carbon tax and electricity feed in tariff are both considered to compare with the performances of following maximum electric efficiency of the PGU (Max-eff) strategy. The results show that the proposed system performed well on COST, CDE and PEC reduction and the ATC are all increased except that of Max-eff strategy with carbon tax and electricity feed in tariff. When carbon tax and electricity feed in tariff are considered, performances of the Max-eff strategy is the best. Otherwise, the application of FEL is better. Finally, for the Max-eff and FEL strategy, sensitivity analysis is performed and results are presented with varying of electricity and gas price. (C) 2016 Elsevier Ltd. All rights reserved.
This paper presents a new topology for waveform-generation using two current conveyors, and a grounded capacitor or a resistor for tuning. It uses current-conveyors in place of voltage op-amps to offer better linearity, bandwidth, slew rate and thermal stability. Measured results obtained using commercially available devices AD844AN and passive components show excellent linearity and tunability for both grounded resistor and capacitor topologies over the range of interest. Component sensitivity and temperature-sensitivity from -150 degrees C to +150 degrees C are studied. A comparison with existing candidate-designs shows superiority of the proposed design on all aspects. Grounded-connection of tuning components makes digital control easy.
Methods. The expression of Cyr61 and NF-kappa B pathway molecules was examined by western blotting. CCL2 expression was assessed by northern blotting and ELISA. Interaction between NF-kappa B and Cyr61 promoter was evaluated by electrophoretic mobility shift assay. In rat CIA, osteoblastic expression of Cyr61 was examined by immunohistochemistry and disease progression was assessed by clinical, radiographic and histological examinations. Results. EGCG inhibited Cyr61 expression stimulated by cytokines in primary human osteoblasts and human osteoblastic cell line U2OS. In U2OS, oncostatin M (OSM) induced I kappa B-alpha degradation through the mTOR/rictor/Akt pathway, and EGCG attenuated the action. Electrophoretic mobility shift assay revealed that the OSM-enhanced NF-kappa B/DNA binding was reduced by EGCG, possibly through abrogating nucleus localization of p65 and p50. Cyr61 enhanced OSM-induced expression of CCL2. Moreover, EGCG diminished OSM-stimulated CCL2 expression at least partially via suppressing Cyr61 induction. Co-distribution of CD68(+) macrophages and Cyr61(+) osteoblasts in osteolytic areas was obvious in the CIA model. Clinical, radiographic and immunohistochemical analyses revealed that administration of EGCG markedly diminished the severity of CIA, macrophage infiltration, and the number of Cyr61-synthesizing osteoblasts. Conclusion. By modulating the mTOR/rictor/Akt/NF-kappa B pathway, EGCG attenuated Cyr61 production in osteoblastic cells and in turn diminished macrophage chemotaxis. Our data support the therapeutic potential of EGCG on arthritis.
This study examined the effect of resistance exercise on the production, recruitment, percentage, and adhesion characteristics of granulocytes with andwithout polyphenol (PPB) supplementation. Thirty-eight untrained men were randomized into three groups: PPB (n=13, 21.8 +/- 2.5 years, 171.2 +/- 5.5cm, 71.2 +/- 8.2kg), placebo (PL; n=15, 21.6 +/- 2.5years, 176.5 +/- 4.9cm, 84.0 +/- 15.7kg), or control (CON; n=10, 23.3 +/- 4.3years, 173.7 +/- 12.6cm, 77.3 +/- 16.3kg). Blood samples were obtained pre (PRE), immediately (IP), 1h (1H), 5h (5H), 24h (24H), 48h (48H), and 96h (96H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Plasma concentrations and intramuscular content of interleukin-8 (IL-8), granulocyte (G-CSF), and granulocyte-macrophage colony stimulating factor (GM-CSF) were analyzed via multiplex assays. Changes in relative number of circulating granulocytes and adhesion receptor (CD11b) were assessed using flow cytometry. Intramuscular IL-8 was significantly elevated at 1H, 5H, and 48H (P<0.001). Area under the curve analysis indicated a greater intramuscular IL-8 content in PL than PPB (P=0.011). Across groups, circulating G-CSF was elevated from PRE at IP (P<0.001), 1H (P=0.011), and 5H (P=0.025), while GM-CSF was elevated at IP (P<0.001) and 1H (P=0.007). Relative number of granulocytes was elevated at 1H (P<0.001), 5H (P<0.001), and 24H (P=0.005, P=0.006) in PPB and PL, respectively. Across groups, granulocyte CD11b expression was upregulated from PRE to IP (P<0.001) and 1H (P=0.015). Results indicated an increase in circulating CD11b on granulocytes, and IL-8 within the muscle following intense resistance exercise. Polyphenol supplementation may attenuate the IL-8 response, however, did not affect granulocyte percentage and adhesion molecule expression in peripheral blood following resistance exercise.
Most immune cell communication takes place by intercellular transfer of cytokines or the contact-dependent interaction of surface receptors in immunological synapses. In this issue of the European Journal of Immunology, Gardell and Parker (Eur. J. Immunol. 2017, 47, 41-50) point to a new, hybrid mechanism for Th1-cell delivery of help to B cells, based on contact-dependent CD40L transfer. The transfer process and its specificity are both cell contact dependent and antigen dependent. CD40 expression is also required on the B-cell surface to capture the CD40L presented by the Th1 cell. While further studies are needed to confirm the phenomenon in vivo and to test the role of transferred CD40L in other aspects of T-cell help, this study provides an exceptional take-off point and makes excellent use of mouse genetics to work out some possible rules for B cells being able to order help 'to go'.
Background: Abnormal expression of some CD44 molecules in tumor tissues can induce the degradation of the extracellular matrix, and is closely associated with axillary lymph node metastasis, angiogenesis, cancer progression, and drug resistance. Patients and Methods: We measured and confirmed the expression of CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal tissues of postoperative non-small cell lung cancer (NSCLC) patients with either adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative reverse transcription polymerase chain reaction, gene sequencing, and immunohistochemical analysis. Results: CD44st and MMP2 expression were closely associated with the histopathological classification, lymph node metastasis, and TNM stage of the tumors, and the difference was statistically significant (p < 0.05). The median overall survival (OS) for the high CD44st expression group was 30.52 months (95% confidence interval (Cl) 24.02-36.15); for the low expression group it was 43.23 months (95% Cl 31.81-52.02) (p = 0.020). The median OS for the high MMP-2 expression group was 30.53 months (95% Cl 26.69-33.31); for the low expression group it was 40.06 months (95% Cl 33.55-46.45) (p = 0.022). Conclusion: The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas than in adenocarcinomas, were closely associated with lymph node metastasis and TNM stage, and affected patients' prognoses. (C) 2017 S. Karger GmbH, Freiburg
alpha 1-antitrypsin (AAT), a circulating glycoprotein that rises during acute phase responses and healthy pregnancies, exhibits immunomodulatory properties in several T-cell-dependent immune pathologies. However, AAT does not directly interfere with T-cell responses; instead, it facilitates polarization of macrophages and dendritic cells towards M2-like and tolerogenic cells, respectively. AAT also allows NK cell responses against tumor cells, while attenuating DC-dependent induction of autoimmune NK cell activities. Since AAT-treated macrophages bear resemblance to cancer-promoting tumor-associated macrophages (TAMs), it became imperative to examine the possible induction of tumor permissive conditions by AAT. Here, AAT treatment is examined for its effect on tumor development, metastatic spread, and tumor immunology. Systemic AAT treatment of mice inoculated with B16-F10 melanoma cells resulted in significant inhibition of tumor growth and metastatic spread. Using NK cell-resistant RMA cells, we show that AAT interferes with tumor development in a CD8(+) T-cell-dependent manner. Unexpectedly, upon analysis of tumor cellular composition, we identified functional tumor-infiltrating CD8(+) T-cells alongside M1-like TAMs in AAT-treated mice. Based on the ability of AAT to undergo chemical modifications, we emulated conditions of elevated reactive nitrogen and oxygen species. Indeed, macrophages were stimulated by treatment with nitrosylated AAT, and IFN gamma transcripts were significantly elevated in tumors extracted soon after ischemia-reperfusion challenge. These context-specific changes may explain the differential effects of AAT on immune responses towards tumor cells versus benign antigenic targets. These data suggest that systemically elevated levels of AAT may accommodate its physiological function in inflammatory resolution, without compromising tumor-targeting immune responses.
Proliferation of endometrial cells is a prerequisite step for functional differentiation in the uterus A tumor suppressor gene Cyclin dependent kinase 2 associated protein 1 (Cdk2ap1) mRNA was detected in the pregnant uterus and was suggested to be involved in cell proliferation However its roles and the mechanisms regulating its expression are largely unknown In this study the role of steroid hormones in the expression of Cdk2ap1 was examined using RT PCR Northern blotting and in situ hybridization methods Cdk2ap1 mRNA was highly expressed during the proestrus phase and was mainly localized in the epithelium and subepithelium Its expression was induced by a single injection of estradiol and progesterone but the effect of progesterone was stronger than that of estradiol Injections of progesterone (P1 2) on 2 consecutive days induced Cdk2ap1 expression in the endometrium with the same patterns ob served in the proestrus phase but injections of estradiol (El 2) on 2 consecutive days did not induce expression The Cdk2ap1 mRNA level was decreased by combined treatment of progesterone and estradiol (E1+P2 3) RU486 suppressed completely the Cdk2ap1 mRNA expression in P1,2 while ICI 182 780 did not in E1+P2 3 In the uteri on day 4 of gestation expression of Cdk2ap1 also was regulated by progesterone as expected Cdk2ap1 mRNA expression was totally suppressed by RU486 but not by ICI 182 780 Thus it is suggested that Cdk2ap1 expression is primarily regulated by progesterone and the progesterone receptor in uterus and is mainly localized to proliferating tissues (J Endocrinol Invest 33 650 656 2010) (c) 2010 Editrice Kurtis
Background: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. Methods: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA). Functional effects of Cdk5 overexpression, genetic knockdown by siRNA and shRNA, and pharmacologic inhibition by the small molecule roscovitine were tested in migration, invasion, cell death, and tumorsphere assays and in tumour establishment in vivo. For mechanistic studies, molecular biology methods were applied. Results: In fact, here we pin down a novel function of Cdk5 in TICs: knockdown and pharmacological inhibition of Cdk5 impaired tumorsphere formation and reduced tumour establishment in vivo. Conversely, Cdk5 overexpression promoted tumorsphere formation which was in line with increased expression of Cdk5 in human breast cancer tissues as shown by staining of a human TMA. In order to understand how Cdk5 inhibition affects tumorsphere formation, we identify a role of Cdk5 in detachment-induced cell death: Cdk5 inhibition induced apoptosis in tumorspheres by stabilizing the transcription factor Foxo1 which results in increased levels of the pro-apoptotic protein Bim. Conclusions: In summary, our study elucidates a Cdk5-Foxo1-Bim pathway in cell death in tumorspheres and suggests Cdk5 as a potential target to address TICs.
CDK8, a member of the transcriptional subtype of the cyclin-dependent kinases (CDKs) family, shows remarkable cancer tissue specific expression profile and rather more selective contribution to the regulation of gene expression levels involved in some signaling pathways. However, the effect of CDK8 on the malignant phenotype of human laryngeal squamous cell carcinoma (LSCC) cells and the potential molecular mechanisms remain unclear. In the present study, we evaluated the expression levels of CDK8 by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry in tissue samples of 60 LSCC patients. Then we analyzed and correlated the results with clinicopathological features. We demonstrated that CDK8 was significantly overexpressed in LSCC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis and advanced clinical stages. Kaplan-Meier analysis showed that high expression levels of CDK8 miRNA significantly correlated with short OS survival. In addition, down-regulation of CDK8 using small interfering RNA(siRNA) reduced the proliferation and migration of LSCC in vitro. To explore the potential mechanism, we investigated the effect of CDK8 on Wnt signaling pathway and found that CDK8 was involved in the EMT progress by regulating beta-catenin of the Wnt signaling. In summary, our data suggest for the first time that CDK8 appears to contribute to the malignant mechanism of LSCC and may represent a significant prognostic marker for LSCC patients.
4-Coumarate: coenzyme A ligase (4CL) is one of the key enzymes in phenylpropanoid metabolism leading to series of phenolics, including water-soluble phenolic acids, which are important compounds determining the medicinal quality of Danshen (Salvia miltiorrhiza Bunge), a traditional Chinese medicinal herb. To investigate the function of 4CL in the biosynthesis of water-soluble phenolic acid in Danshen, we have cloned two cDNAs (Sm4CL1 and Sm4CL2) encoding divergent 4CL members by applying nested reverse transcription-polymerase chain reaction (RT-PCR) with degenerate primers followed by 5'/3' rapid amplification of cDNA ends (RACE) (Note, these sequence data have been submitted to the GenBank database under accession numbers AY237163 and AY237164). Either of the coding regions was inserted into a pRSET vector and a kinetic assay was performed with purified recombinant proteins. The substrate utilization profile of Sm4CL1 was distinct from that of Sm4CL2. The K(m) values of Sm4CL1 and Sm4CL2 to 4-coumaric acid were (72.20 +/- 4.10) and (6.50 +/- 1.45) mu mol/L, respectively. These results, in conjunction with Northern blotting and other information, imply that Sm4CL2 may play an important role in the biosynthesis of water-soluble phenolic compounds, whereas Sm4CL1 may play a minor role in the pathway. Southern blotting analysis suggested that both Sm4CL1 and Sm4CL2 genes are present as a single copy and are located at different sites in the genome.
Fresh-cut papaya fruit undergo rapid tissue deterioration during storage. A comparative gene expression study was conducted to isolate genes differentially expressed upon fresh-cut processing by means of mRNA differential display RT-PCR. Differential display analysis was performed on intact and fresh-cut papaya fruit stored in parallel for 12h at 5 degrees C with three different one-base-anchored oligo dT and eight arbitrary primers. Confirmation of true positive bands was performed by northern blotting. Fourteen differentially expressed cDNAs ranging from 154 to 777 bp were cloned, sequenced and compared to GenBank sequences. The partial cDNAs showed significant homologies to signaling pathway genes, membrane proteins, cell-wall enzymes, proteases, ethylene biosynthetic enzymes, and enzymes involved in plant defense responses. Northern blot analysis with probes of each of the partial clones revealed that most of the genes corresponding to partial cDNAs were expressed in a fresh-cut dependent manner during 8 days storage. The transcripts for PC18-5, PA19-3 and PC17 were not detectable on northern blots. The results suggest that fresh-cut processing induces the expression of proteins involved in membrane degradation, free radical generation, and enzymes involved in global stress responses. (c) 2006 Elsevier B.V. All rights reserved.
The cDNA encoding a protease of Perinereis aibuhitensis Grube (PPA) was cloned. The deduced amino acid sequence analysis showed that the protein had 49% identity to the C-terminal amino acid 169-246 of serine protease of Heterodera glycines. Northern blotting analysis indicated that the cDNA could hybridize with mRNA of approximately 260 bases isolated from the marine earthworm. The cDNA was amplified by polymerase chain reaction and cloned into pMAL-p2 to construct expression vector pMAL-PPA. pMAL-PPA was introduced into Escherichia coli BL21(DE3) and overexpression of PPA fused with maltose binding protein was achieved by isopropyl-beta-D-thiogalactopyranoside induction. The fusion protein was purified by affinity chromatography on an amylose resin column and ion-exchange chromatography on a diethylaminoethyl-Sepharose 4B column. Rabbits were immunized with the purified protein and antiserum was prepared. The antibody could react with a protein of approximately 9 kDa extracted from the marine earthworm as shown by Western blotting analysis. The activity analysis of the recombinant PPA suggested that it was probably a plasminogen activator.
The basic helix-loop-helix transcription factor Math1, which is transiently expressed in proliferating neural precursors in multiple domains of the developing nervous system, is also related to the cell fate decision of enteroendocrine, goblet, and Paneth cells in the intestine. On the other hand, the transcription factor Cdx2, which is normally confined to intestinal epithelial cells, is related to the differentiation of these cells. Therefore, we investigated the relationship between Math1 and Cdx2 in intestinal epithelial cells. The Math1 and Cdx2 expressions in normal intestinal mucosa and intestinal metaplastic mucosa from mouse and human stomachs, as well as an intestinal crypt-derived cell line, were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and Northern blotting, and Math1 enhancer element was analyzed by luciferase reporter assays. Math1-positive epithelial cells co-expressing Cdx2 were found in normal intestinal mucosa from humans and mice. Furthermore, Math1-producing epithelial cells that showed positive immunostaining for Cdx2 were also observed in intestinal metaplastic mucosa from human and Cdx2 transgenic mouse stomachs, although they were not detected in normal gastric mucosa of humans and mice. Expression of Cdx2 stimulated endogenous Math1 mRNA expression in the intestinal crypt-derived cell line IEC-6, corroborating observations in Cdx2-expressing intestinal metaplastic mucosa. Furthermore, expression of Cdx2 in IEC-6 cells conferred the ability to express a Math1 reporter gene containing a Math1 enhancer. Based on these results, we hypothesize that Cdx2 is involved in activating Math1 expression in intestinal epithelial cells.
As bacterial resistance becomes increasingly common, a new hybrid peptide, cecropinA-magainin (KWALSKEGPGKFLGKKKKF), has been developed that can kill a broad spectrum of bacteria without damaging human cells. The mechanism of antibacterial toxicity for the hybrid peptides is unknown. Herein, we investigate the localization of the hybrid peptide in methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was 64 mu g/mL. The hybrid peptides could enhance the hydrophobicity of MRSA. Dye leakage experiments showed that the hybrid peptides caused dye leakage from liposomes. The hybrid peptides influenced the permeability of the outer membrane and plasma membrane of MRSA. After cecropinA-magainin treatment of MRSA, the membrane ultrastructure was damaged and the concentration of K+ increased. Ultimately, the peptide destroyed the integrity of the bacterial cell membrane, allowing the dye propidium iodide to enter the cytoplasm. Therefore, the hybrid antibacterial peptide can kill MRSA. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 805-811, 2016
Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.
Background: Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. Objective: We aimed at evaluating the role of MCs in the pathogenesis of CD. Methods: Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration and MC distribution. Moreover, MC reactivity to gliadin and its peptides was characterized by using in vitro assays. Results: Infiltrating MCs were associated with the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. MCs were found to directly respond to nonimmunodominant gliadin fragments by releasing proinflammatory mediators. Immunohistochemical characterization of infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an increase in proinflammatory MC function in advanced stages of the disease. This was also associated with increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage. Conclusion: We provide a description of the progressive stages of CD, in which MCs are the hallmark of the inflammatory process. Thus the view of CD should be revised, and the contribution of MCs in the onset and progression of CD should be reconsidered in developing new therapeutic approaches.
AimTo investigate the effect of simvastatin on lipopolysaccharide (LPS)-stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor-B (NF-B) transcription factors in human dental pulp cells (HDPCs). MethodologyThe effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. NF-B transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova). ResultsThe viability of cells exposed to different concentrations of E.coli LPS, P.gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P>0.05). LPS significantly increased interleukin (IL)-1 (P<0.05) and IL-6 mRNA expression (P<0.05) and vascular cell adhesion molecule-1 (VCAM-1) (P<0.05) and intercellular adhesion molecule-1 (ICAM-1) protein expression (P<0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS-stimulated production of IL-1, IL-6, VCAM-1 and ICAM-1 (P<0.05). Treatment with simvastatin decreased LPS-induced expression of p65 and phosphorylation of IB and also significantly decreased the phosphorylation of p65 and IB in the cytoplasm and the level of p65 in the nucleus (P<0.05). ConclusionsSimvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-B transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy.
Background and Aim: Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS. Methods: Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor-A (VEGF-A) levels, angiogenesis, and alveolar-arterial oxygen gradient (AaPO(2)). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK-19), and enzymatic changes. Results: Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF-A levels, and angiogenesis in CBDL animal lung and improved AaPO(2) levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal. Conclusions: Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease.
Background: In previous studies by the authors, it was demonstrated that a fibronectin ( FN)- derived oligopeptide, termed F20, stimulates osteoblast differentiation in vitro and bone formation in vivo. However, the fundamental molecular mechanism by which F20 stimulates osteogenesis remains unknown. Therefore, in this study the molecular mechanism underlying the effect of F20 in osteoblast differentiation is investigated. Methods: The role of F20 in osteoblast differentiation was examined using mouse bone- marrow- derived ST2 cell line. The effect of Smad1/ 5 was determined following small interfering RNA knockdown. Runt- related transcription factor ( Runx) 2, alkaline phosphatase ( Alp), and osteocalcin ( Oc) mRNA levels were determined by quantitative real- time polymerase chain reaction, and their transcriptional activation was assessed using luciferase reporter assays. Extracellular signalregulated kinase ( ERK) phosphorylation was visualized via immunoblotting. Results: Synthetic oligopeptide F20 stimulated expression of bone marker genes Runx2, Alp, and Oc in ST2 cells via Smad and ERK or mitogen- activated protein kinase signaling pathways as did bone morphogenic protein 2 ( BMP2). Furthermore, Runx2 acted as a transcription factor during F20induced osteoblast differentiation. Conclusions: Collectively, these results indicate that F20 induces osteoblast differentiation with a pattern similar to that mediated by BMP2 signaling pathway. The authors' previous data also showed that FN- derived oligopeptide improved wound healing, and it is suggested that F20 might serve as a therapeutic biomolecule to facilitate periodontal tissue regeneration.
Life is driven by a set of biological events that are naturally dynamic and tightly orchestrated from the single molecule to entire organisms. Although biochemistry and molecular biology have been essential in deciphering signaling at a cellular and organismal level, biological imaging has been instrumental for unraveling life processes across multiple scales. Imaging methods have considerably improved over the past decades and now allow to grasp the inner workings of proteins, organelles, cells, organs and whole organisms. Not only do they allow us to visualize these events in their most-relevant context but also to accurately quantify underlying biomechanical features and, so, provide essential information for their understanding. In this Commentary, we review a palette of imaging (and biophysical) methods that are available to the scientific community for elucidating a wide array of biological events. We cover the most-recent developments in intravital imaging, light-sheet microscopy, super-resolution imaging, and correlative light and electron microscopy. In addition, we illustrate how these technologies have led to important insights in cell biology, from the molecular to the whole-organism resolution. Altogether, this review offers a snapshot of the current and state-of-the-art imaging methods that will contribute to the understanding of life and disease.
Perennial monoculture forming grasses are very important natural remediators of pollutants. Their genetic improvement is an important task because introduction of key transgenes can dramatically improve their remediation potential. Transfer of key genes for mercury phytoremediation into the salt marsh cordgrass (Spartina alterniflora) is reported here. S. alterniflora plays an important role in the salt marsh by cycling of elements, both nutrients and pollutants, protects the coastline from erosion, is a keystone species in the salt marsh supporting a large food web, which in turn supports a significant segment of economy, including tourism, has an impact on cloud formation and consequently on global weather, and is thus an ecologically important species relevant for our life-support systems. Embryogenic callus of S. alterniflora was co-inoculated with a pair of Agrobacterium strains LBA4404 carrying the organomercurial lyase (merB) and mercuric reductase (merA) genes, respectively, in order to co-introduce both the merA and the merB genes. Seven stable geneticin resistant lines were recovered. The presence of merA and merB genes was verified by PCR and Southern blotting. All but one transgenic lines contained both the merA and the merB sequences proving that co-introduction into Spartina of two genes from separate Agrobacterium strains is feasible and frequent, although the overall frequency of transformation is low. Northern blotting showed differences in relative expression of the two transgenes among individual transformants. The steady-state RNA levels appeared to correlate with the phenotype. Line #7 showed the highest resistance to HgCl2 (up to 500 mu M), whereas line #3 was the most resistant to phenylmercuric acetate (PMA). Wild-type (WT) callus is sensitive to PMA at 50 mu M and to HgCl2 at 225 mu M.
Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell-cell transmission and cell-free viral transmission. Moreover, powerful methods such as Forster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have shed light on the protein-protein interactions HIV-1 engages within the host to hijack the cellular machinery. Specific advancements in live cell imaging in combination with the use of multicolor viral particles have become indispensable to unravelling the dynamic nature of these virus-host interactions. In the current review, we outline novel imaging methods that have been used to study the HIV-1 lifecycle and highlight advancements in the cell culture models developed to enhance our understanding of the HIV-1 lifecycle.
Growing leaves do not expand at a constant rate but exhibit pronounced diel growth rhythms. However, the mechanisms giving rise to distinct diel growth dynamics in different species are still largely unknown. As a first step towards identifying genes controlling rate and timing of leaf growth, we analysed the transcriptomes of rapidly expanding and fully expanded leaves of Populus deltoides Bartr. ex. Marsh at points of high and low expansion at night. Tissues with well defined temporal growth rates were harvested using an online growth-monitoring system based on a digital image sequence processing method developed for quantitative mapping of dicot leaf growth. Unlike plants studied previously, leaf growth in P. deltoides was characterised by lack of a base-tip gradient across the lamina, and by maximal and minimal growth at dusk and dawn, respectively. Microarray analysis revealed that the nocturnal decline in growth coincided with a concerted down-regulation of ribosomal protein genes, indicating deceleration of cytoplasmic growth. In a subsequent time-course experiment, Northern blotting and real-time RT-PCR confirmed that the ribosomal protein gene RPL12 and a cell-cycle gene H2B were down-regulated after midnight following a decrease in cellular carbohydrate concentrations. Thus, we propose that the spatio-temporal growth pattern in leaves of P. deltoides primarily arises from cytoplasmic growth whose activity increases from afternoon to midnight and thereafter decreases in this species.
The tigrina (tig)-d.12 mutant of barley is impaired in the negative control limiting excess protochlorophyllide (Pchlide) accumulation in the dark. Upon illumination, Pchlide operates as photosensitizer and triggers singlet oxygen production and cell death. Here, we show that both Pchlide and singlet oxygen operate as signals that control gene expression and metabolite accumulation in tig-d.12 plants. In vivo labeling, Northern blotting, polysome profiling, and protein gel blot analyses revealed a selective suppression of synthesis of the small and large subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (RBCSs and RBCLs), the major light-harvesting chlorophyll a/b-binding protein of photosystem II (LHCB2), as well as other chlorophyll-binding proteins, in response to singlet oxygen. In part, these effects were caused by an arrest in translation initiation of photosynthetic transcripts at 80S cytoplasmic ribosomes. The observed changes in translation correlated with a decline in the phosphorylation level of ribosomal protein S6. At later stages, ribosome dissociation occurred. Together, our results identify translation as a major target of singlet oxygen-dependent growth control and cell death in higher plants.
Exogenous short biologically active peptides epitalon (Ala-Glu-Asp-Gly), bronchogen (Ala-Glu-Asp-Leu), and vilon (Lys-Glu) at concentrations 10(-7)-10(-9) M significantly influence growth, development, and differentiation of tobacco (Nicotiana tabacum) callus cultures. Epitalon and bronchogen, in particular, both increase growth of calluses and stimulate formation and growth of leaves in plant regenerants. Because the regulatory activity of the short peptides appears at low peptide concentrations, their action to some extent is like that of the activity of phytohormones, and it seems to have signaling character and epigenetic nature. The investigated peptides modulate in tobacco cells the expression of genes including genes responsible for tissue formation and cell differentiation. These peptides differently modulate expression of CLE family genes coding for known endogenous regulatory peptides, the KNOX1 genes (transcription factor genes) and GRF (growth regulatory factor) genes coding for respective DNA-binding proteins such as topoisomerases, nucleases, and others. Thus, at the level of transcription, plants have a system of short peptide regulation of formation of long-known peptide regulators of growth and development. The peptides studied here may be related to a new generation of plant growth regulators. They can be used in the experimental botany, plant molecular biology, biotechnology, and practical agronomy.
Background and Objectives: Early growth response-1 is a nuclear transcription factor implicated in regulating cell proliferation. Fibroblast growth factor-1 is the prototypic fibroblast growth factor involved in the proliferation and differentiation of various cell types. Expression of early growth response-1 induced by fibroblast growth factor-1 thus may be very important for cell growth, during both development and wound healing in oral tissue. However, little is known about the expression and kinetics of early growth response-1 in fibroblast growth factor-1-stimulated oral cells. The aim of this study was to investigate the effects of fibroblast growth factor-1 on the expression of early growth response-1 in human periodontal ligament cells. Material and Methods: Periodontal ligament cells were cultured in medium containing 1, 10 or 100 ng/mL of fibroblast growth factor-1 for 45 min or with 10 ng/mL of fibroblast growth factor-1 for 15, 30, 45, 60 or 120 min. The proliferation of periodontal ligament cells was evaluated by measuring 5-bromo-2'-deoxyuridine incorporation. The expression of early growth response-1 mRNA and protein, and the localization of early growth response-1 protein, were examined by western blotting, northern blotting and immunocytostaining. Results: 5-Bromo-2'-deoxyuridine incorporation correlated directly with increases in fibroblast growth factor-1 concentration, and 5-bromo-2'-deoxyuridine incorporation peaked 45 min after starting treatment. Early growth response-1 protein was expressed in response to a concentration of fibroblast growth factor-1 as low as 1 ng. Peak expression of early growth response-1 mRNA was observed at 15 min and that of early growth response-1 protein at 60 min. The 140-kDa early growth response-1 protein was not detected in the nuclear fraction, and the peak expression of the 80-kDa early growth response-1 protein occurred at 60 min. Early growth response-1 localized in or around the nucleus at 30 min. Conclusion: These results show that a concentration of fibroblast growth factor-1 as low as 1 ng induces the expression of early growth response-1 protein, and that the 80-kDa early growth response-1 protein functions in the nucleus of periodontal ligament cells treated with fibroblast growth factor-1.
The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (I-Kr), which is important for cardiac repolarization. Dysfunction of hERG causes long QT syndrome and sudden death, which occur in patients with cardiac ischemia. Cardiac ischemia is also associated with activation, up-regulation, and secretion of various proteolytic enzymes. Here, using whole-cell patch clamp and Western blotting analysis, we demonstrate that the hERG/I-Kr channel was selectively cleaved by the serine protease, proteinase K (PK). Using molecular biology techniques including making a chimeric channel between protease-sensitive hERG and insensitive human ether-a-go-go (hEAG), as well as application of the scorpion toxin BeKm-1, we identified that the S5-pore linker of hERG is the target domain for proteinase K cleavage. To investigate the physiological relevance of the unique susceptibility of hERG to proteases, we show that cardiac ischemia in a rabbit model was associated with a reduction in mature ERG expression and an increase in the expression of several proteases, including calpain. Using cell biology approaches, we found that calpain-1 was actively released into the extracellular milieu and cleaved hERG at the S5-pore linker. Using protease cleavage-predicting software and site-directed mutagenesis, we identified that calpain-1 cleaves hERG at position Gly-603 in the S5-pore linker of hERG. Clarification of protease-mediated damage of hERG extends our understanding of hERG regulation. Damage of hERG mediated by proteases such as calpain may contribute to ischemia-associated QT prolongation and sudden cardiac death.
Aim: To enhance survival and generation of definitive endoderm cells from human embryonic stem cells in a simple and reproducible system. Main methods: Definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced under a chemical-defined condition withdrawn insulin supplement and serum albumin. We dissected influence of "alternative growth factors", WNT3A, BMP4 and bFGF in activin A-driven differentiation by detection of DE-associated genes expression and cell viability. Expression of DE-associated SOX17 and FOXA2 genes was analyzed by real time reverse transcription polymerase chain reaction (RT-PCR) and Western blot assays. Quantitative evaluation of DE efficiency was performed by flow cytometry analysis of CXCR4-expressed cell population. Cell viability during DE differentiation was analyzed by an Annexin V/PI double staining test. Key findings: Supplementation with WNT3A, BMP4 or bFGF promoted DE generation in a dose- and time-dependent manner. Cell apoptosis elicited by activin A was significantly ameliorated by a cocktail with WNT3A, BMP4 and bFGF. This allowed for sustained cell viability without insulin-containing supplements, thereby indirectly improving the efficiency of DE generation. Therefore, the cocktail containing is optimal for efficient DE generation in the presence of activin A and an insulin/albumin-free condition. Significance: This optimal condition facilitates the balance between the productivity and the viability maintenance, and could be valuable for mass production of DE with minimal variation. (C) 2017 Elsevier Inc. All rights reserved.
Background. Hepatocyte nuclear factor-4 (HNF-4) plays a central role in the differentiation process of hepatic cells. We investigated the effects of an overexpression of HNF-4 on hepatic progenitor cells isolated from a fetal mouse liver and transplantation of the cells in a mouse model of liver fibrosis. Methods. Hepatic progenitor cells were isolated from the embryonic day 14.0 fetal mouse livers and were purified by magnetic cell sorting to remove the hematopoietic cells. We transfected adenovirus-mediated HNF-4 into the cells, and analyzed the expressions of the liver-specific functions using reverse-transcription polymerase chain reaction and Northern blotting. HNF-4-overexpressing hepatic progenitor cells were then injected into recipient mice, which were treated with dimethylnitrosamine and 30% partial hepatectomy. Results. After 5 days of culture, the cells located in the center of the aggregates were stained positive for albumin, but the peripheral cells for cytokeratin 19. Adenovirus-mediated HNF-4 gene transfer resulted in increases in the expressions of HNF-4, apolipoprotein (Apo)A1, ApoC3, and pregnane X receptor messenger RNA. The mice treated with HNF-4-transfected progenitor cells survived significantly longer than the control mice (P=0.004). The plasma levels of albumin, total cholesterol, and glucose were higher in the mice treated with cells transfected by HNF-4 than in the control mice. Conclusions. These findings demonstrate that adenovirus-mediated HNF-4 transfection induces the differentiation from hepatic progenitor cells to hepatic parenchymal cells in vitro. These cells may be useful as a source for cell transplantation in liver diseases.
Nutritional immunology, immunometabolism and identification of novel immunotherapeutic targets are areas of active investigation in parasitology. There is a well-documented crosstalk among immune cells and cells in metabolically active tissues that is important for homeostasis. The numbers and function of these cells are altered by obesity leading to inflammation. A variety of helminths spend some part of their life cycle in the gastrointestinal tract and even entirely enteral nematode infections exert beneficial effects on glucose and lipid metabolism. The foundation of this review is the ability of enteric nematode infections to improve obesity-induced type 2 diabetes and the metabolic syndrome, which are significant health issues in developed areas. It considers the impact of nutrition and specific nutritional deficiencies, which are occur in both undeveloped and developed areas, on the host's ability mount a protective immune response against parasitic nematodes. There are a number of proposed mechanisms by which parasitic nematodes can impact metabolism including effects gastrointestinal hormones, altering epithelial function and changing the number and/or phenotype of immune cells in metabolic tissues. Nematodes can also exert their beneficial effects through Th2 cytokines that activate the transcription factor STAT6, which upregulates genes that regulate glucose and lipid metabolism.
Pollination is composed of cell-cell communication and complicated signaling cascades that regulate pollen tube growth and guidance toward the ovules for double fertilization, and is critical for successful sexual reproduction. Exploring expression profiles of in vivo grown pollen tubes is important. Nevertheless, it is difficult to obtain accessible pollen tubes for profiling studies in most model plants. By taking advantage of the hollow styles of lily (Lilium longiflorum), in vivo pollen tubes harvested from pollinated styles which had been cut open were used here to study their protein and transcript profiles. Pollination quantitatively and qualitatively altered the total protein composition of elongating pollen tubes. cDNAs generated and amplified from total RNAs of 24 h in vivo grown and 12 h in vitro cultured pollen tubes were used for suppression subtractive hybridization analyses and preparation of home-made array chips. Microarray analyses conducted with different probe sets revealed 16 transcripts specifically present and/or enriched in in vivo pollen tubes. Reverse transcription-PCR (RT-PCR), in situ hybridization and Northern blotting were applied to validate their unique pollination-induced expression features. Interestingly, several transcripts were simultaneously detected on the stylar transmitting tract epidermis, where in vivo pollen tubes tightly adhered during pollination. Their deduced amino acid sequences showed that most of them encoded small proteins and could be classified into several families. Transient assay revealed filament-like structures decorated by these proteins and one probably localized in the generative cell. These small peptides might be critical for pollen tube growth during pollination, and further exploration of their biological functions and mechanisms of action are of great interest.
In this paper, we propose a new floor field Cellular Automaton (CA) model with considering the swapping behaviors of pedestrians. The neighboring pedestrians in opposite directions take swapping in a probability decided by the linear density of pedestrian flow. The swapping which happens simultaneously with the normal movement is introduced to eliminate the gridlock in low density region. Numerical results show that the fundamental diagram is in good agreement with the measured data. Then the model is applied to investigate the counterflow and four typical states such as free flow, lane, intermediate and congestion states are found. More attention is paid on the intermediate state which lane-formation and local congestions switch in an irregular manner. The swapping plays a vital role in reducing the gridlock. Furthermore, the influence of the corridor size and individual's eyesight on counterflow are discussed in detail. (C) 2017 Elsevier B.V. All rights reserved.
The development of methods for the detection of aflatoxin BI (AFB(1)) in foods is a very important practice for ensuring food quality and safety. Most tests of AFB(1) are still conducted with conventional methods (i.e. antibody-based ELISA tests, high performance liquid chromatography HPLC); however biosensor methods are being developed to date as screening tools for 'field analysis. Compared to immunology/ELISA-like tests or chromatography methods, biosensors are able to provide rapid, sensitive, robust and cost effective quantitative methods for on-site testing. In this work we propose a cellular biosensor based on Vero cells, membrane engineered with anti-AFB1 antibody as the biological recognition element reacting with AFBi molecules on gold nanoparticle/screen printed electrodes (SPEs) (three electrode system). In order to culture the cells on the SPEs surfaces the working electrodes were coated with poly L-lysine to facilitate cell adhesion. The SPEs were connected to a potentiostat device through a transducer and chronoamperometric (CA) and cyclic voltammetric (CV) measurements were performed. Quantitative results obtained using the cellular biosensor method for AFB(1) were compared to those obtained using the HPLC method in pistachio samples spiked with AFB(1). The method displayed good sensitivity (r(2) = 0.87) and detection limit (0.5 ng/mL). (C) 2016 Elsevier Ltd. All rights reserved.
The adaptive growth of the uterus during pregnancy is a critical event that involves increased synthesis of extracellular matrix (ECM) proteins and dynamic remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since the myometrium at term is exposed to considerable mechanical stretching of the uterine wall by the growing fetus(es), the objective of the present study was to examine its role in the regulation of FN and ITGA5 expression at late gestation and during labor. Using myometrial tissues from unilaterally pregnant rats, we investigated the temporal changes in Itga5 gene expression in gravid and empty uterine horns by Northern blotting and real-time PCR, in combination with immunoblotting and immunofluorescence analyses of the temporal/spatial distributions of the FN and ITGA5 proteins. In addition, we studied the effects of early progesterone (M) withdrawal on Itga5 mRNA levels and ITGA5 protein detection. At all time-points examined, the Itga5 mRNA levels were increased in the gravid uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P < 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle layer, increased with gestational age in the circular muscle layer of the gravid horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid horn exhibited a continuous layer of variable thickness associated directly with the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during late pregnancy; and 2) facilitates force transduction during the contractions of labor by anchoring hypertrophied SMCs to the uterine ECM.
This paper analyses the changing conceptualisation of cellular differentiation during the twentieth century. This involved a move away from a view of this process as irreversible to an understanding of it as contingent. We examine the import of this shift for the transformation of stem cell biology, including the therapeutic promise attributed to this field, and how it came to challenge historical conceptions of both the cell and stem cell. We take as our starting point the 2012 Nobel Prize for Physiology and Medicine awarded jointly to John Gurdon and Shinya Yamanaka. In the view of the Nobel Committee, their work delineates a paradigm shift in the understanding of cellular differentiation, one that incorporates the concept of 'plasticity'. We explore the emergence, uses and meanings of this concept within this specific biological context, examining and emphasising its role as an epistemological tool. In this setting, 'plasticity' was introduced by cell biologist Helen Blau in the course of research undertaken in the 1980s into the genetics of cell differentiation. We argue that Blau's experimental and theoretical contributions were seminal to a reconceptualisation of this process and provide a crucial link between the work of Gurdon and Yamanaka. Overall, the paper highlights the contested process of conceptual change within the biomedical sciences. It also draws attention to the dynamic and reciprocal relationship between conceptual and technical change, exemplified here in the changing conceptions of cell differentiation following from the analysis of gene expression using new cell fusion and cloning techniques. More broadly, the paper also affords a window onto the shifting priorities, goals and values within late twentieth-century biomedical research.
Background and ObjectivePeriodontitis is an infectious disease in which the host immune and inflammatory responses play essential roles in resistance to bacterial infection, as well as the induction of tissue destruction if the immune response is dysregulated. The triggering receptor expressed on myeloid cells (TREMs) modulates inflammatory and innate immune signaling. TREM-1 is considered as an amplifier of the immune response, while TREM-2 is a negative regulator that has yet to be explored in periodontal disease before. We hypothesized that TREMs participated in the innate immune responses during the pathogenesis of periodontitis. Therefore, the aim of this study was to evaluate TREM-1 and TREM-2 expression in the gingival tissues from patients with chronic periodontitis and healthy subjects as well as their correlation with clinical periodontal parameters. This study is the first to identify TREM-2 in periodontal tissue, as well as the protein expression changes of TREM-1 and TREM-2 in periodontal tissues. Material and MethodsGingival tissue sections were collected from 31 healthy subjects and 53 patients with chronic periodontitis. Immunohistochemistry and quantitative real-time polymerase chain reaction were employed to evaluate the protein and mRNA expression of these receptors in gingival tissues. The recorded clinical parameters were probing depth, clinical attachment loss, plaque index and bleeding on probing. ResultsIn addition to myeloid cells in gingival connective tissues, TREM-1 and TREM-2 were also found expressed in gingival epithelial cells. In particular, TREM-1 was detected in almost all gingival epithelium from both healthy and inflamed biopsies. The expression levels of TREM-1 and TREM-2 were significantly increased in the periodontitis group compared to the healthy group. Increased levels of these receptors are to be positively correlated with site-specific periodontal parameters. ConclusionThe increased expression of TREM-1 and TREM-2 levels in periodontitis may confer diagnostic and potential therapeutic targets as well as indicating their association with the clinical severity of the disease.
We used PCR-based methods to clone and sequence four previously unidentified cellulase cDNAs: cbhI-I, cbhI-II, cbhII-I and egII. CbhI-I, cbhI-II and cbhII-I consist of 1710, 1610 and 1453 bp, respectively, and encode for 512, 458 and 442 amino acids, respectively. EgII consists of 1180bp encoding for 310 amino acids, and belongs to family 61 of the glycosyl hydrolases. CbhI-I, cbhII-I and egII all have a modular structure, with the catalytic domain (CD) and cellulose-binding domain (CBD) located at the C-terminus in cbhI-I and egII, and at the N-terminus in cbhII-I. CbhI-II shows high homology to cbhI-I but lacks a CBD. Northern blotting revealed that cbhI-I, cbhI-II and cbhII-I were coordinately expressed at various stages of the mushroom developmental cycle (substrate colonization to mature fruit body), although the number of cbhI-I transcripts was much smaller. No egII expression was detectable during the substrate colonization phase but transcription levels increased as fruit body morphogenesis progressed.
Background and ObjectivesAmelogenin proteins are the major constituent of developing extracellular enamel matrix and are believed to have an exclusively epithelial origin. Recent studies have suggested that amelogenins might induce the differentiation and maturation of various cells, including cementoblast lineage cells. However, the residues comprising the active site of amelogenin remain unclear. The purpose of this study was to identify the active site region of amelogenin by studying the effects of amelogenin fragments on the osteogenic differentiation of cementoblasts. Material and MethodsAmelogenin fragments lacking the C-terminus (rh163) and N-terminus (rh128) and a fragment consisting of the C-terminal region of rh174 (C11 peptide) were synthesized and purified. Human cementoblast lineage cells were cultured in osteogenic differentiation medium and treated with 0, 10, 100 or 1000 ng/mL of rh163, rh128 or C11 peptide. The mRNA levels of bone markers were examined by real-time polymerase chain reaction analysis. Alkaline phosphatase activity and calcium deposition were also determined. Mineralization was evaluated by alizarin red staining. ResultsThe osteogenic differentiation of human cementoblast lineage cells was significantly enhanced by treatment with rh128 or C11 peptide, whereas rh163 had no significant effect as compared with untreated controls. ConclusionsThe C-terminus of amelogenin promotes the osteogenic differentiation of human cementoblast lineage cells, indicating the possible utility of C11 peptide in periodontal tissue regeneration.
This paper assesses the feasibility of determining key household characteristics based on temporal load profiles of household electricity demand. It is known that household characteristics, behaviours and routines drive a number of features of household electricity loads in ways which are currently not fully understood. The roll out of domestic smart meters in the UK and elsewhere could enable better understanding through the collection of high temporal resolution electricity monitoring data at the household level. Such data affords tremendous potential to invert the established relationship between household characteristics and temporal load profiles. Rather than use household characteristics as a predictor of loads, observed electricity load profiles, or indicators based on them, could instead be used to impute household characteristics. These micro level imputed characteristics could then be aggregated at the small area level to produce 'census-like' small area indicators. This work briefly reviews the nature of current and future census taking in the UK before outlining the household characteristics that are to be found in the UK census and which are also known to influence electricity load profiles. It then presents descriptive analysis of a large scale smart meter-like dataset of half-hourly domestic electricity consumption before reviewing the correlation between household attributes and electricity load profiles. The paper then reports the results of multilevel model-based analysis of these relationships. The work concludes that a number of household characteristics of the kind to be found in UK census-derived small area statistics may be predicted from particular load profile indicators. A discussion of the steps required to test and validate this approach and the wider implications for census taking is also provided. (C) 2016 The Authors. Published by Elsevier Ltd.
The central carbon metabolism (glycolysis, the pentose phosphate pathway [PPP], and the tricarboxylic acid [TCA] cycle) plays an essential role in the supply of biosynthetic precursors and energy. How the central carbon metabolism changes with the varying growth rates in the in vitro cultivation of rapidly proliferating mammalian cells, such as cancer cells and continuous cell lines for recombinant protein production, remains elusive. Based on relationships between the growth rate and the activity of seven key enzymes from six cell clones, this work reports finding an important metabolic characteristic in rapidly proliferating glutamine synthetase-Chinese hamster ovary cells. The key enzymatic activity involved in the TCA cycle that is responsible for the supply of energy became elevated as the growth rate exhibited increases, while the activity of key enzymes in metabolic pathways (glycolysis and the PPP), responsible for the supply of biosynthetic precursors, tended to decreasesuggesting that rapidly proliferating cells still depended predominantly on the TCA cycle rather than on aerobic glycolysis for their energetic demands. Meanwhile, the growth-limiting resource was most likely biosynthetic substrates rather than energy provision. In addition, the multifaceted role of glucose-6-phosphate isomerase (PGI) was confirmed, based on a significant correlation between PGI activity and the percentage of G2/M-phase cells. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Ask any neuroscientist to name the most profound discoveries in the field in the past 60years, and at or near the top of the list will be a phenomenon or technique related to genes and their expression. Indeed, our understanding of genetics and gene regulation has ushered in whole new systems of knowledge and new empirical approaches, many of which could not have even been imagined prior to the molecular biology boon of recent decades. Neurochemistry, in the classic sense, intersects with these concepts in the manifestation of neuropeptides, obviously dependent upon the central dogma (the established rules by which DNA sequence is eventually converted into protein primary structure) not only for their conformation but also for their levels and locales of expression. But, expanding these considerations to non-peptide neurotransmitters illustrates how gene regulatory events impact neurochemistry in a much broader sense, extending beyond the neurochemicals that translate electrical signals into chemical ones in the synapse, to also include every aspect of neural development, structure, function, and pathology. From the beginning, the mutability - yet relative stability - of genes and their expression patterns were recognized as potential substrates for some of the most intriguing phenomena in neurobiology - those instances of plasticity required for learning and memory. Near-heretical speculation was offered in the idea that perhaps the very sequence of the genome was altered to encode memories. A fascinating component of the intervening progress includes evidence that the central dogma is not nearly as rigid and consistent as we once thought. And this mutability extends to the potential to manipulate that code for both experimental and clinical purposes.
Projection neurons play a key role in carrying long-distance information between spatially distant areas of the nervous system and in controlling motor circuits. Little is known about how projection neurons with distinct anatomical targets are organized, and few studies have addressed their spatial organization at the level of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric nervous system of the crab Cancer borealis, projection neurons convey sensory, motor, and modulatory information to several distinct anatomical regions. While the functions of descending projection neurons (dPNs) which control downstream motor circuits in the stomatogastric ganglion are well characterized, their anatomical distribution as well as that of neurons projecting to the labrum, brain, and thoracic ganglion have received less attention. Using cell membrane staining, we investigated the spatial distribution of CoG projection neurons in relation to all CoG neurons. Retrograde tracing revealed that somata associated with different axonal projection pathways were not completely spatially segregated, but had distinct preferences within the ganglion. Identified dPNs had diameters larger than 70% of CoG somata and were restricted to the most medial and anterior 25% of the ganglion. They were contained within a cluster of motor neurons projecting through the same nerve to innervate the labrum, indicating that soma position was independent of function and target area. Rather, our findings suggest that CoG neurons projecting to a variety of locations follow a generalized rule: for all nerve pathway origins, the soma cluster centroids in closest proximity are those whose axons project down that pathway.
There is evidence that both the centrality of a loss-event as well as reduced self-concept clarity are involved in emotional problems after the death of a loved one. One issue that is still unexplored is the relative importance of these two concepts in predicting bereavement outcome. The current study examined the degree to which both concepts contribute to emotional distress after loss, both concurrently and longitudinally. Data were available from 124 individuals, all bereaved within the previous half year, who completed measures of prolonged grief, posttraumatic stress, and depression at inclusion into the study and again 6 months later. Loss-centrality and self-unclarity were associated with all three outcome measures, in cross-sectional analyses. Longitudinal analyses indicated that loss-centrality predicted symptom levels of prolonged grief, self-unclarity predicted symptom levels of depression, and both loss-centrality and self-unclarity were associated with posttraumatic stress 6 months after baseline. Implications of these findings are discussed.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by multiple alterations in the TGF-beta signaling pathway. Yes-associated protein (YAP65) interacts with Smad7 thereby influencing TGF-beta signaling. In the present study, the expression of YAP65 in PDAC was analyzed in order to elucidate the potential role of this molecule in the pathogenesis of pancreatic cancer. YAP65 mRNA expression levels in human pancreatic tissue samples and cell lines were analyzed by Northern blotting and quantitative RT-PCR. Immunohistochemistry was carried out to localize and quantify YAP65 expression in relation to Smad7 expression and Smad4 mutations. The effects of TGF-beta 1 on Smad7 and YAP65 mRNA expression were analyzed by quantitative RT-PCR. Enhanced expression of YAP65 mRNA was identified by Northern blotting and quantitative RT-PCR in PDAC in comparison to the normal pancreas (2.5-fold increase) and to chronic pancreatitis (1.3-fold increase). In the normal pancreas, YAP65 was absent in acinar cells, large ducts and islet cells, but exhibited moderate to strong immunoreactivity in centro-acinar cells and ductules. Tubular complexes in CP and CP-like lesions in PDAC also exhibited strong staining. In contrast, weak to moderate YAP65 immunoreactivity was present in the cancer cells. There was no correlation between YAP65 immunostaining and Smad7 staining or Smad4 mutations in the cancer samples. TGF-beta 1 strongly induced Smad7 mRNA in Colo-357 and in Panc-1 cells, but only slightly induced YAP65 rnRNA in Colo-357 cells. In conclusion, YAP65 is expressed mainly in centroacinar and small ductal cells in the normal pancreas. In PDAC, YAP65 is present in tubular complexes and to a lesser extent in cancer cells. Together with the known function of YAP65 in different growth and differentiation regulating pathways, it is suggested that this gene plays a role in the normal and diseased pancreas.
The neural basis of autism spectrum disorder (ASD) is not yet understood. ASD is marked by social deficits and is strongly associated with cerebellar abnormalities. We studied the organization and cerebellar connectivity of the temporoparietal junction (TPJ), an area that plays a crucial role in social cognition. We applied localized independent component analysis to resting-state fMRI data from autistic and neurotypical adolescents to yield an unbiased parcellation of the bilateral TPJ into 11 independent components (ICs). A comparison between neurotypical and autistic adolescents showed that the organization of the TPJ was not significantly altered in ASD. Second, we used the time courses of the TPJ ICs as spatially unbiased "seeds" for a functional connectivity analysis applied to voxels within the cerebellum. We found that the cerebellum contained a fine-grained, lateralized map of the TPJ. The connectivity of the TPJ subdivisions with cerebellar zones showed one striking difference in ASD. The right dorsal TPJ showed markedly less connectivity with the left Crus II. Disturbed cerebellar input to this key region for cognition and multimodal integration may contribute to social deficits in ASD. The findings might also suggest that the right TPJ and/or left Crus II are potential targets for noninvasive brain stimulation therapies.
Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including "theory of mind" (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical "disconnection" could in part underlie autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging (fMRI) to investigate the potential RS connectivity changes between the cerebellar dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD pathophysiology. When comparing ASD patients to controls, we found decreased connectivity between the left DN and cerebral regions known to be components of the ToM network and the default mode network, implicated in specific aspects of mentalizing, social cognition processing, and higher order emotional processes. Further, a pattern of overconnectivity was also detected between the left DN and the supramodal cerebellar lobules associated with the default mode network. The presented RS-fMRI data provide evidence that functional connectivity (FC) between the dentate nucleus and the cerebral cortex is altered in ASD patients. This suggests that the dysfunction reported within the cerebral cortical network, typically related to social features of ASDs, may be at least partially related to an impaired interaction between cerebellum and key cortical social brain regions.
Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.
The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. The decreases of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion. Transcriptional profiling by microarray hybridization indicated that the Toll-like receptor and mitogen-activated protein kinase (MAPK) signaling pathways were upregulated during cerebral ischemia without reperfusion. In relation to the PPP, upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling pathway and was confirmed through real-time polymerase chain reaction. Immunoblotting showed a slight increase in HSP27 protein expression and a marked increase in HSP27 phosphorylation at serine 85 after 60-min and 120-min MCAO without reperfusion. Corresponding upregulation of glucose 6-phosphate dehydrogenase (G6PD) activity and an increase in the NADPH/NAD(+) ratio were also observed after 120-min MCAO. Furthermore, intracerebroventricular injection of ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently, G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be part of an endogenous antioxidant defense neuroprotection mechanism during the earliest stages of ischemia. These findings have important therapeutic implications for the treatment of stroke. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Objective Cerebral palsy (CP) is the most common cause of chronic disability that restricts participation in areas of occupations for children. The main aim of rehabilitation is enhancement of their clients for participation in occupations. The aim of this study was to overview of the factors influencing the participations of children with CP in Iran. Materials & Methods A systematic, evidence-based process (Duffy 2005) was used. For data gathering electronic databases including Google scholar and Iranian and foreigner famous journals in the fields of pediatrics, were used. The main key words for search were Activity of Daily Living (ADL),Instrumental Activity of Daily Living (IADL), play, leisure, work, rest/sleep, social participation, and education. All the papers of this study were about the factors influencing the participation of Iranian CP children during 2000-2016. Totally, 156 articles were found eligible as for Iranian CP children study, of which 100 articles were discarded. Because of repetitive and duplicability of some articles, 17 articles were removed as well. Results The most studies about Iranian CP children participations in life areas were in the ADL area of participation (N=12), and the lowest articles were in the area in the field of: Work (N=2), play (N=2), and sleep/rest (N=2). Most of the occupational therapists do not focus on the all life areas. Conclusion In Iran, many researchers do not pay attention to the participation of CP children. Many articles just paid attention to the sensory, motor or cognitive components of their clients.
Anatase (A) TiO2 is widely used as a support of the supported vanadium-based and non-vanadium-based catalysts for NH3-SCR reaction. However, there is lack of enough attention for brookite (B) and rutile (R) TiO2. Therefore, in the present work, we synthesize a series of TiO2-A, TiO2-B, and TiO2-R, and then used as supports to prepare CeO2/TiO2-A, CeO2/TiO2-B, and CeO2/TiO2-R catalysts with the purpose of clarifying the crystal form effect of TiO2 supports on the physicochemical properties and catalytic performance of these supported ceria-based catalysts for NH3-SCR reaction. Characterization results exhibit that H-2 consumption (responding to reduction property), acid amounts, surface Ce3+ content, surface adsorbed oxygen species, and catalytic performance of these supported ceria-based catalysts give the order of CeO2/TiO2-R>CeO2/TiO2-B >CeO2/TiO2-A, which is related to the interaction (i.e., Ce3+ Ti4+Ce4+Ti3+) between CeO2 and TiO2 (anatase, brookite, and rutile). Especially, CeO2/1102-R catalyst exhibits the optimal catalytic performance for NH3-SCR reaction among these supported ceria-based catalysts owing to the most excellent reduction property as well as the largest amounts of acid sites, surface Ce3+ content, and surface adsorbed oxygen species. (C) 2017 Elsevier B.V. All rights reserved.
Despite widespread applications of tetravalent cerium compounds in organic synthesis and catalysis, the coordination and organometallic chemistry of cerium(IV) complexes has not been well explored, due, in part, to the high oxidizing power of Ce(IV). Using chelating O-donor supporting ligands, stable tetravalent cerium complexes bearing various ligand functionalities have been isolated, thus making it possible to investigate the reaction chemistry of cerium(IV) complexes systematically. This review summarizes the recent developments of the coordination chemistry of cerium(IV) complexes bearing O-, N-, and C-donor ligands. Special attention will be directed to cerium(IV) complexes supported by a tripodal oxygen ligand. (C) 2016 Elsevier B.V. All rights reserved.
Objective: By primary cultivation of clinical specimens of human cervical cancer, the main and side population cells were isolated and their biological characteristics were analyzed. Methods: Clinical specimens of human cervical tissue were cultured to get the primary cells. After staining by Hoechst33342, flow cytometry was used for sorting to get the main and side population cells. Their molecular biology, morphology and tumorigenicity were compared with that of Hela cells. Results: The primary cervical cancer and side population cells were isolated successfully, and the two cells have obvious tumor cell morphology. CK17, CK19, P63 and beta 1-integrin and other related markers were expressed. Tumorigenicity of side population cells was significantly higher than the main group of cells. Distribution of the cytoskeleton and expression associated tumor markers were not affected before and after tumorigenesis of the two cells. Conclusion: Side population cells which were cultured and isolated from clinical specimens of human cervical cancer have the characteristics of tumor stem cell, which can be used for further study of targeted therapy for cervical cancer.
We aimed to explore the correlations between eukaryotic translation initiation factor 3, subunit A (eIF3a) polymorphisms and susceptibility to and chemoradiotherapy efficacy in cervical carcinoma. Between August 2007 and August 2011, 176 patients with cervical carcinoma were enrolled as the case group, and 180 healthy individuals were selected as the control group. elF3a Arg803Lys C >T genotypes were detected by hemi-nested polymerase chain reaction restriction fragment length polymorphism. All patients received chemoradiotherapy and were evaluated for efficacy. Compared with carriers of the CC genotype, carriers of the T genotype of the elF3a Arg803Lys C >T polymorphism had a higher risk of cervical carcinoma. The elF3a Arg803Lys C >T polymorphism was associated with tumor size, differentiation degree, Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (LNM). The overall response rate of the case group was 69.32% (122/176). The response rate of CC genotype carriers was higher compared to patients with the CM+TT genotypes. Binary-logistic regression analysis showed that tumor size, FIGO stage, LNM, and the e1F3a Arg803Lys C >T polymorphism were influencing factors for chemoradiotherapy efficacy. Univariate analysis revealed that age, e1F3a Arg803Lys C >T polymorphism, differentiation degree, FIGO stage, and LNM were prognostic factors of cervical carcinoma, and multivariate analysis showed that age >= 60 years, higher FIGO stage, and LNM, as well as the CT and TT genotypes of the elF3a Arg803Lys C >T polymorphism, were risk factors related to the prognosis of cervical carcinoma. The e1F3a Arg803Lys C >T polymorphism is connected with a higher susceptibility to cervical carcinoma and may affect chemoradiotherapy efficacy in and prognosis of cervical carcinoma. Copyright (C) 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.
It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix (p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls (p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical carcinogenesis and potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis.
Objective: To quantify cell free fetal DNA (cffDNA) with fetal specific epigenetic marker, hypermethylated RASSF1A, in maternal plasma of normal pregnant women from 20 weeks of gestation and to assess its relationship with maternal age, height, pre-pregnancy weight and body mass index (BMI). Methods: Hundred normal pregnant women within the gestational age of 21-40 weeks were randomly selected and grouped into five (n = 20). Group 1: 21-24, Group 2: 25-28, Group 3: 29-32, Group 4: 33-36 and Group 5: 37-40 weeks. Maternal plasma DNA was extracted, digested with methylation-sensitive restriction enzyme, BstUI and the fetal specific DNA (cffDNA) was quantified by Real-time polymerase chain reaction (qRT-PCR). Results: The mean hypermethylated RASSF1A concentrations in different gestational groups were Group 1: 30.1 +/- 14.9, Group 2: 52.6 +/- 22.18, Group 3: 93.2 +/- 19.08, Group 4: 172.8 +/- 26.81 and Group 5: 337.8 +/- 52.9 copies/ml. Pearson's correlation analysis showed highly significant positive correlation between cffDNA and gestational age (r = 0.899, p < 0.001). BMI was also found to be positively related to cffDNA (r = 0.217, p < 0.05). However, it did not show any correlation with maternal age, height and pre-pregnancy weight. Conclusions: The gestational age-dependent increase of hypermethylated RASSF1A; the fetal specific epigenetic marker in maternal plasma was demonstrated, in an Indian study group of normal pregnant women. Findings would form the basis of future studies involving pregnancy complications that would aid in the early diagnosis of placental pathologies with hypermethylated RASSF1A.
The current feedback instrumentation amplifier (CFIA) designed for EEG detection systems is presented. This CFIA includes two digitally programmable operational transconductance amplifiers (DPOTAs) and a current feedback operational amplifier (CFOA) where the digital control of DPOTA is done using 4-bit current division network (CDN). PSpice simulation results are carried out using 0.25 mu m IBM CMOS process under +/- 0.8V supply voltage. The CFIA reaches 126.6dB common mode rejection ratio (CMRR), consumes 695 mu W, and has 9.4777 mu V/root Hz input referred noise. The achieved gain is from 22.236dB to 45.386dB. These results make the CFIA suitable for the EEG detection systems.
In this work, the low-voltage current feedback operational amplifier (CFOA) with bulk-driven, quasi-floating-gate (QFG) transistor and bulk-driven-quasi-floating-gate (QFG) transistor techniques to operate under low supply voltage is proposed. The proposed circuits were design based on the voltage follower and current follower while the output stages are designed base on the voltage follower. The CFOA circuits are designed by using the 0.18 mu m CMOS technology and supply voltage operated 1 V. Simulation results shows output impedance of CFOA with bulk-driven, quasi-floating-gate (QFG) MOS transistor and bulk-driven-quasi-floating-gate (BD-QFG) MOS transistor are 55.72 Omega dB, 43.88 Omega dB, and 41.63 Omega dB, respectively. Finally, the proposed BD, QFG and BD-QFG MOS transistors techniques can used before the ultra-low voltage and low-power CFOA circuits.
Protein based therapeutics have started to dominate the pharmaceutical landscape primarily due to the high efficacy that they have demonstrated against complex diseases. Despite the significant success, issues with regards to safety, efficacy and quality of biotherapeutics have been a point of considerable debate and concern among the various stakeholders. The correlation between the glycoform profile and the safety and efficacy of a drug, in particular, has garnered significant attention of researchers worldwide. An escalated emphasis is presently given to develop an understanding of how the various process parameters as well molecular biology considerations contribute to glycan heterogeneity. This paper aims to review the major developments that have occurred in this area over the last decade. The impact of the various process parameters on glycan expression, methods for obtaining a pre-determined glycan levels/profiles of a protein therapeutic and developments in the area of real-time glycan monitoring and control are discussed. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1091-1102, 2016
Symptomatic chronic Chagas disease affects up to 40% of patients infected with Trypanosoma cruzi. The lack of reliable early markers of cure after therapy hinders disease management and clinical trials with new drugs. We performed a study with 18 months of follow-up to compare changes in immune parameters and T. cruzi-specific immune responses as surrogate markers of response to therapy between patients treated with benznidazole and untreated patients. This was a pilot, open-label, randomised clinical trial of treatment with benznidazole versus no treatment in patients with indeterminate chronic T. cruzi infection. In both groups we investigated changes in T-cell activation, T-cell subpopulations, regulatory T-cell counts, 16, and sCD14 levels, and T. cruzi-specific immune responses (Th1, Th2, and Th17 responses). Fourteen patients were included in the study (seven in each group). Median age was 35 years (F25-75 31-43), 57% were female, and 93% were Bolivian. Benznidazole was administered at 5 mg/kg/day for 60 days. Three patients discontinued benznidazole owing to adverse reactions and were not evaluated. At the end of the follow-up period, treated patients showed significantly less immune activation and lower regulatory T-cell counts, with an increased Th17 and Thl response. This randomised pilot clinical trial administering benznidazole to patients with indeterminate chronic Chagas disease brings about changes in the adaptive immunity, leading to a general decrease in inflammatory status. This apparently beneficial response could act as the basis for monitoring new antiparasitic drugs. (C) 2016 Elsevier B.V. All rights reserved.
The parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas disease, is widely distributed throughout the Americas, from the southern United States (US) to northern Argentina, and infects at least 6 million people in endemic areas. Much remains unknown about the dynamics of T. cruzi transmission among mammals and triatomine vectors in sylvatic and peridomestic eco-epidemiological cycles, as well as of the risk of transmission to humans in the US. Identification of T. cruzi DTUs among locally-acquired cases is necessary for enhancing our diagnostic and clinical prognostic capacities, as well as to understand parasite transmission cycles. Blood samples from a cohort of 15 confirmed locally-acquired Chagas disease patients from Texas were used for genotyping T. cruzi. Conventional PCR using primers specific for the minicircle variable region of the kinetoplastid DNA (kDNA) and the highly repetitive genomic satellite DNA (satDNA) confirmed the presence of T. cruzi in 12/15 patients. Genotyping was based on the amplification of the intergenic region of the miniexon gene of T. cruzi and sequencing. Sequences were analyzed by BLAST and phylogenetic analysis by Maximum Likelihood method allowed the identification of non-TcI DTUs infection in six patients, which corresponded to DTUs TcII, TcV or TcVI, but not to TcIII or TcIV. Two of these six patients were also infected with a TcI DTU, indicating mixed infections in those individuals. Electrocardiographic abnormalities were seen among patients with single non-TcI and mixed infections of non-TcI and TcI DTUs. Our results indicate a greater diversity of T. cruzi DTUs circulating among autochthonous human Chagas disease cases in the southern US, including for the first time DTUs from the TcII-TcV-TcVI group. Furthermore, the DTUs infecting human patients in the US are capable of causing Chagasic cardiac disease, highlighting the importance of parasite detection in the population. (C) 2017 Elsevier B.V. All rights reserved.
The flotation response of chalcopyrite and molybdenite when using a novel compound, acetic acid-[(h ydrazinylthioxomethypthiol-sodium (AHS), as the depressant was investigated through micro-flotation and batch flotation in this study. The depressing mechanisms were studied by means of zeta potential, MR and XPS measurements. The micro and bench flotation results indicated that AHS exhibited a strong influence on the depression of chalcopyrite and had little effect on the flotation of molybdenite minerals; these results might be attributed to the significant improvement of the molybdenite/chalcopyrite selectivity index after the addition of AHS. The results of the FTIR spectra, zeta potential and XPS measurements indicated that AHS chemisorbs onto the chalcopyrite surface through its S and N atoms, forming a five-membered cheat ring. A possible depressant mechanism along with a postulated adsorption mode for the surface interaction between AHS and chalcopyrite are provided. (C) 2017 Elsevier BN. All rights reserved.
In this, study, a type-2 fuzzy chance-constrained programming (TFCP) method is developed for supporting energy systems planning (ESP) under uncertainty. TFCP incorporates chance-constrained programming within a type-2 fuzzy programming framework to handle uncertainties (i.e. type-2 fuzzy sets and probabilistic distributions) in the objective and constraints, as well as to examine the reliability of satisfying (or risk of violating) system constraints. A TFCP-based energy system (TFCP-ES) model is then formulated for energy systems planning of Shanghai, where multi-energy resources, multi-processing technologies, multi-conversion technologies and multi-end users are considered. Solutions of energy supply, electricity generation, capacity expansion, and air-pollutant emission associated with different constraint-violation risks are obtained. Results reveal that (i) natural gas is one of the major energy-supply sources for the city in the future (increasing by 13.0%); (ii) the city's electricity-generation structure tends to the transition from coal-dominated into clean energy-dominated (e.g., natural gas, onshore wind, offshore wind, and photovoltaic power); (iii) the city's energy-supply security is enhanced by provoking the utilization of renewable energies (increasing by 1.0%). The results are helpful for managers to adjust the city's current energy structure, enhance the energy supply security, as well as make tradeoff between system cost and constraint-violation risk. (C) 2017 Elsevier Ltd. All rights reserved.
The sociological interpretation of reality and the processes occurring in it is determined by various approaches to understanding its nature. The diversity of these approaches is eventually reduced to its definition as a reality of the social world, which reflects, on the one hand, objectively existing phenomena and processes and, on the other hand, people's subjective perceptions about the objective reality. Social actuality as objective social reality exists beyond the subject of social cognition, i.e. objectively. Each new generation inherits from their parent generations a complex system of economic, social and political structures, institutions, organizations and t5he established relationships which form the social infrastructure of objective reality (social reality). But people perceive directly only the part of objective reality in which they have their own knowledge. Due to knowledge of its particular sphere or different objects of reality, people get its more or less adequate subjective perception. Therefore, the study of social reality focuses on the process of formation of subjective ideas about the objects of social actuality and attitudes to it, which is included in the subject area of sociology of knowledge. That is, from the standpoint of sociology of knowledge, the research object is not reality, but ideas about the reality. Based on subjective perceptions of reality, people construct their own reality. These perceptions change under the influence of various factors affecting the changes in social reality in the process of its formation. A significant change factor is the crisis which affects all spheres of the Russian society. The article analyzes the impact of the crisis on the changes in social reality in different population groups in Russia and the way it is reflected on people's attitudes to each other, to family, work and education. Based on analysis of data from nationwide studies it has been revealed that there is a contradiction between Russians' traditional attitudes to each other, family, work and education and the emerging modern attitudes. Amid crisis, this contradiction tends to exacerbate due to the impossibility of maintaining the traditional principles underlying the old way of life, which leads to uncertainty and formation of new forms of certainty through the change in life paradigm.
The multidirectional multiscroll chaotic attractors generated by second-generation current conveyor (CCII) are investigated. A fourth-order and a fifth-order grid multiscroll chaotic system are presented by designing staircase function and shifted voltage sign functions in the high-order Jerk system. Using the CCIIs, a chaotic circuit is designed and implemented, which can generate 4 x 2 x 2 x 2- and 4 x 2 x 2 x 2 x 2-scroll chaotic attractors, respectively, via switching control. Compared with the voltage operational-amplifier-based circuit, the proposed circuit has better performance in terms of circuit structure and bandwidth. Numerical simulations and experimental results are accordant.
As an important signal source, chaotic circuit can play key blocks of Codec in fields of weak signal detection and high speed security communication and non-linear control. First we review the chaotic circuit design methodology into three kinds of methods like blocks stickiness with 3-blocks, decreasing- or increasing-type, for root cause of period three implying chaos. Then two new chaotic circuits are designed and demonstrated in core features of 1L-1C plus 1 multiplier and 1 operational amplifier, and 2L-3C plus 1T-MOSFET. The phase diagrams and FFT spectrums of tested independent variables show that new circuits are chaotic with the greatest Lyapunov's Exponents more than zero. At last our conclusions throw up both the birth of Lee's circuits under logic steps and deep thinking of precision measurements based on chaos in voltage-or current-mode.
Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum that binds newly synthesized N-linked glycoproteins during their folding in the ER including MHC class I molecule. This manuscript reports the identification of two unique cDNA clones of calnexin in rainbow trout. Both encode putative mature proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide. Sequence analysis revealed that only one of the two cDNA clones encodes a putative ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved with mammalian homologs. Amino acid sequence alignment illustrated conservation of the calnexin luminal domain, which consists of a globular and a P domain, in both copies. Southern blotting revealed that there are at least two copies of the calnexin gene in the trout genome and northern blotting showed a wide tissue distribution of an estimated 3 kbp calnexin transcript with an additional minor transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in RTS11. Importantly, the smaller transcript was predominantly upregulated in RTS11 after a 24 h treatment with the calcium ionophore A23187. In western blots, calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a 100 kDa band was most prominently expressed. These results suggest that in salmonids there are two differentiated versions of the calnexin gene which encode proteins that may have diverged to perform unique biological functions. (C) 2013 Elsevier Ltd. All rights reserved.
Interspecific aggression between sibling species may enhance discrimination of competitors when recognition errors are costly, but proximate mechanisms mediating increased discriminative ability are unclear. We studied behavioral and neural mechanisms underlying responses to conspecific and heterospecific vocalizations in Alston's singing mouse (Scotinomys teguina), a species in which males sing to repel rivals. We performed playback experiments using males in allopatry and sympatry with a dominant heterospecific (Scotinomys xerampelinus) and examined song-evoked induction of egr-1 in the auditory system to examine how neural tuning modulates species-specific responses. Heterospecific songs elicited stronger neural responses in sympatry than in allopatry, despite eliciting less singing in sympatry. Our results refute the traditional neuroethological concept of a matched filter and instead suggest expansion of sensory sensitivity to mediate competitor recognition in sympatry.
Considering the importance of mother's support in the adaptation of a sexually abused child, it is relevant to determine if the mothers and children involved in an intergenerational cycle of child sexual victimization differ from dyads in which only the child has been abused. The purpose of this study was to compare mother-child dyads with sexually abused children according to whether the mother had herself been victim of child sexual abuse. The sample included 87 dyads with sexually abused children aged 3-18years old and their mothers (44 reporting maternal and child abuse), followed by social welfare services of the province of Quebec (Canada). The two groups of mothers were compared on their past family abuse experiences and past family relations, their mental health history, their current psychological distress, their parenting behaviors, and their current levels of family functioning. Children were compared on their adaptation. Multivariate analyses indicated that mothers reporting child sexual abuse were more likely to report more other maltreatments in their childhood and greater prevalence of lifetime history of alcohol abuse disorders, dysthymia, and panic disorder compared with mothers who had not experienced CSA. Compared to children whose mothers had not experienced CSA, those whose mothers had experienced CSA showed higher rates of problems behaviors and were more likely to report having been sexually abused by a trusted person. These results highlight the specific clinical needs for the assessment and treatment for sexually abused children whose mothers experienced child sexual abuse.
The measurement and analysis of low level vibrations and Acoustic Emissions in components, fabrications and structures, is often accomplished by the utilisation of multiple distributed piezoelectric sensors. The frequencies of interest usually commence in the upper audio range above 2 kHz, but are more typically ultrasonic frequencies (up to 1MHz). Such measurements are intrinsically limited in terms of their dynamic range due to the signal to noise ratio of the overall system (comprising the transducer and front end signal amplification, together with associated interconnection cables). This paper demonstrates that the latest bipolar operational amplifier technologies (rather than traditional FET technologies) can provide a better solution at higher frequencies in these ultra low noise systems, whilst still delivering the high gain bandwidth needed. This paper also presents a comparative noise analysis for the three principle operational amplifier circuit topologies commonly utilised for piezoelectric sensors: (single ended charge amplifiers, differential charge amplifiers and voltage mode amplifiers). The effects of transducer cables and system configuration are also considered from the noise perspective. The theoretical analysis has been verified by practical experiment.
This paper presents a standalone 5.6 nV/root Hz chopper op-amp that operates from a 2.1-5.5 V supply. Frequency compensation is achieved in a power-and area-efficient manner by using a current attenuator and a dummy differential output. As a result, the overall op-amp only consumes 1.4 mA supply current and 1.26 mm(2) die area. Up-modulated chopper ripple is suppressed by a local feedback technique, called auto correction feedback (ACFB). The charge injection of the input chopping switches can cause residual offset voltages, especially with the wider switches needed to reduce thermal noise. By employing an adaptive clock boosting technique with NMOS input switches, the amount of charge injection is minimized and kept constant as the input common-mode voltage changes. This results in a 0.5 mu V maximum offset and 0.015 mu V/degrees C maximum drift over the amplifier's entire rail-to-rail input common-mode range and from -40 degrees C to 125 degrees C. The design is implemented in a 0.35 mu m CMOS process augmented by 5 V CMOS transistors.
The aim of this research is to design a charge pump to improve current matching, wide range of output voltage, fast switching operation and reduce charge sharing in transistor. The design of charge pump is proposed and simulated in cadence virtuoso ADE and ADXL tools at 90nm CMOS technology. Current mismatching is analysed with Monte Carlo simulation and output variation is calculated on PVT. The designed charge pump achieves wide output voltage swing 0.5 similar to 1V, improve current mismatching approximate 0.5% and power dissipation of 320 mu W.
The paper deals with the design of a charge pump circuit after analyzing the current mismatch problem. Charge sharing problem is eliminated by using transistors. For enhancing the matching characteristics a cascode type current mirror circuit is used. This design provides a technique by which the value of I-UP and I-DN is matched in way that there is no time mismatch between the UP and DN signals. The proposed design has a added advantage of low power consumption. All simulations are done at 1.8v power supply.
A power and area efficient metal-oxide semiconductor field-effect transistor (MOSFET)-only 1.5-bit fully differential pipelined analog-to-digital converter (ADC) stage is proposed and designed in TSMC 0.18 mu m digital CMOS technology with supply voltage of 1.8 V. It is based on charge pump based technique to achieve the stage voltage gain of 2. Various capacitances are implemented by MOSCAPs (capacitance offered by the MOSFET), offering compatibility with cheaper digital complimentary metal-oxide semiconductor (CMOS) process in order to reduce the much required manufacturing cost. The proposed stage suffers from only linear gain error with full signal swing of 2 V peak-to-peak (p-p) differential. Using the proposed stage, un-calibrated signal-to-noise and distortion ratio (SNDR) and spurious-free dynamic range (SFDR) for 10-bit, 100 MS/s pipelined ADC are 40.11 and 40.86 dB, respectively, which can be further increased by using a simple digital calibration technique. Comparison between the proposed stage and conventional operational amplifier based stage shows insensitivity towards capacitor mismatch along with power savings and design simplicity.
A simple low-power and low-area metal-oxide-semiconductor field-effect transistor-only fully differential 1.5-bit pipelined analog-to-digital converter stage is proposed and designed in Taiwan Semiconductor Manufacturing Company 0.18m-technology using BSIM3v3 parameters with supply voltage of 1.8V in inexpensive digital complementary metal-oxide semiconductor (CMOS) technology. It is based on charge pump technique to achieve the desired voltage gain of 2, independent of capacitor mismatch and avoiding the need of power hungry operational amplifier-based architecture to reduce the power, Si area and cost. Various capacitances are implemented by metal-oxide semiconductor capacitors, offering compatibility with cheaper digital CMOS process in order to reduce the much required manufacturing cost.
To draw an accurate relationship between power dissipation and speed is a challenging problem in operational Amplifier with switch capacitance. However, transformation of current steer circuit into charge steer is an efficient technique to reduce power dissipation even at higher speed. In this paper, an efficient model is proposed to estimate the 1st and 2nd stage operational Amplifier's power dissipation and delay, which can further used to design higher order Operational Amplifier, Voltage controlled Oscillator, Analog to Digital converters and other efficient power CMOS circuits. Analysis of 1st and 2nd stage Amplifier with BSIM4 model for CMOS in Tanner environment is done. The result shows that the power dissipation is reduced approximately 63% for 1st stage and 53: 5% for 2nd stage Amplifier using charge steering technique at 90nm.
A differential-hybrid charge sensitive preamplifier (CSP) was designed by taking a monolithic dual N-Channel Junction Field-effect Transistor (JFET) and a high-speed, low-noise, operational amplifier as the core parts. Input-stage of the circuit employs low-noise differential dual JFET, which ensures high input impedance and low noise. The differential dual transistor makes the quiescent point of the first-stage differential output stable, which is convenient for connecting with the post stage high-speed operational amplifier. Broadband could be amplified by connecting to the double differential dual transistors through the folded cascode-bootstrap. The amplifying circuit which replaces the interstage and post stage discrete components of a traditional CSP with integrated operational amplifier is simpler and more reliable. It simplifies the design of the quiescent point, gives full play to advantages of releasing large open-loop gain, and improves charge-voltage conversion gain stability. Particularly, the charge-voltage conversion gain is larger under a smaller feedback capacitor, thus enabling to gain better signal-noise ratio. The designed CSP was tested, reporting 3.3 x10(13) V/C charge sensitivity, about 90 ns rise time of signals, 35:1 signal-noise ratio to gamma-rays of Cs-137 (662 keV) and a 0.023 fC/pF noise slope. Gamma-rays of Am-241 (59.5 keV) were measured by the BPX66 detector and the designed CSP under room temperature, providing 1.97% energy resolution.
In today's world power consumption is a burning issue. Research is going on to find out various new power efficient design techniques. Power dissipation could be reduced by transforming continuous-time current-steering circuits into discrete-time charge-steering circuits. Charge steering shows all potential to emerge as an effective technique to reduce power dissipation for high-speed circuits. This technique can be exploited in the design of both analog and semi-analog circuits such as an op-amp, latches and clock-data recovery (CDR) circuits. This paper discusses the design techniques of charge steering circuits like op-amp and latches. Both 1st stage and 2nd stage op-amp circuits and different type of latches in a single stage and cascade forms are designed. The power and performances of the charge steering circuits are also compared with conventional design techniques like current mode logic (CML) circuits to show the improvements. The results show that the op-amp power dissipation is reduced by approximately 87% with better gain. All circuits have been designed using UMC's 180 nm CMOS technology.
Objectives This study aimed to develop a performance assessment tool for the history-taking components of the medical evaluation of physical abuse in young children by (1) determining the consensus-based injury history and social components for documentation, (2) identifying preliminary performance standards, (3) assessing current level-specific performance using the created tools, and (4) evaluating reliability and validity of the created tools. Methods The Physical Abuse Assessment Tool (PHAAT) was developed in 2 steps: (1) a modified Delphi survey was used to identify the injury history and social components for documentation in a medical evaluation for physical abuse, and (2) level-specific (novice, competent, expert) practice standards (minimum passing scores) were created using the identified components via the Angoff method. To evaluate validity, reliability, and level-specific performance of the PHAAT, a chart review of 50 consecutive cases from each of the 3 levels was performed. Results Seventy-one child abuse pediatricians and 39 social workers participated in the modified Delphi survey, and 67 child abuse pediatricians and 27 social workers participated in the Angoff method. The resulting PHAAT included 2 checklists for use based on presence or absence of a history of an injurious event. One-way analysis of variance shows significant differences in performance based on team level (P < 0.001), indicating construct validity. Intrarater and interrater reliability evaluations showed strong (r(s) = 0.64-0.92) and moderate to strong (intraclass correlation coefficient = 0.81-0.98) correlations, respectively. Conclusions Initial evaluation suggests the PHAAT may be a reliable and valid practice assessment tool for the medical evaluation of physical abuse.
Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hepatitis B (CHB) patients contained both HBV nucleic acids and HBV proteins, and transferred HBV to hepatocytes in an active manner. Notably, HBV nucleic acids were detected in natural killer (NK) cells from both CHB patients and healthy donors after exposure to HBV-positive exosomes. Through real-time fluorescence microscopy and flow cytometry, 1,1'-dioctadecyl-3,3,3', 3',-tetramethylindodicarbocyanine, 4-chlorobenzenesulfnate salt (DiD)-labeled exosomes were observed to interact with NK cells and to be taken up by NK cells, which was enhanced by transforming growth factor-beta treatment. Furthermore, HBV-positive exosomes impaired NK-cell functions, including interferon (IFN)-gamma production, cytolytic activity, NK-cell proliferation and survival, as well as the responsiveness of the cells to poly (I: C) stimulation. HBV infection suppressed the expression of pattern-recognition receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells, resulting in the dampening of the nuclear factor kappa B (NF-kappa B) and p38 mitogen-activated protein kinase pathways. Our results highlight a previously unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during CHB infection. Cellular & Molecular Immunology (2017) published online 30 May 2016
Objectives: To develop and provide validity evidence for a performance checklist to evaluate the child abuse screening behaviors of prehospital providers. Methods: Checklist Development: We developed the first iteration of the checklist after review of the relevant literature and on the basis of the authors' clinical experience. Next, a panel of six content experts participated in three rounds of Delphi review to reach consensus on the final checklist items. Checklist Validation: Twenty-eight emergency medical services (EMS) providers (16 EMT-Basics, 12 EMT-Paramedics) participated in a standardized simulated case of physical child abuse to an infant followed by one-on-one semi-structured qualitative interviews. Three reviewers scored the videotaped performance using the final checklist. Light's kappa and Cronbach's alpha were calculated to assess inter-rater reliability (IRR) and internal consistency, respectively. The correlation of successful child abuse screening with checklist task completion and with participant characteristics were compared using Pearson's chi squared test to gather evidence for construct validity. Results: The Delphi review process resulted in a final checklist that included 24 items classified with trichotomous scoring (done, not done, or not applicable). The overall IRR of the three raters was 0.70 using Light's kappa, indicating substantial agreement. Internal consistency of the checklist was low, with an overall Cronbach's alpha of 0.61. Of 28 participants, only 14 (50%) successfully screened for child abuse in simulation. Participants who successfully screened for child abuse did not differ significantly from those who failed to screen in terms of training level, past experience with child abuse reporting, or self-reported confidence in detecting child abuse (all p >0.30). Of all 24 tasks, only the task of exposing the infant significantly correlated with successful detection of child abuse (p < 0.05). Conclusions: We developed a child abuse checklist that demonstrated strong content validity and substantial inter-rater reliability, but successful item completion did not correlate with other markers of provider experience. The validated instrument has important potential for training, continuing education, and research for prehospital providers at all levels of training.
The western blotting technique for transfer and detection of proteins, named following the discovery of southern and northern blotting for DNA-and RNA-blotting, respectively, has traditionally relied on the use of X-ray films to capture chemiluminescence. Recent advancements use super-cooled charge coupled devices (CCD) cameras to capture both chemiluminescence and fluorescence images, which exhibit a greater dynamic range compared to traditional X-ray film. Chemiluminescence detected by a CCD camera records photons and displays an image based on the amount of light generated as a result of a dynamic chemical reaction. Fluorescent detection with a CCD camera, on the other hand, is measured in a static state. Despite this advantage, researchers continue to widely use chemiluminescent detection methods due to the generally poor performance of fluorophores in the visible spectrum. Infrared imaging systems offer a solution to the dynamic reactions of chemiluminescence and the poor performance of fluorophores detected in the visible spectrum, by imaging fluorophores in the infrared spectrum. Infrared imaging is static, has a wide linear range, high sensitivity, and reduced autofluorescence and light scatter. A distinct advantage of infrared imaging is the ability to detect two target proteins simultaneously on the same blot which increases accuracy of quantification and comparison, while minimizing the need for stripping and reprobing. Here, we compare the methodology for chemiluminescent (UVP BioChemi) and infrared (UVP Odyssey) detection of salivary total and phosphorylated fetuin-A, a multifunctional protein associated with cardio-metabolic risk, and discuss the advantages and disadvantages of these methodologies.
Background. Although human stromal vascular fraction (SVF) has been regarded as an attractive stem cell source, its therapeutic mechanism in wound healing has not been fully elucidated. Aims. In this study, we investigated the molecular characteristics and therapeutic property of SVF for wound healing. Methods. Microarray data showed that SVF cells are enriched with a higher level of wound healing or epithelium development related genes and micro RNA. Results. Quantitative polymerase chain reaction (PCR) and reverse transcriptase PCR results revealed that the epithelialization growth factor, epidermal growth factor (EGF), chemokines, stromal cell derived factor (SDF-1 or CXCL12), neutrophil-activating protein-2 (NAP-2 or CXCL7), chemokine receptors (CXCR1, CCR2 and CCR3) and wound healing genes were up-regulated in SVF compared with those in adipose-derived mesenchymal stem cells (ASCs). An in vitro scratch wound closure experiment demonstrated that co-culture with SVF substantially accelerated the wound closure of fibroblasts. Wounds in nude mice were created by skin excisions followed by injections of SVF with Pluronic hydrogel. SVF implantation highly accelerated wound closure and increased cellularity and re-epithelialization. In addition, the transplanted SVF exhibited high engraftment rates in the wound area, suggesting direct benefits for cutaneous closure. Conclusions. Taken together, these data suggest that SVF possesses high therapeutic capability for wound healing via the secretion of epithelialization and chemotactic growth factors and enhanced engraftment properties.
Stromal derived factor-alpha (SDF-1-alpha) is a CXC chemokine which has been demonstrated as a recruitment factor for leukocytes to the site of inflammation, infection, injury and following stress. This chemokine has been shown to be expressed by liver cells and in liver diseases. Hence, the aim of this study was to examine the expression of SDF-1 by hepatocytes in responses to the stress Imposed during isolation by collagenase perfusion and under heat shock Stimulation. In this study hepatocytes (2-5 x 10(6)) were isolated from male Sprague Dawley rat liver and Cultured in plates that were pre-coated with collagen Type-I matrix. The western and northern blotting analysis were employed to detect SDF-1 at protein and mRNA levels in isolated and cultured hepatocytes in response to isolation and heat shock stresses. The SDF-1 is expressed by isolated rat hepatocytes immediately after isolation and early culture and decreased with time. SDF-1 protein was highly expressed in freshly isolated cells and decreased by time (27h) (P<0.05). mRNA was also expressed in freshly isolated cells (0h) but decreased after 24h of culture (P<0.01). This results also demonstrated that expression of SDF-1 by hepatocytes was increased in response to heat shock at different time points comparing with control (P<0.01). These results demonstrated that the isolation and heat shock stresses induced the expression of SDF-1 in hepatocytes in a time-dependent manner. Accordingly, it seems that hepatocytes mimic the experiences that fiver experience after injury in vivo and therefore, produce stress related agents like chemokines to overcome such a injurious condition.
Background and ObjectivePeriodontal disease pathogenesis is comprised of the complex inflammatory immune response to oral bacterial dysbiosis. Like other inflammatory diseases, there is sexual dimorphism evident in periodontal diseases. During periodontitis, inflammatory chemokines direct neutrophils to migrate to the site of infection to neutralize the pathogen. Interestingly, these same chemokines are also involved in regulating pathogen-induced osteoclast formation. Previous reports show differences in bone turnover and lymphocyte recruitment between sexes. We hypothesize that chemokine expression is differentially regulated by sex and thus results in differential osteoclast formation. Material and MethodsMale and female mice were utilized to isolate neutrophils based on expression of Ly6G-specific, as well as defined osteoclast progenitors. Cells were stimulated with lipopolysaccharide (LPS; 100 ng/mL) then analyzed for neutrophil infiltration and gene expression. Defined osteoclast progenitors were primed: macrophage-colony stimulating factor (25 ng/mL), receptor activator of NF-B ligand (50 ng/mL), then stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression analysis via quantitative polymerase chain reaction. ResultsIn response to LPS, male neutrophils in vitro respond with increased chemokine expression and significantly more osteoclast formed in response to LPS compared to females. ConclusionsFindings support observations in humans regarding a sexual dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong inflammatory response to bacterial infection, resulting in increased inflammatory microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-driven bone loss in response to differential expression of key chemokines.
Thiocyanate is a C1 compound containing carbon, nitrogen, and sulfur. It is a (by) product in a number of natural and industrial processes. Because thiocyanate is toxic to many organisms, including humans, its removal from industrial waste streams is an important problem. Although a number of bacteria can use thiocyanate as a nitrogen source, only a few can use it as an electron donor. There are two distinct pathways to use thiocyanate: (i) the "carbonyl sulfide pathway," which has been extensively studied, and (ii) the " cyanate pathway," whose key enzyme, thiocyanate dehydrogenase, was recently purified and studied. Three species of Thioalkalivibrio, a group of haloalkaliphilic sulfur-oxidizing bacteria isolated from soda lakes, have been described as thiocyanate oxidizers: (i) Thioalkalivibrio paradoxus ("cyanatepathway"), (ii) Thioalkalivibrio thiocyanoxidans (" cyanate pathway") and (iii) Thioalkalivibrio thiocyanodenitrificans (" carbonyl sulfide pathway"). In this study we provide a comparative genome analysis of these described thiocyanate oxidizers, with genomes ranging in size from 2.5 to 3.8 million base pairs. While focusing on thiocyanate degradation, we also analyzed the differences in sulfur, carbon, and nitrogen metabolism. We found that the thiocyanate dehydrogenase gene is present in 10 different Thioalkalivibrio strains, in two distinct genomic contexts/genotypes. The first genotype is defined by having genes for flavocytochrome c sulfide dehydrogenase upstream from the thiocyanate dehydrogenase operon (present in two strains including the type strain of Tv. paradoxus), whereas in the second genotype these genes are located downstream, together with two additional genes of unknown function (present in eight strains, including the type strains of Tv. thiocyanoxidans). Additionally, we found differences in the presence/absence of genes for various sulfur oxidation pathways, such as sulfide: quinone oxidoreductase, dissimilatory sulfite reductase, and sulfite dehydrogenase. One strain (Tv. thiocyanodenitrificans) lacks genes encoding a carbon concentrating mechanism and none of the investigated genomes were shown to contain known bicarbonate transporters. This study gives insight into the genomic variation of thiocyanate oxidizing bacteria and may lead to improvements in the application of these organisms in the bioremediation of industrial waste streams.
Neuropathy target esterase (NTE) was proposed as the initial target during the process of organophosphate-induced delayed neuropathy (OPIDN) in human and some sensitive animals. Adult hens are usually the animal model for experimental studies of OPIDN. However, little is known about the sequence and characteristics of chicken NTE. We report here the cloning of the 5' and 3' cDNA ends of chicken NTE through rapid amplification of cDNA ends (RACE) and their expression profiles in different tissues with northern blotting. The cloned 3' cDNA end of chicken NTE is 801 base pair (bp) in length with an open reading frame (ORF) of 379 bp. It contains a termination codon (TAG) and a 422-nucleotide noncoding sequence with the polyA sequence (GenBank accession no. DQ126678). The chicken NTE 5'cDNA end is 665 bp in length with an ORF of 552 bp. It contains an iniation codon (ATG) and a 113-bp untranslated region (GenBank accession no. DQ 126677). The deduced proteins from 5' and 3'cDNA ends have a high degree of homology to humans and mouse NTE at the amino acid level. Chicken NTE is suggested to be a transmembrane protein by the transmembrane helix prediction of the deduced N-terminal sequence. The chicken NTE gene is expressed as a 4.5 kb transcript in different tissues, including brain, kidney, liver and testis. Moreover, the mRNA expression of chicken NTE is highest in brain, and the mRNA levels of chicken NTE in testis, kidney and liver are about 75%, 47% and 24% of that in brain, respectively. These results should be helpful in cloning chicken full-length NTE gene. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
MHM is a chicken Z chromosome-linked locus that is methylated and transcriptionally silent in male cells, but is hypomethylated and transcribed into a long non-coding RNA in female cells. MHM has been implicated in both localised dosage compensation and sex determination in the chicken embryo, but direct evidence is lacking. We investigated the potential role of MHM in chicken embryonic development, using expression analysis and retroviral-mediated mis-expression. At embryonic stages, MHM is only expressed in females. Northern blotting showed that both sense and antisense strands of the MHM locus are transcribed, with the sense strand being more abundant. Whole mount in situ hybridization confirmed that the sense RNA is present in developing female embryos, notably in gonads, limbs, heart, branchial arch and brain. Within these cells, the MHM RNA is localized to the nucleus. The antisense transcript is lowly expressed and has a cytoplasmic localization in cells. Mis-expression of MHM sense and antisense sequences results in overgrowth of tissues in which transcripts are predominantly expressed. This includes altered asymmetric ovarian development in females. In males, MHM mis-expression impairs gonadal expression of the testis gene. DMRT1. Both MHM sense and antisense mis-expression cause brain abnormalities, while MHM sense causes an increase in male-biased embryo mortality. These results indicate that MHM has a role in chicken normal embryonic development, including gonadal sex differentiation. (C) 2012 Elsevier Inc. All rights reserved.
Interferon-inducible transmembrane protein (IFITM) family proteins are antivirus factors. In the present study, we examined the expression pattern of chicken IFITM10 using quantitative reverse transcription-polymerase chain reaction. In adult chickens, IFITM10 levels were markedly lower than those of IFITM3, which exhibits antivirus activity. On the other hand, IFITM10 was expressed in levels similar to those of IFITM3 in embryonic organs. Primordial germ cells in 2.5-d embryos expressed high levels of IFITM10, which gradually decreased with time. The interferon- stimulation of embryonic fibroblast cells did not enhance the expression of IFITM10. The forced expression of IFITM10 slightly inhibited the infectivity of the VSV-G-pseudotyped lentiviral vector. Furthermore, cell fusion was inhibited by IFITM10 when HeLa cells transfected with the VSV-G expression vector were treated with low pH buffer. Although it remains unclear whether IFITM10 inhibits viral infections under physiological conditions, these results suggest that chicken IFITM10 exhibits antivirus activity.
Twenty chickpea accessions belonging to ten different countries of the world have been subjected to phylogeny and length variations from nuclear ribosomal DNA (nr DNA). ITS1-5.8S-ITS2 regions of Cicer accessions were used for amplification in two sets, each comprising a reverse and forward ITS primers. Lengths of ITS-1 of C. arietinum and C. reticulatum ranged from 340 to 350bp whereas that of ITS-2 from 400 to 410bp. In all the 20 accessions investigated, GC content in ITS-1 ranged from 40 to 55% and in ITS-2 from 42 to 55%. Sequencing of polymerase chain reaction product from ITS-1 showed variability in 278 and 290bp due to adenine and guanine nucleotide base pairs. BLAST search for ITS-1 region revealed highest homology (99%) with four strains of C. arietinum accessions. Whereas, ITS2 showed 100% homology with C. arietinum and 99% homology with that of C. echinospermum.
In the late 1920s the government of the Federal Territory of Quintana Roo introduced the cooperative system in the chicle industry, which was controlled by U.S. chewing-gum companies and its contratistas, intermediaries between the companies and the chicle producers. However, the project ended in failure, because of various factors, including the impact of the Great Depression, U.S. companies' boycott, the competition between chicle and other raw materials for chewing-gum, the corruption and inefficiencies in the government, or the discord between the local and federal governments.
Research examining child abuse and neglect (CAN) profiles among adult offender populations is lacking. Therefore, the primary aim of the present study was to address this limitation by using latent class analysis (LCA) to identify meaningful classes of individuals who have experienced physical abuse, emotional abuse, sexual abuse, as well as neglect. Another aim was to estimate the association between CAN class membership and external criteria (psychopathy factors, self-esteem, attitudes towards male sexual violence in dating relationships, child sexual abuse myth acceptance, violent offending, and age). Data were collected among a large systematically selected sample of adult male inmates (N=1261). Based on LCA, three unique classes of CAN were distinguished, including a 'low abuse' group (43.4% of the sample), a 'high physical and emotional abuse' group (51.3%), and a 'poly-victimized' group (5.3%). The analysis revealed that the CAN classes were differentially associated with affective responsiveness, cognitive responsiveness, personal self-esteem, prison self-esteem, attitudes towards male sexual violence in dating relationships, and violent offending. Findings highlight the unique nature of CAN constellations among criminal justice involved participants. The significance of the present results is discussed in relation to past and future research. Potential contributions to treatment strategies are also presented. (C) 2016 Elsevier Ltd. All rights reserved.
Across the United States, child abuse law is governed by state statute. Pediatricians must report suspected child abuse/neglect in accordance with their state's specific reporting requirements; failure to make a timely report creates civil liability exposures and triggers criminal penalties. The pediatrician's initial report may instigate further investigation by child protective services, and the reporting pediatrician may later become involved as a critical fact witness in ensuing legal proceedings, including criminal prosecutions, custody determinations, and medical malpractice controversies. The reporting pediatrician's testimony may influence the disposition of those matters and significantly affect the well-being of the involved children. As such, dutifully reporting pediatricians promulgate and engage in peerless child advocacy.
Research suggests that early care and education (ECE) services, particularly center-based ECE, may help prevent child maltreatment and also mitigate some of the negative developmental outcomes associated with child maltreatment. There is also preliminary evidence to suggest that ECE could reduce the likelihood that maltreatment allegations will be substantiated by child welfare authorities and/or result in children being placed in out-of home care. However, little is known about rates of ECE participation among children receiving child welfare services, nor the factors that determine ECE participation for this population. Data from the first wave of the National Survey of Child and Adolescent Wellbeing II, a nationally representative sample of children referred to the United States (U.S.) child welfare system (CWS) for suspected maltreatment, were used to measure the frequency with which 0-5 year olds participate in center-based ECE. Additionally, logistic regression analyses explored the effects of maltreatment type, substantiation, and children's living arrangements (Le., with parents, relatives, or foster parents) on this outcome, controlling for a range of child and family covariates associated with ECE participation in the general population. Results indicate that less than a third of 0-5 year olds receiving child welfare services in the U.S. are participating in center-based ECE. Among the various categories of maltreatment type measured, being reported to the CWS for suspected physical abuse was associated with decreased odds of center based ECE participation; however, other types of maltreatment, substantiation, and living arrangement were unrelated to center-based ECE participation. These findings suggest that, despite recent efforts by the U.S. federal government to promote ECE participation for CWS-supervised children, the vast majority of young children in the U.S. CWS are not receiving center-based ECE, and physically abused children are particularly disadvantaged when it comes to accessing these services. (C) 2016 Elsevier Ltd. All rights reserved.
Background and Aim: Child maltreatment, i.e. abuse and neglect, is a significant problem worldwide and can cause impaired physical and mental health throughout life. The true extent still remains unknown in all countries, including Turkey. The aim of this study was to apply the two versions of the International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool of ICAST-C and ICAST-P, which are used to assess child and parent feedback and to compare reports given by children and those given by parents. This is the first study of its kind conducted in Turkey. Methods: First, ICAST was translated into Turkish by bilingual experts. Students and their parents were asked to complete ICAST-C and ICAST-P respectively, with the help of trained researchers. In total, data from 2,608 matched reports (2,608 children and 2,608 parents) was obtained. Descriptive statistics were used to evaluate demographical variables, and chi-square tests were employed to investigate the statistical significance of comparisons. Results: The present study demonstrated that Turkish parents consider rebukes, insults and corporal punishment effective ways of disciplining children. According to parents' reports, the use of psychological abuse was most prevalent against boys aged 16, while the use of physical abuse was most prevalent against boys aged 13. A statistically significant relationship was found between parents' economic conditions and child abuse (p0.05). However, the relationship between paternal educational background and psychological abuse was observed to be significant (p < 0.05). A comparison of children's and parents' reports shows that parents tended to under-report child maltreatment. Conclusions: The results show that there is a significant healthcare problem in Turkey, since child maltreatment is prevalent, but parents are not generally aware of its extent. Possible approaches to changing this situation include efforts to increase education levels, promoting public awareness, and strengthening political commitments.
Most victims of child abuse have experienced more than one type of maltreatment, yet there is a lack of understanding of the impact of specific combinations of types of maltreatment. This study aimed to identify meaningful classes of maltreatment profiles and to associate them with short-term clinical outcomes. A total of 358 German children and adolescents aged 4-17 with a known history of child maltreatment were included in the study. Through interviews and questionnaires, information was obtained from participants and their primary caregivers on history of maltreatment, sociodemographics, psychopathology, level of psychosocial functioning, and health-related quality of life. Types of abuse were categorized into six major groups: sexual abuse in general, sexual abuse with penetration, physical abuse, emotional abuse, neglect, and exposure to domestic violence. A latent class analysis (LCA) was performed to determine distinct multi-type maltreatment profiles, which were then assessed for their associations with the sociodemographic and clinical outcome variables. The LCA revealed that participants could be categorized into three meaningful classes according to history of maltreatment: (1) experience of multiple types of maltreatment excluding sexual abuse (63.1%), (2) experience of multiple types of maltreatment including sexual abuse (26.5%), and (3) experience of predominantly sexual abuse (10.3%). Members of Class 2 showed significantly worse short-term outcomes on psychopathology, level of functioning, and quality of life compared to the other classes. Three distinct profiles of multiple types of maltreatment were empirically identified in this sample. Exposure to multiple types of abuse was associated with poorer outcomes. (C) 2016 Elsevier Ltd. All rights reserved.
Child maltreatment and other adverse childhood experiences adversely influence population health and socioeconomic outcomes. Knowledge of the risk factors for child maltreatment can be used to identify children at risk and may represent opportunities for prevention. We examined a range of possible child, parent and family risk factors for child maltreatment in a prospective 27-year population-based birth cohort of 2443 Australians. Physical abuse, sexual abuse, emotional abuse, neglect and witnessing of domestic violence were recorded retrospectively in early adulthood. Potential risk factors were collected prospectively during childhood or reported retrospectively. Associations were estimated using bivariate and multivariate logistic regressions and combined into cumulative risk scores. Higher levels of economic disadvantage, poor parental mental health and substance use, and social instability were strongly associated with increased risk of child maltreatment. Indicators of child health displayed mixed associations and infant temperament was uncorrelated to maltreatment. Some differences were observed across types of maltreatment but risk profiles were generally similar. In multivariate analyses, nine independent risk factors were identified, including some that are potentially modifiable: economic disadvantage and parental substance use problems. Risk of maltreatment increased exponentially with the number of risk factors experienced, with prevalence of maltreatment in the highest risk groups exceeding 80%. A cumulative risk score based on the independent risk factors allowed identification of individuals at very high risk of maltreatment, while a score that incorporated all significant risk and protective factors provided better identification of low-risk individuals. (C) 2016 Elsevier Ltd. All rights reserved.
Social support by family, friends and significant others is known to buffer the impact of adverse life events on children's well-being and functioning, however little is known about pathways explaining this association. We investigated whether maltreatment-related cognitions mediate the association between social support and posttraumatic stress symptoms (PTSS). Furthermore, age was introduced as moderator. We assessed the history of maltreatment in 200 maltreated children and adolescents (age 8-17 years) using a semi-structured interview. Participants' perceived current social support, maltreatment-related negative cognitions related to the subjectively "worst" experience of maltreatment and PTSS during the past month were assessed using self-report questionnaires. A set of mediation analyses demonstrated, that negative maltreatment-related appraisals mediated the relation between perceived social support and PTSS. The hypothesized negative associations of social support with PTSS and dysfunctional cognitions did not differ between children (8-11:11 years) and adolescents (12-17;11 years). Thus, the protective function of social support after maltreatment can be explained by fewer negative beliefs maltreated youth have about themselves and the world. These results provide support to models of social-cognitive processing and emphasize the importance of cognitive coping in regard to episodes of maltreatment which can be shaped within social interactions with non-abusive caregivers, friends, and significant others. (C) 2016 Elsevier Ltd. All rights reserved.
Child abuse and neglect occur in epidemic numbers in the United States and around the world, resulting in major physical and mental health consequences for abused children in the present and future. A vast amount of information is available on the signs and symptoms and short- and long-term consequences of abuse. A limited number of instruments have been empirically developed to screen for child abuse, with most focused on physical abuse in the context of the emergency department, which have been found to be minimally effective and lacking rigor. This literature review focuses on physical, sexual, and psychological abuse and neglect, occurring in one or multiple forms (polyabuse). A systematic, in-depth analysis of the literature was conducted. This literature review provides information for identifying children who have been abused and neglected but exposes the need for a comprehensive screening instrument or protocol that will capture all forms of child abuse and neglect. Screening needs to be succinct, user-friendly, and amenable for use with children at every point of care in the healthcare system.
Child abuse is a global public health problem and a serious social issue in Japan. Social support is beneficial for parents faced with childrearing challenges. The aim of this study was to clarify the association between social support and child abuse potential. A cross-sectional study was conducted using a structured questionnaire. The target population was mothers of children at nine public nursery schools. Bivariate and multiple linear regression analysis were performed to examine the effects of socio-demographic, social support and psychological distress factors on child abuse potential. Among 309 mothers, 29 (9.4%) had a high child abuse potential score. Bivariate analysis indicated that mothers with a higher child abuse potential score were more likely to be divorced or unmarried (P < 0.001); living in single-female-parent households (P < 0.001); have low perceived economic status (P < 0.001); have a low level of child care support (P = 0.01); have a low Multidimensional Scale of Perceived Social Support (MSPSS) score (P < 0.001); and/or a high General Health Questionnaire -12 score (GHQ -12) (P < 0.001). Important predictors of child abuse potential among the mothers surveyed included living in single-female-parent households, having low perceived economic status, low MSPSS score, and high GHQ -12 score. Improving approaches that help mothers build social support relationships and ease them into child rearing in a psychologically healthy condition is recommended to prevent child abuse. (C) 2016 Elsevier Ltd. All rights reserved.
The current study presents a preliminary evaluation of a Spanish adaptation of an implicit analog procedure, the Parent-child Aggression Acceptability Movie task (Spanish Parent-CAAM). Based on Social Information Processing theory, Spanish Parent-CAAM scores were expected to relate to self-reported PCA attitudes, negative child attributions, and child abuse risk in Spanish students; 245 undergraduates in Spain completed the Spanish Parent-CAAM along with self-report measures of PCA attitudes, negative children attributions, inclination to punish misbehavior, and child abuse risk. Findings indicate Spanish Parent-CAAM scores were significantly related to explicit measures of PCA, attributions of intentional child misbehavior, propensity to punish such misbehavior, and increased child abuse potential. Results are considered within the cultural context of Spain's corporal punishment ban and PCA attitudes.
The objective of this study was to investigate whether acute pain in abused children was under recognized by doctors and nurses compared to children evaluated for accidental injuries. We hypothesize that an abused child's reaction to physical pain could be an additional symptom of this challenging diagnosis. For the observational prospective case control study in an emergency department, children were eligible when: younger than six years old, the reported trauma occurred within the previous seven days, the trauma comprised a bone injury or burn, and the child was able to express his or her pain. The case group comprised children for whom the medical team reported their abuse suspicions and supporting information to a court, and whose cases Of abuse were subsequently confirmed. The control group consisted of children with a plausible cause for their injury and no obvious signs of abuse. The children were matched according to their age and type of trauma. The pain was assessed by doctors and nurses before analgesic administration using a certified pain scale. Among the 78 included children, pain was significantly less recognized in the abused children vs. the controls (relative risk = 0.63; 95% CI: 0.402-0.986; p=0.04). We observed a discrepancy between the nurses' and doctors' scores for the pain assessments (Kappa coefficient = 0.59, 95% CI: 0.40-0.77). Our results demonstrate that pain expression in abused children is under recognized by medical staff. They also suggest that abused children may have reduced pain expression after a traumatic event. Paying particular attention to the pain of abused children may also optimize the analgesic treatment. (C) 2017 Elsevier Ltd. All rights reserved.
This article compares multiple types of child maltreatment among Puerto Rican youth. We seek to expand the limited knowledge of the effects of multiple types of maltreatment on depressive symptoms in a specific Latino population as emerging studies indicate that children who are exposed to one type of maltreatment are often exposed to other types. This study examines the predictive strength of different and multiple types of lifetime child maltreatment (i.e., physical, sexual, and emotional abuse; and neglect), and the effect of youth support from parents, youth coping, youth self-esteem, and place of residence on depressive symptoms among Puerto Rican youth. Secondary data analyses were performed using three annual waves (2000-2004) of data from the Boricua Youth Study. The analytic sample consists of 1041 10-13 year old Puerto Rican youth living in New York and Puerto Rico. Results indicate that: (1) youth who experienced 'sexual abuse only', 'multiple maltreatment' (2 or more types of maltreatment), 'physical abuse only' have a significant increase in depressive symptoms (75.1%, 61.6%, and 40.5% respectively) compared to those without maltreatment; and (2) place of residence, exposure to violence, and mental disorders were significant risk factors. When developing psychosocial interventions, professionals should particularly focus on youth who report past lifetime experience with child maltreatment. Particular attention should be given to children living in the Bronx, New York and similar urban low-income areas who report past lifetime experience with multiple types of child maltreatment and who present symptoms or a diagnosis of co-occurring mental health problems. (C) 2016 Elsevier Ltd. All rights reserved.
Background: Smoking behavior and smoking cessation are complex. Interpersonal factors such as childhood adversity are associated with smoking, especially in women. Identifying how and in whom these individual factors contribute to smoking behavior may support individualized smoking cessation strategies. Attachment insecurity (attachment avoidance and attachment anxiety) involves biological and psychological processes in close relationships and is associated with both childhood adversity, and in select populations, smoking. This study aims to identify an association between attachment insecurity and smoking in adults and to determine if attachment insecurity is a plausible mediator between childhood adversity and smoking.Methods: In a cross-sectional survey, 348 primary care patients reported childhood adversity, attachment insecurity and smoking status. Statistical analyses were performed using regression and PRODCLIN.Results: Sixty-one percent of participants had experienced childhood adversity and 20% were current smokers. In women, attachment anxiety was associated with both childhood adversity (p=.002) and current smoking (p=.04). The PRODCLIN test indicated that attachment anxiety may be a mediator between childhood adversity and current smoking in women (95%CI 0.003, 0.236). In men, current smoking was not associated with childhood adversity (p=.673) or attachment anxiety (p=.29). Attachment avoidance was not related to current smoking in men (p=.31) or in women (p=.16).Conclusions: In women but not in men, attachment anxiety is associated with current smoking and may mediate the relationship between childhood adversity and current smoking. Childhood adversity and attachment anxiety may be factors to consider in the design of cessation strategies for women.
Research has begun to explore the relationship between cancer and child abuse. Thus far, work has shown that child abuse is associated with higher odds of cancer in adulthood. Unfortunately, the current research is plagued by three interrelated issues: (1) there is no agreement as to what actions constitute abuse and how abuse types (i.e., physical, sexual, and emotional abuse) are distinct or interrelated; (2) analytic strategies limit the types of conclusions that can be drawn because of how they treat or measure abuse and related concepts; and (3) few theories exist to explain the connection between abuse and cancer. Each of these issues and their implications is described. Then an integrated theoretical framework that attempts to address current shortcomings is proposed. Going forward, abuse research should carefully consider the measures and mechanisms linking abuse to disease in order to test meaningful hypotheses and advance our theoretical understanding of these connections.
Increasing research efforts are exploring the racial/ethnic composition of the population served by the U.S. child welfare system (CWS); however, only limited research has examined the unique experiences of CWS-involved Latino/Latina children and families, particularly those reported for child sexual abuse (CSA). This lack of research is troubling given that Latinos/Latinas are this country's largest and fastest growing minority group. To address this knowledge gap, this secondary data analysis uses data from the 2012 National Child Abuse and Neglect Data System Child File to examine a sample of children reported to the CWS (N = 2,401,304) and subsample of children involved in CSA reports (n = 179,199). Using descriptive and bivariate analyses, we describe a national profile of CWS-involved Latino/Latina children reported for CSA. This profile is developed based on the child characteristics of the analytic sample, rates of case substantiation, report sources, perpetrator characteristics, and caretaker risk factors. We then compare the profile of this subgroup of Latino/Latina children with the profiles of children who are non-Latino/Latina Black or non-Latino/Latina White. Results indicate several significant differences exist between the profiles of CWS-involved Latino/Latina children with a CSA report as compared with their counterparts in other racial/ethnic groups. Findings are discussed with the aim of informing practice, policy, and research on sexual abuse prevention and intervention strategies for Latino/Latina populations. (C) 2016 Elsevier Ltd. All rights reserved.
This study examined the patterns and correlates of the types of maltreatment experienced by adolescents aged 9-12, participating in an ongoing longitudinal study on the impact of neglect on children's development. Using case record abstraction, the study compared the child protection classification and findings from the case record abstraction with regard to the rates of four types of maltreatment (i.e. physical, sexual, emotional abuse and neglect) as well as co-occurrence across multiple types of maltreatment. Next, the study examined the frequently observed patterns of child maltreatment. Finally, the study investigated whether aspects of caretaker functioning and the detailed incident characteristics in the cases of neglect differed by the number of different types of maltreatment the children experienced. Results showed significant discrepancies between the Child Protective Service classification and case record abstraction. Child Protective Service classification considerably underestimated the rate of co-occurrence across multiple types of maltreatment. Neglect accompanied by physical and emotional abuse was the most common form. Some of the caretaker functioning variables distinguished the number of types of maltreatment. Based on the findings, future-research directions and practice implication were discussed.
OBJECTIVE. Physicians have an ethical and legal mandate to identify abused children so that they may be protected from further harm and are simultaneously required to think broadly and objectively about differential diagnoses. The medical literature is replete with examples of medical diseases that mimic abuse, potentially leading to misdiagnoses and subsequent harm to children and families. CONCLUSION. This review highlights some of the common and uncommon diseases that mimic physical and sexual abuse of children.
Responding to Ross E. Cheit's Witch-Hunt Narrative, this article is a commentary chronicling the emergence of child sexual abuse as a social issue in Los Angeles County in the 1980s. Based on the responses to child sexual abuse in Los Angeles County as experienced by one social worker during the McMartin years, it discusses the impact of the McMartin case on the identification and intervention in child sexual abuse cases and tracks the evolution and changes that took place in the 1980s and 1990s in Southern California. It offers some insight into a rationale for the denial of child sexual abuse which continues to this day.
Psychiatrists are mandated to report suspicions of child abuse in America. Potential for harm to children should be considered when one is treating parents who are at risk. Although it is the commonly held wisdom that mental illness itself is a major risk factor for child abuse, there are methodologic issues with studies purporting to demonstrate this. Rather, the risk from an individual parent must be considered. Substance abuse and personality disorder pose a separate risk than serious mental illness. Violence risk from mental illness is dynamic, rather than static. When severe mental illness is well-treated, the risk is decreased. However, these families are in need of social support.
Across the eight jurisdictions of Australia, mandatory reporting obligations and thresholds for reporting vary. Teachers are one group of the professionals who are mandated to report child maltreatment, yet some teachers are still reluctant to make such a report. This paper examines the barriers that discourage teachers from reporting child maltreatment and also whether teachers consider it necessary to question a child about the maltreatment before they decide if a report should be made. Thirty semi-structured interviews with Victorian primary school teachers were thematically analysed and revealed that inadequate and inconsistent mandatory reporting training, the need for certainty before initiating a report and the ambiguous concept of neglect were barriers to teachers identifying and reporting child maltreatment. Analyses further revealed that teachers gather evidence to confirm or disconfirm their suspicions of maltreatment by questioning the suspected child victim. The consequences of this practice are discussed along with recommendations to help overcome the barriers to making a formal report when child maltreatment is suspected.
Using administrative child welfare data from the Ontario Child Abuse and Neglect Data System (OCANDS), this study compared the profiles of Asian-Canadian and White-Canadian children and families that experienced a case closure after an investigation instead of being transferred to ongoing child protection services (CPS). Child protection investigations involving Asian-Canadian and White-Canadian children and families that were transferred to ongoing CPS presented a different profile of case characteristics and caregiver and child clinical needs. Asian-Canadian children and families received ongoing CPS for over a month longer than White-Canadian children and families and were less likely (odds ratio [OR] = 0.39) to be reinvestigated for any form of maltreatment-related concerns within 1 year after case closure. It appears that child protection investigations involving Asian-Canadian children and families are less likely to be closed prematurely than White-Canadian children and families, and the child protection system may be meeting the needs of Asian-Canadian communities. Alternatively, it is possible there is unaccounted biases that may be reflective of systemic problem of discriminative practices in the child protection system. Further research is needed to explore this phenomenon.
Introduction: Numerous data sources suggest a decline in child sexual abuse (CSA) in the United States since the early 1990s. Some evidence also indicates that an earlier period of higher CSA incidence began following World War II. This study examines prevalence estimates of sexual abuse reported retrospectively as having occurred in childhood (ChSA) in two nationally representative surveys of the Canadian population. Methods: Data are from 13 931 respondents aged 18 to 76 years from the 2004/2005 Canadian Gender, Alcohol, and Culture: An International Study (GENACIS), and from 22 169 household residents aged 18 years or older who participated in the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH). We present inter-and intrasurvey comparisons of ChSA prevalence specific to sex and age groups. Results: Findings from both surveys suggest a decline in CSA since 1993, consistent with declines observed in the United States. Results also suggest that 1946 to 1992 was a period of higher risk of CSA, relative to the period before 1946. The evidence was more robust for women. Conclusion: Evidence of a decline in CSA in Canada since the early 1990s is encouraging, given the long-term debilitating effects with which it is associated. Continued monitoring is critical. The long-term negative effects associated with CSA underscore the importance of continuing to move from lower risk to zero risk.
To develop a prediction model for the first recurrence of child maltreatment within the first year after the initial report, we carried out a historical cohort study using administrative data from 716 incident cases of child maltreatment (physical abuse, psychological abuse, or neglect) not receiving support services, reported between April 1, 1996 through March 31, 2011 to Shiga Central Child Guidance Center, Japan. In total, 23 items related to characteristics of the child, the maltreatment, the offender, household, and other related factors were selected as predictive variables and analyzed by multivariate logistic regression model for association with first recurrence of maltreatment. According to the stepwise selection procedure six factors were identified that include 9-13 year age of child (AOR =3.43/95%CI = 1.52-7.72), <40 year age of the offender (AOR= 1.65/95%CI = 1.09-2.51), offender's history of maltreatment during childhood (AOR = 2.56/95%Cl = 1.31-4.99), household financial instability or poverty (AOR= 1.64/95%Cl =1.10-2.45), absence of someone in the community who could watch over the child (AOR= 1.68/95%Cl = 1.16-2.44), and the organization as the referral source (AOR = 2.21/95%CI = 1.24-3.93). Using these six predictors, we generated a linear prediction model with a sensitivity and specificity of 45.2% and 82.4%, respectively. The model may be useful to assess the risk of further maltreatment and help the child and family welfare administrations to develop preventive strategies for recurrence. (C) 2016 The Author(s). Published by Elsevier Ltd.
Recognizing the clinical presentation of a child with abusive injuries is crucial. This review article gives an updated summary on inflicted intraoral, esophageal, and abdominal visceral injuries, including current recommendations on recognition, evaluation, screening value, and management of at risk children. Physical abuse should be suspected in precruising infants with intraoral injuries. When sexual abuse is suspected, referral to specialized centers equipped to conduct comprehensive examination and forensic testing by an experienced provider adhering to chain of evidence protocol is recommended. Abdominal trauma is the second most common cause of death in children who have been abused. The diagnosis and management of these injuries require careful consideration. Routine screening hepatic transaminases should be guided by the age of child and clinical scenario. A definitive confirmatory computed tomography scan of the abdomen and pelvis should be performed for those with transaminase levels more than 80 IU/L, or in all concerning cases with history and examination consistent with abusive abdominal trauma.
We examine associations between childhood sexual abuse (CSA) and substance abuse, the role of mental health indicators as mediators in these associations and whether or not associations differ by gender. Data are from 14,063 respondents aged 18-76 years from the 2004-2005 Canadian Gender, Alcohol, and Culture: An International Study (GENACIS). Multiple logistic regression models were used to examine associations between CSA and substance abuse variables, controlling for socio-demographic factors. Odds were adjusted by indicators of mental health to assess if these variables mediated associations between CSA and substance abuse. Tests of interactions between sex and CSA were conducted to see if gender differences exist in associations. In 2004/2005, CSA was reported by 14% of women and 5% of men. CSA was associated with heavy drinking, hazardous drinking, and the use of marijuana, other illicit drugs, and off-label drugs. Associations were only very marginally attenuated when controlling for depression and self-perceived emotional/mental health. In all cases previously observed significant associations persisted. Evidence of gender differences in associations between CSA and substance abuse was negligible. Preventing CSA may also reduce substance abuse. Crown Copyright (C) 2016 Published by Elsevier Ltd.
Background: In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program "Early Preventive Intervention and Child Protection" was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction. Methods: In a pre-post design, users are requested to complete questionnaires that assess three measures of expertise: theoretical knowledge of relevant fields, the ability to correctly identify subtle signals of infant communication, and the ability to assess maternal sensitivity. This article presents the contents of the program and the pre-training results (N = 1.294 participants). Descriptive analyses as well as Pearson correlations and Bonferroni corrections of error were conducted using the statistical program SPSS v. 21.0. Results: The findings show that a wide range of professionals are making use of the program, and that their existing theoretical knowledge about early preventive intervention, as well as their ability to identify subtle signals of infant communication, is relatively good. However, their ability to assess maternal sensitivity, which is considered a crucial indicator for the risk of child abuse, was low. Conclusions: The outcome of the pre-training results indicates that professionals working in the area of child protection need to develop more capability in recognizing maternal sensitivity, in order to ensure early detection of families who are at risk and thus in need of support. Finally, the number of years of professional experience did not correlate with the scores on any of the three measures, which emphasizes the importance of providing interdisciplinary training in this area for all those working in child and family services, regardless of background.
In high-conflict divorce cases, the emotional toll on the family unit is unquestionably destructive. While the physical and mental health of the children should be the primary focus, the emotional turmoil of a high-conflict divorce often moves the focus away from the children as parents struggle emotionally and financially. Although the best interests of the children are always in the judicial purview, the repeated, lengthy, and hostile litigation process often associated with high-conflict dissolution has lasting effects on the physical and mental health of children, similar to those associated with physical abuse and neglect. Child Protective Services (CPS) must step in and protect the emotional well-being of children during high-conflict divorce cases.
Interest in child maltreatment research has been growing in the last two decades. The main approach underlying this research has relied upon self and family reports. These methods may be problematic because they often require conscious awareness, generate socially desirable over accurate responses or can be biased by parents' unrealistic expectations, misattributions and perceptual errors. Simultaneously, research has been adapting methods from social cognition research in an attempt to access the implicit and spontaneous processes underlying the information processing related to parent-child interactions, exploring parental cognitions and emotions that may constitute important contributions to explain abusive and neglectful parenting. In this paper we review the research on child abuse and neglect using implicit measures. Using combinations of words related with child abuse and neglect, and with autonomic and affective variables assessed by the implicit measures, we have conducted a systematic review of 33 studies, and we examined the variables explored, the type of measures used and the results obtained. The research reviewed points out the importance of assessing parental representations in parent-child interactions and analyzing the differences between maltreating and non-maltreating parents. Specifically, physically abusive parents tend to show more difficulties in recognizing children's emotions, reveal more biases in their perceptions and attributions about children and behave more aggressively. Further research with maltreating parents, namely neglectful, using implicit measures is still required. (C) 2016 Elsevier Ltd. All rights reserved.
Parental maltreatment of children has been steadily increasing in Korea despite national efforts to curb it. Children and adolescents who experience maltreatment develop psychological and social maladjustment. Therefore, mediating variables alleviating the negative effects of parental maltreatment on child development should be investigated to develop effective intervention programs. We identified the direct effects of parental abuse and neglect on adolescents' school adjustment and the mediating effects of adolescents' self-esteem and peer attachment on the relationships between parental abuse and neglect and their school adjustment. We used data from 2351 middle school students who participated in the Korean Children and Youth Panel Survey. Structural equation modeling revealed the following: child neglect directly and negatively related with adolescents' school adjustment, whereas child abuse did not. Further, while adolescents' self-esteem and peer attachment mediated the relationship between child neglect and school adjustment, adolescents' self-esteem alone mediated the relationship between child abuse and school adjustment. These findings imply that there is a need to develop different intervention programs based on child maltreatment types. Finally, we suggested that the negative effects of parental neglect on adolescents' school adjustment could be alleviated by adolescents' self-esteem recovery resulting from peer support. On the other hand, in the case of adolescents experiencing parental abuse, self-esteem recovery through education and counseling provided by teachers or respected adults could be prioritized.
This study systematically reviews research on child maltreatment and risk of gambling problems in adulthood. It also reviews adult problem gamblers' risk of abusing or neglecting their own children. Multiple database searches were conducted using pre-defined search terms related to gambling and child abuse and neglect. We identified 601 unique references and excluded studies if they did not report original research, or did not specifically measure child maltreatment or gambling. Twelve studies that included multivariable analysis of childhood maltreatment exposure and problem gambling were identified. Six of seven studies examining childhood sexual abuse and four of five examining physical abuse showed a significant positive association between abuse and later gambling problems (odds ratios for sexual abuse 2.01-3.65; physical abuse 2.3-2.8). Both studies examining psychological maltreatment and two of three examining neglect identified positive associations with problem gambling. In most studies, risks were reduced or eliminated when controlling for other mental health disorders. The three studies measuring risk of child abuse and neglect among current problem gamblers suggest an increased risk for child physical abuse and medical conditions indicative of neglect although there is a considerable amount of variation among studies. Child abuse is associated with increased risk of gambling problems - gambling treatment providers should ask about maltreatment history as part of their clinical assessment. Problem gamblers may be more likely to physically abuse or neglect their children, but data here are more limited. Child welfare professionals should consider asking questions about parental gambling when assessing family risk. (C) 2016 Elsevier Ltd. All rights reserved.
Child maltreatment most often occurs within the family and is often an expression of the inability of parents to cope with the child's needs. Parental distress results in inadequate, conscious or unconscious but never accidental overreactions, resulting in severe physical and psychological sequelae. Furthermore, the individual and healthcare costs to society are extensive; therefore, early identification of children and adolescents at risk is of paramount importance and due to the position of trust in relationship to families, pediatricians play an important role. The recommended preventive medical check-ups are regular contacts, which provide the opportunity for early recognition of child maltreatment and implementation of measures to prevent further harm. Knowledge of risk factors, potential triggers and availability of community programs and resources to help affected families are indispensable prerequisites.
Despite wide recognition that increased social support is associated with positive parenting behaviors, there is limited understanding regarding the mechanisms through which the neighborhood context can increase or hinder social connections. In a sample of 1,050 parents in Franklin County, OH, this study examines the role of availability of social services in child maltreatment. Through negative binomial regression, the study finds that greater availability of social services is associated with lower levels of child abuse and neglect. Additionally, the availability of social services moderates the relationship between social support and child maltreatment, such that the relationship between social support and child maltreatment is weaker for parents in neighborhoods with greater availability of services. The findings suggest that increasing services and awareness of such services might be an opportunity for child maltreatment prevention.
Background: It is well established that childhood maltreatment (CM) is a risk factor for various mental and substance use disorders. To date, however, little research has focused on the possible long-term physical consequences of CM. Diabetes is a chronic disease, for which an association with CM has been postulated. Methods: Based on data from a sample of 21,878 men and women from the 2012 Canadian Community Health Survey - Mental Health (CCHS - MH), this study examines associations between three types of CM (childhood physical abuse (CPA), childhood sexual abuse (CSA), and childhood exposure to intimate partner violence (CEIPV)) and diabetes in adulthood. Multiple logistic regression models were used to examine associations between CM and diabetes controlling for the effects of socio-demographic characteristics and risk factors for type 2 diabetes. Results: When controlling socio-demographic characteristics, diabetes was significantly associated with reports of severe and frequent CPA (OR = 1.8) and severe and frequent CSA (OR = 2.2). A dose-response relationship was observed when co-occurrence of CSA and CPA was considered with the strongest association with diabetes being observed when both severe and frequent CSA and CPA were reported (OR = 2.6). Controlling for type 2 diabetes risk factors attenuated associations particularly for CPA. CEIPV was not significantly associated with having diabetes in adulthood. Conclusion: CPA and CSA are risk factors for diabetes. For the most part, associations between CPA and diabetes are mediated via risk factors for type 2 diabetes. Failure to consider severity and frequency of abuse may limit our understanding of the importance of CM as a risk factor for diabetes.
Adult victims of child physical abuse (CPA) are more likely to perpetrate intimate partner violence (IPV) than are nonvictims. However, not all CPA victims go on to become violent toward their partners, suggesting that other factors moderate risk for IPV perpetration. Drawing on the background-situational model (Riggs & O'Leary, 1989, 1996), this study examines the independent and interactive effects of CPA history and negative affect arising during conflict with an intimate partner in predicting physical IPV perpetration. Fifty-three heterosexual dating couples completed questionnaires assessing CPA history and perpetration of physical IPV. Couples discussed the largest source of conflict in their relationship for 10 min. Videos of these discussions were coded for negative affect. Using an actor partner interdependence model approach to account for the dyadic interdependence of the data, findings revealed that at average levels of negative affect, CPA severity predicted greater IPV perpetration for both men and women. However, at average levels of CPA, negative affect during conflict was positively predictive of IPV perpetration for men only. Findings further revealed an interaction such that for men, the positive association between CPA severity and IPV perpetration became stronger as their negative affect during conflict increased.
BackgroundThere have been no previous studies on the adequacy of combined evaluation of possible abusive head trauma cases by frontline medical personnel, hospital-based child protection teams, and child protective services in local districts of Japan. MethodsWe conducted a questionnaire survey of hospitalized patients under 24months old with a diagnosis of intracranial hemorrhage (ICH) from January 2011 to December 2013. Eleven large-scale general hospitals in Yokohama, Japan were surveyed, which provide centralized inpatient care to moderately-severely ill children. ResultsA total of 51 ICH patients were listed from eight hospitals. Median patient age was 7months, and 84% were younger than 12months. The most common diagnosis on computed tomography was subdural hematoma (n=26; 51%). Of a total of 51 cases, 31 (61%) occurred inside the home; the injury scene was unknown in six cases (12%). We reviewed these 37 cases from the viewpoint of evaluation with concern for suspected child abuse. Three out of 37 patients (8%) were not examined for inflicted skin lesions, and skeletal surveys and funduscopy were not conducted in 14 (38%) and 15 (41%), respectively. Thirteen out of 37 cases (35%) were not reported to hospital-based child protection teams and 22 (59%) were not reported to regional child protective services. ConclusionThe sociomedical evaluation of possible child abuse appears to be systematically inadequate in Yokohama.
Removing a child from parental care is an important and difficult decision to make. There are far reaching consequences for the child and family. Whilst there is a plethora of literature in relation to child protection practice generally, research on decision making is minimal. In this practice paper, I present 12 decision-making criteria to assist practitioners make decisions about child removal. It is important for child protection practitioners to apply the same set of principles and consider the same factors when making these decisions. These criteria are as follows: the severity of the abusive incident; the presence of cumulative harm; whether the perpetrator has access to the child; the functioning of the parent; whether the perpetrator has been responsible for child abuse or intimate partner violence in the past; the cooperation of the parent; the intent of the perpetrator; the age of the child; the functioning of the child; the voice and expressed wishes of the child; protective relationships available to the child and the statutory requirement to cause no further harm. Referring to these criteria will assist practitioners be clear and explicit about how they reach a decision, and result in greater consistency of outcome for children and families.
Children participating in research, like other children, may be being maltreated. There is also potential for exposure to abuse during research. Research training, practices and protocols to respond to disclosure and discovery of abuse to protect both researchers and children may not be sufficiently robust. Our aim was to compare and contrast research practices reported in the literature related to protecting children and to recommend safer ways to conduct research. The simultaneous increase in research with children, along with an increased willingness to listen to child victims of abuse, means that researchers must consider the protection of children in the research setting. Twenty-three papers were identified in a literature review. These studies reported a wide variation of ethical considerations, methods, methodology and came from different disciplines. From the 23 papers, two overarching themes were identified: social justice and research and safer research. To make research safer teams should consider training, safety protocols and support for child protection, which includes support to report safeguarding concerns to social care. Further work is required to ensure that training, protocols and support are effective in facilitating researchers to identify and make appropriate child abuse referrals. Ethics practices in abuse research need further debate.
The role of teachers in safeguarding the welfare of children is long acknowledged. However, recent research in Ireland found that the training provided to teachers on child protection issues was lacking (Buckley and McGarry, ). The frequent interactions that teachers have with children and their expertise in terms of typical child development place them in an ideal position for identifying possible signs of abuse. Yet despite this advantage, research indicates that schools fail to report a substantial proportion of suspected child abuse cases (Kenny, ). The oft-cited reasons for this may be conceptualised as: explicit reasons, such as a lack of knowledge about child abuse issues; and implicit reasons, such as the individual teacher's belief system about abuse. The current paper discusses implicit as well as explicit obstacles to teachers' engagement' with, and consequent barriers to their responding to, child protection issues. The current changes in initial teacher education and the introduction of mandatory reporting for professionals in Ireland, offer an opportune time to raise this issue and highlight the need for holistic education in child protection for teachers. Copyright (c) 2015 John Wiley & Sons, Ltd.
There is convincing evidence that many young people who are in the justice system have had contact with child protection services and that victims of childhood maltreatment are at increased risk of subsequent youth justice involvement. In Australia, however, there have been few longitudinal studies that have examined these associations and relatively less is known in this area. This study examines the overlap between the child protection and youth justice involvement in South Australia, and determines how substantiated maltreatment and variations in these experiences (e.g., the type, timing and recurrence of maltreatment) relate to criminal convictions as a youth. The results show that although the majority of child-protection involved youth do not become convicted offenders, the odds of subsequent convictions are significantly greater both for those with notifications and substantiated maltreatment and for those who had been placed in out-of-home care. Multivariate analyses revealed that the strongest predictors for receiving a conviction among maltreated youth were: male gender, Aboriginal and Torres Strait Islander ethnicity, experiences of physical abuse and emotional abuse, a greater number of substantiations (recurrence), experiencing maltreatment that commenced in childhood and continued into adolescence, and placement in out-of-home care. The mechanisms through which maltreatment might be linked with behavior are then considered, along with directions for future research in this area. (C) 2016 Elsevier Ltd. All rights reserved.
AimChildhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. MethodsThis study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. ResultsChildren exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. Conclusion CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.
A growing awareness of child sexual exploitation (CSE) in the United Kingdom and throughout the world has prompted human service and legal/policy professionals to seek ways of engaging young people experiencing sexual exploitation, although much remains unknown regarding effective practice, and whether or not current knowledge regarding best practices with young people can be expanded to address CSE. This paper considers how principles of harm reduction, a public health approach widely used to engage adults and young people in help-seeking behaviours, can be considered as part of a children's rights-centred approach to policy and practice with young people experiencing CSE. (C) 2015 The Authors. Children & Society published by National Children's Bureau and John Wiley & Sons Ltd.
While the link between educational attainment and future health and wellness is well understood, little investigation has considered the potential impacts of distinct forms of childhood maltreatment on high school completion. In the present study, the relationship between five categories of childhood maltreatment (physical, emotional, and sexual abuse, and physical and emotional neglect) and completion of high school education were examined using the Childhood Trauma Questionnaire (CTQ). From September 2005 to May 2013, data were collected for the At-Risk Youth Study (ARYS), a cohort of street-involved young people who use illicit drugs in Vancouver, Canada. We used logistic regression to examine the relationship between childhood maltreatment and high school completion, while controlling for a range of potential confounding variables. Specifically, five separate models for each category of maltreatment and two combined models were employed to examine the relative associations between, and cumulative impact of, different forms of childhood maltreatment and educational attainment. Among 974 young people, 737 (76%) reported not completing high school. In separate multivariable analyses physical abuse, emotional abuse, physical neglect, and emotional neglect remained positively and independently associated with an incomplete high school education. In a combined multivariable model with all forms of childhood maltreatment considered together, emotional abuse (adjusted odds ratio=2.08; 95% confidence interval: 1.51-2.86) was the only form of maltreatment that remained significantly associated with an incomplete high school education. The cumulative impact assessment indicated a moderate dose-dependent trend where the greater the number of different forms of childhood maltreatment the greater the risk of not completing a high school education. These findings point to the need for trauma-informed interventions to improve educational attainment among vulnerable young people, as well as evidence-based prevention programmes, such as the Nurse-Family Partnership, aimed at supporting at-risk families before maltreatment occurs.
Children often need help before their parents are ready to stop fighting. Children at the center of high-conflict disputes, particularly those who resist contact with a parent, face extraordinary risks of maladjustment. Years of investigation and litigation may precede any meaningful attempt at intervention, based on the questionable belief that all elements of causality (or blame) must be established before any effective treatment can occur. Children's functioning may continue to deteriorate during this time, undermining their future adjustment and reducing the chance of successful intervention later. We illustrate the application of the coping-focused, multisystemic Child Centered Conjoint Therapy model to assisting these families. Methods to assist children without compromising external investigations are discussed.
Among children visiting child and adolescent mental health care (CAM), the prevalence of exposure to family violence (FV) is reported to exceed prevalence in community samples, as are potentially traumatic interpersonal events (IPE) outside the family. The aim of the study was to relate CAM patients' self-reported experiences of violence exposure to their current psychiatric symptoms and to compare patients exposed to violence with patients who reported no exposure. We asked 305 consecutive 9- to 17-year-old patients in CAM about their current and previous exposure to violence in and outside of the family. Prevalence of exposure to any kind of violence was 67%. Reported exposures were 19% to IPE, 21% to FV, and 27% to both. Children exposed to both FV and IPE were more negatively affected by the events than children exposed to FV or IPE only. Children in the FV + IPE group reported more mental health symptoms than those in the no violence (33%) group. In general, IPE was related to the outcome measures only in combination with FV. Degree of violence exposure seemed to have a dose-response relationship with the diagnosis of post-traumatic stress disorder.
It is widely accepted that the classic metaphyseal lesion (CML) is a traumatic lesion, strongly associated with abuse in infants. Nevertheless, various non-traumatic origins for CMLs continue to be suggested in medical and legal settings. No studies to date systematically describe the association of CMLs with other traumatic injuries. The primary objective of this study is to examine the association of CMLs with other traumatic injuries in a large data set of children evaluated for physical abuse. This was a retrospectively planned secondary analysis of data from a prospective, observational study of children < 120 months of age who underwent evaluation by a child abuse physician. For this secondary analysis, we identified all children a parts per thousand currency sign12 months of age with an identified CML and determined the number and type of additional injuries identified. Descriptive analysis was used to report frequency of additional traumatic injuries. Among 2,890 subjects, 119 (4.1%) were identified as having a CML. Of these, 100 (84.0%) had at least one additional (non-CML) fracture. Thirty-three (27.7%) had traumatic brain injury. Nearly half (43.7%) of children had cutaneous injuries. Oropharyngeal injuries were found in 12 (10.1%) children. Abdominal/thoracic injuries were also found in 12 (10.1%) children. In all, 95.8% of children with a CML had at least one additional injury; one in four children had three or more categories of injury. CMLs identified in young children are strongly associated with traumatic injuries. Identification of a CML in a young child should prompt a thorough evaluation for physical abuse.
Missing a fracture in a child on skeletal surveys for suspected non-accidental trauma can have devastating results. Double-read has the potential to improve fracture detection. However the yield of double-read is unknown. To determine the advantage of double-read versus single-read of radiographic skeletal surveys for suspected non-accidental trauma. The study was performed in two phases. In the first phase (April 2013 to September 2013), double-read was performed for all skeletal surveys obtained during weekday working hours. Because we had no new double-read findings in studies initially read as negative, we conducted a second phase (January 2014 to March 2014). In the second phase we limited double-reads to skeletal surveys found positive on the first read. At the end of this period, we retrospectively performed double-read for all initially negative skeletal surveys. We excluded follow-up skeletal surveys. The difference in discrepancy (new fracture or false diagnosis of a fracture) ratio between negative and positive skeletal surveys was evaluated using the Fisher exact test, and change in discrepancy ratio between the first and second study phases was evaluated using the stratified Cochran-Mantel-Haenszel test. Overall in the two phases, 178 skeletal surveys were performed in 178 children (67 girls) with mean age of 9 months (range 3 days to 3.7 years). Double-read found 16 discrepancies in 8/178 (4.5%) skeletal surveys. Seven of these studies showed additional fractures (n=15). In one study, an initial read of a skull fracture was read as a variant on the second read. There was a significant (P=0.01) difference between rate of disagreement in negative skeletal surveys (1/104, 1.0%) and positive skeletal surveys (7/74, 9.5%). No significant change in disagreement rate was demonstrated between the two phases of the study (P=0.59). Double-read of skeletal survey for suspected non-accidental trauma found false-negative fractures in a few cases and rarely found false-positive diagnosis of a fracture. Double-read uncommonly found discrepancies in an initially normal skeletal survey. Limiting double-read to initially positive studies improves the yield of the double-read.
Aim: To assess plasma levels of cortisol and cytokines between cocaine-dependent women with and without childhood maltreatment (CM) history during cocaine detoxification treatment. Method: We assessed immunoendocrine and clinical parameters of 108 crack cocaine female users during 3 weeks of inpatient detoxification treatment, and 24 healthy women to obtain reference values. Women with (CM+, n = 53) or without (CM-, n = 55) CM history were identified answering the Childhood Trauma Questionnaire (CTQ). Blood samples and clinical assessment were collected before lunch during the first, second and third week post-treatment admission. Flow cytometry was used to assess TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6, IL-10, IL-17A plasma levels and ELISA assay was used to measure plasma cortisol levels. Results: At baseline, lower Th1 and Thl 7-related cytokines levels and higher Th2 cytokines levels were observed in crack cocaine users compared with reference values. Cytokines levels of cocaine dependents gradually became closer to reference values along detoxification treatment. However, when CM+ and CM groups were compared, increased levels of IL-6, IL-4 and TNF-alpha across time were observed in CM+ group only. Additionally, a Th1/Th2 immune imbalance was observed within CM+ group, which was negatively correlated with the severity of the crack withdrawal. Finally, loading trauma exposure severity, immunoendocrine and clinical parameters in factor analysis, we identified three clusters of observed variables during detoxification: (1) systemic immunity and trauma exposure, (2) pro-inflammatory immunity and (3) behavior Conclusion: Our results suggest the existence of an immunological phenotype variant associated with CM exposure during crack cocaine detoxification of women. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Commercial sexual exploitation of children (CSEC) is associated with child abuse, neglect, poverty, homelessness, and societal causes. Sex trafficking is the participation in commercial sex acts in which force, fraud, or coercion occur. This article discusses the scope of CSEC and sex trafficking, and the necessary identification skills and medical evaluations needed to help these patients.
The perceptions and judgments of social workers who interview the child and family are especially significant factors in child abuse assessment process. The current study describes and compares child protection workers' assessment processes in Korea and the USA through the use of case vignettes and in-depth interview. The responses from social workers in these two countries were compared and discussed in the areas of: risk assessment; perception of the main problems; tolerance of corporal punishment; and judgments about appropriateness of interventions. Most revealing was that Korean social workers determined abuse based on their child abuse definition and the US Army FAP social workers determined abuse based on their definition, which was affected by legal standards and cultural differences. Korean social workers are more likely to remove a child from the home, even in mild cases, but US FAP social workers would recommend child removal from the home as a last option. The social workers that participated in this survey play a vital role in the safety of children in child protective services. Both countries can benefit from sharing information to improve the child protection services delivered. Social workers' professional judgment leads to objective and consistent outcomes and are less likely to compromise child safety in the decision making process.
Primary prevention programs of pediatric abusive head trauma (PAHT) exist and early screening is proposed, but negative effects of mislabeling parents as abusers, an important issue, are not well documented. The aim of our study was to simulate the possible impact of programs for the primary prevention and screening of PAHT. We developed Markov models that simulate the life histories of PAHT with no intervention, with primary prevention program only, with screening program, and with both programs in a hypothetical cohort of 800,000 newborns in a high-income country. Screening program would be addressed to all families until children are 2 years old, during repeated consultations. Potential side effects for parents being mislabeled as abusers were supposed to increase the probability of PAHT and decrease participation in screening. Time horizon was 2 years with cycles of 15 days. Outcomes were number of deaths and abused children avoided. Uncertainty was specified with probability distributions. After 2 years, the median number of deaths avoided through primary prevention would vary from 6 (95% confidence interval [CI] 2-11) to 28 (95% CI 6-51) per 100,000 newborns. Screening could prevent up to 6 (95% CI 0-29) or cause up to 66 (95% CI 0-361) deaths per 100,000 children born alive. The impact of both programs was uncertain. Our model confirmed the potential benefits of primary prevention and documented the uncertainty associated with screening of PAHT.
The domestic violence against children (DVAC) interferes in the psychological development leading to sequels that manifest and persist up to the adulthood. The physical evidences of domestic violence are more easily observed in the orofacial complex, becoming eventually detected by dentists. The present systematic literature review aimed to investigate the perception, knowledge and attitude of dentists towards the detection and management of DVAC cases. A systematic search was performed in 6 data-bases: PubMed, ScienceDirect, LILACS, SciELO, GoogleScholar, and OpenGrey. Cross-sectional articles assessing the perception, knowledge, and attitude of dentists facing potential cases of DVAC were selected. No restriction of language, time, and publication status was considered. The search resulted in 1.024 articles, of which 18 fit the eligibility criteria. The knowledge for detecting cases of DVAC obtained during the undergraduation course was classified by the dentists (in 39% of the articles) as "insufficient". When suspecting of cases involving domestic violence, most of the dentists (in 77.75% of the articles) considered reporting to the competent authorities. However, the dentists are not sure about who these authorities are (in 31.25% of the articles). More attention must be given to the Forensic education in Dentistry. Specifically, proper training is necessary to support the dentists on the detection and management of pediatric patients under domestic violence. (C) 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
All paediatricians and health professionals working with young children need to be aware of the potential for child abuse to be a cause of physical injuries, such as fractures. Clinical experience, Serious Case Reviews and research show us that maltreatment should be kept in mind, in order for investigations to be carried out where appropriate and to prevent further harm. Whilst accidental fractures are common, fractures may also be the sentinel injury that alerts professionals to the possibility of child abuse, presenting clinically or detected as an occult injury on imaging for other reasons or when investigating a case of suspected maltreatment. The health professional evaluating a child with any fracture should be aware of features that raise the suspicion of abuse as a cause and be familiar with current recommendations for further investigations. This article outlines the current research concerning abusive fractures in children. It offers guidance on how to optimize radiological investigations and avoid common pitfalls in clinical practice.
Background: A psychosocial phenotype of interstitial cystitis/bladder pain syndrome (IC/BPS), a urogenital condition without known organic causes, was proposed. While psychosocial variables, including interpersonal maltreatment and negative affect, were studied in association with IC/BPS, the specificities of the relationships between childhood trauma by close others, psychiatric dysfunctions (negative affect and post-traumatic psychopathology), and urogenital symptoms have not been established. Methods: 94 IC/BPS patients were recruited together with 47 patients with acute cystitis who served as clinical controls. Standardized scales were used to assess various potentially traumatizing events in childhood and adulthood as well as psychiatric (dissociation and negative affect) and urogenital symptoms. Results: Among the potentially traumatizing events, those perpetrated by close others during childhood were found to be the most salient features discriminating the IC/BPS group from the control group. When divided into 2 subgroups according to their history of childhood trauma by close others, only IC/BPS patients with childhood trauma by close others had more dissociative and anxiety symptoms compared with the control group. These two subgroups did not differ in urogenital symptom severity. Conclusions: Childhood trauma by close others, rather than other types of interpersonal trauma, was a differentiating characteristic in IC/BPS patients, and a childhood trauma related psychosocial phenotype with a distinct clinical profile of dissociation and anxiety proneness was identified. Future studies should investigate whether a distinct set of pathogenic factors exists in IC/BPS patients with a history of childhood trauma by close others, even if this subgroup is not readily differentiated by urogenital symptoms. (C) 2016 Elsevier Inc. All rights reserved.
The introduction of the concept of child abuse has radically changed the mode of interaction between pediatricians and children, but also the practice of sanitary personnel in primary care centers, who are often the first to see victims of maltreatment. This study aims at illustrating the results of a questionnaire sent to family doctors, pediatricians and hospitals in Milan and surrounding areas. concerning child abuse. Among all the operators, 273 returned the questionnaires. The results show scarce knowledge on how to report to judicial authority in cases of child abuse (51.5%), mainly because of lack of basilar information concerning the manner of reporting. For what concerns specific training, almost half the subjects recruited for the study admitted not to have attended any congress or meeting concerning child maltreatment in the last three years. In the same time span, more than one third has not read any scientific articles concerning child abuse. In addition, 75.6% admit to not ever having attended any professional training course concerning child maltreatment. This study highlights the scarce knowledge on the behalf of pediatricians and general practitioners regarding how to deal with child abuse and the importance of proper training programs.
Background: Prehospital care providers are in a unique position to provide initial unadulterated information about the scene where a child is abusively injured or neglected. However, they receive minimal training with respect to detection of Child Abuse and Neglect (CAN) and make few reports of suspected CAN to child protective services. Aims: To explore barriers and facilitators to the recognition and reporting of CAN by prehospital care providers. Design/Methods: Twenty-eight prehospital care providers participated in a simulated case of infant abusive head trauma prior to participating in one-on-one semi-structured qualitative debriefs. Researchers independently coded transcripts from the debriefing and then collectively refined codes and created themes. Data collection and analysis continued past the point of thematic saturation. Results: Providers described 3 key tasks when caring for a patient thought to be maltreated: (1) Medically managing the patient, which included assessment of the patient's airway, breathing, and circulation and management of the chief complaint, followed by evaluation for CAN; (2) Evaluating the scene and family interactions for signs suggestive of CAN, which included gathering information on the presence of elicit substances and observing how the child behaves in the presence of caregivers; and (3) Creating a safety plan, which included, calling police for support, avoiding confrontation with the caregivers and sharing suspicion of CAN with hospital providers and child protective services. Reported barriers to recognizing CAN included discomfort with pediatric patients; uncertainty related to CAN (accepting parental story about alternative diagnosis and difficulty distinguishing between accidental and intentional injuries); a focus on the chief complaint; and limited opportunity for evaluation. Barriers to reporting included fear of being wrong; fear of caregiver reactions; and working in a fast-paced setting. In contrast, facilitators to reporting included understanding of the mandated reporter role; sharing thought processes with peers; and supervisor support. Conclusions: Prehospital care providers have a unique vantage point in detecting CAN, but limited resources and knowledge related to this topic. Focused education on recognition of signs of physical abuse; increased training on scene safety; real-time decision support; and increased follow-up related to cases of CAN may improve their detection of CAN.
Background: Children exposed to maltreatment show neural sensitivity to facial cues signalling threat. However, little is known about how maltreatment influences the processing of social threat cues more broadly, and whether atypical processing of social threat cues relates to psychiatric risk. Methods: Forty-one 10- to 14-year-old children underwent a social rejection-themed emotional Stroop task during functional magnetic resonance imaging: 21 children with a documented history of maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F). Groups were matched on age, pubertal status, gender, IQ, socioeconomic status, ethnicity and reading ability. Classic colour Stroop stimuli were also administered in the same paradigm to investigate potential differences in general cognitive control. Results: Compared with their peers, children who had experienced maltreatment showed reduced activation in the Rejection versus Neutral condition, across circuitry previously implicated in abuse-related posttraumatic stress disorder (PTSD), including the left anterior insula, extending into left ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior parietal cortex (STS); and bilateral visual association cortex, encompassing the cuneus and lingual gyrus. No group differences in neural or behavioural responses were found for the classic colour Stroop conditions. Significant negative associations between activity in bilateral cuneus and STS during the rejection-themed Stroop and higher self-reported PTSD symptomatology, including dissociation, were observed in children exposed to maltreatment. Conclusion: Our findings indicate a pattern of altered neural response to social rejection cues in maltreated children. Compared to their peers, these children displayed relative hypoactivation to rejection cues in regions previously associated with PTSD, potentially reflecting an avoidant coping response. It is suggested that such atypical processing of social threat may index latent vulnerability to future psychopathology in general and PTSD in particular.
IntroductionNo previous study has investigated the association between early trauma and suicidal behavior in Zonguldak. The aim of this study was to investigate the incidence of childhood abuse and neglect in the general population living in Zonguldak province and the relationship between childhood trauma and suicidal ideations and attempts. MethodsThe present study was carried out with 897 people in the general population, as assessed in a representative sample from Zonguldak province. The cluster sampling method was used. After obtaining written consent from the people who agreed to participate in the study, the Socio-demographic Information Form, Suicide Probability Scale, Childhood Trauma Questionnaire, Beck Depression Inventory, and Beck Anxiety Inventory were administered. ResultsThe lifetime prevalence of suicidal ideations was 18.3% among those who experienced at least one type of early trauma, and it was 9.6% among those without a history of childhood trauma (P<0.001). Only emotional abuse exhibited a significantly high odds ratio for lifetime suicidal ideations (odds ratio [OR]=3.168, 95% confidence interval [CI]=1.731-5.798) and attempts (OR=3.467, 95% CI=1.343-8.952). Emotional neglect showed a high odds ratio only for lifetime suicidal attempts (OR=3.282, 95% CI=1.287-8.371). There were significant correlations among the Beck Depression Inventory, Beck Anxiety Inventory, and Suicidal Probability Scale sub-scores and all six Childhood Trauma Questionnaire scores. DiscussionEmotional abuse and neglect in childhood are significantly associated with lifetime suicidal ideations and attempts in the general population living in Zonguldak province. Therefore, clinicians should be aware of the importance of the childhood trauma in the patients with suicidal ideations and attempts.
Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW;2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29-36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.
The present study aimed to examine professionals' experiences, perceptions, and knowledge regarding violence-exposed children in order to clarify the status and opportunities these children have in the Swedish legal system. A questionnaire was distributed to 63 professionals, representing police, prosecutors, social personnel, and treatment personnel. Findings revealed several problems that hindered effective work. Routines and guidelines were lacking and knowledge gaps regarding these children were found among all professions. Perceptions that children remember and tell were widely held, although conditions enabling sufficient reports are seldom met. Results can be used to guide necessary changes in national routines and guidelines to ensure recovery and maintaining of societal rights of this group of psychologically abused victims.
Child maltreatment can lead to acute and long-term consequences, and it is important that at-risk children are identified early. Child healthcare (CHC) nurses in Sweden are in a position to identify child maltreatment, as they follow children and their parents from the child's birth to school age. Therefore, the aim was to describe CHC nurses' experiences when encountering families in which child maltreatment was identified or suspected. Individual open interviews with eight CHC nurses were performed and analysed using a qualitative content analysis. Findings revealed that keeping the child in focus, while supporting the family was essential for the nurses. This family-centred approach was assumed to benefit the child's interests. Meeting families where child maltreatment was identified or suspected influenced the nurses, emotionally in different ways. Nevertheless, it was important to keep an open mind and communication build on honesty. Furthermore, the nurses requested professional supervision in order to help them learn from the situation ahead of the next time. This knowledge about CHC nurses' experiences may form a basis for the development of interventions that aim to support the CHC nurses in their professional role, and thereby improve support to children and parents in the future.
Over the last 3 decades, researchers have elucidated the cognitive and motivational conditions that affect the capacity and willingness of young alleged victims to describe their experiences to forensic interviewers. Applied researchers have also studied the contents and features of training programs designed to help interviewers take advantage of the research on developmentally appropriate interviewing. The latter studies have highlighted a knowledge transfer problem-scientists understand best-practice techniques well, many interviewers believe that they both understand and employ those practices, but widespread training has had a limited impact on the actual quality of interviews conducted in the field. There is now clear evidence that improvements in interviewing practice occur reliably only when training courses involve multiple modules, distributed over time, with repeated opportunities for interviewers to consolidate learning and to obtain feedback on the quality of the interviews they do conduct. Barriers to the implementation of such training are discussed.
Forensic medical evaluation rates for child abuse victims in Texas are low relative to national rates. In exploring reasons, researchers collected quantitative and qualitative interview and focus group data from multidisciplinary child abuse response team members across the state. This paper presents results of a secondary analysis of (N = 19) health care providers' interview and focus group transcripts, looking specifically at experiences with conducting forensic evaluations thoughts, struggles, and ethical issues. The analysis was conducted from a critical realist perspective using content and discourse analysis. A theme of ambivalence was identified and explored. Three discursive themes were identified: ambivalence about the legal role, the health care role, and about unintended outcomes of evaluations. Extra-discursive elements related to the physical body, resource distribution, and funding policy were examined for their interaction with discursive patterns. ImplicatiOns of findings include addressing issues in the current approach to responding to child abuse (e.g., uniting around common definitions of abuse; refining parameters for when FME is helpful; shoring up material resources for the abuse response infrastructure) and considering modification of providers' roles and activities relative to forensic work (e.g., deploying providers for prevention activities versus reactive activities). (C) 2017 Elsevier Ltd. All rights reserved.
The current article reports on perpetrator characteristics gathered in the first large-scale prevalence study on interpersonal violence against children in sport in the Netherlands and Belgium. Using retrospective web survey design, 4043 adults answered questions on their experiences in youth sport. The study looks at the number of perpetrators as well as individual descriptive characteristics (sex, age, and role in the sport organization) of perpetrators of psychological, physical and sexual violence as reported retrospectively by victim-respondents. This information was then clustered to provide an overview of the most common perpetrator profiles. Results show that in all types of interpersonal violence in sport, perpetrators are predominantly male peer athletes who frequently operate together in (impromptu) groups. Several differences between the three types of interpersonal violence are highlighted. While incidents of physical violence perpetrated by coaches tend to be less severe compared to those by other perpetrators, acts of sexual violence committed by a coach are significantly more severe. The presented findings shed new light on perpetrators of interpersonal violence in sport, nuancing the predominant belief that the male coach is the main perpetrator while providing nuanced information that can be utilized to improve prevention and child protection measures and other safeguarding initiatives in sport. (C) 2016 Elsevier Ltd. All rights reserved.
Little is known about the link between child abuse and health risk behaviors among Chinese college students. This cross-sectional study examined the prevalence of child abuse and its relations with individual and clusters of health risk behaviors among Chinese college students. A total of 507 students participated in this survey. The prevalence of child abuse from the highest to the lowest was emotional neglect (53.9%), physical neglect (49.0%), emotional abuse (21.8%), physical abuse (18.3%), and sexual abuse (18.1%), respectively. Males were more likely to report child abuse than females (p < 0.01). For males, emotional abuse was associated with internet addiction [OR = 2.28; 95%CI (1.00, 5.20)] and suicidal behavior [OR = 12.47, 95%CI (2.61, 59.54)]; while sexual abuse was associated with internet addiction [OR = 2.30, 95%CI (1.14, 4.66)]. For females, emotional abuse was significantly associated with increased risks for self-harm behavior [OR = 15.03, 95%CI (3.59, 63.07)] and suicidal behavior [OR = 5.16, 95%CI (1.63, 16.40)]. Physical abuse was related to risks for internet addiction [OR = 2.50, 95%CI (1.03, 6.04)] significantly. Two-step cluster analysis showed that participants in clusters with more health risk behaviors reported higher scores of child abuse. These findings suggest that child abuse was associated with both individual and clustering of health risk behaviors among Chinese college students.
Child Protective Services (CPS) identifies over 700,000 victims of child maltreatment in the United States annually. Research shows that risk factors for these children may persist despite CPS intervention. Mothers have unique and often untapped perspectives on the experiences and consequences of CPS intervention that may inform future practice. We explored these perspectives through interviews with 24 mothers after a first-time CPS finding of maltreatment not resulting in out-of-home placement. Male partners were primary perpetrators in 21 cases, with mothers or sitters identified as perpetrators in remaining cases. Data were analyzed using grounded theory. Mothers described risk factors or Roots of maltreatment prior to CPS involvement and reported variable experiences with Recognition of and Response to maltreatment. Divergent Outcomes emerged: I Feel Stronger and We're No Better. These findings provide an understanding of household experiences around child maltreatment that may support practice and policy changes to improve outcomes for vulnerable children.
Child abuse includes all forms of physical and emotional ill treatment, sexual abuse, neglect, and exploitation that results in actual or potential harm to the child's health, development, or dignity. In Taiwan, the Child Protection Medical Service Demonstration Center (CPMSDC) was established to protect children from abuse and neglect. We further analyzed and compared the trends and clinical characteristics of cases reported by CPMSDC to evaluate the function of CPMSDC in approaching child abuse and neglect in Taiwan. We prospectively recorded children with reported child abuse and neglect in a CPMSDC in a tertiary medical center from 2014 to 2015. Furthermore, we analyzed and compared age, gender, scene, identifying settings, time of visits, injury type, injury severity, hospital admission, hospitalization duration, and outcomes based on the different types of abuse and the different settings in which the abuse or neglect were identified. Of 361 child abuse cases (mean age 4.8 +/- 5.36 years), the incidence was highest in 1- to 6-year-old children (n=198, 54.85%). Physical abuse and neglect were predominant in males, while sexual abuse was predominant in females (P<0.001). Neglect was most common (n=279, 75.85%), followed by physical (n=56, 15.51%) and sexual abuse (n=26, 7.2%). The most common identifying setting was the emergency department (n=320, 88.64%), with neglect being most commonly reported. Head, neck, and facial injuries were more common in physically abused children than in neglected and sexual abused children (P<0.005), leading to longer hospitalization (P=0.042) and a higher Injury Severity Score (P=0.043). There were more skin injuries in neglect (P<0.001). The mortality rate was 2.49% (n=9). The CPMSDC could enhance the ability, alertness, and inclination of professionals to identify suspected cases of child abuse, and to increase the rate of registry. Cases of physical abuse had a higher Injury Severity Score, longer duration of hospitalization, and more injuries of head, face, and neck compared with other types of abuse. The reported rate of neglect was highly elevated after the CPMSDC established during the study period. Recognition of neglect is not easy, but the consequent injury, especially asphyxia, may lead to mortality.
Aim In the Netherlands, preventive child healthcare workers (PCHWs) have an important role in identifying signs of abuse, because they reach virtually all children. A closer cooperation of PCHWs and forensic physicians could improve the detection of child abuse. The aim of the study was to evaluate the use of forensic expertise by PCHWs. Subjects and methods In November 2013, a survey was distributed among PCHWs employed by the Amsterdam Public Health Service (n = 221). Results Forty-nine percent of PCHWs indicated suspicions of physical abuse during the last 6 months (response rate: 43 %). In all, 89 % rated the consultation of forensic physicians as useful. In a 1-year period, only three respondents sought advice from a forensic doctor. Conclusions Although PCHWs regularly have suspicions of physical child abuse and have a very positive attitude towards consulting a forensic physician, consultation rates are very low. More research is needed to understand barriers to consultation of forensic physicians.
Background: Childhood maltreatment is an important risk factor for mental and physical health problems. Adolescents living in residential youth care (RYC) have experienced a high rate of childhood maltreatment and are a high-risk group for psychiatric disorders. Quality of life (QoL) is a subjective, multidimensional concept that goes beyond medical diagnoses. There is a lack of research regarding the associations between childhood maltreatment and QoL. In the present study, we compare self-reported QoL between adolescents in RYC in Norway with and without maltreatment histories, and adolescents from the general population. We also study the impact of number of types of adversities on QoL. Methods: Adolescents aged 12-23 years living in RYC in Norway were invited to participate in the study; 400 participated, yielding a response rate of 67 %. Maltreatment histories were assessed through interviews with trained research assistants, and completed by 335 adolescents. Previous exposure to maltreatment was reported by 237 adolescents. The Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents (KINDL-R) was used. Nonexposed peers in RYC (n = 98) and a sample of adolescents from the general population (n = 1017) were used for comparison. General linear model analyses (ANCOVA) were conducted with five KINDL-R life domains as dependent variables. Linear regression was used to study the effect of number of types of adversities. Results: Exposed adolescents in RYC reported poorer QoL than peers in control groups. Compared with nonexposed peers in RYC, the 95 % confidence intervals for mean score differences on the KINDL-R subdomains (0-100 scale) were 1.9-11.4 (Physical Well-being), 2.2-11.1 (Emotional Well-being), -0.7-10.0 (Self-esteem), and 1.8-10.9 (Friends). Compared with the general population sample, the 95 % confidence intervals for mean score differences were 9.7-17.6 (Physical Well-being), 7.9-15.3 (Emotional Well-being), 3.6-12.5 (Self-esteem), and 5.3-12.8 (Friends). Number of types of adversities was associated with a poorer QoL score on all subdomains (Physical-and Emotional Well-being, Self-esteem, Friends, and School). Conclusions: Childhood maltreatment was associated with a poorer QoL score. We suggest the use of QoL and maltreatment measures for all children and adolescents in RYC.
Background: Childhood maltreatment is a potent predictor of poor mental health across the life span. We argue that there is a need to improve the understanding of the mechanisms that confer psychiatric vulnerability following maltreatment, if we are to progress from simply treating those with a manifest disorder, to developing effective preventative approaches that can help offset the likelihood that such disorders will emerge in the first place. Methods: We review extant functional neuroimaging studies of children and adolescents exposed to early neglect and/or maltreatment, including physical, sexual and emotional abuse across four neurocognitive domains: threat processing, reward processing, emotion regulation and executive control. Findings are discussed in the context of 'latent vulnerability', where alterations in neurocognitive function are considered to carry adaptive value in early adverse caregiving environments but confer long-term risk. Results: Studies on threat processing indicate heightened as well as depressed neural responsiveness in maltreated samples, particularly in the amygdala, thought to reflect threat hypervigilance and avoidance respectively. Studies on reward processing generally report blunted neural response to anticipation and receipt of rewards, particularly in the striatum, patterns associated with depressive symptomatology. Studies on emotion regulation report increased activation of the anterior cingulate cortex (ACC) during active emotion regulation, possibly reflecting greater effortful processing. Finally, studies of executive control report increased dorsal ACC activity during error monitoring and inhibition. Conclusions: An emerging body of work indicates that altered neurocognitive functioning following maltreatment: (a) is evident even in the absence of overt psychopathology; (b) is consistent with perturbations seen in individuals presenting with psychiatric disorder; (c) can predict future psychiatric symptomatology. These findings suggest that maltreatment leads to neurocognitive alterations that embed latent vulnerability to psychiatric disorder, establishing a compelling case for identifying those children at most risk and developing mechanistically informed models of preventative intervention. Such interventions should aim to offset the likelihood of any future psychiatric disorder.
Child abuse refers to the actions or non-actions which, mediated or immediately, affect the physical or psychic integrity of an infant, and negatively influence his normal physical, emotional and social development. Neglect represents the willful failure of either parent or tutor to assure to the child access to a healthcare system, thus jeopardizing his growth and evolution. In the field of pediatric dentistry, both abuse and neglect ultimately lead to complex dento-facial disabilities, with long-term consequences. The pediatric dentist is expected to establish complex professional medical relations, based on clearly-defined deontological principles, continuously targeting child superior interest. In this way, the dental practitioner may identify quite various situations which, according to the fundamental principle of a medical good action, require the involvement, in the medical relation, of a third responsible person. Accordingly, child's superior interest will represent a priority, granting all his rights to life and health, as well as - if such be the case his special protection. When potentially or really dangerous situations for child security and well-being are to be faced, the medical staff is obliged to announce the specialized structures of child assistance and protection; in such cases, the secondary principles on professional medical confidentiality and interdiction of making public the professional medical secret should be left aside. Such type of intervention in the physician-patient relation is characterized by both risks and advantages, most of them derived from the promptness with which the general and even forceful methods for protection of children in a civilized community are to be applied.
Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR SS genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions.
Background: Child abuse is often unrecognized at out-of-hours primary care (OOH-PC) services. The aim of our study was to evaluate the clinical outcome of the screening instrument SPUTOVAMO-R2 for child abuse (checklist), followed by a structured approach (reporting code), at OOH-PC services. The reporting code with five steps should ensure consistent action in case of a suspicion. Methods: All children attending one of the five participating OOH-PC services in the region of Utrecht, the Netherlands, in a year time, were included. The checklist is an obligatory field in the electronic patient file and was filled in for all children. In case of a positive checklist, the steps in the reporting code were followed. Additionally, the case was evaluated in a multidisciplinary team to determine the probability of child abuse. Results: The checklist was filled in for 50671 children; 108 (0.2 %) were positive. The multidisciplinary team diagnosed child abuse in 24 (22 %) of the 108 positive checklists, and no child abuse in 36 (33 %). Emotional neglect was the most frequent type of abuse diagnosed. For all abused children, care was implemented according to the protocol. The most frequent care given was a referral to the hospital (N = 7) or contact with child's own general practitioner (N = 6). Conclusion: A checklist followed by a reporting code guarantees consistent actions and care for children with a suspicion of child abuse. The percentage of positive checklists is lower than expected. Validity of the checklist should be assessed in a diagnostic study.
This study uses large, longitudinal, multisector administrative datasets of families investigated by child welfare services for maltreatment to explore which children are more likely to later enter psychiatric residential treatment facilities. This question is grounded in a pressing interest to understand these costly, highly restrictive mental health treatment settings. We use statewide data from one Southeastern state linked from multiple systems (child welfare services, income maintenance, and Medicaid). We use Cox regression analyses to develop models predicting psychiatric residential treatment facilities entry among children 5-17 years, whose families were investigated for maltreatment between 2003 and 2012 (n = 182,676). Findings show children from these families who enter foster care have a heightened risk for psychiatric residential treatment facilities entry (hazard ratio = 11.63), after controlling for other factors. Study findings build on a body of research underscoring the importance of the overlap of child welfare and mental health systems to child well-being.
Objective: Child abuse can have devastating mental health consequences. Fortunately, not all individuals exposed to child abuse will suffer from poor mental health. Understanding what factors are related to good mental health following child abuse can provide evidence to inform prevention of impairment. Our objectives were to 1) describe the prevalence of good, moderate, and poor mental health among respondents with and without a child abuse history; 2) examine the relationships between child abuse and good, moderate, and poor mental health outcomes; 3) examine the relationships between individual- and relationship-level factors and better mental health outcomes; and 4) determine if individual- and relationship-level factors moderate the relationship between child abuse and mental health. Method: Data were from the nationally representative 2012 Canadian Community Health Survey: Mental Health (n = 23,395; household response rate = 79.8%; 18 years and older). Good, moderate, and poor mental health was assessed using current functioning and well-being, past-year mental disorders, and past-year suicidal ideation. Results: Only 56.3% of respondents with a child abuse history report good mental health compared to 72.4% of those without a child abuse history. Individual- and relationship-level factors associated with better mental health included higher education and income, physical activity, good coping skills to handle problems and daily demands, and supportive relationships that foster attachment, guidance, reliable alliance, social integration, and reassurance of worth. Conclusions: This study identifies several individual- and relationship-level factors that could be targeted for intervention strategies aimed at improving mental health outcomes following child abuse.
The identification of potential child maltreatment using reliable and valid screening instruments is of particular importance in high risk populations. The current study investigates the psychometric properties of the Brief Child Abuse Potential (BCAP) Inventory in mothers enrolled in opioid substitution therapy. The BCAP Risk Abuse scale had strong internal reliability. Comparisons between valid and invalid protocols (ae4 on the Lie scale, >1 Random Responding) failed to find systematic differences across most variables although those with a faking good profile had significantly lower scores on psychological well being. A six-factor solution was obtained and was conceptually strong. Subsequent analyses suggested Rigidity may be an independent subscale that needs further investigation. These results add further evidence for the potential utility of the BCAP as a measure of child abuse potential. Replication studies are needed to ascertain whether the subscales derived have convergent and predictive utility.
Practitioners and researchers alike face the challenge that different sources report inconsistent information regarding child maltreatment. The present study capitalizes on concordance and discordance between different sources and probes applicability of a multisource approach to data from three perspectives on maltreatmentChild Protection Services (CPS) records, caregivers, and children. The sample comprised 686 participants in early childhood (3- to 8-year-olds; n = 275) or late childhood/adolescence (9- to 16-year-olds; n = 411), 161 from two CPS sites and 525 from the community oversampled for psychosocial risk. We established three components within a factor-analytic approach: the shared variance between sources on presence of maltreatment (convergence), nonshared variance resulting from the child's own perspective, and the caregiver versus CPS perspective. The shared variance between sources was the strongest predictor of caregiver- and self-reported child symptoms. Child perspective and caregiver versus CPS perspective mainly added predictive strength of symptoms in late childhood/adolescence over and above convergence in the case of emotional maltreatment, lack of supervision, and physical abuse. By contrast, convergence almost fully accounted for child symptoms for failure to provide. Our results suggest consistent information from different sources reporting on maltreatment is, on average, the best indicator of child risk.
The evolution of the concept of child abuse leads to consider new types of maltreatment that in the future will certainly be taken into account with a new era of social pediatrics. Pediatric care has been based on the increased awareness of the importance of meeting the psychosocial and developmental needs of children and of the role of families in promoting the health.
ObjectiveTo determine whether staff responses to abuse disclosures had improved since the introduction of a trauma policy and training programme. MethodThe files of 250 clients attending four New Zealand mental health centres were audited. ResultsThere was a significant improvement, compared to an audit prior to the introduction of the policy and training, in the proportion of abuse cases included in formulations, and, to a lesser extent, in treatment plans. There was no significant improvement in the proportion referred for relevant treatment, which remained at less than 25% across abuse categories. The proportion of neglect disclosures responded to was significantly lower than for abuse cases. Fifty percent of the files in which abuse/neglect was recorded noted whether the client had been asked about previous disclosure, and 22% noted whether the client thought there was any connection between the abuse/neglect and their current problems. Less than 1% of cases were reported to legal authorities. People diagnosed with a psychotic disorder were significantly less likely to be responded to appropriately. ConclusionFuture training may need to focus on responding well to neglect and people diagnosed with psychosis, on making treatment referrals, and on initiating discussions about reporting to authorities.
Background. Child abuse and neglect (CAN) is a risk factor for the development of psychiatric disorders. Untreated, disorders can sustain into adulthood. Objectives. This study compares rates of psychiatric disorders to mental health care utilization in victims of CAN. Methods. From three regions in Germany, 322 children and adolescents aged between 4 and 17 and a non-abusive caregiver were assessed for the child's history of CAN, mental health and mental health care utilization via semi-structured interviews. Results. Approximately two thirds of the participants (present state 64.29 %; lifetime 69.57 %) suffered from a psychiatric disorder classifiable with ICD-10. Posttraumatic stress disorder (25.16 %), conduct disorders (21.34%) and attention and hyperactivity disorders (16.15 %) were most frequently diagnosed. Merely 19.88% were using mental health care at the time of the assessment. Conclusions. The provision of mental health care for victims of CAN is insufficient. To improve access to appropriate services for this vulnerable clientele, cooperation between psychiatrists and psychotherapists and the child welfare system is essential. The implementation and dissemination of evidence-based diagnostic methods and treatments must be further advanced.
International estimates of the incidence of non-accidental burns (NAB) in children admitted to burn centres vary from 1% to 25%. Hardly any data about Dutch figures exist. The aim of this study was to evaluate the incidence, treatment and outcome of burns due to suspected child abuse in paediatric burns. We described the process of care and outcome, including the accuracy of the SPUTOVAMO screening tool and examined child, burn and treatment characteristics related to suspicions of child abuse or neglect. A retrospective study was conducted in children aged 0-17 years with a primary admission after burn injuries to the burn centre Rotterdam in the period 2009-2013. Data on patient, injury and treatment characteristics were collected, using the Dutch Burn Repository R3. In addition, medical records were reviewed. In 498 paediatric admissions, suspected child abuse or neglect was present in 43 children (9%). 442 screening questionnaires (89%) were completed. In 52 out of 442 questionnaires (12%) the completed SPUTOVAMO had one or more positive signs. Significant independent predictors for suspected child abuse were burns in the genital area or buttocks (OR = 3.29; CI: 143-7.55) and a low socio-economic status (OR = 2.52; 95%CI: 1.30-4.90). The incidence of suspected child abuse indicating generation of additional support in our population is comparable to studies with a similar design in other countries. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.
Partial or complete division of the parietal bones resulting in anomalous cranial sutures is a rare entity and may raise concern for fracture and potential abuse when identified on radiological examination in young children. We present a case of a 4-week-old male found to have anomalous intraparietal sutures originally interpreted as fractures during a comprehensive evaluation for nonaccidental trauma. Our goal is to raise awareness of a complex branching pattern of accessory intraparietal sutures, which has not been previously described. Additionally, we will review the characteristics that aid in the radiologic differentiation of accessory cranial sutures and fractures. (C) 2016 Elsevier Inc. All rights reserved.
Introduction: The social developmental processes by which child maltreatment increases risk for marijuana use are understudied. This study examined hypothesized parent and peer pathways linking preschool abuse and sexual abuse with adolescent and adult marijuana use. Methods: Analyses used data from the Lehigh Longitudinal Study. Measures included child abuse (physical abuse, emotional abuse, domestic violence, and neglect) in preschool, sexual abuse up to age 18, adolescent (average age = 18 years) parental attachment and peer marijuana approval/use, as well as adolescent and adult (average age = 36 years) marijuana use. Results: Confirming elevated risk due to child maltreatment, path analysis showed that sexual abuse was positively related to adolescent marijuana use, whereas preschool abuse was positively related to adult marijuana use. In support of mediation, it was found that both forms of maltreatment were negatively related to parental attachment, which was negatively related, in turn, to having peers who use and approve of marijuana use. Peer marijuana approval/use was a strong positive predictor of adolescent marijuana use, which was a strong positive predictor, in turn, of adult marijuana use. Conclusions: Results support social developmental theories that hypothesize a sequence of events leading from child maltreatment experiences to lower levels of parental attachment and, in turn, higher levels of involvement with pro-marijuana peers and, ultimately, to both adolescent and adult marijuana use. This sequence of events suggests developmentally-timed intervention activities designed to prevent maltreatment as well as the initiation and progression of marijuana use among vulnerable individuals. (C) 2016 Elsevier Ltd. All rights reserved.
Background: An estimated one billion children experience child abuse each year, with the highest rates in low- and middle-income countries. The Sinovuyo Teen programme is part of Parenting for Lifelong Health, a WHO/UNICEF initiative to develop and test violence-prevention programmes for implementation in low-resource contexts. The objectives of this parenting support programme are to prevent the abuse of adolescents, improve parenting and reduce adolescent behavioural problems. This trial aims to evaluate the effectiveness of Sinovuyo Teen compared to an attention-control group of a water hygiene programme. Methods/Design: This is a pragmatic cluster randomised controlled trial, with stratified randomisation of 37 settlements (rural and peri-urban) with 40 study clusters in the Eastern Cape of South Africa. Settlements receive either a 14-session parenting support programme or a 1-day water hygiene programme. The primary outcomes are child abuse and parenting practices, and secondary outcomes include adolescent behavioural problems, mental health and social support. Concurrent process evaluation and qualitative research are conducted. Outcomes are reported by both primary caregivers and adolescents. Brief follow-up measures are collected immediately after the intervention, and full follow-up measures collected at 3-8 months post-intervention. A 15-24-month follow-up is planned, but this will depend on the financial and practical feasibility given delays related to high levels of ongoing civil and political violence in the research sites. Discussion: This is the first known trial of a parenting programme to prevent abuse of adolescents in a low- or middle-income country. The study will also examine potential mediating pathways and moderating factors.
Musculoskeletal manifestations of child maltreatment represent common presentations to the emergency department. The recognition of child maltreatment is an essential role for the practicing emergency physician, as it can directly prevent further serious injury. Orthopedic trauma in children presents very differently than that in adults. Understanding of the unique properties of pediatric bone as well as the developmental capabilities of children in relation to injury mechanism is essential in the interpretation of these injuries. Children younger than 3 years are most vulnerable to bony injury from child maltreatment. Common presenting findings include complex skull fractures, rib fractures, long bone fractures, and metaphyseal corner fractures. Skeletal survey remains the mainstay of detection for injuries, but recent work has also elucidated a role for other modalities in fracture detection. Management should include proper orthopedic interventions, along with mandatory reporting of possible maltreatment to the local child protective services or other equivalent agency.
Child abuse in its various types such as physical, emotional, sexual, and neglect has been document throughout history. However, before the mid-20th century, inflicted injuries to children was overlooked in part because children were often viewed as property. According to the World Health Organization, 57,000 children were the victims of homicide in the year 2000. In this paper we present the skeletal and radiological manifestation of physical abuse and fatal neglect and provide recommendations to assess child maltreatment from past populations. Pediatric biomechanical factors and healing are discussed as it is important to keep in mind that children are not just small adults. Skeletal and radiological indicators of nonaccidental or inflicted injuries are reviewed from the literature. Inflicted injuries are presented based on specificity to identify child abuse. In addition, skeletal indicators that could help assess fatal starvation are also reviewed and metabolic diseases are proposed as potential evidence of neglect. A recent child homicide is presented and used to illustrate the difficulty in assessing child maltreatment. Present-day clinical child abuse protocols are used to provide recommendations to assess child abuse in a bioarchaeological context. Clin. Anat. 29:844-853, 2016. (c) 2016 Wiley Periodicals, Inc.
Over the past two decades there has been a growing awareness that sport may not be a positive experience for all children. For example, we know that some children experience sexual abuse in the context of organised sport, and that these offences are often committed by trusted adults, including coaches and club officials. However, less attention has been given to the physical abuse of child athletes. This paper presents a study that explored children's experiences of organised sport, as recounted by young people between the ages of 18 and 25 years in Australia. The study explored the experience of child physical abuse in organised sport including violence, overtraining, and training while injured. A mixed methods research design produced 107 survey responses and 10 in-depth interviews with young adults. Most respondents reported the positive impact that participating in sport had had on their development, but more than a third of the respondents also described experiences of overtraining, being forced to train when injured or of direct physical violence. Drawing upon a thematic analysis of the qualitative data, a conceptual model has been developed and is presented to assist in the understanding of the dynamic of secrecy, which may facilitate ongoing physical harm to children in this context.
Ross Cheit's book The Witch-Hunt Narrative highlights the difficulties of prosecuting child sexual abuse. Drawing examples from a single case, Alex A., we examine the ways in which false acquittals of sexual abuse are likely to occur. First, prosecutors tend to question children in ways that undermine their productivity and credibility. Second, prosecutors have difficulty in explaining to juries the dynamics of sexual abuse and disclosure, making children's acquiescence to abuse and their failure to disclose when abuse first occurs incredible. Third, attorneys undermine children's credibility by pushing them to provide difficult to estimate temporal and numerical information. A post-script to the Alex A. case illustrates the costs of wrongful acquittals.
Much of the fabric in today's society is at odds with planning a robust and generative public health response to child maltreatment prevention. A critical component of this problem is the absence of a public policy framework and related infrastructure that can create common ownership of the problem while recognizing the vast differences in individual willingness and capacity to alter their parenting behaviors. To address this challenge, it seems prudent to begin building a universal system of assessment and support that will touch all children and all families at multiple points in the developmental process. Such a system would not simply identify those at highest risk. Rather this system would be built on the premise that all parents have issues and concerns and differ only in the extent to which they have the capacity to address these issues. This commentary outlines the key elements of such a system and its benefits in strengthening both the impacts of interventions and the collective will to support all children.
To compare the nature and determinants of child discipline in Qatar and Palestine among young adults through retrospective survey to develop legislation, policies and interventions for effective prevention of child maltreatment, and educational materials to promote positive discipline among parents and caregivers. Cross-sectional random household surveys were conducted in each country (Qataris N = 697, Palestinians N = 2064) using ISPCAN Child Abuse Screening Tool -Retrospective (ICAST-R) for young adults (18-24 years), to investigate child discipline methods into the maltreatment range. Qatari young adults were more educated (p < 0.001) and had more full-time employment (p = 0.004) than Palestinian young adults. Qatar reported lower physical and emotional abuse compared to their counterparts in Palestine, e.g. Hit/Punch, Kick (p < 0.001) and Insult/Criticize, Threaten to be hurt/killed (p < 0.001). Qatari participants found any harsh discipline they received in childhood was not reasonable and not justified compared to Palestinian participants. The more advantaged Qatari population was less likely to experience disciplinary methods that experts developing the ICAST-R defined as abuse compared to Palestinians where the higher incidence of child abuse could be attributed to lower economic advantage, lower level of education and greater exposure to violence. Suggestions are made for future studies in Qatar and Palestine to develop survey methodology with a more culturally appropriate level of intrusion, such as indirect yet meaningful child maltreatment questions. (C) 2016 Elsevier Ltd. All rights reserved.
Recognition of physical child abuse is imperative for ensuring children's safety. Screening tools (ST) may increase identification of physical abuse; however, the extent of their use is unknown. This study assessed use of STs for physical abuse in children's hospitals and determined attitudes regarding STs. A web-based survey was sent to child abuse program contacts at 103 children's hospitals. The survey assessed institutional use of a ST for physical abuse and characteristics of the ST used. Respondents were asked to identify benefits and liabilities of STs used or barriers to ST use. Seventy-two respondents (70 %) completed the survey; most (64 %) were child abuse pediatricians. Nine (13 %) respondents reported using a ST for physical abuse; STs varied in length, population, administration, and outcomes of a positive screen. Most respondents (86 %) using a ST felt that it increased detection of abuse. Barriers noted included lack of time for development and provider completion of a ST. While few respondents endorsed use of a ST for physical abuse, most believed that it increased detection of abuse. Future research should focus on development of a brief, uniform ST for physical abuse which may increase detection in at-risk children.
Objective: Traumatic brain injury causes substantial morbidity and mortality in children. Posttraumatic seizures may worsen outcomes after traumatic brain injury. Posttraumatic seizures risk factors are not completely understood. Our objective was to clarify posttraumatic seizures risk factors in a large cohort of children with severe traumatic brain injury. Design: Retrospective cohort study of a probabilistically linked dataset from the National Trauma Data Bank and the Pediatric Health Information Systems database, 2007-2010. Setting: Twenty-nine U.S. children's hospitals. Patients: A total of 2,122 children (age, < 18 yr old at admission) with linked National Trauma Data Bank and Pediatric Health Information Systems records, severe (emergency department Glasgow Coma Scale, < 8) traumatic brain injury, hospital length of stay more than 24 hours, and nonmissing disposition. Interventions: None. Measurements and Main Results: The outcome was posttraumatic seizures, identified using validated International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Prespecified candidate predictors of posttraumatic seizures included age, injury mechanism, emergency department Glasgow Coma Scale, intracranial hemorrhage type, hypoxia, hypotension, and cardiac arrest. Posttraumatic seizures were diagnosed in 25.2% of children with severe traumatic brain injury. In those without abuse/assault or subdural hemorrhage, the posttraumatic seizures rate varied between 36.6% in those less than 2 years old and 16.4% in those 14-17 years old. Age, abusive mechanism, and subdural hemorrhage are each significant predictors of posttraumatic seizures. The risk of posttraumatic seizures has a complex relationship with these predictors. The estimated odds of posttraumatic seizures decrease with advancing age, odds ratio equal to 0.929 (0.905-0.954) per additional year of age with no abuse/assault and no subdural hemorrhage; odds ratio equal to 0.820 (0.730-0.922) per additional year of age when abuse and subdural hemorrhage are present. An infant with accidental traumatic brain injury and subdural hemorrhage has approximately the same estimated probability of posttraumatic seizures as an abused infant without subdural hemorrhage (47% [95% CI, 39-55%] vs 50% [95% CI, 41-58%]; p = 0.69). The triad of young age, injury by abuse/assault, and subdural hemorrhage confers the greatest estimated probability for posttraumatic seizures (60% [95% CI, 53-66%]). Conclusions: Posttraumatic seizures risk in children with severe traumatic brain injury is greatest with a triad of younger age, injury by abuse/assault, and subdural hemorrhage. However, posttraumatic seizures are common even in the absence of these factors.
Many studies have explored the negative outcomes of childhood maltreatment, including psychopathology, risk-taking behaviors, and death by suicide. Being male may exacerbate negative symptoms following maltreatment and result in a decreased sense of psychological well-being. Much remains unexamined when exploring factors that may buffer the negative outcomes of maltreatment. Self-compassion has been suggested to aid in the improvement of psychological well-being and in the recovery of traumatic events. This study examined the relationship between self-compassion and psychological well-being among a sample of men who had and had not experienced childhood maltreatment. Testing a model of mediation, findings reflected that self-compassion, while not a full mediator between maltreatment and psychological well-being, served as partial mediator. Implications and future directions are explored.
Physical, emotional and sexual child abuse are major problems in South Africa. This study investigates whether children know about post-abuse services, if they disclose and seek services, and what the outcomes of help-seeking behaviour are. It examines factors associated with request and receipt of services. Confidential self-report questionnaires were completed by adolescents aged 10-17 (n = 3515) in South Africa. Prevalence of frequent (>weekly) physical abuse was 7.4%, frequent emotional abuse 12.4%, and lifetime contact sexual abuse 9.0%. 98.6% could name one suitable confidante or formal service for abuse disclosure, but only 20.0% of abuse victims disclosed. Of those, 72% received help. Most common confidantes were caregivers and teachers. Of all abuse victims, 85.6% did not receive help due to non-disclosure or inactivity of services, and 14.4% received help: 4.9% from formal health or social services and 7.1% through community vigilante action. Emotional abuse, sexual abuse and female gender were associated with higher odds of help-seeking. While children in South Africa showed high knowledge of available services, access to and receipt of formal services among abused children was low. Notably fewer children received help from formal services than through community vigilante action. Urgent action is needed to improve service access for child abuse victims.
Objective To identify areas of deficiencies and gaps in child protection services in Northern Sri Lanka. Also, to help in recommending strategies, programmes of interventions for addressing issues of child abuse and advice the legal system. Methods A retrospective study was done to determine the socio-demographic details, type of abuse, clinical profile, relationship of the perpetrator and nature of abuse among children admitted to a tertiary care centre from 2009 through 2014, a period after cessation of a 60-y conflict. Data were obtained from hospital based records and records maintained at the district probation office. Results Seven hundred twenty cases were referred to the tertiary care centre with abuse. Majority of the children were from the Jaffna district, the northern city of the war affected area and mean age of the children affected was 14.5 +/- 2.6 y. Females were affected more than the males and 352 children were seen following sexual abuse. The clinical examination showed penetrative injury in 15 %. The perpetrator was known in 70 % of the situations and the victim was coerced into a relationship for abuse. Attempted suicide was seen in significant numbers during the immediate post war period and school dropout and delinquent behaviour was seen in later years. Conclusions The problem of child abuse is considerable in this region and there is an urgent need to strengthen the services offered to the victims. Urgent steps are needed to safeguard these children, especially in the war affected areas.
The high prevalence of child sexual abuse (CSA) is concerning, particularly as survivors are at increased risk for multiple adverse outcomes, including poor mental health across the lifespan. Children born at an extremely low birth weight (ELBW;2500 g) participants at ages 22-26 and 29-36. At age 22-26, CSA was associated with increased odds of clinically significant internalizing (OR= 7.32, 95% CI: 2.31-23.23) and externalizing (OR = 4.65, 95% CI: 1.11-19.51) problems among ELBW participants exposed to CSA compared to those who did not, though confidence intervals were wide. At age 29-36, CSA was linked to increased odds of any current (OR = 3.43, 95% CI: 1.08-10.87) and lifetime (OR= 7.09, 95% CI: 2.00-25.03) non -substance use psychiatric disorders, however, this did not hold after adjustment for covariates. Statistically significant differences in mental health outcomes were not observed in NBW participants exposed to CSA compared to NBW participants who were not exposed. Survivors of significant perinatal adversity who are also exposed to CSA may be at higher risk for psychopathology through the fourth decade of life. (C) 2016 Elsevier Ltd. All rights reserved.
Child sexual abuse (CSA) affects over 62,000 children annually in the United States. A primary obstacle to the success of a public health prevention strategy is the lack of knowledge around community level risk factors for CSA. We evaluated community level characteristics for children seeking care for suspected CSA in the Greater Houston area for 2009. There was a total incidence rate of medical evaluations for suspected CSA of 5.9/1000 children. We abstracted the medical charts of 1982 (86 %) children who sought a medical evaluation for suspected CSA at three main medical systems in the Greater Houston area for 2009. We evaluated 18 community level variables from the American Community Survey for the 396 zip codes these children lived in. The mean number of cases per Greater Houston zip code was 2.77 (range 0-27), with 62 % of zip codes not having a case at any of the three sites surveyed. Zip codes with a higher than Houston average rate of vacant houses, never married females and unemployed labor force with high family poverty rate, were associated with an increased rate of children seeking care for suspected CSA. We demonstrated zip codes level characteristics which were associated with an increased rate of children seeking care for suspected CSA. Our modelling process and our data have implications for community based strategies aimed at improved surveillance or prevention of CSA. The process of identifying locally specific community level factors suggests target areas which have particular socioeconomic characteristics which are associated with increased rate of seeking CSA evaluations.
Fractures are the second most common presentation of child abuse following soft-tissue bruising and burns. It is often difficult to determine potential abuse in a child presenting with a non-rib fracture(s) and without soft-tissue injuries. One hundred and fifteen consecutive patients aged a parts per thousand currency sign2 years who presented with a fracture between January 2010 and June 2012 to our emergency department (ED) or pediatric fracture clinic were retrospectively analyzed. Statistical analyses were carried out for non-accidental fractures based on age (< 1 year vs 1-2 years), location of presentation (ED vs pediatric fracture clinic), type of long bone fracture, number of fractures, and patient demographics. Fractures in 19 of 115 (17 %) patients were reported as non-accidental trauma (NAT). Eighty (70 %) of the 115 patients first reported to the ED. Thirty-two percent of fractures in children aged < 1 year and 5 % of fractures in children aged 1-2 years were reported as NAT (p < 0.001). Sixteen of 19 (84 %) patients reported for abuse had multiple fractures; 15 of these patients were aged < 1 year. Eight of 11 (73 %) reported femoral fractures were transverse fractures. Corner fractures (12) only occurred in children aged < 1 year and never occurred in isolation; all of them were reported as NAT. Four of 60 patients (7 %) with commercial insurance and 15 of 55 patients (28 %) with Medicaid were reported as NAT. Age less than 1 year, multiple fractures, corner fractures, transverse fractures, and covered by Medicaid were the most common factors associated with reporting of NAT.
Objective: Child abuse exerts a deleterious impact on a broad array of mental health outcomes. However, the neurobiological mechanisms that mediate this association remain poorly characterized. Here, we use a longitudinal design to prospectively identify neural mediators of the association between child abuse and psychiatric disorders in a community sample of adolescents. Method: Structural magnetic resonance imaging (MRI) data and assessments of mental health were acquired for 51 adolescents (aged 13-20; M=16.96; SD=1.51), 19 of whom were exposed to physical or sexual abuse. Participants were assessed for abuse exposure (time 1), participated in MRI scanning and a diagnostic structured interview (time 2), and 2 years later were followed-up to assess psychopathology (time 3). We examined associations between child abuse and neural structure, and identified whether abuse-related differences in neural structure prospectively predicted psychiatric symptoms. Results: Abuse was associated with reduced cortical thickness in medial and lateral prefrontal and temporal lobe regions. Thickness of the left and right parahippocampal gyrus predicted antisocial behavior symptoms, and thickness of the middle temporal gyrus predicted symptoms of generalized anxiety disorder. Thickness of the left parahippocampal gyrus mediated the longitudinal association of abuse with antisocial behavior. Conclusion: Child abuse is associated with widespread disruptions in cortical structure, and these disruptions are selectively associated with increased vulnerability to internalizing and externalizing psychopathology. Identifying predictive biomarkers of vulnerability following childhood maltreatment may uncover neurodevelopmental mechanisms linking environmental experience with the onset of psychopathology.
With government's response to child abuse and neglect seen as one of the most daunting challenges for public policy and law, legislative reform on this issue struggles to adequately protect children while preserving the integrity of family. The authors utilize the Child Abuse Prevention and Treatment Act (CAPTA) as an example of the funding and policy challenges in reforming federal child welfare law, as well as a lens through which advocates can locate both conventional and unconventional tools to move forward. CAPTA is examined as an important but weak and flawed federal statute. Authors present an array of opportunities to improve CAPTA during the next reauthorization cycle. Noting exemplary successes, in other recent and related legislation reforms, are suggested for CAPTA to more effectively address ongoing challenges of child welfare.
Child and adolescent abuse and neglect of children is a growing social problem that is not limited to medical, legal or social services professions; Dental professionals must be able to identify, document, report and often help treat these patients and their families. This study is descriptive with retrospective Cross-sectional design, with a population consisting of all children and adolescents treated in Forensic Medicine of the CICPC ( Merida, Venezuela) during the period from January 2010 to June 2013 with the aim of describing the clinical findings of dental interest in child and adolescent victims of abuse. Information was collected on a tab and the results are presented in tables and graphs of percentage bar. The findings showed that physical injuries caused by violent events are usually unnoticed, the most susceptible age group was 14-16 years, wounds located in lips were the most frequent injuries, most of present dental lesions required general dental treatment. It is recommended to promote more research in order to know the magnitude of the impact of child and adolescent abuse.
Attachment theory promoted an impressive body of research on the psychic developmental processes, resulting in studies on both typical and atypical development. Much of the diffusion of the attachment theory in the clinical field was related to the design of reliable instruments to evaluate the organization of attachment in infancy as well as in adulthood. Until recently, the lack of a suitable instrument to assess attachment in middle childhood as well as in adolescence hindered the expansion of research in these developmental phases during which the parent-child relationship takes on a different, albeit still crucial, role. The Child Attachment Interview (CAI), a measure that was recently designed to assess attachment at a representational level in middle childhood and adolescence, filled the measurement gap. The aim of the current review was to summarize previous empirical investigations concerning CAI in order to (a) provide an overview of the state of current research, (b) identify unanswered questions, and (c) propose future research directions. A narrative review was conducted to map the current research findings by searching for the term "Child Attachment Interview" in the Medline, Scopus, Web of Science, and PsychINFO databases, followed by a search in Mendeley. Limits were set to exclude dissertations, chapters in books, and qualitative or theoretical papers, while empirical studies were included if they used the CAI and were published in English language, peer-reviewed journals by July, 2016. The review, which ultimately included 39 studies meeting the criteria, showed that the CAI is a reliable instrument to assess attachment organization in clinical and non-clinical samples, thus providing a worthwhile contribution to the investigation of the influence of the parent-child relationship beyond infancy and early childhood. Nevertheless, the review pointed out a number of relevant open issues, the most critical of which concerned the CAI coding and classification system. In particular, some relevant questions arose about (a) how opportune it would be to maintain a distinct classification for mother and father, (b) coding challenges regarding both the father and the Preoccupied and Disorganized classification, and finally (c) the advantage of a dimensional vs. a categorical approach.
This research examines how victim and offender characteristics, as well as contextual factors are related to the lethality of assaults for children less than 5 years old. The National Incident-Based Reporting System (NIBRS) data for 2006 to 2011 were analyzed using logistic regression techniques to estimate two models designed to explore factors associated with the death of preschoolers. Results indicate that the probability of fatality is significantly influenced by victim and offender characteristics, victim-offender relationship, weapon used, time of incident, and region of the United States in which the incident occurred.
Previous research has investigated the deleterious effects of child maltreatment on child development; however, little research has examined the development of children who live with caregivers who are at risk of maltreatment on child development outcomes. This study utilized self-report data from caregivers that included the Child Abuse Potential Inventory (CAPI), Parenting Stress Inventory-Short Form (PSI/SF), and Adaptive Behavior Assessment System-2nd Edition (ABAS-II) for 116 children ages 3-12 from a rural, Appalachian community. Caregivers with lower child abuse potential, children who used fewer school services, older children, and caregivers with lower household income had better total adaptive skills. Caregivers with lower child abuse potential, children who used fewer school services and older children had better functioning on the academic skills subscale. Children who used fewer school services, were older, and had lower family income had greater self-care skills. Finally, children who used fewer school services had greater communication skills. Parent-child dysfunction was not related to child development outcomes. The findings demonstrate that educators are in a unique position to intervene and support children at risk of maltreatment.
A maternal history of childhood maltreatment is thought to be a potent risk factor for child abuse and neglect, yet the extent of continuity across generations is unclear, with studies reporting vastly different rates of intergenerational transmission. Disparate findings may be due to lack of attention to the nature of maltreatment experiences in each generation. We sought to expand the current literature by examining the role of maltreatment type, perpetrator identity, and substantiation status of reports to child protective services (CPS) on intergenerational maltreatment among adolescent mothers (n = 417) and their children. We found that when mothers had at least one report of childhood maltreatment (substantiated or not), the odds that they maltreated their children increased by 72% (OR = 2.52), compared to mothers who are not maltreated, but the odds were considerably lower when we limited analysis to substantiated reports. Both a maternal history of substantiated neglect and multiple type maltreatment (neglect and physical or sexual abuse) were associated with increased risk of child maltreatment, yet the likelihood of children experiencing multiple maltreatment perpetrated with their mothers identified as perpetrators increased over 300% when mothers had a childhood history of multiple maltreatment. (C) 2016 Elsevier Ltd. All rights reserved.
Aim: Although considerable efforts have been made to improve relationships between professionals and parents suspected of child maltreatment, little research has been conducted to examine the ways in which parents escalate their negative cognition and behavior involving professionals. This study developed a model of parents' negative reinforcement of their cognitive behavior and the factors influencing reductions in this reinforcement. Method: Interview data were collected from 21 parents, who had experienced outreach and child protection issues, and analyzed using the grounded theory approach. Result: In the outreach phase, the analysis initially produced the negative image of help-seeking behavior category, followed by the dissatisfaction with outreach and reinforcement of negative cognition categories. In this phase, the analysis also identified the social support and support groups step as a means of reducing negative cognition. In contrast, in the child protection phase, the analysis produced the anger and psychological conflict with child protection services and unwilling consent categories. In this phase, the analysis also identified the psychoeducation and timely feedback step as an acceptable means of minimizing the escalation of negative cognition. Conclusion: The hypothetical model revealed the ways in which parents changed their cognition and behavior and demonstrated the factors influencing reductions in the reinforcement of negative cognition and behavior. These results could be useful for practice in child maltreatment cases. (C) 2016 The Authors. Published by Elsevier Ltd.
A correlation between socioeconomic disadvantage and child maltreatment has long been observed, but the drivers of this association are poorly understood. We sought to estimate the effects of economic factors on risk of child maltreatment after adjusting for other known influences using the Australian Temperament Project, a population-based birth cohort of 2443 individuals and their parents. We used logistic regression to estimate associations of childhood economic factors (parental education, occupation, and unemployment; type of housing; and retrospective perception of poverty) with retrospective reports of perceived child maltreatment (physical abuse, sexual abuse, emotional abuse, neglect, and witnessing of domestic violence), controlling for demographic factors, parental mental health and substance use, and child health. We then used these estimates to approximate the proportions of child maltreatment population attributable fractions that are theoretically preventable by addressing childhood economic disadvantage. Economic factors were associated with all types of child maltreatment. For the most part, these associations diminished only partially when controlling for noneconomic con-founders, supporting hypotheses of causal relationships. Jointly, economic factors were significant predictors of physical abuse, sexual abuse, and witnessing of domestic violence but not of emotional abuse or neglect. Retrospective perceptions of childhood poverty were, in particular, strongly associated with most forms of child maltreatment but not with sexual abuse after accounting for other economic factors. We estimated that 27% of all child maltreatment was jointly attributable to economic factors. These findings suggest that strategies that reduce economic disadvantage are likely to hold significant potential to reduce the prevalence of child maltreatment. (C) 2016 Elsevier Ltd. All rights reserved.
Crime is a major public health and safety threat. Many studies have suggested that early exposure to child maltreatment increases an individual's risk for persistent serious crime in adulthood. Despite these findings about the connection between child maltreatment and criminal behavior, there is a paucity of empirically-based knowledge about the processes or pathways that link child maltreatment to later involvement in crime. Using a community sample of 337 young adults (ages 18-25) in a U.S. metropolitan area, the present study examined the role of various facets of impulsivity in linking child maltreatment to crime. A series of factor analyses identified three types of crime including property crime, violent crime, and fraud. Structural equation modelings were conducted to examine the associations among childhood maltreatment, four facets of impulsivity, and criminal behavior, controlling for sociodemographic information, family income and psychological symptoms. The present study found that child emotional abuse was indirectly related to property crime and fraud through urgency while a lack of premeditation mediates the relationship between child neglect and property crime. Child physical abuse was directly related to all three types of crime. Personality traits of urgency and lack of premeditation may play a significant role in the maltreatment-crime link. Preventive interventions targeting impulsivity traits such as urgency and a lack of premeditation might have promising impacts in curbing criminal behavior among maltreatment victims. (C) 2016 Elsevier Inc. All rights reserved.
A cost of illness (COI) study was undertaken to estimate the magnitude and range of lifetime effects associated with child maltreatment in Australia, using an incidence-based approach. Costs were primarily estimated through calculation of population attributable fractions (PAFs) to determine the marginal effects of child maltreatment on a range of outcomes. PAFs were then applied to estimates of expenditure, inflated to 2014-15 Australian dollars, projected over the life course, according to a baseline age of incident cases for child maltreatment in 2012-13, and discounted at 7% per annum. Sensitivity analysis was conducted using a best and lower bound estimate of incidence of child abuse. The best estimate of the total estimated lifetime financial costs for incident cases of child maltreatment in 2012-13 was $9.3 billion (a cost per child maltreated of $176,437), with a lower bound of $5.8 billion. The best estimate of lifetime costs associated with reduced quality of life and premature mortality (non-financial costs) for all incident cases of child maltreatment in 2012-13 was $17.4 billion, or $328,757 per child maltreated. The considerable lifetime costs associated with child maltreatment warrants an expansion of existing investment in primary and secondary prevention and targeted support services for children and families at risk. (C) 2016 Elsevier Ltd. All rights reserved.
In cases of maltreatment involving children of U.S. Army service members, the U.S. Army Family Advocacy Program (FAP) is responsible for providing services to families and ensuring child safety. The percentage of cases of maltreatment that are known to FAP, however, is uncertain. Thus, the objective of this retrospective study was to estimate the percentage of U.S. Army dependent children with child maltreatment as diagnosed by a military or civilian medical provider who had a substantiated report with FAP from 2004 to 2007. Medical claims data were used to identify 0-17 year old child dependents of soldiers who received a medical diagnosis of child maltreatment. Linkage rates of maltreatment medical diagnoses with corresponding substantiated FAP reports were calculated. Bivariate and multivariable analyses examined the association of child, maltreatment episode, and soldier characteristics with linkage to substantiated FAP reports. Across 5945 medically diagnosed maltreatment episodes, 20.3% had a substantiated FAP report. Adjusting for covariates, the predicted probability of linkage to a substantiated FAP report was higher for physical abuse than for sexual abuse, 25.8%, 95% CI (23.4, 28.3) versus 14.5%, 95% CI (11.2, 17.9). Episodes in which early care was provided at civilian treatment facilities were less likely to have a FAP report than those treated at military facilities, 9.8%, 95% CI (7.3, 12.2) versus 23.6%, 95% CI (20.8, 26.4). The observed low rates of linkage of medically diagnosed child maltreatment to substantiated FAP reports may signal the need for further regulation of FAP reporting requirements, particularly for children treated at civilian facilities. (C) 2016 Elsevier Ltd. All rights reserved.
The study examines family characteristics that put adolescent girls at increased risk of abuse, mainly physical, sexual and emotional abuse and neglect. Stratified random sampling was done among classes 7th to 12th of government girls' schools of a semi-urban area of Delhi, and a total of 1060 adolescent girls participated. Majority were in mid-adolescence. Approximately 70% study subjects faced at least one form of maltreatment. Physical abuse was faced by 42.6%, sexual abuse by 26.6%, emotional abuse by 37.9% and neglect by 40.1% of study subjects. The most frequent perpetrator of physical and emotional abuse was mother, and of sexual abuse were friends, relatives or neighbours. No or low education of father increased odds of physical and emotional abuse, while odds of physical abuse and neglect were lower if mothers were housewives. Excessive arguments between parents and history of maltreatment in parents increased odds of child maltreatment in study subjects.
Although people with a history of child abuse are known to be at elevated risk for later difficulties in relationships, there is debate over whether these effects are enduring and relatively immutable or are moderated by characteristics and behaviors of the partner. To reconcile these competing perspectives, we conducted a longitudinal study of 414 newlywed couples living in low-income neighborhoods, testing whether the association between abuse history and relationship satisfaction is dependent on the partners' aggression, depression, substance abuse, observed communication, and other demographic risk factors. Spouses who had been abused as children (25% of husbands, 31% of wives) reported more symptoms of depression and substance abuse and, among husbands, displayed more negative communication. Spouses with a history of child abuse were also less satisfied with their marriage, even as newlyweds; abused wives also declined in satisfaction over time compared to those without this history. However, interactions between abuse history and all of the proposed moderators were not significant, indicating that partner and relationship characteristics failed to strengthen or weaken the association between abuse history and relationship satisfaction. Childhood experiences of abuse appear to have lasting and broad effects on individual and relational outcomes, and these effects are neither heightened nor mitigated by the partner's characteristics or behaviors.
Objective: Early victimization elevates children's risk for developing psychopathology. Recent findings suggest that disruptions in developmental processes related to symptoms of posttraumatic stress (PTS) may partially account for the association between early victimization and subsequent psychopathology. The present study prospectively tested the temporal sequencing of these associations using, multiinformant measurements in a large, diverse sample of children at high risk for victimization. Method: This study measured victimization (i.e., direct, indirect, familial, and nonfamilial violence), PTS, externalizing, and internalizing problems among 1154 children (561 girls and 593 boys) who participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Results: Structural equation modeling revealed that, in addition to directly impacting psychopathology, childhood victimization contributed to escalations in internalizing and externalizing problems as children transitioned from middle to late childhood indirectly through PTS. The mediational role of PTS was largely similar for girls and boys and for those who were investigated for early reports of maltreatment and those identified early as at-risk for victimization. Conclusions: This study delineated the role of PTS in the development of psychopathology following early victimization. These findings highlight the importance of carefully assessing for underlying trauma symptoms when considering diverse presentations of psychopathology among youth who have been victimized.
Educators periodically encounter the need to report a suspicion of child abuse or neglect. Studies show that school professionals recognize more than half of maltreated children. Because of uncertainty with reporting policies, practices, and procedures, this experience may be difficult for the educator before, during, or after a report is made, which precipitates a variety of emotions and a need for support. Many educators often encounter challenges and barriers with reporting procedures within the school settings. Educators who lack support in their educational institution may fail to report their suspicion of child maltreatment. This article explores child maltreatment reporting practices from the point of view of an educator in a school setting and proposes strategies to address reporting practices effectively. Appropriate intervention and services are required to meet the needs of children when there is a suspicion of abuse and neglect and are built into a model that can shape training, policies, and procedures. Therefore, strategies that cultivate immediately and legally responsive environments are imperative in the educational setting to begin to reduce the number of maltreated child cases that are unreported.
There is strong evidence that poverty and economic disadvantage are associated with child maltreatment; however, research in this area is underdeveloped in Canada. The purpose of this paper is to examine the relationship between economic hardship and maltreatment for families and children identified to the Ontario child protection system for a maltreatment concern. Secondary analyses of the Ontario Incidence Study of Reported Child Abuse and Neglect-2013 (OIS-2013) were conducted. The OIS-2013 examines the incidence of reported maltreatment and the characteristics of children and families investigated by child welfare authorities in Ontario in 2013. Descriptive and bivariate chi-square analyses were conducted in addition to a logistic regression predicting the substantiation of maltreatment. In 9% of investigations, the household had run out of money for food, housing, and/or utilities in the past 6 months. Children in these households were more likely to have developmental concerns, academic difficulties, and caregivers with mental health concerns and substance use issues. Controlling for key clinical and case characteristics, children living in families facing economic hardship were almost 2 times more likely to be involved in a substantiated maltreatment investigation (OR = 1.91, p < 0.001). The implications in regard to future research and promoting resilience are discussed.
Background: The Texas Department of Family and Protective Services (DFPS) created a statewide network of child abuse pediatricians working at 6 academic centers in 2006. Methods: Case data for the period 9/1/2012-8/31/2014 were reviewed for child demographics, risk factors, physician determinations, injury descriptors, and information made available to the physician. Results: 8061 of 410,315 DFPS cases (2%) were referred during the period. Network utilization rates ranged from 7.5% in counties served by San Antonio to 1.4% in Austin-served counties. Cases from outlying counties were less likely to involve older children. African American children were over-represented in referrals, and Caucasian and Asian children were underrepresented. Prevalent risk factors included prior DFPS history, single parent-household, mental illness, substance abuse, and domestic violence. Network providers found no or only nonspecific evidence for maltreatment in 45% of cases. Determinations were hindered by poor quality photographs in 188 cases and inadequate skeletal surveys in 121. Insufficient information precluded case completion for 65 cases of children <2 years. Conclusions: Our data indicate that child abuse centers in Texas are underutilized, and there are practice differences with respect to medical referrals across different regions. Our findings concerning ethnic differences and risk factors are consistent with national trends. The problems of inadequate photographs and case information may improve with better training of workers; the issue of poor quality skeletal surveys requires further study. Standard DFPS criteria for referrals to child abuse pediatricians should mitigate some of the problems identified by this study. (C) 2016 Elsevier Ltd. All rights reserved.
Criminal justice research frequently investigates relationships between punishment decisions and demographic characteristics of the accused, such as gender, race, and age. While there are many similarities between criminal justice and child welfare cases, research on child maltreatment has yet to examine potential demographic influences on case outcomes. The current study examines relationships between parent gender, type of maltreatment, and child removal among agency responses to child maltreatment cases. Using data collected by the National Data Archive on Child Abuse and Neglect Data System (NCANDS), we identify differences in the likelihood of child removal from the parental home across type of maltreatment and perpetrator gender. Our results indicate that mother perpetrators of physical abuse not only face significantly higher likelihood of removal than mother perpetrators of neglect, but are more at risk for losing their children than father perpetrators of both physical abuse and neglect. Findings suggest that gendered attributions and stereotypes regarding parenting can shape assessments of parents' blameworthiness, dangerousness, and rehabilitative potential. We propose that future research on child maltreatment cases adapt and apply justice concepts and frameworks to uncover potential unwarranted demographic disparities in agency decision-making. (C) 2016 Elsevier Ltd. All rights reserved.
The current study tested the hypothesis that mothers who have experienced child maltreatment and aggression within their adult relationships may be at particular risk for misinterpreting infant emotions, leading to less sensitive parenting behaviors. Participants were 120 pregnant women recruited for a larger, longitudinal study investigating the role of psychosocial and environmental risk on women and their young children. Data were collected during the third trimester of pregnancy, and when children were 1 and 2 years of age. Participants completed a projective test designed to elicit individual differences in perceptions of infant emotions and an observer-rated assessment of parenting behaviors was conducted in the family home. Using structural equation modeling, we tested associations between maternal interpersonal aggression exposure and perceptions of infant emotion and parenting behaviors. Results demonstrated that a history of child abuse and intimate partner conflict were associated with a maternal tendency to view ambiguous infant facial expressions as negative (i.e., negative attribution bias), and in turn, with less parenting sensitivity over time. Findings suggest that negative attributions of infant emotion may be 1 mechanism by which a history of trauma and violence exposure contributes to less sensitive parenting for some mothers. Implications for intervention include the need for trauma-informed clinical services and psychoeducational methods that help mothers more accurately read and respond to infant emotional expression and bids for connection.
Although Child Protective Services (CPS) and other child welfare agencies aim to prevent further maltreatment in cases of child abuse and neglect, recidivism is common. Having a better understanding of recidivism predictors could aid in preventing additional instances of maltreatment. A previous study identified two CPS interventions that predicted recidivism: psychotherapy for the parent, which was related to a reduced risk of recidivism, and temporary removal of the child from the parent's custody, which was related to an increased recidivism risk. However, counter to expectations, this previous study did not identify any other specific risk factors related to maltreatment recidivism. For the current study, it was hypothesized that (a) cumulative risk (i.e., the total number of risk factors) would significantly predict maltreatment recidivism above and beyond intervention variables in a sample of CPS case files and that (b) therapy for the parent would be related to a reduced likelihood of recidivism. Because it was believed that the relation between temporary removal of a child from the parent's custody and maltreatment recidivism is explained by cumulative risk, the study also hypothesized that that the relation between temporary removal of the child from the parent's custody and recidivism would be mediated by cumulative risk. After performing a hierarchical logistic regression analysis, the first two hypotheses were supported, and an additional predictor, psychotherapy for the child, also was related to reduced chances of recidivism. However, Hypothesis 3 was not supported, as risk did not significantly mediate the relation between temporary removal and recidivism. (C) 2016 Elsevier Ltd. All rights reserved.
Parental criminal justice involvement is prevalent in the United States and potentially associated with a range of negative outcomes for children including child abuse and neglect. However, the association between prior parental criminal justice involvement and child maltreatment is not well understood. This paper reviewed the existing literature regarding maltreatment victimization among children of parents with prior criminal justice involvement. Results from ten reviewed studies demonstrated an association between prior parental criminal justice involvement and child maltreatment, but did not provide sufficient evidence to determine whether parental criminal justice involvement is an independent risk factor for child maltreatment or of the specific mechanisms through which this association occurs. Recommendations for future research include use of multivariate analysis methods that account for variations in the type and timing of parental criminal justice involvement and child maltreatment. Implications for practice include the development of strategies to address the adverse family contexts commonly found among these parents and children. (C) 2016 Elsevier Ltd. All rights reserved.
Child maltreatment has been demonstrated to. have many short- and long-term harmful consequences for victims, but whether or not child abuse is associated with an increased risk of peer victimization during adolescence is unclear. This study analyzed prospective data from 831 children and parents participating in the Longitudinal Studies on Child Abuse and Neglect (LONGSCAN) to investigate the relationships between child physical and sexual abuse and adolescent victimization by peers, as well as the potential for gender to moderate these relationships. Results from ordinal logit regression models indicated that children who were physically abused prior to age 12, based on official reports, parent reports, and child reports, had a greater risk of experiencing more intimidation and physical assault by peers at age 16. Having a history of sexual abuse predicted more physical assault but not intimidation. There was no evidence that gender moderated these relationships; in all cases, the relationship between abuse and revictimization was similar for boys and girls. The findings emphasize the need to provide victims of abuse with assistance to help prevent a cycle of victimization. (C) 2016 Elsevier Ltd. All rights reserved.
We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner's curse. Most studies were underpowered. Future directions for research are suggested.
Although cases of child abuse among migrant families are often reported by social media, the issue of child maltreatment among migrant families in China has received little empirical attention. This study investigated both the prevalence of child maltreatment by parents among migrant families, and the individual, family and community-level risk factors associated with child abuse in this context. A survey was conducted with 667 migrant and 496 local adolescents in Shenzhen, South China, with a stratified two-stage cluster sampling design. Logistic regression analysis was conducted to compare the prevalence of maltreatment between migrant and local adolescents, and also to explore risk factors associated with the psychological and physical maltreatment in both groups. The results showed that parent-to-child abuse was more prevalent among migrant than local adolescents, with migrant adolescents 1.490 and 1.425 times more likely to be psychologically and physically abused by their parents than their local counterparts. Low academic performance, delinquent behavior, family economic adversity and low parent attachment put migrant adolescents at increased risk of both psychological and physical maltreatment, and neighborhood disorganization was significantly related to psychological aggression among migrant adolescents. The findings confirm that child abuse perpetuated by parents is a serious problem in Mainland China, especially among migrant families, and implications for policy and practice are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
The experience of maltreatment during childhood is associated with chronic low-grade inflammation in adulthood. However, the molecular mechanisms underlying this pro-inflammatory phenotype remain unclear. Mitochondria were recently found to principally coordinate inflammatory processes via both inflammasome activation and inflammasome-independent pathways. To this end, we hypothesized that alterations in immune cell mitochondrial functioning and oxidative stress might be at the interface between the association of maltreatment experiences during childhood and inflammation. We analyzed pro-inflammatory biomarkers (levels of C-reactive protein, cytokine secretion by peripheral blood mononuclear cells (PBMC) in vitro, PBMC composition, lysophosphatidylcholine levels), serum oxidative stress levels (arginine:citrulline ratio, L-carnitine and acetylcarnitine levels) and mitochondrial functioning (respiratory activity and density of mitochondria in PBMC) in peripheral blood samples collected from 30 women (aged 22-44 years) with varying degrees of maltreatment experiences in form of abuse and neglect during childhood. Exposure to maltreatment during childhood was associated with an increased ROS production, higher levels of oxidative stress and an increased mitochondria! activity in a dose-response relationship. Moreover, the increase in mitochondrial activity and ROS production were positively associated with the release of pro-inflammatory cytokines by PBMC. Decreased serum levels of lysophosphatidylcholines suggested higher inflammasome activation with increasing severity of child maltreatment experiences. Together these findings offer preliminary evidence for the association of alterations in immune cell mitochondrial functioning, oxidative stress and the pro-inflammatory phenotype observed in individuals with a history of maltreatment during childhood. The results emphasize that the early prevention of child abuse and neglect warrants more attention, as the experience of maltreatment during childhood might have life-long consequences for physical health. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
A social information processing (SIP) theory of parenting risk posits that social-cognitive and neuro-cognitive incapacities characterize at-risk parents, and that these cognitive difficulties operate across relational domains. This study focused on highly disadvantaged mothers of preschoolers and compared mothers with histories of perpetrating child neglect (n = 69) to demographically similar mothers without such histories (n = 76). Participants completed measures of unrealistic expectations for children and other adults, social problem-solving in parenting and nonparenting situations, executive functioning (EF), and attributions for children and other adults. As predicted, associations among these measures were found within and across relational domains. Exploratory factor analysis revealed two distinct clusters that distinguished the two groups. The first included measures of expectations and attributions (for both children and other adults) and the second included problem-solving difficulties and EF. When group differences were examined on individual variables, mothers with histories of perpetrating neglect exhibited more unrealistic expectations of children and other adults, more hostile attributions toward children and other adults, and poorer performance on tests of EF than comparisons. Only interpersonal problem-solving (in both parenting and nonparenting situations) failed to differentiate the neglect group from comparisons. In regression analyses, both parenting and nonparenting social cognition and EF contributed significantly to child neglect. These findings provide some support for this cognitive model of parenting risk and suggest widespread disturbances in parenting and nonparenting social cognition and neurocognition, may play a role in child neglect.
In relation to child abuse, child neglect has been understudied even though it is more common and causes at least as much harm. While child maltreatment (in a single category) has been linked to substance use disorders (SUD), and while child abuse alone (without neglect) has been linked to SUD, it remains unclear whether differences exist in the link between SUD and child abuse alone (without neglect) versus SUD and child neglect alone (without abuse). Utilising the National Survey of Child and Adolescent Well-Being II (NSCAW II, 2014): Wave I - 2008-09; Wave II - 18months later: N=5872), we used logistic regression to longitudinally assess whether past-year abuse versus past-year neglect in Wave I are equally influential in predicting newly diagnosed substance dependence in Wave II (among youth without SUD in Wave I). After adjusting for several factors, we found that past-year child neglect in Wave I was a significant predictor of newly diagnosed substance dependence in Wave II among youth who did not have SUD in Wave I. Other forms of youth maltreatment were unrelated. The findings suggest that child welfare and substance abuse professionals could pay special attention to youth with past-year neglect in order to help prevent the emergence of new substance dependence disorders. Copyright (c) 2015 John Wiley & Sons, Ltd.
Objectives: It is hypothesized that parents who have physically abused a child or who are at high risk to physically abuse a child form more negative/less positive impressions about children than nonabusive/low-risk-for-abuse parents. However, to date, the overall evidence from the several individual studies testing this hypothesis has been inconclusive. Method: The current meta-analysis compared the impressions that abusive/high-risk-for-abuse parents and nonabusive/low-risk-for-abuse parents form about children (k = 27, N = 1,645). Results: Overall, we estimated the difference in parents' impressions of children to be about 1/3 of 1 standard deviation in the hypothesized direction (d = 0.32, 95% confidence interval [0.19, 0.44]). This difference was found among studies using a variety of procedures and a variety of dependent variables. Further, an analysis of the distribution of p values from the published studies corroborated this finding. Conclusions: Collectively, the current meta-analysis confirms differences between abusive/high-risk-for-abuse parents' and nonabusive/low-risk-for-abuse parents' impressions of children. However, despite the clear evidence for the existence of an effect, the current results suggest the magnitude of this effect is modest. Future research should determine whether parents' impressions are meaningfully related to parents' child-directed behaviors. Such research would be informative as to whether parents' impressions of children should be targeted in interventions aimed at reducing physically abusive parenting behaviors.
Aims To assess the knowledge, attitudes and experience of a group of Malaysian dental health care providers regarding child physical abuse (CPA) cases in terms of frequency of occurrence, diagnosis, risk factors and reporting. Methods A questionnaire was distributed to all dental health care providers attending a national paediatric dentistry conference in Kuantan, Malaysia, and demographical variables, knowledge, attitudes and experience about CPA, risk factors and the reasons for not reporting abuse cases were collected. Descriptive statistics and bivariance analysis were performed. A 5 % level of statistical significance was applied for the analyses (p <= 0.05). Results The response rate was 74.7 %. Half of the respondents (52.8 %) stated that the frequency of occurrence of CPA is common in Malaysia. Full agreement between dental health care providers was not determined concerning the identification of signs of CPA and its risk factors. Although 83.3 % were aware that reporting CPA is a legal requirement in Malaysia, only 14.8 % have reported such cases. Lack of adequate history was the main reason for not reporting. Virtually two-thirds of the respondents (62 %) indicated that they had not received sufficient information about CPA and were willing to be educated on how to diagnose and report child abuse cases (81.5, 78.7 %, respectively). Conclusions There were considerable disparities in respondents' knowledge and attitudes regarding the occurrence, signs of suspected cases, risk factors and reporting of CPA. Despite being aware of such cases, only a handful was reported. Enhancement in the education of Malaysian dental health care providers on recognising and reporting CPA is recommended.
This paper addresses child abuse and the Social Services protection and builds upon a study of verdicts concerning 2 Care of Young Persons Act (CYPA). The aim was to explore the extent of, and what characterised, the violence the children were being subjected to. A central finding was that of all the applications of 2 CYPA during one year concerning 196 children, 13-18 years, 70% concerned children reported as subjected to violence. The violence was in most cases described as severe and systematically exerted over many years with intimidating tactics of power and control. More girls than boys were in question for care because of violence. Girls were also to a greater extent reported as having been subjected to sexual abuse or coercive control of their sexuality in relation to standards regarding honour and virginity. In an international perspective the findings can be said to confirm the need to analyse such factors as gender, power and control when research and interventions concerns children abused by their parents. In a Swedish context the findings can be said to suggest that the 2 CYPA is a crucial intervention to protect children from violence.
Children in Scotland who are subject to child protection interviews should be interviewed jointly by specially trained police officers and social workers who have attended training based on a national curriculum. This study, which was conducted in two Strands, explores the effectiveness of the training, focusing specifically on the free narrative phase of the interview. Strand A explores respondents' self-evaluation, obtained through semi-structured interviews with 16 participants, while Strand B comprises an analysis of 21 role-play interviews. The findings show a considerable discrepancy between perceived practitioner confidence in ability and actual skill levels observed in role-plays, where interviewers showed a persistent overuse of specific and closed questions, while neglecting the use of open prompts and open questions to encourage free narrative. The study concludes that the national curriculum is not as effective in preparing participants for the free narrative phase of the interview as perceived by participants. Possible reasons are explored. Copyright (c) 2015 John Wiley & Sons, Ltd.
Child protection and welfare have become international issues in a globalized world. Ideas about childhood and the upbringing of children vary widely, depending upon the prevailing economic, socio-cultural, religious, and political contexts. These have had dramatic effects on the way societies value children, and the role acquired by the state in their protection and advancing their well-being. Children, however, remain at risk. They are placed at risk by the breakdown of extended family systems as a result of urbanization, and as a result of impaired functioning of some nuclear families, in the absence of kinship safety nets. Some traditional cultural practices place children at risk, especially girl children. Poverty creates risks for all children but it can create specific catastrophic risks for girls. Countries can enact visionary laws intended to protect children, but they will be ineffective against entrenched social attitudes, especially if only limited resources can be provided to implement and enforce them. This is the ultimate challenge that the world community must address if the vision of the United Nations Convention on the Rights of the Child is to be realized.
The risk for using child abuse images (CAI) is difficult to assess, especially as it mostly remains undetected by legal authorities. The present study investigates the association of aspects of sexual preference and dynamic risk factors with CAI only and mixed offending (CAI and child sexual abuse) over lifetime and within six months prior to assessment. A sample of 190 undetected, self-identified pedo- and/or hebephiles was investigated. Multinomial logistic regression analyses revealed that sexual preoccupation is of great importance, especially for recent CAI only and mixed offending, as well as lifetime mixed offending. Although inconclusive, a sexual preference for early-pubescent children seems to be of interest for recent and lifetime offending. A sexual preference for prepubescent children, additional paraphilias and sexualised coping have shown some, although no statistically meaningful association with lifetime offending. Gender preference, exclusivity of pedohebephilia and offence-supportive attitudes did not show any significant relation with offending behaviour.
The view of what constitutes child abuse and neglect is dependent on the laws, cultural context, local thresholds and the availability. Since 1982, the International Society for the Prevention of Child Abuse and Neglect (ISPCAN) has conducted surveillance of child maltreatment and child protection every two years, published in World Perspectives on Child Abuse. It is hoped that up to date information will inform the development of laws, policies and programs to better address child abuse and neglect. This article is based on data on child sexual abuse and exploitation from 73 countries gathered online in 2015-16 for the 12 edition of World Perspectives. Respondents were key informants who were knowledgeable professionals in the child protection field. They were encouraged to consult with colleagues so as to provide accurate information. Countries were grouped into different regions of the world and into income level categories. The findings focus on definitions of abuse and neglect, laws, policies and programs to address and prevent maltreatment and barriers to prevention. It is evident that there is considerable variability across regions and country income categories, and that programs and services need to be considerably strengthened, even in high income countries. (C) 2017 Published by Elsevier Ltd.
Interpreters play a crucial role in many investigative interviews with child complainants of sexual abuse; however, little has been written about the interpreting process from the perspective of the interviewers. This study elicited interviewers' perspectives about the challenges of using interpreters, with the aim of understanding how investigative interviews could be improved. The participants consisted of 21 investigative interviewers and prosecutors of child abuse cases (from a range of jurisdictions) who use interpreters on a regular basis. Thematic analysis of semi-structured interviews with the professionals about the interpreting process revealed two main challenges particular to child abuse interviews, namely the interpreters' lack of preparedness to deal with the traumatic and sensitive nature of children's abuse histories, and an insufficient understanding of best-practice' child interview process. The recommendations focus on the need for more specialised training for, and screening of, interpreters, and more extensive use of pre-conferencing to familiarise children with the interpreter-mediated interview process.
The present pilot study sought to identify predictors of delays in child sexual abuse (CSA) disclosure, specifically whether emotional and physical abuse by a parental figure contributes to predicting delays over and above other important victim factors. Alleged CSA victims (N= 79), whose parental figures were not the purported sexual abuse perpetrators, were interviewed and their case files reviewed, across two waves of a longitudinal study. Regression analyses indicated that experiencing both emotional and physical abuse by a parental figure was uniquely predictive of longer delays in disclosure of CSA perpetrated by someone other than a parental figure. Victim-CSA perpetrator relationship type and sexual abuse duration also significantly predicted CSA disclosure delay, whereas victim age at the time of the police report, victim gender, and victims' feelings of complicity were not significant unique predictors. Child abuse victims' expectations of lack of parental support may underlie these findings. Parent-child relationships are likely crucial to timely disclosure of CSA, even when a parent is not the CSA perpetrator. (C) 2016 Elsevier Ltd. All rights reserved.
In the past three decades, there has been an exponential increase in the worldwide availability of Internet access and devices that are able to access online materials. This literature review investigated whether increased accessibility of Internet child pornography (CP) increases the risk of in-person child sexual exploitation. The current review found little to no evidence that availability of the Internet has increased the worldwide incidence or prevalence of in-person child sexual abuse. In fact, during the time period in which the Internet has flourished, international crime statistics have shown a steady decrease of in-person child sexual abuse. The only exception to this trend is an increase in Internet child pornography or luring offenses (e.g., Stats Can, 2014), which involves child abuse by definition. This article reviews the impact of the Internet on child sexual abuse. It also reviews the characteristics of online CP offenders. Treatment of these offenders and prevention of such offenses is also discussed.
Introduction: Estimating the national prevalence of child sexual abuse (CSA) and its association with health and developmental outcomes is the first step in developing prevention strategies. While such data are available from many countries, less is known about the epidemiology of CSA in Japan. Methods: For this systematic review, we searched English databases: Embase, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Ovid OLDMEDLINE(R), PsycINFO, and Japanese databases: Cinii, J-Stage, Children's Rainbow Center Japan, Japan Child and Family Research Institute, Japanese Journal of Child Abuse and Neglect to identify articles published before July 2015 examining the lifetime prevalence of CSA in Japan using non-clinical samples. Data were extracted from published reports. Results: We initially identified 606 citations and after abstract review, retrieved 120 publications. Six studies that met the selection criteria and additional two relevant studies were reviewed. The range of contact CSA for females was 10.4%-60.7%, and the prevalence of this type of CSA for males was 4.1%. The range of penetrative CSA for females was 1.3%-8.3% and that for males was 0.5%-1.3%. A number of methodological issues were identified, including a lack of validated measures of CSA, and low response rates. Conclusion: In contrast to a lower prevalence of penetrative CSA, the prevalence of contact CSA among Japanese females may be comparable or higher in relation to international estimates. Future research on children's perceptions of and exposure to sexual abuse, crime and exploitation in Japan is discussed. (C) 2017 Elsevier Ltd. All rights reserved.
The population of potential child abuse offenders has largely been unstudied. In the current study, we examine whether a six-component model used for primary diabetes prevention could be adapted to child sexual abuse pre-offenders, whereby individuals who are prone to sexual abuse but have not yet committed an offense can be prevented from committing a first offense. The six components include: define and track the magnitude of the problem, delineate a well-established risk factor profile so that at-risk persons can be identified, define valid screening tests to correctly rule in those with the disease and rule out those without disease, test effectiveness of interventionsthe Dunkelfeld Project is an example, produce and disseminate reliable outcome data so that widespread application can be justified, and establish a system for continuous improvement. By using the diabetes primary prevention model as a model, the number of victims of child sexual abuse might be diminished.
Although researchers have found that child welfare placement disruptions are associated with elevated youth physical and mental health problems, the mechanisms that explain this association have not been previously studied. The present study built on a previous investigation of the physical and behavioral consequences of long-term permanent placement patterns among youth who participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). The current investigation (n = 251) aimed to (a) report the early adolescent living situations of youth with different long-term placement patterns, and (b) to delineate the roles of adverse childhood experiences (ACEs) and post-traumatic stress (PTS) reactions in the association between unstable long-term placement patterns and physical and mental health problems during the transition to adolescence. Information about youth's living situations, ACEs, and physical and mental health was gathered prospectively from child protective services records and biannual caregiver and youth interviews when youth were 4-14 years old. The majority of youth remained with the same caregiver during early adolescence, but youth with chronically unstable permanent placement patterns continued to experience instability. Path analyses revealed that ACEs mediated the association between unstable placement patterns and elevated mental, but not physical, health problems during late childhood. Additionally, late childhood PTS mediated the association between unstable placement patterns and subsequent escalations in physical and mental health problems during the transition to adolescence. Findings highlight the importance of long-term permanency planning for youth who enter the child welfare system and emphasize the importance of trauma-focused assessment and intervention for these youth. (C) 2016 Elsevier Ltd. All rights reserved.
Amendments made to the Child Abuse Prevention and Treatment Act in 2003 and the Individuals with Disabilities Education Improvement Act in 2004 opened the door to a promising partnership between child welfare services and early intervention (EI) agencies by requiring a referral to EI services for all children under age 3 involved in a substantiated case of child abuse, neglect, or illegal drug exposure. However, little research has been conducted to assess the implications of these policies. Using data drawn from a nationally representative study conducted in 2008-2009, we observed less than a fifth of all children in substantiated cases to receive a referral to developmental services (18.2%) approximately 5 years after the passage of the amendments. Of children in contact with the U.S. child welfare system, Hispanic children of immigrants demonstrated the greatest developmental need yet were among the least likely to receive EI services by the end of the study period. Implications for policy and practice are discussed.
The purpose of this article was to examine the potential impact of child welfare services on the risk for fatal child maltreatment. This was conducted using a subsample of children who were identified as prior victims in the National Child Abuse and Neglect Data System from 2008 to 2012. At the multivariate level, the analyses show that case management services act to protect children from death as do family support services, family preservation services, and foster care, but that the results vary by type of maltreatment experienced. The author recommends that before strong conclusions are drawn, additional research in this area is warranted.
Child wellbeing is identified as one of the three primary goals for child welfare outcomes, thus strong wellbeing assessment tools are crucial to the monitoring of child welfare success. Data from wellbeing measures can serve to identify child needs, inform case planning, monitor change over time, and evaluate intervention impact at the individual, local, state, and national levels. This paper examines the goals, strengths, and challenges of four wellbeing measures currently used with child welfare populations, namely: the Child and Adolescent Functional Assessment Scale (CAFAS), the Child and Adolescent Needs and Strengths Assessment Tool (CANS), the Child Behavior Checklist and related tools from the Achenbach System of Empirically Based Assessment (CBCL/ASEBA), and the Treatment Outcomes Package (TOP). For each measure, we describe the content, practical attributes, clinical applications, and evidence of reliability and validity. We explore implementation considerations and provide recommendations for system changes to ensure the optimal use of each instrument. Agencies are encouraged to carefully consider their needs, goals, capacities, and implementation infrastructure to inform selection of tools that will aid them in successfully supporting and monitoring child wellbeing over time. (C) 2016 Elsevier Ltd. All rights reserved.
David Stoesz offers a sweeping critique of the Children's Bureau and social work education by claiming the existence of a child welfare cartel. He also attacks the quality of social work education and research, which he claims has poorly invested government funding and helped create the unmitigated failures of the American child welfare system. However, closer examination reveals that many of his claims, while dramatic, are actually ill conceived and unsupportable. We attempt to clarify and inform readers about some significant aspects of the field of child welfare and the contemporary responses being made by the federal government in partnership with social work educators and researchers.
Childhood and adolescence coincide with rapid structural and functional maturation of brain networks implicated in Theory of Mind (ToM); however, the impact of paediatric traumatic brain injury (TBI) on the development of these higher order skills is not well understood. ToM can be partitioned into conative ToM, defined as the ability to understand how indirect speech acts involving irony and empathy are used to influence the mental or affective state of the listener; and affective ToM, concerned with understanding that facial expressions are often used for social purposes to convey emotions that we want people to think we feel. In a sample of 84 children with mild-severe TBI and 40 typically developing controls, this study examined the effect of paediatric TBI on affective and conative ToM; and evaluated the respective contributions of injury-related factors (injury severity/lesion location) and non-injury-related environmental variables (socio-economic status (SES)/family functioning) to long-term ToM outcomes. Results showed that the poorest ToM outcomes were documented in association with mild-complicated and moderate TBI, rather than severe TBI. Lesion location and SES did not significantly contribute to conative or affective ToM. Post-injury family affective responsiveness was the strongest and most significant predictor of conative ToM. Results suggest that clinicians should exercise caution when prognosticating based on early clinical indicators, and that group and individual-level outcome prediction should incorporate assessment of a range of injury-and non-injury-related factors. Moreover, the affective quality of post-injury family interactions represents a potentially modifiable risk factor, and might be a useful target for family-centred interventions designed to optimise social cognitive outcomes after paediatric TBI.
AimTo identify nurses' role and experiences of keeping children safe. BackgroundApproaches to preventing, identifying and responding to child abuse and neglect have moved towards a multidisciplinary approach where all professionals are expected to contribute to the goal of keeping children safe. Frequently in contact with children and families, nurses well positioned to contribute to keeping children safe from abuse and neglect. Much has been published around nurses' experiences of their role in keeping children safe, but this literature has not yet been synthesized to determine the challenges and potential scope of this role. DesignIntegrative review following an Integrative Review framework. Data sourcesStudies were identified through a search of the electronic databases CINAHL, Medline, Web of Science, Scopus and Informit to identify literature published between 2005-2015. Review methodsAll the studies were critically appraised for methodological quality using the Critical Skills Appraisal Programme. Data from each study were extracted and categorized according to the review aims and the study's major findings. ResultsInclusion criteria were met in 60 studies. Three main findings were identified including nurses' insufficient knowledge, need for validation and improved communication and balancing surveillance and support for vulnerable families. ConclusionsNurses have many roles and experiences in keeping children safe but often felt they did not have the knowledge, skills and support to take action in this area. Further research is needed to understand why nurses feel inadequate and disempowered to advocate and intervene on the behalf of children at risk of abuse or neglect.
Sexual abuse perpetrated by a parent particularly the mother creates turmoil in the child who has to depend on the very person who betrays their trust. A review of the literature confirms that there are only a few case studies of mother-child incest reported in the psychoanalytic literature; the incidence of such incest, however, is unknown. Considerably, more information is available in the forensic and child abuse literatures along with an increase in research; yet, there is a paucity of data. Child sexual abuse by women as highly prevalent is described in early societies, and that there is a bias in peoples' minds about the capacity of females to sexually abuse children is raised by many writers. The fact of being abused by one's mother brings up specific issues for survivors of maternal incest. Shame and the fear of not being believed, which was the experience of my female patient and a sense of specialness and failure of recognition of incest by the males, created particular difficulties which had to be dealt with in psychotherapy. This paper describes three teenagers, one female and two males who were sexually abused by their mothers. I have condensed several years of treatment to provide an account of the female patient and a summary of each of the males, and I attempt to explore the dynamics of relatedness in the abused and the abuser.
Objective: To understand effective ways for EMS providers to interact with distressed family members during a field intervention involving a recent or impending out-of-hospital ( OOH) pediatric death. Methods: Eight focus groups with 98 EMS providers were conducted in urban and rural settings between November 2013 and March 2014. Sixty-eight providers also completed a short questionnaire about a specific event including demographics. Seventy-eight percent of providers were males, 13% were either African American or Hispanic, and the average number of years in EMS was 16 years. They were asked how team members managed the family during the response to a dying child, what was most helpful for families whose child suddenly and unexpectedly was dead in the OOH setting, and what follow up efforts with the family were effective. Results: The professional response by the EMS team was critical to family coping and getting necessary support. There were several critical competencies identified to help the family cope including: ( 1) that EMS provide excellent and expeditious care with seamless coordination, ( 2) allowing family to witness the resuscitation including the attempts to save the child's life, and ( 3) providing ongoing communication. Whether the child is removed from the scene or not, keeping the family appraised of what is happening and why is critical. Exclusion of families from the process in cases of suspected child abuse is not warranted. Giving tangible forms of support by calling friends, family, and clergy, along with allowing the family time with the child after death, giving emotional support, and follow-up gestures all help families cope. Conclusion: The study revealed effective ways for EMS providers to interact with distressed family members during an OOH pediatric death
Background Children that living with addicted parents are at risk for intentionally and unintentionally poisoning. Present study aimed to evaluate the effect of parental addiction on unintentional childhood poisoning. Materials and Methods: Totally, 140 admitted children with poisoning in Loghman hospital, Tehran-Iran, as referral center were recruited from March 2013 to July 2014. Cases were matched with 280 controls by age (within a caliper of six months), gender, and date of hospital attendance in Tehran, Iran. Parents were interviewed using an objective checklist about the risk factors of childhood poisoning. Conditional logistic regression with within-group varying weights was used to adjust for measured confounders. Vary weights within the matched set was defined by inverse probability weighting (IPW). Results: Sixty-two of cases (74.7%) were poisoned with Methadone. The odds ratio [OR] 95% confidence interval [CI] of having addicted parents in poisoned children compared to the controls in three scenarios of ordinary, un-stabilized weighted and stabilized weighted conditional regression logistic ORs (95% CI) were 17.3 (8.7, 34.6), 2.6 (1.9, 3.3) and 3.6 (2.9, 4.3) respectively. Conclusion The results indicate that child abuse and neglect have been linked to parental substance abuse. Education on preventive interventions such as safe storage of methadone and store poisoning product out of reach and sight of children are necessary in substance abusing families.
Facial traumas are common in children but often unconsidered. Facial injury is responsible of impressive bleeding because of the rich vascularization of the face; this bleeding is often underestimated because of the immediate arterial vasoconstriction that is very strong for children. The blood volume is 80 ml/kg for a newborn, with a total of 250 ml, reaching 70 ml/kg at one year of age. The evaluation must be rigorously performed due to the risk of a sudden decompensation. Regarding the wounds, the primary repair must be performed directly neat or optimal in case of damaged tissues. The rule is to keep maximum of the integrity and to limit debridement. Careful repair often requires general anesthesia, especially in young children, to facilitate a perfect joining of the edges and of the mucocutaneous lines. Losses of substance should be treated by directed cicatrization. Flaps are never performed in children as a first intention for reasons developed below. Given the elasticity of the facial skeleton, fractures require a brutal shock to occur, but the clinical signs can be misleading. For instance, too specific and sometimes ignored, fractures can show weakly symptomatic signs : the fractures of the condylar and the orbital floor, with their respective complication that are temporomandibular bone ankylosis and definitive diplopia. Possible children abuse should be suspected in case of different age lesions and discrepancies between the told story and types of injuries. Once the vital urgency is eliminated, the orbital emergency should be first considered in facial traumas within the ophthalmology specialty because wounds and contusions of the globe are often under-evaluated and threaten the vision. The second emergency is the orbital floor fracture in its 'trapdoor' type, specific to the child. Combined with a motionless eye and uncontrollable vomiting, this is the second true urgency because it involves the prognosis of the oculomotricity and requires emergency surgery. Finally, dental trauma should not be overlooked because of their functional and aesthetic consequences. Primary cicatrization is usually rapid but scars remain inflammatory during a long time. The risk of hypertrophy exists in case of contusions and lacerations associated with wounds but also during puberty and in some locations. Age interfere with the result because growth will either improve or worsen the initial result, depending on the location and mechanism. The secondary specialized and prolonged managing and monitoring is capital on the functional, aesthetic and psychological points of view. (C) 2016 Elsevier Masson SAS. All rights reserved.
Background: The relation between viral load and disease severity in childhood acute respiratory tract infections (ARI) is not fully understood. Objectives: To assess the clinical relevance of the relation between viral load, determined by cycle threshold (CT) value of real-time reverse transcription-polymerase chain reaction assays and disease severity in children with single-and multiple viral ARI. Study design: 582 children with ARI were prospectively followed and tested for 15 viruses. Correlations were calculated between CT values and clinical parameters. Results: In single viral ARI, statistically significant correlations were found between viral loads of Respiratory Syncytial Virus (RSV) and hospitalization and between viral loads of Human Coronavirus (HCoV) and a disease severity score. In multiple-viral ARI, statistically significant correlations between viral load and clinical parameters were found. In RSV-Rhinovirus (RV) multiple infections, a low viral load of RV was correlated with a high length of hospital stay and a high duration of extra oxygen use. The mean CT value for RV, HCoV and Parainfluenza virus was significantly lower in single-versus multiple infections. Conclusion: Although correlations between CT values and clinical parameters in patients with single and multiple viral infection were found, the clinical importance of these findings is limited because individual differences in host-,viral and laboratory factors complicate the interpretation of statistically significant findings. In multiple infections, viral load cannot be used to differentiate between disease causing virus and innocent bystanders. (C) 2017 Elsevier B.V. All rights reserved.
Introduction: It is important to elucidate the psychologically positive aspects of childbirth for mothers, and not only the negative aspects such as perinatal depression. This study aimed to examine psychological growth after childbirth and its related variables by focussing on five factors of posttraumatic growth: relating to others, new possibilities, personal strength, spiritual change and appreciation of life.Methods: Pregnant women during mid-pregnancy were consecutively recruited at a women's hospital in Japan and followed up 1 month after childbirth. Psychological growth was assessed by the Posttraumatic Growth Inventory.Results: Among 177 participants, 117 (66.1%) completed follow-up assessments 1 month after childbirth. Multivariable regression analysis revealed that primipara, higher resilience and less fear at childbirth were associated with posttraumatic growth factors of relating to others and new possibilities. High resilience and less fear at childbirth were also associated with personal strength. On the other hand, being primiparous and high depressive symptoms were associated with greater appreciation of life. No variables were associated with spiritual change.Discussion: These findings suggest that giving birth for the first time could be a highly challenging life event as well as an opportunity which leads to PTG, and that giving birth with low fear might lead to mothers' psychological growth. On the other hand, appreciation of life might need attention as it might signify some sorts of coping response. These findings contribute to our understanding of the psychological changes experienced by mothers.
Background: Recent studies have suggested that the interactions among several factors affect the onset, progression, and prognosis of major depressive disorder. This study investigated how childhood abuse, neuroticism, and adult stressful life events interact with one another and affect depressive symptoms in the general adult population. Subjects and methods: A total of 413 participants from the nonclinical general adult population completed the Patient Health Questionnaire-9, the Child Abuse and Trauma Scale, the neuroticism subscale of the shortened Eysenck Personality Questionnaire - Revised, and the Life Experiences Survey, which are self-report scales. Structural equation modeling (Mplus version 7.3) and single and multiple regressions were used to analyze the data. Results: Childhood abuse, neuroticism, and negative evaluation of life events increased the severity of the depressive symptoms directly. Childhood abuse also indirectly increased the negative appraisal of life events and the severity of the depressive symptoms through enhanced neuroticism in the structural equation modeling. Limitations: There was recall bias in this study. The causal relationship was not clear because this study was conducted using a cross-sectional design. Conclusion: This study suggested that neuroticism is the mediating factor for the two effects of childhood abuse on adulthood depressive symptoms and negative evaluation of life events. Childhood abuse directly and indirectly predicted the severity of depressive symptoms.
Objective: To investigate whether individual differences in coping self-efficacy mediated the association of child abuse and symptoms of ADHD in young adults. Method: Self-reported measures of coping self-efficacy, child abuse, and ADHD were obtained from 66 adults. Results: Adults who reported childhood physical or sexual abuse (prior to the age of 17) had significantly higher levels of ADHD than those who did not. Individual differences in coping self-efficacy fully mediated the association between child abuse and ADHD symptoms in adulthood, such that individuals who endorsed child abuse had lower coping self-efficacy, and coping self-efficacy negatively predicted ADHD symptoms. Discussion: The findings suggest a potential causal mechanism by which childhood physical and sexual abuse may result in ADHD symptoms later in life. Interventions that improve coping skills may be useful in preventing later ADHD symptoms among adults with a childhood history of physical and sexual abuse.
Violence against children is a human rights problem that cuts across gender, race, geographical, religious, socio-economic status and cultural boundaries. The risk of violence towards disabled children during their lifetime is three to four times greater than towards non-disabled children. It starts in early childhood, is more severe and linked to disablist structures in society. Violence is perpetrated by individuals and through institutional practices that are part of disabled children's everyday life. Violence is often misdiagnosed as related to individual impairment, and not recognised by professionals or the victims themselves. Presenting disabled women's reflections of childhood violence, help-seeking and responses to disclosure, this article seeks to raise an awareness of violence towards disabled girls and the need for these to be recognised as a serious child protection issue to be included in official definitions of child abuse.
Objective We aimed to find the prognostic factors to detect the patients who fail the treatment of epilepsy, in the early stages of the disease. Materials&Methods This study was done on the epileptic patients attending the Neurology Clinic of Mofid Children's Hospital, Tehran, Iran from September 2013 to October 2014. After defining the criteria for exclusion and inclusion, the patients were divided to two groups based on responding to the medical treatment for their epilepsy and indices were recorded for all the patients to be used in the statistical analyses. Results The patients' age ranged from 1 to 15 yr. There was 188 patients with refractory seizure in group 1 (experimental group) and 178 patient with well controlled seizure in group 2(control group). There was a significant different between serum drug level in both groups and patients with refractory seizure group had a lower serum drug level than control group. In both groups tonic-clonic was the most common type of seizure. Also the prevalence of brain imaging Abnormalityand other neurologic disorders was significantly higher in patients with refractory seizure in compare with control group. Conclusion Children with seizure who suffer from refractory epilepsy need more attention and exact observation by the medical staff.
The increase of violence against children is a diagnosed social problem in the Costa Rican society. This article focuses on the presence of an ideological bias in the opinion writings of the local newspapers: La Nacion and Diario Extra. It explains how some visions of the sources are ideological and do not contribute to the end of the violence, nor to an effective promotion of childrens Human Rights. In order to avoid violence we must develop a pro-children cultural change, complex multi-institutional social networking, children autonomy and a critic to the family institution.
This study explored the influences on living arrangements of orphans and vulnerable children (OVC) housed at a community-based home in Johannesburg, South Africa. A total of 50 OVC (males = 36%, females = 64%; age range 11 to 18 years) completed an open-ended questionnaire, while some of them also participated in individual interviews and focus group discussions on how they became residents of the community-based home. The data were thematically analysed. Findings suggest their choice to live in a community-based care setting to have been influenced by homelessness with accompanying poverty, health issues, experiences of child abuse and neglect, discrimination, and domestic violence. School psychologists working with OVC from community-based homes should consider pathways by which the children could be provided with needed support for resilient health and wellness.
Background: Obesity is genetically heterogeneous and highly heritable, although polymorphisms explain the phenotype in only a small proportion of obese children. We investigated the presence of copy number variations (CNVs) in "classical" genes known to be associated with (monogenic) early-onset obesity in children. Methods: In 194 obese Caucasian children selected for early-onset and severe obesity from our obesity cohort we screened for deletions and/or duplications by multiplex ligation-dependent probe amplification reaction (MLPA). As we found one MLPA probe to interfere with a polymorphism in SIM1 we investigated its association with obesity and other phenotypic traits in our extended cohort of 2305 children. Results: In the selected subset of most severely obese children, we did not find CNV with MLPA in POMC, LEP, LEPR, MC4R, MC3R or MC2R genes. However, one SIM1 probe located at exon 9 gave signals suggestive for SIM1 insufficiency in 52 patients. Polymerase chain reaction (PCR) analysis identified this as a false positive result due to interference with single nucleotide polymorphism (SNP) rs3734354/rs3734355. We, therefore, investigated for associations of this polymorphism with obesity and metabolic traits in our extended cohort. We found rs3734354/rs3734355 to be associated with body mass index-standard deviation score (BMI-SDS) (p = 0.003), but not with parameters of insulin metabolism, blood pressure or food intake. Conclusions: In our modest sample of severely obese children, we were unable to find CNVs in well-established monogenic obesity genes. Nevertheless, we found an association of rs3734354 in SIM1 with obesity of earlyonset type in children, although not with obesity-related traits.
There is a growing interest in English-speaking jurisdictions, including Australia, North America, Canada, the United Kingdom and New Zealand, about the prevention of sexual abuse perpetrated by children against other children. The aim of this review was to identify opportunities for research, policy and practice which could enhance the prevention agenda relating to the perpetration of sexual abuse by children through conducting a Critical Interpretive Synthesis. Eleven electronic databases were searched in the period from 22 April to 23 May 2013 and included: SocINDEX, Social Services Abstracts, Applied Social Sciences Index and Abstracts, Family and Society Studies Worldwide, Project Muse, PsychINFO, Family and Society Plus, Jstor, Expanded Academic ASAP, Web of Science and Google Scholar. Key individual journals were also searched, including Child Abuse and Neglect and the Journal of Interpersonal Violence, as well as the grey literature. The search was guided by the research question: How could the prevention agenda relating to sexual abuse perpetrated by children be enhanced? The systematic literature search yielded 3323 titles, and 34 of these papers were included in the final synthesis. The authors identified five domains operating in the evidence base: characteristics, causes, communications, interventions and treatments. A synthesising construct emerged from the review: prevention-enhancing interactions. This construct referred to the potential for enhancing the prevention agenda which exists as the evidence domains interact with one another, and with the public health model of prevention. The authors consider this review to be a timely contribution to the current agenda pertaining to sexual abuse perpetrated by children. It provides researchers, policy makers and practitioners in the field with an evidence-informed conceptualisation of opportunities for enhancing prevention work.
Immigrants from East Asia make up 14.21% of the total number of immigrants in Canada. These families face many challenges as they acculturate to North America, but, sadly, some of these children may be at risk for sexual abuse. In this article, we outline the ways in which East Asian children, compared with Western nonimmigrant children, are at a particular disadvantage when considering prosecution of those who perpetrate abuse. We focus specifically on 3 areas of concern: (1) cultural differences that can shape children's memory recall, (2) cultural differences that can impact the path of disclosure of sexual abuse, and (3) language differences that reduce the chances that perpetrators will be prosecuted for sexual abuse. The consequences for East Asian immigrant youth who allege (or are suspected) that they are victims of abuse are serious. East Asian children face an uphill battle to see justice in sexual abuse cases. Thus, a significant portion of immigrant children will not see their abusers punished, and, worse, the knowledge that prosecution is unlikely may make East Asian immigrant children vulnerable.
Introduction: The success of the vaccines available on the market has significantly increased interest in vaccine development.Areas covered: The main aim of this paper is to discuss the most important vaccines of pediatric interest that are currently being developed. New pneumococcal vaccines and vaccines against group B Streptococcus, Staphylococcus aureus and respiratory syncytial virus are analyzed in detail.Expert commentary: Advances in understanding human immunology, including human monoclonal antibody identification, sequencing technology, and the ability to solve atomic level structures of vaccine targets have provided tools to guide the rational design of future vaccines. It is likely that some of these vaccines will reach the market in the future and will thus partially contribute to the prevention of very severe diseases that significantly affect the morbidity and mortality of children. However, further studies in animals and several clinical trials in children must be performed before new vaccines become licensed.
Children in pre-school age present a limited cognitive development, a restricted vocabulary and a short attention span, which do not allow conducting classical taste sensitivity measures as developed for adults. The aim of this study was to develop and validate an age-appropriate protocol for sensitivity testing of the five basic tastes with pre-schoolers. One hundred and forty children aged 3-4 years (mean age 46.3 months, SD 3.4) performed a paired comparison task consisting of discriminating water from "magic water" by relying on their affect. In order to accommodate the age group, the task was gamified and did not require verbal responses. Sweet (sucrose, ranging from 0.94 to 4.32 g/l), sour (citric acid monohydrate, 0.20-0.38 g/l), umami (monosodium glutamate, 0.17-0.49 g/l), salty (sodium chloride, 0.34-0.98 g/l), and bitter (quinine hydrochloride dihydrate, 0.0014-0.0038 g/l) water dilutions were tested at four levels. Subsets of about 20 children per taste participated in retest sessions. Individual sensitivity scores were derived in two manners, following the experimenter's success criterion (water with taste is classified as magic) and the child's criterion for "magic water" (children's individual magic-labelling strategies). Results show that the protocol was highly engaging, that the children performed the task consistently, and that the children's performances were not dependent on cognitive level differences, thus validating the protocol for this study. On average, the children were clearly more sensitive to sour stimuli selected dilutions were not equivalent across tastes. Different sensitivity distributions of the children were obtained across taste modalities and scoring criteria. The key elements of an age-appropriate protocol for pre-schoolers are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: This study examines how socio-demographic and clinical characteristics influence suicide risk among a large, urban sample of children (ages 12 and younger) receiving Psychiatric Emergency Services (PES). Methods: Bivariate and binomial logistic regression analyses were employed to analyze data for a sample of 951 urban children presenting for pediatric PES. Results: Approximately 17.2% of patients presented had a history of suicidal thought and behavior. Despite the larger number of black children presenting for PES, we found no significant difference in suicide risk across ethnic group, though the prevalence rates were increasingly higher in Whites, Latinos, and Black respectively. Of those presenting with suicidality: 65.1% were diagnosed with a behavioral disorder, 263% were diagnosed with a mood disorder, 3.8% with a psychotic disorder, and 4.8% with another disorder. About one in ten suicidal cases admitted to prior child abuse. Furthermore, patients admitted to the hospital for suicidality were more likely to be female, to have a mood disorder, and to be appropriately discharged to an inpatient setting following initial hospital care. Conclusions: The study points to the importance of screening publically insured (Medicaid) urban children experiencing psychological distress regardless of ethnicity and age for suicide risk. Clinicians should consider these findings when working with children in psychiatric crisis. (C) 2016 Published by Elsevier Ltd.
The aim of this article is to systematically review the literature studying the association between television viewing and children's executive function, academic performance, attention, language and play. Using keywords: television, children, infants, attention, language, education and cognition, five online databases were searched. Seventy-six studies that met all the inclusion criteria were reviewed. The findings suggest the relationship between television viewing and children's development is complex. First, the likely effects of television may depend on children's individual characteristics, family and social context. Second, the features of television, such as content and editing pace, and the type of exposure (foreground or background) may affect outcomes. Specifically, watching high-quality educational content during preschool years improves children's basic academic skills and predicts subsequent positive academic performance. Conversely, television viewing in infancy is disruptive to play; it reduces the quality and quantity of child-parent interactions and is associated with inattentive/hyperactive behaviours, lower executive functions, and language delay, at least in the short-term. It remains unclear whether these interactions between television and cognition are long lasting. Future research should focus on the systematic investigation of the pathways that link particular components of television and the type of exposure with individual and contextual factors, to investigate their potential unique and combined effects on development. Researchers must also address the challenge of investigating the diverse and rapidly changing technologies to which the current generation of children are exposed.(C) 2017 Elsevier Inc. All rights reserved.
In European industrial countries severe underweight children due to malnutrition are uncommon. The case of a 7aEuromonth-old infant girl hospitalized with severe underweight is presented. The child suffered from considerable chronic malnutrition with a severe reduction of body weight (3470 g) and reduced growth as well as general retardation. In hospital the infant quickly recovered after adequate food supply. A predisposition to disease could be clinically excluded. In such cases the degree of malnutrition as well as the duration of food shortage has to be estimated with a classification as acute or chronic malnutrition.
Background: Vernal keratoconjunctivitis (VKC) is a chronic and often severe bilateral conjunctivitis. VKC etiology still remains unclear although endocrine, genetic, neurogenic and environmental factors have been implicated. Vitamin D is a fat-soluble prohormone whose main function is the regulation of calcium and phosphate metabolism. The aim of this study was to evaluate serum vitamin D in children affected by VKC compared to the healthy children and investigate the relationship between its levels and disease severity. Methods: A total of 110 children, 47 affected by VKC, aged between 5 and 12 years were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, "Sapienza" University of Rome. Used as controls were 63 healthy children with negative skin prick test (SPT), without allergic, ocular and systemic disease. Serum samples were obtained in April from all the children included in the study. Vitamin D dosage was repeated in October in 20 patients after therapy and in 20 controls. A conjunctival scraping was performed in all children affected by VKC. Results: Children affected by VKC had lower vitamin D levels compared to healthy controls and we found an increase in vitamin D levels after therapy with cyclosporine eye drops 1% although this increase was lower than that of healthy controls. Moreover we found significant correlations between vitamin D level and the severity of the disease. Conclusions: The study shows that children affected by VKC have lower vitamin D levels when compared to healthy controls and highlights a significant correlation between its levels and disease severity.
Objectives: To test the performance of a single 3D IR T2-Weighted sequence compared to a Whole-body MRI protocol including DWI, T1-Weighted and STIR 3D IR (3S) in a pediatric population. Methods: Two radiologists (15 and 30 years of experience),reviewed WBMRIs: first the STIR alone and 2 weeks later the 3S protocol. The indications were variable. Only positive findings were explicitly reported. A third reader compared the results to gold standard (GS) exams specific for the pathology. Agreement between the two readers, sensitivity and positive predictive value of STIR were calculated. Results: fifty-four WBMRIs were included (16 suspected child abuse, 8 chronic recurrent multifocal osteomyelitis (CRMO), 11 lymphomas, 4 osteosarcomas, 9 neuroblastomas, 6 histiocytosis). The mean age was 6 years 10 months, range: 1 month to 15 years. Agreement between readers was of 0.87 [0.82-0.91] for 3D STIR, and 0.89 [0.83-0.93] for the 3S protocol. For reader 1 sensitivity of 3D STIR was 81.6% and of 3S 81.0%. For reader 2 it was 74.1% for 3D STIR and 74.7% for 3S. For both readers and for both protocols, the positive predictive value (PPV) depended on the type of disease (for example 100% histocytosis and osteosarcomas, >90% for child abuse, >85% CRMO but <70% for lymphoma and neuroblastoma). Conclusions: Sensitivities were not different between the 2 protocols, for each reader and were different between the 2 readers for each protocol. (C) 2017 Elsevier B.V. All rights reserved.
Familiarising researchers and practitioners with different countries' policies for police interviews with children contributes to an exchange of knowledge and strengthens global approaches against child abuse. We start by describing the system of videotaped testimonies in Cyprus during the first 10years of this system's implementation. We then continue on to the effects of tourism on police interviews with children. Police forces in destinations with high tourist numbers need to comprehend how tourist seasons could influence police interviews with children. No studies investigated whether children of tourists testified in police departments during their holidays. We explored how tourist seasons affected the number of testimonies obtained by Cyprus police forces, taking into account the presence of non-Cypriot and non-native speaking children, the number of testimonies taken in languages other than Greek, and the presence of translators during the interviews. We analysed the national sample of police interviews with children for a period of a decade using official police records and copies of transcripts of children's testimonies. As expected, the results revealed no significant differences in police interviews with children during tourist seasons but show a slight increase in the number of interviews with non-Cypriot children during tourist seasons. Copyright (c) 2016 John Wiley & Sons, Ltd.
Patients with B-cell hematologic malignancies who progress through first-or second-line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T-cell expansion. The major toxicity associated with CAR T-cell infusions is cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment-related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab-refractory patients. Other toxicities of CAR T-cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients' medications is imperative to eliminate medications that may contribute to treatment-related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long-term follow-up will help establish the place of CAR T cells in therapy.
Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology. We report here meeting highlights on the covered topics of diagnostic pitfalls, implications by the new WHO classification, insights from discovered genomic lesions as well as TCR-centric concepts of cellular dynamics in host defense, auto-immunity and tumorigenic clonal escape, including predictions to be derived from in vivo imaging and mathematical modeling. Presentations on novel treatment approaches were supplemented by strategies of optimizing T-cell immunotherapies. Work packages, that in joint efforts would advance the field of MTCL more efficiently, are identified.
In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3-ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense-antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3' untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5' and 3' rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 59 RACE and analyses of deep sequencing data from LNCaP cells treated +/- androgens revealed six high-confidence sense-antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense-antisense chimeric transcription.
Background: In cat visual cortex, critical period neuronal plasticity is minimal until approximately 3 postnatal weeks, peaks at 5 weeks, gradually declines to low levels at 20 weeks, and disappears by 1 year of age. Dark rearing slows the entire time course of this critical period, such that at 5 weeks of age, normal cats are more plastic than dark reared cats, whereas at 20 weeks, dark reared cats are more plastic. Thus, a stringent criterion for identifying genes that are important for plasticity in visual cortex is that they show differences in expression between normal and dark reared that are of opposite direction in young versus older animals. Results: The present study reports the identification by differential display PCR of a novel gene, alpha-chimaerin, as a candidate visual cortex critical period plasticity gene that showed bidirectional regulation of expression due to age and dark rearing. Northern blotting confirmed the bidirectional expression and 5'RACE sequencing identified the gene. There are two alternatively-spliced alpha-chimaerin isoforms: alpha 1 and alpha 2. Western blotting extended the evidence for bidirectional regulation of visual cortex alpha-chimaerin isoform expression to protein in cats and mice. alpha 1- and alpha 2-Chimaerin were elevated in dark reared compared to normal visual cortex at the peak of the normal critical period and in normal compared to dark reared visual cortex at the nadir of the normal critical period. Analysis of variance showed a significant interaction in both cats and mice for both alpha-chimaerin isoforms, indicating that the effect of dark rearing depended on age. This differential expression was not found in frontal cortex. Conclusions: Chimaerins are RhoGTPase-activating proteins that are EphA4 effectors and have been implicated in a number of processes including growth cone collapse, axon guidance, dendritic spine development and the formation of corticospinal motor circuits. The present results identify alpha-chimaerin as a candidate molecule for a role in the postnatal critical period of visual cortical plasticity.
In this paper, we reviewed four key themes in the study of clean power transition in China, the resources potential, the technology advancement, the air pollution control, and the policy and reform of the power sector. In each theme, we summarized the ongoing research development and highlighted some key areas for further study. Given that China's power sector transition is a huge task, we hope this review will add some discussions into the ongoing conversation. (C) 2016 Elsevier B.V. All rights reserved.
Much attention is being given to estimating cement-related CO2 emissions in China. However, scant explicit and systematical exploration is being done on regional and national CO2 emission volumes. The aim of this work is therefore to provide an improved bottom-up spatial-integration system, relevant to CO2 emissions at factory level, to allow a more accurate estimation of the CO2 emissions from cement production. Based on this system, the sampling data of cement production lines were integrated as regional- and national-level information. The integration results showed that each ton of clinker produced 883 kg CO2, of which the process, fuel, and electricity emissions accounted for 58.70%, 35.97%, and 5.33%, respectively. The volume of CO2 emissions from clinker and cement production reached 1202 Mt and 1284 Mt, respectively, in 2013. A discrepancy was identified between the clinker emission factors relevant to the two main production processes (i.e., the new suspension preheating and pre-calcining kiln (NSP) and the vertical shaft kiln (VSK)), probably relevant to the energy efficiency of the two technologies. An analysis of the spatial characteristics indicated that the spatial distribution of the clinker emission factors mainly corresponded to that of the NSP process. The discrepancy of spatial pattern largely complied with the economic and population distribution pattern of China. The study could fill the knowledge gaps and provide role players with a useful spatial integration system that should facilitate the accurate estimation of carbon and corresponding regional mitigation strategies in China.
With the global environmental pollution and fossil energy shortage problems getting increasingly serious, renewable energy sources (RES) are drawing more and more attention. In China, RES are experiencing rapid development. However, because of the randomness of RES and the volatility of power output, energy storage technology is needed to chip peak off and fill valley up, promoting RES utilization and economic performance. So to speak, energy storage is the precondition of large-scale integration and consumption of RES. However, China's energy storage industry is at the exploration stage and far from commercialization. This restricts the development of RES to certain extent. For this reason, this paper will concentrate on China's energy storage industry. First, it summarizes the developing status of energy storage industry in China. Then, this paper analyzes the existing problems of China's energy storage industry from the aspects of technical costs, standard system, benefit evaluation and related policies. Finally, solutions are proposed based on the above problems to promote the sound development of China's energy storage industry.
Chinese cherry (Prunus pseudocerasus L) is an allotetraploid species and exhibits natural self-compatibility However, the full-length cDNA sequences, functional analysis and the transcripts of S-RNase alleles in Chinese cherry cultivars are not known. In the two cultivars Taixiaohongying and Laiyang Short Cherry with S(1)S(2)S(3)S(4) genotypes, two S-RNases were transcribed in Northern blotting, and the two full-length cDNAs of S-RNase were cloned and analyzed. As the result, the transcribed S-RNases were S(1)-RNase and S(2)-RNase The two complete cDNA sequences of S(1)-RNase and S(2)-RNase were registered as EU073938 and EU073939, respectively, and had characteristic structure of rosaceous S-RNases based on their sequences indicating that they had normal function for S-RNase in the style The S(3)-RNase and S(4)-RNase were not transcribed in the style and were nonfunctional for S-RNase, so S(3m) and S(4m) could be used to represent the nonfunctional S(4)-RNase and S(4)-RNase. The phylogenetic analysis implied that the S-RNases of Prunus. including Chinese cherry, had lower intra-specific similarity and diverged earlier than the divergence of species in Prunus
Sialic acid is a sugar typically found at the N-glycan termini of glycoproteins in mammalian cells. Lec3 CHO cell mutants are deficient in,epimerase activity, due to a defect in the gene that encodes a bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sialic acid modification on the cell surface is partially affected in these cells. We have mutagenized Lec3 CHO cells and isolated six mutants (termed C2m) deficient in the cell surface expression of polysialic acid (PSA). Mutant C2m9 was partially defective in expression of cell-surface PSA and wheat germ agglutinin (WGA) binding, while in the other five mutants, both cell-surface PSA and WGA binding were undetectable. PSA expression was restored by complementation with the gene encoding the CMP-sialic acid transporter (CST), indicating that CST mutations were responsible for the phenotypes of the C2m cells. We characterized the CST mutations in these cells by Northern blotting and RT-PCR. C2m9 and C2m45 carried missense mutations resulting in glycine to glutamate substitutions at amino acids 217 (G217E) and 256 (G256E), respectively. C2m13, C2m39 and C2m31 had nonsense mutations that resulted in decreased CST mRNA stability, and C2m34 carried a putative splice site mutation. PSA and CD15s expression in CST-deficient Lec2 cells were partially rescued by G217E CST, but not by G256E CST, although both proteins were expressed at similar levels, and localized to the Golgi. These results indicate that the novel missense mutations isolated in this study affect CST activity.
Chinese tallow (Sapium sebiferum L.) is a promising landscape and bioenergy plant. Measuring gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) can provide valuable information on gene function. Stably expressed reference genes for normalization are a prerequisite for ensuring the accuracy of the target gene expression level among different samples. However, the reference genes in Chinese tallow have not been systematically validated. In this study, 12 candidate reference genes (185, GAPDH, UBQ, RPS15, SAND, TIP41, 60S, ACT7, PDF2, APT, TBP and TUB) were investigated with qRT-PCR in 18 samples, including those from different tissues, from plants treated with sucrose and cold stresses. The data were calculated with four common algorithms, geNorm, BestKeeper, NormFinder, and the delta cycle threshold (Delta Ct). TIP41 and GAPDH were the most stable for the tissue-specific experiment, GAPDH and 60S for cold treatment, and GAPDH and UBQ for sucrose stresses, while the least stable genes were 60S, TIP41, and 18S respectively. The comprehensive results showed APT, GAPDH, and UBQ to be the top-ranked stable genes across all the samples. The stability of 60S was the lowest during all experiments. These selected reference genes were further validated by comparing the expression profiles of the chalcone synthase gene in Chinese tallow in different samples. The results will help to improve the accuracy of gene expression studies in Chinese tallow.
To improve the quality of Chinese traditional Paocai, two psychrotolerant lactic acid bacteria (LAB) strains were isolated from Paocai, and the quality of Chinese Paocai product using these two strains as starter cultures was compared to a control sample fermented with aged brine at 10 degrees C. The results suggested that the physicochemical and sensory features of Paocai fermented with psychrotolerant LAB were more suitable for industrial applications. The nitrite content of Paocai fermented with psychrotolerant LAB was 1 mg/kg, which was significantly lower than that of the control Paocai (P < 0.05). Low temperature fermentation with the starter cultures of psychrotolerant LAB could effectively prevent overacidity and over-ripening of the Paocai products. Additionally, Paocai fermented with psychrotolerant LAB harbored relatively simple microbial flora as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. This study provides a basis for improving the quality of Chinese traditional Paocai and the large-scale production of low-temperature Chinese traditional Paocai products.
Vector-borne diseases (VBD) are of major importance to human and animal health. In recent years, VBD have been emerging or re-emerging in many geographical areas, alarming new disease threats and economic losses. The precise diagnosis of many of these diseases still remains a major challenge because of the lack of comprehensive data available on accurate and reliable diagnostic methods. Here, we conducted a systematic and in-depth review of the former, current, and upcoming techniques employed for the diagnosis of VBD.
Chromatin immunoprecipitation followed by qPCR analysis (ChIP-qPCR) is a widely used technique to study gene expression. A large number of students in molecular biology and more generally in life sciences will be confronted with the use of this technique, which is quite difficult to set up and can lead to misinterpretation if not carefully managed. This article describes a four-session laboratory practical designed for Masters students to introduce this technique. During the practical, students work in pairs. They extract chromatin from MCF-7 culture cells stimulated or not by estrogens, then immunoprecipitate the transcription factor estrogen receptor alpha using an antibody directed against it. Students then measure the enrichment of promoter DNA target sequences from the chromatin that coprecipitates by qPCR. These are two estrogen responsive genes, pS2 (trefoil factor one) and PGR (the progesterone receptor). They learn how to analyze their ChIP-qPCR data by two methods: percent input and fold enrichment, and are taught about the interpretation limits of these two calculation methods. Thus, this practical is a good framework for an in-depth discussion of how this technique can be used to study gene expression and for raising awareness of the importance of careful interpretation of results. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2): 152-160, 2017.
Radiation hardness of different samples of the same ICs can vary greatly from lot to lot, depending on the year or the country of production. However, it is assumed that radiation hardness of the samples from the same lot is the same too. The new chip uniformity test method based on ionization response comparison is offered.
Fusarium head blight (FHB) and Fusarium seedling blight (FSB) of wheat, caused by Fusarium pathogens, are devastating diseases worldwide. We report the expression of RNA interference (RNAi) sequences derived from an essential Fusarium graminearum (Fg) virulence gene, chitin synthase (Chs) 3b, as a method to enhance resistance of wheat plants to fungal pathogens. Deletion of Chs3b was lethal to Fg; disruption of the other Chs gene family members generated knockout mutants with diverse impacts on Fg. Comparative expression analyses revealed that among the Chs gene family members, Chs3b had the highest expression levels during Fg colonization of wheat. Three hairpin RNAi constructs corresponding to the different regions of Chs3b were found to silence Chs3b in transgenic Fg strains. Co-expression of these three RNAi constructs in two independent elite wheat cultivar transgenic lines conferred high levels of stable, consistent resistance (combined type I and II resistance) to both FHB and FSB throughout the T-3 to T-5 generations. Confocal microscopy revealed profoundly restricted mycelia in Fg-infected transgenic wheat plants. Presence of the three specific short interfering RNAs in transgenic wheat plants was confirmed by Northern blotting, and these RNAs efficiently down-regulated Chs3b in the colonizing Fusarium pathogens on wheat seedlings and spikes. Our results demonstrate that host-induced gene silencing of an essential fungal chitin synthase gene is an effective strategy for enhancing resistance in crop plants under field test conditions.
The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.
Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a C. muridarum challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a Chlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.
Chlamydia suis infections are endemic in domestic pigs in Europe and can lead to conjunctivitis, pneumonia, enteritis and reproductive failure. Currently, the knowledge on the zoonotic potential of C.suis is limited. Moreover, the last decades, porcine tetracycline resistant C.suis strains have been isolated, which interfere with treatment of chlamydial infections. In this study, the presence of C.suis was examined on nine Belgian pig farms, using Chlamydia culture and a C.suis specific real-time PCR in both pigs and farmers. In addition to diagnosis for C.suis, the farmers' samples were examined using a Chlamydia trachomatis PCR. Additionally, the Chlamydia isolates were tested for the presence of the tet(C) resistance gene. C. DNA was demonstrated in pigs on all farms, and eight of nine farmers were positive in at least one anatomical site. None of the farmers tested positive for C. trachomatis. Chlamydia suis isolates were obtained from pigs of eight farms. Nine porcine C.suis isolates possessing a tet(C) gene were retrieved, originating from three farms. Moreover, C.suis isolates were identified in three human samples, including one pharyngeal and two rectal samples. These findings suggest further research on the zoonotic transfer of C.suis from pigs to humans is needed.
The objective of the present study was to characterize the pattern of gene expression at the last stage of ovarian maturation in Chlamys farreri. Dynamic transcriptomic analysis of ovaries was performed at four time points prior to ovulation, using the Illumina HiSeq 2500 platform. A total of 174,928 unigenes were obtained, among which 42,534 were annotated according to bioinformatics databases, such as NT, NR, Swiss-Prot, KOG, GO, and KEGG. Results from the transcriptome analysis revealed a time-dependent pattern of global transcriptional responses. When compared to the 0 d library, 99, 152, and 3248 differently expressed genes (DEGs) were obtained in the 3, 10, and 21 d libraries, respectively. Those three libraries shared only 10 DEGs, the majority of which were time-specific. Pairwise comparisons of each profile demonstrated that DEGs were related to hormone metabolism and receptors, cell division, gametogenesis, and vitellogenesis pathways. Notably, when adjacent sampling time point groups were compared, the only DEG throughout the experimental period was related to the G protein-coupled receptor signaling pathway. The present study provides the first dynamic transcriptomic analysis of C. farreri for evaluation of the molecular basis of gonadal maturation. (C) 2016 Elsevier Inc. All rights reserved.
The present report describes a 13 month pilot remediation study that consists of a combination of Cr(VI) (4.4 to 57 mg/l) geofixation and dechlorination of chlorinated ethenes (400 to 6526 mu g/l), achieved by the sequential use of nanoscale zerovalent iron (nZVI) particles and in situ biotic reduction supported by whey injection. The remediation process was monitored using numerous techniques, including physical-chemical analyses and molecular biology approaches which enabled both the characterization of the mechanisms involved in pollutant transformation and the description of the overall background processes of the treatment. The results revealed that nZVI was efficient toward Cr(VI) by itself and completely removed it from the groundwater (LOQ 0.05 mg/l) and the subsequent application of whey resulted in a high removal of chlorinated ethenes (97 to 99%). The persistence of the reducing conditions, even after the depletion of the organic substrates, indicated a complementarity between nZVI and the whey phases in the combined technology as the subsequent application of whey phase partially assisted the microbial regeneration of the spent nZVI by promoting its reduction into Fe(II), which further supported remediation conditions at the site. Illumina sequencing and the detection of functional vcrA and bvcA genes documented a development in the reducing microbes (iron-reducing, sulfate-reducing and chlororespiring bacteria) that benefited under the conditions of the site and that was probably responsible for the high dechlorination and/or Cr(VI) reduction. The results of this study demonstrate the feasibility and high efficiency of the combined nano-biotechnological approach of nZVI and whey application in-situ for the removal of Cr(VI) and chlorinated ethenes from the groundwater of the contaminated site. (C) 2016 Elsevier B.V. All rights reserved.
Thermal tetrachloroethene (PCE) remediation by steam injection in a sandy aquifer led to the release of dissolved organic carbon (DOC) from aquifer sediments resulting in more reduced redox conditions, accelerated PCE biodegradation, and changes in microbial populations. These changes were documented by comparing data collected prior to the remediation event and eight years later. Based on the premise that dual C-Cl isotope slopes reflect ongoing degradation pathways, the slopes associated with PCE and TCE suggest the predominance of biotic reductive dechlorination near the source area. PCE was the predominant chlorinated ethene near the source area prior to thermal treatment. After thermal treatment, cDCE became predominant. The biotic contribution to these changes was supported by the presence of Dehalococcoides sp. DNA (Dhc) and Dhc targeted rRNA close to the source area. In contrast, dual C-CI isotope analysis together with the almost absent VC C-13 depletion in comparison to cDCE C-13 depletion suggested that cDCE was subject to abiotic degradation due to the presence of pyrite, possible surface-bound iron (II) or reduced iron sulphides in the downgradient part of the plume. This interpretation is supported by the relative lack of Dhc in the downgradient part of the plume. The results of this study show that thermal remediation can enhance the biodegradation of chlorinated ethenes, and that this effect can be traced to the mobilisation of DOC due to steam injection. This, in turn, results in more reduced redox conditions which favor active reductive dechlorination and/or may lead to a series of redox reactions which may consecutively trigger biotically induced abiotic degradation. Finally, this study illustrates the valuable complementary application of compound-specific isotopic analysis combined with molecular biology tools to evaluate which biogeochemical processes are taking place in an aquifer contaminated with chlorinated ethenes. (C) 2016 Elsevier B.V. All rights reserved.
Chloroplast development is regulated by many biological processes. However, these processes are not fully understood. Leaf variegation mutants have been used as powerful models to elucidate the genetic network of chloroplast development since the degree of leaf variegation is regulated by developmental and environmental cues. The thylakoid formation 1 (thf1) mutant is unique for its variegation in both leaves and cotyledons. Here, we reported a new suppressor gene of thf1 leaf variegation, designated sot8. Map-based cloning and DNA sequencing results showed that a single nucleotide mutation from G to A was detected in the second exon of the gene encoding the ribosomal protein small subunit 9 (PRPS9) in sot8-1, resulting in an amino acid change and a partial loss of PRPS9 function. However, sot8-1 was unable to rescue the thf1 phenotype in low photosystem II activity (Fv/Fm). In addition, we identified two T-DNA insertion mutants defective in plastid-specific ribosomal proteins (PSRPs), psrp2-1, and psrp5-1. Genetic analysis showed that knockdown of PSRP5 expression but not PSRP2 expression suppressed leaf variegation. Northern blotting results showed that precursors of plastid rRNAs over-accumulated in prps9-1 and psrp5-1, indicating that mutations in PRPS9 and PSRP5 cause a defect in rRNA processing. Consistently, inhibition of plastid protein synthesis by spectinomycin led to increased levels of plastid rRNA precursors in wild-type plants, suggesting that rRNA processing and plastid ribosomal assembly are coupled. Taken together, our data indicate that downregulating the expression of specific plastid ribosomal proteins suppresses thf1 leaf variegation, and provide new insights into a role of THF1 in plastid gene expression.
The plastid genome of plants is the smallest and most gene-rich of the three genomes in each cell and the one generally present in the highest copy number. As a result, obtaining plastid DNA sequence is a particularly cost-effective way of discovering genetic information about a plant. Until recently, the sequence information gathered in this way was generally limited to small portions of the genome amplified by polymerase chain reaction, but recent advances in sequencing technology have stimulated a substantial rate of increase in the sequencing of complete plastid genomes. Within the last year, the number of complete plastid genomes accessible in public sequence repositories has exceeded 1000. This sudden flood of data raises numerous challenges in data analysis and interpretation, but also offers the keys to potential insights across large swathes of plant biology. We examine what has been learnt so far, what more could be learnt if we look at the data in the right way, and what we might gain from the tens of thousands more genome sequences that will surely arrive in the next few years. The most exciting new discoveries are likely to be made at the interdisciplinary interfaces between molecular biology and ecology.
Objectives. TNF-alpha, IL-1 and IL-6 are known to have primary roles in the pathogenesis of rheumatoid arthritis and other inflammatory diseases. The anti-rheumatic drug chloroquine has been shown to inhibit TNF-alpha, IL-1 and IL-6 production from mononuclear phagocytes. We examined the underlying mechanisms involved in the chloroquine-induced inhibition of cytokine production. Methods. Human peripheral blood mononuclear cells and monocytes/macrophages and monocytic U-937 and THP-1 cells were stimulated with lipopolysaccharide, and TNF-alpha, IL-1 beta and IL-6 production was measured by ELISA. Levels of mRNA were measured by northern blotting and reverse transcription-polymerase chain reaction. Synthesis of 26-kDa TNF-alpha precursor was measured by metabolic labelling and immunoprecipitation analysis. Transcription rate was determined by nuclear run-on assay. Results. TNF-alpha release from the cells was inhibited by chloroquine, whereas the steady-state level of TNF-alpha mRNA and synthesis of 26-kDa TNF-alpha precursor were not changed by chloroquine. In contrast, chloroquine-induced inhibition of IL-1 beta and IL-6 release was accompanied by a decrease in their steady-state mRNA levels. The transcription rates of the IL-1 beta and IL-6 genes were not changed by chloroquine, whereas the stability of IL-1 beta and IL-6 mRNA was decreased by chloroquine. Weak-base amines such as methylamine and ammonium chloride had no effect on the production of TNF-alpha, whereas they partially blocked the production of IL-1 beta and IL-6. Conclusions. Our results indicate that chloroquine-mediated inhibition of TNF-alpha, IL-1 beta and IL-6 synthesis occurs through different modes in lipopolysaccharide-stimulated human monocytes/macrophages: it blocks the conversion of cell-associated TNF-alpha precursor to mature soluble protein, whereas it reduces the levels of IL-1 beta and IL-6 mRNA, at least in part, by decreasing their stability and by a pH-dependent mechanism.
Mammalian cell cultures are the preferred expression systems for the production of biopharmaceuticals requiring posttranslational processing. Usually, cell cultures are cultivated in medium supplemented with serum, which supports cell proliferation, viability, and productivity. However, due to scientific and regulatory concerns, serum-free conditions are required in recombinant protein production. Cell lines that are intended for commercial recombinant protein production have to adapt to serum- or protein-free conditions early in their development. This is a labor- and time-consuming process because of the specific cell requirements related to their adaptation in new microenvironment. In the present study, a Chinese hamster ovary (CHO) cell line producing glycosylated recombinant human erythropoietin (rhEPO) was adapted for growth and rhEPO production in serum- and protein-free conditions. The physiology, growth parameters, and morphology of the CHO cells and rhEPO biosynthesis and structure were closely monitored during the adaptation process to avoid unwanted selection of cell subpopulations. The results showed that the CHO cells were successfully adapted to suspension growth and rhEPO production in the protein-free conditions and that the structure of rhEPO remained nearly unchanged. In addition, during rhEPO production in the protein-free suspension conditions, the agitation rate seem to be significant for optimal process performance in contrast to the initial cell concentration, evaluated through evolutionary operation method. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed.
Cholangiocarcinoma (CC) is an intrahepatic bile duct carcinoma with a high mortality rate and a poor prognosis. Sarcomatous change/epithelial mesenchymal transition (EMT) of CC frequently leads to aggressive intrahepatic spread and metastasis. The aim of this study was to identify the genetic alterations and gene expression pattern that might be associated with the sarcomatous change in CC. Previously, we established 4 human CC cell lines (SCK, JCK1, Cho-CK, and Choi-CK). In the present study, we characterized a typical sarcomatoid phenotype of SCK, and classified the other cell lines according to tumor cell differentiation (a poorly differentiated JCK, a moderately differentiated Cho-CK, and a well differentiated Choi-CK cells), both morphologically and immunocytologically. We further analyzed the genetic alterations of two tumor suppressor genes (p53 and FHIT) and the expression of Fas/FasL gene, well known CC-related receptor and its ligand, in these four CC cell lines. The deletion mutation of p53 was found in the sarcomatoid SCK cells. These cells expressed much less Fas/FasL mRNAs than did the other ordinary CC cells. We further characterize the gene expression pattern that is involved in the sarcomatous progression of CC, using cDNA microarrays that contained 18,688 genes. Comparison of the expression patterns between the sarcomatoid SCK cells and the differentiated Choi-CK cells enabled us to identify 260 genes and 247 genes that were significantly over-expressed and under-expressed, respectively. Northern blotting of the 14 randomly selected genes verified the microarray data, including the differential expressions of the LGALS1, TGFBI, CES1, LDHB, UCHL1, ASPH, VDAC1, VIL2, CCND2, S100P, CALB1, MAL2, GPX1, and ANXA8 mRNAs. Immunohistochemistry also revealed in part the differential expressions of these gene proteins. These results suggest that those genetic and gene expression alterations may be relevant to the sarcomatous change/EMT in CC cells.
The purpose of this study was to determine whether the superior colliculus (SC) of the microbat has the same neurochemical makeup as that of other mammals. We examined the organization of choline acetyltransferase (ChAT)- and tyrosine hydroxylase-immunoreactive (TH-IR) fibers/cells using standard immunohistochemistry with antibodies against ChAT and TH. ChAT-IR fibers observed in the superficial layers were denser than those in the deeper layers, and these fibers were classified into two types: small varicose fibers and large varicose fibers. ChAT-IR cells were predominantly located in the superficial layers with diverse morphologies. Among the well-known sources of cholinergic fibers in the mammalian SC, pedunculopontine tegmental nucleus (PPTN) and laterodorsal tegmental nucleus (LDTN) contained strongly labeled ChAT-IR cells, while no cholinergic structures were found in the parabigeminal nucleus (PBG) in the microbat brain. TH-immunoreactivity was found within fibers but not within cells. The density of TH-IR fibers was high in the zonal layer, moderate in the superficial gray and optic layers, and low in the deeper layers. Well-labeled TH-IR cells were also observed within area 13 and the locus coeruleus, known as the sources of catecholaminergic fibers in other mammalian SC. Although there are some cytoarchitectural variations among species, our results clearly showed elaborately organized ChAT-IR and TH-IR fibers/cells in the microbat SC. Our findings will contribute significantly to the understanding of actively constructed microbat visual systems.
Osteosarcoma has a well-recognized bimodal distribution, with the first peak in adolescence and another in the elderly age-group. The elderly patients have different clinical features and a poorer prognosis as compared to adolescents. To better understand the biological features of osteosarcoma in the elderly population, we established a new human osteosarcoma cell line from a 58-year-old man with primary chondroblastic osteosarcoma. After 6 months of continuous culture in vitro for over 50 passages, an immortalized cell line CHOS was established. The cell line was well-characterized by cytogenetic, biomarker, functional, and histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a doubling time of 36h. Cytogenetic analysis of CHOS cells revealed the loss of chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate. The cell line was highly tumorigenic and maintained the histological characteristics and invasive nature of the original tumor. Furthermore, on immunohistochemical analysis, the xenografts and metastases were found to co-express collagen II, aggrecan, vimentin and S100A4 that resembled the original tumor cells. Our results indicate, the potential of CHOS cell line to serve as a useful tool for further studies on the molecular biology of osteosarcoma, especially in the elderly patients. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016.
The input offset voltage is a quit important performance parameter for operational amplifiers, and the low frequency l/f noise has a great effect on the offset voltage. In this paper, chopping technology which is an efficient approach to decrease the l/f noise and offset voltage of CMOS amplifiers is adopted. In the low pass filter, the multiplier composed of R and C is used to filter out the modulation noise. The circuit of the presented chopper amplifier is designed and simulated with 45nm CMOS process and a 1V supply. Simulated results show that the total harmonic distortion of chopper amplifier is 54.1dB and the chopper frequency is 10 kHz. The input referred noise is 2.54 nV/root Hz @1kHz, and the average power consumption is 65.5 mu W. The proposed technology has a pleasurable preference.
The paper presents three approaches for frequency compensation in chopper offset-stabilized amplifiers with symmetrical passive RC notch filter with two cutoff frequencies. The filter has two cutoff frequencies: the chopping frequency itself and the fifth harmonic of the chopping frequency. The frequency compensation network is connected either at the input of the notch filter, or at its output, or between its two sections. The large signal transient response is evaluated in terms of the overshoot/undershoot and the settling time. Three circuits using these techniques were fabricated and evaluated. The approach that uses the frequency compensation network connected between the sections of the filter has the best results, except for the chopping ripple rejection.
This paper deals with the susceptibility of analog integrated circuits to radio frequency interferences (RFI) and it concentrates on the effects induced by RFI on the operation of offset compensated chopped CMOS operational amplifiers. The first part of the work explains the causes of the additional output DC offset induced by input RF disturbances in chopped systems. Afterwards, the design of a chopped CMOS operational transconductance amplifier (OTA) is briefly treated and in the final part of the paper the results of some simulations performed on such OTA are presented in order to highlight the concepts discussed in the first and second paragraphs.
This paper presents a thyristor-based tap changing transformer and a diode rectifier for variable-voltage high-current dc applications. Back-to-back thyristors are connected in series with the transformer taps on the primary side. Thyristors are phase controlled in a continuous manner to achieve variable ac voltage at the secondary side of the transformer. This leads to a variable voltage at the output of the three-phase diode rectifier connected at the secondary side of the transformer. A passive filter is added at the primary side to achieve power factor improvement over the range of output voltage. This scheme is optimized to determine optimum turns ratio of the transformer and optimum reactive power rating of the passive filter. Design guidelines are presented for various values of power factor along with optimum turns ratios and passive filter rating. A 62.5-kW experimental system with a passive filter of 17.5 kVA (reactive) is developed to verify the system performance. In the end, a comparison of the proposed topology with other state-of-the-art topologies is also presented.
This paper presents a chopper instrumentation amplifier designed in 28nm CMOS technology. The operational amplifier has a rail-to-rail folded cascode input stage, which ensures a constant gm over the available common-mode range. It is characterized by a Nested Miller compensation. All transistors operate in sub-threshold region; thus the opamp has been designed through a specific procedure for sub-threshold operation. The chopper technique is exploited to reduce the input referred offset and noise. The circuit operates with 0.9V supply voltage and exhibits a simulated 106dB DC gain and 329kHz GBW. Montecarlo simulations demonstrate an offset distribution with 2.2 mu V standard deviation. The input noise spectral density is equal to 27nV/Hz, giving a noise efficiency factor of 8.
Background: Chordoma are malignant tumors of the axial skeleton, which arise from remnants of the notochord. The Notochord (chorda dorsalis) is an essential embryonic structure involved in the development of the nervous system and axial skeleton. Therefore, the notochord seems to be the most biologically relevant control tissue to study chordoma in molecular biology research. Nevertheless, up to now mainly different tissues but not the notochord have been used as control for chordoma, due to difficulty of isolating notochordal tissue. Here, we describe a fast and precise method of isolating notochordal cells. Methods: Examination of human fetuses, with a gestation of 9, 11 and 13 weeks, using (immuno) histochemical methods was performed. To isolate pure notochord cells for further molecular biology investigation five flash frozen fetuses between 9 and 10 weeks of gestation were dissected by microtome slicing. Thereafter pure notochord cells for further molecular biology investigation where harvested by using laser capture microdissection (LCM). RNA was extracted from these samples and used in quantitative PCR. Results: This study illustrates notochord of embryonic spines in three different stages of gestation (9-1113 weeks). Immunohistochemical staining with brachyury showed strong staining of the notochord, but also weak staining of the intervertebral disc and vertebral body. LCM of notochord slices and subsequent total RNA extraction resulted in a good yield of total RNA. qPCR analysis of two housekeeping genes confirmed the quality of the RNA. Conclusion: LCM is a fast and precise method to isolate notochord and the quality and yield RNA extracted from this tissue is sufficient for qPCR analysis. Therefore early embryo notochord isolated by LCM is suggested to be the gold standard for future research in chordoma development, classification and diagnosis. (C) 2016 Elsevier B.V. All rights reserved.
Chorioamnionitis is an acute inflammation of the gestational (extraplacental) membranes, most commonly caused by ascending microbial infection. It is associated with adverse neonatal outcomes including preterm birth, neonatal sepsis, and cerebral palsy. The decidua is the outermost layer of the gestational membranes and is likely an important initial site of contact with microbes during ascending infection. However, little is known about how decidual stromal cells (DSCs) respond to microbial threat. Defining the contributions of individual cell types to the complex medley of inflammatory signals during chorioamnionitis could lead to improved interventions aimed at halting this disease. We review available published data supporting the role for DSCs in responding to microbial infection, with a special focus on their expression of pattern recognition receptors and evidence of their responsiveness to pathogen sensing. While DSCs likely play an important role in sensing and responding to infection during the pathogenesis of chorioamnionitis, important knowledge gaps and areas for future research are highlighted.
Background. Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized. Methods. Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 10(7) colony-forming units of Ureaplasma parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later. We performed comprehensive assessments of inflammation and immune effects in multiple fetal and maternal tissues. Results. Although U. parvum grew well in amniotic fluid, there was minimal chorioamnionitis. U. parvum colonized the fetal lung, but fetal systemic microbial invasion was limited. Fetal lung inflammation was mild, with elevations in CXCL8, tumor necrosis factor (TNF) alpha, and CCL2 levels in alveolar washes at day 7. Inflammation was not detected in the fetal brain. Significantly, U. parvum decreased regulatory T cells (Tregs) and activated interferon gamma production in these Tregs in the fetus. It was detected in uterine tissue by day 7 and induced mild inflammation and increased expression of connexin 43, a gap junction protein involved with labor. Conclusions. U. parvum colonized the amniotic fluid and caused uterine inflammation, but without overt chorioamnionitis. It caused mild fetal lung inflammation but had a more profound effect on the fetal immune system, decreasing Tregs and polarizing them toward a T-helper 1 phenotype.
Background/aims To assess the efficacy and safety of dexamethasone (DEX) intravitreal implant in patients with active serpiginous choroiditis (SC) already receiving maximal tolerated systemic immunosuppressive therapy. Methods In this retrospective longitudinal study we evaluated patients receiving 0.7mg DEX intravitreal implant for active SC despite maximal systemic immunosuppression. Medical history was reviewed over a period of 18months for each patient. We diagnosed SC activity using direct fundus examination and blue-light fundus autofluorescence. Primary outcomes were the rate of disease control and functional changes at end of follow-up. Secondary outcomes were the incidence of injection-related adverse events and the success of immunosuppression tapering at the last examination. Results We examined eight eyes of seven patients. We controlled SC activity with one injection in five eyes, two injections in one eye, and three injections in two eyes (total of 13 implants). Best-corrected visual acuity at the end of the investigational period improved in two eyes (25%), remained stable in four eyes (50%) and decreased in two eyes (25%). Three eyes showed transient intraocular pressure increase and two eyes disclosed cataract progression. The average dosage of systemic prednisone at baseline and after DEX intravitreal implant decreased from 8.8 to 2.8mg/day. Conclusions Dexamethasone intravitreal implant may be an effective treatment option to control active serpiginous lesions in patients in whom increased systemic corticosteroid therapy is contraindicated.
Sliced ready-to-eat traditional meat products presented in individual packaging with more convenience to the consumer is the way that food industry tries to adapt to the new consumer tendencies. The current work assessed the survival of Listeria monocytogenes in a contaminated sliced vacuum packed chourico with different sugar concentrations, two salt levels, and presence/absence of Lactobacillus sakei as starter culture along the storage period at two temperatures (8 degrees C and 22 degrees C). Neither the inoculation with L. sakei, nor the addition of carbohydrates influenced the survival of the pathogen. Higher amount of salt resulted in a signifi cant reduction of L. monocytogenes, and storage at the higher temperature displayed a safer product. After 7 days, L. monocytogenes was not detected in any samples. The study of the association of the factors contributing for L. monocytogenes survival by logistic regression showed that increasing the level of salt addition from 1.5% to 3% reduces the odds of survival of L. monocytogenes to about one fifth (0.174). Worthy of attention is the signifi cant reduction in the odds (OR=0.028) of fi nding viable L. monocytogenes when the samples are stored at room temperature (22 degrees C), when compared to low temperature (8 degrees C). The general and indiscriminate use of refrigeration for meat products might increase the risk of presence of L. monocytogenes. The competitive advantage that L. monocytogenes has at low temperatures, as the potential inhibition of LAB activity, is probably the reason of the observed behaviour. The amount of salt was an important hurdle to control L. monocytogenes growth, so, manufacturing meat products with lower salt contents to meet the demands of healthy products might represent a risk for safety, since high levels of salt together with low a w are the keys for their conservation.
Background: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre) malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre) malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre) malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk. Methods: 42 patients with firstly diagnosed, radically resected primary OSCC with histopathologically confirmed tumor-free resection margins (treated between 1994 and 2003) were included. Inclusion criteria comprised of follow-up >= 5 years, and radical surgery without postoperative treatment. Formalinf-ixed paraffine-embedded tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and 7 copy number variations (CNV), and to p53 immunohistochemistry (IHC). Results: 11 out of the 42 patients developed a local recurrence within 5 years. FISH analysis showed that nine of eleven recurrences exhibited CI in at least one of the resection margins (p = 0.008). P53 overexpression and routine histopathologic classification were not correlated with recurrent disease. The presence of CI in the resection margins revealed a significantly worse progression-free survival (log-rank p = 0.012). Conclusions: CI in the resection margins of OSCC can reliably identify patients at risk for developing a local recurrence. (C) 2016 Elsevier Ltd. All rights reserved.
We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p<0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.
Increasing evidence suggests that regular physical exercise suppresses chronic inflammation. However, the potential inhibitory effects of swimming on dextran sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain unclear. In this study, rats were orally administered DSS to induce chronic colitis, and subsequently treated with or without swimming exercise. A 7-week swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused colon shortening, colon barrier disruption, spleen enlargement, serum LDH release, and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt depth, and increases in myeloperoxidase activity, infiltration of Ly6G(+) neutrophils and TNF-alpha- and IFN-gamma-expressing CD3(+) T cells, as well as fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine and chemokine production and decreased the protein expression of phosphorylated nuclear factor-kappa B p65 and cyclooxygenase 2, whereas it elevated interleukin-10 levels. Swimming impeded the generation of reactive oxygen species, malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total antioxidant capacity, and superoxide dismutase and glutathione peroxidase activities. Additionally, swimming decreased caspase-3 activity and expression of apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase- 3, but increased Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial effects on DSS-induced chronic colitis by modulating inflammation, oxidative stress, and apoptosis.
BACKGROUND: Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T(H)2 airway inflammation, which is potentially useful in the management of patients with chronic cough. OBJECTIVE: To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. METHODS: A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 3 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from about 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. CONCLUSIONS: We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence. (C) 2016 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology
The number of times a scientific article has been cited reflects its impact on a specific field. Highly cited articles are known as citation classics. Here, we aim to characterize the most frequently cited articles in chronic granulomatous disease (CGD). We searched the ISI Web of Science in Aug 2016 for articles that were cited 100 times or more and evaluated them for several characteristics. The most frequently cited article received 955 citations. The citations mean was 221.6 citations (SD = 162.7). The most recent article was published in 2011. The articles were published in 36 journals, led by The New England Journal of Medicine. Overall authors came from 17 countries, with the United States of America (USA) contributing to 91 (80%) articles. The National Institute of Health was the most common institution of origin for the corresponding author. The most common type of articles was basic science with 77 (67%) articles. These results provide some insights into the most cited research articles in CGD since its first description 60 years ago.
Chronic granulomatous disease (CGD), a disease characterized by inadequate neutrophil killing of microbial pathogens, affects 4 to 5 per million live births. For many decades following its description, CGD was a fatal disease in childhood. With the development of effective preventive therapies and the early recognition of infectious complications, 90% of children with CGD now survive into adulthood. The management of CGD in adults includes unique challenges and potential disease manifestations. In this article, the authors discuss the current approach to the management of CGD in both children and adults. This includes a focus on the importance of a comprehensive multidisciplinary approach in the care of CGD and its potential complications. In addition, a novel approach to improving education about CGD, and subsequently improving adherence to preventive therapies, is discussed. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Chronic granulomatous disease is a rare, inherited immunodeficiency disorder that reduces the superoxide generation ability of phagocytes, leading to recurrent infections and granulomatous inflammation. We report the case of a previously healthy 3-year-old boy who presented with classic features of Crohn disease. Suspicion from histopathologiclogic assessment allowed early diagnosis and treatment for chronic granulomatous disease before the onset of infections.
Little is known about the association between chronic illness and suicidal ideation (SI) among Dominicans living in the United States. This study used data from a community survey of 2753 Dominican adults in New York City. SI included thoughts of self-harm or being better off dead in the past month. Chronic physical illness burden was categorized as having 0, 1, or 2+ diagnosed conditions. Adjusted logistic regressions evaluated the association between number of conditions and SI, overall and stratified by sex and age. Adjusted models yielded a strong association between chronic illness burden and SI among men [odds ratio (OR) 5.57, 95 % confidence interval (CI) 2.19-14.18] but not women (OR 0.80, 95 % CI 0.50-1.29; interaction p = 0.011). The association of interest did not differ significantly between younger and older adults. Screening for SI in health care practice, particularly among Dominican men with multiple chronic health conditions, may be warranted.
Purpose of review Altered differentiation and activation of T-cell subsets occur in patients with chronic kidney disease (CKD), but the impact on graft rejection and protective immunity during transplantation are not fully understood. Recent findings Patients with CKD have decreased frequency of naive T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naive and memory T-cell subsets do not appear to improve following kidney transplantation. Retained thymic output is associated with acute rejection, whereas naive lymphopenia and accumulation of CD8(+) TEMRA cells correlate with long-term graft dysfunction. CD28(null) memory cells accumulate during CKD and appear to confer protection against acute rejection under standard immunosuppression and possibly costimulation blockade. T cells bearing CD57 are also increased in patients with CKD and may underlie rejection during costimulation blockade. Summary The mechanisms by which CKD alters the differentiation and activation status of T-cell subsets is poorly understood. Further research is also needed to understand which cell populations mediate rejection under various immunosuppressive regimens. To date, there is little use of animal models of organ failure in transplant immunology research. CKD mouse models may help identify novel pathways and targets to better control alloimmunity in posttransplant.
Endothelial dysfunction and impaired endothelial regenerative capacity are key contributors to the high incidence of cardiovascular disease in patients with chronic kidney disease (CKD). Uremic toxins are associated with this pathogenesis. Previous studies have revealed that a uremic toxin, para-cresol (p-cresol), exerts an antiproliferation effect on human endothelial progenitor cells (EPCs), but the mechanism remains unclear. In the present study, reactive oxygen species (ROS) were confirmed to function as signaling molecules that regulate growth factor-dependent EPC proliferation. EPCs were treated with p-cresol for 72 h, using a concentration range typically found in CKD patients. ROS production was analyzed by fluorescence microscopy and flow cytometry, and protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase, a major source of ROS, were analyzed by western blot analysis. mRNA expression levels of antioxidant genes were assessed by reverse transcription-quantitative polymerase chain reaction analysis. The results revealed that p-cresol partially inhibits ROS production, and this effect may be associated with a significant reduction in cytochrome b-245 alpha and beta chain expression in EPCs. An increase of glutathione peroxidase 4 mRNA expression was also detected. In conclusion, the present study revealed that the antiproliferation effect of p-cresol on EPCs might act via its antioxidant activity. The results of the present study may facilitate understanding of uremic toxin toxicity on the cardiovascular system.
ObjectivesThis study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome. MethodsWe retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry. ResultsAt transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response, and 11% had refractory disease. After transplant, 61% of the patients achieved CR with undetectable MRD status. By multivariate analysis, reaching CR with undetectable MRD 12 months after transplant was the only factor associated with better progression-free survival (P = 0.02) and attaining undetectable MRD, independently of the time of negativity, was the only factor that correlated with better overall survival (P = 0.04). ConclusionThus, achieving undetectable MRD status after allo-SCT for CLL is a major goal to improve post-transplant outcome.
Chemotherapy is the main treatment method for patients with chronic myeloid leukemia (CML) and has achieved marked results. However, the acquisition of multidrug resistance (MDR) has seriously affected the quality of life and survival rate of patients. The overexpression of the inhibitors of apoptosis proteins (IAPs) and the adenosi ne triphosphate (ATP) dependent binding cassette (ABC) transporters are the two main causes of MDR. Apollon and MDR1 are the most important and representative members, respectively, among the IAPs and ABC transporters. In the present study, we investigated the role of Apollon and MDR1 in chemotherapy resistance and their mechanism of interaction. We respectively knocked down the expression of Apollon and MDR1 using short hairpin RNA (shRNA) in adriamycin (ADM) resistant human CML K562 cells and examined the drug sensitivity, the consequences with regard to ADM accumulation and the alterations in the expression of Apollon and MDR1. The expression levels of Apollon and MDR1 mRNA were higher in the K562/ADM cells compared with the parental K562 cells as determined by reverse transcription-polymerase chain reaction (RT-PCR). The plasmids of Apollon and MDR1 shRNA were respectively stably transfected into K562/ADM cells using Lipofectamine 2000. The transfection efficiency was detected by fluorescence microscopy. Cell Counting Kit-8 (CCK-8) assay revealed that Apollon or MDR1 knockdown significantly increased the chemosensitivity of the K562/ADM cells to ADM. Flow cytometric assay revealed that K562/ADM/shMDR1 cells exhibited a significantly increased intracellular accumulation of ADM, and that changes were not found in the K562/ADM/shApollon cells. Compared with the parental K562/ADM cells, a significantly decreased expression of Apollon mRNA and protein was determined in the K562/ADM/shApollon cells without affecting the expression of MDR1 as determined by RT-PCR and western blotting. Likewise, the expression levels of MDR1 mRNA and protein also markedly downregulated in the K562/ADM/shMDR1 cells had no effect on Apollon expression. Collectively, our findings demonstrated, for the first time, that downregulation of Apollon or MDR1 through stable transfection with the Apollon- or MDR1-targeting shRNA induced MDR reversal through respective inhibition of Apollon or MDR1 expression and function. However, the reversal mechanism of Apollon and MDR1 revealed no direct interaction with each other.
Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP.
Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients. hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7. Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V >M (g.1222G >A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3' end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients. hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.
Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I) suffer from chronic candidosis caused mainly by Candida albicans, and repeated courses of azole antifungals have led to the development of resistance in the APECED patient population in Finland. The aim of our study was to address whether the patients are persistently colonized with the same or genetically closely related strains, whether epidemic strains are present and which molecular mechanisms account for azole resistance. Sets of C. albicans (n = 19) isolates from nine APECED patients reported with decreased susceptibility to fluconazole isolated up to 9years apart were included. The strains were typed by multilocus sequence typing. CDR1/2, MDR1 and ERG11 mRNA expression was analysed by northern blotting and Cdr1, Cdr2 and Mdr1 protein expression by western blotting, and TAC1 and ERG11 genes were sequenced. All seven patients with multiple C. albicans isolates analysed were persistently colonized with the same or a genetically closely related strain for a mean of 5 years. All patients were colonized with different strains and no epidemic strains were found. The major molecular mechanisms behind the azole resistance were mutations in TAC1 contributing to overexpression of CDR1 and CDR2. Six new TAC1 mutations were found, one of which (N740S) is likely to be a gain-of-function mutation. Most isolates were found to have gained multiple TAC1 and ERG11 point mutations. Despite clinically successful treatment leading to relief of symptoms, colonization by C. albicans strains is persistent within APECED patients. Microevolution and point mutations occur within strains, leading to the development of azole-resistant isolates.
Introduction: Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val (66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Methods: Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Results: Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p<0.001). No interaction effect was found for the BDNF pathway with life stress in the associations with chronic pain presence and severity. Conclusions: This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain.
Objectives: Interleukin-36 (IL-36) is a recently described proinflammatory cytokine, characterized by the induction of inflammatory mediators. In the present study, we investigated the biological activity and the signal transduction of IL-36 alpha in human pancreatic myofibroblasts. Methods: The mRNA and protein expression of inflammatory mediators was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of IL-36 alpha and its receptor in the pancreatic tissue was evaluated using immunohistochemical technique. Intracellular signaling pathways were evaluated using immunoblotting and specific small interference RNA-transfected cells. Results: Interleukin-36 alpha and its receptor complex IL-36R/IL-1RAcP were detected in fibrotic tissue of chronic pancreatitis. Interleukin-36 alpha dose-and time-dependently induced the mRNA expression and protein secretion of CXCL1, CXCL8, MMP-1, and MMP-3 from human pancreatic myofibroblasts. Interleukin-36 alpha assembled MyD88 adaptor proteins (MyD88, TRAF6, IRAK1, and TAK1) into a complex. Furthermore, IL-36 alpha induced the phosphorylation of mitogen-activated protein kinases and the activation of nuclear factor kappa B and activator protein 1. Mitogen-activated protein kinase inhibitors and small interference RNAs specific for nuclear factor kappa B and activator protein 1 significantly suppressed the protein secretion of inflammatory mediators induced by IL-36 alpha stimulation. Conclusions: It was suggested that IL-36 alpha plays an important role in the pathophysiology of inflammation and fibrosis in the pancreas via an autocrine function.
Background and ObjectiveMore than 100 salivary constituents have been found to show levels significantly different in patients with oral squamous cell carcinoma (OSCC) from those found in healthy controls, and therefore have been suggested to be potential salivary biomarkers for OSCC detection. However, many of these potential OSCC salivary biomarkers are also involved in chronic inflammation, and whether the levels of these biomarkers could be affected by the presence of chronic periodontitis was not known. The objective of this pilot study was therefore to measure the levels of seven previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and compare them to levels found in patients with OSCC and healthy controls. The seven salivary mRNAs were interleukin (IL)-8, IL-1, dual specificity phosphatase 1, H3 histone family 3A, ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and spermidine/spermine N1-acetyltransferase 1. Material and MethodsUnstimulated whole saliva samples were collected from a total of 105 human subjects from the following four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree, non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and healthy controls. Levels of each mRNA in patient groups (OSCC or chronic periodontitis) relative to the healthy controls were determined by a pre-amplification reverse transcription-quantitative polymerase chain reaction approach with nested gene-specific primers. Results were recorded and analyzed by the Bio-Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs. control groups were analyzed by the Mann-Whitney U-test with Bonferroni corrections. ResultsOnly S100P showed significantly higher levels in patients with OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The difference in S100P levels between patients with OSCC and healthy controls was also marginally significant (p = 0.009). There was no significant difference in the levels of salivary IL-8, IL-1 and dual specificity phosphatase 1 mRNAs between patients with OSCC and patients with CPNS (p = 0.510, 0.058 and 0.078, respectively); no significant difference in levels of salivary ornithine decarboxylase antizyme 1 and spermine N1-acetyltransferase mRNAs between patients with OSCC and patients with CPS (p = 0.318 and 0.764, respectively); and no significant difference in levels of the H3 histone family 3A mRNA between patients with OSCC and either CPS (p = 0.449) or healthy controls (p = 0.107). ConclusionsSalivary S100P mRNA could be a reliable biomarker for OSCC detection, regardless of the presence of chronic periodontitis. The presence of chronic periodontitis could significantly affect the levels of the other six mRNAs, and negatively influence reliability for using them as biomarkers for oral cancer detection.
Chronic stress is a precipitating factor for disorders including depression. The basolateral amygdala (BLA) is a critical substrate that interconnects with stress-modulated neural networks to generate emotion and mood-related behaviors. The current study shows that 3 h per day of restraint stress for 14 days caused mice to exhibit long-term depressive behaviors, manifested by disrupted sociality and despair levels, which were rescued by fluoxetine. These behavioral changes corresponded with morphological and molecular changes in BLA neurons, including chronic stress-elicited increases in arborization, dendritic length, and spine density of BLA principal neurons. At the molecular level, calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) within the synaptosome exhibited an increased GluR1:GluR2 subunit ratio. We also observed increased GluR1 phosphorylation at Ser 845 and enhanced cyclic AMP-dependent protein kinase (PICA) activity in the BLA. These molecular changes reverted to the basal state post-treatment with fluoxetine. The expression of synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95) at BLA neuronal synapses was also enhanced by chronic stress, which was reversed post-treatment. Finally, chronic stress-provoked depressive behavior was overcome by local blockage of CP-AMPARs in the BLA via stereotaxic injection (IEM-1460). Chronic stress-elicited depressive behavior may be due to hypertrophy of BLA neuronal dendrites and increased of PICA-dependent CP-AMPAR levels in BLA neurons. Furthermore, fluoxetine can reverse chronic stress triggered cytoarchitectural and functional changes of BLA neurons. These findings provide insights into depression-linked structural and functional changes in BLA neurons. (C) 2017 Elsevier Inc. All rights reserved.
Introduction: Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression.Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS.Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.
ObjectiveDetermine whether the elimination of pain improves accuracy of clinical diagnostic criteria for adult chronic rhinosinusitis. Study DesignRetrospective cohort study. MethodsHistory, symptoms, nasal endoscopy, and computed tomography (CT) results were analyzed for 1,186 adults referred to an academic otolaryngology clinic with presumptive diagnosis of chronic rhinosinusitis. Clinical diagnosis was rendered using the 1997 Rhinosinusitis Taskforce (RSTF) Guidelines and a modified version eliminating facial pain, ear pain, dental pain, and headache. ResultsFour hundred seventy-nine subjects (40%) met inclusion criteria. Among subjects positive by RSTF guidelines, 45% lacked objective evidence of sinonasal inflammation by CT, 48% by endoscopy, and 34% by either modality. Applying modified RSTF diagnostic criteria, 39% lacked sinonasal inflammation by CT, 38% by endoscopy, and 24% by either modality. Using either abnormal CT or endoscopy as the reference standard, modified diagnostic criteria yielded a statistically significant increase in specificity from 37.1% to 65.1%, with a nonsignificant decrease in sensitivity from 79.2% to 70.3%. Analysis of comorbidities revealed temporomandibular joint disorder, chronic cervical pain, depression/anxiety, and psychiatric medication use to be negatively associated with objective inflammation on CT or endoscopy. ConclusionClinical diagnostic criteria overestimate the prevalence of chronic rhinosinusitis. Removing facial pain, ear pain, dental pain, and headache increased specificity without a concordant loss in sensitivity. Given the high prevalence of sinusitis, improved clinical diagnostic criteria may assist primary care providers in more accurately predicting the presence of inflammation, thereby reducing inappropriate antibiotic use or delayed referral for evaluation of primary headache syndromes. Level of Evidence4. Laryngoscope, 127:1011-1016, 2017
Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced pessimism.' After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.
Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p<.001, p<.001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p=.002, p=.001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p= .042, p= .038, p= .035, p= .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression.
BACKGROUND: Patients who have failed traditional treatment of chronic urticaria may require trials of alternative medications. Safety profiles, continuous laboratory monitoring, and physician comfort are often barriers to treatment. OBJECTIVES: To evaluate the safety of alternative agents used in chronic urticaria. METHODS: A retrospective chart review of electronic medical records from a single-center allergy and immunology clinic in a major academic hospital was conducted. One hundred twenty-six charts of patients with chronic urticaria treated with alternative agents were reviewed. RESULTS: Adverse effects were reported in 39 of 73 (53%) patients on dapsone, 19 of 47 (40%) patients on sulfasalazine, 15 of 36 (42%) patients on tacrolimus, 7 of 45 (16%) patients on hydroxychloroquine, 9 of 27 (33%) patients on mycophenolate, 6 of 8 (75%) patients on cyclosporine, and 3 of 24 (4%) patients on omalizumab. Most of these adverse effects were mild, did not require discontinuation of the medication, and resolved after stopping the medication or decreasing the dose. CONCLUSIONS: The use of alternative agents for the treatment of chronic urticaria angioedema is generally safe when proper laboratory and clinical monitoring is observed. (C) 2016 American Academy of Allergy, Asthma & Immunology
Social jet lag is a term describing misalignment between social and biological times. In this article, it is argued that the currently used formula for social jet lag captures not only this misalignment, but also sleep debt resulting from sleep deprivation during workdays. It is proposed to adopt the sleep-corrected formula for social jet lag, which takes the form of the difference between the sleep onset on free days and workdays in the case of subjects with longer sleep and later (or equal) sleep onset on free days compared to workdays; it takes the form of the difference between the sleep offset on free days and workdays for subjects with longer sleep and earlier (or equal) sleep offset on workdays compared to free days.
Chronotype is an emerging predictor of health and longevity, and understanding its influence on chronic diseases is important for constructing conceptual models of long-term pathways to health. We assessed the associations of chronotype with health status in the general Finnish adult population. Our population-based data were derived from the National FINRISK 2012 study and consisted of 4414 participants, aged 25-74 years, living in Finland. As part of their health examination, participants were asked about their circadian preference to the daily activities (morningness-eveningness) and a diagnosis or treatment for a set of common noncommunicable medical conditions and chronic diseases during the past 12 months. We found that there were 1935 (43.8%) morning types (MTs) and 595 (13.5%) evening types (ETs) and that 1884 (42.7%) were intermediates. As compared with the MTs, the ETs had significantly greater odds for depression (OR = 2.44, 95% CI = 1.52-3.90, p < 0.001) and other mental disorders (OR = 5.18, 95% CI = 2.32-11.52, p < 0.001). The odds were also increased for gallstones, and chronic obstructive pulmonary disease, but these did not remain significant after controlling for multiple testing. Responses to the single-item subjective estimation on the chronotype yielded the association of the definitely evening type of persons with the diagnosis or treatment of cardiac insufficiency (OR = 1.99, 95% CI = 1.02-3.88, p = 0.044) that was corroborated as the greater the eveningness score was, the more common the diagnosis or treatment of cardiac insufficiency was (beta= 0.92, 95% CI = 0.85-0.98, p = 0.013). This exploratory study adds further support to the role of evening chronotype in chronic disease risk, albeit underlying mechanisms remain to be elucidated.
Agroinfiltration was tested as a method of inoculation of chrysanthemum plants with chrysanthemum stunt viroid (CSVd). Binary vectors harboring dimeric CSVd sequences in sense and antisense orientations were constructed, and Agrobacterium transfected with these binary vectors was infiltrated into chrysanthemum leaves. Northern blotting and reverse transcription polymerase chain reaction analysis showed that local infection was established within 7 days and systemic infection within 20 days. CSVd polarities showed no difference in infectivity. This study showed that agroinfiltration of chrysanthemum plants is an easy, rapid, and cost-effective method for CSVd inoculation. (C) 2016 Elsevier B.V. All rights reserved.
A full-length cDNA (Slctlp2) encoding a chymotrypsin-like serine protease was cloned from Spodoptera litura. This cDNA encoded a putative serine protease with a predicted molecular mass of 30.6 kDa, which contained a serine protease catalytic motif GDSGGPL. Temporal and spatial expression of Slctlp2 mRNA and protein detected by Northern blotting, RT-PCR, qPCR and Western blotting analyses revealed that both Slctlp2 mRNA and protein were mainly present in the foregut and midgut of the 5th and 6th instar larvae during the feeding stages. In situ hybridization and immunohistochemistry confirmed that both Slctlp2 mRNA and protein were predominately present in the midgut. Expression of the gene was not induced by bacterial infection. Juvenile hormone III induced the gene expression, while 20-hydroxyecdysone had no impact on the expression. The expression of Slctlp2 mRNA and protein was down-regulated by starvation but up-regulated by re-feeding. The SlCTLP2 protein was detected in the lumen residues of the anterior, middle and posterior midgut and feces of the feeding 6th instar larvae, suggesting that it was secreted from the epithelium into the lumen of the gut. The results suggest that this Slctlp2 gene may be involved in digestive process of food proteins during the feeding stages of the larval development. (C) 2010 Elsevier Ltd. All rights reserved.
Two dehydrin genes were identified from a Cichorium intybus EST database. They were among the most abundant sequences obtained from 10 cDNA libraries constructed from chicory roots grown under field conditions. The full length cDNA sequences, designated CiDHN1 and CiDHN2, were 1,176 and 1,055 bp long and encoded predicted polypeptides of 262 and 261 amino acids, respectively. The deduced CiDHN1 protein contains a S-segment and four lysine-rich consensus motifs (K-segments) which represent a typical SK(4) structure of dehydrins. The CiDHN2 sequence contains two Y motifs and two K-segments classifying CiDHN2 as Y(2)K(2)-type dehydrin. Southern-blotting analysis suggested that CiDHN1 and CiDHN2 are single copy genes. Northern-blotting analysis revealed that both CiDHN genes are expressed in roots and leaves, with seasonal variations in transcript accumulation. The effect of cold on the CiDHN1 and CiDHN2 transcript level was demonstrated. CiDHN1 and CiDHN2 promoter analysis revealed the presence of low temperature-responsive and ABA-responsive elements.
In the present article we report europium-doped strontium ortho-silicates, namely Sr2SiO4:xEu(3+) (x=1.0, 1.5, 2.0, 2.5 or 3.0mol%) phosphors, prepared by solid state reaction method. The crystal structures of the sintered phosphors were consistent with orthorhombic crystallography with a Pmna space group. The chemical compositions of the sintered phosphors were confirmed by energy dispersive X-ray spectroscopy (EDS). Thermoluminescence (TL) kinetic parameters such as activation energy, order of kinetics and frequency factors were calculated by the peak shape method. Orange-red emission originating from the D-5(0)-F-7(J) (J=0, 1, 2, 3) transitions of Eu3+ ions could clearly be observed after samples were excited at 395nm. The combination of these emissions constituted orange-red light as indicated on the Commission Internationale de l'Eclairage (CIE) chromaticity diagram. Mechanoluminescence (ML) intensity of the prepared phosphor increased linearly with increasing impact velocity of the moving piston that suggests that these phosphors can also be used as sensors to detect the stress of an object. Thus, the present investigation indicates that the piezo-electricity was responsible for producing ML in the prepared phosphor.
Cigarette smoke has been considered a major contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth muscle layer has been observed to be markedly thickened and the proliferation of airway smooth muscle cells (ASMCs) was therefore used by the present study as a model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to various concentrations of CSE and the proliferation of the cells was analyzed by an MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-binding protein alpha (C/EBP-) in CSE-stimulated ASMCs were determined by polymerase chain reaction and western blot analyses. In addition, the effects of RNA interference (RNAi) to knockdown calreticulin and/or C/EBP- on ASMC proliferation were studied. CSE was found to promote the proliferation of ASMCs, which was associated with increased expression of calreticulin and decreased expression of C/EBP-. Knockdown of calreticulin resulted in the upregulation of C/EBP- and inhibition of cell proliferation, while simultaneous knockdown of C/EBP- promoted cell proliferation. The present study revealed that CSE promoted the proliferation of ASMCs, which was mediated by inhibition of C/EBP-. These findings shed new light on airway remodeling in COPD and may provide novel approaches for therapies.
Using data from the state and national Youth Risk Behavior Surveys for the period 1991-2005, Carpenter and Cook (2008) find a strong, negative relationship between cigarette taxes and youth smoking. We revisit this relationship using four extra waves of YRBS data (from 2007, 2009, 2011, and 2013). Our results suggest that youths have become much less responsive to cigarette taxes since 2005. In fact, we find little evidence of a negative relationship between cigarette taxes and youth smoking when we restrict our attention to the period 2007-13. We conclude that policy makers interested in reducing youth smoking may have to adopt alternative strategies.
The stearoyl-acyl carrier protein desaturase (SAD) is a key enzyme that determines the ratio of saturated to unsaturated fatty acids in higher plants. Using reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends, a full-length cDNA of SAD was obtained from developing leaves of Cinnamomum longepaniculatum. Sequence analysis showed that the deduced amino acid sequence had high similarity to other reported SADs. The CSAD gene was functionally expressed in Escherichia coli, and the desaturating activity of the recombinant protein was markedly detected when assayed in vitro by adding spinach ferredoxin. Southern blot analysis indicated that the gene was a member of a small gene family. Northern blotting revealed that the CSAD gene was highly expressed in developing leaves of C. longepaniculatum. These results would provide opportunities for modifying fatty acid composition in C. longepaniculatum.
Although it has long been established that estrogen alters circadian rhythms in behavior, physiology, and reproductive functions in mammals, the molecular mechanism for these effects remains unknown. To explore the possibility that estrogen affects circadian rhythms by changing the expression of clock-related genes, we investigated the effects of chronic treatment with 17 beta-estradiol (E2) on the expression of Per1 and Per2 genes in the brain (suprachiasmatic nucleus and cerebral cortex) and periphery (liver, kidney, and uterus) of ovariectomized rats by means of in situ hybridization and northern blotting. In the brain, E2 treatment advanced the peak of Per2 mRNA expression in the SCN; however, it failed to affect the rhythm of Per2 mRNA expression in the CX and Per1 mRNA expression in both the SCN and the CX. In nonreproductive peripheral tissues (liver and kidney), E2 delayed the phase and increased the amplitude of Per1 mRNA expression. In the reproductive tissues (uterus), biphasic rhythms in Per1 and Per2 mRNA were observed after E2 treatment. These findings suggest that the effects of estrogen are different between central and peripheral clock in the brain, and between reproductive and nonreproductive tissues in the periphery. (c) 2005 Wiley-Liss, Inc.
Objective: Symptoms of airway diseases are often associated with specific times of the day. For example, midnight worsening of cough is a frequent complaint of patients with laryngitis and bronchitis. We speculate that these symptoms are under the control of the circadian clock, and the clock genes in the airway epithelium play some important roles. In the present study, we tried to prove the time specific expressions of clock oscillating genes in the murine larynx. Materials and methods: Adult wild-type C57/B16 mice and mCry1(-/-)mCry2(-/-) mutant mice were used for this study. We employed immunohistochemistyr and/or Northern blotting for examining the circadian expression of mPer1, mPer2, C/EBPbeta, HNF3beta, and MUC5b. Results: The expression of mPer2 mRNA showed a strong day-night expression difference, which was abolished after the lesion of the suprachiasmatic nucleus, and in mCry1(-/-)mCry2(-/-) mutant mice. mPER1 and mPER2 proteins both showed very similar expression profiles in the epithelium and submucosal glands with a peak in the evening and a trough in the early morning. Other nuclear proteins such as C/EBPbeta and HNF3beta did not show the rhythms. MUC5b protein showed circadian oscillation in the laryngeal submucosal gland. Conclusion: In this study, we confirmed the existence of a local laryngeal clock which is controlled by the central clock in the suprachiasniatic nucleus. MUC5b protein in the submucosal mucous gland also showed circadian rhythm. We consider that these rhythmic expressions may cause the time specific symptoms among laryngeal diseases. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
A switchable operational amplifier (opamp) is examined in this brief. It is based on a current-mirror opamp with switchable transconductance values. Contrary to switched opamp (SO) and partial SO, it can be used to realize both half-delay and full-delay switched-capacitor integrators. The added circuit design complexity is shown to be minimal. Optimal switching is developed in this brief. It is also shown in this brief that the absolute average power consumption can be less as compared with an SO design. The experimental results of a delta-sigma modulator prototype (designed in 1-V 65-nm CMOS), employing the designated switchable-opamp technique, show power reduction without any degradation in SNDR (58.5 dB) or SFDR (67 dB).
Circulating tumor cells (CTC) have become a field of interest for oncologists based on the premise that they constitute the underpinning for metastatic dissemination. The lethal nature of cancer is no longer attributed to solid tumor formation, but rather to the process of metastasis; shifting the focus of current studies towards the isolation and identification of metastatic progenitors, such as CTCs. CTCs originate from primary tumor masses that undergo morphologic and genetic alterations, which involve the release of mesenchymal-like cancer cells into the bloodstream, capable of invading nearby tissues for secondary tumor development. Cancerous cells contained in the primary tumor mass acquire the motile mesenchymal phenotype as a result of the Epithelial-to-Mesenchymal Transition, where substantial variations in protein expression and signaling pathways take place. CFCs that migrate from the primary tumor, intravasate into the systemic vasculature, are transported through the bloodstream, and invade tissues and organs suitable for secondary tumor development. While only a limited number of CTCs are viable in the bloodstream, their ability to elude the immune system, evade apoptosis and successfully metastasize at secondary tumor sites, makes CTCs promising candidates for unraveling the triggers that initiates the metastatic process. In this article, these subjects are explored in greater depth to elucidate the potential use of CFCs in the detection, disease staging and management of metastatic melanoma. (C) 2017 Elsevier B.V. All rights reserved.
Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication. Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis. Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization. A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22-47), during which 31% were hospitalized [median IQR mths 12.5 (3-27)] and 12% were re-hospitalized [10.5 mths (3-28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01-2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1-1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1-2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1-4.3, p = 0.03). Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients.
Patients with decompensated cirrhosis have high morbidity and are commonly hospitalized with acute kidney injury. We examined serum levels of Siglec-7, a transmembrane receptor that regulates immune activity, as a biomarker for mortality in patients with cirrhosis and acute kidney injury. Serum Siglec-7 was measured in hospitalized patients with cirrhosis and acute kidney injury, as well as in reference groups with acute liver injury/acute kidney injury, cirrhosis without acute kidney injury, and sepsis without liver disease. Clinical characteristics and subsequent outcomes were examined using univariate and multivariable analyses according to initial Siglec-7 levels. Primary outcome was death by 90 days. One hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute kidney injury and were used in the primary analysis. Average Model for End-Stage Liver Disease (MELD) score was 24 [95 % CI 23, 26], and serum creatinine was 2.5 [2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of 1.96 [1.04, 3.69; p = 0.04]. There was no difference in Siglec-7 levels by etiology of AKI (p = 0.24). Addition of serum Siglec-7 to MELD score improved discrimination for 90-day mortality [category-free net reclassification index = 0.38 (p = 0.04); integrated discrimination increment = 0.043 (p = 0.04)]. Serum Siglec-7 was associated with increased mortality among hospitalized patients with cirrhosis and acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination to predict 90-day mortality.
Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation reaction kinetics) that determine site-specific toxicity; second, the impact on RNA molecules. Knowledge of the RNA world' has dramatically changed our understanding of cellular and molecular biology. The inherent RNA-crosslinking properties should make platinum-based drugs interact with coding and non-coding RNAs. Third, we will discuss the impact on the immune system, which is now recognized to substantially contribute to chemotherapy efficacy. Together, platinum drugs are in fact old drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave the way to new drugs or an improved application of the already existing compounds.
The newly discovered Citrus leprosis virus cytoplasmic type 2 (CiLV-C2) is one of the causal virus of citrus leprosis disease complex; which leads to substantial loss of citrus production in the states of Meta and Casanare of Colombia. Specific and sensitive detection methods are needed to monitor the dissemination of CiLV-C2 in Colombia, and to prevent introduction of CiLV-C2 to other citrus growing countries. Toward this end, putative coat protein gene (CPG) of CiLV-C2 was amplified from CiLV-C2 infected citrus tissues. The CPG was cloned, expressed and purified a recombinant coat protein of 31 kDa which used to generate monoclonal antibodies and polyclonal antisera. Four monoclonal antibodies and two polyclonal antisera were selected as being specific following Western blotting. The monoclonal antibody MAb E5 and polyclonal antiserum PAb UF715 were selected testing with an extract of CiLV-C2 infected leaves using triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA). In addition, an immunocapture RT-PCR was standardized using MAb E5 for specific and sensitive detection of CiLV-C2. The standardized TAS-ELISA and IC-RT-PCR were able to detect CiLV-C2 in the extracts of symptomatic citrus leprosis tissues up to the dilutions of 1:160 and 1:2580, respectively. Result demonstrated that CiLV-C2 is present in citrus orchards in Meta and Casanare citrus growing areas of Colombia. TAS-ELISA could be used for routine detection of CiLV-C2, epidemiological studies, and for border inspections for quarantine purposes. IC-RT-PCR could be valuable for CiLV-C2 validation and viral genome analysis. (C) 2017 Elsevier B.V. All rights reserved.
Citrus tristeza virus (CTV) is a major pathogen of Citrus. A single dominant gene Ctv present in the trifoliate relative of Citrus, Poncirus trifoliata confers broad spectrum resistance against CTV. Refinement of genetic maps has delimited this gene to a 121 kb region, comprising of ten candidate Ctv resistance genes. The ten candidate genes were individually cloned in Agrobacterium based binary vector and transformed into three CTV susceptible grapefruit varieties. Two of the candidate R-genes, R-2 and R-3 are exclusively expressed in transgenic plants and in Poncirus trifoliata, while five other genes are also expressed in non-transformed Citrus controls. Northern blotting with a CTV derived probe for assessment of infection in virus inoculated plants over a span of three growth periods, each comprising of six to eight weeks, indicates either an absence of initiation of infection or it's slow spread in R-2 plant lines or an initial appearance of infection and it's subsequent obliteration in some R-1 and R-4 plant lines. Limited genome walk up- and downstream form R-1 gene, based on it's 100% sequence identity between Poncirus and Citrus, indicates promoter identity of 92% between the two varieties. Further upstream and downstream sequencing indicates the presence of an O-methyl transferase and a Copia like gene respectively in Citrus instead of the amino acid transporter like gene upstream and a sugar transporter like gene downstream in Poncirus. The possibility of recombinations in the resistance locus of Citrus and the need for consistent monitoring for virus infection and gene expression in the transgenic Citrus trees is discussed.
MicroRNAs (miRNAs) are a new family of small RNA molecules found in plants and animals. We developed a comprehensive strategy for identifying new miRNA homologues by mining the repository of available citrus expressed sequence tags (ESTs). By adopting a range of filtering criteria, we identified a total of 38 potential miRNAs - nine, five, nine and 15 miRNAs in Citrus trifoliata (ctr-miRNAs), C. clementina (ccl-miRNAs), C. reticulata (crt-miRNAs) and C. sinensis (csi-miRNAs), respectively - from more than 430,000 EST sequences in citrus. Using the potential miRNA sequences, we conducted a further BLAST search of the mRNA database and found six potential target genes in these citrus species. Eight miRNAs were selected in order to verify their existence in citrus using Northern blotting, and the functions of several miRNAs in miRNA-mediated gene regulation are experimentally suggested. It appears that all these miRNAs regulate expression of their target genes by cleavage, which is the most common situation in gene regulation mediated by plant miRNAs. Our achievement in identifying new miRNAs in citrus provides a powerful incentive for further studies on the important roles of these miRNAs.
The study of microRNA (miRNA), a component of low molecular weight RNA (LMW RNA), has received increasing attention in recent years. A critical prerequisite in miRNA studies is acquisition of high quality LMW RNA. LMW RNA is generally obtained from total RNA or from total nucleic acids solutions. Most traditional methods for LMW RNA isolation involve many steps and chemical reagents which upon degradation may negatively affect results. We employed a simple and quick method involving trizol for total RNA extraction from citrus tissues, then generation of LMW RNA using 4M LiCl, which have been successfully utilized in studies in our laboratory. Compared with traditional methods, this method is less expensive and produced high RNA yields while avoiding the use of phenol or other toxic reagents. In addition, the entire procedure can be completed within 4 hours with many samples being processed simultaneously. Therefore, this is a practical and efficient method for LMW RNA extraction from woody fruit crops containing high levels of polysaccharide and polyphenolics. Using the extracted LMW RNA, miRNAs were successfully detected and characterized by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blotting.
MicroRNAs (miRNAs) are a class of non-protein-coding small RNAs. Considering the conservation of many miRNA genes in different plant genomes, the identification of miRNAs from non-model organisms is both practicable and instrumental in addressing miRNA-guided gene regulation. Citrus is an important staple fruit tree, and publicly available expressed sequence tag (EST) database for citrus are increasing. However, until now, little has been known about miRNA in citrus. In this study, 27 known miRNAs from Arabidopsis were searched against citrus EST databases for miRNA precursors, of which 13 searched precursor sequences could form fold-back structures similar with those of Arabidopsis. The ubiquitous expression of those 13 citrus microRNAs and other 13 potential citrus miRNAs could be detected in citrus leaf, young shoot, flower, fruit and root by northern blotting, and some of them showed differential expression in different tissues. Based on the fact that miRNAs exhibit perfect or nearly perfect complementarity with their target sequences, a total of 41 potential targets were identified for 15 citrus miRNAs. The majority of the targets are transcription factors that play important roles in citrus development, including leaf, shoot, and root development. Additionally, some other target genes appear to play roles in diverse physiological processes. Four target genes have been experimentally verified by detection of the miRNA-mediated mRNA cleavage in Poncirus trifoliate. Overall, this study in the identification and characterization of miRNAs in citrus can initiate further study on citrus miRNA regulation mechanisms, and it can help us to know more about the important roles of miRNAs in citrus.
This paper introduces the adaptive slope compensation method into the digital clamping current control at various input voltages to improve the power factor (PF) and the total harmonic distortion (THD) of the universal input. The controller conducts a phase-management mechanism for various input voltages and load conditions to raise the circuit conversion efficiency. The optimal switching timing for one-and two-phase operations can be determined from the power loss distribution. A digital signal processor chip TMS320F28035 is used to implement the digital platform. A 300-W laboratory prototype with a universal line voltage 80-V dc output voltage is designed and tested to verify the feasibility. The values of efficiency from light load (10% of rated power) to full load at 115- and 230-V inputs are greater than 95%. PF values from medium to full load are greater than 0.94. Input current harmonics also meet the norm of IEC 61000-3-2 Class D.
In this paper, a three-stage class AB operational transconductance amplifier (OTA) with large slew rate is presented. The reversed nested Miller compensation technique is used to stabilize the proposed OTA, allowing the slew rate enhancement to be achieved by using class AB input and output stages. A flipped-voltage follower cell in the first stage in combination with a switched-capacitor level shifter in the last stage are utilized to implement the class AB operation. Circuit level simulation results are provided using HSPICE and a 90 nm CMOS technology which show 306 % enhancement in the large-signal FoM with approximately the same power dissipation compared to the class A OTA. The achieved settling time with 0.02 % accuracy for the proposed class AB and conventional class A OTAs are 7.5 and 15.3 ns, respectively.
In this paper we extend the figures of merit for class AB symmetrical OTAs to the fully differential case and compare topologies from the literature. This analysis shows that the power consumption of the CMFB can have a significant role in determining the efficiency of the OTA, but on the other hand a CMFB is needed both to set the desired output common mode voltage and to improve the CMRR. We propose the complementary triode CMFB, i.e. a triode CMFB applied both at the NMOS and PMOS current mirrors, as suitable for class AB symmetrical OTAs, and show some case studies in deep submicron CMOS technology to assess the effectiveness of the proposed solution. Copyright (C) 2015 John Wiley & Sons, Ltd.
In recent years, it is desired that the bandwidth of a class-D amplifier is widened using sampling frequencies as low as possible. For example, it is expected in the application of the power amplifier of vibration generator that the bandwidth is kept 5[kHz] within the load impedance infinity similar to 2 [Omega]. In this paper, it is shown that this demand to the class-D amplifier can be attained by an A2DOF (Approximate 2-Degree-Of-Freedom) digital controller with 200[kHz] switching and sampling frequencies. The controller is implemented by a FPGA and it is shown from experiments that this demand is attained enough.
The present study reports US independent classic articles published by American scientists from 1900 to 2014. We examined those articles that had been cited at least 1000 times since publication to the end of 2014 using the Science Citation Index Expanded in the Web of Science (WoS). We also applied a bibliometric indicator, the Y-index, to assess the contributions of the authors of these articles. The results showed that 4909 classic articles were published between 1916 and 2013, and that the most productive categories from the WoS were multidisciplinary sciences, biochemistry and molecular biology, and general and internal medicine. Science published most of these articles, and the three most productive institutions were Harvard University, Massachusetts Institute of Technology and Stanford University. The physicist, Edward Witten was the most prolific author and an article written by the biochemist, Marion Bradford at University of Georgia in 1976 had the highest number of citations. In addition, the article by Perdew, Burke and Ernzerhof at Tulane University had the highest number of citations in 2014.
Renewable energy projects in Korea have two avenues that provide subsidies to increase their financial viability. Feed-in-Tariffs (FITs) offer cost based prices for renewable electricity to compete with conventional energy producers. The Clean Development Mechanism (CDM) issues certified emission reduction (CER) credits that generate additional revenues, enhancing renewable projects' return on investment. This study investigated how these subsidies impact the financial returns on Korea's CDM projects. An investment analysis was performed on four cases including solar, hydropower, wind and landfill gas projects. Revenues from electricity sales, FITs and CERs were compared using financial indicators to measure their relative contributions on profitability. Results indicate that CDM is partial towards large scale projects with high emission reductions. Moreover, conflicts with FIT schemes can deter small scale, capital intensive projects from pursuing registration. The analysis highlights CDM's bias for particular project types, which is in part due to its impartiality towards carbon credit prices. It also reveals that Korea, a key benefactor of CDM, is susceptible to such biases, as demonstrated by the disproportionate distribution of issued CERs. Improving incentives for bundled, small scale projects, CER price differentiation, and excluding domestic subsidies during additionality testing are proposed as possible reforms.
This review attempts to put together the sequential pathogenesis of VHL mutant metastatic ccRCC with links between driver pathways, epigenetics, biochemistry and immune evasion, with a translational perspective. We reflect on the gap between our understanding of the molecular pathogenesis and currently accepted standard of care in metastatic RCC, and present ideas to bridge the gap with better translational research.Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all RCC, and biallelic Von Hippel-Lindau (VHL) gene defects occur in 75% of sporadic ccRCC. The etiopathogenesis of VHL mutant metastatic RCC, based on our understanding to date of molecular mechanisms involved, is a sequence of events which can be grouped under the following: (i) loss of VHL activity (germline/somatic mutation + inactivation of the wild-type copy); (ii) constitutive activation of the hypoxia-inducible factor (HIF) pathway due to loss of VHL activity and transcription of genes involved in angiogenesis, epithelial-mesenchymal transition, invasion, metastasis, survival, anaerobic glycolysis and pentose phosphate pathway; (iii) interactions of the HIF pathway with other oncogenic pathways; (iv) genome-wide epigenetic changes (potentially driven by an overactive HIF pathway) and the influence of epigenetics on various oncogenic, apoptotic, cell cycle regulatory and mismatch repair pathways (inhibition of multiple tumor suppressor genes); (v) immune evasion, at least partially caused by changes in the epigenome. These mechanisms interact throughout the pathogenesis and progression of disease, and also confer chemoresistance and radioresistance, making it one of the most difficult metastatic cancers to treat. This article puts together the sequential pathogenesis of VHL mutant ccRCC by elaborating these mechanisms and the interplay of oncogenic pathways, epigenetics, metabolism and immune evasion, with a perspective on potential therapeutic strategies. We reflect on the huge gap between our understanding of the molecular biology and currently accepted standard of care in metastatic ccRCC, and present ideas for better translational research involving therapeutic strategies with combinatorial drug approach, targeting different aspects of the pathogenesis.
This paper analyzes the impacts of flexible demands on day-ahead market outcomes in a system with significant wind power production. We use a two-stage stochastic market-clearing model, where the first stage represents the day-ahead market and the second stage represents the real-time operation. On one hand, flexibility of demands is beneficial to the system as a whole since such flexibility reduces the operation cost, but on the other hand, shifts in demands from peak periods to off-peak periods may influence prices in such a way that demands may not be willing to provide flexibility. Specifically, we investigate the impacts of different degree of demand flexibility on day-ahead prices. A number of scenarios modeling the uncertainty associated with wind production at the operation stage, and nonconvexities due to start-up costs of generators and their minimum power outputs are taken into account.
The changes in endopolygalacturonase (endo-PG) levels and endo-PG expression in nonmelting flesh (NMF) and melting flesh (MF) peach fruits (Prunus persica) during softening were studied. The endo-PG gene was analysed to identify polymorphisms exploitable for early marker-assisted selection WAS) of flesh texture. The role of endo-PG in softening was assessed by western and northern blotting and by biochemical analyses. Polymorphisms in the endo-PG gene were revealed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. An endo-PG protein was detected in both NMF and MF fruits. The levels of this endo-PG protein were higher and increased with softening in MF fruits, but remained lower and were constant in NMF fruits. The different levels of endo-PG appeared to be caused by the differential expression of an endo-PG gene, whose open-reading frame (ORF) showed five single nucleotide polymorphisms (SNPs) in NMF 'Oro A' compared with MF 'Bolero'. One of these SNPs allowed us to determine the allelic configuration at the melting flesh M locus and also seemed to be exploitable for early MAS in other NMF/MF phenotypes. The NMF phenotype does not seem to be caused by a large deletion of the endo-PG gene.
Background: Carbohydrates, also called glycans, play a crucial but not fully understood role in plant health and development. The non-template driven formation of glycans makes it impossible to image them in vivo with genetically encoded fluorescent tags and related molecular biology approaches. A solution to this problem is the use of tailor-made glycan analogs that are metabolically incorporated by the plant into its glycans. These metabolically incorporated probes can be visualized, but techniques documented so far use toxic copper-catalyzed labeling. To further expand our knowledge of plant glycobiology by direct imaging of its glycans via this method, there is need for novel click-compatible glycan analogs for plants that can be bioorthogonally labelled via copper-free techniques. Results: Arabidopsis seedlings were incubated with azido-containing monosaccharide analogs of N-acetylglucosamine, N-acetylgalactosamine, L-fucose, and L-arabinofuranose. These azido-monosaccharides were metabolically incorporated in plant cell wall glycans of Arabidopsis seedlings. Control experiments indicated active metabolic incorporation of the azido-monosaccharide analogs into glycans rather than through non-specific absorption of the glycan analogs onto the plant cell wall. Successful copper-free labeling reactions were performed, namely an inverse-electron demand Diels-Alder cycloaddition reaction using an incorporated N-acetylglucosamine analog, and a strain-promoted azide-alkyne click reaction. All evaluated azido-monosaccharide analogs were observed to be non-toxic at the used concentrations under normal growth conditions. Conclusions: Our results for the metabolic incorporation and fluorescent labeling of these azido-monosaccharide analogs expand the possibilities for studying plant glycans by direct imaging. Overall we successfully evaluated five azido-monosaccharide analogs for their ability to be metabolically incorporated in Arabidopsis roots and their imaging after fluorescent labeling. This expands the molecular toolbox for direct glycan imaging in plants, from three to eight glycan analogs, which enables more extensive future studies of spatiotemporal glycan dynamics in a wide variety of plant tissues and species. We also show, for the first time in metabolic labeling and imaging of plant glycans, the potential of two copper-free click chemistry methods that are bio-orthogonal and lead to more uniform labeling. These improved labeling methods can be generalized and extended to already existing and future click chemistry-enabled monosaccharide analogs in Arabidopsis.
Aim: The purpose of this study was to examine clients' perspectives regarding the helpful aspects of pluralistic therapy for depression. Method: Thirty-nine clients received psychological treatment in a multi-site study exploring alternative interventions to standardised 'evidence-based' approaches. Eighteen of them consented to a face-to-face or telephone change interview at the end of their treatment. Change interviews aim to elicit clients' perspective regarding changes that they noticed during, and after, therapy and also the possible causes of these changes. Their descriptions were transcribed and analysed thematically using explicit coding of themes which were audited by the research team. Findings: The data were categorised in three a priori domains consisting of specific themes. The first domain constitutes of client-originated helpful factors including clients' positive perspectives of therapy, clients' overall effort to change and clients' contribution in the decision-making process of therapy. Therapists were perceived as helpful when they were accepting and respectful, empathic, responding to clients' needs, making clients feel comfortable, challenging, empowering, using techniques, flexible and reassuring. Treatment outcomes such as change in perspectives, behaviour and response to problems as well as increased insight were also considered helpful factors of therapy. Conclusion: These findings suggest that clients in pluralistic therapy are active agents of change and their willingness to engage with treatment is crucial. Helping clients feel comfortable by creating a safe therapeutic environment, challenging dysfunctional patterns associated with depression and empowering them to believe that change is possible through reassurance and non-intrusive guidance were considered beneficial.
Although species traits have the potential to disentangle long-term effects of multiple, potentially confounded drivers in ecosystems, this issue has received very little attention in the literature. We aimed at filling this gap by assessing the relative effects of hydroclimatic and water quality factors on the trait composition of invertebrate assemblages over 30 years in the Middle Loire River (France). Using a priori predictions on the long-term variation of trait-based adaptations over the three decades, we evaluated the ability of invertebrate traits to indicate the effects of warming, discharge reduction and water quality improvement. Hydroclimatic and water quality factors contributed to up to 65% of the variation in trait composition. More than 70% of the initial trait response predictions made according to observed long-term hydroclimatic changes were confirmed. They supported a general climate-induced trend involving adapted resistance and resilience strategies. A partial confounding effect of water quality improvement acting on trophic processes was also highlighted, indicating that improved water quality management can significantly help to reduce some adverse effects of climate change. This trait-based approach can have wider implications for investigating long-term changes driven by multiple, potentially confounded factors, as frequently encountered in the context of global change.
Electricity is the basic tool that drives industrialization, technological advancement, engineering transformation and economic growth all over the world. The situation of Nigeria's electricity power sector is one that has defied virtually every effort made to resurrect it from its state of dilapidation. A major concern is "can there ever be stable and cost effective electricity in Nigeria?" The authors are positive this can be realised, but not without considering other forms of electricity energy resources available in Nigeria other than the conventional sources of electricity which is currently the mainstay. A deliberate transition from conventional sources of electricity energy to renewable and environmental friendly sources is critical for national development, even though recent development show the Nigerian government is backsliding in adopting renewable energy technologies. This paper will be used to highlight the different sources of renewable energy which is critical to solve the lingering problem of electricity generation in Nigeria. Hence, based on the literature, modeled scenarios and field experience, the authors discovered it is much easier for individuals to drive this transition to 100% renewable energy than to continue to depend on government forever.
This paper focuses on the effectiveness of passive adaptation measures against climate change, in the medium (2036-2065) and long term (2066-2095), for three case studies located in Florence (central Italy). In order to identify and highlight the passive measures which can provide comfort conditions with the lowest net heating and cooling energy demand, the input assumptions consider a constant thermal comfort level and don't take into account either the effect of HVAC system's performance and the degradation of the materials by ageing. The study results show that, in case of poorly insulated buildings, on the medium term, the reduction of energy needed for heating could be bigger than the increase for cooling, resulting in a total annual net energy need decrease, while in the long term the opposite happens. Conversely, considering a high level of thermal insulation, due to the large increase in cooling demand, the total annual energy need rises in both periods. Furthermore, attention should be paid to internal loads and solar gains that, due to the projected climate change, could become main contributors to the energy balance. In general, since the magnitude of energy need increase for cooling and decrease for heating is very significant on the long term, and varies in function of the type of building, the passive measure adopted and the level of thermal insulation, the research results lead to pay close attention to different types of energy refurbishment interventions, that should be selected in function of their effectiveness over time.
Introduction: There are now more than 50,000 hospitalists working in the United States. Limited empiric research has been performed to characterize clinical excellence in hospital medicine. We conducted a qualitative study to discover elements judged to be most pertinent to excellence in clinical care delivered by hospitalists. Methods: The chiefs of hospital medicine at five hospitals were asked to identify their "clinically best" hospitalists. Data collection, in the form of one-on-one interviews, was directed by an interview guide. Interviews were transcribed verbatim, and the informants' perspectives were analyzed using editing analysis to identify themes. Results: A total of 26 hospitalists were interviewed. The mean age of the physicians was 38 years, 13 (50%) were women, and 16 (62%) were non-white. Seven themes emerged that related to clinical excellence in hospital medicine: communicating effectively, appreciating partnerships and collaboration, having superior clinical judgment, being organized and efficient, connecting with patients, committing to continued growth and development, and being professional and humanistic. Discussion: This qualitative study describes how respected hospitalists think about excellence in clinical care in hospital medicine. Their perspectives can be used to guide continuing medical education, so that offered programs can pay attention to enhancing the skills of learners so they can develop towards excellence, rather than using only competence as the desired target objective.
The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients are not well known. We performed a prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow-up of 3.4 years (interquartile range 2.5-4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case-control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID. A large prospective study of the epidemiology of respiratory viruses in lung transplant recipients using molecular assays demonstrates a very high incidence of respiratory viral infection and an association between respiratory virus infectious diseases, immediate allograft dysfunction, and the development of acute rejection and opportunistic infection.
DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs.
The recent outbreak of Ebola virus disease in West Africa has led to more than 11,000 deaths, with a peak in mortality from August through December of 2014. A meeting convened by the World Health Organization (WHO) in September 2014, concluded that an urgent unmet need exists for efficacy and safety testing of the Ebola virus vaccine candidates and that clinical trials should be expedited. These vaccines could be used both in an outbreak setting and to provide long-term protection in populations at risk of sporadic outbreaks. A number of vaccines have been evaluated in phase 1 trials, but the two most advanced first-generation Ebola vaccine candidates are the live replicating vesicular stomatitis virus (rVSV) and the replication-defective chimpanzee adenovirus 3 (ChAd3). This review focuses on these two vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola virus vaccines. Crown Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.
Breast cancer is the second leading cause of cancer death in women, affecting 1.7 million patients every year worldwide. As a result of its heterogeneous nature, the genetic profile and associated clinical feature varies greatly among different breast cancer subtypes. With the advancement of molecular biology, our understanding of breast cancer has improved greatly in recent years. In this review, we examine different types of breast cancer and summarize their clinical features, current treatment schemes, and potential drug resistance profiles in response to treatments. We believe that the understanding of the molecular mechanisms of each treatment and subsequent drug resistance development will eventually lead to the discovery of more effective and efficient second-line therapeutics.
We have isolated the cDNA of Ca2+/H+ antiporter which was designated as Suaeda salsa cation exchanger 1 (SsCAX1) from the C-3 halophyte S. salsa L. To ascertain the location of SsCAX1 in the cell, a peptide-specific antibody to SsCAX1 was prepared, and Western blotting analysis showed that it reacted only with a 48.8-kDa protein from S. salsa vacuolar membrane. Furthermore, SsCAX1 could resume yeast vacuolar Ca2+ transport mutants growth in high Ca2+ concentration (200 mM) culture medium. Northern blotting analysis showed that SsCAX1 expression was mainly found in the leaves and stems and slightly in the roots of S. salsa seedlings. Moreover, SsCAX1 expression levels and the protein amounts were significantly upregulated by CaCl2 and NaCl treatment, respectively. In addition, the upregulation of the expression levels of V-H+-ATPase subunit c coordinated with the expression levels of the Ca2+/H+ antiporter under salinity. These results suggested that SsCAX1 from halophyte S. salsa might be a Ca2+ transporter at tonoplast and plays a key role in maintaining cytosolic Ca2+ homeostasis under saline condition.
It is known that the neutral/cytosolic alpha-mannosidase (Man2c1) which can cleave alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues, is stimulated by cobalt and is inhibited by furanose analogues swainsonine (SW) and 1,4-dideoxy-1,4-imino-D-mannitol (DIM). The enzyme is involved in the degradation of oligomannosides derived from dolichol intermediates and the degradation of newly synthesized glycoproteins. An immunological relationship has been demonstrated between the rat endoplasmic reticulum alpha-mannosidase and the cytosolic alpha-mannosidase. In fact antibodies raised against the soluble alpha-mannosidase recognized the membrane form of the ER alpha-mannosidase. A cDNA encoding the mouse cytosolic alpha-mannosidase was obtained by RZPD (Deutsches Ressourcenzentrum fur Genomforschung GmbH), Berlin, Germany. Comparison of the mouse genomic sequence with the cDNA sequence revealed the presence of 25 introns within the cytosolic alpha-mannosidase gene. The gene spans 11.5 kb from the major transcription initiation site to the RNA cleavage site. The transcription initiation site of mouse cytosolic alpha-mannosidase was mapped to 170 bases upstream of the ATG codon using 5' RACE. Northern blotting analysis revealed expression of a major transcript of 3.8 kb in all tissues examined. COS cells transfected with the cDNA showed a 20-fold increase in cytosolic alpha-mannosidase activity. This enzyme activity was stimulated by cobalt and inhibited by DIM and EDTA. Furthermore we demonstrated that the expressed enzyme was active towards the radiolabeled substrate Man9GlcNAc1 giving the final product Man5GlcNAc1 through the formation of Man8GlcNAc1 isomer C as intermediate. (c) 2006 Elsevier B.V. All rights reserved.
Parasites are significant groups for carcinogenesis among which liver flukes, including Opisthorchis viverrini and Clonorchis sinensis, are typical representatives causing cholangiocarcinoma (CCA), the second most common primary hepatic malignancy with dismal prognosis. O. viverrini is prevalent in Southeast Asia, infecting 10 million people while C. sinensis has a wider distribution in East Asia and several Southeast Asian countries, affecting more than 35 million people's health. These two worms have some common characteristics and/or discrepancies in life cycle, genome, and transcriptome. As hot spots in recent years, genome and transcriptome research has extracted numerous novel fluke worm-derived proteins, which are excellent for carcinogenic exploration. However, just a handful of these studies have focused on the metabolic pathway. In this study, the main mechanisms of carcinogenesis of both worms, in terms of mechanical damage, metabolic products and immunopathology, and other possible pathways, will be discussed in detail. This review retrospectively describes the main traits of C. sinensis and O. viverrini, their molecular biology and core carcinogenic mechanisms in a contrast pattern.
Clopidogrel resistance in patients with acute coronary syndrome (ACS) is one of the key causes of recurrent cardiovascular disease (CVD) events after percutaneous coronary intervention (PCI). Clopidogrel targets the platelet membrane receptor P2RY12 to inhibit platelet aggregation via adenosine diphosphate (ADP). This study aimed to investigate the relationships between P2RY12 polymorphisms and the risk of clopidogrel resistance and adverse CVD events after PCI. From January 2015 to December 2014, patients who had been diagnosed with ACS undergoing PCI and treated with clopidogrel were recruited for this prospective cohort study (N=498). Data regarding demographics, medication intake, and ACS lesion were recorded, and whole blood samples were collected for biochemical tests, ADP-induced platelet aggregation ratio detection, and P2RY12 genotyping. P2RY12 genotyping was performed by polymerase chain reaction. The left ventricular ejection fraction was calculated by echocardiography. After 3 to 12 months of follow-up, data regarding any adverse CVD event or death were recorded. The allele frequencies for the T variation alleles in C34T and G52T of P2RY12 were 20.3% and 11.6%, respectively. Patients with T variations at C34T or G52T of P2RY12 had a significantly higher risk of clopidogrel resistance (C34T: P<0.001; G52T: P=0.003) and total cardiovascular events (C34T: P=0.013; G52T: P=0.018) compared to those with the wild-type genotype. Moreover, multivariable logistic regression showed that patients with the T variations in C34T (odds ratio [OR]: 2.89 (95% confidence interval [CI]: 1.48-5.64), P=0.002) and G52T (OR: 3.68 [95% CI: 1.71-7.92], P=0.001) also had a significantly higher risk of clopidogrel resistance. Also, the T variations in C34T (OR: 2.68 [95% CI: 1.07-6.73], P=0.035) and G52T (OR: 5.64 [95% CI: 1.52-20.88], P=0.010) significantly increased the risk of post-PCI CVD events after accounting for confounding factors. The P2RY12 gene polymorphisms C34T and G52T were significantly associated with a higher risk of clopidogrel resistance and sequential cardiovascular events in Chinese ACS patients after PCI.
Due to the higher attenuation of switching frequency current harmonics, the LCL filter has been widely used in grid-connected inverters. To deal with the resonance of the LCL filter, the capacitor current is usually fed back to damp the resonance actively. However, the computation and pulsewidth modulation (PWM) delays in the digital control system have a significant influence on the active damping method, resulting in poor system robustness. Meanwhile, these delays also reduce the control bandwidth greatly and thus impose a severe limitation on the low-frequency gains. In this paper, a real-time computation method with dual sampling mode is proposed to remove the computation delay from the inner active damping loop and the outer grid-current control loop simultaneously; thus, the system robustness and the control performance can be greatly improved. Moreover, the time duration between the sampling instant and the switching transition of the inverter bridge is extended by the proposed method, which effectively prevents the switching noise distorting the sampled signals. Therefore, the noise immunity of the inverter is also improved greatly. Experimental results from a 6-kW LCL-type single-phase grid-connected inverter confirm the theoretical expectations and the effectiveness of the proposed method.
Preventing voltage waveform distortion in multifrequency current control during saturated operation is a difficult problem, which so far has been only partially solved. In this paper, a scheme based on the principle of realizable references is proposed. As the converter enters saturated operation, an algorithm recalculates the converter-current reference such that unsaturated operation returns, i.e., the converter-voltage reference does not exceed the space-vector-modulation hexagon. Distortion is thereby avoided, as is integrator windup.
Plant residues are one of the main sources of soil organic matter in paddy fields, and elucidation of the bacterial communities decomposing plant residues was important to understand their function and roles, as the microbial decomposition of plant residues is linked to soil fertility. We conducted a DNA stable isotope probing (SIP) experiment to elucidate the bacterial community assimilating 13-carbon (C-13) derived from plant residue under an anoxic soil condition. In addition, we compared the bacterial community with that under the oxic soil condition, which was elucidated in our previous study (Lee et al. in Soil Biol Biochem 43:814-822, 2011). We used the C-13-labeled dried rice callus cells as a model of rice plant residue. A paddy field soil was incubated with unlabeled and C-13-labeled callus cells. DNA extracted from the soils was subjected to buoyant density gradient centrifugation to fractionate C-13-enriched DNA. Then, polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) analysis of bacterial 16S rDNA band patterns and band sequencing method were used to evaluate bacterial community. DGGE analysis showed that the band patterns in the C-13-enriched fractions were distinctly changed over time, while the changes in the community structure before fractionation were minor. Sequencing of the C-13-labeled DGGE bands revealed that Clostridia were a major group in the bacterial communities incorporating the callus-derived carbon although Gram-negative bacteria, and Actinobacteria also participated in the carbon flow from the callus under the anoxic condition. The proportion of Gram-negative bacteria and Actinobacteria increased on 14 days after the onset of incubation, suggesting that the callus was decomposed by diverse bacterial members on this phase. When the bacterial groups incorporating the C-13 were compared between under anoxic and oxic soil conditions, the composition was largely different under the two opposite conditions. However, some members of Gram-negative bacteria were commonly found under the anoxic and oxic soil conditions. The majority of bacterial members assimilating the callus carbon was Clostridia in the soil under anoxic conditions. However, several Gram-negative bacterial members, such as Acidobacteria, Bacteroidetes, and Proteobacteria, also participated in the decomposition of callus under anoxic soil conditions. Our study showed that carbon flow into the diverse bacterial members during the callus decomposition and the distinctiveness of the bacterial communities was formed under the anoxic and oxic soil conditions.
A mutant strain of Clostridium beijerinckii, with high tolerance to ferulic acid, was generated using atmospheric pressure glow discharge and high-throughput screening of C. beijerinckii NCIMB 8052. The mutant strain M11 produced 7.24g/L of butanol when grown in P2 medium containing 30g/L of glucose and 0.5g/L of ferulic acid, which is comparable to the production from non-ferulic acid cultures (8.11g/L of butanol). When 0.8g/L of ferulic acid was introduced into the P2 medium, C. beijerinckii M11 grew well and produced 4.91g/L of butanol. Both cell growth and butanol production of C. beijerinckii M11 were seriously inhibited when 0.9g/L of ferulic acid was added into the P2 medium. Furthermore, C. beijerinckii M11 could produce 6.13g/L of butanol using non-detoxified hemicellulosic hydrolysate from diluted sulfuric acid-treated corn fiber (SAHHC) as the carbon source. These results demonstrate that C. beijerinckii M11 has a high ferulic acid tolerance and is able to use non-detoxified SAHHC for butanol production. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Purpose of reviewNorovirus infection is an emerging chronic infection in immunocompromised hosts. The aim of this review is to discuss the pathophysiology of Norovirus infection and explore mechanistic models for chronic infection/shedder state, especially in patients with immune deficiency diseases.Recent findingsChronic Norovirus infection is increasingly associated with enteropathy associated with both primary and secondary immune deficiency diseases. There is an ongoing debate in the immune deficiency community whether it is truly a causative agent for the enteropathy or it is an innocent bystander.We describe the historic aspects of Norovirus infection, its immunology and viral structure and the basis for preventive and vaccination strategies.We also postulate in this review a disease model in immune deficiency subjects which creates a milieu for it to become a chronic and explore newer frontiers for disease modification and prevention.SummaryNorovirus is the most common cause of acute gastroenteritis in general population but the factors that lead to its persistence in patients with immune deficiency need further holistic studies. This should include host assessment, microbiome signatures, and viral pathogenic factors assessment.
Background: Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. Design: A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. Results: Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). Conclusions: A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C.difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.
Health care-onset health care facility-associated Clostridium difficile infection (HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C. difficile colonization and the inability of hospitals to limit testing to patients with clinically significant diarrhea. We conducted a quasiexperimental study from 22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test orders at an academic hospital. Real-time electronic patient data tracking was used by the laboratory to enforce testing criteria (defined as the presence of diarrhea [>= 3 un-formed stools in 24 h] and absence of laxative intake in the prior 48 h). Outcome measures included C. difficile test utilization, HO-CDI incidence, oral vancomycin utilization, and clinical complications. During the intervention, 7.1% (164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence of diarrhea and receipt of laxative therapy, respectively. C. difficile test utilization decreased upon implementation from an average of 208.8 tests to 143.0 tests per 10,000 patient-days (P < 0.001). HO-CDI incidence rate decreased from an average of 13.0 cases to 9.7 cases per 10,000 patient-days (P = 0.008). Oral vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per 1,000 patient-days (P = 0.009). Clinical complication rates were not significantly different in patients with 375 canceled orders compared with 869 episodes with diarrhea but negative C. difficile results. Real-time electronic clinical data tracking is an effective tool for verification of C. difficile clinical testing criteria and safe reduction of inflated HO-CDI rates.
Clostridium kluyveri is unique in fermenting ethanol and acetate to butyrate, caproate, and H-2. The genes encoding butyrate-producing enzymes, including electron-bifurcating butyryl-CoA dehydrogenase/electron transfer flavoprotein complex and NADH-dependent reduced ferredoxin:NADP(+) oxidoreductase, form a cluster, which is preceded by a gene annotated as the transcriptional regulator Rex. Northern blotting and RT-PCR experiments indicated that the gene cluster forms a large transcriptional unit that possibly includes several small transcriptional units. The deduced Rex protein contains a winged helix DNA-binding domain and a Rossmann fold potentially interacting with NAD(H). Bioinformatics analysis revealed that Rex can bind the promoter regions of numerous genes, which are involved in carbon and energy metabolism, including NADH oxidation, hydrogen production, ATP synthesis, butyrate formation, and succinate metabolism. Rex may regulate the transcription of genes encoding certain transcriptional regulators and transporters. Electrophoretic mobility shift and isothermal titration calorimetry assays revealed that Rex specifically formed protein-DNA complexes with the promoter regions of target genes, which could be inhibited by NADH but restored by an excess amount of NAD(+). These results suggest that Rex plays a key role in the carbon and energy metabolism of C. kluyveri as a global transcriptional regulator in response to the cellular NADHINAD' ratio. (C) 2016 Elsevier B.V. All rights reserved.
A load estimation algorithm based on k-means cluster analysis was developed. The algorithm applies cluster centres - of previously clustered load profiles - and distance functions to estimate missing and future measurements. Canberra, Manhattan, Euclidean, and Pearson correlation distances were investigated. Several case studies were implemented using daily and segmented load profiles of aggregated smart meters. Segmented profiles cover a time window that is less than or equal to 24 h. Simulation results show that Canberra distance outperforms the other distance functions. Results also show that the segmented cluster centres produce more accurate load estimates than daily cluster centres. Higher accuracy estimates were obtained with cluster centres in the range of 16-24 h. The developed load 'estimation algorithm can be integrated with state estimation or other network operational tools to enable better monitoring and control of distribution networks. (C) 2016 The Authors. Published by Elsevier Ltd.
Background: Bipolar disorder (BD) and schizophrenia (SZ) show substantial overlap. It has been suggested that a subgroup of patients might contribute to these overlapping features. This study employed a cross diagnostic cluster analysis to identify subgroups of individuals with shared cognitive phenotypes. Method: 143 participants (68 BD patients, 39 SZ patients and 36 healthy controls) completed a battery of EEG and performance assessments on perception, nonsocial cognition and social cognition. A K-means cluster analysis was conducted with all participants across diagnostic groups. Clinical symptoms, functional capacity, and functional outcome were assessed in patients. Results: A two-cluster solution across 3 groups was the most stable. One cluster including 44 BD patients, 31 controls and 5 SZ patients showed better cognition (High cluster) than the other cluster with 24 BD patients, 35 SZ patients and 5 controls (Low cluster). BD patients in the High cluster performed better than BD patients in the Low cluster across cognitive domains. Within each cluster, participants with different clinical diagnoses showed different profiles across cognitive domains. Limitations: All patients are in the chronic phase and out of mood episode at the time of assessment and most of the assessment were behavioral measures. Conclusions: This study identified two clusters with shared cognitive phenotype profiles that were not proxies for clinical diagnoses. The finding of better social cognitive performance of BD patients than SZ patients in the Lowe cluster suggest that relatively preserved social cognition may be important to identify disease process distinct to each disorder.
Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia.
Existing and dominant perspectives on determinants of firm internationalization have focused on the firm-specific and country-specific factors, paying less attention to the question if and how can clusters foster internationalization of cluster firms'. To investigate this issue, we conducted the study focused on the Polish clusters. First, we conceptualize the impact of clusters on the internationalization of cluster firms by introducing the concepts of the propensity of internationalization and intensity of internationalization. Second, we assess the internationalization intensity of clusters in Poland and check how cluster managers facilitated the internationalization of cluster firms. The results obtained show that clusters play an important role in neutralizing the liability of foreignness suffered by cluster entities. The findings confirm that the need of internationalization which is related to the internationalization propensity emerges over the time as a cluster matures and internationalization intensity is higher in case of more dense clusters. By combining meso- and microeconomic perspectives, this study offers a more holistic approach for studying internationalization processes.
The ongoing deployment of residential smart meters in numerous jurisdictions has led to an influx of electricity consumption data. This information presents a valuable opportunity to suppliers for better understanding their customer base and designing more effective tariff structures. In the past, various clustering methods have been proposed for meaningful customer partitioning. This paper presents a novel finite mixture modeling framework based on C-vine copulas (CVMM) for carrying out consumer categorization. The superiority of the proposed framework lies in the great flexibility of pair copulas toward identifying multidimensional dependency structures present in load profiling data. CVMM is compared to other classical methods by using real demand measurements recorded across 2613 households in a London smart-metering trial. The superior performance of the proposed approach is demonstrated by analyzing four validity indicators. In addition, a decision tree classification module for partitioning new consumers is developed and the improved predictive performance of CVMM compared to existing methods is highlighted. Further case studies are carried out based on different loading conditions and different sets of large numbers of households to demonstrate the advantages and to test the scalability of the proposed method.
Cytokines and chemokines play a crucial role in regulating the immune system. Understanding how these molecules are co-regulated is important to understand general immunology, and particularly their role in clinical applications such as development and evaluation of novel drug therapies. Cytokines are today widely used as therapeutic targets and as biomarkers to monitor effects of drug therapies and for prog-nosis and diagnosis of diseases. Therapies that target a specific cytokine are also likely to affect the pro-duction of other cytokines due to their cross-regulatory functions and because the cytokines are produced by common cell types. In this study, we have perturbated the production of 17 different cyto-kines in a preclinical rat model of autoimmune arthritis, using 55 commercially available immunomodula-tory drugs and clinical candidates. The majority of the studied drugs was selected for their anti-inflammatory role and was confirmed to inhibit the production of IL-2 and IFN-gamma in this model but was also found to increase the production of other cytokines compared to the untreated control. Correlation analysis identified 58 significant pairwise correlations between the cytokines. The strongest correlations found in this study were between IL-2 and IFN-gamma (r = 0.87) and between IL-18 and EPO (r = 0.84). Cluster analysis identified two robust clusters: (1) IL-7, IL-18 and EPO, and (2) IL-2, IL-17 and IFN-gamma. The results show that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a ther-apeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diag-nostic accuracy. (C) 2016 Elsevier Ltd. All rights reserved.
Introduction: The identification of BCR-ABL expression as the defining leukemogenic event in chronic myeloid leukemia (CML) and the introduction of BCR-ABL tyrosine kinase inhibitors in 2001 have revolutionized disease management, leading to a reduction in mortality rates and accordingly an increase in the estimated prevalence of CML. Case report : Based on medical records and clinical follow-up, the authors present the case of a Philadelphia chromosome-positive CML patient who developed resistance to imatinib. Quantitative reverse transcription-polymerase chain reaction testing revealed a V280G BCR-ABL mutation. Discussion and conclusions: This is the first report describing a new BCR-ABL kinase domain mutation-V280G-that might be associated with resistance to imatinib. Approximately 15% to 30% of patients treated with imatinib discontinue treatment due to resistance or intolerance. More than 90 BCR-ABL mutations were detected so far, conferring variable degrees of drug resistance, with consequent clinical, therapeutic, and prognostic impact.
The aim of the study was to examine the relation between additional chromosomal aberrations (ACAs) with major molecular response (MMR) and BCR-ABL kinase domain (KD) mutations in the long-term follow-up of the chronic myeloid leukemia (CML) disease. The study design was cross-sectional observational and used the CML patients' data of Izmir Ataturk Education and Research Hospital from 2011 to 2015. Conventional cytogenetic, fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (RQ-PCR) test results from 89 CML patients' and pyrosequencing analysis results from 17 patients' were set up for comparison analysis. The chi-square test was used in statistical analysis of the experimental data. There were no statistically significant correlations between ACAs and MMR (p=.361, p>.05) groups or BCR-ABL KD mutations (p=.576, p>.05) groups observed in the study. This study has revealed that MMR and BCR-ABL KD mutations did not correlate with ACAs.
In this paper, we elaborate a program based on multi-objective genetic algorithms (MOGAs) to allow automated optimization of analog circuits. The proposed methodology is used to find the optimal transistors sizes (length and width) in order to obtain operational amplifier performances for analog and mixed CMOS-based circuit applications. Eight performances are considered in this study, direct current (DC) gain, unity-gain bandwidth (GBW), phase margin (PM), power consumption (P), area (A), slew rate (SR), thermal noise and signal to noise ratio (SNR). The program is solved using MATLAB Optimization Toolbox (TM) solvers. Also by using variables obtained from genetic algorithms, the operational transconductance amplifier (OTA) is simulated by using Cadence Virtuoso Spectre circuit simulator in standard TSMC (Taiwan Semiconductor Manufacturing Company) RF 0.18 mu m CMOS technology. A good agreement is observed between the program optimization and electric simulation.
This paper presents a novel adaptive bias technique based on the use of squaring circuits. Here, the tail current of an operational amplifier (OpAmp) is controlled using an auxiliary circuit. By design, it generates a well-controlled tail current which - to a first order approximation-is independent of the OpAmp's common-mode input voltage. As a result, parameters like common-mode rejection ratio (CMRR) and power supply rejection ratio (PSRR) are enhanced. However, when a differential input signal is applied, it generates a tail current proportional to the square of the OpAmp's differential input voltage. In this way, the currents of the OpAmp's input pairs are boosted, thus improving slew rate. Experimental results in 0.5 mu m CMOS technology verify current and slew rate enhancement factors between 10 and 15 with less than 20% static current increase.
A design methodology for three-stage CMOS OTAs operating in the subthreshold region is presented. The procedure is focused on the development of ultra-low-power amplifiers requiring low silicon area but being able to drive high capacitive loads. Indeed, by following the presented methodology we designed a CMOS OTA in a 0.35-mu m technology that occupies only 4.4 . 10(-3) mm(2), is powered with a 1-V supply, exhibits 120-dB DC gain and is able to drive a capacitive load up to 200 pF. Thanks to proposed methodology, the OTA is able to provide a 20-kHz unity gain bandwidth while consuming 195 nW, even under the high load considered. Moreover, the slew rate enhancer circuit in addition to the class AB output stage allows an average slew rate higher than 5 mV/mu s with the 200 pF load. Comparison with prior art shows an improvement factor in the figures of merit higher than 5.
This paper presents a compact, reliable 1.2 V low-power rail-to-rail class AB operational amplifier (OpAmp) suitable for integrated battery powered systems which require rail-to-rail input/output swing and high slew-rate while maintaining low power consumption. The OpAmp, fabricated in a standard 0.18 mu m CMOS technology, exhibits 86 dB open loop gain and 97 dB CMRR. Experimental measurements prove its correct functionality operating with 1.2 V single supply, performing very competitive characteristics compared with other similar amplifiers reported in the literature. It has rail-to-rail input/output operation, 5 MHz unity gain frequency and a 3.15 V/mu s slew-rate for a capacitive load of 100 pF, with a power consumption of 99 mu W. (C) 2014 Elsevier Ltd. All rights reserved.
This paper presents a current driver for an integrated angular acceleration sensor readout circuit. The architecture of the proposed amplifier consists of a voltage follower and an inverting amplifier to achieve a differential output. The amplifier and the follower are based on a three-stage class AB operational amplifier with a power output stage. The output current of current driver is controlled by input voltage and has a maximum value of 80 mA. The proposed circuit is designed in 0.18 mu m CMOS technology. The typical output current flow in an equivalent sensor load of 50 Ohm is 10 rnA with a rise time of 40 ns.
A new simulation based automated CMOS analog circuit design method which applies a multi-objective non-Darwinian-type evolutionary algorithm based on Learnable Evolution Model (LEM) is proposed in this article. The multi-objective property of this automated design of CMOS analog circuits is governed by a modified Strength Pareto Evolutionary Algorithm (SPEA) incorporated in the LEM algorithm presented here. LEM includes a machine learning method such as the decision trees that makes a distinction between high- and low-fitness areas in the design space. The learning process can detect the right directions of the evolution and lead to high steps in the evolution of the individuals. The learning phase shortens the evolution process and makes remarkable reduction in the number of individual evaluations. The expert designer's knowledge on circuit is applied in the design process in order to reduce the design space as well as the design time. The circuit evaluation is made by HSPICE simulator. In order to improve the design accuracy, bsim3v3 CMOS transistor model is adopted in this proposed design method. This proposed design method is tested on three different operational amplifier circuits. The performance of this proposed design method is verified by comparing it with the evolutionary strategy algorithm and other similar methods.
A 60frames/s CMOS image sensor with column-parallel inverter-based sigma-delta (Sigma Delta) ADCs is proposed in this paper. In order to improve the robustness of the inverter, instead of constant power supply, two buffers are designed to provide power supply for inverters. Instead of using of an operational amplifier, an inverter-based switch-capacitor (SC) circuit is adopted to low-voltage low-power Sigma Delta modulator. Detailed analysis and design optimization are provided. Due to the use of the inverter-based Sigma Delta ADCs, the conversion speed is improved while reducing the area and power consumption. The proposed CMOS image sensor has been fabricated with 0.18 mu m CMOS process. The measurement results show that the random noise (RN) is 7e(rms)(-), the pixel conversion gain is 100 mu V/e(-). Since the measured full well capacity of the pixel is 25000e(-), the CMOS image sensor achieves a 71 dB dynamic range (DR). The total power consumption at 60frame/s is 58.2 mW. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents an ultra-low-power low-voltage Class-AB Fully Differential Operational Amplifier designed in 45-nm CMOS technology. The proposed circuit uses transistors operating in sub-threshold region for low-power and low-voltage operation. The proposed Op Amp offers an open-loop gain of 74.6 dB, 1 MHz unity gain frequency, 50-degrees Phase Margin, and 91.55 dB common-mode rejection ratio for 10 pF loads with a power consumption of 0.39 mu W at a +/-0.4 V supply. Simulation results illustrate a Slew Rate of 0.013 V/us and a rail-to-rail output swing, demonstrating its correct functionality.
This paper deals with low offset operational amplifiers. It shows an innovative approach to design an operational amplifier (OpAMP) which combines two different techniques that make it able to handle both the technological and the radio frequency interference (RFI) induced offset.
This paper proposes a novel analog circuit verification approach using causal reasoning. To verify analog circuits, the flow begins with mining the causal reasoning steps (design plan) that produced the circuit, including starting ideas, design step sequence, and their justification [1]. Then, topological structures corresponding to the starting ideas and design step sequences are verified individually by replacing the related devices with ideal amplifier model. Circuit performance is evaluated through Spectre simulation. Comparing simulation results reveals incorrect functional issues and/or performance drawbacks (negative causes) of certain starting ideas or design steps, which might have been omitted during the design process. The paper discusses three operational amplifier designs realized in 0.2-mu m CMOS technology to illustrate the verification approach.
A gain boosted operational amplifier designed using positive feedback technique is presented in this paper. In this design, a differential output differential amplifier merged with a single output differential amplifier is used so that positive feedback can be applied appropriately. The proposed Op-Amp is designed in 0.18 mu m CMOS process using gpdk45nm library in Cadence virtuoso analog design environment. The simulation of proposed circuit results in 116.2dB gain, 281MHz UGB, 72 degree phase margin and 620 mu W power consumption. The Monte Carlo analysis of the circuit indicates that the variation of power supply voltage produces minimal effect on the gain and phase of the circuit.
In this paper a novel high gain Op-Amp design is presented. This Proposed circuit also exhibits high linearity. The Architecture of the Op-Amp presented in this paper is based on cross-coupled differential pair and positive feedback. The proposed Op-Amp is designed in 0.18 mu m CMOS process using UMC90nm library in Cadence virtuoso analog design environment. The simulation of proposed circuit results in 124dB gain, 307MHz UGB and 69 degree phase margin while dissipating 221 mu W power. The THD analysis of the circuit shows a maximum distortion of 63dB at 2V output peak-to peak voltage and 1KHz frequency.
An ultra low power Op-Amp design is presented in this paper. In the proposed design, a gm enhancement technique is used to obtain sufficient gain and bandwidth. In the Op-Amp design, all transistors have been operated in weak inversion region. The proposed Op-Amp has been designed using UMC90nm library and simulated in Cadence analog design environment. The proposed circuit generates a 31dB gain, 52KHz UGBW and 69 degrees phase margin upon simulation, while the resultant power consumption is just 6nW.
This paper describes the design and results of a low-voltage high-gain CMOS operational amplifier (op-amp) which is very appropriate for low-voltage analog and mixed-signal applications. The design is based on folded architecture. The amplifier was designed using standard 180 nm digital n-well CMOS technology to operate with a 1.8 V single supply. The simulated small-signal AC gain of the amplifier is 90.79 dB and slew rate is 11.5 V/us with a 10 pF capacitive and 1 M ohm resistive load. For the same load, the gain bandwidth is 14.23 MHz with a phase margin of 54.8 degree. The amplifier consumes total DC power of 167 uW. The input-referred noise is 110 nV/sqrt(Hz). Furthermore, the presented operational amplifier works perfectly at supply voltage of 1 V.
This work presents a rail-to-rail operational amplifier hardened by design against ionizing radiation at circuit level, using only standard layout techniques. Not changing transistor layout, for instance by using enclosed layout structures, allows design and simulation using the standard models provided by the foundry. The circuit was fabricated on a standard 035 mu m CMOS process, and submitted to a total ionizing dose (TID) test campaign using a Co-60 radiation source, at a dose rate of 0.5 rad((Si)/s, reaching a final accumulated dose of 500 krad(Si). The circuit proved to be radiation tolerant for the tested accumulated dose. The design practices used to mitigate TID effects are presented and discussed in detail. (C) 2016 Elsevier Ltd. All rights reserved.
This article presents a design concept of a time gain-compensation (TGC) amplifier integrated circuit (IC) for ultrasonic echo signal processing. The TGC chain contains pre-amplification, attenuation, filtering and comparison circuit blocks. An on-chip oscillator, bias circuit and digital control core are also included. The presented TGC IC concept blocks are designed and modeled using Cadence's IC design tools using a 250 nm CMOS process. The operational amplifier implemented in the TGC IC has a gain of 35 dB with a -3 dB bandwidth of 750 kHz, which corresponds to ultrasonic signal frequency range. The second order active band pass filter is of a Sallen-Key topology with a 274 MHz center frequency and a filter quality factor of Q = 1.018. A ring oscillator with external tuning capability is modeled at 448 kHz and has a 0.09 % frequency deviation. The ultrasonic echo processing chain has a digital output where the length of the pulse corresponds to the received signal strength. This makes the presented TGC IC concept suitable for both simple and complex ultrasonic, medical, industrial or research equipment.
Due to the compl ex growth in very large scale integration circuits, the task of optimal analog integrated circuit design by hand is very difficult. Optimization is a time consuming process having many conflicting criteria and a wide range of design parameters. Characterization of complex tradeoffs between nonlinear objectives while assuring required specifications makes analog circuit design a tedious process. The design and optimization processes have to be automated with high accuracy. Evolutionary technique may be a proficient implement for automatic design of analog integrated circuits that has been one of the most challenging topics in VLSI design process. This paper presents a competent approach for optimal designs of two analog circuits, namely, complementary metal oxide semiconductor two-stage comparator with P-type metal oxide semiconductor input driver and n-channel input, folded-cascode operational amplifier. The evolutionary technique used is particle swarm optimization (PSO) with an aging leader and challenger (ALC-PSO). The main aim is to optimize the MOS transistors' sizes using ALC-PSO in order to reduce the areas occupied by the circuits and to get better performance parameters of the circuits. To exhibit the performance parameters of the circuits, simulation program with integrated circuit emphasis simulation has been carried out by using the optimal values of MOS transistor sizes and other design parameters. Simulation results demonstrate that design specifications are closely met and required functionalities are accommodated. The simulation results also show that the ALC-PSO is superior to the other algorithms in terms of MOS area, and performance parameters like gain, power dissipation, etc. for the examples considered.
This paper presents the optimal designs of two analogue complementary metal-oxide-semiconductor (CMOS) amplifier circuits, namely differential amplifier with current mirror load and two-stage operational amplifier. A modified Particle Swarm Optimization (PSO), called Craziness-based Particle Swarm Optimization (CRPSO) technique is applied to minimize the total MOS area of the designed circuits. CRPSO is a highly modified version of conventional PSO, which adopts a number of random variables and has a better and faster exploration and exploitation capability in the multidimensional search space. Integration of craziness factor in the fundamental velocity term of PSO not only brings diversity in particles but also pledges convergence close to global best solution. The proposed CRPSO-based circuit optimization technique is reassured to be free from the intrinsic disadvantages of premature convergence and stagnation, unlike Differential Evolution (DE), Harmony Search (HS), Artificial Bee Colony (ABC) and Particle Swarm Optimization (PSO). The simulation results achieved for the two analogue CMOS amplifier circuits establish the efficacy of the proposed CRPSO-based approach over those of DE, HS, ABC and PSO in terms of convergence haste, design conditions and design goals. The optimally designed analogue CMOS amplifier circuits occupy the least MOS area and show the best performance parameters like gain and power dissipation, in compared with the other reported literature. Copyright (c) 2016 John Wiley & Sons, Ltd.
In this paper, a hybrid population based metaheuristic search algorithm named as gravitational search algorithm (GSA) combined with particle swarm optimization (PSO) (GSA-PSO) is proposed for the optimal designs of two commonly used analog circuits, namely, complementary metal oxide semiconductor (CMOS) differential amplifier circuit with current mirror load and CMOS two-stage operational amplifier circuit. PSO and GSA are simple, population based robust evolutionary algorithms but have the problem of suboptimality, individually. The proposed GSA-PSO based approach has overcome this disadvantage faced by both the PSO and the GSA algorithms and is employed in this paper for the optimal designs of two amplifier circuits. The transistors' sizes are optimized using GSA-PSO in order to minimize the areas occupied by the circuits and to improve the design/performance parameters of the circuits. Various design specifications/performance parameters are optimized to optimize the transistor's sizes and some other design parameters using GSA-PSO. By using the optimal transistor sizes, Simulation Program with Integrated Circuit Emphasis simulation has been carried out in order to show the performance parameters. The simulation results justify the superiority of GSA-PSO over differential evolution, harmony search, artificial bee colony and PSO in terms of convergence speed, design specifications and performance parameters of the optimal design of the analog CMOS amplifier circuits. It is shown that GSA-PSO based design technique for each amplifier circuit yields the least MOS area, and each designed circuit is shown to have the best performance parameters like gain, power dissipation etc., as compared with those of other recently reported literature. Still the difficulties and challenges faced in this work are proper tuning of control parameters of the algorithms GSA and PSO, some conflicting design/performance parameters and design specifications, which have been partially overcome by repeated manual tuning. Multiobjective optimization may be the proper alternative way to overcome the above difficulties.
This paper proposes a novel hybrid optimisation algorithm which combines the recently proposed evolutionary algorithm Backtracking Search Algorithm (BSA) with another widely accepted evolutionary algorithm, namely, Differential Evolution (DE). The proposed algorithm called BSA-DE is employed for the optimal designs of two commonly used analogue circuits, namely Complementary Metal Oxide Semiconductor (CMOS) differential amplifier circuit with current mirror load and CMOS two-stage operational amplifier (op-amp) circuit. BSA has a simple structure that is effective, fast and capable of solving multimodal problems. DE is a stochastic, population-based heuristic approach, having the capability to solve global optimisation problems. In this paper, the transistors' sizes are optimised using the proposed BSA-DE to minimise the areas occupied by the circuits and to improve the performances of the circuits. The simulation results justify the superiority of BSA-DE in global convergence properties and fine tuning ability, and prove it to be a promising candidate for the optimal design of the analogue CMOS amplifier circuits. The simulation results obtained for both the amplifier circuits prove the effectiveness of the proposed BSA-DE-based approach over DE, harmony search (HS), artificial bee colony (ABC) and PSO in terms of convergence speed, design specifications and design parameters of the optimal design of the analogue CMOS amplifier circuits. It is shown that BSADE- based design technique for each amplifier circuit yields the least MOS transistor area, and each designed circuit is shown to have the best performance parameters such as gain, power dissipation, etc., as compared with those of other recently reported literature.
To minimize the power consumption of an analog sigma-delta modulator (SDM), a fifth-order loop filter of the SDM has been realized with only three operational amplifiers (op-amp). The analog SDM with shared op-amp is applied to a class-D amplifier for a digital hearing aid. The class-D amplifier with the analog SDM has been realized in a standard 0.13-mu m CMOS process. The maximum output power level of the class-D amplifier is 1.13-mW for a load with 46.5-Omega DC resistance. The total harmonic distortion+noise (THD+N) and the dynamic range (DR) of the class-D amplifier are 0.0038-% and 96-dB, respectively. The fifth-order analog SDM with shared op-amp consumes only 0.2-mW from a 1.2-V power supply.
The paper represents a design procedure of basic two stage CMOS operational amplifier using Miller compensation technique. The LtSpice simulation tool is used to present system result at low capacitive load with different characteristics. The Miller capacitor creates an undesirable right-half-plane (RHP) zero due a non inverting feedforward signal path is induced in the input of the second stage towards its output, which can be eliminated by using voltage buffer. My work shows the two stage amplifier with Miller compensation techniques, simulated using LtSpice simulation tool for 180, 130 and 90 nm CMOS technology process. When a 10-pF capacitive load is drive, the amplifier achieves voltage gain approximate 20 % more with exactly double gain bandwidth (GBW) which shows phase margin of 44.8 degrees, 49.06 degrees, and 53.70 degrees, slew rate of 44.48, 10.29, and 9.77 V/mu s, with dissipating power value of 830 mu W at 2.5 V, 504.06 mu W at 1.5 V, 486 mu W at 1.2 V supply voltage for 180 nm, 130 nm, 90 nm CMOS technology, respectively.
In this paper, a 40 M-1000 MHz 77.2-dB spurious free dynamic range (SFDR) CMOS RF variable gain amplifier (VGA) has been presented for digital TV tuner applications. The proposed RFVGA adopts a wideband operational-amplifier-based VGA and a wideband buffer with differential multiple gated transistor linearization method for wideband operation and high linearity. The SFDR of the proposed RFVGA is also analyzed in detail. Fabricated in a 0.13-mu m CMOS process, the RFVGA provides 31-dB gain range with 1-dB gain step, a minimum noise figure of 7.5 dB at a maximum gain of 27 dB, and maximum in-band output-referred third-order intercept point of 27.7 dBm, while drawing an average current of 27.8 mA with a supply voltage of 3.3 V. The chip core area is 0.54mmx0.4mm. Copyright (c) 2014 John Wiley & Sons, Ltd.
This paper explores the modeling and design of Miller-based operational amplifier structures that are highly immune to electromagnetic interference (EMI). The proposed CMOS Miller-based operational amplifier is derived using the present modeling. It provides higher immunity to EMI that is injected into the amplifier's input over a wide range of frequencies; moreover, the frequency response is comparable to that of a Miller operational amplifier. Simulation results show that the maximum EMI-induced input offset voltage for the proposed CMOS operational amplifier is 5 mV at an EMI frequency of 40 MHz, when a 900 mVpp EMI signal is applied at its input. In contrast, the standard Miller operational amplifier generates an input offset voltage of 32 mV under the same operating conditions. The developed mathematical modeling of the EMI-induced offset correlates with the circuit simulations, providing superior accuracy when designing for high EMI robustness.
In practical printed circuit board (PCB) designs, electromagnetic interference (EMI) is coupled from the ground plane, which is commonly shared among the analog, digital, and mixed-signal integrated circuits. This noisy ground plane couples interference capacitively to all the IC pins, including the output: this effect is exacerbated when the IC is connected to long wires and traces that are routed close to the conductive ground plane. This paper reports on the effect of interference, which is coupled capacitively from the PCB ground plane into all the IC pins of an opamp connected as a voltage buffer. Simulations illustrate the susceptibilities in custom operational amplifier designs, and are corroborated by measurements on several commercial devices. These measurements show that the EMI-induced offset can attain considerable values for the most critical EMI frequencies, which lie between 10 and 100 MHz. Moreover, these illustrate that there is a considerable susceptibility of operational amplifiers to electromagnetic interference coupled to their output pins.
In this paper an operational amplifier of general purpose is presented. The unified current-control model is used to synthesize a standard, two-stage topology based circuit. The design procedure is discussed thoroughly and every step is explained in details. The results obtained include open loop gain of 74 dB, the gain-bandwidth product of 100 MHz and the phase margin higher than 46 degrees. Supply voltage and temperature coefficients are analyzed and discussed within the paper. Process variations are investigated through corner analysis. The results presented are obtained through schematic level simulations using the Spectre Simulator from Cadence Design System and a standard 130 nm CMOS technology process.
This paper presents an efficient and robust circuital implementation of a rail-to-rail input stage with transconductance control, tailored for low-noise operational amplifiers based on differential pairs biased in the sub-threshold region. The proposed g (m) -control circuit design is indeed based on transistors ratio only, and allows efficient control with scaled currents and dimensions. The architecture guarantees nearly constant performance in terms of bandwidth and power consumption over the whole common mode input range in a power- and area-efficient way. The achievable precision of the transconductance control is also analyzed with transistor equations and its deviation predicted with a simple analytical model, which suggests also a strategy for the minimization of the error by proper tuning. A prototype of the input-output rail-to-rail operational amplifier has been fabricated in a standard 0.35 mu m CMOS technology, confirming the validity of the g (m) -control loop. The amplifier consumes 597 mu A from a 3.3 V supply, with an open-loop gain of 107 dB and a gain-bandwidth product of 42.6 MHz.
This paper describes the design of Two Stage Operational Amplifier using three structures and calculation of its various parameters. The three basic designs include CMOS, Hybrid of CMOS and DTMOS, and full DTMOS, which operate at 2.5V power supply and 0.18um technology. In this paper, simulation curves are computed for its different characteristics such as Gain, PM, ICMR, CMRR. Simulation has been carried out in PSPICE tool. All the three design are application specific. The basic CMOS based 2 stage op-amp provides high open loop voltage gain and rail to rail output swing. First proposed design is the Hybrid of CMOS and DTMOS which provides additional gain, increased CMRR and higher phase margin. The second proposed design is Full DTMOS based 2 Stage op-amp which can be used for low power applications as DTMOS is the best alternative for implementation of low power circuits.
Despite the clear need, progress toward a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest, and several vaccine candidates are either in clinical trials or the trials are close to starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and improves pup survival in a guinea pig model of congenital CMV infection (Clin Vaccine Immunol 24: e00300-16, 2017, https://doi.org/10.1128/CVI.00300-16). The combination vaccine appeared to be the most effective.
Purpose: To evaluate the morphological characteristics of posterior corneal regions including keratic precipitates in eyes with cytomegalovirus (CMV) corneal endotheliitis using anterior segment spectral domain optical coherence tomography (SD-OCT). Methods: Thirteen eyes of 13 patients with polymerase chain reaction-proven CMV corneal endotheliitis were included in this study. Slit-lamp images and anterior segment SD-OCT images of the posterior cornea were obtained to analyze the clinical characteristics of corneal structures and keratic precipitates. Morphological changes in the posterior cornea throughout the course of an antiviral treatment were also investigated. Results: Anterior SD-OCT images showed protruding structures at the posterior cornea. These protruding structures exhibited dendritic, dome-shaped, quadrangular, or saw-tooth appearance, and reflectivity of these structures was high. Reflectivity of posterior corneal images including the endothelium and deep stromal corneal regions were also high (76.9%). Because corneal inflammation and corneal edema improved, the protruding structures and high-intensity regions of posterior corneal images were resolved after a course of antiviral treatment. Conclusions: The anterior segment SD-OCT examination represents a useful noninvasive alternative to diagnose and monitor CMV corneal endotheliitis.
Lanzhou lily (Lilium davidii var. unicolor) with symptoms of severe fasciation or dwarfing was observed in the central region of Gansu province, and the disease caused a serious loss in production of the bulb edible crop. In order to determine possible virus infections involved in the described disease, a set of enzyme-linked immunosorbent assays and immunoelectron microscopy had been performed to test the naturally infected plants. A mixed infection which includes Lily symptomless virus (LSV: Flexiviridae, Carlavirus), Cucumber mosaic virus (CMV: Bromoviridae, Cucumovirus) and Lily mottle virus (LMoV: Potyviridae; Potyvirus) has been confirmed by serologic and morphologic evidences. The subsequent thin sectioning observation with a transmission electron microscope on different tissues from infected samples showed that cytopathologic damages happened. Total RNA extracted from different tissues of infected plants was used in the Northern-blotting assays with probes of coat protein gene of each virus, then hybridization data showed a symptomatic infection of related virus. Thus, the study gives reliable serologic, morphologic, cytopathologic and molecular evidences for the diagnosis of the systemic infections. This study is hoped to be useful in prevention of certain viral diseases and to increase the quality and production of this crop in the future.
The transformation of polyp into medusa is one of the most interesting processes in the life cycle of cnidarians. In the polyps of the class Scyphozoa this transformation occurs in the form of strobilation, which is the transverse fission of polyps with the formation of discoidal ephyrae. At present, the endogenous regulation of strobilation in one of scyphozoans, Aurelia aurita, is being investigated by the methods of molecular biology (Fuchs et al., 2014). However, it is still unclear which key environmental factors induce this process. The main purposes of this review are to summarize the literature data on the conditions in which strobilation in A. aurita occurs in nature and in the laboratory and to try to identify the environmental factors that are most likely to play a signaling role in strobilation.
VLSI technology is being adopted widely nowadays for biomedical applications to improve healthcare diagnosis, monitoring and cure. Analog devices such as A/D converters for biomedical applications can be of modest precision but need to be very energy efficient in order to operate for decades. CNTFET can be the future alternative to be used in various high performance, low power devices. In this paper we have presented a low power CNTFET based two stage Op-Amp for biomedical A/D converters. A sample and hold circuit is also implemented using CNTFET based Op-Amp to be used in biomedical ADCs. Simulation results of CNTET based circuits are compared with MOSFET circuits. Results indicate improvement of power consumption up to 80%. The proposed circuit simulations are carried out in HSPICE. It is concluded that CNTFET based circuits can be prime choice for low power applications.
This paper presents an extension of the ballistic carbon nanotube field-effect transistor (CNTFET) Raychowdhury [1] compact model with adding acoustic phonon (AP) and optical phonon scattering (OP) mechanisms. These mechanisms cause noise in the device. To obtain an accurate compact model, the flicker and thermal noise-models should be included. This model can be easily implemented with a hardware description language (HDL)-like Verilog-A in the Agilent Advanced Design System simulation tool ADS. The impact of the AP scattering mechanism on operational amplifier (Op Amp) circuit performances is investigated and the simulation results are compared with respect to Op Amp including both AP and OP scattering and to Amp Op using ballistic model. Hence, degradation in the Op Amp performances with AP and OP scattering models is observed especially in gain and bandwidth figure of merits in addition to the increase of the flicker noise in the device.
Germany appears set to miss its CO2 reduction target in 2020. As a result, ideas for additional political measures have been put forward. One such idea involves an early phase-out of coal-fired power plants. However, the possible impacts of such a phase-out on the energy system have not yet been fully analyzed. We therefore apply a German energy system model to analyze these impacts. To do so, we calculate three different scenarios. The first represents a business-as-usual scenario, while the second takes a coal phase-out into account. The third scenario has to achieve the same CO2 reduction as the second without being forced to implement a coal phase-out. Our three scenarios show that a definitive coal phase-out by 2040 would result in only a relatively small amount of additional CO2. However, an equal CO2 reduction can be obtained using a different strategy and slightly lower costs. In the latter scenario, the additional costs are also distributed more evenly across the sectors. The sensitivities analyzed show the robustness of the conclusions drawn. In summary, this analysis outlines what consequences could arise by excluding several options in parallel from a technology portfolio. (C) 2017 Elsevier Ltd. All rights reserved.
Conversion of coal into dedicated hydrocarbons has been developed in the beginning of the last century and is still practiced in areas of the world with scarcity or insecure oil and gas supply. Given the need for carbon in chemistry, possible political disruptions in oil and gas producing regions and the rise of renewable energy, lignite, as a secure domestic raw material, can serve as a chemical feed-stock. Furthermore, it can serve as an energy storage using polygeneration, i.e. the ratio between power and hydrocarbon products can follow the fluctuating grid requirements. In North-Rhine Westphalia (NRW), a committee for inquiry regarding the future of the chemical industry advocates this idea in its final report released in April 2015. This is in line with the position of RWE Generation (RWEG), which has been pursuing an alternative use of lignite besides the generation of electricity and has been expediting the related technology development for decades. So far, economical reasons prevented this option to be realized in commercial scale in Germany during the last 30 years. Together with partners from science, as well as industry and partly government-funded, RWEG develops innovative plant concepts and technologies for Coal-to-Product concepts. Especially the challenges and chances are taken into consideration resulting from the given circumstances, a changing market situation and shifting political goals. To meet the challenge of high investment costs, RWEG pursues a so called annex approach to improve the economic viability of the alternative use of lignite. Annex means to use synergies on infrastructure at established power plant or chemical sites, when planning a CtL/CtG plant. In addition, the process steps are critically questioned, here the gas treatment plant, whether amine scrubbing can be applied as a less costly alternative to the commonly used Rectisol scrubbing. To reduce the CO2 footprint and to use renewable energy for hydrocarbon products, there is, next to the way of integrating electrolytically produced H-2 into the process, another way, to substitute carbon consumption needed for the gasification temperatures by electrical heating. (C) 2017 Elsevier Ltd. All rights reserved.
The electrochemical detection of ascorbic acid (AA) was investigated using a cobalt(III)-ferritin immobilized on a self-assembled monolayer modified gold electrode in phosphate buffer solution (pH7.5). The modified electrode showed excellent electrochemical activity for oxidation of AA. The response to AA on the modified electrode was examined using cyclic and differential pulse voltammetry techniques. The resulting biosensor showed a linear response to AA in a concentration range from 6.25x10(-6) to 2.31x10(-5) M with sensitivity of 86,437 AM(-1) and detection limit of 4.65 x 10(-6) M based on a signal-to-noise ratio of 3. Electrochemical parameters including the charge transfer coefficient () and the apparent heterogeneous electron transfer rate constant (k(s)) for AA were found to be 0.52 and 1.054 Sec(-1), respectively. It has been shown that, using this modified electrode, AA can be determined with high sensitivity, low detection limit, and high selectivity. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Cobalt-containing metal-on-metal hip replacements are associated with adverse reactions to metal debris (ARMD), including inflammatory pseudotumours, osteolysis, and aseptic implant loosening. The exact cellular and molecular mechanisms leading to these responses are unknown. Cobalt ions (Co2+) activate human Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to Gram negative bacterial lipopolysaccharide (LPS). We investigated the effect of Co2+-mediated TLR4 activation on human microvascular endothelial cells (HMEC-1), focusing on the secretion of key inflammatory cytokines and expression of adhesion molecules. We also studied the role of TLR4 in Co2+-mediated adhesion molecule expression in MonoMac 6 macrophages. We show that Co2+ increases secretion of inflammatory cytokines, including IL-6 and IL-8, in HMEC-1. The effects are TLR4-dependent as they can be prevented with a small molecule TLR4 antagonist. Increased TLR4-dependent expression of intercellular adhesion molecule 1 (ICAM1) was also observed in endothelial cells and macrophages. Furthermore, we demonstrate for the first time that Co2+ activation of TLR4 upregulates secretion of a soluble adhesion molecule, sICAM-1, in both endothelial cells and macrophages. Although sICAM-1 can be generated through activity of matrix metalloproteinase-9 (MMP-9), we did not find any changes in MMP9 expression following Co2+ stimulation. In summary we show that Co2+ can induce endothelial inflammation via activation of TLR4. We also identify a role for TLR4 in Co2+-mediated changes in adhesion molecule expression. Finally, sICAM-1 is a novel target for further investigation in ARMD studies.
While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort. Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30-day residential treatment programme. Differences in cortical thickness and related resting-state functional connectivity between NTSCUs and healthy control subjects were identified. Survival analysis, applying cortical thickness of the identified regions, resting-state functional connectivity of the identified circuits and clinical characteristics to the treatment cohort, was used to predict relapse. Lower cortical thickness in bilateral insula and higher thickness in bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole brain resting-state functional connectivity analyses with these four different anatomical regions as seeds revealed eight weaker circuits including within the salience network (insula seeds) and between temporal pole and elements of the default mode network in NTSCUs. Applying these circuits and clinical characteristics to the independent cocaine-dependent treatment cohort, functional connectivity between right temporal pole and medial prefrontal cortex, combined with years of education, predicted relapse status at 150 days with 88% accuracy. Deficits in the salience network suggest an impaired ability to process physiologically salient events, while abnormalities in a temporal pole-medial prefrontal cortex circuit might speak to the social-emotional functional alterations in cocaine addiction. The involvement of the temporal pole-medial prefrontal cortex circuit in a model highly predictive of relapse highlights the importance of social-emotional functions in cocaine dependence, and provides a potential underlying neural target for therapeutic interventions, and for identifying those at high risk of relapse.
ObjectiveTo compare counts of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis and Fusobacterium nucleatum between crack users and non-users. Materials and methodsA cross-sectional study was conducted involving seventy-four crack cocaine users and eighty-one non-users matched for age, gender and tobacco use. Demographic and clinical variables were analysed. Subgingival bacterial samples were collected from four sites with the greatest probing depths and were analysed using real-time polymerase chain reaction. ResultsNo significant difference was found in the prevalence of total counts for each bacterial species analysed between groups. However, crack users had a 1.85 (95% CI: 1.03-3.31), 2.19 (95% CI 1.24-3.88), 2.53 (95% CI 1.27-5.04) and 2.40 (95% CI 1.22-4.75) greater probability of having the higher counts (75th percentile) for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, respectively. ConclusionAlthough some crack users had higher (>75th percentile) bacterial counts for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, total counts did not differ between crack users and non-users, leading to the hypothesis that the higher occurrence of periodontitis on crack users may be related to other non-bacterial factors.
Knowledge of putative insect species vectors of the coconut lethal yellowing disease (CLYD) in Mozambique is crucial to develop an effective disease management plan. Hemiptera specimens from the families Derbidae and Pentatomidae were collected in the Inhambane and Zambezia provinces of the coastal region of Mozambique in 2014, covering the two main growing seasons. Sequence analyses of the 16S rRNA gene were used for phytoplasma clustering. Polymerase chain reaction (PCR) amplification was performed employing three different primer sets specific for phytoplasma. BLAST sequence comparison and phylogenetic analysis of the 16S rDNA PCR products revealed that collected specimens of Derbidae Diostrombus mkurangai Wilson were carrying the CLYD phytoplasma. Virtual RFLP analyses of the obtained sequences confirmed this assigning the detected phytoplasmas to the 16SrXX-A subgroup, confirming that they are 'Candidatus Phytoplasma palmicola'-related strains. This is the first detection of a 'Candidatus Phytoplasma palmicola'-related strain in D. mkurangai.
Background and ObjectiveThe goal of periodontal therapy is to regenerate/reconstruct the damaged supporting tissues of diseased teeth and to facilitate recovery of their physiological functions. Combination of stem cell transplantation and gene therapy offers a viable method for accelerating periodontal repair and regeneration. In this study, the role of the ephrinB2/EphB4 signaling pathway in regulating osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and crosstalk between PDLSCs and pre-osteoblasts within co-culture was investigated through ephrinB2 transgenic expression in PDLSCs. Material and MethodsPDLSCs isolated from premolar teeth of teenage patients undergoing orthodontic treatment were transfected with transgenic (hEfnB2-GFP-Bsd) vector or empty vector (GFP-Bsd). Vector-PDLSCs, EfnB2-PDLSCs, MC3T3-E1 and co-cultures of vector-PDLSCs with MC3T3-E1, and EfnB2-PDLSCs with MC3T3-E1 were subjected to osteogenic induction. The osteogenic differentiation of EfnB2-PDLSCs, vector-PDLSCs and co-cultures were assessed by reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) assay and Alizarin-red S staining. Protein expression levels of ephrinB2, EphB4, phosphorylated ephrinB2 and EphB4 were analyzed by western blot, immunoprecipitation and co-immunoprecipitation assays. ResultsALP assay and Alizarin-red S staining demonstrated higher ALP activity and increased mineralization with EfnB2-PDLSCs vs. vector-PDLSCs and with co-culture of EfnB2-PDLSCs and MC3T3-E1 vs. vector-PDLSCs and MC3T3-E1. Reverse transcription-polymerase chain reaction revealed that the expression of human odonto/osteogenic markers were significantly enhanced in EfnB2-PDLSCs compared to vector-PDLSCs, and that the expression of mouse odonto/osteogenic markers were significantly higher in co-culture of EfnB2-PDLSCs with MC3T3-E1 vs. vector-PDLSCs with MC3T3-E1. The EphB4 receptor was activated through phosphorylation during osteogenic differentiation. ConclusionOur data indicate that transgenic expression of ephrinB2 in PDLSCs could promote osteogenic differentiation via stimulation of the phosphorylation of ephrinB2 and EphB4, which regulates cell communication between PDLSCs and between PDLSCs and pre-osteoblasts within co-culture.
Varying chemical oxygen demand (COD) and sulphate concentrations in substrate were used to determine reaction kinetics and mass balance of organic matter and sulphate transformation in a microbial fuel cell (MFC). MFC with anodic chamber volume of 1 L, fed with wastewater having COD of 500 mg/L and sulphate of 200 mg/L, could harvest power of 54.4 mW/m(2), at a Coulombic efficiency of 14%, with respective COD and sulphate removals of 90 and 95%. Sulphide concentration, even up to 1500 mg/L, did not inhibit anodic biochemical reactions, due to instantaneous abiotic oxidation to sulphur, at high inlet sulphate. Experiments on abiotic oxidation of sulphide to sulphur revealed maximum oxidation taking place at an anodic potential of -200 mV. More than 99% sulphate removal could be achieved in a MFC with inlet COD/sulphate of 0.75, giving around 1.33 kg/m(3) day COD removal. Bioelectrochemical conversion of sulphate facilitating sulphur recovery in a MFC makes it an interesting pollution abatement technique.
The use of information and communication technologies (ICTs) in developing regions has gained momentum due to their increasing affordability, particularly in rural areas where other ICT infrastructures for information management are often non-existent. Giving potential technology users, the opportunity to actively engage and contribute to the design of an artefact increases adoption and sustainable use. In this paper, we illustrate our application of community-based codesign (CBCD) that led to the development of an ICT intervention to support water management in three rural communities in Uganda. The community-based system helps water managers to track water users, payments and expenditures in a bid to improve transparency, accountability and trust. We present research learnings of the method and how engagement with rural communities can be improved through the use of intermediaries and paying more attention to community values as well as exercising ethics of reciprocity in community-based ICT initiatives.
Objectives Growing evidence supports the view that the diagnosis of coeliac disease (CD) can be made by serological tests alone, although this approach is still not widely accepted. We previously showed in retrospective and prospective studies that in adults an IgA-tissue transglutaminase antibody cut-off can be defined above which the positive predictive value for CD is 100%. Following a change in the analytical method for measuring the antibody, our objectives were to re-examine this finding in a larger series of adults to ascertain whether a diagnosis of CD can be reliably made in a proportion of patients without the need for small bowel biopsy and to re-evaluate the diagnostic guidelines used in our centre. Patients and methods A retrospective analysis was done in an unselected series of 270 adult patients who had small bowel biopsies and serum IgA-tissue transglutaminase antibody levels measured from 2009 to 2014. Results At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8 x upper limit of normal + 2SDs) the positive predictive value for CD in this cohort was 100%; 40% of cases were above this cut-off. Conclusion We have verified that a diagnosis of CD can be reliably made in a high proportion of adults based on serology alone using the IgA-tissue transglutaminase antibody method specified. These results add to the body of evidence that small bowel biopsy should no longer be considered mandatory for the diagnosis of CD. On the basis of these results the diagnostic guidelines in our centre have been modified. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Research about the Chinese film industry is far behind the actual development of practice, especially considering its evolution and main influential factors. Furthermore, existing research on the film industry in economic geography is mostly conducted from the perspective of cluster theory, with lesser attention to institutions or culture. In this paper, the theory of co-evolution is used to tackle these two gaps. The role of institutions, culture and industrial organization as three fundamental elements of co-evolution is pointed out and discussed in the theoretical section. The phenomena of co-evolution in the Shanghai film industry as important examples of the Chinese film industry are analysed in the empirical part. We phase the development process in four periods and differentiate identified effects of co-evolution between institutions, culture and industrial organization based on the specific setting in each particular period.
The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.
Caffeine biosynthesis involves sequential methylation of the purine ring by the transfer of methyl group from the methyl donor S-adenosyl methionine. Genes that code for the individual methyl transferase have a high degree of sequence homology. To achieve decaffeination by genetic engineering of coffee, the effect and efficiency of different post-transcriptional gene silencing (PTGS) constructs were evaluated. Sense, antisense and invert repeat constructs were developed using a 339 bp fragment from the conserved region of the coffee N-methyltransferase genes involved in caffeine biosynthesis. The silencing constructs were mobilized into Agrobacterium tumefaciens (EHA101). Sonication assisted Agrobacterium-mediated transformation of the somatic embryos of C. canephora was performed, followed by regeneration of the transformants. Molecular analysis and identification of flanking regions confirmed the stable integration of the transgenes in the transformants and their integration in non coding regions of the genome, respectively. Effectiveness of the silencing constructs was evaluated by transcript analysis of the targeted genes by RT-PCR and northern blotting. The silencing efficiency was further evaluated by estimation of the purine alkaloid content in the transgenic lines using HPLC. The three constructs differed in their silencing efficiencies and specificity. Though the constructs were not specific to a single N-methyltransferase, transformants obtained were mainly affected in one of the N-methyltransferases. Results show that the use of homologous coding sequence in the PTGS constructs results in a much higher efficiency in silencing the caffeine biosynthetic pathway. Further, the lowering of caffeine content should be the preferred over complete decaffeination due to extremely low survival rate of transgenic plants with extremely low levels of caffeine.
To response to the increasing demands for clean water, a large pressurized water reactor (PWR) with a desalination capability has been studied and demonstrated its potential so far. However, the electricity production of the large nuclear reactor decreases by 10% due to steam bypass for desalination. In this study, the authors evaluate the possibility of a large PWR with a capability of producing both electric power and clean water by using the supercritical CO2 (S-CO2) Brayton cycle technology. The S-CO2 power technology is adopted to minimize the decrease in the electricity production capacity due to desalination process. Two concepts which replace the existing steam based power conversion system with a S-CO2 Brayton cycle were proposed. The first concept is that the low pressure steam turbine section of the power conversion system is replaced with the S-CO2 Brayton cycle. The second concept is that the whole steam based power conversion system is replaced with the S-CO2 Brayton cycle. Several S -CO2 cycle options were considered in terms of power production and the desalination capacity and conducted a comparative analysis of selected layouts and the optimal operating conditions of the suggested layouts were identified. (C) 2017 Elsevier B.V. All rights reserved.
Background. Functional decline among patients with mental illness is not unique to individuals with psychotic disorders. Despite this, research on early predictors of functional outcome mainly focused on individuals thought to have an 'at risk mental state' (ARMS) for psychosis. There is evidence suggesting that certain early vulnerability markers, such as neurological soft signs (NSS), may explain variability in functional outcomes independent of the level of psychosis risk and the traditional diagnostic classification. Method. Structural equation modeling was applied to baseline data from a prospective longitudinal study of 138 young individuals in treatment with secondary services for non-psychotic disorders. We evaluated theoretically based models of pathways to functional outcome starting from NSS. The intervening variables were established according to previous evidence and drawn from two general categories: cognition (neuro-and social-) and negative symptoms (expressive and experiential). Results. A final trimmed model was a single path running from NSS to neurocognition to experiential negative symptoms to outcome. It could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from NSS to outcome was significant. The validity of the model was independent of the ARMS status and the psychiatric diagnosis. Conclusions. Our results provide evidence for a single pathway model in which the starting and intervening variables represent modifiable trans-diagnostic therapeutic targets to improve functional trajectories in young individuals with a recent-onset psychiatric diagnosis and different levels of psychosis risk.
Learning objectives: After participating in this activity, learners should be better able to: Evaluate the evolution of social cognitive abilities as a developmental process Assess the evidence regarding social cognition difficulties in youth at clinical high risk for psychosis Individuals at clinical high risk (CHR) for psychosis exhibit a broad range of difficulties, including impaired social cognition, which may represent a target for early identification and intervention. Several studies have examined various domains of social cognition in CHR individuals. Most focus on adolescent and young adult populations, but given the accumulating evidence that impairment exists before the onset of psychotic disorders, it is critically important to begin to look for these risk markers in younger children. The present article reviews 25 studies on CHR that examine any of the following four domains of social cognition: emotion processing, theory of mind, social perception, or attribution bias. Eligible studies were identified through a comprehensive literature search, conducted using electronic databases, including PubMed/MEDLINE and PsycINFO, and combinations of key social-cognition and CHR search terms. Despite some mixed results, the existing literature establishes that CHR individuals display social-cognitive impairment, though it remains unclear as to how and when that impairment develops. Thus, by using the literature on social cognition in typically developing children as a model and reference, and by looking at the evolution of social-cognitive abilities as a developmental process, our review presents a valuable new perspective that indicates the necessity of further investigation in younger, at-risk populations. Implications for treatment and future research are discussed.
Objectives: In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social cognitive intervention that targets higher level social cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. Method: Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. Results: USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social cognitive measures. Conclusions and Implications for Practice: USS shows promise as a treatment for higher level social cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function.
Alterations in general intellectual ability and social cognition in schizophrenia are core features of the disorder, evident at the illness' onset and persistent throughout its course. However, previous studies examining cognitive alterations in siblings discordant for schizophrenia yielded inconsistent results. Present study aimed to investigate the nature of the association between facial emotion recognition and general IQ by applying genetically sensitive cross-trait cross-sibling design. Participants (total n=158; patients, unaffected siblings, controls) were assessed using the Benton Facial Recognition Test, the Degraded Facial Affect Recognition Task (DFAR) and the Wechsler Adult Intelligence Scale-III. Patients had lower IQ and altered facial emotion recognition in comparison to other groups. Healthy siblings and controls did not significantly differ in IQ and DFAR performance, but siblings exhibited intermediate angry facial expression recognition. Cross-trait within-subject analyses showed significant associations between overall DFAR performance and IQ in all participants. Within-trait cross-sibling analyses found significant associations between patients' and siblings' IQ and overall DFAR performance, suggesting their familial clustering. Finally, cross-trait cross-sibling analyses revealed familial covariation of facial emotion recognition and IQ in siblings discordant for schizophrenia, further indicating their familial etiology. Both traits are important phenotypes for genetic studies and potential early clinical markers of schizophrenia-spectrum disorders. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Background: There is a lack of treatment plurality at step 2 of Improving Access to Psychological Therapies (IAPT) services. This project therefore sought to develop and pilot a cognitive analytic informed guided self-help treatment for mild-to-moderate anxiety for delivery by Psychological Wellbeing Practitioners (PWPs). Method: Medical Research Council treatment development guidelines were used. Phase I included development of the six-session treatment manual using practice guidelines, small-scale modelling (n = 3) and indicated manual iterations. Phase II consisted of a mixed methods case series design (n = 11) to index feasibility, uptake and clinical outcomes. Results: Cognitive analytic guided self-help (CAT-SH) met established quality parameters for guided self-help. A high treatment completion rate was observed, with 10/11 patients who attended the first treatment session subsequently completing full treatment. Six out of ten patients completing full treatment met reliable recovery criteria at follow-up. Effect sizes and recovery rates equate with extant PWP outcome benchmarks. Practitioner feedback indicated that delivery of CAT-SH was feasible. Conclusion: CAT-SH shows promise as a low-intensity treatment for anxiety, and so further, larger and more controlled evaluations are indicated.
The current paper provides an overview of the cultural and religious background of Pakistan; the current situation of mental health in Pakistan with special emphasis on cultural adaptation of cognitive behaviour therapy (CBT) in Pakistan. In the context of Sufism-Islamic Mindfulness, it is interesting to note that it has been easy to explain the concepts of CBT to the therapists and clients in Pakistan, but the process to culturally adapt CBT in Pakistani culture, had to be based on patience while generating evidence for it. Our group has taken the responsibility to do that and so far, have been successful in the endeavours pertaining to research and service development, described in this paper.
According to recent theories, social cognition is based on two different types of information-processing; an implicit or action-based one and an explicit or verbal one. The present study examined whether implicit and explicit social-cognitive information processing interact with each other by investigating young children's and adults' use of verbal (i.e., explicit) information to predict others' actions. Employing eye tracking to measure anticipatory eye-movements as a measure of implicit processing, Experiment 1 presented 1.5-, 2.5-, and 3.5-year-old children as well as adults with agents who announced to move to either of two possible targets. The results show that only the 3.5-year-old children and adults, but not the 1.5-and 2.5-year-old children were able to use verbal information to correctly anticipate others' actions. Yet, Experiments 2 and 3 showed that 2.5-year-old children were able to use explicit information to give a correct explicit answer (Experiment 2) and that they were able to use statistical information to anticipate the other's actions (Experiment 3). Overall, the study is in line with theoretical claims that two types of information-processing underlie human social cognition. It shows that these two inform each other by 3 years of age.(C) 2016 Elsevier B.V. All rights reserved.
Substantial evidence indicates that infants expect agents to move directly to their goals when no obstacles block their paths, but the representations that articulate this expectation and its robustness have not been characterized. Across three experiments (total N = 60), 6-month-old infants responded to a novel, curvilinear action trajectory on the basis of its efficiency, in accord with the expectation that an agent will move to its goal on the least costly path that the environment affords. Infants expected minimally costly action when presented with a novel constraint, and extended this expectation to agents who had previously acted inefficiently. Infants' understanding of goal-directed action cannot be explained alone by sensitivity to specific features of agent's actions (e.g. agents tend to move on straight paths, along supporting surfaces, when facing their goals directly) or extrapolations of agents' past actions to their future ones (e.g. if an agent took the shortest path to an object in the past, it will continue to do so in the future). Instead, infants' reasoning about efficiency accords with the overhypothesis that agents minimize the cost of their actions. (C) 2016 Elsevier B.V. All rights reserved.
When do descriptive regularities (what characteristics individuals have) become prescriptive norms (what characteristics individuals should have)? We examined children's (4-13years) and adults' use of group regularities to make prescriptive judgments, employing novel groups (Hibbles and Glerks) that engaged in morally neutral behaviors (e.g., eating different kinds of berries). Participants were introduced to conforming or non-conforming individuals (e.g., a Hibble who ate berries more typical of a Glerk). Children negatively evaluated non-conformity, with negative evaluations declining with age (Study 1). These effects were replicable across competitive and cooperative intergroup contexts (Study 2) and stemmed from reasoning about group regularities rather than reasoning about individual regularities (Study 3). These data provide new insights into children's group concepts and have important implications for understanding the development of stereotyping and norm enforcement.
The challenge of studying human cognitive evolution is identifying unique features of our intelligence while explaining the processes by which they arose. Comparisons with nonhuman apes point to our early-emerging cooperative-communicative abilities as crucial to the evolution of all forms of human cultural cognition, including language. The human self-domestication hypothesis proposes that these early-emerging social skills evolved when natural selection favored increased in-group prosociality over aggression in late human evolution. As a by-product of this selection, humans are predicted to show traits of the domestication syndrome observed in other domestic animals. In reviewing comparative, developmental, neurobiological, and paleoanthropological research, compelling evidence emerges for the predicted relationship between unique human mentalizing abilities, tolerance, and the domestication syndrome in humans. This synthesis includes a review of the first a priori test of the self-domestication hypothesis as well as predictions for future tests.
In natural situations, speech perception often takes place during the concurrent execution of other cognitive tasks, such as listening while viewing a visual scene. The execution of a dual task typically has detrimental effects on concurrent speech perception, but how exactly cognitive load disrupts speech encoding is still unclear. The detrimental effect on speech representations may consist of either a general reduction in the robustness of processing of the speech signal ('noisy encoding'), or, alternatively it may specifically influence the temporal sampling of the sensory input, with listeners missing temporal pulses, thus underestimating segmental durations ('shrinking of time'). The present study investigated whether and how spectral and temporal cues in a precursor sentence that has been processed under high vs. low cognitive load influence the perception of a subsequent target word. If cognitive load effects are implemented through 'noisy encoding', increasing cognitive load during the precursor should attenuate the encoding of both its temporal and spectral cues, and hence reduce the contextual effect that these cues can have on subsequent target sound perception. However, if cognitive load effects are expressed as 'shrinking of time', context effects should not be modulated by load, but a main effect would be expected on the perceived duration of the speech signal. Results from two experiments indicate that increasing cognitive load (manipulated through a secondary visual search task) did not modulate temporal (Experiment 1) or spectral context effects (Experiment 2). However, a consistent main effect of cognitive load was found: increasing cognitive load during the precursor induced a perceptual increase in its perceived speech rate, biasing the perception of a following target word towards longer durations. This finding suggests that cognitive load effects in speech perception are implemented via 'shrinking of time', in line with a temporal sampling framework. In addition, we argue that our results align with a model in which early (spectral and temporal) normalization is unaffected by attention but later adjustments may be attention-dependent. (C) 2016 Elsevier Inc. All rights reserved.
Cognitive behavioral approaches have been able to demonstrate some of the underlying and perpetuating factors of depression such as cognitive reactivity (CR). The association of CR and the severity of depression is yet to be reported. We aimed to compare the CR of a group of outpatients based on their self-reported severity of depression (SRSD), and to identify the role of specific CR vulnerability markers in depression. The study population consisted of 221 outpatients diagnosed with Major Depressive Disorder. We used the Mini International Neuropsychiatric Interview, and completed a demographic and clinical data form. The participants completed the Leiden Index of Depression Sensitivity-Revised (LEIDS-R), and the Hospital Anxiety and Depression Scale. To identify how well CR, as measured by the scores of the LEIDS-R, could discriminate the groups based on the SRSD, one-way analysis of variance was used. To examine the unique associations between the CR and the SRSD, a hierarchical linear regression analysis was performed. To identify group membership to severe depression, the scores of the LEIDS-R were entered in a logistic regression model. Large, and small group differences emerged on the rumination, and control scores, respectively. The other group differences were all in the medium range. The control, risk aversion, and rumination scores were the subscales which explained a significant proportion of the variance in the SRSD. Overall, the logistic regression model classified 93.7 % of the severely depressed patients correctly. These results indicated that rumination, risk aversion, and perfectionism were particularly associated with severe depression.
Background: Anxiety disorders are the leading cause of mental illness in adolescence. While anxious adolescents show impairments in emotion processing and deficits in emotion regulation, few studies have attempted to improve emotion regulation within these populations. Method: This study used a multi-method design to test a newly developed emotion regulation training aimed at improving insight into emotions and instructing cognitive reappraisal. The efficacy of cognitive reappraisal was investigated in 27 clinically anxious youth (Age: M=12.36, SD=2.59) and 43 healthy controls (Age: M=13.07, SD=2.19) using psychophysiological measures. Specifically, heart rate variability, pupil dilation, and visual fixations were recorded while youth had to up-or downregulate their emotions in response to affective pictures in the Psychophysiological Indicators of Emotion Regulation (PIER) task. Results: The novel training effectively improved self-reported emotion regulation and momentary anxiety in both groups. Moreover, initial group differences in emotional reactivity mostly disappeared when participants were instructed to apply emotion regulation in the task. However, pupil dilation data suggested that participants with anxiety disorders required more cognitive resources for the upregulation of negative affect to counteract this effect. Limitations: The relatively small sample size and large age range could hamper detection of additional group differences that may exist. Conclusions: The current study provides evidence that anxious youth can apply cognitive reappraisal to a similar extent as healthy adolescents after emotion regulation training but may need to exert more effort to do so. This training could be a valuable addition to current treatment programs.
Psychosocial rehabilitation programs received mental health professional support in addition to traditional medication therapy. Many psychosocial programs were developed since the 1990s, including cognitive remediation therapy. In this review, we focus on cognitive remediation therapy in Korea since the 1990s. We review several cognitive rehabilitation programs developed in Korea and their outcome studies and suggest future research directions and prospects. We reviewed cognitive rehabilitation programs including social cognitive training as well as more recent forms of computerized cognitive rehabilitation. Although there are differences in cognitive domains by training targets, almost all neurocognitive remediation trainings in Korea have beneficial effects on early visual processing, various attention types, and executive function. Future studies need to investigate the mechanisms and various mediators underlying the relationships between cognitive functions and functional outcomes. With more comprehensive cognitive and social cognitive programs, we can enhance both cognition and functional outcomes of the patients with schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Objective: This pilot project was designed to develop procedures for and test the feasibility of implementing Cognitive Enhancement Therapy (CET) in a group home environment, with a goal of maximizing treatment efficacy by augmenting social engagement in group CET sessions with ongoing social interaction. Methods: Six participants who met criteria including chronic schizophrenia were recruited in a group home with 30 residents. After two months of CET, pre- and posttest measures, including cognitive tests, were administered and qualitative interviews were conducted periodically. Interaction was observed in the house and staff members were interviewed in a focus group. Results: Five of the initial six participants completed the intervention-which continued for a total of 45 weeks-engaging in weekly group CET sessions and computer exercises outside of the formal sessions. All participants liked the computer exercises, and all but one participated in and reported enjoying the group exercises. Observations and staff comments indicated increased social interaction and sustained impact for some residents. Some aspects of cognitive functioning improved for some participants during the initial two months. Conclusions: CET now needs to be tested more formally to determine if it can be delivered successfully in other group homes with a manualized procedure. The idea should be tested that feedback effects due to the sustained social contact may enhance the effectiveness of CET in group homes and lead to larger, sustained gains in community functioning. Clinicians who provide cognitive interventions should focus attention on the social context in which treatment is delivered and consider providing treatment to patient groups whose daily, ongoing social interaction can enhance its effects. (C) 2016 Elsevier B.V. All rights reserved.
Objective: Individuals with schizophrenia demonstrate cognitive, social cognitive, and motivational deficits that contribute to impairment in real-world functioning. In the current study, we investigated the effects of supplementing computerized neurocognitive training with social cognitive exercises, as compared with neurocognitive training alone. Method: In this ongoing, double-blind, randomized controlled trial of 111 participants with psychosis, we compare the effects of supplementing intensive targeted cognitive training with social cognitive training exercises (TCT + SCT) with the effects of targeted cognitive training alone (TCT-only). Participants were assessed on cognition, symptoms, functional capacity, and functional outcomes, as well as social cognition and measures related to reward processing. Results: Both treatment groups showed significant improvement in multiple cognitive domains and improvement in functional capacity. However, as predicted, TCT + SCT group participants showed significant improvement in prosody identification and reward processing relative to TCT-only participants. Conclusions and Implications for Practice: Our findings indicate that supplementing intensive computerized cognitive training with social cognitive exercises in people with psychosis confers greater benefits in prosody identification and reward processing relative to cognitive training alone, even though both approaches drive significant improvements in cognition and functional capacity. Impairments in both prosody identification and reward processing have been associated with greater negative symptoms and poorer functional outcomes in schizophrenia, raising the possibility that this form of treatment may lead to better long-term outcomes than traditional cognitive training approaches. Follow-up assessments will determine whether results are durable and generalize over time to improvements in symptoms and functioning.
Objective: Cognitive remediation programs often have larger effects on cognition compared with everyday outcomes. We compared changes across cognitive, functional competence, and vocational domains in 2 cognitive remediation programs. Method: A sequential enrollment, nonrandom design with 50 individuals with serious mental illnesses (psychotic and mood disorders) from a community vocational rehabilitation program. Action-Based Cognitive Remediation (ABCR), a new program that combines traditional cognitive training techniques with simulated workplace situations and goal setting for engaging with cognitively demanding activities (N = 24; 19 completers) was compared with traditional cognitive remediation (tCR; N = 26; 15 completers). Both groups met twice-weekly for 2-hr sessions over 10 weeks. Repeated measures analysis of variance was used to examine effects pre-and posttreatment and 10 weeks after treatment. Univariate analysis of variance and chi-square tests were used to compare work outcomes 6 months after intervention. Results: Significantly more ABCR participants (83%) were retained in the intervention compared with tCR (57%) and reported greater increases in perceived competence with cognitively challenging tasks (eta(2) =.23). ABCR effects were significantly larger than tCR on functional competence (eta(2) =.53), with smaller, nonsignificant differences in social cognition (eta(2) =.14) and neurocognition (eta(2) =.16). ABCR participants were marginally more likely to be competitively employed (68.4% vs. 40%) and, among those employed, ABCR participants experienced less job-related stress (eta(2) =.37). Conclusions and Implications for Practice: Cognitive rehabilitative programs for serious mental illness that rely on computer -based training for neuroplasticity should ensure opportunities for active skill development and therapist supported techniques to overcome challenges with generalizing cognitive effects to everyday outcomes.
Objective: Cognitive challenges are prominent features of individuals diagnosed with schizophrenia, impairing occupational, social, and economic functioning. These challenges are predictive of social and work outcomes. Cognitive remediation has been shown to be effective in improving both cognitive and social functions. However, cognitive remediation does not produce improvement in all participants. We investigated demographic, neurocognitive, and psychopathological predictors associated with improvement following cognitive remediation interventions in service recipients with severe mental illnesses. Method: One hundred thirty-seven adult participants with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) were enrolled in 12-week cognitive remediation programs. Assessments of demographic and illness variables, together with baseline and end point assessment of psychopathology (Positive and Negative Syndrome Scale [PANSS]), neurocognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery [MCBB]), and social functions (Personal and Social Performance Scale [PSP]) were conducted. Change in cognitive domains was calculated using the reliable change index. Logistic regression analysis was used to assess predictors of cognitive improvement after the intervention. Results: Sixty-two percent of participants improved on at least 1 of the MCCB domains. Higher baseline speed of processing, attention or vigilance, and working memory predicted a positive response to cognitive remediation. Younger age, higher education level, shorter length of stay, and lower PANSS Negative and Disorganized factors were additional predictors. Conclusions and Implications for Practice: Our results indicate the clinical usefulness of cognitive remediation and identified a pattern of clinical and cognitive predictors of good response to the intervention. Identification of these predictive factors by clinicians may enhance the outcome and aid in the development of individualized rehabilitative cognitive remediation treatment plans.
Background: The objective of this study was to validate the Turkish version of the Quick Mild Cognitive Impairment (Qmci-TR) screen. Methods: In total, 100 patients aged 65 years referred to a geriatric outpatient clinic with memory loss were included. The Qmci was compared to the Turkish versions of the standardized Mini-Mental State Examination and the Montreal Cognitive Assessment (MoCA). Results: The Qmci-TR had higher accuracy than the MoCA in discriminating subjective memory complaints (SMCs) from cognitive impairment (mild cognitive impairment [MCI] or dementia), of borderline significance after adjusting for age and education (P = .06). The Qmci-TR also had higher accuracy than the MoCA in differentiating MCI from SMC, which became nonsignificant after adjustment (P = .15). A similar pattern was shown for distinguishing MCI from dementia. Test reliability for the Qmci-TR was strong. Conclusion: The Qmci-TR is a reliable and useful screening tool for discriminating MCI from SMC and dementia in a Turkish population.
Background: Evidence in the literature suggests that there is an impairment of social cognition in schizophrenia. Theory of Mind (ToM) is defined as one's ability to understand others' wishes, beliefs, intentions, and other psychological states and thereby to judge others' behavior, as an essential component of social cognition. However, there have been limited studies on social cognition, especially ToM in adolescent onset schizophrenia (AOS). The current study aims to investigate ToM abilities in adolescent schizophrenia according to various ToM subcomponents (cognitive ToM and affective ToM) and various ToM orders (first order and second order). Methods: This study examines ToM in 35 adolescent schizophrenic patients and 35 healthy adolescents using the "Yoni task" and "Faux Pas Recognition test" to assess their affective and cognitive ToM abilities. Results: In the Yoni task, patients with AOS showed differences in ToM abilities either on a different order or under different conditions. The Faux Pas Recognition task results revealed that AOS patients were not always able to recognize a faux pas or understand complicated emotions under the faux pas scenario. Furthermore, as indicated by the correlation analysis, neither cognitive ToM nor affective ToM was related to the patients' symptoms, disease duration, dose of medication, or intelligence quotient (IQ). Conclusion: Our findings showed AOS impairment in the performance of ToM tasks. It seemed that impairment in second-order-ToM is more serious. Moreover, these deficits are largely independent of symptom clusters, disease duration, dose of medication, and IQ. It can be speculated that ToM dysfunction may be a hallmark of adolescent schizophrenia.
The swarm cognitive behavior of bees readily translates to swarm intelligence with "social cognition," thus giving rise to the rapid promotion of survival skills and resource allocation. This paper presents a novel cognitively inspired artificial bee colony clustering (ABCC) algorithm with a clustering evaluation model to manage the energy consumption in cognitive wireless sensor networks (CWSNs). The ABCC algorithm can optimally align with the dynamics of the sensor nodes and cluster heads in CWSNs. These sensor nodes and cluster heads adapt to topological changes in the network graph over time. One of the major challenges with employing CWSNs is to maximize the lifetime of the networks. The ABCC algorithm is able to reduce and balance the energy consumption of nodes across the networks. Artificial bee colony (ABC) optimization is attractive for this application as the cognitive behaviors of artificial bees match perfectly with the intrinsic dynamics in cognitive wireless sensor networks. Additionally, it employs fewer control parameters compared to other heuristic algorithms, making identification of optimal parameter settings easier. Simulation results illustrate that the ABCC algorithm outperforms particle swarm optimisation (PSO), group search optimization (GSO), low-energy adaptive clustering hierarchy (LEACH), LEACH-centralized (LEACH-C), and hybrid energy-efficient distributed clustering (HEED) for energy management in CWSNs. Our proposed algorithm is increasingly superior to these other approaches as the number of nodes in the network grows.
Background: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results. Methods: HIV-positive ART naive and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies. Results: Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001. Conclusions: Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.
Background: Although discovery research has identified the importance of dozens of pro-and anti-inflammatory immune mediators in the pathogenesis, maintenance, exacerbation and resolution of inflammatory diseases, most human cohort studies have incorporated few or no immunological intermediate phenotypes in their analyses. Significant hindrances have been (1) the limited panel of biomarkers known to be readily detected in healthy human populations and (2) the stability, hence utility, of such biomarkers to repeated analysis. Methods: The frequency and stability of 14 plasma biomarkers linked to in vivo immune regulation of allergic and autoimmune inflammatory disorders was determined in 140 healthy pediatric and adult participants. The impact of initial and multiple subsequent freeze/thaw cycles on pro-inflammatory (CCL2, CXCL10, IL-18, TNF alpha, IL-6), anti-inflammatory (IL-10, sTNF-RII, IL-1Ra), acute phase proteins (CRP, PTX3) and other biomarkers (sST2, IL-1RAcP) was subsequently quantified. Results: Multiple biomarkers capable of providing an innate immune signature of inflammation were readily detected directly ex vivo in healthy individuals. These biomarker levels were unaffected when comparing paired data sets from freshly obtained, never frozen plasma or serum and matched aliquots despite extensive freeze/thaw cycles. Neither age nor sex affected stability. Similarly, no quantitative differences were found following repetitive analysis of inflammatory biomarkers in culture samples obtained following in vitro stimulation with TLR and RLR ligands. Conclusions: A broad panel of in vivo and ex vivo cytokine, chemokine and acute phase protein biomarkers that have been linked to human chronic inflammatory disorders are readily detected in vivo and remain stable for analysis despite multiple freeze thaw cycles. These data provide the foundation and confidence for large scale analyses of panels of inflammatory biomarkers to provide better understanding of immunological mechanisms underlying health versus disease.
Purpose Keratoconus (KC) is thinning of the central cornea. Its etiology is unknown, but it may result from degrading of collagen type IV. The major protein in the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9 enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1 (TIMP-1). In the present study, we sought to investigate and evaluate the effects of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC in an Iranian population sample. Methods This case-control study was performed on 140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Result Our findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR = 0.26, 95% CI = 0.08-0.82, P = 0.022). rs17576A/G, associated with KC and the A allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06-4.76, P = 0.036). In males, the allele frequency was not associated with KC risk/protection. Conclusions This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.
Affordable and portable indirect impedance measurement techniques with minimum hardware and post-processing requirements are necessary for various applications, and in particular for bioimpedance measurements. In this paper, a new method to extract the single-dispersion Cole bioimpedance model parameters is presented using a simple circuit consisting of a operational amplifier and a set of resistors. We examine the theory behind this magnitude-only method and demonstrate its application for the extraction of impedance data from a number of different fruit samples. Three means to compute the single-dispersion Cole model parameters are given and discussed under different measurement scenarios, and compared with experimental results. (C) 2015 Elsevier B.V. All rights reserved.
Study Design. A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD. Objective. The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD. Summary of Background Data. Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive. Methods. Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarovtype apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed. Results. In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin alpha 2 beta 1 (upregulated) and alpha 10 beta 1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin alpha 1, alpha 2, alpha 11, and beta 1 were upregulated, whereas alpha 10 was downregulated. Similar activation of integrin signaling was observed. Conclusion. Static compression altered collagen and MMP expression, and promoted beta 1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force.
OBJECTIVE Spontaneous subaponeurotic fluid collection (SSFC) is an uncommon and newly described entity of unknown etiology, observed in infants less than 1 year of age. The authors report on series of infants who presented to the Hospital for Sick Children (HSC) with SSFC, focusing on the natural history of this condition. METHODS Data from the Hospital for Sick Children were retrospectively reviewed for the period between January 2004 and June 2015. Patient age and sex, birth history, medical history, laboratory findings, and symptoms were reviewed. SSFC location, imaging characteristics, management, and outcome were also analyzed. A MEDLINE and Embase literature search was performed on the condition, yielding previously reported cases of SSFC in the English language. RESULTS Nine cases involving patients who presented with SSFC during the study period were identified. The patients were 4 male and 5 female infants (age range 5 weeks to 11 months). All cases of SSFC developed spontaneously over a period of days, and the infants had no history of injuries, trauma, or hair manipulation in the immediate period preceding the development of the subgaleal collections. Six patients underwent remote forceps- or vacuum-assisted instrumented births, although none of the patients developed scalp collections or skin discoloration immediately after birth. All of the cases were managed conservatively on an outpatient (6 cases) or inpatient (3 cases) basis. In 1 case, the size of the fluid collection fluctuated over 4 months, but in all of the cases, the collections resolved spontaneously without structural or infectious complications. CONCLUSIONS This is the largest series describing SSFC to date and summarizes 9 cases managed at a large academic neurosurgical center. Although the specific pathophysiology of SSFC remains unknown, in some cases the condition may be associated with a remote history of instrumented delivery. SSFC occurs spontaneously without immediate preceding trauma, and an extensive hematology or child abuse workup is not necessary. A conservative approach with outpatient follow-up is advocated.
The on-line measurement of high-power IGBT collector current is important for the hierarchical control and short-circuit and overcurrent protection of its driver and the sensorless control of the converter. The conventional on-line measurement methods for IGBT collector current are not suitable for engineering measurement due to their large-size, high-cost, low-efficiency sensors, current transformers or dividers, etc. Based on the gate driver, this paper has proposed a current measuring circuit for IGBT collector current. The circuit is used to conduct non-intervention on-line measurement of IGBT collector current by detecting the voltage drop of the IGBT power emitter and the auxiliary emitter terminals. A theoretical analysis verifies the feasibility of this circuit. The circuit adopts an operational amplifier for impedance isolation to prevent the measuring circuit from affecting the dynamic performance of the IGBT. Due to using the scheme for integration first and amplification afterwards, the difficult problem of achieving high accuracy in the transient-state and on-state measurement of the voltage between the terminals of IGBT power emitter and the auxiliary emitter (u(Ee)) has been solved. This is impossible for a conventional detector. On this basis, the adoption of a two-stage operational amplifier can better meet the requirements of high bandwidth measurement under the conditions of a small signal with a large gain. Finally, various experiments have been carried out under the conditions of several typical loads (resistance-inductance load, resistance load and inductance load), different IGBT junction temperatures, soft short-circuits and hard short-circuits for the on-line measurement of IGBT collector current. This is aided by the capacitor voltage which is the integration result of the voltage uEe. The results show that the proposed method of measuring IGBT collector current is feasible and effective.
Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit-8 assay. The apoptosis rate of cells was quantified via flow cytometry following AnnexinV/ propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU-C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose-and time-dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin-induced viability and apoptosis. In addition, emodin altered FASN-involved signaling pathways, including phosphatidylinositol3-kinase/Akt and mitogen-activated protein kinases/extracellular signal-regulated kinases1/2. These results suggested that emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and provide a molecular basis for colon cancer therapy.
Changes in the colonic microbiota are critical to the pathogenesis of diverticular complications such as diverticulitis and peridiverticular abscesses. However, more subtle changes in microbiota composition may well be important to the more chronic manifestations of diverticulosis. Some studies have shown the presence of bacterial overgrowth in subgroups of patients with diverticular disease and recent studies, using molecular biology techniques, found an increase of proteobacteria and actinobacteria in patients with symptomatic uncomplicated diverticular disease (SUDD), compared with healthy controls. The use of probiotics to modulate intestinal microecology in SUDD appears therefore rational. Although several investigations evaluating the clinical efficacy of probiotics have been performed, no definitive results have yet been achieved, mainly due to the heterogeneity of the available studies. Most of the studies used probiotics in combination with poorly absorbed antimicrobials or anti-inflammatory drugs. In only 4 studies, there was a harm using probiotics alone, but only 1 was a placebo-controlled, double-blind trial. The analysis of the available evidence reveals a poor quality of the published studies, whose design was heterogeneous, with only 2 out of 11 trials being double-blind and randomized. Therefore, available data can only suggest a benefit of probiotics in SUDD, but do not allow any evidence-based definite conclusion. As a consequence, current guidelines state that there is insufficient evidence to recommend probiotics for symptom relief in patients with diverticular disease.
Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. Results: An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.
High-power white light-emitting diodes (LEDs) have attracted much attention due to their versatility in a variety of applications and growing demand in markets such as general lighting, automotive lamps, communications devices, and medical devices. In particular, the need for high reliability and long lifetime poses new challenges for the research and development, production, and application of LED lighting. Accurate and effective prediction of the lifetime or reliability of LED lighting has emerged as one of the key issues in the solid-state lighting field. Prognostic is an engineering technology that predicts the future reliability or determines the remaining useful lifetime of a product by assessing the extent of deviation or degradation of a product from its expected normal operating conditions. Prognostics bring benefits to both LED developers and users, such as optimizing system design, shortening qualification test times, enabling condition-based maintenance for LED-based systems, and providing information for return-on-investment analysis. This paper provides an overview of the prognostic methods and models that have been applied to both LED devices and LED systems, especially for use in long-term operational conditions. These methods include statistical regression, static Bayesian network, Kalman filtering, particle filtering, artificial neural network, and physics-based methods. The general concepts and main features of these methods, the advantages and disadvantages of applying these methods, as well as LED application case studies, are discussed. The fundamental issues of prognostics and photoelectrothermal theory for LED systems are also discussed for clear understanding of the reliability and lifetime concepts for LEDs. Finally, the challenges and opportunities in developing effective prognostic techniques are addressed.
Color is a common channel for displaying data in surface visualization, but is affected by the shadows and shading used to convey surface depth and shape. Understanding encoded data in the context of surface structure is critical for effective analysis in a variety of domains, such as in molecular biology. In the physical world, lightness constancy allows people to accurately perceive shadowed colors; however, its effectiveness in complex synthetic environments such as surface visualizations is not well understood. We report a series of crowdsourced and laboratory studies that confirm the existence of lightness constancy effects for molecular surface visualizations using ambient occlusion. We provide empirical evidence of how common visualization design decisions can impact viewers' abilities to accurately identify encoded surface colors. These findings suggest that lightness constancy aids in understanding color encodings in surface visualization and reveal a correlation between visualization techniques that improve color interpretation in shadow and those that enhance perceptions of surface depth. These results collectively suggest that understanding constancy in practice can inform effective visualization design.
Expanding from remote areas of Mexico to a worldwide scale, the ten-striped insect, the Colorado potato beetle (CPB, Leptinotarsa decemlineata Say), has risen from being an innocuous beetle to a prominent global pest. A diverse life cycle, phenotypic plasticity, adaptation to adverse conditions, and capability to detoxify or tolerate toxins make this insect appear to be virtually indestructible. With increasing advances in molecular biology, tools of biotechnological warfare were deployed to combat CPB. In the last three decades, genetically modified potato has created a new challenge for the beetle. After reviewing hundreds of scientific papers dealing with CPB control, it became clear that even biotechnological means of control, if used alone, would not defeat the Colorado potato beetle. This control measure once again appears to be provoking the potato beetle to exhibit its remarkable adaptability. Nonetheless, the potential for adaptation to these techniques has increased our knowledge of this pest and thus opened possibilities for devising more sustainable CPB management programs.
On a broader scale, T cell density and localization in colorectal cancer liver metastases have prognostic and predictive implications. As T cell distribution at higher resolutions has not been fully investigated, a detailed resolution analysis of T cell distribution was performed. Patient tissues were divided into 10 mu m distance classes between the tumor border and adjacent normal liver. Thereby, distinct density patterns of T cell localization in relation to the malignant tissue could be detected. At a distance of 20 to 30 mu m to the tumor, a decrease of CD3 T cells is common. Within this area, cytotoxic Granzyme B and CD8(+) T cells were found to be significantly reduced as well as CD163 macrophages were increased and identified to be in close contact with T cells. Our data suggests a physical or functional border within this region. Survival analysis revealed improved overall survival in patients with high T cells numbers at the direct tumor border. Interestingly, the decreased T cells in the 20 to 30 mu m region were also found to be significantly associated with improved survival. Consequently, the detailed localization of T cells, despite blockade, could be associated with improved clinical outcome. The high-resolution analysis represents new insights into relevant heterogenous T cell distributions especially related to clinical responses. As the paradoxical observation of localization-dependent prognostic relevance of T cell densities is only detectable by detailed spatial analyses, this investigation of spatial profiles at higher resolutions is suggested as a new biomarker for survival and response to therapies.
AIM To investigate the use of droplet digital polymerase chain reaction (ddPCR) for detecting host mRNA markers in stools as a non-invasive test for colorectal cancer screening. METHODS ddPCR and quantitative PCR were compared side by side for their performance in the detection of ITGA6 and ITGA6A transcripts in stool samples obtained from patients with various types of colorectal lesions (advanced adenomas and stage II - IV colorectal cancers) and control (patients displaying no pathological findings) using duplex TaqMan reactions for both methods. ITGA6 and ITGA6A were chosen for this proof-of-concept study based on their relative medium and low abundance in stool samples, respectively, as established in a previous study. RESULTS We found that the ddPCR and qPCR methods performed equally well in this TaqMan duplex assay for the detection of ITGA6 and ITGA6A transcripts in stools of patients with colorectal lesions. For ITGA6, receiver operating characteristic (ROC) curve analysis showed comparable areas under the curve of 0.91 (P < 0.0001) and 0.89-0.90 (P < 0.0001) for the prediction of advanced adenomas and colorectal cancers, respectively. ITGA6A, which was detected at very low levels in control patients, was found to be significantly elevated (over 40 times) in stage. and. colorectal cancers (P < 0.0002). Comparison of the two sets of data revealed a strong correlation of the copy numbers obtained by ddPCR and qPCR for both ITGA6 and ITGA6A. CONCLUSION We found that ITGA6 and ITGA6A detection in stools of patients with colorectal cancers with ddPCR is comparable to that of qPCR using TaqMan assays.
Background and Aim: Long intergenic noncoding RNAs (lincRNAs) have critical roles in elevating efficacy of anticancer therapy and tumor progression. Recent studies show that Regulator of Reprogramming (ROR) is aberrantly expressed in several types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a standard preoperative treatment. However, a considerable number of CRCs are resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in radiotherapy for CRC and detected the underlying molecular mechanism. Methods: Real-time polymerase chain reaction was employed to quantify the expression level of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and apoptosis assays were used to confirm the radiotherapy-mediated effects by lincRNA-ROR altered expression. The direct impact of lincRNA-ROR on the expression of p53/miR-145 by loss-of-function and gain-of-function strategy was also analyzed. A xenograft mouse model was used to evaluate the role of linc-ROR in CRC treatment. Results: We discovered that lincRNA-ROR was upregulated in CRC cell lines and tissue samples. We further showed that knockdown of lincRNA-ROR enhanced the sensitivity to radiotherapy for CRC by inhibiting cell viability and promoting apoptosis. Activity of the p53/miR-145 pathway may help explain the role of lincRNA-ROR for stress-induced regulation in CRC therapy. Combined specific knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model resulted in a significant reduction in the tumor growth. Conclusion: LincRNA-ROR decreases sensitivity to radiotherapy via the negative regulation of p53/miR-145 and may represent a potential target for the treatment of CRC.
Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image-enhanced endoscopic technique; and management of these lesions.
People living nowadays with HIV and AIDS may be treated effectively regarding virus replication and immunology. However, non-AIDS-defining cancer is of growing relevance due to high incidence and unfavorable outcome. The aim of this review is to summarize current knowledge on gastrointestinal (GI) carcinoma. Although literature on GI cancer is rare, an increased incidence of esophageal, gastric, pancreatic, hepatocellular, and colorectal carcinoma has been demonstrated. However, there are only few reports on therapy strategies and outcome, so that, despite increased occurrence of many GI carcinomas, only little is known about individualized treatment options and outcome in HIV-positive patients. More efforts have to be undertaken to close this gap. (C) 2017 S. Karger GmbH, Freiburg
Purpose of reviewDespite the large investment of resources from screening, the fact that colorectal cancer remains the second leading cause of cancer deaths among Americans underscores the need for alternative strategies. Thus, a major clinical and research imperative is personalize clinical care, while focusing on risk stratification for screening, surveillance, chemoprevention, and therapeutic intervention.Recent findingsA complicating factor that colorectal cancer is biologically heterogeneous for at least four consensus molecular subtypes presents clear challenges for developing robust molecular biomarkers.SummaryThe purpose of the review is to discuss the genetics and molecular biology of colonic neoplasia, high and low penetrance, and racial disparities in colonic neoplasia. Finally, we put forth the emerging concept of greater genomic landscape and the idea of chromatin protection therapy as a novel adjuvant to chemotherapy.
Purpose: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in China and fourth worldwide. Metastatic dissemination of primary tumors is considered main cause for CRC related mortality. The serine-threonine kinase 31 (STK31) gene is a novel cancer testis (CT) antigen. It was found significantly highly expressed in gastrointestinal cancers. In our study we aimed to analyze the correlation between STK31 expression patterns and metastasization, tumor stage and grade in CRC patients. Results: Relative STK31 expression level was significantly higher in patients with lymph node metastasis. STK31 expression levels in primary tumorous tissues of metastatic patients were significantly higher than in ANCTs and in lymph nodes samples, both at the RNA level and the protein level. Materials and Methods: Surgical specimens of cancerous tissues, paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with different clinicopathological features were collected. Expression of STK31 was detected and measured by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). Conclusions: Our data suggest that STK31 might be a potential biomarker in detecting, monitoring and predicting the metastatic risk of colorectal cancer.
UNC5C is a member of the UNC5H family of transmembrane receptors and functions as a dependence receptor. The expression of UNC5C is lost or markedly reduced in a large proportion of cancers at the messenger RNA level. However, there is little information available regarding the protein expression of UNC5C, the relationship between UNC5C protein expression and UNC5C methylation, and the correlation between patient clinical features and UNC5C protein expression in colorectal cancer. In this study, the methylation and protein expression of UNC5C were examined in 36 adenomatous polyps, 73 colorectal cancers, and 28 corresponding normal mucosa, and the correlation between the methylation, as well as protein expression status, and the clinicopathologic features was evaluated. Furthermore, the relationship between the methylation and protein expression of UNC5C, and correlation between UNC5C protein expression and overall survival were analyzed. The results showed that aberrant methylation of UNC5C was observed in colorectal cancers (78%) and adenomatous polyps (64%). The methylation-specific polymerase chain reaction results were confirmed by bisulfite sequencing of UNC5C promoter region. UNC5C methylation was significantly higher in early tumor, node, metastasis stage (I + II) of colorectal cancers. Compared with the corresponding normal tissues, protein expression of UNC5C was significantly lower in colorectal cancers (42%) and adenomatous polyps (81%). Protein expression of UNC5C was significantly higher in early tumor, node, metastasis stage (I + II) of colorectal cancers compared with advanced tumor, node, metastasis stage. Furthermore, patients with UNC5C-negative expression had a poorer prognosis than those with UNC5C-positive expression through Kaplan-Meier survival analysis (p = 0.038), univariate (p = 0.044) and multivariate analysis (p = 0.045). According to Spearman rank correlation analysis, UNC5C methylation and protein expression were negatively correlated (r = -0.461, p < 0.001). Together, these results suggest that UNC5C methylation may be an earlier event in the development of colorectal cancer, which was negatively correlated with protein expression. UNC5C may have a critical role in the pathogenesis of colorectal cancers and be a valuable prognostic factor of colorectal cancers patients. UNC5C may be identified as an attractive therapeutic target for the treatment of colorectal cancers in the further studies.
Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation. However, few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC). This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms. Methods The 40 CRC, adjacent nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were collected, respectively, and the total RNA and protein were isolated routinely. The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. Smoothened (SMO, possible target of miR-338-3p) mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting. nniR-338-3p expression patterns were compared between nontumor mucosa and CRC samples, graded by progression-related factors. Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival (DFS) and overall survival (OS) of patients. Moreover, SMO 3'-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid. The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected. Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues, and the value was negatively related to advanced TNM stage and local invasion (P <0.01). Furthermore, miR-338-3p value was decreased markedly in SW-620 cell line relative to SW-480 (P <0.01). Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates. Moreover, RT-PCR and Western blotting analysis demonstrated that there was no significant difference in SMO mRNA expression between the corresponding CRCs and nontumorous tissues, whereas SMO protein markedly increased in CRCs (P <0.01). A significant increase in luciferase activity was detected in CRC cells, which were cotransfected with the luciferase reporter plasmid construct and anti-miR-338-3p (P <0.01). Conclusions nniR-338-3p is expressed differentially in CRC and associated with progression and prognosis of CRC. SMO might be a possible target of miR-338-3p, which made it a potential antitumor candidate for treatment and prevention of CRC.
Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine.
In the present work, a solid chemical sensor using mesoporous silica nanospheres as scaffold, was applied for preconcentration and spectrophotometric determination of the Hg(II), Ag(I), Au(III), and Pd(II) in electronic wastes. Digital Image-Based Colorimetric Analysis was also used for determination of the concentrations of the metal ions as a fast and low-cost colorimetric detections for quantitative chemical analysis. At the optimum conditions, the analytical characteristics of the two methods (e.g., limit of detection and linear range) were evaluated. Linearity was obeyed.in the range of 0.5-10 ng m1(-1) of Au(III) with a linear correlation coefficient of 0.999. The new sensor displayed high sensitivity for very low concentrations of the detectable metals analytes up to 10(-10) mol L-1 in solution. Results showed evidence that Thiomichler's Ketone (TMK) sensor will attract worldwide attention as a promising technological means of recovering and recycling silver, gold and palladium. (C) 2017 Elsevier B.V. All rights reserved.
Compressed air energy storage technologies can improve the supply capacity and stability of the electricity grid, particularly when fluctuating renewable energies are massively connected. While incorporating the combined cooling, heating and power systems into compressed air energy storage could achieve stable operation as well as efficient energy utilization. In this paper, a novel combined cooling, heating and power based compressed air energy storage system is proposed. The system combines a gas engine, supplemental heat exchangers and an ammonia-water absorption refrigeration system. The design tradeoff between the thermodynamic and economic objectives, i.e., the overall exergy efficiency and the total specific cost of product, is investigated by an evolutionary multi-objective algorithm for the proposed combined system. It is found that, with an increase in the exergy efficiency, the total product unit cost is less affected in the beginning, while rises substantially afterwards. The best trade-off solution is selected with an overall exergy efficiency of 53.04% and a total product unit cost of 20.54 cent/kWh, respectively. The variation of decision variables with the exergy efficiency indicates that the compressor, turbine and heat exchanger preheating the inlet air of turbine are the key equipment to cost-effectively pursuit a higher exergy efficiency. It is also revealed by an exergoeconomic analysis that, for the best trade-off solution, the investment costs of the compressor and the two heat exchangers recovering compression heat and heating up compressed air for expansion should be reduced (particularly the latter), while the thermodynamic performance of the gas engine need to be improved significantly. (C) 2017 Elsevier Ltd. All rights reserved.
Recent energy policy has favored a massive introduction of Renewable Energy Sources on electricity markets, which has greatly impacted their performance. First, the electricity price has decreased as a consequence of the so-called merit-order effect. Another relevant effect is associated to the intermittent nature of Renewable Energy, which has increased the cost of ancillary services. A third and important aspect, less addressed in the literature, is the induced change in the strategic behavior of the conventional electricity producers. In principle, the entry of new generators in a concentrated market would make it more competitive and change the strategic behavior of the incumbents. We test this hypothesis for the Spanish wholesale market. While we find no significant change in behavior for Nuclear, Hydropower and Coal, a change is observed in Combined Cycle bidding strategies after the entry of renewable generators. Our analysis shows that the massive entry of Renewable Energy Sources made other generators' behavior more competitive in the short run, but the effect was not persistent.
Active demand side response (DSR) will provide a significant opportunity to enhance the power system flexibility in the Great Britain (GB). Although electricity peak shaving has a clear reduction on required investments in the power system, the benefits on the gas supply network have not been examined. Using a Combined Gas and Electricity Networks expansion model (CGEN+), the impact of DSR on the electricity and gas supply systems in GB was investigated for the time horizon from 2010 to 2050s. The results showed a significant reduction in the capacity of new gas-fired power plants, caused by electricity peak shaving. The reduction of gas-fired power plants achieved through DSR consequently reduced the requirements for gas import capacity up to 90 million cubic meter per day by 2050. The cost savings resulted from the deployment of DSR over a 50-year time horizon from 2010 was estimated to be around 60 billion for the GB power system. Although, the cost saving achieved in the gas network was not significant, it was shown that the DSR will have a crucial role to play in the improvement of security of gas supply. (C) 2016 The Authors. Published by Elsevier Ltd.
Purpose: Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. Methods: The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. Results: The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. Conclusions: Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.
The widespread overuse of antibiotics in aquaculture has led to the emergence of antibiotic-resistance shrimp pathogens, the negative impact on shrimp gut microbiota, and the presence of antimicrobial residues in aquaculture products, with negative consequences on human health. Alternatively, probiotics have positive effects on immunological responses and productive performance of aquatic animals. In this study, three probiotic bacteria, (Bacillus licheniformis MAt32, B. subtilis MAt43 and B. subtilis subsp. subtilis GAtB1), isolated from the Anadara tuberculosa were included in diets for juvenile shrimp, Litopenaeus vannamei, to evaluate their effects on growth, survival, disease prevalence, and immune-related gene expression. Shrimp naturally infected with WSSV and IHHNV were fed with the basal diet (control, T1) and diets supplemented with four levels of bacilli probiotic mix (1:1:1) at final concentration of (T2) 1 x 10(6), (T3) 2 x 10(6), (T4) 4 x 10(6), and (T5) 6 x 10(6) CFU g(-1) of feed. The specific growth rate of shrimp was significantly higher in T2 than in Tl (control) treatment, and the final growth as well as the survival were similar among treated groups. The prevalence of WSSV and IHHNV infected shrimp was reduced in T2 and T4 treatments, respectively, compared with control. The mRNA expression of proPO gene was higher in treatment T4 than control. The LvTo111 gene was significantly up-regulated in treatments T4 and T5 compared to control. The SOD gene was up-regulated in treatment T5 compared to control. In contrast, the mRNA expression of the Hsp70 gene was down -regulated in treatments T4 and T5 respect to control, and the TGase gene remained unaffected by the level of bacillus probiotic mix. As conclusion, the bacilli probiotic mix (Bacillus spp.) enhanced immune-related gene expression in WSSV and IHHNV naturally infected shrimp. This is the first report of probiotic potential of bacteria isolated from A. tuberculosa on the immune response and viral prevalence in shrimp Litopenaeus vannamei. (C) 2016 Elsevier Ltd. All rights reserved.
An increasing body of evidence indicates the relevance of microbiota for pulmonary health and disease. Independent investigations recently demonstrated that the lung harbors a resident microbiota. Therefore, it is intriguing that a lung microbiota can shape pulmonary immunity and epithelial barrier functions. Here, we discuss the ways how the composition of the microbial community in the lung may influence pulmonary health and vice versa, factors that determine community composition. Prominent microbiota at other body sites such as the intestinal one may also contribute to pulmonary health and disease. However, it is difficult to discriminate between influences of lung vs. gut microbiota due to systemic mutuality between both communities. With focuses on asthma and respiratory infections, we discuss how microbiota of lung and gut can determine pulmonary immunity and barrier functions.
Energy storage resources (ESRs) inherent in building structures are a viable, attractive option to improve power system operation by providing demand-side flexibility. This paper proposes a two-stage optimisation framework for price-based demand response of commercial buildings that include variable speed heat pumps (VSHPs). The proposed framework aims at assisting commercial building aggregators to devise a beneficial strategy for exploiting thermal ESRs in response to electricity prices. Specifically, in this paper, the thermal dynamics of VSHPs are modelled in detail using a set of piecewise linear equations for two different methods of room temperature control. The energy consumption and reserve provision of VSHPs, as well as plug-in electric vehicles, are then co-optimised considering the operating conditions of distribution networks (DNs) for the pre- and post-contingency states of wind power generation. Simulation case studies are performed to estimate the effects of building ESRs on the optimal operation of power systems and commercial buildings under various conditions characterised by: (1) temperature control methods, (2) ESR penetration levels, and (3) DN operational constraints. (C) 2017 Elsevier Ltd. All rights reserved.
Traffic flow in cities is affected by numerous factors, including land use (especially commercial land use because of its trip-making nature). This phenomenon can be more effective when combined with accessibility factors and street connectivity. The case of Bojnourd has been selected for this study. The most important reason to choose this case is that the municipality gives commercial construction permits to developers in this city without paying attention to traffic consequences. Bojnourd is a medium-sized city and the capital of the North Khorasan province. The ultimate goal of this study is to determine the effectiveness of both commercial land use and route configuration on number of trips. For this purpose, analysis of secondary data has been used as the method of study. Findings showed that there is a significant relationship between commercial land use and trip volume in Bojnourd city. Findings also indicated a strong correlation between the syntax of routes and traffic flow in the case of Bojnourd. The combined effect of both commercial land use and route configuration on the number of trips was examined and both factors that influence the number of trips were significant. (C) 2016 American Society of Civil Engineers.
Identifying parasitized nests and eggs is a prerequisite for studying conspecific brood parasitism. Previous studies on the effectiveness of egg morphology to identify parasitic eggs of different species have produced mixed results. Brood parasitism and egg measurements (length, width and weight) were monitored in Common Coot (Fulica atra; n = 85) nests. Maximum Euclidean distance was calculated for each nest. Results indicated that maximum Euclidean distance values of non -parasitized and parasitized nests were significantly different (t(83) = 9.747, P < 0.01). The optimal split value of recursive partitioning analysis for Common Coot nests was 2.98 (R-2 = 0.65), which can identify 93.3% non-parasitized and 88.0% parasitized nests successfully. However the most dissimilar egg in parasitized nests calculated by maximum average Euclidean distance only identified 39.3% of the parasitic eggs correctly. Egg morphology is effective for detecting conspecific brood parasitism of Common Coot nests, but is not accurate enough to determine parasitic eggs. As a result, this method should be used with caution and combined with observational or molecular biology methods.
Primary antibody deficiencies (PADs) are the most common form of primary immunodeficiency and predispose to severe and recurrent pulmonary infections, which can result in chronic lung disease including bronchiectasis. Chronic lung disease is among the most common complications of PAD and a significant source of morbidity and mortality for these patients. However, the development of lung disease in PAD may not be solely the result of recurrent bacterial infection or a consequence of bronchiectasis. Recent characterization of monogenic immune dysregulation disorders and more extensive study of common variable immunodeficiency have demonstrated that interstitial lung disease (ILD) in PAD can result from generalized immune dysregulation and frequently occurs in the absence of pneumonia history or bronchiectasis. This distinction between bronchiectasis and ILD has important consequences in the evaluation and management of lung disease in PAD. For example, treatment of ILD in PAD typically uses immunomodulatory approaches in addition to immunoglobulin replacement and antibiotic prophylaxis, which are the stalwarts of bronchiectasis management in these patients. Although all antibody-deficient patients are at risk of developing bronchiectasis, ILD occurs in some forms of PAD much more commonly than in others, suggesting that distinct but poorly understood immunological factors underlie the development of this complication. Importantly, ILD can have earlier onset and may worsen survival more than bronchiectasis. Further efforts to understand the pathogenesis of lung disease in PAD will provide vital information for the most effective methods of diagnosis, surveillance, and treatment of these patients. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Intergeneric hybridization is an important strategy to introgress alien genes into common wheat for its improvement. But presence of crossability barrier mechanism regulated by Kr1 gene played a major destructive role for hybridization than other reported genes. In order to know the underlying molecular mechanism and to dissect out this barrier, cDNA-AFLP (Amplified Fragment Length Polymorphism) transcriptional analysis was carried out using chromosome 5B RIL (Recombinant Inbred Line) population. Totally 14 differentially expressed fragments for Kr1 gene were identified, cloned and sequenced. Further the expression was confirmed by northern blotting analysis. Sequence analysis of the resulted clones revealed several classes of putative genes, including stress responsive, signal transduction and flowering related genes. The probable relation between other genes, Vrn1 and Ph1, located along with Kr1 gene was discussed.
A loop stability compensation technique for continuous-time common-mode feedback (CMFB) circuits is presented. A Miller capacitor and nulling resistor in the compensation network provide a reliable and stable operation of the fully-differential operational amplifier without any performance degradation. The amplifier is designed in a 130 nm CMOS technology, achieves simulated performance of 57 dB open loop DC gain, 1.3-GHz unity-gain frequency and 65 degrees phase margin. Also, the loop gain, bandwidth and phase margin of the CMFB are 51 dB, 27 MHz, and 76 degrees, respectively.
This paper proposes a gravity heat pipe exchanger used for cooling the communication base station to replace the traditional air conditioning system during winter and transition seasons. Tests were conducted on a commercial available gravity heat pipe exchanger. The experiment was performed to study the effects of the air flow rate and temperature on the cooling capacity, the heat transfer unit number (NTU) and cooling efficiency of the heat pipe exchanger. The results showed that the larger the air flow rate, the smaller the NTU and the larger the cooling capacity. Based on the analysis of the experimental data, it proved that the gravity heat pipe exchanger could reduce running time and operating cost of air conditioning system. According to the practical applications, the yearly cooling loads of a typical communication base station were further calculated for five typical cities which represent the five climatic zones of China. The results validated that the energy saving by using the gravity heat pipe exchanger is significant. The highest annual electricity-saving rate is achieved by Kunming, about 48.6%, while the lowest annual electricity-saving rate is obtained in Guangzhou, about 18.7% among the five climatic zones. The fitted correlation of cooling capacity in term of outdoor temperature is generic to evaluate approximately the performance of applying the gravity heat pipe exchanger in the actual applications subject to various outdoor temperatures. (C) 2016 Elsevier Ltd. All rights reserved.
The Door-in-the-Face (DITF) sequential message strategy was investigated in a threestudy analysis of existing experimental findings. The current study predicted there would be a positive relationship between concession size and compliance rates in DITF studies. Study 1 included 25 comparisons where size of concession was quantifiable as measured by percentage reduction from initial to target request in the DITF condition. Study 2 data relied on a panel of undergraduate students to provide an index of concession size in 12 additional observations. A third study validated the panel procedure of rating concession size and also provided 9 additional independent observations from the pool of published studies on DITF. Results from each study indicated a positive relationship between concession size and effect size (r = 0.35, 0.55, 0.68, respectively). Study findings provide support for reciprocal concessions explanation for DITF effects.
A method for determining mRNA half-lives in the polymorphic fungus Candida albicans is described. It employs growth in a defined medium, the inhibition of transcription with thiolutin (10-20 mu g/mL), and quantitative Northern blotting. The method is effective for the A72, SC5314, and CAI-4 strains of C. albicans, and for mRNAs that have a wide variety of decay rates and steady-state abundances. The range of half-lives detected (from 4-168 min) shows that this method is effective for mRNAs with widely varying half-lives. The mRNA decay rates obtained are compared with those for orthologous mRNAs from Saccharomyces cerevisiae. This procedure should work for a broad range of C. albicans strains and can be adapted to other fungal species.
This paper describes a high temperature voltage comparator and an operational amplifier (op-amp) in a 1.2-mu m silicon carbide (SiC) CMOS process. These circuits are used as building blocks for designing a high-temperature SiC low-side over current protection circuit. The over current protection circuit is used in the protection circuitry of a SiC FET gate driver in power converter applications. The op-amp and the comparator have been tested at 400 degrees C and 550 degrees C temperature, respectively. The op-amp has an input common-mode range of 0-11.2 V, a dc gain of 60 dB, a unity gain bandwidth of 2.3 MHz, and a phase margin of 48 degrees at 400 degrees C. The comparator has a rise time and a fall time of 38 and 24 ns, respectively, at 550 degrees C. The over current protection circuit, implemented with these analog building blocks, is designed to sense a voltage across a sense resistor up to 0.5 V.
In the context of a doubly fed induction generator (DFIG) connected to the utility grid under unbalanced voltage conditions, the controller design needs to ensure additional challenges such as restricting the total harmonic distortion (THD) in grid current, minimizing the pulsations in generated power, torque, dc-link voltage, etc., apart from facilitating the generator power control. In this study, a negative-sequence compensation scheme for the magnetizing current in a DFIG is investigated. The reference currents are modified to include the negative-sequence compensating component for the magnetizing current. A rotor-side converter is employed to compensate the pulsations in magnetizing current thereby minimizing the ripple in power and torque. A grid-side converter is used to maintain unity power factor and a constant dc-link voltage. It is revealed that controlling the magnetizing current as a single control target enables simultaneous reduction of pulsations in torque, power, and dc-link voltage and also minimizes unbalance in currents. The effectiveness of the scheme is validated through detailed analysis and numerical simulations in PSCAD/EMTDC for a practical 250 kW DFIG wind generation system and further, through experimental results for a 2.3 kW DFIG test setup. Typical experimental results for the laboratory test setup show an improved performance.
The digital low dropout regulator (D-LDO) has drawn significant attention recently for its low-voltage operation and process-scalability. However, the D-LDO inherently suffers from limit cycle oscillation (LCO). To address this issue, the modes and amplitudes of LCO are calculated in this work and verified by SPICE simulation in a 65-nm CMOS process. An LCO reduction technique for the D-LDO is then proposed, by adding two unit power transistors in parallel with the main power MOS array as a feedforward path. This technique sets the LCO mode to 1 and effectively reduces the ripple amplitude for a wide (0.5-20 mA) load current range. When compared with the dead-zone scheme, this technique minimizes LCO with negligible circuit complexity and design difficulty.
Numerous breast cancer patients experience cognitive changes during and after chemotherapy. Chemotherapy-related cognitive impairment can significantly affect quality of life. This pilot study attempted to determine the effects of a compensatory cognitive training on the objective and subjective cognitive functioning of breast cancer patients receiving adjuvant chemotherapy. Fifty-four patients were assigned to either a compensatory cognitive training or waitlist condition. They were assessed at baseline (T1), the completion of the 12-week intervention (T2), and 6 months after intervention completion (T3). Outcomes were assessed using the standardized neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), version 3. Raw data were converted to T-scores based on baseline scores, and a repeated-measures ANCOVA, adjusting for age, intelligence, depression, and treatment, was used for analysis. The effect sizes for differences in means were calculated. The intervention group improved significantly over time compared to the waitlist group on objective cognitive function. Among ten individual neuropsychological measures, immediate memory, delayed memory, verbal fluency in category, and verbal fluency in letter showed significant group x time interaction. In subjective cognitive function, scores of the waitlist group significantly decrease over time on perceived cognitive impairments, in contrast to those of the intervention group. The 12-week compensatory cognitive training significantly improved the objective and subjective cognitive functioning of breast cancer patients. Because this was a pilot study, further research using a larger sample and longer follow-up durations is necessary.
Chen J-K, Chen J, Thomas G, Kozma SC, Harris RC. S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy. Am J Physiol Renal Physiol 297: F585-F593, 2009. First published May 27, 2009; doi:10.1152/ajprenal.00186.2009. - Removal of one kidney stimulates synthesis of RNA and protein, with minimal DNA replication, in all nephron segments of the remaining kidney, resulting in cell growth (increase in cell size) with minimal cell proliferation (increase in cell number). In addition to the compensatory renal hypertrophy caused by nephron loss, pathophysiological renal hypertrophy can occur as a consequence of early uncontrolled diabetes. However, the molecular mechanism underlying renal hypertrophy in these conditions remains unclear. In the present study, we report that deletion of S6 kinase 1 (S6K1) inhibited renal hypertrophy seen following either contralateral nephrectomy or induction of diabetes. In wild-type mice, hypertrophic stimuli increased phosphorylation of 40S ribosomal protein S6 (rpS6), a known target of S6K1. Immunoblotting analysis revealed that S6K1(-/-) mice exhibited moderately elevated basal levels of rpS6, which did not increase further in response to the hypertrophic stimuli. Northern blotting indicated a moderate upregulation of S6K2 expression in the kidneys of S6K1(-/-) mice. Phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1, another downstream target of the mammalian target of rapamycin (mTOR), was stimulated to equivalent levels in S6K1(-/-) and S6K1(+/+) littermates during renal hypertrophy, indicating that mTOR was still activated in the S6K1(-/-) mice. The highly selective mTOR inhibitor, rapamycin, inhibited increased phosphorylation of rpS6 and blocked 60-70% of the hypertrophy seen in wild-type mice but failed to prevent the similar to 10% hypertrophy seen in S6K1(-/-) mice in response to uninephrectomy (UNX) although it did inhibit the basal rpS6 phosphorylation. Thus the present study provides the first genetic evidence that S6K1 plays a major role in the development of compensatory renal hypertrophy as well as diabetic renal hypertrophy and indicates that UNX- and diabetes-mediated mTOR activation can selectively activate S6K1 without activating S6K2.
ObjectiveClinical supervision is fundamental to the training of psychologists. Neuropsychology (NP) is recognised as a distinct discipline of psychology and is an area of endorsement; however, specific training in NP supervision has received limited attention. Reflective practice is a supervisor competency required by the Psychology Board of Australia (PBA) and is one element of NP foundational competencies. Reflective practice can be described as the process of consciously analysing decision-making, and drawing upon theory and experience, in order to improve clinical practice. This discussion paper aims to improve the supervision of neuropsychologists in Australia by providing an explicit framework to incorporate reflective practice into NP supervision. MethodAs a discussion paper, the first stage is to review the NP supervision literature; and second to provide a practical supervision framework to integrate reflective practice in accordance with current research, NP-specific requirements, and the PBA. ResultsThe extant literature on NP supervision is exceedingly limited. NP supervision training frameworks were based upon developmental and competency-based models and indicate that reflective practice is a core element. A practical framework for the implementation of reflective practice was effectively developed. ConclusionsThe reflective approach allows supervisees to attain core functional and foundational neuropsychological competencies, and is flexible to allow for different contexts and potentially new supervision training requirements. Importantly, the reflective practice framework supports ongoing professional development and competency throughout the neuropsychologists' professional career span.
A recent theoretical model suggests that intraspecific competition is an important determinant of the severity of inbreeding depression. The reason for this is that intraspecific competition is density dependent, leading to a stronger negative effect on inbred individuals if they are weaker competitors than outbred ones. In support of this prediction, previous empirical work shows that inbred individuals are weaker competitors than outbred ones and that intraspecific competition often exacerbates inbreeding depression. Here, we report an experiment on the burying beetle Nicrophorus vespilloides, in which we recorded the outcome of competition over a small vertebrate carcass between an inbred or outbred male resident caring for a brood and a size-matched inbred or outbred male intruder. We found that inbred males were more successful as intruders in taking over a carcass from a male resident and were injured more frequently as either residents or intruders. Furthermore, inbred males gained less mass during the breeding attempt and had a shorter adult life span than outbred males. Finally, successful resident males reared a substantially smaller brood comprised of lighter larvae when the intruder was inbred than when it was outbred. Our results shows that inbred males increased their competitive effort, thus contradicting previous work suggesting that inbred males are weaker competitors. Furthermore, our results shows that inbred intruders impose a greater cost to resident males, suggesting that outbred individuals can suffer fitness costs as a result of competition with inbred ones.
Wind power integration in an existing power system needs more attention due to its uncertain nature. If a difference creates between the actual and forecasted wind speeds and the power delivery contract is signed between the Generation Companies (GENCOs) and Distribution Companies (DISCOs) as per the forecasted speed, then the GENCOs may be awarded or penalized by the Independent System Operator (ISO) for their surplus or deficit power supply. This paper proposes an approach to assess the uncertainties of wind speed of the wind integrated electrical system within a completely deregulated environment. In this work, twelve spots in India have been chosen randomly for the application of the proposed approach and to verify the outcome of the proposed approach. The real time data for actual wind speed (AWS) and forecasted wind speed (FWS) of all selected spots have been also considered. The imbalance cost due to mismatch between the forecasted and actual wind speeds is evaluating by formulation of surplus charge rate and deficit charge rate. Modified IEEE 14-bus and modified IEEE 30-bus systems are considered for analyzing the effectiveness of the proposed approach. (C) 2017 Elsevier Ltd. All rights reserved.
Reproduction is energetically costly, and females frequently trade off their reproductive effort with allocation to other physiological processes. One of these processes is the maintenance of a functional immune defence. However, such interactions between immunity and reproduction have rarely been explored in mammals under natural conditions. In our study on females of an individually marked European rabbit Oryctolagus cuniculus colony, we measured different components of the maternal immune system from peripheral blood and serum 1day after parturition, and we associated variation in these measures with differences in mothers' reproductive effort. We used total litter mass as a measure of the mother's current reproductive effort. In addition, we recorded whether or not mothers gave birth and nursed another litter shortly before and considered this a measure of prior reproductive effort. Mothers with higher current or prior reproductive effort showed generally lower concentrations of white blood cells, in particular neutrophils and lymphocytes, but a higher activity of the complement system and higher IgG serum concentrations than females with lower reproductive effort. We obtained similar results when comparing individual changes in immune parameters measured post-partum across repeated reproductive events. Cell concentrations of neutrophils and lymphocytes increased when individual females decreased their reproductive effort. In contrast, IgG serum concentrations and the activity of the complement system increased when mothers increased their reproductive effort. In conclusion, the results underline differential responses of different branches of the maternal post-partum immune system to variation in reproductive effort. On the one hand, our study indicates that females might compromise at least some cellular immune parameters for reproduction. On the other hand, the positive association between IgG concentrations and reproductive effort could be adaptive as a higher litter mass and higher number of pups requires an intensified transfer of this immune parameter via placenta or colostrum and milk. This positive association might constitute an additional, immunological component of the energetic costs of reproduction.
Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.
Immunology is the science of biological warfare between the defenses of our immune systems and offensive pathogenic microbes and cancers. Over the course of his scientific career, Eckhard R. Podack made several seminal discoveries that elucidated key aspects of this warfare at a molecular level. When Eckhard joined the complement laboratory of Muller-Eberhard in 1974, he was fascinated by two questions: (1) what is the molecular mechanism by which complement kills invasive bacteria? and (2) which one of the complement components is the killer molecule? Eckhard's quest to answer these questions would lead to the discovery C9 and later, two additional pore-forming killer molecules of the immune system. Here is a brief account of how he discovered poly-C9, the pore-forming protein of complement in blood and interstitial fluids: Perforin-1, expressed by natural killer cells and cytotoxic T lymphocytes; and Perforin-2 (MPEG1), expressed by all cell types examined to date. All the three killing systems are crucial for our survival and health.
There is a large body of experimental and clinical evidence that complement activation contributes to glomerular injury in multiple different diseases. However, the underlying mechanisms that trigger complement activation vary from disease to disease. Immune complexes activate the classical pathway of complement in many types of glomerulonephritis, whereas the alternative pathway and mannose-binding lectin pathways are directly activated in some diseases. Eculizumab is an inhibitory antibody to C5 that has been approved for the treatment of atypical hemolytic uremic syndrome, and case reports suggest that it is also effective in other types of glomerulonephritis. Furthermore, new complement-inhibitory drugs are being developed that target additional proteins within the complement cascade, raising the possibility of blocking the specific complement proteins involved in a given disease. This review examines the rationale for targeting different proteins within the complement cascade, the new anti-complement drugs currently in development and some of the challenges that investigators will face in bringing these drugs to the clinic.
We develop and fabricate a 0.5-V rail-to-rail operational amplifier (op-amp) with ultralow-power operation in a 0.18-mu m standard complementary metal-oxide-semiconductor process. The op-amp has a two-stage structure that comprises a complementary input stage and a novel cross-coupled output stage. The cross-coupled output stage increases the transconductances of the metal-oxide-semiconductor field-effect transistors of the output stage without requiring an additional chip area. Hence, it increases the gain of the op-amp and drivability for a capacitive load. Our experimental results showed that the dc gain was 77 dB at the common-mode input voltage of 0.25 V with a supply voltage of 0.5 V. DC gains of more than 40 dB were obtained for common-mode input voltages ranging 50-450 mV. Furthermore, the unitygain frequency was 4.0 kHz and the phase margin was 56 degrees, with a capacitive load of 40 pF. The power consumption was 70 nW, including all bias circuits.
An upper bound for the roots of X-d + a(1) Xd-1 + ... + a(d-1) X + a(d) is given by the sum of the largest two of the terms This bound by Lagrange has gained attention from different sides recently, while a succinct proof seems to be missing. We present a short, original proof of Lagrange's bound. Our approach leads to some definite improvements. To benefit computationally from these improvements, we construct a modified Lagrange bound which at the same asymptotic computational complexity is at most 11 per cent from optimal for degrees d >= 16. (C) 2017 Elsevier Ltd. All rights reserved.
Metal hydrides have received much attention due to the flourishing concept of a hydrogen economy. In addition, recent studies of metal hydride materials have shown that technological implementation of these compounds not only lies in the storage of hydrogen, but for a range of multi-functional applications; including, smart optical windows, energy storage materials in fuel cells for both stationary and mobile devices, and as thermal energy storage materials for concentrating solar thermal plants. This review concentrates on the molecular structures, thermodynamic properties and other physical properties of the complexes of [NiH4](4), [FeH6](4), [CoH5](4) and [RuH6](4). The synthesized derivatives of these compounds have also been reviewed to give a full overview on the advancement of these systems and will allow for a fresh prospective for future studies to fully understand the physical and chemical nature of these complex transition metal hydrides. (C) 2017 Elsevier B.V. All rights reserved.
Life is so remarkable, and so unlike any other physical system, that it is tempting to attribute special factors to it. Physics is founded on the assumption that universal laws and principles underlie all natural phenomena, but is it far from clear that there are 'laws of life' with serious descriptive or predictive power analogous to the laws of physics. Nor is there (yet) a 'theoretical biology' in the same sense as theoretical physics. Part of the obstacle in developing a universal theory of biological organization concerns the daunting complexity of living organisms. However, many attempts have been made to glimpse simplicity lurking within this complexity, and to capture this simplicity mathematically. In this paper we review a promising new line of inquiry to bring coherence and order to the realm of biology by focusing on 'information' as a unifying concept.
Objective: To compare the outcomes of percutaneous nephrolithotomy (PCNL) in immunocompromised patients with those of PCNL in healthy population. Patients and Methods: A matched case-control study was performed from January 2009 through December 2014 using our prospectively collected kidney stone database. Patients with positive serology to human immunodeficiency virus (HIV), hepatitis C (cellular immune dysfunction), and patients on high dose of immunosuppressive drugs for treatment of autoimmune diseases composed the case group. Control group included patients with kidney stones and no other comorbidity. Patients were randomly matched based on Guy's score as a surrogate of case complexity. Results: Sixty-two patients were enrolled in this study, 21 cases and 42 controls. There were no significant differences in age, gender, and body mass index between groups. Regarding PCNL technique, there were no differences in patient positioning, number of accesses, and operative time. Complication rate was higher in the case group (38.1% vs 14.3%; p = 0.032); however, major complications, defined by Clavien score >= 3, were not statistically different (4.8% vs 2.4%; p = 0.611). There was a tendency of more postoperative urinary tract infection in the case group (19% vs 4.8%; p = 0.069). Mean decrease in hemoglobin level (3.3 vs 2.4 mg/dL; p = 0.037) and blood transfusion rate (23.8% vs 4.8%; p = 0.036) was significantly higher in the case group. Immunocompromised patients had a 2.8-fold increased risk of complications (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.01, 7.74) and a 5.8-fold increased risk of blood transfusion (OR = 5.8, 95% CI 1.29, 26.55). There were no differences in stone-free rate, nephrostomy tube time, and length of hospital stay. Conclusion: Immunocompromised patients are at higher risk for complications such as bleeding after PCNL.
In many applications, offset of the OP-AMPs should be canceled to high accuracy be accomplished. In this work, an asymmetrical differential input circuit with active DC offset rejection circuit was implemented to minimize the systematic offset of the amplifier. The proposed OP-AMPs show that the systematic offset voltages is less than 80 mu V.
Soybean oil is an important carbon source in kitasamycin fermentation by Streptomyces kitasatoensis. In this study, three different surfactants, Tween 80, Tween 85, and sodium dodecyl sulfate (SDS), were added in the fermentation medium to improve soybean oil utilization. Results indicated that all of these surfactants promote kitasamycin biosynthesis. When 0.5 g/L SDS was added at the beginning of fermentation, kitasamycin production increased by 55% and A(5) content improved by 12%, compared with the control treatment (i.e., no surfactant added). Oil consumption rate and lipase activity were also improved in the presence of SDS, producing more organic acids benefiting kitasamycin biosynthesis. High butyric acid concentration in the fermentation medium containing SDS repressed C-3 acetylation and promoted A(5) component accumulation. Additionally, utilization of oil components by S. kitasatoensis was altered. Specifically, linoleic acid was primarily used in the fermentation process with SDS, whereas oleic acid was primarily used in the fermentation process where no surfactant had been added. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 895-900, 2016
This paper describes macromodeling of operational amplifiers for overdrive circuit design. Macromodels have been applied to operational amplifier simulations with good convergence. Also, macromodels allow the accurate simulation with not only double-power supply but also single-power supply. In this study, a macromodel has been applied to an overdrive circuit for sound effect design. Output waveform using the macromodel is compared with that using a pre-set model only with double-power supply and experiment. The output of the macromodel shows more accurate in amplitude, a frequency, and distortion than that of the pre-set model. From this result, the macromodel of the operational amplifier is suitable than the pre-set model in the overdrive circuit design.
This paper highlights the digital control problems and issues during the controller design and suggests the solutions to resolve them. For this purpose, digital controller designed on the basis of digital redesign or emulation technique is applied to a buck converter working in continuous conduction mode. Nonlinearities due to the ADC and DAC quantizers, loop-delay, etc. are introduced into the control loop and their adverse effects on performance are interrogated. The nonlinearities are suppressed by retuning the digital controller. The order of the controller may increase and require more resources for its implementation. The quantizers' nonlinearities add quantization noise into the loop and may cause offsets and limit cycle oscillations (LCOs). The overall phase margin gets reduced due to the delay thus keeping the bandwidth limited and leading the system towards instability. The well-tuned loop remains asymptotically stable if the nonlinearities are neglected. MATLAB/Simulink environment is used to address all the issues.
Composite lymphomas (CLs) are defined as two unrelated lymphomas occurring at the same time within the same tissue. The incidence of these tumors is low. Of all possible combinations between lymphomas, the least frequent are the ones combining peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma (HL). We recently identified five cases of CL composed of PTCL and classical HL, mixed cellularity type. We investigated histological and clinical features of these cases. Immunostaining was performed on paraffin sections. PTCL cells were positive for CD8 and TIA-1 in four of the five cases. Hodgkin and Reed-Sternberg (HRS) cells were positive for CD30 and weakly positive for PAX5 in all cases, positive for CD15 in three of five cases, positive for CD20 in one of five cases, and negative for EBER. Monoclonal rearrangement of the T-cell receptor (TCR) and immunoglobulin heavy chain (IGH) genes was confirmed by polymerase chain reaction (PCR) using whole paraffin sections. We concluded more precisely the monoclonality of the IGH rearrangement of HRS cells based on single-cell PCR for IGH and DNA sequencing analysis after laser microdissection of single cells in one case. HL can occur in CD8-positive and TIA-1-positive PTCL. Clinicians should recognize the possibility of these CL.
Carbon fiber-reinforced polymers (CFRPs) have attracted attention from the aerospace industry due to their light weight, excellent mechanical properties, and resistance to corrosion. However, CFRP composites are difficult to recycle as their recycling process must be performed under extreme conditions; end-of-life regulations do not directly address the problem with reusing these composites. Thus, the objective of this study is to explore solutions that minimize the use of CFRPs and prolong their useful life in the airline industry. To achieve this goal, this work conducted a review of the state of the art of CFRP fiber recycling, emphasizing the recycling processes, restrictions, and regulations. One solution is to develop a CFRP recycling market that would allow the sequential use of recycled materials among industries in descending order of the required structural performance of the composite.
In recent years, compressed sensing has received considerable attention from the signal processing community because of its ability to represent sparse signals with a number of samples much less than that is required by the Nyquist sampling theorem. -minimization is a powerful tool for sparse signal reconstruction from few measured samples, but its computational complexity is a burden for real applications. Recently, a number of greedy algorithms based on orthogonal matching pursuit (OMP) have been proposed, and they have near -minimization performance with much less processing time. In this work, a new OMP-type two-stage sparse signal reconstruction algorithm, namely data-driven forward-backward pursuit (DD-FBP), is proposed. It is based on a former work called forward-backward pursuit (FBP). DD-FBP iteratively expands and shrinks the estimated support set, and these constitute the forward and backward stages. In DD-FBP, unlike FBP, the forward and backward step sizes are not constants, but they are dependent on the correlation and projection values, respectively, which are calculated in each iteration. The recovery performance by using noiseless and noisy sparse signal ensembles, as well as a natural sparse image, indicates that DD-FBP surpasses the other methods in terms of success rate and processing time.
Sequential estimation of the delay and Doppler parameters for sub-Nyquist radars by analog-to-information conversion (AIC) systems has received wide attention recently. However, the estimation methods reported are AIC-dependent and have poor performance for off-grid targets. This paper develops a general estimation scheme in the sense that it is applicable to all AICs regardless whether the targets are on or off the grids. The proposed scheme estimates the delay and Doppler parameters sequentially, in which the delay estimation is formulated into a beamspace direction-of-arrival problem and the Doppler estimation is translated into a line spectrum estimation problem. Then the well-known spatial and temporal spectrum estimation techniques are used to provide efficient and high-resolution estimates of the delay and Doppler parameters. In addition, sufficient conditions on the AIC to guarantee the successful estimation of off-grid targets are provided, while the existing conditions are mostly related to the on-grid targets. Theoretical analyses and numerical experiments show the effectiveness and the correctness of the proposed scheme.
Strategic bidding problems in electricity markets are widely studied in power systems, often by formulating complex bi-level optimization problems that are hard to solve. The state-of-the-art approach to solve such problems is to reformulate them as mixed-integer linear programs (MILPs). However, the computational time of such MILP reformulations grows dramatically, once the network size increases, scheduling horizon increases, or randomness is taken into consideration. In this paper, we take a fundamentally different approach and propose effective and customized convex programming tools to solve the strategic bidding problem for producers in nodal electricity markets. Our approach is inspired by the Schmudgen's Positivstellensatz Theorem in semi-algebraic geometry; but then we go through several steps based upon both convex optimization and mixed-integer programming that results in obtaining close to optimal bidding solutions, as evidenced by several numerical case studies, besides having a huge advantage on reducing computation time. While the computation time of the state-of-the-art MILP approach grows exponentially when we increase the scheduling horizon or the number of random scenarios, the computation time of our approach increases rather linearly.
This paper presents a method to evaluate the computational cost of a function in embedded systems. This method, which uses the Least Squares method, is useful to see the sample time choice feasibility, in control applications. In this work, the developed method is used to evaluate the computational cost of the model-based predictive control to speed control of a shunt direct current motor. The method was tested using two embedded devices allowing to find the correct sample time for each device evaluated.
In three-phase induction motor drives, addition of certain zero-sequence signal which divides the null vector time equally between the two zero states is known to improve the harmonic performance over sinusoidal modulation. Similarly, in split-phase induction motor (SPIM) drives also, addition of such a zero-sequence signal to each set of three-phase sinusoidal modulating waves leads to reduction in total harmonic distortion (THD) in a motor current. However, the above method known as double zero-sequence injection pulse width modulation (DZIPWM) is significantly inferior to four-dimensional 24-sector space vector pulse width modulation (4D24SEC PWM) in terms of THD. This paper investigates and attempts to determine the zero-sequence signal, if any, whose injection could result in a harmonic performance comparable to that of 4D24SEC PWM. Such a zero-sequence signal is determined and is shown to be quite different from that used in DZIPWM. The analytical findings are used to propose a computationally efficient, carrier-based approach to implement the 4D24SEC PWM, whose implementation is otherwise highly resource intensive. The feasibility, computational efficiency, and accuracy of the proposed approach are demonstrated and validated on a 6-kW split-phase motor drive, controlled from a field programmable gate array platform. This paper enables good harmonic performance of the split-phase drive with low computational effort and resources.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that act as efficient post-transcriptional regulators of gene expression. In 2012, the first cross-kingdom miRNA-based interaction had been evidenced, demonstrating that exogenous miRNAs act in a manner of mammalian functional miRNAs. Starting from this evidence, we defined the concept of cross-kingdom functional homology between plant and mammalian miRNAs as a needful requirement for vegetal miRNA to explicit a regulation mechanism into the host mammalian cell, comparable to the endogenous one. Then, we proposed a new dedicated algorithm to compare plant and mammalian miRNAs, searching for functional sequence homologies between them, and we developed a web software called MirCompare. We also predicted human genes regulated by the selected plant miRNAs, and we determined the role of exogenous miRNAs in the perturbation of intracellular interaction networks. Finally, as already performed by Pirro` and coworkers, the ability of MirCompare to select plant miRNAs with functional homologies with mammalian ones has been experimentally confirmed by evaluating the ability of mol-miR168a to downregulate the protein expression of SIRT1, when its mimic is transfected into human hepatoma cell line G2 (HEPG2) cells. This tool is implemented into a user-friendly web interface, and the access is free to public through the website http://160.80.35.140/MirCompare
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression at posttranscriptional level. They might regulate tolerance to abiotic stress. However, this has not been studied in Tradescantia (BNL clone 3340), an important bio-indicator for measuring the effect of radiation. Up to date, gamma irradiation (gamma-IR) responsive miRNAs and their expressions patterns in plants in response to gamma-IR stress have not been reported yet. Therefore, putative gamma-IR responsive miRNAs from a cDNA library of Tradescantia after radiation stress were predicted in this study by using comprehensive genomic approaches. Here, we identified 37 miRNAs belonged to 36 different miRNA families. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis of five randomly selected miRNAs were confirmed that their responsiveness to gamma-IR stress. Target prediction revealed that 37 miRNAs targeted 149 genes involved in stress tolerance regulation, light response, redox systems, signaling pathways, DNA repair, and transcription factors. A coordinated reverse expression changes between miRNAs and their target genes further validated that these predicted miRNAs could be gamma-IR responsive and likely to be directly involved in stress regulatory networks of Tradescantia. Altogether, these results will provide novel insights to the understanding of molecular mechanisms of miRNAs involved in plant response to gamma-IR.
New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.
Young children with suspected abusive head trauma often receive skull radiographs to evaluate for fractures as well as computed tomography (CT) of the head to assess for intracranial injury. Using a CT as the primary modality to evaluate both fracture and intracranial injury could reduce exposure to radiation without sacrificing performance. To evaluate the sensitivity of CT head with (3-D) reconstruction compared to skull radiographs to identify skull fractures in children with suspected abusive head trauma. This was a retrospective (2013-2014) cross-sectional study of infants evaluated for abusive head trauma via both skull radiographs and CT with 3-D reconstruction. The reference standard was skull radiography. All studies were read by pediatric radiologists and neuroradiologists, with ten percent read by a second radiologist to evaluate for interobserver reliability. One hundred seventy-seven children (47% female; mean/median age: 5 months) were included. Sixty-two (35%) had skull fractures by radiography. CT with 3-D reconstruction was 97% sensitive (95% confidence interval [CI]: 89-100%) and 94% specific (CI: 87-97%) for skull fracture. There was no significant difference between plain radiographs and 3-D CT scan results (P-value = 0.18). Kappa was 1 (P-value < 0.001) between radiologist readings of CTs and 0.77 (P = 0.001) for skull radiographs. CT with 3-D reconstruction is equivalent to skull radiographs in identifying skull fractures. When a head CT is indicated, skull radiographs add little diagnostic value.
The increasing levels of criminal media being shared in peer-to-peer (P2P) networks pose a significant challenge to law enforcement agencies. One of the main priorities for P2P investigators is to identify cases where a user is actively engaged in the production of child sexual abuse (CSA) media - they can be indicators of recent or on-going child abuse. Although a number of P2P monitoring tools exist to detect paedophile activity in such networks, they typically rely on hash value databases of known CSA media. As a result, these tools are not able to adequately triage the thousands of results they retrieve, nor can they identify new child abuse media that are being released on to a network. In this paper, we present a new intelligent forensics approach that incorporates the advantages of artificial intelligence and machine learning theory to automatically flag new/previously unseen CSA media to investigators. Additionally, the research was extensively discussed with law enforcement cybercrime specialists from different European countries and Interpol. The approach has been implemented into the iCOP toolkit, a software package that is designed to perform live forensic analysis on a P2P network environment. In addition, the system offers secondary features, such as showing on-line sharers of known CSA files and the ability to see other files shared by the same GUID or other IP addresses used by the same P2P client. Finally, our evaluation on real CSA case data shows high degrees of accuracy, while hands-on trials with law enforcement officers demonstrate the toolkit's complementarity to extant investigative workflows. (C) 2016 The Authors. Published by Elsevier Ltd.
In the last years, there is a greater interest in using computers in education, and in particular, in engineering education. Software programs have a great impact on studying many physical phenomena that otherwise could be described only using very complex mathematical algorithms. Furthermore, by computer simulation it can be studied the behavior of many engineering systems before its launching in production. However, the focus many times exclusively could be a handicap for the future engineers from a different perspective: lack of real measurement and future data manipulation and interpretation. At the same time, experimental stands could be often very expensive for many university laboratories. In this article, the author presents a methodology that could be a compromise between the use of software dedicated programs and of really electrical systems. The use of electronic simulators releases the university laboratory of expensive acquisitions and does not put a very large gap between practice and theoretical concepts. Based on the block system diagram of a real system, it is constructed the electronic simulator using basic Operational Amplifier structures' circuits. The result is an electronic system simulator.
Background: Computer-delivered cognitive behavioural therapy (cCBT) is an effective alternative to provider-delivered treatment for depression and anxiety, but high attrition poses a significant challenge to its use. Peer support is a feasible approach to improving cCBT engagement, but less is known about its acceptability among Veterans. Aims: To obtain feedback from Veterans (n = 24) with depression and/or anxiety on their preferences for (a) activities of Veterans Administration Peer Support Specialists (VA PSS) in helping Veterans use Moving Forward, a cCBT-based protocol developed by VA, and (b) methods for delivering support to Veterans using this programme. Method: Four focus groups (5-7 Veterans per group) provided feedback to be used in the development of a peer-supported engagement intervention to help Veterans with depression and anxiety use Moving Forward. Content areas included roles that a VA PSS might play in supporting the use of and engagement in Moving Forward, as well as methods of delivering that support. Results: Veteran preferences for PSS activity focused on practical aspects of using Moving Forward, including orientation to the programme, technical support, and monitoring progress. Feedback also suggested that Veterans preferred more personal roles for the PSS, including emotional support, as well as application of Moving Forward to real life' problems. Conclusions: The findings extend the literature on online, patient-facing mental health protocols by identifying emotional support and real life' skills application as Veteran-preferred components of a peer-support protocol designed to enhance use of and engagement in cCBT for depression and anxiety.
How do older adults mobilize social support, with and without digital media? To investigate this, we focus on older adults 65+ residing in the Toronto locality of East York, using 42 interviews lasting about 90 minutes done in 2013-2014. We find that digital media help in mobilizing social support as well as maintaining and strengthening existing relationships with geographically near and distant contacts. This is especially important for those individuals (and their network members) who have limited mobility. Once older adults start using digital media, they become routinely incorporated into their lives, used in conjunction with the telephone to maintain existing relationships but not to develop new ones. Contradicting fears that digital media are inadequate for meaningful relational contact, we found that these older adults considered social support exchanged via digital media to be real support that cannot be dismissed as token. Older adults especially used and valued digital media for companionship. They also used them for coordination, maintaining ties, and casual conversations. Email was used more with friends than relatives; some Skype was used with close family ties. Our research suggests that policy efforts need to emphasize the strengthening of existing networks rather than the establishment of interventions that are outside of older adults' existing ties. Our findings also show that learning how to master technology is in itself a form of social support that provides opportunities to strengthen the networks of older adults.
Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples. (C) 2016 Wiley Periodicals, Inc.
Backround: Previous studies have demonstrated the contributions of genetic variants and positive psychological traits (e.g. gratitude and forgiveness) to well-being. However, little is known about how genes interact with positive traits to affect well-being. Methods: To investigate to what extent the COMTVa1158Met polymorphism modulates well-being and to what extent dispositional gratitude and forgiveness mediate the individual differences in well-being, 445 participants were recruited and required to complete a battery of questionnaires. Results: We found that individuals with a smaller number of the Met alleles reported greater well-being, less depressive symptoms, and greater tendencies for gratitude and forgiveness. Moreover, dispositional gratitude and forgiveness mediated the genotype effects on well-being and depressive symptoms. These results remained significant after controlling for non-genetic factors (socioeconomic status, religious beliefs, romantic relationship status, parenting style). Limitation: The sample size limits the generalizability of results. Conclusion: This study demonstrates the contribution of the COMT Va1158Met polymorphism to individual differences in well-being and suggests a potential psychobiological pathway from dopaminergic and noradrenergic systems to happiness.
Solar Tower Technology is a promising way to generate sustainable electricity from concentrated solar radiation. In one of the most effective variants of this technology, a so called volumetric air receiver is used to convert concentrated radiation into heat. This component consists of a high temperature resistant cellular material which absorbs radiation and transfers the heat to an air flow which is fed from the ambient and from recirculated air. It is called volumetric, because the radiation may penetrate into the "volume" of the receiver through the open, permeable cells of the material. In this way a larger amount of heat transfer surface supports the solid to gaseous heat transfer in comparison to a tubular closed receiver. Finally the heated air is directed to the steam generator of a conventional steam turbine system. In this study an advanced cellular metal honeycomb structure has been designed, manufactured and tested for use as an open volumetric receiver. It consists of winded pairs of flat and corrugated metal foils. The technology is based on a one which has been primarily developed for the treatment of combustion engine exhaust gases. A number of variations of the pure linear honeycomb structure have been introduced to increase local turbulence and radial flow. Firstly, a set of samples has been tested in laboratory scale experiments to determine effective properties and the solar-to-thermal efficiency. After that, results have been compared with theoretical predictions. Finally, the three most promising materials have been used for a 500 kW test on the research platform of the Solar Tower Julich. Air outlet temperatures of more than 800 degrees C have been achieved with efficiencies of about 80%, which is about 5% more than the state-of-the-art technology, which is currently used at the main receiver of the Solar Tower. Next to this, lifetime models will be developed to increase the overall reliability of the technology. (C)2017 Elsevier Ltd. All rights reserved.
High concentration photovoltaics, equipped with high efficiency multijunction solar cells, have great potential in achieving cost-effective and clean electricity generation at utility scale. Such systems are more complex compared to conventional photovoltaics because of the multiphysics effect that is present. Modelling the power output of such systems is therefore crucial for their further market penetration. Following this line, a multiphysics modelling procedure for high concentration photovoltaics is presented in this work. It combines an open source spectral model, a single diode electrical model and a threedimensional finite element thermal model. In order to validate the models and the multiphysics modelling procedure against actual data, an outdoor experimental campaign was conducted in Albuquerque, New Mexico using a high concentration photovoltaic monomodule that is thoroughly described in terms of its geometry and materials. The experimental results were in good agreement (within 2.7%) with the predicted maximum power point. This multiphysics approach is relatively more complex when compared to empirical models, but besides the overall performance prediction it can also provide better understanding of the physics involved in the conversion of solar irradiance into electricity. It can therefore be used for the design and optimisation of high concentration photovoltaic modules. (C) 2017 Elsevier Ltd. All rights reserved.
One of the possible research lines for improving the Concentrated Solar Power (CSP) technology is the enhancement of the thermophysical properties of the Heat Transfer Fluids (HTF) used. This enhancement leads to reduce costs for producing electricity using this technology. So, this study presents the preparation of nanofluids in which Ag nanoparticles were added to a base fluid composed of a eutectic mixture of diphenyl oxide and biphenyl. The base fluid is a heat transfer fluid commonly used in concentrating solar power plants. The nanofluids were shown to have improved thermal properties, the heat transfer coefficient increasing by up to 6% compared with the base fluid. Thus, their use could lead to enhancements in the overall efficiency of CSP plants. Accordingly, nanofluids were prepared with varying nanoparticle concentrations and their properties were characterized, including their physical and chemical stability, viscosity, isobaric specific heat and thermal conductivity. In addition, molecular dynamic calculations were performed to reach a better understanding of the nanofluid system at a molecular level. The isobaric specific heat and thermal conductivity values followed the same experimental tendency. An analysis of the radial distribution functions (RDFs) and spatial distribution functions (SDFs) shows that there is a first layer of base fluid molecules around the metal in which the oxygen atoms play an important role. This first layer encourages the directionality of the movement in the heart of the nanofluid, which leads to enhanced thermal properties. (C) 2017 Elsevier Ltd. All rights reserved.
The main aim of this study was to conduct preliminary analysis on the performance of two conceptual designs that integrate the production of potable water, electricity, and salt. We used reverse osmosis (RO), pressure-retarded osmosis (PRO), and electrodialysis (ED) to produce potable water, electricity, and salt, respectively. The objective of the analysis is to observe how the relative positions of RO and PRO in the integrated process affect the five key parameters, i.e. the total dissolved solids (TDS) of potable water, permeate rate, the total energy requirement of the RO and ED units, net delivered power, and salt potential. We simulated each integrated design using previously validated mathematical expressions of RO, PRO, and ED. We found that the net delivered power is higher When the RO unit is located before the PRO unit. The same sequence also results in lower energy requirement for producing potable water, although the permeate rate is smaller than that of the rival sequence. On the other hand, the salt potential is not affected by the relative positions of the RO and PRO units. (C) 2017 Elsevier B.V. All rights reserved.
Adhesively bonding fiber-reinforced polymer (FRP) composites to reinforced concrete members is a simple and highly effective method to restore strength, increase loading capacities, and extend the service life of structures. With growing demand and wider applications of these strengthening systems, it is their durability that has recently received significant attention from the research community, largely in the form of laboratory testing of deteriorated FRP-to-concrete joints. To develop generalized deterioration factors, a database of shear tests has been collected to quantitatively assess the change in bond characteristics across a number of environmental conditions. It has been identified that a major shortcoming of existing test data is that reporting of the full-range load-displacement behavior is very limited. To supplement existing data, an experimental study is devised to further assess the deterioration of carbon FRP bonded systems under three aqueous conditions. The investigation consists of continually immersing specimens in water, a 5% salt solution, and, for the first time, a sulfuric acid solution of pH 4.0 to simulate the pooling of acid rain. Results show that sulfuric acid attack is most detrimental to the durability of the bond. Then, using a mechanics-based numerical model, bond properties are extracted from the present results as well those in published literature, to determine conservative deterioration factors for the change in bond characteristics with environmental exposure. (C) 2017 American Society of Civil Engineers.
Objective: A previous study conducted by our group found theory of mind (ToM) differences in preschool children who sustained mild traumatic brain injury (mTBI) compared with typically developing peers, 6 months postinjury. The goals of the current longitudinal study were to determine whether these findings are the result of a brain-injury-specific effect or rather a general-injury effect, to examine the long-term evolution of ToM skills following preschool mTBI, as well as to investigate the links between ToM abilities and general social functioning. Method: Seventy-two children who sustained mTBI between the ages of 18 and 60 months were evaluated 6 and 18 months postinjury on ToM tasks including desires and emotions reasoning and false belief understanding. They were compared with 58 participants who sustained an orthopedic injury (OI) and 83 typically developing children (TDC). Results: The 3 groups did not differ on demographic and baseline characteristics. The mTBI group obtained poorer scores relative to both comparison groups on the desires and emotions reasoning task, both at 6 and 18 months injury. No correlations were found between injury characteristics and ToM performance. For the mTBI group, associations were found between ToM performance and global social competence. Conclusion: These findings suggest a brain-injury-specific effect that persists in the long-term following mTBI in preschool children.
Background: The density of a host population is a key parameter underlying disease transmission, but it also has implications for the expression of disease through its effect on host physiology. In response to higher densities, individuals are predicted to either increase their immune investment in response to the elevated risk of parasitism, or conversely to decrease their immune capacity as a consequence of the stress of a crowded environment. However, an individual's health is shaped by many different factors, including their genetic background, current environmental conditions, and maternal effects. Indeed, population density is often sensed through the presence of info-chemicals in the environment, which may influence a host's interaction with parasites, and also those of its offspring. All of which may alter the expression of disease, and potentially uncouple the presumed link between changes in host density and disease outcomes. Results: In this study, we used the water flea Daphnia magna and its obligate bacterial parasite Pasteuria ramosa, to investigate how signals of high host density impact on host-parasite interactions over two consecutive generations. We found that the chemical signals from crowded treatments induced phenotypic changes in both the parental and offspring generations. In the absence of a pathogen, life-history changes were genotype-specific, but consistent across generations, even when the signal of density was removed. In contrast, the influence of density on infected animals depended on the trait and generation of exposure. When directly exposed to signals of high-density, host genotypes responded differently in how they minimised the severity of disease. Yet, in the subsequent generation, the influence of density was rarely genotype-specific and instead related to ability of the host to minimise the onset of infection. Conclusion: Our findings reveal that population level correlations between host density and infection capture only part of the complex relationship between crowding and the severity of disease. We suggest that besides its role in horizontal transmission, signals of density can influence parasite epidemiology by modifying mechanisms of resistance across multiple generations, and elevating variability via genotype-by-environment interactions. Our results help resolve why some studies are able to find a positive correlation between high density and resistance, while others uncover a negative correlation, or even no direct relationship at all.
The efforts for more reliable power conversion systems have been gaining momentum in recent years. The majority of the studies concerning reliability of power switches focus on the package-related failures, mainly caused by the cyclic thermal stress. The basic failure precursor for this type of stress has been identified as increased on-state resistance for power MOSFETs in the recent literature. On-state resistance monitoring during converter operation is a challenging and costly task as it requires current and voltage sensing circuits, which can block the high voltage across the switch during off-state to protect the measurement or control unit. This paper proposes a software frequency response analysis method to determine the health status of high-voltage power MOSFETs with high on-state resistance. This is achieved by analyzing and evaluating the variation in the plant model at double pole frequency using the same DSP that is used for control purposes. The proposed concept is analyzed for boost converter; however, it can be used to detect the on-state resistance variation in other types of converters operating in continuous condition mode (CCM). The proposed algorithm is embedded in a low cost DSP and experimentally verified on a dc/dc boost converter.
This paper presents a new stochastic operation scheduling model for microgrid in day-ahead electricity market considering the forecast uncertainties of wind generations, microgrid's load, and locational marginal price of the point of common coupling, as well as the uncertainties pertaining to availability of generation units of the microgrid. The financial risk caused by these uncertainties is modeled by conditional value-at-risk criterion. The proposed approach is formulated as a risk-minimizing two-stage stochastic model based on mixed-integer linear programming framework. This model minimizes the expected scheduling cost together with the cost of financial risk. The impacts of different uncertainty sources on the model's results in both grid-connected and islanded operation modes are extensively studied. Additionally, higher effectiveness of the proposed stochastic model compared with common deterministic approach, regarding total operation cost and convergence behavior, is illustrated through an out-of-sample analysis.
Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual's life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS + SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS + SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS + SI male mice. When attempting to elucidate the mechanism underlying downregulation of the Dl receptor in the NAc of MS + SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region. (C) 2017 Elsevier B.V. All rights reserved.
This paper proposes a predictive control algorithm that includes conduction-mode detection for power factor correction (PFC) converter. In PFC converters, the line current is usually distorted because of the characteristics of the proportional-integral (PI) current controller. To improve the quality of the current, the PI current controller requires additional circuits or algorithms. However, because of the optimal duty cycle determined by estimating the next-state current in both the continuous-conduction mode and the discontinuous-conduction mode, the proposed predictive control method has a fast dynamic response and accuracy compared to the PI current-control method. Moreover, the proposed algorithm can detect the conduction mode without any additional circuitry or mode-detection algorithm using the characteristic of the optimal duty cycle calculated by the predictive control. These advantages of the proposed algorithm improve the quality of the line current for PFC converters. We verify the proposed method by performing experiment using a 1.5-kW PFC converter.
Condyloma acuminata (CA) are warty lesions caused by human papilloma virus (HPV) that generally affect the external genitalia and mucocutaneous junctions. Involvement of the urinary tract is rare, and involvement of the urinary bladder is thought to be due to immunosuppression. A 30-year-old woman was diagnosed with urethral CA 12 months after renal transplantation. She underwent transurethral resection (TUR) of the urethral lesions. During the operation, multiple sessile warty lesions were found incidentally inside the bladder and were also removed by TUR. The patient's postoperative course was uneventful. Pathological examination confirmed that the lesions were CA. Multiplex real-time polymerase chain reaction was performed to confirm the HPV genotype and revealed type 45 HPV DNA. CA of the urethra are uncommon, and bladder involvement is extremely rare. This case is the first reported, to our knowledge, to involve HPV type 45 in bladder condyloma. TUR may be the preferred option for the management of CA in the urinary bladder.
Introduction: National conference didactic lectures have traditionally featured hour-long lecture-based presentations. However, there is evidence that longer lectures can lead to both decreased attention and retention of information. The authors sought to identify trends in lecture duration, lecture types, and number of speakers at four national emergency medicine (EM) conferences over a 6-year period. Methods: The authors performed a retrospective analysis of the length, number of speakers, and format of didactic lectures at four different national EM conferences over 6 years. The authors abstracted data from the national academic assemblies for the four largest not-for-profit EM organizations in the United States: American Academy of Emergency Medicine, American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine. Results: There was a significant yearly decrease in the mean lecture lengths for three of the four conferences. There was an increase in the percentage of rapid fire sessions over the preceding 2 years with a corresponding decrease in the percentage of general educational sessions. There was no significant difference in the mean number of speakers per lecture. Discussion: An analysis of 4210 didactic lecture sessions from the annual meetings of four national EM organizations over a 6-year period showed significant decreases in mean lecture length. These findings can help to guide EM continuing medical education conference planning and research.
Expectation of reward can be shaped by the observation of actions and expressions of other people in one's environment. A person's apparent confidence in the likely reward of an action, for instance, makes qualities of their evidence, not observed directly, socially accessible. This strategy is computationally distinguished from associative learning methods that rely on direct observation, by its use of inference from indirect evidence. In twenty-three healthy human subjects, we isolated effects of first-hand experience, other people's choices, and the mediating effect of their confidence, on decision-making and neural correlates of value within ventromedial prefrontal cortex (vmPFC). Value derived from first-hand experience and other people's choices (regardless of confidence) were indiscriminately represented across vmPFC. However, value computed from agent choices weighted by their associated confidence was represented with specificity for ventromedial area 10. This pattern corresponds to shifts of connectivity and overlapping cognitive processes along a posterior-anterior vmPFC axis. Task behavior and self-reported self-reliance for decision-making in other social contexts correlated. The tendency to conform in other social contexts corresponded to increased activation in cortical regions previously shown to respond to social conflict in proportion to subsequent conformity (Campbell-Meiklejohn et al., 2010). The tendency to self-monitor predicted a selectively enhanced response to accordance with others in the right temporoparietal junction (rTPJ). The findings anatomically decompose vmPFC value representations according to computational requirements and provide biological insight into the social transmission of preference and reassurance gained from the confidence of others.
Three studies examined the hypothesis that bilinguals can more rapidly disengage attention from irrelevant information than monolinguals by investigating the impact of previous trial congruency on performance in a simple flanker task. In Study 1, monolingual and bilingual young adults completed two versions of a flanker task. There were no differences between language groups on mean reaction time using standard analyses for congruent or incongruent trials or the size of the flanker effect. Sequential congruency effects (SCEs) however, which account for previous trial congruency, were smaller for bilinguals than for monolinguals. This finding was strongest at the shortest response-to-stimulus interval (RSI). Study 2 replicated this effect using a slightly different flanker task and a shorter RSI than study 1. Study 3 showed that at long RSIs, where behavioral SCE differences between groups disappear because of sufficient time to recover from the previous trial, event-related potentials demonstrated a continued influence of previous trial congruency for monolinguals but not bilinguals at both the N2 and the P3, replicating the reaction time effects in Studies 1 and 2. Together, these studies demonstrate that bilinguals experience less influence from previous trial congruency and have greater ability to disengage attention from the previous trial in order to focus attention on the current trial than is found for monolinguals. (C) 2017 Elsevier B.V. All rights reserved.
The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.
Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether simultaneous vaccination with both antigens enhances protection. We undertook evaluation of a novel bivalent vaccine based on nonreplicating lymphocytic choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB [gB(dCt)] and full-length pp65 from human CMV in mice. Immunization with the gB(dCt) vector alone elicited a comparable gB-binding antibody response and a superior neutralizing response to that elicited by adjuvanted subunit gB. Immunization with the pp65 vector alone elicited robust T cell responses. Comparable immunogenicity of the combined gB(dCt) and pp65 vectors with the individual monovalent formulations was demonstrated. To demonstrate proof of principle for a bivalent rLCMV-based HCMV vaccine, the congenital guinea pig cytomegalovirus (GPCMV) infection model was used to compare rLCMV vectors encoding homologs of pp65 (GP83) and gB(dCt), alone and in combination versus Freund's adjuvanted recombinant gB. Both vectors elicited significant immune responses, and no loss of gB immunogenicity was noted with the bivalent formulation. Combined vaccination with rLCMV-vectored GPCMV gB(dCt) and pp65 (GP83) conferred better protection against maternal viremia than subunit or either monovalent rLCMV vaccine. The bivalent vaccine also was significantly more effective in reducing pup mortality than the monovalent vaccines. In summary, bivalent vaccines with rLCMV vectors expressing gB and pp65 elicited potent humoral and cellular responses and conferred protection in the GPCMV model. Further clinical trials of LCMV-vectored HCMV vaccines are warranted.
Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide, with an estimated incidence in developed countries of 0.6-0.7% of all live births. The burden of disease related to congenital CMV in substantial, as it is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities in children. Despite its clinical significance, congenital CMV infection often goes undetected because the majority of infected infants are asymptomatic at birth and screening programs have not been substantially implemented. Other than behavioral measures, effective interventions aimed at the prevention of maternal infection and of mother-to-child transmission are lacking. Due to a convergence of recent advances in both diagnostic and therapeutic strategies in infants with congenital CMV, though, the field likely will be changing rapidly over just the next few years. Specifically, a highly-sensitive screening test with high throughput potential has been developed, and treatment of infants symptomatically infected with congenital CMV has proven to be well-tolerated and effective in improving long-term hearing and neurodevelopmental outcomes. This review highlights the clinical importance of congenital CMV infection, the developments in laboratory diagnostics, and the benefits of antiviral therapy. It also identifies the global efforts still required in the prevention of maternal infection and in the optimization of antiviral therapy to further reduce the burden of congenital CMV disease.
Background: Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH. Materials and Methods: Pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D19 and D21 and divided into control and CDH groups. Immunohistochemistry and quantitative real-time polymerase chain reaction (RT-PCR) were performedto determine the expression ofEPOin the fetal liver and kidney. We also estimated the expression of EPO receptor in the fetal lung. Results: The relative EPO mRNA expression in the liver on D19 and in the kidney on D21 were significantly lower in the CDH group than in the controls (P = 0.0008 and P = 0.0064, respectively). In addition, the results of immunohistochemistry supported the findings from the RT-PCR analysis. No significant changes were noted in the expression pattern or EPO receptor levels in the fetal lungs of the CDH group compared to the controls. Conclusions: Our results reveal the suppressed EPO synthesis in the CDH fetus, which may contribute to the pathogenesis of lung hypoplasia and modification of pulmonary vasculature in the CDH rat model. (C) 2016 Wiley Periodicals, Inc.
Super-majorities have occurred frequently in Congress but have escaped scholarly attention. This paper employs new measures of positive agenda control and a unique data set of 3,407 nontrivial bills from 1981 to 2008 to answer two questions: how did legislative leaders construct veto-proof coalitions, and what did presidents do with them? Legislative leaders, we argue, deployed procedures to expand and sustain veto-proof coalitions, despite increasing polarization. The resulting history, which signaled members' commitment to a bill, provided information to the president that reduced uncertainty about possibilities for interbranch bargaining and the likely success of a veto. We find that positive agenda control increased the probability of vote tallies of two-thirds or more, especially after the 1994 election. In addition, we demonstrate that presidents concentrated veto activity on bills with outcomes of less than two-thirds, rejected some veto-proof bills for reputational gains, and deployed signing statements strategically. The analysis suggests that congressional leaders paradoxically gained capacity for nurturing large, bipartisan alliances as the institution became more polarized. Moreover, it demonstrates that strategic activity by legislative leaders is critical to explaining variation in presidential options for veto bargaining and signing statements.
Human judgment often violates normative standards, and virtually no judgment error has received as much attention as the conjunction fallacy. Judgment errors have historically served as evidence for dual-process theories of reasoning, insofar as these errors are assumed to arise from reliance on a fast and intuitive mental process, and are corrected via effortful deliberative reasoning. In the present research, three experiments tested the notion that conjunction errors are reduced by effortful thought. Predictions based on three different dual-process theory perspectives were tested: lax monitoring, override failure, and the Tripartite Model. Results indicated that participants higher in numeracy were less likely to make conjunction errors, but this association only emerged when participants engaged in two-sided reasoning, as opposed to one-sided or no reasoning. Confidence was higher for incorrect as opposed to correct judgments, suggesting that participants were unaware of their errors.
In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes. (C) 2008 Elsevier Inc. All rights reserved.
Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scoreswas found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se.
Human brain asymmetries have been well described. Intriguingly, a number of asymmetries in brain phenotypes have been shown to change throughout the lifespan. Recent studies have revealed topological asymmetries between hemispheric white matter networks in the human brain. However, it remains unknown whether and how these topological asymmetries evolve from adolescence to young adulthood, a critical period that constitutes the second peak of human brain and cognitive development. To address this question, the present study included a large cohort of healthy adolescents and young adults. Diffusion and structural magnetic resonance imaging were acquired to construct hemispheric white matter networks, and graph-theory was applied to quantify topological parameters of the hemispheric networks. In both adolescents and young adults, rightward asymmetry in both global and local network efficiencies was consistently observed between the 2 hemispheres, but the degree of the asymmetry was significantly decreased in young adults. At the nodal level, the young adults exhibited less rightward asymmetry of nodal efficiency mainly around the parasylvian area, posterior tempo-parietal cortex, and fusiform gyrus. These developmental patterns of network asymmetry provide novel insight into the human brain structural development from adolescence to young adulthood and also likely relate to the maturation of language and social cognition that takes place during this period.
Adverse conditions during fetal life have been associated to both structural and functional changes in neurodevelopment from the neonatal period to adolescence. In this study, connectomics was used to assess the evolution of brain networks from infancy to early adolescence. Brain network reorganization over time in subjects who had suffered adverse perinatal conditions is characterized and related to neurodevelopment and cognition. Three cohorts of prematurely born infants and children (between 28 and 35 weeks of gestational age), including individuals with a birth weight appropriated for gestational age and with intrauterine growth restriction (IUGR), were evaluated at 1, 6, and 10 years of age, respectively. A common developmental trajectory of brain networks was identified in both control and IUGR groups: network efficiencies of the fractional anisotropy (FA)-weighted and normalized connectomes increase with age, which can be related to maturation and myelination of fiber connections while the number of connections decreases, which can be associated to an axonal pruning process and reorganization. Comparing subjects with or without IUGR, a similar pattern of network differences between groups was observed in the three developmental stages, mainly characterized by IUGR group having reduced brain network efficiencies in binary and FA-weighted connectomes and increased efficiencies in the connectome normalized by its total connection strength (FA). Associations between brain networks and neurobehavioral impairments were also evaluated showing a relationship between different network metrics and specific social cognition-related scores, as well as a higher risk of inattention/hyperactivity and/or executive functional disorders in IUGR children.
Objective: The aim of this study was to evaluate the association between two haplotype-tag single nucleotide polymorphisms (SNPs) (rs6658835 and rs10495098) of TGF-2 and conotruncal heart defects (CTDs).Methods: Two polymorphisms of TGF-2 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) from 259 CTDs patients and 310 control subjects.Results: The association between SNP rs6658835 in TGF-2 and CTDs has been found. The frequency of G allele in CTDs patients was significantly higher than that in control subjects (52.7% versus 40.3%, p<0.001, OR =1.649).Conclusion:TGF-2 gene polymorphisms may serve as a novel genetic marker for the risk of CTDs.
Introduction. The aim of this study was to evaluate the effects of consecutive night shifts (CNS) and shift length on cognitive performance and sleepiness. Materials and methods. This study evaluated the sleepiness and performance of 30 control room operators (CROs) working in 7 nights, 7 days, 7 days off (7N7D7O) and 30 CROs working in 4 nights, 7 days, 3 nights, 7 days off (4N7D3N7O) shift patterns in a petrochemical complex on the last night shift before swinging into the day shift. To assess cognitive performance, the n-back test, continuous performance test and simple reaction time test were employed. To assess sleepiness, the Karolinska sleepiness scale was used. Results. Both schedules indicated that the correct responses and response times of working memory were reduced (p=0.001), while intentional errors and sleepiness increased during the shift work (p=0.001). CNS had a significant impact on reaction time and commission errors (p=0.001). Conclusion. The main duty of CROs at a petrochemical plant is checking hazardous processes which require appropriate alertness and cognitive performance. As a result, planning for appropriate working hours and suitable number of CNS in a rotating shift system is a contribution to improving CRO performance and enhancing safety.
Introduction: The high success rate in the management medulloblastoma achieved in the western world is not exactly mirrored in developing countries including India. Socio-demographic differences, health-care disparity, and lack in uniformity of care with resultant widespread variations in the clinical practice are some of the reasons that may partly explain this difference in outcomes. Patients with medulloblastoma require a multi-disciplinary team approach involving but not limited to neuro-radiology, neurosurgery; neuropathology, molecular biology, radiation oncology, pediatric medical oncology and rehabilitative services for optimizing outcomes. Methods: The Indian Society of Neuro-Oncology (ISNO) constituted an expert multi-disciplinary panel with adequate representation from all stakeholders to prepare national consensus guidelines for the contemporary management of medulloblastoma. Results: Minimum desirable, as well as preferable though optional recommendations (as appropriate), were developed and adopted for the pre-surgical work-up including neuroimaging; neurosurgical management including surgical principles, techniques, and complications; neuropathology reporting and molecular testing; contemporary risk-stratification in the molecular era; appropriate adjuvant therapy (radiotherapy and chemotherapy); and follow-up schedule in medulloblastoma. Conclusions: The current document represents a broad consensus reached amongst various stakeholders within the neuro-oncology community involved in the contemporary curative-intent management of children with medulloblastoma. It provides both general as well as specific guidelines and recommendations to be adopted by physicians and health care providers across India to achieve uniformity of care, improve disease-related outcomes, and compare results between institutions within the country.
The optimal use of biomass from a global warming mitigation perspective depends upon numerous factors, including competition for land and other constraints. The goal of this study is identifying optimal uses of domestic biomass resources for the case of Denmark, with the objectives of minimizing global warming contribution and fossil energy resource consumption. For this purpose, consequential life cycle assessment of the different options for biomass was performed. Optimal solutions were identified, given specific national environmental targets, using linear programming. Results highlighted that utilizing the energy potential of manure and straw represents the primary opportunity for further global warming mitigation. For this purpose, co-digestion (for manure) and combustion with heat-and-power production (for straw) appear as the most promising technologies. The utilization of biomass (or biogas) for electricity/heat is generally preferred, as long as coal/oil is still used within the energy system. Yet, to fulfill environmental targets for renewable energy in the transport sector, the diversion of a significant share of biogas (and/or other biofuels) from these more beneficial uses is necessary. To completely phase out coal/oil, additional biomass (to current domestic resources) must be included, either through domestic energy crops cultivation or biomass/biofuel import; alternatively, natural gas could be used. (C) 2017 Elsevier Ltd. All rights reserved.
Research indicates that inducing high-level construal (processing that highlights invariant, essential features) relative to low-level construal (processing that highlights idiosyncratic, peripheral features) promotes self-control (Fujita & Carnevale, 2012). In the present work, we investigate to what extent people recognize the self-control benefits of high-level construal, and explore the consequences of this knowledge. Studies 1 and 2 provide initial evidence that individuals are aware that high-level relative to low-level construal promotes self-control in the dieting domain. Studies 3 and 4 find that individual differences in this knowledge predict self-control success outcomes (i.e., body mass index) among those who are motivated by dieting goals. Examining academics as a domain of self-control, Study 5 demonstrates that those with higher knowledge of construal level's impact on self-control earned higher end-of-semester grades to the extent that they were motivated to do well academically. Theoretical and practical implications of these findings are discussed.
The aim of this study was to assess the environmental impact of microbial fuel cells (MFCs) implerriented in constructed wetlands (CWs). To this aim a life cycle assessment (LCA) was carried out comparing three scenarios: 1) a conventional CW system (without MFC implementation); 2) a CW system coupled with a gravel-based anode MFC, and 3) a CW system coupled with a graphite-based anode MFC. All systems served a population equivalent of 1500 p.e. They were designed to meet the same effluent quality. Since MFCs implemented in CWs improve treatment efficiency, the CWs coupled with MFCs had lower specific area requirement compared to the conventional CW system. The functional unit was 1 m(3) of wastewater. The LCA was performed with the software SimaPro (R) 8, using the CML-IA baseline method. The three scenarios considered showed similar environmental performance in all the categories considered, with the exception of Abiotic Depletion Potential. In this impact category, the potential environmental impact of the CW system coupled with a gravel-based anode MFC was around 2 times higher than that generated by the conventional CW system and the CW system coupled with a graphite based anode MFC. It was attributed to the large amount of less environmentally friendly materials (e.g. metals, graphite) for MFCs implementation, especially in the case of gravel-based anode MFCs. Therefore, the CW system coupled with graphite-based anode MFC appeared as the most environmentally friendly solution which can replace conventional CWs reducing system footprint by up to 20%. An economic assessment showed that this system was around 1.5 times more expensive than the conventional CW system. (C) 2017 Elsevier B.V. All rights reserved.
Roofers have long suffered from low back disorders (LBDs), which are a primary nonfatal injury in construction. Ergonomic studies have identified several risk factors associated with LBDs in workplaces and developed biomechanical models for general LBD risk assessments. However, these models cannot be directly used for assessments in roof workplaces because they are designed for general tasks without considering roofers' posture variance and effects of working on slanted roof surfaces. This paper examined the relationship between roofing work-related factors and LBD risk among roofers using a laboratory assessment. A pitch-configurable wood platform was built to mimic the rooftop. The maximum trunk flexion angle and normalized electromyography (EMG) signals were measured as indicators using a motion capture system and a skeletal muscle signal recording system under different settings, i.e., different roof slopes, postures, facing directions, and working paces. The results indicated the measured factors with significant effects on the LBD development and revealed unfavorable conditions (e.g., using a stooped posture to work on low-pitch rooftops at a fast pace) where the work on rooftops needs particular attention. Such information is useful for systematic understanding of roofing nonfatal LBD developments among construction professionals and may enable development of interventions and guidelines for reducing the prevalence of LBDs at roofing jobsites. (C) 2017 American Society of Civil Engineers.
Many animal toxins may target the same molecules that need to be controlled in certain pathologies; therefore, some toxins have led to the formulation of drugs that are presently used, and many other drugs are still under development. Nevertheless, collecting sufficient toxins from the original source might be a limiting factor in studying their biological activities. Thus, molecular biology techniques have been applied in order to obtain large amounts of recombinant toxins into Escherichia coli. However, most animal toxins are difficult to express in this system, which results in insoluble, misfolded, or unstable proteins. To solve these issues, toxins have been fused with tags that may improve protein expression, solubility, and stability. Among these tags, the SUMO (small ubiquitin-related modifier) has been shown to be very efficient and can be removed by the Ulp1 protease. However, removing SUMO is a labor- and time-consuming process. To enhance this system, here we show the construction of a bicistronic vector that allows the expression of any protein fused to both the SUMO and Ulp1 protease. In this way, after expression, Ulp1 is able to cleave SUMO and leave the protein interest-free and ready for purification. This strategy was validated through the expression of a new phospholipase D from the spider Loxosceles gaucho and a disintegrin from the Bothrops insularis snake. Both recombinant toxins showed good yield and preserved biological activities, indicating that the bicistronic vector may be a viable method to produce proteins that are difficult to express.
Over recent decades, water conservation have become increasingly an utmost important issue for debate, and this includes the domestic sector. Reducing demand water by improving the efficiency of water use in domestic sector requires an understanding of how water is used and in what ways water savings can be realized. The focus of this global, web-based, consumer questionnaire survey was to analyze individual consumer attitudes towards using water in manual dishwashing and understand the likelihood of a prospect of changing the daily manual dishwashing method resulting to a more efficient domestic usage of water. This study was designed to investigate the manual dishwashing technique used in the 5249 households of nine different countries - China, Germany, Italy, Russia, Indonesia, Brazil, India, South Africa and Argentina. Besides socio-demographics, technical questions like cleaning steps, hygiene questions motivational question, environmental awareness questions, questions on payment for water and electricity, questions on information sources about household work were included in the study. It was found that the awareness to conserve water was common among the Asian participants but it necessarily was not practiced in the households as individual washing of dishes was found to be quite high. Among the many outcomes, important one was that running tap method' was found to be most prevalent (86%) among Russian participants, complimenting their detached approach towards conserving domestic water usage. In South American countries like Brazil (66%) and Argentina (51%), high occurrence of running tap rinse' was found to be a common practice, confirming the lack of conscious use of water in manual dishwashing in the subcontinent. Based on the overall responses, awareness of a new and efficient technique of manual dishwashing could be propagated through the most voted mediums of Internet (81%) and TV (69%).
Research question: Scholars have paid little attention to consumer response to the termination of a sponsorship. The purpose of this study was to examine the reaction of fans of a professional cycling team to a sponsorship terminating, which ultimately led to the team disbanding.Research methods: The research purpose was pursued through digital ethnography (via message boards and weblog), examining the case of Basque professional cycling fans. Comments were analysed to understand fans' reaction to the 2013 cessation of Euskaltel-Euskadi, a Basque professional cycling team, after its sponsor, Euskaltel, exited the partnership.Results and findings: Fan reaction to Euskaltel ending its sponsorship was somewhat paradoxical, in that the terminated sponsorship ultimately led to the team disbanding, yet fans appeared to be appreciative of Euskaltel. They continued to celebrate the team's corporate sponsor colour as they mourned the end of Euskaltel-Euskadi and questioned the future of Basque cycling. This reaction is made more logical by understanding the long-term duration of the partnership, and how Euskaltel's support of the team for nearly two decades led to the intermeshing of the team and its sponsor, thus avoiding negative sentiment.Implications: This study makes a meaningful contribution to the sponsorship literature, particularly sponsorship termination. This study is one of the first to examine consumer response to sponsorship termination in a real-world setting, and suggests a potential legacy effect of long-term sponsorship, such that fan reaction to a long-term sponsorship terminating may not be negative, especially if fans understand the sponsor's contribution over time.
Green energy has gained significant research attention across the globe due to its ability to reduce environmental damage. However, for complete acceptance of green energy, only government regulations are not enough; the willingness to use green energy and contribute to the wellbeing of the environment should spring from within consumers. Such willingness may be developed by enhancing consumers' perceived value of green energy. However, in order to do so, it is necessary to assess existing levels of consumers' perceived value towards green energy. The present study develops a multidimensional green perceived value scale to measure existing levels of consumers' perceived value. The scale considers green perceived value as a multidimensional second order construct comprising functional value, social value, conditional value and emotional value dimensions. Such an attempt has not been made before which highlights the originality value of the present study. The scale can be used to assess consumers' perception towards green energy. Such information would help in formulating strategies that encourage consumers to voluntarily adopt green energy. The study also reveals that it is not only the financial aspects that lead consumers to decide on adoption of green energy; consumers are also driven by emotional and social considerations. Thus, policy makers could formulate pro-green energy programmes and mass messages that appeal to consumers' sense of responsibility to voluntarily adopt green energy without having to rely on financial incentives. Researchers could examine the considered dimensions of the scale further with respect to other constructs related to consumer behaviour. (C) 2017 Elsevier Ltd. All rights reserved.
Effective HIV prevention requires knowledge of the structure and dynamics of the social networks across which infections are transmitted. These networks most commonly comprise chains of sexual relationships, but in some populations, sharing of contaminated needles is also an important, or even the main mechanism that connects people in the network. Whereas network data have long been collected during survey interviews, new data sources have become increasingly common in recent years, because of advances in molecular biology and the use of partner notification services in HIV prevention and treatment programmes. We review current and emerging methods for collecting HIV-related network data, as well as modelling frameworks commonly used to infer network parameters and map potential HIV transmission pathways within the network. We discuss the relative strengths and weaknesses of existing methods and models, and we propose a research agenda for advancing network analysis in HIV epidemiology. We make the case for a combination approach that integrates multiple data sources into a coherent statistical framework. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
The present study focuses on measuring the effects of industrial wastewater disposed from thermal electricity power plant as by-product on the geotechnical properties of sandy soil and applying washing process to remediate the contaminated soil samples and measure the efficiency of washing technique. The disturbed sandy soil samples were obtained from Al-Kufa City located to the southwest of Iraq and the industrial wastewater obtained from Al-Musayib thermal electricity power plant. The intact sandy soil was contaminated in the laboratory with four percentages of industrial wastewater (10, 20, 40 and 100%) calculated according to the weight of dry soil. The industrial wastewater is mixed with distilled water to constitute the solution used in the contamination process of soil through soaking the soil by this solution for 30 days. The study results showed that with increasing the percentages of the contaminant, there was a slight increase in both the liquid limit and particle size, while there was a significant increase in the optimum water content. Nevertheless, a slight decrease was observed in the specific gravity, maximum dry unit weight, and void ratio, while, a considerable decrease was noticed in the angle of the internal friction and coefficient of permeability of soil. The proposed remediation technique "soil washing" is efficient, economical, and time saving when used to remediate sandy soils. After remediation, the results showed an increase in the cohesion, angle of internal friction and maximum dry unit weight. Also, a slight increase was observed in the specific gravity, void ratio and permeability coefficient of remediated soil samples when compared with that of contaminated samples. The removal efficiencies of contaminant from soil were (97.63, 96.79, 96.58, and 93.87%) for the soil samples contaminated with industrial wastewater by (10, 20, 40 and 100%), respectively.
Starting with a computational analysis of brightness matching, we develop a novel variational framework able to model perceptual context-driven effects that may be extended to non-physical judgments as well. The most important feature of the variational framework is the description of these phenomena as a suitable balance between contrast and dispersion. The optimal balance is defined through the simultaneous minimization of functionals characterized by two terms in opposition to each other. When the minimum is reached, the equilibrium between contrast and dispersion is attained. To show the flexibility of the proposed framework, we discuss several examples of such functionals in the field of color perception and cognition which show adherence between theoretical predictions and empirical results. With regard to social cognition theories, the simultaneous occurrence of contrast and dispersion conflicts with sequential models, thus supporting the idea of a concurrent presence of both effects in each judgment. The variational framework can serve as a view from above on perceptual and cognitive phenomena that may help in deriving new constraints for disambiguating alternative theories. (C) 2016 Elsevier Inc. All rights reserved.
The anterior cingulate cortex (ACC) is commonly associated with cognitive control and decision making, but its specific function is highly debated. To explore a recent theory that the ACC learns the reward values of task contexts (Holroyd & McClure in Psychological Review, 122, 54-83, 2015; Holroyd & Yeung in Trends in Cognitive Sciences, 16, 122-128, 2012), we recorded the event-related brain potentials (ERPs) from participants as they played a novel gambling task. The participants were first required to select from among three games in one "virtual casino," and subsequently they were required to select from among three different games in a different virtual casino; unbeknownst to them, the payoffs for the games were higher in one casino than in the other. Analysis of the reward positivity, an ERP component believed to reflect reward-related signals carried to the ACC by the midbrain dopamine system, revealed that the ACC is sensitive to differences in the reward values associated with both the casinos and the games inside the casinos, indicating that participants learned the values of the contexts in which rewards were delivered. These results highlight the importance of the ACC in learning the reward values of task contexts in order to guide action selection.
This paper analyzes the effect of operational amplifier (OPAMP) input offset on continuous-time (CT) delta-sigma (Delta Sigma) modulators with current-mode feedback digital-to-analog converters (DAC). Our analysis shows that the input offset leads to either increased harmonics or increased noise floor of the modulator, depending on whether a DAC shuffling scheme, such as data-weighted averaging (DWA), is applied or not. Analysis and mathematical derivation are given and verified by transistor-level simulations. An input-offset cancellation scheme is proposed and demonstrated by simulation results.
The current practice of discrete-time electricity pricing starts to fall short in providing an accurate economic signal reflecting the continuous-time variations of load and generation schedule in power systems. This paper introduces the fundamental mathematical theory of continuous-time marginal electricity pricing. We first formulate the continuous-time unit commitment problem as a constrained variational problem, and subsequently define the continuous-time economic dispatch (ED) problem where the binary commitment variables are fixed to their optimal values. We then prove that the continuous-time marginal electricity price equals to the Lagrange multiplier of the variational power balance constraint in the continuous-time ED problem. The proposed continuous-time marginal price is not only dependent to the incremental generation cost rate, but also to the incremental ramping cost rate of the units, thus embedding the ramping costs in calculation of the marginal electricity price. The numerical results demonstrate that the continuous-time marginal price manifests the behavior of the constantly varying load and generation schedule in power systems.
An approach to mass measurement for the electronic balance based on continuous-time sigma-delta (CT Sigma-Delta) modulator is described in this paper. As an effect of multifarious interfering noises, the accuracy of the electronic balance is restricted. The general idea of this proposed approach is to apply an electromagnetic-force-compensated load cell (EMCC), a related signal processing circuit, and a composite filter. The circuit mainly consists of a proportional-integral-differential controller and a pulsewidth modulator, which combine with the EMCC to form a CT Sigma-Delta modulator. As the CT Sigma-Delta modulator possesses inherent antialiasing filtering, oversampling, and noise-shaping characteristics, the interfering noises can be effectively removed by the composite filter that is composed of two sinc(N) filters. The simulations for both of the electronic balance models adopting the proposed approach and working in conventional pulse current mode are analyzed by adding the white Gaussian noise in Simulink. The simulation results demonstrate the effectiveness of this proposed approach, the proposed electronic balance in the field can improve its signal-to-noise ratio, and the testing results meet the requirement for the weighing accuracy of the special-class scale defined by Organisation Internationale De Metrologie Legale R76 nonautomatic weighing instruments.
Precise knowledge of the plant time constant L/R is essential to perform a thorough analysis and design of the current control loop in voltage source converters (VSCs). From the perspective of the current controller dynamics in the low-frequency range, such plant time constant is also suitable for most cases in which an LCL filter is used. As the loop behavior can be significantly influenced by the VSC working conditions, the effects associated to converter losses should be included in the model, through an equivalent series resistance. In addition, the plant inductance may also present important uncertainties with respect to the value of the VSC L/LCL interface filter measured at rated conditions. Thus, in this paper, a method is presented to estimate both parameters of the plant time constant, i.e., the equivalent inductance and resistance in the plant model of current-controlled VSCs. The proposed technique is based on the evaluation of the closed-loop transient responses of both axes of the synchronous reference frame when a proportional-integral current controller is implemented. The method gives a set of resistance and inductance values that should be employed for a rigorous design of the current controllers. Experimental results validate the approach.
Regression analysis using orthogonal polynomials in the time domain is used to derive a digital filter with an infinite impulse response that satisfies maximally flat design constraints near dc. The low-frequency phase, and high-frequency gain, may be adjusted for lead or lag compensation of plant dynamics. Simulated design examples are used to show how the compensating filter may be intuitively tuned for the desired closed-loop response. It is shown that the second-order instantiation of the compensating filter reduces to a proportional-differential plus filter controller, with improved noise attenuation; closed-form expressions for the filter coefficients, as a function of two design parameters, are provided.
In conventional relative gene expression analysis (Northern blotting, RT-PCR, and in situ hybridization), housekeeping genes such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin genes, whose expression levels are considered stable, have been used as control genes for normalization of RNA quantitation. However, it has been reported that the expression levels of these two control genes are affected by ischemia. Therefore, we have been searching for novel control genes whose expression levels are stable in a mouse model of transient forebrain ischemia. Using the GeneChip Mu6500 array set, we monitored the expression levels of approximately 6000 murine genes in the mouse hippocampus during 24 h of ischemia-reperfusion. To select stable genes, we applied the restricted criterion of a 1.5-fold change in expression level as the threshold. By adding statistical analysis with this criterion, we identified 10 genes as candidates for control genes from the GeneChip data. In this criterion, GAPDH and beta-actin genes were not included in the 10 genes as candidates for control genes. The present findings might be relevant to the use of control genes in quantitation of RNA, particularly in the study of mouse transient forebrain ischemia.
The use of nuclear energy to generate electric power is crucial to meet the high energy demand of a modern economy. In newly constructed nuclear power plants (NPPs), the trend among control systems is to replace the obsolete analog hard-wired systems with the contemporary digital and cyber-based systems. Therefore, cyberphysical security as well as dependability are critical issues in safety critical NPPs. In this paper, we present different levels/layers of protection to manage cyber/physical security. We also discuss the interrelationship between cyber and physical attacks. We adopt generalized stochastic Petri nets to quantitatively evaluate the intrusion probability. We then propose a new cyberframework and show that the proposed framework not only prevents cyberattacks but also conforms to cybersecurity regulations. We also propose a physical framework to prevent potential physical attacks. Finally, we discuss dependability through three metrics, i.e., reliability, maintainability, and availability. A case study is presented to demonstrate that the proposed cyberframework is highly dependable through analyzing steady-state probabilities.
Home energy management system (HEMS) is essential for residential electricity consumers to participate actively in demand response (DR) programs. Dynamic pricing schemes are not sufficiently effective for end-users without utilizing a HEMS for consumption management. In this paper, an intelligent HEMS algorithm is proposed to schedule the consumption of controllable appliances in a smart household. Electric vehicle (EV) and electric water heater (EWH) are incorporated in the HEMS. They are controllable appliances with storage capability. EVs are flexible energy-intensive loads, which can provide advantages of a dispatchable source. It is expected that the penetration of EVs will grow considerably in future. This algorithm is designed for a smart household with a rooftop photovoltaic (PV) system integrated with an energy storage system (ESS). Simulation results are presented under different pricing and DR programs to demonstrate the application of the HEMS and to verify its' effectiveness. Case studies are conducted using real measurements. They consider the household load, the rooftop PV generation forecast and the built-in parameters of controllable appliances as inputs. The results exhibit that the daily household energy cost reduces 29.5%-31.5% by using the proposed optimization-based algorithm in the HEMS instead of a simple rule-based algorithm under different pricing schemes. (C) 2017 Elsevier B.V. All rights reserved.
The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.
A simple, convenient, easy-to-use, and low-cost platform for rapid molecular detection of H1N1 virus is designed and implemented based on convective polymerase chain reaction (CPCR) and dipstick assay at the point of care (POC) settings. A fully disposable chemically-heated thermal processor is developed to heat the capillary tube from the bottom at a fixed temperature for amplification without the need for electrical power. Amplification is achieved when reagents in the capillary tube are spontaneously and repeatedly transported through different temperature zones, which significantly shortens the amplification time by eliminating the need for controlled time-domain temperature cycling. A rapid one-step nucleic acid dipstick assay is adopted to facilitate the detection of amplification products with the eye instead of instrumentation. The utility of our POC diagnostic system was demonstrated by detecting H1N1 virus with sensitivity of 1.0 TCID50/mL within 35 min. The developed system is particularly desired for resource poor settings, for example, developing countries, outside centralized laboratories, doctor's offices and homes, to relieve the requirements for laboratory facilities and trained personnel. (C) 2016 Elsevier B.V. All rights reserved.
In this paper, a parallel structure fractional repetitive control (RC) scheme is proposed to improve the performance of pulsewidth-modulation (PWM) inverters in fractional cases where the sampling rate of the digital control system is not an integral multiple of the fundamental frequency. By introducing a correction factor, the new control scheme increases the control gains for all harmonics and locates poles accurately at targeted harmonic frequencies. As a result, the proposed control scheme achieves better tracking and rejection performance than conventional RC. Moreover, the parallel structure fractional repetitive controller requires less data memory. Dynamic response is also improved. The stability and convergence of this method are proved. Experimental results on a single-phase PWM inverter illustrate the advantages of this control scheme.
Entomopathogenic fungi play a pivotal role in the regulation of insect populations in nature, and representative species have been developed as promising environmentally friendly mycoinsecticides. Recent advances in the genome biology of insect pathogenic fungi have revealed genomic features associated with fungal adaptation to insect hosts and different host ranges, as well as the evolutionary relationships between insect and noninsect pathogens. By using species in the Beauveria and Metarhizium genera as models, molecular biology studies have revealed the genes that function in fungus-insect interactions and thereby contribute to fungal virulence. Taken together with efforts toward genetic improvement of fungal virulence and stress resistance, knowledge of entomopathogenic fungi will potentiate cost-effective applications of mycoinsecticides for pest control in the field. Relative to our advanced insights into the mechanisms of fungal pathogenesis in plants and humans, future studies will be necessary to unravel the gene-for-gene relationships in fungus-insect interactive models.
The cement production process is energy intensive both in terms of the thermal energy (firing the kiln, drying and De carbonation) and electrical energy for driving the numerous drives within the process line. The average specific power consumption of the case study plant was 111kWh/ton of cement with an average peak demand of 9.7MW. The high cost of electric power at 0.14USD/kWh results in very high cost of production that significantly lowers the company's profit margin and limits its competitive advantage. The generation of electrical power from waste heat recovery would reduce the electricity power bill through partially substituting the power procured from the national grid. This research evaluated the potential that the plant has for generating electrical power from the hot waste gases vented into the atmosphere and it was found that the plant has the potential to generate 3.4MWh of electrical power. This results to a net potential to generate 2.89MWh of electrical power after factoring in the auxiliary power consumption by Waste heat recovery plant system at 15%. This ultimately gave a reduction of 33% in the electricity power bill of the case study plant. The paper recommends the installation of a steam rankine cycle for the power generating plant. In this work the authors designed the steam boilers for the waste heat recovery plant for conversion of thermal energy to electrical energy, selected a commercial steam turbine and evaluated its economic feasibility and established that the designed plant would have a simple payback period of 2.7years.
This paper presents the Local Vector Control ( LVC) algorithm that is applicable to power electronic systems. This controller does not differentiate between linear or non-linear systems and can operate, without change, in stationary or rotating reference frames. The performance of this current controller with particular emphasis on current clamp minimisation will be the paper's focus. A comparison between the LVC, PI and predictive dead- beat current controllers ( PCC) is presented.
This paper presents a digital Active Gate Drive (AGD) methodology for power semiconductor devices. The inherent latency limitation of digital signal processing systems is addressed by a sequential optimization procedure that uses voltage and current signals recorded at the previous switching edge to develop an optimized gate drive waveform for the next switching edge. Experimental results using a half-bridge circuit operating at 180 V/100 A show that the proposed scheme is capable of minimizing switching losses whilst constraining the overvoltage peaks occurring at turn-on and turn-off to as low as 200 V and 300 V respectively.
Demand response (DR) is a recent effort to improve the efficiency of the electricity market and the stability of the power system. A successful implementation relies on both appropriate policy design and enabling technology. This paper presents a multiagent system to evaluate optimal residential DR implementation in a distribution network, in which the main stakeholders are modeled by heterogeneous home agents (HAs) and a retailer agent (RA). The HA is able to predict and control electricity load demand. A real-time price prediction model is developed for the HA and the RA. The optimal control of electricity consumption is formulated into a convex programming problem to minimize electricity payment and waiting time under real-time pricing. Simulation results show that the peak-to-average power ratio and electricity payments are significantly reduced using the proposed algorithms. The HA, with the proposed optimal control algorithms, can be embedded into a home energy management system to make intelligent decisions on behalf of homeowners responding to DR policies. The proposed agent system can be utilized to evaluate various strategies and emerging technologies that enable the implementation of DR.
This study investigated interactive exchange in lovers and the associated interpersonal brain synchronization (IBS) using functional near-infrared spectroscopy (fNIRS)-based hyperscanning. Three types of female-male dyads, lovers, friends, and strangers, performed a cooperation task during which brain activity was recorded in right frontoparietal regions. We measured better cooperative behavior in lover dyads compared with friend and stranger dyads. Lover dyads demonstrated increased IBS in right superior frontal cortex, which also covaried with their task performance. Granger causality analyses in lover dyads revealed stronger directional synchronization from females to males than from males to females, suggesting different roles for females and males during cooperation. Our study refines the theoretical explanation of romantic interaction between lovers. Hum Brain Mapp 38:831-841, 2017. (c) 2016 Wiley Periodicals, Inc.
Cooperative behavior is widespread among animals, yet the neural mechanisms have not been studied in detail. We examined cooperative territory defense behavior and associated neural activity in candidate forebrain regions in the cichlid fish, Astatotilapia burtoni. We find that a territorial male neighbor will engage in territory defense dependent on the perceived threat of the intruder. The resident male, on the other hand, engages in defense based on the size and behavior of his partner, the neighbor. In the neighbor, we find that an index of engagement correlates with neural activity in the putative homolog of the mammalian basolateral amygdala and in the preoptic area, as well as in preoptic dopaminergic neurons. In the resident, neighbor behavior is correlated with neural activity in the homolog of the mammalian hippocampus. Overall, we find distinct neural activity patterns between the neighbor and the resident, suggesting that an individual perceives and processes an intruder challenge differently during cooperative territory defense depending on its own behavioral role. (C) 2017 Elsevier Inc. All rights reserved.
Through a study of agricultural service cooperatives in Russia's Belgorod region, this article addresses two gaps in the literature: first, the dearth of empirical studies on cooperatives in post-socialist Russia; second, the lack of attention to top-down cooperatives in the global literature, and the overly negative approach to the topic in the few extant studies. Whereas state attempts to establish agricultural cooperatives in Russia in a top-down fashion have largely failed, such cooperatives have sprung up widely in Belgorod. The article investigates: (1) what influence the (regional) state exerts on the cooperatives, and how that affects their daily functioning and viability; and (2) to what extent such top-down cooperatives might evolve into less state-led forms, such as classic member-driven or business-like cooperatives.
Although it is well established that rhythmically coordinating with a social partner can increase cooperation, it is as yet unclear when and why intentional coordination has such effects. We distinguish three dimensions along which explanations might vary. First, pro-social effects might require in-phase synchrony or simply coordination. Second, the effects of rhythmic movements on cooperation might be direct or mediated by an intervening variable. Third, the pro-social effects might occur in proportion to the quality of the coordination, or occur once some threshold amount of coordination has occurred. We report an experiment and two follow-ups which sought to identify which classes of models are required to account for the positive effects of coordinated rhythmic movement on cooperation. Across the studies, we found evidence (1) that coordination, and not just synchrony, can have pro-social consequences (so long as the social nature of the task is perceived), (2) that the effects of intentional coordination are direct, not mediated, and (3) that the degree of the coordination did not predict the degree of cooperation. The fact of inter-personal coordination (moving together in time and in a social context) is all that's required for pro-social effects. We suggest that future research should use the kind of carefully controllable experimental task used here to continue to develop explanations for when and why coordination affects pro-social behaviors.
Background: Some COPD patients are more susceptible to exacerbations than others. Mechanisms underlying these differences in susceptibility are not well understood. We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight frequent exacerbators (>= 3 diary-card exacerbations/year) and 16 infrequent exacerbators (< 3 diary-card exacerbations/year). Detailed multi-parameter flow cytometry was used to study differences in innate and adaptive systemic immune function between frequent and infrequently exacerbating COPD patients. Results: The 24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV1 1.43 (0.60) L, 53.3 (18.3)% predicted. PBMCs of frequent exacerbators (FE) contained lower frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035). This observation was also apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 x 10(Lambda)6/mL; IE = 0.25 x 10(Lambda)6/mL; p = 0.035). PBMCs of FE contained a lower frequency of CD8+ T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related) compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007). Conclusion: Differences in the adaptive systemic immune system might associate with exacerbation susceptibility in the `frequent exacerbator' COPD phenotype. These differences include fewer CD4+ T central memory cells and CD8+ T effector memory cells.
Nutrients have been known to have a significant role in maintaining the health of the skeleton, both bone and cartilage. The nutrients that have received the majority of the attention are Vitamin D and calcium. However, limited attention has been directed toward three trace elements that may have mechanistic impact upon the skeletal tissues and could compromise skeletal health resulting from inadequate intakes of copper, iron, and selenium. The role of copper and selenium has been known, but the role of iron has only received recent attention. Copper deficiency is thought to impact bone health by a decrease in lysyl oxidase, a copper-containing enzyme, which facilitates collagen fibril crosslinking. Iron deficiency impact upon bone has only recently been discovered but the exact mechanism on how the deficient states enhance bone pathology is speculative. Selenium deficiency has an impact on cartilage thereby having an indirect impact on bone. However, several studies suggest that a mycotoxin when consumed by humans is the culprit in some cartilage disorders and the presence of selenium could attenuate the pathology. This review summarizes the current knowledge base with respect to skeletal integrity when each of these three trace elements are inadequate in diets of both animals and humans.
Aims: FIP-gsi, a fungal immunomodulatory protein found in Ganoderma sinense, has antitumour, anti-allergy and immunomodulatory activities and is regulated by the fip-gsi gene. In this study, we aimed to express the fip-gsi gene from G. sinense in Coprinopsis cinerea to increase yield of FIPs-gsi. Methods and Results: A fungal expression vector pBfip-gsi containing the gpd promoter from Agaricus bisporus and the fip-gsi gene from the G. sinense was constructed and transformed into C. cinerea. PCR and Southern blotting analysis verified the successful integration of the exogenous gene fip-gsi into the genome of C. cinerea. RT-PCR and Northern blotting analysis confirmed that the fip-gsi gene was transcribed in C. cinerea. The yield of the FIP-gsi protein reached 314 mg kg-1 fresh mycelia. The molecular weight of the FIP-gsi was 13 kDa, and the FIP-gsi was capable of hemagglutinating mouse red blood cells, but no such activity was observed towards human red blood cells in vitro. Conclusions: The fip-gsi from G. sinense has been successfully translated in C. cinerea, and the yield of bioactive FIP-gsi protein was high. Significance and Impact of the Study: This is the first report using the C. cinerea for the heterologous expression of FIP-gsi protein and it might supply a basis for large-scale production of the protein.
Effective and sensitive methods for the molecular detection of Echinococcus multilocularis in faecal samples of final hosts are crucial for the prevention and control of human alveolar echinococcosis and for studies on the epidemiology of the parasite. Little is known about the suitability of commercial test kits for isolating DNA of E. multilocularis from fox faeces and the performance of standard Polymerase Chain Reaction (PCR) protocols in relation to the quality of DNA extracted by these kits. We compared four different kits: ZR Faecal DNA MiniPrep (TM) (Zymo Research), FastDNA (R) SPIN Kit for Soil (MP Biomedicals), QIAamp (R) Fast DNA Stool Mini Kit (QIAGEN) and NucleoSpin (R) Soil Kit (Macherey-Nagel) for the extraction of DNA from E. multilocularis eggs present in faeces of foxes. Negative faecal samples were spiked with 600, 300, 150, 75, 37, 18, 9, 5 or 2 E. multilocularis eggs, and each egg concentration was tested 10 times with each of the DNA extraction kits. Each extracted DNA sample was amplified using three PCR protocols: i. conventional PCR (cPCR, Platinum (R) Taq, Invitrogen), ii. qPCR with the iQ (TM) Supermix (Bio-Rad) and iii. qPCR with the QuantiTect (R) Multiplex -Master Mix (QIAGEN). The highest analytical sensitivities for molecular detection of E. multilocularis eggs in spiked fox faeces were observed when combining either the QIAamp (R) Fast DNA Stool Mini Kit or the ZR Faecal DNA MiniPrep (TM) kit with the qPCR using the QuantiTect (R) Multiplex -Master Mix (Sensitivities 97% and 94%, respectively). Combinations including the remaining test kits (NucleoSpin (R) Soil Kit and FastDNA (R) SPIN Kit for Soil) showed a markedly lower analytical sensitivity for PCR examinations. The results of the present study indicate that it is of utmost importance to select suitable DNA extraction kits in combination with robust PCR methods or reagents to achieve acceptable analytical sensitivity in the molecular detection of E. multilocularis eggs in fox faecal samples. (C) 2017 Elsevier B.V. All rights reserved.
This paper examines the political activity of the Coptic diaspora in the United States in support of the Coptic minority in Egypt. Analysing its strategy reveals that for years it has focused on lobbying the United States and international bodies, in order to raise international awareness of the Coptic minority status. By using this strategy, it has framed the struggle for Copts' rights in a manner that contradicts the Egyptian unity narrative, and the strategic choices of those they are struggling for. This paper shows that understanding the limitations of this strategy alongside a change in the structure of opportunities in Egypt has led to a change in the pattern of activity of the diaspora activists. Alongside lobbying for international involvement, they have developed additional strategies, including strengthening their influence in the homeland and even direct action vis-a-vis the Egyptian authorities. This paper, which emphasises the pattern of action of diaspora activists that represent minorities, directs attention to the structure of opportunities in the homeland, the variety of relationships between the diaspora and the homeland, and their effect on the ability of the diaspora activists to become a significant force in shaping the life of the minority.
Recently early diagnosis of squamous cell carcinoma antigen (SCCA) as a tumor maker of various cancers has increasingly attracted a lot of attention with heightening of incidence rate of cancer. The SCCA with low concentration in human serum should be diluted before detecting. Thus, an immunoassay with high sensitivity is significant for early detecting SCCA. Therefore, a nonenzymatic sandwich-type electrochemical immunosensor herein was conducted to quantitative detection of squamous cell carcinoma antigen (SCCA). The amino functionalized cobaltosic oxide @ ceric dioxide nanocubes with core-shell morphology were prepared to combine sea-urchin like gold @ platinum nanoparticles (Co3O4@CeO2-Au@Pt), and used as labels to conjugate with secondary antibodies for signal amplification. Due to the synergetic effect, excellent electrochemical property and superior auxiliary catalytic activity of Co3O4@CeO2-Au@Pt, high electrocatalytic current responses toward the reduction of hydrogen peroxide (H2O2) were achieved. Besides, the electrodeposited gold nanoparticles (D-Au NPs) which were modified on glassy carbon electrodes (GCE) were used as antibodies carriers and sensing platforms. With the well cooperation of Co3O4@CeO2-Au@Pt and D-Au NPs, a broad linear range from 100 fg/mL to 80 ng/mL with a low detection limit of 33 fg/mL for detecting SCCA was achieved. In addition, the immunosensor displayed with good reproducibility, high selectivity and stability. The results are satisfactory when the proposed method has been applied to analyze human serum samples, indicating that the potential application is promising in clinical monitoring of tumor markers.
Rabbit cells and models are frequently used in pharmacological experiments and toxicity tests and are particularly useful for corneal transplant experiments. Here, we obtained a corneal endothelial cell line from normal rabbit corneal endothelium that had acquired infinite proliferative potential without requiring gene transfer. These infinitely proliferative rabbit corneal endothelial cells (iRCECs) could be cultured for >250 generations and exhibited a greater ability to proliferate than did normal rabbit corneal endothelial cells (RCECs) cultivated by conventional methods. The results of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining analyses revealed that the expression profiles of corneal endothelial markers, such as collagen type VIII1 and Na+/K+-ATPase, were similar to those of RCECs and in vivo corneal endothelium. Scanning electron microscopy showed that many microvilli were present on the surface of the cells and that the ultrastructure was maintained. In addition, we verified that the iRCECs had similar levels of pump function as did RCECs using an Ussing chamber system. The results of a soft agar colony-formation assay suggested that the iRCECs were not tumourigenic. Taken together, our results demonstrated that the iRCECs exhibited gene expression profiles and properties that were equivalent to those of native rabbit corneal endothelium, making these cells useful for corneal endothelial research studies. Copyright (c) 2015 John Wiley & Sons, Ltd.
Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60.53 +/- 8.6 years and 56.55 +/- 7.7 years, respectively (p = 0.000). Anthropometric and demographic data showed BMI values significantly higher among CAD patients and control subjects (26.98 +/- 4.9 vs 24.04 +/- 4.7, p = 0.000). We observed pronounced central obesity in both CAD patients and controls, even at the lowest BMI values (< 23 kg/m(2)). Dyslipidemia was highly prevalent in CAD patients compared to control subjects. Genotypic data showed significantly higher frequency of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No significant difference was observed in the distribution of ID genotypes between CAD patients and control subjects. Logistic regression analysis of data demonstrate that DD genotype was associated with 1.8 fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22-2.66; p = 0.003). The frequency of D allele was significantly higher in CAD patients (p = 0.001). No significant difference was observed in the clinical and biochemical characteristics of CAD patients and controls when the data was stratified according to the genotypes of ACE gene. In conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in Asian Indian population.
Background: Electrocardiographic (ECG) monitored outpatient cardiac rehabilitation (OP-CR) is routinely performed following a variety of cardiovascular procedures and conditions. Objective: The aim of this study is to determine if diagnostic-quality ECG monitoring in patients with coronary artery disease (CAD) during OP-CR is useful in identifying asymptomatic myocardial ischemia, resulting in change(s) in care or medical management. Methods: A retrospective analysis of ECG monitoring was done on all OP-CR patients diagnosed with CAD (n = 1213) from January 2000 through June 2013. Results: Nearly a quarter of the patients (24%; n = 288) displayed at least 1 mm of asymptomatic ST-segment depression at 80 milliseconds after the J-point during at least 1 session of OP-CR. Of these patients, 57% had medical management change(s) compared with 24% for those who did not show ECG changes suggesting ischemia (P < .0001). In patients with asymptomatic ischemia having medical management change(s), 84% resulted directly from OP-CR staff detection. Fewer patients diagnosed with myocardial infarction and coronary artery bypass graft surgery demonstrated ECG signs of ischemia, whereas more patients diagnosed with stable angina and percutaneous coronary interventions demonstrated ECG signs of ischemia. Conclusion: This study demonstrates that most patients with CAD showing asymptomatic ECG signs suggesting ischemia undergo medical management change(s) as a result of the finding. Diagnostic-quality ECG monitoring during OP-CR appears warranted in this population.
Previous research has found patients with the Fc gamma RIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated Fc gamma RIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fc gamma receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating Fc gamma RIIA and inhibitory Fc gamma RIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the Fc.RIIA and Fc.RIIB expression levels, as well as a luciferase assay of Fc gamma RIIA. We found a considerable increase in methylation of both Fc gamma RIIA and Fc gamma RIIB in KD patients undergoing IVIG treatment. Promoter methylation of Fc gamma RIIA inhibited reporter activity in K562 cells using luciferase assay. The Fc gamma RIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. Fc gamma RIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the Fc gamma RIIA/ IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. Fc gamma RIIA and Fc gamma RIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. Fc gamma RIIA expression influenced the IVIG treatment response of KD patients. The Fc gamma RIIA/ IIB mRNA expression ratio was greater in KD patients with CAL formation.
The significant contribution of microbial corrosion to material degradation in industrial environments has been widely investigated, especially in recent years. However, the process remains largely underestimated and, more than ever today, its control is proved to be difficult. Indeed, some recent environmental issues and regulatory led to the reduction of the biocides and anticorrosive treatments, often without an appropriate revision of procedures and without a careful monitoring, thus affecting the effectiveness of the treatments. A multitude of bacterial species lives within the "corrosive" biofilm, where organisms interacts in synergistically or competitive way adapting themselves to external agents, even in extreme conditions. Combining modern electrochemical techniques and molecular biology it is possible today to monitor the biocorrosion risk and to highlight the complexity of the phenomenon. The relevant involvement of specific bacterial strains, including the sulphate reducers and other bacteria of the sulfur cycle, as well as the role of enzymes of the oxidative metabolism has been confirmed by these techniques. These enzymes can be expressed by a vast number of microorganisms, both aerobic and anaerobic, as function of environmental conditions.
The expression of cytochrome P-450 and cytochrome P-450 reductase (CPR) genes in the conterminous biotransformation of corticosteroids and PAHs was studied in Cunninghamella elegans 1785/21Gp. We had previously used this strain as a microbial eucaryotic model for studying the relationship between mammalian steroid hydroxylation and the metabolization of PAHs. We reported that cytochrome P-450 reductase is involved in the biotransformaton of cortexolone and phenanthrene. RT-PCR and Northern blotting analyses indicated that the cytochrome P-450 and CPR genes appear to be inducible by both steroids and PAHs. The expression of the cytochrome P-450 gene was increased ninefold and the expression of the CPR gene increased 6.4-fold in cultures with cortexolone and/or phenanthrene in comparison with controls. We conclude that the increase in cytochrome P-450 gene expression was accompanied by an increase in cytochrome P-450 enzymatic activity levels.
Background: Cognitive empathy is supported by the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. Methods: 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. Results: Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p < 0.05) and impaired cognitive empathy across all measures (all p < 0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p0.10). Conclusions: Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Epileptiform discharges on an isolated cortex are explored using neural field theory. A neural field model of the isolated cortex is used that consists of three neural populations, excitatory, inhibitory, and excitatory bursting. Mechanisms by which an isolated cortex gives rise to seizure-like waveforms thought to underly pathological EEG waveforms on the deafferented cortex are explored. It is shown that the model reproduces similar time series and oscillatory frequencies for paroxysmal discharges when compared with physiological recordings both during acute and chronic deafferentation states. Furthermore, within our model ictal activity arises from perturbations to steady-states very close to the dynamical system's instability boundary; hence, these are distinct from corticothalamic seizures observed in the model for the intact brain which involved limit-cycle dynamics. The results are applied to experiments in deafferented cats.
Secreted phosphoprotein 1 (SPP1, also known as osteopontin) is expressed in large pyramidal neurons in the primary motor cortex (M1) of certain primate species, including macaque monkeys, but not of rodents. Based on this, we suggested that SPP1 expression may reflect the functional or structural specialization of highly developed corticospinal systems. In the present study, we further characterized SPP1 in the human central nervous system by investigating its expression in the primary somatosensory cortex (S1) and spinal cord, in addition to M1. Although a small number of SPP1-positive pyramidal neurons were observed in S1, the number was smaller than that in M1. In the cervical segment of the spinal cord, SPP1 was principally expressed in choline acetyltransferase-positive motor neurons in lamina IX. We also examined SPP1 expression in patients with amyotrophic lateral sclerosis (ALS), a disease characterized by the degeneration of motor neurons. When SPP1 expression was compared in neurons of the same size range, expression in both M1 and the spinal cord of ALS patients was lower than that of subjects without ALS. SPP1 expression was especially reduced in surviving large neurons in both M1 and the spinal cord of ALS patients. The results further support the concept that SPP1 has a role in the specialization of motor projection neurons and suggest that its reduced expression may be implicated in the neurodegeneration seen in ALS.
Virtually nothing is known about glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) gene expression in any avian species. Here we report the cloning of partial cDNAs for chicken GR and MR. These partial cDNAs were used as probes to characterize expression of GR and MR mRNA and to identify the full-length transcripts within the chicken genome. Chicken GR and MR sequences predicted from the genome sequence were compared with those of representatives of other vertebrate classes. GR and MR genes are located on chicken chromosomes 13 and 4, respectively. Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) results indicate that GR and MR are widely expressed in many tissues. Characterization of mRNA levels in the anterior pituitary gland during chick embryonic development by quantitative real time RT-PCR demonstrates decreased MR and increased GR gene expression between embryonic days 12 and 17. Plasma levels of corticosteroids increased during this same period. This is the first study of GR and MR gene expression in any avian species and the first analysis of changes in pituitary MR gene expression during embryonic development of any species. (C) 2006 Elsevier Inc. All rights reserved.
Background: Pregnant victims of childhood maltreatment are more likely to deliver preterm. The mechanisms explaining this relationship are unclear. The goal of the current pilot study was to investigate whether momentary stress and cortisol serve as mechanisms linking maltreatment history to gestational length. Methods: Seventeen women enrolled in the study (35% maltreated). Women completed two study sessions at 27 and 34 weeks gestation. Following each session, at four times/day over two days, women reported their momentary stress levels by text message and provided corresponding salivary cortisol samples. Gestational length was determined by medical chart review. Results: Higher reports of momentary stress were associated with shortened gestational length. High stress predicted lower cortisol concentrations for women with maltreatment histories but higher concentrations among women without maltreatment. Conclusion: Results from this pilot study provide preliminary evidence for understanding mechanisms explaining increased risk for preterm birth among childhood maltreatment victims.
Chronic breathlessness is a common source of psychological and physical stress in patients with advanced or progressive disease, suggesting that hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be prevalent. The aim of this study was to measure the salivary diurnal cortisol profile in patients receiving supportive and palliative care for a range of malignant and non-malignant conditions and to compare the profile of those experiencing moderate-to-severe disability due to breathlessness against that of patients with mild/no breathlessness and that of healthy controls. Saliva samples were collected over two consecutive weekdays at 3, 6, and 12 h after awakening in 49 patients with moderate-to-severe breathlessness [Medical Research Council (MRC) dyspnoea grade >= 3], 11 patients with mild/no breathlessness (MRC dyspnoea grade <= 2), and 50 healthy controls. Measures of breathlessness, stress, anxiety, depression, wellbeing and sleep were examined concomitantly. The diurnal cortisol slope (DCS) was calculated for each participant by regressing log-transformed cortisol values against collection time. Mean DCS was compared across groups using ANCOVA. Individual slopes were categorised into one of four categories: consistent declining, consistent flat, consistent ascending and inconsistent. Controlling for age, gender and socioeconomic status, the mean DCS was significantly flatter in patients with moderate-to-severe breathlessness compared to patients with mild/no breathlessness and healthy controls [F (2,103) = 45.64, p<0.001]. Furthermore, there was a higher prevalence of flat and ascending cortisol profiles in patients with moderate-to-severe breathlessness (23.4%) compared to healthy controls (0%). The only variable which correlated significantly with DCS was MRC dyspnoea grade (rs=0.29, p<0.05). These findings suggest that patients with moderate-to-severe breathlessness have evidence of HPA axis dysregulation and that this dysregulation may be related to the functional disability imposed by breathlessness. (C) 2017 Elsevier Ltd. All rights reserved.
Two genes encoding methionine adenosyltransferase, SAM2 from Saccharomyces cerevisiae and metK from Corynebacterium glutamicum, were individually cloned into pDXW-8, the shuttle vector between Escherichia coli and C. glutamicum, and overexpressed in E. coli DH5 and C. glutamicum ATCC13032. In DH5, both genes were overexpressed and their protein products showed the activity of methionine adenosyltransferase. In ATCC13032, metK was overexpressed, its product MetK showed the enzyme activity and could convert l-methionine to S-adenosyl-l-methionine (SAM). However, when SAM2 was overexpressed in ATCC13032, neither the enzyme activity nor the conversion of SAM from l-methionine was observed. Reverse transcription PCR analysis and SDS-PAGE showed that SAM2 was transcribed but not translated in C. glutamicum. Therefore, SAM2-C, a mutant SAM2, was constructed by codon optimization, and overexpressed in ATCC13032; it was well transcribed and translated, and could convert l-methionine to SAM. Finally, SAM2-C and metK were individually overexpressed in E. coli BL21(DE3), and their products SAM2-C and MetK were purified and characterized. The optimum activity for both enzymes was found at pH 8.5 and 35 degrees C; SAM2-C and MetK have similar K-m for ATP, but quite different K-m for l-methionine. These results suggest that SAM2-C and MetK can be useful for developing C. glutamicum to produce SAM. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
The SWIPE detector of the Ballon Borne Mission LSPE (see e.g. the contribution of P. de Bernardis et al. in this conference) intends to measure the primordial 'B-mode' polarization of the Cosmic Microwave Background (CMB). For this scope microwave telescopes need sensitive cryogenic bolometers with an overall equivalent noise temperature in the nK range. The detector is a spiderweb bolometer based on transition edge sensor and followed by a SQUID to perform the signal readout. This contribution will concentrate on the design, description and first tests on the front-end electronics which processes the squid output (and controls it). The squid output is first amplified by a very low noise preamplifier based on a discrete JFET input differential architecture followed by a low noise CMOS operational amplifier. Equivalent input noise density is 0.6 nV/Hz and bandwidth extends up to at least 2 MHz. Both devices (JFET and CMOS amplifier) have been tested at liquid nitrogen. The second part of the contribution will discuss design and results of the control electronics, both the flux locked loop for the squid and the slow control chain to monitor and set up the system will be reviewed. The digital interface to the control computer will be presented.
Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community.
Internal energy reserves of animals are limited, and the current investment in reproduction often decreases survival or future reproductive success. Some studies showed that copulatory activities impair the strength of immune function in insects, while the recent evidence is contradictory. In this study we tested whether copulatory activity affects the rate of encapsulation response in males of Calopteryx splendens damselfly in allopatric populations, and in sympatric populations where C. splendens stay together with their superior competitor C. virgo. We also counted the number of eugregarines, which are common parasites of damselflies. Copulation activity did not affect the immunity of C. splendens males in allopatric populations. In sympatric populations C. splendens males had more gut parasites, and we found a significant interaction between parasite number and copulatory activity on the rate of encapsulation. Our results suggest that the costs of reproduction are higher in infected males, which may affect reproductive investment and sexual selection.
Households in the USA state of Oklahoma serviced by investor owned electric utilities that have smart meters may select to be charged based on either a traditional meter rate schedule, a smart meter schedule, or they may install a household grid-tied wind turbine and be subject to a different rate schedule. The objective of the research was to determine the economic consequences of installing microgeneration grid-tied wind turbine systems (6 kW; 10 kW) given alternative pricing structures for households at five unique locations with different wind resources. Twenty years of hourly wind speed data, and hourly electricity use data for representative households, were obtained for each location. The annual household electricity cost among the five locations ranged from $894 to $1199 for the smart meter rates and $870-$1191 for the traditional meter rates. The estimated annual cost of $5389 for the least costly household grid-tied 6 kW wind turbine system, is five times greater than the annual cost of purchasing from the grid. If external consequences of electricity generation and distribution are ignored, given current and proposed rate structures and prices, household wind turbine electricity generation systems are not economically competitive in the region. (C) 2017 Elsevier Ltd. All rights reserved.
The absence of markers of inflammation in the cerebrospinal fluid (CSF) commonly predicts the absence of herpes simplex virus (HSV) central nervous system (CNS) infection. Consequently, multiple authors have proposed and validated criteria for deferring HSV PCR testing of CSF in immunocompetent hosts with normal CSF white blood cell and protein levels (<= 5 cells/mm(3) and= 2 years old and have not had HIV or an organ transplant. Adoption of the criteria may erroneously exclude HSV-infected persons from a necessary diagnostic test or, alternatively, reduce the costs associated with HSV tests with minimal to no effect on patient care. Little is known about the cost-effectiveness of this approach. A decision analysis model was developed to evaluate the adoption of criteria for screening HSV tests of CSF. Estimates of input parameter values combined available literature with a multiyear multisite review at two of the largest health care systems in the United States. Adoption of criteria to screen for HSV test need proved cost-effective when less than 1 in 200 patients deferred from testing truly had an HSV CNS infection. Similar to prior studies, none of the deferred cases had HSV encephalitis (n = 3120). Adoption of these criteria in the United States would save an estimated $127 million ($ 95 million to $158 million [+/- 25%]) annually. The model calculations remained robust to variation in test cost, prevalence of HSV infection, and random variation to study assumptions. The adoption of criteria to screen HSV PCR tests in CSF represents a cost-effective approach.
Renewable energies have great potential to contribute to CO2 emissions reductions by substituting for fossil fuels. This study examines whether renewable energies with learning-by-doing technical change can compete with forest carbon sequestration to cost-efficiently achieve the EU carbon target for 2050. Cost-efficient abatement solutions are obtained using a dynamic optimisation model that accounts for three kinds of mitigation options: renewable energies and abatement in the forest and fossil fuel sectors. The results show a net present cost of reaching the target of approximately 225 billion Euros and a carbon price of 306 Euro/ton CO2 in 2050. Furthermore, the stock of renewables in 2050 can deliver almost twice as much as the current electricity production from renewables, which implies a contribution of 8.2% to meeting the emissions target. However, the average cost per unit emissions reduction is more than twice as high for renewables as for forest carbon sequestration. Hence, the results indicate that renewables are unable to compete with forest carbon sequestration unless they receive continued government support. (C) 2017 Elsevier Ltd. All rights reserved.
Salinity is one of the major environmental factors limiting plant growth and productivity. An H+-PPase gene, TsVP from Thellungiella halophila, was transferred into cotton (Gossypium hirsutum) in sense and antisense orientations under control of the cauliflower mosaic virus (CaMV) 35S promoter. Southern and Northern blotting analysis showed that the sense or antisense TsVP were integrated into the cotton genome and expressed. Transgenic plants overexpressing the vacuolar H+-PPase were much more resistant to 150 and 250 mM NaCl than the isogenic wild-type plants. In contrast, the plants from the antisense line (L2), with lower H+-PPase activity, were more sensitive to salinity than the wild-type plants. Overexpressing TsVP in cotton improved shoot and root growth and photosynthetic performance. These transgenic plants accumulated more Na+, K+, Ca2+, Cl- and soluble sugars in their root and leaf tissues under salinity conditions compared with the wild-type plants. The lower membrane ion leakage and malondialdehyde (MDA) level in these transgenic plants suggest that overexpression of H+-PPase causes the accumulation of Na+ and Cl- in vacuoles instead of in the cytoplasm, thus reducing their toxic effects. On the other hand, the increased accumulation of ions and sugars decreases the solute potential in cells, and facilitates water uptake under salinity, which is an important mechanism for the increased salt tolerance in TsVP-overexpressing cotton.
An increasing number of microRNAs (miRNAs) have been shown to play crucial regulatory roles in the process of plant development. Here, we used high-throughput sequencing combined with computational analysis to characterize miRNAomes from the ovules of wild-type upland cotton and a fiberless mutant during fiber initiation. Comparative miRNAome analysis combined with northern blotting and RACE-PCR revealed seven fiber initiation-related miRNAs expressed in cotton ovules and experimentally validated targets of these miRNAs are involved in different cellular responses and metabolic processes, including transcriptional regulation, auxin and gibberellin signal transduction, actin bundles, and lignin biosynthesis. This paper describes a complex regulatory network consisting of these miRNAs expressed in cotton ovules to coordinate fiber initiation responses. In addition, 36 novel miRNAs and two conserved miRNAs were newly identified, nearly doubling the number of known cotton miRNA families to a total of 78. Furthermore, a chromatin remodeling complex subunit and a pre-mRNA splicing factor are shown for the first time to be miRNA targets. To our knowledge, this study is the first systematic investigation of fiber initiation-related miRNAs and their targets in the developing cotton ovule, deepening our understanding of the important regulatory functions of miRNAs in cotton fiber initiation.
Arabinogalactan proteins (AGPs) are a large family of highly glycosylated of hydroxyproline-rich glycoproteins that play important roles in plant growth, development, and signal transduction. A cDNA encoding a putative classical AGP named GhH6L was isolated from cotton fiber cDNA libraries, and the deduced protein contains 17 copies of repetitive motif of X-Y-proline-proline-proline (where X is serine or alanine and Y is threonine or serine). Northern blotting analysis and quantitative RT-PCR results showed that it was preferentially expressed in 10 days post-anthesis (dpa) fibers and was also developmentally regulated. A promoter fragment was isolated from cotton (Gossypium hirsutum) by genome walking PCR. Expression of beta-glucuronidase (GUS) gene under the GhH6L promoter was examined in the transgenic Arabidopsis plants; only petiole and pedicel were stained, no staining was detected in other tissues. Subcellular localization indicated that GhH6L was localized to the plasma membrane and in the cytoplasm. These data further our understanding of GhH6L as well as shed light on functional insight to GhH6L in cotton.
Enzymatic treatments have gained recognition in textile industry because they are stereo specific, nontoxic, environment friendly and energy conserving alternatives. Enzymes are virtually applicable to all manufacturing steps of textile chemical processing. Amylases for textile desizing; cellulases employed for bio-polishing & denim washing; proteases for wool modifications are important to mention in this category. However in spite of lot potentials, enzymes have limited industrial acceptance due to extreme pH and temperature conditions employed in textile processing leading to their reduced properties and action. Advances in enzymology and molecular biology provide possibilities for new enzymes identification and modifications in existing enzymes as well as in enzyme-based processes suitable/to fit for environment friendly option. Enzyme immobilization is one such approach which stabilizes enzymes, extends useful life and improves action in some cases too. Additionally, recyclability & reuse of enzymes make process even more economical. This review summarizes the potential research involved in the development of enzymatic processing in textile chemical processing. The paper highlights the significance and limitations of native enzymes as well as immobilized enzymes applications in textile chemical industry. (C) 2017 Elsevier Ltd. All rights reserved.
Cotton is a stubborn plant for genomic DNA isolation due to its high-level of polyphenolics, polysaccharides and secondary metabolites. Genomics and molecular biology studies require high quality and large quantity of DNA. We have standardized an efficient miniprep protocol for cotton genomic DNA isolation, which not only provides higher yield from 800 to 1400 lg of DNA from 200 to 300 mg of fresh leaf tissue but also provide excellent purity. The DNA is amenable to all elementary enzymatic preparations, PCR techniques, Southern blotting and to high end genomic studies. The technique does not require liquid nitrogen, needs small amount of sample, less time, fewer chemicals and one can process up to 100 samples per day. The genomic DNA extracted was good for transgenic event characterization and marker assisted selection.
Understanding pathogenic variation in plant pathogen populations is key for the development and use of host resistance for managing verticillium wilt diseases. A highly virulent defoliating (D) pathotype in Verticillium dahliae has previously been shown to occur only in one clonal lineage (lineage 1A). By contrast, no clear association has yet been shown for race 1 with clonal lineages. Race 1 carries the effector gene Ave1 and is avirulent on hosts that carry resistance gene Ve1 or its homologues. The hypothesis tested was that race 1 arose once in a single clonal lineage, which might be expected if V. dahliae acquired Ave1 by horizontal gene transfer from plants, as hypothesized previously. In a diverse sample of 195 V. dahliae isolates from nine clonal lineages, all race 1 isolates were present only in lineage 2A. Conversely, all lineage 2A isolates displayed the race 1 phenotype. Moreover, 900-bp nucleotide sequences from Ave1 were identical among 27 lineage 2A isolates and identical to sequences from other V. dahliae race 1 isolates in GenBank. The finding of race 1 in a single clonal lineage, with identical Ave1 sequences, is consistent with the hypothesis that race 1 arose once in V. dahliae. Molecular markers and virulence assays also confirmed the well-established finding that the D pathotype is found only in lineage 1A. Pathogenicity assays indicated that cotton and olive isolates of the D pathotype (lineage 1A) were highly virulent on cotton and olive, but had low virulence on tomato.
Until the banking reform in 1936, banks and industrial companies in Italy were strongly intertwined (both in terms of ownership and interlocking directorates). Using Imita.db-a large dataset containing data on over 300,000 directors of Italian joint-stock companies-this paper analyzes what would have happened to the Italian corporate network in the years 1913, 1921, 1927 and 1936 if the German-type universal banks and their directors would have not been there. Our test shows that new centers of the system would have emerged (financial, electricity, and phone companies), confirming the interconnected nature of the Italian capitalism. We also analyze two industries (textiles and iron and steel) characterized by different labor-to-capital intensities to check for sectoral differences. Contrary to conventional wisdom, we find that local banks were important in funding both industries.
This paper explores the proposal that there is a close link between counterfactual thinking and lying. Both require the imagination of alternatives to reality and we describe four studies which explore this link. In Study 1 we measured individual differences in both abilities and found that individuals with a tendency to generate counterfactual thoughts were also more likely to generate potential lies. Studies 2 and 3 showed that counterfactual availability influences people's ability to come up with lies and the extent to which they expect others to lie. Study 4 used a behaviotiral measure of deception to show that people tend to lie more in situations also known to elicit counterfactual thoughts. Overall, the results show that the imagination of alternatives to the past plays an important role in the generation of lies. We discuss the implications for the fields of counterfactual thinking and deception. (C) 2017 Elsevier B.V. All rights reserved.
Holographic algorithms, alternatively known as Pfaffian circuits, have received much attention for giving polynomial-time algorithms to a subset of problems in #P. Much work has been done determining the power of this machinery. One intriguing aspect is that these circuits must be planar. We investigate relaxations of this planarity condition. We show that an approach using orbit closures does not work, but give a different technique that allows one SWAP gate to be used in a Pfaffian circuit given suitable bases and restricted types of graphs. This is done by exploiting the fact that Pfaffian gates lie in a hyperplane. (C) 2016 Elsevier Inc. All rights reserved.
This article focuses on the design and investigation of a pair of unequally sized wireless electricity (Witricity) devices that are equipped with integrated planar coil strips. The proposed pair of devices consists of two different square-shaped resonator sizes of 120 mm x 120 mm and 80 mm x 80 mm, acting as a transmitter and receiver, respectively. The devices are designed, simulated and optimized using the CST Microwave Studio software prior to being fabricated and verified using a vector network analyzer (VNA). The surface current results of the coupled devices indicate a good current density at 10 mm to 30 mm distance range. This good current density demonstrates that the coupled devices' surface has more electric current per unit area, which leads to a good performance up to 30 mm range. Hence, the results also reveal good coupling efficiency between the coupled devices, which is approximately 54.5 % at up to a 30 mm distance, with both devices axially aligned. In addition, a coupling efficiency of 50 % is achieved when a maximum lateral misalignment (LM) of 10 mm, and a varied angular misalignment (AM) from 0 degrees to 40 degrees are implemented to the proposed device.
A battery-free, wireless neural probe system was developed for reading neural signals in the brain by using a one-port surface acoustic wave (SAW) reflective delay line, neural firing-dependent varicap diode, two antennas, and a network analyzer as measurement unit. The one-port SAW reflective delay line replaces existing complex wireless transceiver system composed of similar to 5000 electronic components and makes battery-free, wireless measurements possible. The varicap diode interconnected with sharp metal shank via operational amplifier (op-amp) was electrically linked to the corresponding split-type reflectors on a one-port SAW reflective delay line. A 4.3 nH inductor was also placed in between the split-type reflector on one-port SAW reflective delay line and varicap diode to obtain a large linearity and high sensitivity through impedance matching effect. As electrical pulses imitating neural signals were applied to the sharp metal shanks, overall impedance perturbations between the split-type reflector and external varicap diode under reverse bias were observed, giving rise to amplitude changes in the reflection peaks in the time domain depending on the magnitude of the electrical pulses. Good linearity and sensitivity were observed at the amplitude variations in terms of electrical pulses. Coupling-of-modes (COM) modeling and impedance matching simulations were also performed to predict device performances and compare experimental results. (C) 2014 Elsevier B.V. All rights reserved.
Integration of research experience into classroom is an important and vital experience for all undergraduates. These course-based undergraduate research experiences (CUREs) have grown from independent instructor lead projects to large consortium driven experiences. The impact and importance of CUREs on students at all levels in biochemistry was the focus of a National Science Foundation funded think tank. The state of biochemistry CUREs and suggestions for moving biochemistry forward as well as a practical guide (supplementary material) are reported here. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):7-12, 2017.
This article describes a court improvement initiative designed to promote uniformity and improved court practice with the ultimate goal of the improvement of outcomes for children and families. The article focuses on the results of interviews and focus groups conducted as part of the evaluation of this initiative. Twelve jurisdictions were purposively selected to exhibit a range of family court and non-family court jurisdictions in rural and middle-sized locations. The discussion of the qualitative results focuses on changes in court practice and the impact of the initiative on case time. Key Points for the Family Court Community: This initiative was undertaken to promote consistency of practice in family law matters. We explain how the rules impact the following areas: divorce; property distribution as a result of divorce; custody, visitation, and child support; adoption; termination of parental rights; domestic violence, child abuse, and neglect; and status offenses. We describe the impact of a state-wide court improvement initiative. We identify areas of improvement within court operations that may be modified in other jurisdictions.
Q fever is a worldwide zoonotic infection caused by the obligate intracellular bacterium Coxiella burnetii that can course with acute or chronic disease. This series describes 7 cases of acute Q fever admitted in a Portuguese University Hospital between 2014 and 2015. All cases presented with hepatitis and had epidemiological history. Diagnosis was done by PCR on majority (5) and by serology and PCR in only 2. Serological tests can be negative in the initial period of the disease. Molecular biology methods by polymerase chain-reaction are extremely important in acute disease, allowing timely diagnosis and treatment. (C) 2016 The Authors.
Increasingly, anthropogenic perturbations of the biosphere manifest in a broad array of global phenomena, causing widespread contamination of most ecosystems, with high dispersion rates of many contaminants throughout different environmental compartments, including metals. Chromium (Cr) contamination in particular, is, increasingly, posing a serious threat to the environment, emerging as a major health hazard to the biota. However, although the molecular and physiological mechanisms of plant responses to many heavy metals, especially lead (Pb) and cadmium (Cd), have been focused upon in recent years, chromium has attracted significantly less attention. In this context, this review discusses aspects of Cr uptake and transport, some physiological and biochemical effects of Cr exposure in plants, and molecular defense mechanisms against this metal. Recent advances in determining these responses, in fields of knowledge such as genomics, proteomics and metallomics, are discussed herein.
As a precursor of the major yolk protein vitellin (Vn), vitellogenin (Vg) has been studied in crustacean for decades, mainly in shrimp. However, little is known about the Vg molecule in crabs. In the present study, we report a cDNA encoding Vg in the marine crab Portunus trituberculatus, an important commercial species in aquaculture. The cDNA sequence is 7846 bp in length, containing a 7680 bp open reading frame, that encodes 2560 amino acid residues. The deduced amino acid sequence showed 32-75% identity with other known crustacean Vgs. Seven potential cleavage sites (RXXR) were identified in the deduced Vg precursor. SDS-PAGE and Westem blotting analysis demonstrated that Vns in the ovary of the mature crab consisted of three major polypeptides (102, 100 and 85 kDa). Northern blotting analysis revealed that Vg was mainly expressed in hepatopancreas in vitellogensis females. A Vg transcript was also identified in the ovary of the crab by reverse transcription-polymerase chain reaction analysis. (c) 2005 Elsevier Inc. All fights reserved.
Culture-based pathogen identification in skull base osteomyelitis, particularly for fungi, is often inaccurate. We report the case of patient with fungal skull base osteomyelitis cured by sustained antifungal therapy after 16 months of debilitating illness. Due to medical complications, a strong clinical rationale was needed to justify long-term antifungal therapy. The offending fungus was identified by experimental molecular technology (Ibis T5000 universal biosensor); invasive fungal disease was corroborated by biochemical assays. Our discussion will help familiarize the otolaryngologist with existing biochemical and molecular diagnostics for invasive fungal disease. We encourage future investigators to study their application in cases of skull base osteomyelitis.
The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.
The eastern oyster Crassostrea virginica once supported one of the largest fisheries in the eastern United States. Oyster populations and the reefs they form have suffered chronic long-term decline throughout the species' range, including in northwest Florida's Pensacola Bay estuary system (PBS). To guide efforts to rebuild oyster populations in the PBS, connectivity patterns were evaluated among historic and extant reef locations using an integrated biophysical numerical model. Water quality parameters and oyster recruitment were monitored in May 2007 and then monthly from July 2007 through July 2008. Resultant salinity data were used to calibrate an Estuarine Coastal Ocean Model-based numerical circulation model of Pensacola Bay, which was then coupled to an existing, individual-based, oyster larvae routine to predict ontogenetic larval distribution. Three-dimensional Lagrangian transport algorithms were used to simulate transport of modeled larvae during four 20-day time periods during those summer and autumn months when oyster recruitment was empirically recorded in the bay. Based on outcomes from contemporaneous sampling of oyster larvae, the model was shown to represent the salient features of oyster larval distribution in Pensacola Bay. There were, however, instances of incongruity between modeled and sampled outcomes, indicating that model outcomes not validated with field data must be interpreted with caution. Larval supply was highly variable and spatially complex, but potentially limiting to successful recruitment and reef replenishment. Larval transfer rates within and among previously identified oyster reefs in Pensacola Bay were determined and were used to predict optimal oyster reef restoration or rehabilitation sites. Finally, larval exports from the bay were estimated and considered within the context of larval exchange among north Florida estuaries and potential repercussions to the long-term health of the Gulf of Mexico oyster metapopulation.
Background: Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. Methods: We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. Results: CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). Conclusions: In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and post traumatic stress pathology. (C) 2017 The Authors. Published by Elsevier Ltd.
The study aimed to generate a mouse line with green fluorescent protein (GFP) specifically expressed in male germ cells to assess testicular toxicity. The mouse line with GFP specifically expressed in male germ cells was generated by mating a germ cell-specific transgenic Cre male mouse with a double-fluorescent reporter female mouse using Cre/loxP. The mouse line was administered ethylene glycol monomethyl ether (EGME) by oral gavage. Then, the green fluorescence intensity in the testes was used as an indicator to examine the potential for testicular toxicity testing by molecular biology, histopathology, and in vivo imaging techniques. Specific testicular GFP expression was observed in mice. GFP was mainly expressed in the germ cell lineage and concentrated in secondary spermatocytes/spermatocytes and spermatozoa. After administration of EGME, at the organ level, the green fluorescent intensity of the testes was decreased by 11 days and had disappeared by 34 days. Frozen testicular sections stained with DAPI showed significantly decreased green fluorescence in secondary spermatocytes and sperm cells. These observations were consistent with the testis weight and results of testicular histopathology. With the application of in vivo imaging becoming popular, this mouse line with GFP specifically expressed in the male germ cells may have some advantages for the study of reproductive toxicity.
Inadequate regulation of spatial development is at the origin of the current global crisis and increases, in years of crisis, the unequal distribution of wealth. The importance of the related risks for democracy draw attention to the systems of spatial governance and planning, through which States regulate spatial development. In Europe, the countries most affected by the unequal effects of the crisis have spatial planning systems that are traditionally based on the preventive assignation of rights for land use and development through a plan. The systems of other countries had established beforehand that new rights for land use and for spatial development are rather assigned only after the public control of development projects and their distributional effects. Despite the evidence that some models can operate better than others in ensuring public government of spatial development, the improvement of spatial planning systems is, however, limited by their complex nature of institutional technologies'. Especially in a context of crisis, planners are responsible for the increase in public awareness concerning the role of spatial governance in economic and social life.
Research on fungal pathogens with the aim to identify virulence determinants strictly relies on the generation of defined, recombinant strains, a task that is executed by means of a sophisticated molecular biology toolbox. Recent developments in fungal genome engineering have opened a new frontier by implementing the CRISPR-Cas9 technology, based on expression of the Cas9 endonuclease that is loaded by a single guiding RNA (sgRNA) molecule to target a defined site in the recipient genome. This novel approach has been adapted successfully to engineer fungal genomes, among them the one of the human-pathogenic mould Aspergillus fumigatus. Implementation of the required components was achieved by various means that differ with respect to expression of the Cas9 enzyme and sgRNA delivery. Validation of CRISPR-Cas9-mediated mutagenesis could be executed by targeting selected candidate genes of A. fumigatus to provide a promising perspective for screening and multiplexing approaches to scrutinize the virulome of this opportunistic fungal pathogen in a comprehensive manner, such as by analyzing genetic polymorphisms or the function of gene families.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function. More recently, this technology has been increasingly applied to the study or treatment of human diseases, including Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, beta-Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9) genome editing has been used to correct disease-causing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome (AIDS) or promoting anti-tumor immunotherapy. Furthermore, this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials, including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has been teamed with induced pluripotent stem (iPS) cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation. This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases. Copyright (C) 2016, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions. In particular, we focus on the role of mass spectrometry in integrated structural and molecular biology investigations of biological macromolecular complexes and cellular machineries, highlighting work on CRISPR-Cas systems and eukaryotic transcription complexes.
In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and -quartz (Min-U-Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2-deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells. For instance, two-dimensional gel electrophoresis data indicated that the expression of proteins in the cell death (e.g., ALDH1A1, HTRA2 and PRDX6) and cell proliferation (e.g., FSCN1, HNRNPAB and PGK1) pathways were significantly different between the two silica particles. Reverse transcription-polymerase chain reaction data provided additional evidence supporting the proteomic findings. Preliminary assessment of the physical differences between CR and MI suggested that the extent of surface interaction between particles and cells could explain some of the observed biological effects. However, the differential dose-response curves for some other genes and proteins suggest that other physical attributes of particulate matter can also contribute to particulate matter-related cellular toxicity. Our results demonstrated that toxicoproteomic and gene expression analyses are sensitive in distinguishing subtle toxicity differences associated with silica particles of varying physical properties compared to traditional cytotoxicity endpoints. Copyright (c) 2016 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
The traditional critical conduction mode (CRM) flyback PFC converter with constant on-time control strategy usually suffers low power factor (PF) and high total harmonic distortion (THD) due to the nonsinusoidal input current waveform. In order to solve this problem, an improved variable on-time control strategy for the CRM flyback PFC converter is proposed in this letter. A simple analog divider circuit consisting of an operational amplifier, two signal switches, and an RC filter is proposed to modulate the turn-on time of the primary switch, and the PF and THD of the CRM flyback PFC converter can be evidently improved. The theoretical analysis is presented and the experiment results verify the advantages of the proposed control scheme.
Actuated by spatial universal rotating magnetic vector through digital control, the steering navigation of the spiral-type capsule robot in the gastrointestinal (GI) tract becomes possible. However, as a potential risk, the fluid resistance torsion moment generated by the rotating spiral-type capsule robot would distort the GI tract with insufficient fluid. It is difficult to investigate the fluid distorting effect on the GI tract, because online measurement of the fluid resistance torsion moment still remains unsolved. In this paper, an innovative method employing critical coupling magnetic moment for indirectly detecting the fluid resistance torsion moment is proposed. To reduce fluid distorting effect, a petal-shaped capsule robot, whose surface is composed of four petal-shaped tiles, is proposed, and fluid resistance torsion moment-weaken effect of the petal-shaped capsule robot is discovered and investigated, which happens to the fluid when it travels through a convergent wedge-like gap between the surface of each of the four petal-shaped tiles and the inner pipe wall. Simulations and experiments have demonstrated that the twist impact on the GI tract by the petal-shaped capsule robot is reduced, while the non-contact driving performance in the GI tract is improved greatly isolated by fluid membrane with high dynamic pressure.
The purpose of this paper is to analyze the concept of transformative pedagogy' (TP) in physical education and sport pedagogy (PESP) and research in order to provide an alternative perspective on freedom, justice and the limits of transformation. Although some of the limits of TP have already been pointed out in the literature, such limits have been presented as though originating and having to be resolved out there, in socio-cultural-political contexts. In an attempt to redirect the attention from the social to the personal, this paper points out the possibility of TP's limits being also within critical pedagogues and researchers ourselves. After analyzing three barriers to (self-)consciousness/knowledge (SC/K), two viable methods for developing SC/K and transformation are provided.
Introduction: As many inflammatory bowel disease (IBD) patients do not benefit from long-term antitumour necrosis factor treatment, new anti-inflammatories are urgently needed. After the discovery of the interleukin (IL) 23/17 axis being pivotal in IBD pathogenesis, many different compounds were developed, targeting different components within this pathway. Areas covered: A literature search to March 2016 was performed to identify the most relevant reports on the role of the IL-23/IL-17 axis in IBD and on the different molecules targeting this pathway. First, the authors briefly summarize the immunology of the IL-23/IL-17 pathway to elucidate the mode of action of all different agents. Second, they describe all different molecules targeting this pathway. Besides discussing efficacy and safety data, they also explore immunogenicity, exposure during pregnancy and pharmacokinetics. Expert opinion: A new era in IBD treatment has recently been initiated: besides immuno-modulators and TNF-antagonists, anti-adhesion molecules and monoclonal antibodies targeting the IL-23/IL-17 pathway have been developed. Biomarkers for personalized medicine are urgently needed. This therapeutic (r) evolution will further improve disease-related and patient-reported outcome, though a lot of questions should still be addressed in future years.
Effective disease management of crops is crucial to sustain food security and safeguard potential losses in crop production that worth billions of dollars. The key to success in plant disease management is having the ability to detect the causal pathogen(s) early and accurately. Polymerase chain reaction (PCR) has been a gold standard in nucleic acid-based diagnostics. Apart from PCR, within the last decade, the development of a technique called "loop-mediated isothermal amplification" or LAMP has facilitated the development of hundreds of simple assays for plant disease diagnostics. There are now more than 200 LAMP publications per year, of which 20% identify plant disease pathogens. Among them, LAMP assays are available for pathogen detection of 50 plant viruses, 20 bacterial plant diseases, 7 fungal plant diseases and several phytoplasmas. Here, we provide a comprehensive analysis of all LAMP assays available for detecting plant diseases, including various detection chemistries used. We also discuss how to avoid pitfalls when developing LAMP assays. Finally, we offer perspectives of the applications of LAMP in plant disease management, addressing the questions as to which extent the assays are helpful and whether they should be used outside the laboratory. This review will be a "handbook" for researchers developing LAMP assays for plant disease diagnostics.
We examined 261 5-, 7-, and 10-year-olds' (147 in Hong Kong, 114 in the USA) evaluations of hypothetical scenarios where mothers sought to control personal domain events by prohibiting, persuading, or shaming the child. The scenarios also varied in their description of personal events as either essential or peripheral to the self. Compliance was endorsed least (and emotions attributed to actors were most positive) when mothers gently persuaded and endorsed most (with emotion attributions most negative) when mothers prohibited personal choices. Evaluations of compliance and associated emotions for shaming fell in-between. When mothers were described as gently persuading, young children (and Chinese children) gave priority to personal choices more when acts were described as essential rather than peripheral to the self, based on personal reasons. When mothers were described as shaming, noncompliance increased with age, along with pragmatic justifications for choices, particularly when events were essentialized. Positive emotions in response to shaming also increased with age, but differentially for Chinese and American children.
Background: Crustaceans have been studied extensively as model systems for nervous system function from single neuron properties to behavior. However, lack of molecular sequence information and tools have slowed the adoption of these physiological systems as molecular model systems. In this study, we sequenced and performed de novo assembly for the nervous system transcriptomes of two decapod crustaceans: the Jonah crab (Cancer borealis) and the American lobster (Homarus americanus). Results: Forty-two thousand, seven hundred sixty-six and sixty thousand, two hundred seventy-three contigs were assembled from C. borealis and H. americanus respectively, representing 9,489 and 11,061 unique coding sequences. From these transcripts, genes associated with neural function were identified and manually curated to produce a characterization of multiple gene families important for nervous system function. This included genes for 34 distinct ion channel types, 17 biogenic amine and 5 GABA receptors, 28 major transmitter receptor subtypes including glutamate and acetylcholine receptors, and 6 gap junction proteins - the Innexins. Conclusion: With this resource, crustacean model systems are better poised for incorporation of modern genomic and molecular biology technologies to further enhance the interrogation of fundamentals of nervous system function.
A new member of antimicrobial protein genes of the Crustin family was cloned from haemocytes of the Chinese shrimp Fenneropenaeus chinensis by 3' and 5' RACE. The full-length cDNA of Crustin-like gene contains a 390 bp open reading frame, encoding 130 amino acids. The deduced peptide contains a putative signal peptide of 17 amino acids and mature peptide of 113 amino acids. The molecular mass of the deduced mature peptide is 12.3 ku. It is highly cationic with a theoretical isoelectric point of 8.5. The deduced amino acids sequence of this Crustin showed high homology with those of Penaeus (Litopenaeas) setferus. Northern blotting showed that the cloned Crustin gene was mainly expressed in haemocytes, gill, intestine, and RNA in situ hybridization indicated that the Crustin gene was constitutively expressed exclusively in haemocytes of these tissues. Capillary electrophoresis RT-PCR analysis showed that Crustin was up-regulated dramatically from 12 to 48 h after a brief decrease of mRNA during first 6 h in response to microbe infection. The level of Crustin mRNA began to restore at 72 h post-challenge. This indicated that Crustin gene might play an important role when shrimps are infected by bacterial pathogen.
To realize a multipixel camera for astronomical observation, we developed cryogenic multi-channel readout systems using gallium arsenide junction field-effect transistor (GaAs JFET) integrated circuits (ICs). Based on our experience with these cryogenic ICs, we designed, manufactured, and demonstrated operational amplifiers requiring four power supplies and two voltage sources. The amplifiers operate at 4.2 K with an open-loop gain of 2000. The gain-bandwidth product can expect 400 kHz at a power dissipation of 6 mu W. In performance evaluations, the input-referred voltage noise was 4 mu V-rms/Hz(0.5) at 1 Hz and 30 nV(rms)/Hz(0.5) at 10 kHz, respectively. The noise power spectrum density was of type 1/f and extended to 10 kHz. (C) 2015 Elsevier Ltd. All rights reserved.
This paper describes the main characteristics and the performance of a saturated core type fault current limiter (FCL) rated 45MVA(33 kV-800 A) to be provided by ASG Power Systems. The FCL, which has been submitted to preliminary laboratory testing, will be installed at a 275/33 kV substation in the U.K. and will reduce the fault current by 38%. The device is based on an open geometry of the magnetic cores which allows reduced size and the weight. Magnetic saturation of the cores is obtained by means of two magnesium diboride (MgB2) magnets. A numerical model of the FCL has been developed and validated and the interaction of the device with the power grid has been investigated. Details and results of the model are also discussed in the paper.
Altered mental status in cryptococcal meningitis results in poorer survival, but underlying causes of altered mentation are poorly understood. Within two clinical trials, we assessed risk factors for altered mental status (GCS score<15) considering baseline clinical characteristics, CSF cytokines/chemokines, and antiretroviral therapy. Among 326 enrolled participants, 97 (30%) had GCS<15 and these patients had lower median CSF cryptococcal antigen titers (P = .042) and CCL2 (P = .005) but higher opening pressures (320 vs. 269 mm H2O; P = .016), IL-10 (P = .044), and CCL3 (P = .008) compared with persons with GCS = 15. Altered mental status may be associated with host immune response rather than Cryptococcus burden.
Cryptosporidium and Giardia are important causes of diarrhoeal illness. Adequate knowledge of the molecular diversity and geographical distribution of these parasites and the environmental and climatic variables that influence their prevalence is important for effective control of infection in at-risk populations, yet relatively little is known about the epidemiology of these parasites in Africa. Cryptosporidium is associated with moderate to severe diarrhoea and increased mortality in African countries and both parasites negatively affect child growth and development. Malnutrition and HIV status are also important contributors to the prevalence of Cryptosporidium and Giardia in African countries. Molecular typing of both parasites in humans, domestic animals and wildlife to date indicates a complex picture of both anthroponotic, zoonotic and spill-back transmission cycles that requires further investigation. For Cryptosporidium, the only available drug (nitazoxanide) is ineffective in HIV and malnourished individuals and therefore more effective drugs are a high priority. Several classes of drugs with good efficacy exist for Giardia, but dosing regimens are suboptimal and emerging resistance threatens clinical utility. Climate change and population growth are also predicted to increase both malnutrition and the prevalence of these parasites in water sources. Dedicated and co-ordinated commitments from African governments involving "One Health" initiatives with multidisciplinary teams of veterinarians, medical workers, relevant government authorities, and public health specialists working together are essential to control and prevent the burden of disease caused by these parasites.
Structural and molecular properties of antidepressants 1-(3-(dimethylamino)propyI)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile were examined using quantum mechanics of Density Functional Theory (DFT)/B3LYP and PBEPBE methods with 6-311 ++G(d,2p) and LanL2DZ basis sets to study the therapeutic properties of the drug. For this, the structure of desired material was optimized by the computer calculation method and with the use of powerful Gaussian 09 software. Then the lowest energy value and the bond length, bond angle and dihedral angle between its constituent atoms in the crystal structure of the desired material were measured from the optimized values. Then the amount of positive and negative charges, polarizability and dipole moment of its atoms using Mulliken charge and Natural atomic charges, DFT/B3LYP and PBEPBE methods with 6311 ++ G(d,2p) and LanL2DZ basis sets were determined and the results were compared with each other for individual atoms and by mentioned methods. Also the type of stretching vibrations and bending vibrations between the constituent atoms of the molecule were specified using mentioned computational methods and FT IR vibrational spectra. The experimental spectrum of this material was taken to determine the functional groups and the computational and experimental values were compared to each other and Nuclear Magnetic Resonance (NMR) was used to specify the isomer shift between the carbons and protons in the presence of polar and non polar solvents. Also Natural Bond Orbital (NBO) was used to determine the type of electron transfers in (sigma ->sigma* and pi ->pi* and LP(1) ->sigma* and LP(2) sigma* and the amount of hardness and softness in molecule was determined using the difference between ionization energy and electron affinity energy in constituent atoms of that molecule in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and in the presence of solvents H2O, CH3CN and C6H12. UV-Vis spectrum of the drug was taken using DFT/B3LYP and PBEPBE methods with 6-311 ++ G(d,2p) and LanL2DZ basis sets as well as solvents H2O, CH3CN and C6H12 and the associated transmissions were examined. (C) 2017 Elsevier B.V. All rights reserved.
Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11 (nsp11) was shown to have NendoU activity and play essential roles in the viral life cycle. Here, we report three crystal structures of porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants. The structures of arterivirus nsp11 contain two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV endoribonucleases are similar and conserved in the arterivirus, but they are greatly different from that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoV), representing important human pathogens in the Nidovirales order. The catalytic center of NendoU activity is located in the CTD, where a positively charged groove is next to the key catalytic residues conserved in nidoviruses. Although the NTD is nearly identical, the catalytic region of the arterivirus nsp11 family proteins is remarkably flexible, and the oligomerization may be concentration dependent. In summary, our structures provide new insight into this key multifunctional NendoU family of proteins and lay a foundation for better understanding of the molecular mechanism and antiviral drug development. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus are two major members of the arterivirus family. PRRSV, a leading swine pathogen, causes reproductive failure in breeding stock and respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or effective drug treatment and the quick spread of these viruses, infected animals either die quickly or must be culled. PRRSV costs the swine industry around $ 644 million annually in the United States and almost (sic)1.5 billion in Europe every year. To find a way to combat these viruses, we focused on the essential viral nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such as RNA processing and suppression of the infected host innate immunity system. The three structures solved in this study provide new insight into the molecular mechanisms of this crucial protein family and will benefit the development of new treatments against these deadly viruses.
Melanoma is a form of cancer that initiates in melanocytes. Melanoma has multiple phenotypically distinct subpopulation of cells, some of them have embryonic like plasticity which are involved in self-renewal, tumor initiation, metastasis and progression and provide reservoir of therapeutically resistant cells. Cancer stem cells (CSCs) can be identified and characterized based on various unique cell surface and intracellular markers. CSCs exhibit different molecular pattern with respect to non-CSCs. They maintain their stemness and chemoresistant features through specific signaling cascades. CSCs are weak in immunogenicity and act as immunosupressor in the host system. Melanoma treatment becomes difficult and survival is greatly reduced when the patient develop metastasis. Standard conventional oncology treatments such as chemotherapy, radiotherapy and surgical resection are only responsible for shrinking the bulk of the tumor mass and tumor tends to relapse. Thus, targeting CSCs and their microenvironment niche addresses the alternative of traditional cancer therapy. Combined use of CSCs targeted and traditional therapies may kill the bulk tumor and CSCs and offer a promising therapeutic strategy for the management of melanoma.
Electricity generated using photovoltaic system can only be commercial if the photovoltaic modules operate reliably for 20-25 years under field conditions. Understanding the performance degradation of photovoltaic modules is critical for optimizing its financial viability. Performance degradation of photovoltaic modules is due to multiple factors such as installation site and module technologies. In order to gain insight on performance degradation of crystalline silicon PV technology in harsh environment, a degradation effects study of c-Si photovoltaic modules in desert environment was carried. The main contribution of this paper is focused on the evaluation of c-Si PV modules performance that operated in extreme environmental conditions. This evaluation usually consists of I-V curve field measurements and visual inspections. (C) 2017 Elsevier Ltd. All rights reserved.
Analysis of the genome of Chaetoceros salsugineum nuclear inclusion virus (CsNIV) revealed the presence of six putative open reading frames (ORFs) in the genome. We further characterized ORF3, which encodes a putative coat protein. Polymerase chain reaction (PCR) using ORF3 gene-specific primers amplified a single DNA band nearly 1.2 kb. This amplified product was gel-purified, cloned, sequenced, and expressed in Escherichia coli. Specific antiserum was raised against the recombinant protein and used for Western blotting to test whether the ORF3 protein is the CsNIV coat protein. One major CsNIV protein of approximately 46 kDa reacted positively with the antiserum, suggesting that this antiserum is specific for the CsNIV coat protein. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis of the 46 kDa structural band revealed 14 peptide sequences that matched the ORF3 regions of CsNIV. The expression of ORF3 in host cells was examined by constructing a cDNA library of CsNIV-infected cells. Nucleotide sequences of the cDNA clones were complementary to various regions of both CsNIV ORF3 and ORF4; however, no clones containing only the ORF3 region were identified. Also, Northern blotting revealed a single 2.5-kb transcript, indicating that ORF3 could be transcribed together with ORF4. (C) 2009 Elsevier B.V. All rights reserved.
Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the blood stream that are thought to have a key role in cancer metastasis. Investigation of CTCs is an exciting area of research but remains in its infancy, and the presence of CTCs has been associated with worse prognosis in several major cancer types. Gastric cancer (GC) is a highly lethal malignancy and a serious public health concern in East Asia especially in China. There is an urgent need for identifying new, better prognostic markers to enhance diagnosis and prognosis, facilitate drug development, and to improve the treatment of gastric cancer patients. There are considerable interests in gastric CTCs given their potential use as gastric cancer biomarkers. This review highlights recent advances in studies of gastric CTCs, including the isolation and biological molecular characteristics of gastric CTCs, and their clinical significance.
Introduction: Connective tissue growth factor (CTGF/CCN2) has been shown previously to be aberrantly expressed in a high proportion of paediatric precursor B cell acute lymphoblastic leukaemia (pre-B ALL), suggesting a potential oncogenic role in this tumour type. We therefore assessed CTGF mRNA transcript diversity in B-lineage ALL using primary patient specimens and cell lines. Methods: CTGF mRNA expression was evaluated by quantitative real-time PCR and Northern blotting. We performed a structural analysis of CTGF mRNA by nested reverse-transcriptase PCR and examined CTGF protein diversity by immunoblotting. Results: Northern blot analysis of pre-B ALL cell lines revealed short CTGF transcripts that were expressed in association with the active phase of cellular growth. Structural analysis confirmed the synthesis of several novel CTGF mRNA isoforms in B-lineage ALL cell lines that were uniformly characterised by the retention of the coding sequence for the C-terminal (CT) domain. One of these novel spliceforms was expressed in a majority (70%) of primary pre-B ALL patient specimens positive for canonical CTGF mRNA. Evidence that these alternative transcripts have coding potential was provided by cryptic CTGF proteins of predicted size detected by immunoblotting. Conclusion: This study identifies for the first time alternative splicing of the CTGF gene and shows that a short CTGF splice variant associated with cell proliferation is expressed in most cases of primary CTGF-positive pre-B ALL. This novel variant encoding only the CT domain may play a role in pre-B ALL tumorigenesis and/or progression. (C) 2015 Elsevier Ltd. All rights reserved.
The past 20 years have heralded fascinating developments in the field of CTLA-4 biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and its absence provokes severe lymphoproliferative disease. In a surprising twist, the generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell can modify the behaviour of another cell. This was followed by the demonstration that CTLA-4 is highly expressed in regulatory T cells and can contribute to their suppressive activity. In line with a cell-extrinsic function, increasing evidence indicates that CTLA-4-positive cells can modify the phenotype of antigen presenting cells (APC), thereby regulating the priming of naive T cells. Notably, CTLA-4 is able to down regulate expression of costimulatory ligands on APC via a process of trans-endocytosis. The identification of patients with mutations in the ctla4 gene has provided an opportunity to study the contribution of CTLA-4 to Treg function and immune regulation in the human immune system. Finally. it has become apparent that CTLA-4 also plays a role in controlling humoral immunity, via the regulation of CD28-driven follicular helper T cell differentiation. At the recent German Society for Immunology congress, I discussed some of the contributions of my own lab to the unfolding of the CTLA-4 story, in the context of the work of others in the field. Despite the enormous clinical potential associated with modulation of the CTLA-4 pathway, including the use of soluble CTLA-4 molecules in autoimmune settings and blocking antibodies in cancer, it is clear there is still much to learn about this important pathway. (C) 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Conclusions: The levels of expression of various C-type lectin receptors (CLRs) messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas than in normal skin, suggesting that these CLRs may be involved in the pathogenesis of cholesteatoma. Objectives: Altered expression of pattern recognition receptors may be associated with immune responses in patients with cholesteatoma. This study assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma. Methods: Cholesteatoma specimens were obtained from 38 patients with acquired cholesteatoma. The levels of expression of various CLR mRNAs were assessed quantitatively using real-time RT-PCR (Reverse transcription polymerase chain reaction) and correlated with age, sex, the presence of bacteria, hearing level, frequency of surgery, and degree of ossicle destruction. Results: The levels of CD206 (cluster of differentiation 206), DEC-205 (Dendritic and epithelial cell-205), MGL (monoacylglycerol lipase), CLEC5A (C-type lectin domain family 5 member A), Dectin-2 (dendrite cell-associated C-type lectin-2), BDCA2 (Blood dendritic cell antigen 2), Mincle, DCIR (dendritic cell immunoreceptor), Dectin-1, MICL (Myeloid inhibitory C type-like lectin), and CLEC12B (C-type lectin domain family 12, member B) mRNAs were significantly higher in cholesteatoma than in control skin samples (p= 2 than <= 1 destroyed ossicles (p<0.05), and the levels of MGL, Mincle, Dectin-1, and CLEC12B mRNAs were significantly higher in recurrent than initial cholesteatoma specimens (p<0.05). The level of CLEC5A mRNAs was significantly higher in patients with severe than mild-to-moderate hearing loss (p<0.05). \
Lectin is regarded as a potential molecule involved in immune recognition and phagocytosis through opsonization in crustacean. Knowledge on lectin at molecular level would help us to understand its regulation mechanism in crustacean immune system. A novel C-type lectin gene (Fclectin) was cloned from hemocytes of Chinese shrimp Fenneropenaeus chinensis by 3' and 5' rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA consists of 1482 bp with an 861 bp open reading frame, encoding 287 amino acids. The deduced amino acid sequence contains a putative signal peptide of 19 amino acids. It also contains two carbohydrate recognition domains/C-type lectin-like domains (CRD1 and CRD2), which share 78% identity with each other. CRD1 and CRD2 showed 34% and 30% identity with that of mannose-binding lectin from Japanese lamprey (Lethenteron japonicum), respectively. Both CRD1 and CRD2 of Fclectin have I I amino acids residues, which are relatively invariant in animals' C-type lectin CRDs. Five residues at Ca2+ binding site I are conserved in Fclectin. The potential Ca2+/carbohydrate-binding (site 2) motif QPD, E, NP (Gln-Pro-Asp, Glu, Asn-Pro) presented in the two CRDs of Fclectin may support its ability to bind galactose-type sugars. It could be deduced that Fclectin is a member of C-type lectin superfamily. Transcripts of Fclectin were found only in hemocytes by Northern blotting and RNA in situ hybridization. The variation of mRNA transcription level in hemocytes during artificial infection with bacteria and white spot syndrome virus (WSSV) was quantitated by capillary electrophoresis after RT-PCR. An exploration of mRNA expression variation after LPS stimulation was carried out in primarily cultured hemocytes in vitro. Expression profiles of Fclectin gene were greatly modified after bacteria, LPS or WSSV challenge. The above-stated data can provide us clues to understand the probable role of C-type lectin in innate immunity of shrimp and would be helpful to shrimp disease control. (c) 2006 Elsevier Ltd. All rights reserved.
Former studies suggest that the core features of psychopathy, namely the callous-unemotional (CU) traits are associated with emotional dysfunction characterized by atypical processing of other people's distress. Using a dimensional approach to CU traits, the current study aims to test neural activity during performance of a facial expression recognition task in a community sample of young adults. Forty-one participants (25 females, M age = 25.44, SD = 4.03) completed the Inventory of Callous-Unemotional Traits. Functional magnetic resonance imaging data were collected to measure neural responses to fearful, happy and sad faces as compared with neutral facial expressions. Region-of-interest analyses revealed that during exposure to fearful face expressions, blood oxygenation level-dependent responses were negatively associated with CU traits in the right anterior cingulate gyms (ACCg), but not in the amygdala. These findings support that CU traits are related to a unique neural response to fearful faces in noncriminal population as well. It also highlights the importance of taking into account other regions outside the amygdala, in particular the ACC, when testing the relation between CU traits and fear response. 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
A growing body of evidence indicates that lysozyme plays a significant role as an indicator for many diseases and a drug for treatment of infections, ulcers and to study the spatial conformation, enzyme kinetics, and molecular immunology. Therefore, highly sensitive determination of lysozyme is necessary and vital in a wide variety of fields. In this work, we put forward a simple but effective strategy for colorimetric visualization of lysozyme based on iodide-responsive Cu@Au nanoparticles (Cu@Au NPs) as well as the iodide-catalyzed H2O2-TMB (3,3,5,5-tetramethylbenzidine) reaction system. Colorimetric detection is applied because of its simplicity, fast response for analysis, high detection limit, low costs and practicality. In our strategy, iodide is applied for the reason that it can induce an obvious color change of the Cu@Au nanoparticles solution from gray to red, along with the change of morphologies of the Cu@Au nanoparticles from irregular to spherical. Consequently, this phenomenon results in colorimetric signal variation of the iodide-catalytic H2O2-TMB system. What's more, by quite simple biomolecule modification on the Cu@Au nanoparticles surface, an all-purpose colorimetric platform is established for the accurate detection of lysozyme, which could lead to the change of Cu@Au NP concentration through molecular recognition. The results show that modified Cu-Au NPs successfully achieved a simple, selective, visualized, and ultrasensitive detection of lysozyme with a linear range from 10(-7) to 10(-3) M and a detection limit of 60 nM.
The 2b protein encoded by Cucumber mosaic virus (CMV) plays an important pathogenicity role in many solanaceous hosts, but mechanism of inducing disease is still unknown. In order to investigate virulence of the 2b protein on Nicotiana glutinosa plants, in terms of chloroplast structure and photosynthesis, a mutant Fny-CMV Delta 2bpro, which cannot express the 2b protein, was achieved by introducing mutant sites in the 2b gene of Fny-CMV. N. glutinosa seedlings were inoculated with wild-type Fny-CMV and the mutant Fny-CMV Delta 2bpro, and were analyzed for symptom expression, chlorophyll content, photosynthetic rate, and ultra-structural alteration of chloroplast. Up to 30 days post inoculation, wild-type Fny-CMV caused symptoms of severe mosaic, leaf deformation, and stunting, reduced photosynthetic rate and chlorophyll content, and altered the ultra-structure and morphological characters of the chloroplasts. However, host seedlings inoculated with the mutant Fny-CMV Delta 2bpro expressed only slight mosaic symptom. Their photosynthetic rates and chlorophyll contents were not significantly different from those of the mock-inoculated plants, and the ultra-structure and morphological characters of their chloroplasts appeared to be normal. The observed low photosynthetic rates and chlorophyll contents were related to the breakage of the chloroplast morphology and ultra-structure. Results of Northern blotting showed that the virulence of 2b protein was associated with high accumulation level of CMV progeny RNAs in systemic leaves. Non-expression of the 2b protein reduced the accumulation levels of its genomic RNAs I and 2. The level of subgenomic RNA4, encoding CP protein, was found to be significantly decreased.
Full length cDNAs of Cucumber mosaic virus (CMV) CB7 strain, causing necrosis on Nicotiana glutinosa, were obtained by RT-PCR, using viral genomic RNAs as templates. cDNAs of CNW-CB7 genomic RNAs were cloned and sequenced and results indicated that RNAI, 2 and 3 was 3 356 nt, 3 045 nt and 2 218 nt, respectively (accordingly Accession Number EF216866, DQ785470 and EF216867). Infectious RNA transcripts from cDNA clones of CMV-CB7 were inoculated onto N. glutinosa and the seedlings of host plants displayed necrosis symptom, whist that of CMV-Fny induced typical mosaic symptoms. Through pseudorecombination between CMV-CB7 and CNW-Fny genomic RNAs, the genetic determinant of necrosis phenotype was mapped to RNA2. Chimeric infectious clones consisting of partial sequences of RNA2 derived from CNW-CB7 and CNW-Fny, respectively, were obtained by Overlapping PCR. Pathogenic analysis with those chimeric RNA2 revealed that 2b gene or 3' UTR of CMV-CB7 RNA2 was responsible for the necrotic pathotype. Northern blotting analysis reflected that both necrotic and non-necrotic viruses accumulated to similar levels of genomic RNAs in host plants. Therefore, necrotic phenotype induced on N. glutinosa was not related to the level of accumulation of CMV genomic RNAs.
Sex differentiation of flower buds is an important developmental process that directly affects fruit yield of cucumber (Cucumis sativus L). Plant hormones, such as gibberellins (GAs) and ethylene can promote development of male and female flowers, respectively, however, the regulatory mechanisms of GA-induced male flower formation and potential involvement of ethylene in this process still remain unknown. In this study, to unravel the genes and gene networks involved in GA-regulated cucumber sexual development, we performed high throughout RNA-Seq analyses that compared the transcriptomes of shoot tips between GA(3) treated and untreated gynoecious cucumber plants. Results showed that GA(3) application markedly induced male flowers but decreased ethylene production in shoot tips. Furthermore, the transcript levels of M (CsACS2) gene, ethylene receptor CsETR1 and some ethylene-responsive transcription factors were dramatically changed after GA(3) treatment, suggesting a potential involvement of ethylene in GA regulated sex expression of cucumber. Interestingly, GA(3) down-regulated transcript of a C-class floral homeotic gene, CAG2, indicating that GA may also influence cucumber sex determination through an ethylene-independent process. These results suggest a novel model for hormone-mediated sex differentiation and provide a theoretical basis for further dissection of the regulatory mechanism of male flower formation in cucumber. Statement: We reveal that GA can regulate sex expression of cucumber via an ethylene dependent manner, and the M (CsACS2), CsETR1, and ERFs are probably involved in this process. Moreover, CAG2, a C-class floral homeotic gene, may also participate in GA-modulated cucumber sex determination, but this pathway is ethylene-independent.
We exploited the potential of cucurbits for ectopic gene expression. Agroinfiltration is a simple and commonly used method to obtain transient expression of foreign genes in plants. In contrast to in vitro transformation techniques, agroinfiltration can be used for genetic modification of mature plant tissues. Although the cucurbits are commonly used as model plants for molecular biology and biotechnology studies, to date there are no literature sources on the possibility of transient gene expression in mature cucurbit tissues. Our research has shown that mature leaves of Luffa cylindrica L. (luffa), in contrast to other cucurbit species, can be successfully transiently transformed with Agrobacterium tumefaciens. We efficiently transformed luffa leaves with a reporter gene encoding beta-glucuronidase (GUS). The GUS activity in transiently transformed leaf tissues was detected within 24 h after the infiltration with bacteria. Additionally, we have shown that the activity of a transiently expressed the GUS gene can be monitored directly in the EDTA-exudates collected from the cut petioles of the agroinfiltrated leaves. The results suggest that luffa leaves can be useful as a plant expression system for studies of physiological and biochemical processes in cucurbits.
Background: Mosquitoes of the Culex pipiens complex, competent vectors for West Nile virus (WNV) and Rift Valley fever virus (RVFV) are widely targeted by insecticide treatments. The intensive application of chemical insecticides led to the development of resistance in many insects including Culex pipiens mosquitoes. The absence of data on resistance mechanisms in Morocco allow us to assess the levels of lambda-cyhalothrin resistance and the frequency of the mutated gene L1014F kdr in different forms of Cx. pipiens complex from three regions of Morocco. Methods: Mosquito adults were reared from immature stages collected in three different regions in Morocco (Tangier, Casablanca and Marrakech). Standard WHO insecticide susceptibility tests were conducted on adults emerged from collected larvae. Specimens were identified as belonging to the Culex pipiens complex using a multiplex PCR assay with diagnostic primers designed from the flanking region of microsatellite CQ11. Identified mosquitoes were then tested for the presence of the L1014F kdr mutation using PCR assay. Results: Our results showed that 21% of the tested population has a resistance to lambda-cyhalothrin. The molecular identification of survivors shows that 43% belonged to the Cx. pipiens pipiens and only 9.5% to the Cx. pipiens molestus form. On the other hand, 416 specimens were screened for the L1014F kdr mutation. L1014F mutation was detected in different forms of Cx. pipiens in different sites. The frequency of L1014F mutation was similar between the Cx. pipiens pipiens form and hybrid form, while it was lower in the Cx. pipiens molestus form. The presence of the L1014F kdr allele was significantly associated with resistance to lambda-cyhalothrin in Cx. pipiens pipiens (P < 0.0001) and hybrid form (P < 0.0001). Conclusion: Resistance to lambda-cyhalothrin of Cx. pipiens populations appears to be largely due to the L1014F kdr mutation. To our knowledge, the frequencies of L1014F kdr mutation are examined for the first time in natural populations of the Culex pipiens complex in Morocco. These findings will provide important information to propose more adapted vector control measures towards this mosquito species, potential vector of arboviruses.
The purpose of this paper, on the occasion of the 125(th) anniversary of The New York Botanical Garden, is to provide an overview of NYBG's graduate studies program along with updated information since the last major review of the program, 25 years ago. Graduate student education has always been, and continues to be, a core mission of The New York Botanical Garden. The program is affiliated six major universities: the City University of New York, Columbia University, New York University, Yale University, Cornell University, and Fordham University. In the 125 year history of the program, the Garden has produced more than 300 graduates, including 216 Ph.D.s and 87 Master's degrees. Students have focused on floristics, systematics, structural botany, and economic botany; the program has evolved to keep up with the continuous changes in science, with students using the most modern techniques to study plant diversity. Since 1996, the program has produced 93 graduates, including 81 Ph.D.s and 12 Master's degrees; the Garden's affiliation with Yale's School of Forestry and Environmental Studies has produced a dozen graduates; and the Garden's affiliation with Fordham University, which was reinitiated in 2008, has produced its first graduates. With the growth of the Cullman Program for Molecular Systematics and the Genomics Program in the mid-1990s, student research projects began to incorporate molecular biology (primarily based on DNA sequencing) and to address questions related to genome evolution and evolutionary developmental biology. Technological advances have also changed economic botany research. On the 125(th) anniversary of NYBG, the hallmark of the graduate studies program is its excellence in teaching and training, with students continuing to integrate data from modern and traditional sources to better understand plant diversity.
The primary goal of the current study was to examine cultural differences in Chinese and U.S. adolescents' and parents' perceptions and evaluations of adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents (ages 11-19 years) and 255 parents participated in this study. Each participant generated adolescent misconduct behaviors and rated each misconduct behavior as to the degree of wrongness. The misconduct behaviors were coded into 10 categories across three themes (moral offenses, drugs, and conventions). Results revealed significant cultural differences in a number of adolescent misconduct behaviors. For example, the United States generated more misconduct behaviors in weapon offenses and drug use than did China. These cultural differences were further complicated by an interaction between culture and generation. Chinese adolescents were more likely than U.S. adolescents to use categories of school, home, and social conventional violations, and considered these adolescent misconduct behaviors to be more wrong. However, it was the U.S. parents who considered adolescent misconduct behaviors in these categories to be more wrong than did Chinese parents.
Objective: There are limited data regarding Xpert performance to detect Group B Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected women.Methods: At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs were collected for two GBS assays in a cohort of sequentially included HIV-infected women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS (Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity, specificity, positive and negative-likelihood ratios were estimated.Results: From June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman was later excluded, due to failure to obtain a result in the index test; 336 were included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85% (95% CI: 91.55-96.91), respectively. Positive and negative predictive values were 79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22), respectively.Conclusions: GeneXpert GBS is an acceptable test for the identification of GBS colonization in HIV-infected pregnant women and represents a reasonable option to detect GBS colonization in settings where culture is not feasible.
The diversity and dynamics of the dominant bacterial communities arising during the pickling process of bamboo shoots (Dendrocalamus latiflorus) were investigated by nested polymerase chain reaction denaturing gradient gel electrophoresis combined with quantitative real-time polymerase chain reaction. Results showed only several kinds of halophilic bacteria during early sampling time (0-3days). After pickling for 7days, Lactococcus lactis significantly increased (P<0.05, quantities were 6.39x10(5) copiesL(-1)) and became the first dominant bacterium. After pickling for 14days, Weissella sp. bands appeared and quickly became dominant on the 21st day (4.07x10(6) copiesL(-1)). As maturation progressed, Lc.lactis decreased in intensity whereas Weissella sp. increased in intensity. Finally, the quantities of Weissella sp. (2.50x10(7) copiesL(-1)) became higher than those of Lc.lactis (1.43x10(7) copiesL(-1)) after pickling for 56days. The pickling process was initiated by Lc.lactis, followed by Lc.lactis and Weissella sp., and was finally succeeded by Weissella sp.
Salt stress as a major limiting factor negatively affects many physiological processes in plants. Salinity promotes the generation of reactive oxygen species and subsequently oxidative damage of cellular components. Plant salt stress tolerance requires activation of antioxidative pathways to prevent plant cell from injurious effects. In this study real-time quantitative reverse transcription-polymerase chain reaction was used to determine the protective role of two antioxidant genes, i.e. iron-superoxide dismutase (Fe-SOD) and catalase (CAT) in Cuminum cyminum L. after their treatment with 50, 100, 150 and 200 mM NaCl. Enzymatic activities were assayed spectrophotometrically for three antioxidants. Moreover, growth parameters, protein content and proline accumulation were measured. In comparison with the control plants, those plants which were exposed to 50 and 100 mM NaCl concentration accumulated higher levels of proline. At 50, 100 and 150 mM of NaCl plants showed higher superoxide dismutase, ascorbate peroxidase and catalase activities. The same condition also induced expression of the Fe-SOD and CAT genes at mRNA level. Protein content of the treated plants was significantly decreased at 50 mM NaCl and remained constant at other concentrations. Whereas, the growth parameters, with one exception in case of shoot length, did not change at plants receiving low and mild salt concentrations of up to 150 mM NaCl, 200 mM of NaCl affected these parameters negatively. From these details, it can be concluded that C. cyminum respond to salt stress by antioxidant system efficiency and proline accumulation.
DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel drugs, especially for neurodegenerative disorders. In recent years, there has been increased interest in small molecules that can cross the blood-brain barrier for the treatment of neurodegenerative diseases. Therefore, comparing the neuronal differentiative effects of a natural compound curcumin and a synthetic small molecule RG108 was the aim of this study. The effects of curcumin and RG108 on neuronal differentiation and neurite outgrowth were investigated in the PC-12 Adh cell line. First, a nontoxic concentration was determined to be 100nM with WST-1 assay. Subsequently, cells were treated with 100nM curcumin and RG108 alone or in combination with 50nM nerve growth factor (NGF). Cell differentiations were evaluated by a real-time cell analyzer system. Neurite outgrowth was determined and morphologically shown by immunofluorescence staining with anti-beta III tubulin antibody on PC-12 Adh cells. Also, growth-associated protein-43 (GAP-43) and b-tubulin III mRNA expression levels, associated with neurite outgrowth promotion, were determined with real-time polymerase chain reaction (RT-PCR). According to our results, 100nM curcumin and RG108 significantly induced neurite outgrowth of PC-12Adh cells with 50nM NGF. Curcumin + NGF combination further increased cell differentiations and total neurite lengths more than curcumin alone and RG108 + NGF combination groups. Strikingly, curcumin and NGF combination upregulated GAP43 and b-tubulin mRNA expression levels excessively. In conclusion, curcumin was found to be more effective than RG108 on neuronal differentiation and neurite outgrowth of PC-12Adh cells in a combination with NGF. Therefore, natural DNMT1 inhibitors, such as curcumin, can be a novel approach for the neurodegenerative disorders treatment.
Objectives: New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Racl-Guanosine triphosphate (Racl-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model. Methods: Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively. Results: Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Racl, Racl-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We also observed an escalation of protein thiol groups, increased enzyme activity of serum antioxidant markers (e.g., superoxide dismutase) and a decrease of carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05). Conclusions: Curcumin attenuated liver damage through the downregulation of Racl, Racl-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats. (C) 2016 Elsevier Inc. All rights reserved.
This paper presents hybrid cascode compensation with current amplifiers (HCCCA) for nano-scale area-efficient three-stage amplifiers driving ultra-large capacitive loads. The total compensation capacitor is split and placed among two high-speed feedback loops, each with a unique current amplifier. By using HCCCA, the load-dependent non-dominant poles are pushed to much higher frequencies, thereby achieving improved performance especially for heavy capacitive loads. The employed current amplifiers make it possible to significantly reduce the physical size of the compensation capacitors and to save more silicon area. The effectiveness of the proposed technique has been verified in 90-nm CMOS process, where an HCCCA amplifier prototype is designed to drive up to 10 nF load capacitor using a compensation capacitor of only 0.5 pF. It achieves a 1.0 MHz gain-bandwidth product and 0.19 V/A mu s slew-rate while consuming 80 A mu W power from a 1.2 V supply. The achieved large-signal and small-signal performance metrics are superior to those topologies reported in the literature.
Development of renewable power generation systems (RPGSs) is continually increasing worldwide with Germany, China, Japan, Italy and the USA are the leaders contributing to the largest, development in each region. Due to the increasing number of RPGSs connected to the utility grid, power quality, safe operation, and islanding protection of RPGSs are becoming important issues, among others. One of the most important elements is the current control technique that must meet the requirements for grid interconnection according to international standards and practices. The RPGS itself must be safe and highly efficient for reliable and secure grid interconnection operations. This paper presents a review of the state-of-the-art of the current control techniques for three-phase grid-interconnection of RPGSs. Several current control architectures, their operations including advantages and disadvantages were discussed. Performance comparison and evaluation of several controllers were also reviewed. (C) 2016 Elsevier Ltd. All rights reserved.
In this paper, a serial-parallel hybrid (SPH) power system formed by a fuel cell (FC), an auxiliary storage device (ASD), and the current-controlled dc-dc converters responsible for the power management are realized by using the digital signal controller (DSC) TMS32F28335. The main energy management goal is to transfer energy from the sources (FC or ASD) to the load while ensuring dc bus voltage regulation and high power conversion efficiency. In addition, a safe and reliable operation of the system has to be achieved. The selected converter and its controller features are noninverting voltage step up and step down, high efficiency, regulation of input and output currents and low ripple values, and the ability to change from input to output current regulation loop, suddenly and smoothly, and vice versa. All these features allow it to be positioned in different FC system localizations and simplify the design of the master control. Simulation and experimental results have been validated on a 48-V 1200-W dc bus.
A digital dead-beat current controller for voltage source converters is presented in this paper. The control structure is specified in a digital hardware description language, synthesized, and deployed on a field-programmable gate array chip. By updating, with negligible computation delay, the duty cycle twice in a switching period, the reference current error is nulled in half a modulation period, so that the controller's small-signal bandwidth is maximized. In addition, due to a simple transient detection circuit, the large-signal response delay is reduced to a small fraction of the modulation period, which is determined by the chosen current signal oversampling rate. The controller can effectively support different voltage-source inverter applications, such as active filters, uninterruptible power supplies, microgrid distributed energy resource controllers, and dc-dc converter applications, including interface converters for renewable energy sources, laboratory battery chargers, and electronic welding machines.
This work presents a control system suitable for high-precision pulsed current sources. The proposed control system is based on the detection of events so as to define changes in the power converter state to produce the required current waveform with a good dynamic response. Additionally, this control system is designed to regulate the flat-top current with a well-defined precision. In order to mitigate the effect of the measurement noise, an estimation algorithm for the controlled current is incorporated. This algorithm generates a filtered version of the controlled variable without affecting the control dynamics. The use of the estimated current allows to improve the detection of the events and to avoid an increase in the number of commutations due to possible erratic comparisons. Then, the estimator gains are tuned by using genetic algorithm techniques to optimize the root-mean-square value for a typical pulse. Furthermore, in order to independently perform the required set of tasks, the proposed control system is implemented by using a digital platform based on a field-programmable gate array. Additionally, due to the demanding precision in these applications, different considerations regarding its implementation, such as the digital wordlength, binary point position, rounding method, and overflow behavior, have been taken into account. Experimental results obtained from the application of the proposed control system to a laboratory prototype are presented.
A fully digital, nonlinear, wide-bandwidth current controller for dc-ac and dc-dc voltage source converters is presented in this paper. Exploiting over-sampling, the controller mimics an analog hysteresis current controller, but it does not employ analog comparators, digital-to-analog converters, or any other analog signal pre- or postprocessing circuitry. Indeed, it fully virtualizes the hysteresis controller's operation and, based only on a nonlinear, efficient current error processing algorithm, drives the power converter at almost constant switching frequency. Overall, it offers the same excellent dynamic performance of the analog hysteresis controller and, at the same time, solves most of the related problems. Because the current error sample processing algorithm is inherently parallel in structure, the controller is suited for VHDL synthesis and field-programmable gate-array implementation, which guarantees flexibility and low cost, together with minimum computation and signal conversion delays. Its intended application areas include active filters, uninterruptible power supplies, microgrid distributed energy resource controllers, laboratory battery testers, and welding machines.
The current controller with fast transient response and satisfactory steady state characteristics is required in PMSM Servo System. In this paper, the application of active disturbance rejection control (ADRC) for current loop is proposed and the design proceeding of a first-order ADRC controller in the current loop is elaborated. Then, by taking use of the ADRC controller and the analysis of the digital control delay effect, an improved method focusing on delay effects is presented. By taking these measures, the current regulation can achieve high performance. Simulation and experimental results verify the correctness and feasibility of the proposed method.
This paper presents the analysis, design, and hardware implementation of a digital polynomial Regulation, Steady-State Error and Tracking (RST) current controller-based third-harmonic modulated boost-type power factor correction (PFC) rectifier. The proposed rectifier is used at the front end of a vector controlled induction motor drive (VCIMD) to eliminate harmonics at the input AC supply. The proposed PFC rectifier modifies the input current to a sinusoid with unity power factor apart from offering DC bus voltage regulation. In this paper, a digital proportional-integral (PI) and RST current controllers are compared in terms of total harmonic distortion (THD) and power factor (PF) at the point of common coupling for different loading conditions. The RST current controller tracks the set-point accurately with zero steady-state error and offers good disturbance rejection that enables further reduction of supply current THD as compared to a conventional PI current controller. The control algorithm for the PFC front end rectifier along with vector control technique is implemented using a digital signal processor, and the dynamic performance is analyzed for step changes in reference speed and load torques, demonstrating significant improvement in the performance indices.
This paper presents new topologies for emulating floating immittance functions using three to five passive elements and only two current-feedback operational-amplifiers (CFOAs). The feasibility of using only two CFOAs and two passive components is explored. The proposed topologies can emulate lossy positive and negative inductances and capacitance-, inductance-, resistance-multipliers, and frequency dependent negative and positive conductances. The functionality of the proposed circuits was experimentally verified using the commercially available AD844 CFOA. The experimental results are in excellent agreement with theoretical calculations.
This paper presents a new topology for emulating floating lossless negative inductance, positive frequency dependent resistance and resistance-controlled resistance and capacitance multipliers. The circuit uses three current-feedback operational-amplifiers (CFOAs), and three passive elements. The functionality of the proposed circuit is verified using the Advanced Design System (ADS) software and the AD844 CFOA. The simulation results are in excellent agreement with the theoretical calculations.
It is shown that the recently-proposed modified current feedback operational amplifier (MCFOA) is quite a versatile element in that given a realization for a system function using MCFOAs, we can obtain three alternate realizations using the same MCFOA but by appropriately connecting the y, x, w, and z terminals of the MCFOA to the remaining part of the original realization. Using the results concerning the transpose of a multi-terminal element, it is further shown that the transpose of an MCFOA is another MCFOA. Thus, using the results of transposition, given a voltage-mode circuit using MCFOAs, we can directly obtain four current-mode circuits using the same MCFOAs or vice versa. Copyright (c) 2015 John Wiley & Sons, Ltd.
New voltage-mode electronically tunable notch, bandpass, highpass and lowpass shadow filters are presented. The filters are built around the current-feedback operational-amplifier. In each case one or more of the parameters of the filter can be electronically controlled by adjusting the gain of an external amplifier built around the current-feedback operational-amplifier. Contrary to the current-mode shadow filters where a summing junction must be used, no summing amplifiers are used in these voltage-mode realizations. Experimental results obtained using the AD844 current-feedback operational-amplifier are presented. The results obtained confirm the functionality of the proposed circuits.
This paper presents the experimental results obtained from a memristor-based Wien-bridge oscillator implemented using a new memristor emulator. The memristor emulator can be implemented using off-the-shelf components. The experimental results show that nonlinear chaotic as well as linear oscillations can be obtained from the same circuit by careful adjustment of the value of a single resistor. The proposed circuit can be easily presented in an undergraduate laboratory course to demonstrate the use of memristors in generating chaotic oscillators.
Using a unified representation for the two current-feedback operational-amplifiers (CFOAs) based sinusoidal oscillators, new structures and circuits of this type are systematically discovered. Three catalogues for three different structures with each structure realizing 17 oscillator circuits are presented. Some of the new circuits are enjoying the attractive features of using grounded capacitors and/or independent/orthogonal tuning for the frequency and condition of oscillation. However, the classification of independent/orthogonal tuning may be misleading as it is based on using the Barkhausen criterion. Therefore, it is shown that using the roots of the characteristic equation of a specific oscillator circuit; while not leading to accurate results, may avoid any misleading conclusion regarding the orthogonal tuning of the frequency and condition of oscillation. Experimental results using the AD844 CFOA are included.
This paper presents a low power, high slew rate, high gain, ultra wide band two stage CMOS cascode operational amplifier for radio frequency application. Current mirror based cascoding technique and pole zero cancelation technique is used to ameliorate the gain and enhance the unity gain bandwidth respectively, which is the novelty of the circuit. In cascading technique a common source transistor drive a common gate transistor. The cascoding is used to enhance the output resistance and hence improve the overall gain of the operational amplifier with less complexity and less power dissipation. To bias the common gate transistor, a current mirror is used in this paper. The proposed circuit is designed and simulated using Cadence analog and digital system design tools of 45 nanometer CMOS technology. The simulated results of the circuit show DC gain of 63.62 dB, unity gain bandwidth of 2.70 GHz, slew rate of 1816 V/mu s, phase margin of 59.5 degrees, power supply of the proposed operational amplifier is 1.4 V ( rail- to- rail +/- 700 mV), and power consumption is 0.71 mW. This circuit specification has encountered the requirements of radio frequency application.
This paper presents a new current mode implementation of a balanced-output-signal generator that utilizes an operational floating current conveyor (OFCC) as a basic building block. The OFCC, as a current-mode device, shows flexible properties with respect to other current or voltage-mode circuits. The advantages of the proposed current mode balanced-output-signal generator (CMBG) are threefold. Firstly, it offers an accurate phase and amplitude performance over a wide bandwidth without requiring matched resistors. Secondly, it has a differential input and it can provide either current or voltage outputs. Finally, the proposed CMBG circuit offers a significant improvement in accuracy compared to other CMBGs based on the current conveyor. The proposed CMBG has been analyzed, simulated and experimentally tested. The experimental results verify that the proposed CMBG outperforms existing CMBGs in terms of the number of basic building blocks used and accuracy.
In this paper, a single current sensor technique (SCST) is proposed for single-phase full-bridge inverters. The proposed SCST measures the currents of multiple branches at the same time, and reconstructs the average inductor, capacitor, and load current in a single switching cycle. Since all of the branches' current in the LC filter and the load are obtained using the SCST, both the inductor and the capacitor current feedback schemes can be selectively applied while taking advantages of each other. This paper also analyzes both of the current feedback schemes from the view point of the closed-loop output impedance. The proposed SCST and the analysis in this paper are verified through experiments on a 3kVA single-phase uninterruptible power supply (UPS).
This paper presents a temperature-compensated CMOS current reference with low line regulation current mirror. The circuit is based on a bandgap reference voltage that achieves the temperature compensation of resistor by the negative temperature coefficient (TC) of a high-resistance polysilicon (HR poly) resistor with the positive TC of an n-well resistor. The low line regulation current mirror is implemented by using a negative feedback connected operational amplifier. Prototypes of 1 mu A current reference from 0.35 mu m CMOS process show a maximum temperature coefficient of 139 ppm/A degrees C for a temperature range of 0-80 A degrees C. The line regulation is reduced to 0.5 %/V for supply voltage of 3.5 to 5.5 V.
This paper presents a chopper amplifier for precision current sensing, capable of handling common mode input voltages outside the supply rails. For high common mode rejection ratio (CMRR) and DC gain, the amplifier employs a three-stage topology with nested-Miller frequency compensation. By using the chopping technique, a referred to input offset voltage of +/-90 mu V is obtained. To reduce the output ripples caused by the chopping technique the amplifier employs a notch filter. A CMRR of 123dB has been obtained, considering a supply voltage of 5V, for a common mode input voltage range from 4V to 80V. The stability of the operational amplifier (OA) is ensured for a minimum closed loop gain of 20V/V.
This paper presents a current sense amplifier (CSA) capable of performing measurements at high input common mode (CM) voltages independent of the power supply rail. The proposed circuit employs a fully low voltage amplifier cell, a correction block for maintaining the linearity of the input stage over the entire input CM and a protection circuit against high differential input voltages (DIFF). Furthermore, a trimming procedure that enables the use of typical polysilicon gain resistors without losing accuracy and precision is discussed. The proposed architecture has been implemented in a standard 0.25 mu m BCD technology and its performances have been confirmed by both simulations and measurements.
This paper presents a high accuracy and high bandwidth current sense circuit for digitally controlled DC-DC buck converters. The circuit uses lossless inductor DCR current sensing and a sigma delta modulator ADC to sense the average current in the inductor to high accuracy. These accurate but low bandwidth measurements are unsuitable for use in feedback control loops as their acquisition delay would limit the achievable loop bandwidth. To solve this issue a Kalman Filter estimates the inductor current at the switching frequency of the converter. The output of the estimator is shown through experimental results to achieve 0.3A static current accuracy when used in a buck converter switching at 1MHz and using a power efficient inductor with a DCR of only 165 mu Ohms.
Current sensors are usually protected against electromagnetic interference (EMI) by means of filters placed at the PCB level. The literature has plenty of solutions aimed at keeping EMI filters' attenuation as high as possible in the widest possible frequency range. However such filters are less effective than expected because of the parasitic elements introduced by interconnects. As a consequence, EMI can be propagated into ICs causing temporary or definitive operation failures. This paper points out the causes of EMI-induced errors in high-side current sensors based on low-offset chopper OTAs. Analyses presented in the paper are supported by direct power injection measurements carried out on a test chip.
The design of a High Stability Voltage Controlled Current Source (VCCS) for Cervical Cancer Detection (CCD) applying Electrical Bio-Impedance Spectroscopy (EBS) is presented. The circuit was designed and simulated in TSMC 130 nm CMOS technology at 1.3V power supply. The proposed Howland Current Source is based on Self-Biased Complementary Folded Cascode (SB-CFC) Operational Amplifier (OA). Complying with the requirements for medical electrical equipment of international standard ABNT-NBR-IEC-60601-1 the sinusoidal current peak amplitude was settled at 10. A. In accordance with the requirements of the EBS for CCD, the specifications for the SB-CFC-OA were calculated to meet the 100 Hz to 1 MHz frequency range for the sinusoidal output current and the output impedance higher than 1 M Omega at 1 MHz frequency. Post-layout simulations were run and the main results were: 10 +/- 0.0335 mu A for the output current peak amplitude over the specified frequency range and with 5 k Omega load impedance; values above 1.6 M Omega output impedance @ 1 MHz; nominal current amplitude variations lower than 0.4% for load impedances in the range of 10 Omega up to 5 k Omega. From these results, the performance of the VCCS is adequate for EBS-CCD applications.
The design of a high stability voltage controlled current source (VCCS) for cervical cancer detection (CCD) applying electrical bio-impedance spectroscopy (EBS) is presented. The circuit was designed, simulated and fabricated in TSMC 130 nm CMOS technology at 1.3 V power supply. The proposed Howland current source is based on self-biased complementary folded cascode (SB-CFC) operational amplifier (OA). Complying with the requirements for medical electrical equipment of international standard ABNT-NBR-IEC-60601-1 the sinusoidal current peak amplitude was settled at 10 mu A. In accordance with the requirements of the EBS for CCD, the specifications for the SB-CFC-OA were calculated to meet the 100 Hz-1 MHz frequency range for the sinusoidal output current and the output impedance higher than 1 Ma"broken vertical bar at 1 MHz frequency. Post-layout simulations were run and the main results were: 10 +/- 0.0335 mu A for the output current peak amplitude over the specified frequency range and with 5 ka"broken vertical bar load impedance; values above 1.6 Ma"broken vertical bar output impedance at 1 MHz; nominal current amplitude variations lower than 0.4 % for load impedances in the range of 10 a"broken vertical bar up to 5 ka"broken vertical bar. And the experimental result for maximum non-linearity was 2.19 % of full scale. From these results, the performance of the VCCS is adequate for EBS-CCD applications.
This article presents a new topology for implementing an electronically tunable bandpass filter using the current-feedback operational amplifier. The electronic tuning of the center frequency of the proposed circuit is achieved using an externally connected voltage amplifier in the feedback path without disturbing the constituents of the filter itself, that is a shadow filter. The proposed circuit can be used for developing an undergraduate experiment which illustrates the operation of bandpass filter and the electronic control of its center frequency using the concept of shadow filter. Experimental results obtained using the AD844 current-feedback operational amplifier are included.
This paper presents a new topology for emulating floating lossless negative immittance functions. The proposed circuit uses three current-feedback operational-amplifiers (CFOAs), and three passive elements. The functionality of the proposed circuit is verified using the Advanced Design System (ADS) software and the AD844 CFOA. The simulation results obtained from a floating negative lossless inductance emulator are in excellent agreement with the theoretical calculations.
This paper proposes a macromodel to emulate the nonlinear behavior of current-feedback operational amplifiers (CFOAs) at low-frequency. The main difference between this macromodel and those reported previously in the literature is that herein, real physical active device performance parameters along with parasitic elements associated to the input-output terminals of the amplifier are considered. To validate the deduced behavioral model, a saturated nonlinear function series (SNFS) based on CFOAs is built and numerical simulations are generated. In this point, the modeling problem is cast in terms of an augmented set of equations but that, unlike a piece-wise linear (PWL) approach, the dynamic behavior of each CFOA is considered. Afterwards, the SNFS is experimentally tested by using commercially available active devices, confirming good agreement among theoretical simulations and experimental tests at two operating frequencies and showing a better accuracy compared with a PWL approach and a linear model for CFOAs. Because the derived nonlinear macromodel for CFOAs is used for generating the behavioral model of the SNFS, one concludes that the latter is also both accurate and efficient with respect to traditional techniques, such as PWL approaches. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents a new topology for implementing a bandpass shadow filter using the current-feedback operational amplifier (CFOA). The proposed circuit uses CFOAs, and avoids the use of external summing circuit to implement a shadow bandpass filter with controlled center frequency. Experimental results obtained using the AD844 CFOA are included.
This paper presents a gray-box equivalent circuit model (ECM) in order to predict the performance of direct methanol fuel cell (DMFC) unit. The ECM is composed of electronic components ranging from operational amplifier resistors to diodes. The current-voltage profiles and current-power profiles of this ECM are validated by the simulation results of the COMSOL model. Afterward, the influences of methanol concentration, operating temperature, and oxygen concentration on the performance of the single passive DMFC are all validated experimentally. All validations show that the ECM provides a good approximation of the behavior of the DMFC. In addition, a simulated application of a circuit system employing the ECM is explained. The simulated result is validated experimentally. This research makes it possible to analyze the behavior of a DMFC in real applications.
This paper presents a reference modification model digitally controlled dc-dc converter. The proposed method is able to obtain superior transient response because it modifies a reference of conventional feedback loop against the change of output voltage. The modifying process operates only in the transient state. During the steady state, the feedforward control cancels a steady-state-error. Since the feedforward control uses the load current value, this paper discusses two current-sensing methods. One is the output current-sensing method using the sensing resistor, and the reactor current-sensing method using the R-C filter is discussed in order to reduce a performance loss by the sensing resistor. As a result, the output current-sensing method is effective in case that high-transient-response performance is required. On the other hand, it is better to use the reactor current-sensing method when efficiency is important.
This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important techniques, students acquire novel biochemical data in their kinetic analysis of mutant enzymes. The experiments are designed to build on students' work from week to week in a way that requires them to apply quantitative analysis and reasoning skills, reinforcing traditional textbook biochemical concepts. Students are assessed through lab reports focused on journal style writing, quantitative and conceptual question sheets, and traditional exams. (C) 2016 by The International Union of Biochemistry and Molecular Biology
Eucalyptus spp. and hybrids remain among the mostly widely-planted species in the world, owed principally to its diverse genome, its site-adaptability, and relatively fast growth rates. Numerous pure species, and yet more hybrid clones have been globally deployed in plantations, as industry seeks to meet growing demands for wood and their products. As a result, various propagation approaches have been explored, from seeds to vegetative propagation by cuttings and trough in vitro method, with a view to remaining cost-effective, yet efficient, and sustainable. Vegetative propagation of eucalypts is preferred, as it conserves valuable germplasm and offers predictability in commercial foplantations. The range of eucalypt species and hybrids in commercial use, however, has resulted in an array of propagation protocols, as researchers seek to optimise growth conditions to enhance the quality and yields of rooted cuttings and in vitro propagules. The exogenous supply of plant growth regulators (PGRs) is central to the objectives of these protocols. The present review traces recent developments in Eucalyptus propagation, and presents a selection of published protocols for a variety of species, explants and PGR supply. With advancements in plant physiology, molecular biology and biochemistry, a clearer picture of the vegetative physiological growth requirements steadily develops, leading researchers to more accurately manipulate and improve Eucalyptus propagation. Furthermore, the recent completion of the E. grandis genome sequence will drive advancements in eucalypt genomics, metabolomics, and proteomics. Collectively, these developments will present future opportunities to accurately decipher, augment and significantly enhance sustainable growth, yields, valuable traits and germplasm conservation of the eucalypts.
BACKGROUND: In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients. OBJECTIVE: The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia. METHODS: Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia. RESULTS: Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n [56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4D T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID). CONCLUSIONS: The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Leukocyte populations change profoundly in the human endometrium during the menstrual cycle. However the predominant cell, the uterine natural killer (uNK) cell does not contain steroid receptors. From gene array analysis we identified a transcript encoding chemokine (C-X-C motif) ligand 14 (CXCL14) which is markedly up-regulated in the secretory phase of the cycle. We confirm this data by northern blotting and quantitative PCR. Using in situ hybridization we localized CXCL14 mRNA to the glandular epithelial cells where it was detected only in the secretory phase of the cycle. Candidate progesterone response elements were identified at positions -2028/-2007 and -722/-697 (PRE1 and PRE2, respectively) relative to the translation start site. These were functionally tested using luciferase reporter deletion constructs, electrophoretic mobility shift assays and site-directed mutagenesis. The deletion/mutation of these sites reduced progesterone induction by 40 and 20%, respectively. Finally, we demonstrated that recombinant CXCL14 stimulated uNK cell chemotaxis in vitro. We therefore conclude that CXCL14 is likely to be regulated by progesterone in human endometrium and that it may exert a chemoattractive effect on uNK cells and in part be responsible for their clustering around the epithelial glands.
Background: Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Methods: Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. Results: We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3 beta/beta-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and beta-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. Conclusion: In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.
The accurately estimated state is of great importance for maintaining a stable running condition of power systems. To maintain the accuracy of the estimated state, bad data detection (BDD) is utilized by power systems to get rid of erroneous measurements due to meter failures or outside attacks. However, false data injection (FDI) attacks, as recently revealed, can circumvent BDD and insert any bias into the value of the estimated state. Continuous works on constructing and/or protecting power systems from such attacks have been done in recent years. This survey comprehensively overviews three major aspects: constructing FDI attacks; impacts of FDI attacks on electricity market; and defending against FDI attacks. Specifically, we first explore the problem of constructing FDI attacks, and further show their associated impacts on electricity market operations, from the adversary's point of view. Then, from the perspective of the system operator, we present countermeasures against FDI attacks. We also outline the future research directions and potential challenges based on the above overview, in the context of FDI attacks, impacts, and defense.
A frequency-domain approach to the design of digital feedback controls for SISO systems is presented. The noise gain is minimized, subject to a phase margin constraint. The controller is expressed as a repeated-pole expansion, which reduces the optimization to a quadratic problem and a linear system of equations. PID+filter controls are produced as a limiting case.
Researchers are concerned with identifying the risk and protective factors associated with adolescents' involvement in cyberharassment. One such factor is parental mediation of children's electronic technology use. Little attention has been given to how different parental mediation strategies (i.e., instructive, restrictive, co-viewing) relate to adolescents' cyberharassment (i.e., cyberbullying, cybertrolling) perpetration and victimization, and how gender might impact these associations. To this end, the present study examined the moderating effect of gender on the longitudinal association between parental mediation strategies and adolescents' cyberharassment involvement. This focus was examined using a sample of 568 (53% female) adolescents from the 8th grade in the United States. The association between restrictive mediation and cybervictimization was more positive for girls when compared to boys, while the relationship between instructive mediation and cybervictimization was more negative for girls than for boys. The findings underscore the importance of considering parents in adolescents' cyberharassment involvement. (C) 2017 Elsevier Ltd. All rights reserved.
Type 4 cyclic nucleotide phosphodiesterases (PDE4) are major members of a superfamily of enzymes (PDE) involved in modulation of intracellular signaling mediated by cAMP. Broadly expressed in most human tissues and present in large amounts in the liver, PDEs have in the last decade been key therapeutic targets for several inflammatory diseases. Recently, a significant body of work has underscored their involvement in different kinds of cancer, but with no attention paid to liver cancer. The present study investigated the effects of two PDE4 inhibitors, rolipram and DC-TA-46, on the growth of human hepatoma HepG2 cells. Treatment with these inhibitors caused a marked increase of intracellular cAMP level and a dose- and time-dependent effect on cell growth. The concentrations of inhibitors that halved cell proliferation to about 50% were used for cell cycle experiments. Rolipram (10 mu M) and DC-TA-46 (0.5 mu M) produced a decrease of cyclin expression, in particular of cyclin A, as well as an increase in p21, p27 and p53, as evaluated by Western blot analysis. Changes in the intracellular localization of cyclin D1 were also observed after treatments. In addition, both inhibitors caused apoptosis, as demonstrated by an Annexin-V cytofluorimetric assay and analysis of caspase-3/7 activity. Results demonstrated that treatment with PDE4 inhibitors affected HepG2 cell cycle and survival, suggesting that they might be useful as potential adjuvant, chemotherapeutic or chemopreventive agents in hepatocellular carcinoma. (C) 2016 Wiley Periodicals, Inc.
The aim of the present study was to investigate the association between methylation of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and telomerase activity in children with acute lymphoblastic leukemia (ALL). A total of 72 children with ALL and 12 children with immune thrombocytopenia (ITP) were subjected to bone marrow aspiration and methylation-specific polymerase chain reaction analysis, and modified telomeric repeat amplification protocol assay analyses, to evaluate CDKN2B methylation and telomerase activity, respectively. The results of the present study demonstrated that, of these 72 children with ALL, 31 exhibited CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited no CDKN2B methylation (36.9%). However, no CDKN2B methylation was detected in the ITP controls. Furthermore, the mean level of telomerase activity was 39.52 +/- 39.33 total product generated (TPG) units in children with ALL, which was significantly increased compared with 2.49 +/- 2.27 TPG units in the ITP controls (P=0.002). The mean levels of telomerase were 49.09 +/- 44.43 and 29.99 +/- 32.43 TPG units in children with ALL with and without CDKN2B methylation, respectively (P=0.041), therefore children with ALL exhibited significantly increased levels of telomerase. The increased telomerase activity was significantly associated with increased risk of childhood ALL (P=0.023). A total of 22/31 children with ALL with methylated CDKN2B (71.0%) and 17/41 children with ALL with unmethylated CDKN2B (41.46%) exhibited increased telomerase activity (>15 TPG units). The results of the present study suggest that hypermethylation of CDKN2B CpG islands and hyperactivity of telomerase are common events in childhood ALL, and hypermethylation of CDKN2B CpG islands was significantly associated with upregulated telomerase activity (P=0.013).
Intestinal subepithelial myofibroblasts (SEMFs) is a specific population of cells involved in intestinal inflammation and carcinogenesis via an elaborate network of cytokines, chemokines and other inflammatory factors, including PGE2. Sphingosine-1-phosphate (S1P) has been implicated as an important mediator of inflammation and cancer and in certain cell types increases cyclooxygenase-2 (COX-2) expression. In the present study, we aimed to assess involvement of S1P in COX-2 expression by SEMFs. Primary SEMFs were obtained from C57BL/6J mouse and their identity was verified by fluorescent staining of specific marker proteins. Expression of S1P receptors 1, 2, 3 and sphingosine kinases 1 and 2 in SEMFs were determined by RT-PCR analysis. COX-2 expression and PGE2 production were assayed by Western blotting and ELISA, respectively. COX-2 mRNA stability was assayed by Northern blotting. S1P produced dose-dependent increase in COX-2 expression, resulting in increased PGE2 release from SEMFs. Using specific inhibitors, we show that actions of p38, ERK, IKK, and PKC were involved in S1P-induced COX-2 expression. On the other hand, p38 and PKC had lesser roles in IL-1 beta-induced COX-2 expression. Inhibition of sphingosine kinase to block S1P production did not affect IL-1 beta-induced COX-2 expression, but S1P amplified IL-1 beta-induced p38 activation and COX-2 expression. PKC inhibition blocked S1P amplified COX-2 expression. S1P addition increased COX-2 mRNA stability. In SEMFs, S1P amplifies IL-1 beta-induced COX-2 expression through increased mRNA stability. These observations point to involvement of S1P in activation of SEMFs that may contribute to intestinal inflammation and carcinogenesis.
Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor beta (TGF-beta) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-beta can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-beta-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-beta. We also evaluated the effects of tristetraprolin (UP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-beta. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-beta, suggesting that TGF-beta-induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-beta rapidly and transiently induced the expression of UP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased UP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-beta. Furthermore, we showed that Smad3 is essential to UP-dependent down-regulation of COX-2 expression in response to TGF-beta. Conclusion The results of this study show that TGF-beta down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin (PG) biosynthesis, plays a key role in inflammation, tumorigenesis, development and circulatory homeostasis. COX-2 expression is rapidly and sensitively regulated by various stimuli, and also its regulation is distinct among cell types at transcriptional and posttranscriptional levels. Therefore, it is important to consider these features of COX-2 expression in the reporter assays we describe in this chapter. Emphasis should be made with regard to two points. Firstly, COX-2 reporter assays should be evaluated by intrinsic COX-2 expression, such as RT-PCR, northern blotting, western blotting, or by PGE(2) measurement. Secondly, one must carefully choose several conditions in the reporter assays for experimental purposes.
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein alpha (FAP alpha) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAP alpha, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment. This study evaluated the efficacy of a previously unreported CY combination strategy to enhance the limited anti-tumor effect of a DNA vaccine targeting FAP alpha. The results suggested CY administration could promote the percentage of splenic CD8(+)T cells and decrease the proportion of CD4(+)CD25(+)Foxp3(+)Tregs in spleen. In tumor tissues, levels of immunosuppressive cytokines including IL-10 and CXCL-12 were also reduced. Meanwhile, the CY combination did not impair the FAP alpha-specific immunity induced by the DNA vaccine and further reduced tumor stromal factors. Most importantly, FAP-vaccinated mice also treated with CY chemotherapy showed a marked suppression of tumor growth (inhibition ratio =80%) and a prolongation of survival time. Thus, the combination of FAP alpha immunotherapy and chemotherapy with CY offers new insights into improving cancer therapies.
The retinoic acid metabolizing enzyme Cyp26a1 plays a pivotal role in vertebrate embryo development. Cyp26a1 was characterized previously as a differentially expressed gene in peri-implantation rat uteri via suppressive subtracted hybridization analysis. However, the role of Cyp26a1 in rat embryo implantation remained elusive. The expression of Cyp26a1 in the uteri of early pregnancy, pseudopregnancy and artificial decidualization was detected by northern blotting, real time-PCR, in situ hybridization, western blotting and immunofluorescent staining. The effect of Cyp26a1 on apoptosis of endometrial stromal cells (ESCs) isolated from rat uteri was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst staining. Apoptosis-related proteins in ESCs were detected by western blotting. Cyp26a1 showed distinctive expression patterns in embryos and uteri during the peri-implantation period, with a remarkable increase (P < 0.01 versus Days 4-5) in mRNA and protein in the implantation phase (Days 5.5-6.5 of pregnancy). CYP26A1 was specifically localized in glandular epithelium, luminal epithelium and decidua basalis. The level of CYP26A1 protein was significantly increased in uteri of artificial decidualization (P < 0.01 versus control). Forced Cyp26a1 overexpression significantly reduced the sensitivity of ESCs to etoposide-induced apoptosis, with reductions in p53 (P < 0.01) and Fas (P < 0.05) proteins versus control, while in contrast, FasL (P < 0.01) and proliferating cell nuclear antigen (P < 0.05) proteins increased. Cyp26a1 is spatiotemporally expressed in the uterus during embryo implantation and decidualization. Overexpression of Cyp26a1 attenuates the process of uterine stromal cell apoptosis, probably via down-regulating the expression of p53 and FasL.
Introduction: Clopidogrel is an antiplatelet drug widely used in patients with acute coronary syndromes or stroke. Despite adequate antiplatelet therapy, some patients develop acute ischemic events. This is partly attributed to the fact that they have poor inhibition of platelet reactivity, despite treatment. This study aimed to assess the impact of clinical and demographic variables and of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms on platelet response to clopidogrel evaluated using impedance aggregometry in an East European population. Methods: The study included 189 clopidogrel-treated patients with acute coronary syndromes and noncardiogenic ischemic stroke. Platelet aggregation was evaluated by impedance aggregometry. CYP2C19 loss-of-function polymorphisms were detected using the polymerase chain reaction restriction fragment length polymorphism technique. Various clinical and demographic data were also recorded. Results: In our data set, 81% of the patients were responders and 19% nonresponders to clopidogrel therapy. The distribution of CYP2C19 polymorphisms was as follows: 61.1% of patients were CYP2C19 wild-type homozygotes, 27.7% of patients were CYP2C19*2 heterozygotes, 1.1% of patients were CYP2C19*3 heterozygotes, and 10% of patients were CYP2C19*2 homozygotes. The highest level of association with clopidogrel response status was found for CYP2C19 polymorphisms, concomitant aspirin treatment, leukocyte and platelet count, history of myocardial infarction, arterial hypertension, and ward where patients were admitted. Conclusion: The prevalence of clopidogrel resistance in our East European population was in line with that reported for Western populations. Clopidogrel response was significantly influenced by the presence of CYP2C19 polymorphisms. Interestingly, the concomitant use of aspirin had a significant impact on platelet response to clopidogrel, indicating a synergic interaction between these drugs.
Purpose: Asian populations have around 40-60% frequency of reduced function allele CYP2D6*10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6*10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6*10 allele or two CYP2D6*10 alleles has not been reported in large Asian populations. Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with CYP2D6*1/*1 (n = 22), CYP2D6*1/*10 (n = 93), CYP2D6*10/*10 (n = 85), and CYP2D6*5/*10 (n = 35) were phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios (MR) were calculated as the ratio of parent drug to metabolite in 0-3 h urine, 3 h plasma, and 3 h saliva for each sample type. Results: The urinary, plasma, or salivary MRs increased successively in subjects with CYP2D6*1/*1, *1/*10, *10/*10, and *5/* 10 (all P < 0.001). In the normal metabolizer group, homozygous CYP2D6*10/*10 decreased the CYP2D6 enzyme activity further than heterozygous CYP2D6* 1/* 10. Urinary, plasma, and salivary MRs were highly correlated. Conclusion: The normal metabolizer group calls for a more detailed classification. The activity score system could more accurately predict enzyme activity than by grouping a number of genotypes into a single phenotype group. Single-point plasma samples and saliva samples could be used as alternative phenotyping methods for clinical convenience.
Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides leading to resistance in insect populations. A polyphagous pest, Spodoptera litura, has developed resistance to a wide range of insecticides. In the present study, a novel P450 gene, CYP321B1, was cloned from S. litura. The function of CYP321B1 was assessed using RNA interference (RNAi) and monitoring resistance levels for three commonly used insecticides, including chlorpyrifos, beta-cypermethrin and methomyl. The full-length complementary DNA sequence of CYP321B1 is 1814 bp long with an open reading frame of 1488 bp encoding 495 amino acid residues. Quantitative reverse-transcriptase polymerase chain reaction analyses during larval and pupal development indicated that CYP321B1 expression was highest in the midgut of fifth-instar larvae, followed by fat body and cuticle. The expression of CYP321B1 in the midgut was up-regulated by chlorpyrifos, beta-cypermethrin and methomyl with both lethal concentration at 15% (LC15) (50, 100 and 150 mu g/mL, respectively) and 50%(LC50) dosages (100, 200 and 300 mu g/mL, respectively). Addition of piperonyl butoxide (PBO) significantly increased the toxicity of chlorpyrifos, beta-cypermethrin and methomyl to S. litura, suggesting a marked synergism of the three insecticides with PBO and P450-mediated detoxification. RNAi-mediated silencing of CYP321B1 further increased mortality by 25.6% and 38.9% when the fifth-instar larvae were exposed to chlorpyrifos and beta-cypermethrin, respectively, at the LC50 dose levels. The results demonstrate that CYP321B1 might play an important role in chlorpyrifos and beta-cypermethrin detoxification in S. litura.
Our previous studies have found that the levels of cytochrome P450 and oxidative activities of cytochrome P450 monooxygenases were enhanced in a fenvalerate-resistant strain (HDFR) of Helicoverpa armigera (Hubner) in China, comparing with those of a susceptible strain (HDS). Here, we report the molecular cloning and gene expression of a specific P450 CYP6B7 from HDFR and HDS strain of H. armigera. Comparison of the deduced amino acid sequence showed that there were three substitutions of amino acids in the coding region of CYP6B7 cDNA of HDFR strain, comparing with that of HDS strain. Meanwhile, there were three mutative nucleotides in the intron of CYP6B7 genomic DNA in HDFR strain. Northern blotting analysis showed that the expression of CYP6B7 mRNA in HDFR strain of H. armigera was more than 5-fold higher than that in HDS strain. Further studies indicated that the expression of CYP6B7 mRNA increased as the larvae developed; however, it was rarely detected in the pupae and adult stages. The results suggested that cytochrome P450 CYP6B7 plays an important role in the pyrethroid insecticide fenvalerate resistance of HDFR strain of H. armigera; over-expression of CYP6B7 combined with relevant substitution of amino acids might be responsible for fenvalerate-resistance in H. armigera from China.
Although herpesviruses such as cyprinid herpesvirus 3 (CyHV-3) can establish lifelong latent infections, little is known about latency conditions in farmed koi populations in China. We used nested polymerase chain reaction targeting the TK gene and an indirect antibody ELISA to screen asymptomatic fish obtained from southern China for evidence of CyHV-3 infection. CyHV-3 DNA could be detected either in peripheral blood leukocytes or from gills of asymptomatic koi. Most koi sera did not contain anti-CyHV-3 antibodies; however, 5 samples were ELISA positive, providing evidence of prior CyHV-3 infections. These findings suggest that koi may survive CyHV-3 infections and become virus carriers.
Two genotypes showing differential immunity against Karnal bunt (Tilletia indica) were used to investigate the role of three members of cystatin gene family in growth stage dependent immunity in wheat (Triticum aestivum L.). Three members of cystatin gene family (WC1, WC2, and WC4) were cloned and sequenced. Analysis of sequenced data showed that there was 76-99% nucleotide and protein sequence identity between different genes of the wheat cystatin. In silico amino acid sequence analysis revealed the presence of a conserved signature pattern of residues and also the functional domains were presumed to be actively involved in imparting cysteine protease inhibition capability. The semi-quantitative and quantitative levels of these members were measured by means of RT-PCR, northern blotting, western blotting, and by ELISA techniques. The members of cystatin gene family were expressed in both resistant (HD 29) and susceptible genotypes (WH 542); however, the expression level was significantly (P0.05) in contrary to WC1 family whose expression gradually increased from S-v to S-2 stage. According to the intensity of the detected band in RT PCR, northern blot and western blot, WC1 family seems to be expressed more than the other gene families. The immunoassay results further showed that WC1 protein was abundantly expressed in resistant genotype and high expression was observed at the S2 stage as compared to susceptible genotype (P < 0.001) suggesting that low level of expression of WC1 in S2 stage is responsible for KB infection. The results of the present study clearly indicate the role of cystatin gene family in differential and stage dependent immunity against KB.
A cysteine protease inhibitor (CPI) with an apparent molecular mass of 11.5 kDa was purified from larval hemolymph of the tobacco hornworm (Manduca sexta) by gel filtration on Sephadex G-50 followed by hydrophobic and ion-exchange column chromatographies. The purified cysteine proteinase inhibitor, denoted as MsCPI, strongly inhibited the plant cysteine protease, papain, with a K-i value of 5.5 x 10(-9)M. Nucleotide sequence analysis of a partial cDNA encoding MsCPI indicated that MsCPI consists of 105 amino acid residues in a sequence that is similar to sarcocystatin A from Sarcophaga peregrina. However, northern blotting and PCR analyses using the specific primers of MsCPI suggested that the mRNA encoding MsCPI had a size of more than 12 kilobases, which included at least six tandemly repeated MsCPI segments. MsCPI was expressed in Escherichia coli and the recombinant protein effectively inhibited cysteine proteases from plants as well as from animals such as cathepsins B (K-i, 6.8 nM), H (3.0 nM), and L (0.87 nM). There was no inhibition exhibited toward trypsin, chymotrypsin, subtilisin, pepsin or themolysin. (c) 2007 Elsevier Ltd. All rights reserved.
The oomycete Phytophthora capsici is a plant pathogen responsible for important losses to vegetable production worldwide. Its asexual reproduction plays an important role in the rapid propagation and spread of the disease in the field. A global proteomics study was conducted to compare two key asexual life stages of P. capsici, i.e. the mycelium and cysts, to identify stage-specific biochemical processes. A total of 1200 proteins was identified using qualitative and quantitative proteomics. The transcript abundance of some of the enriched proteins was also analysed by quantitative real-time polymerase chain reaction. Seventy-three proteins exhibited different levels of abundance between the mycelium and cysts. The proteins enriched in the mycelium are mainly associated with glycolysis, the tricarboxylic acid (or citric acid) cycle and the pentose phosphate pathway, providing the energy required for the biosynthesis of cellular building blocks and hyphal growth. In contrast, the proteins that are predominant in cysts are essentially involved in fatty acid degradation, suggesting that the early infection stage of the pathogen relies primarily on fatty acid degradation for energy production. The data provide a better understanding of P. capsici biology and suggest potential metabolic targets at the two different developmental stages for disease control.
Mice homozygous for a defect in the PTCD2 (pentatricopeptide repeat domain protein 2) gene were generated in order to study the role of this protein in mitochondrial RNA metabolism. These mice displayed specific but variable reduction of ubiquinol-cytochronic c reductase complex activity in mitochondria of heart, liver and skeletal muscle due to a decrease in the expression of mitochondrial DNA-encoded cytochrome b, the catalytic core of the complex. This reduction in mitochondrial function has a profound effect on the myocardium, with replacement of ventricular cardiomyocytes by fibro-fatty tissue. Northern blotting showed a reduction in the mRNA for the mitochondrial DNA encoded proteins cytochrome b (cytb) and ND5 (NADH dehydrogenase subunit 5) and an elevation in a combined pre-processed ND5-CYTB transcript. This suggests that the PTCD2 protein is involved in processing RNA transcripts involving cytochrome b derived from mitochondrial DNA. This defines the site for PTCD2 action in mammalian mitochondria and suggests a possible role for dysfunction of this protein in the actiology of heart failure.
Previous studies performed in our laboratory have measured the effect of atrazine exposure on cytochrome P450-dependent monooxygenase activity and have found increased activity in midge larvae (Chironomus tentans) as a result of atrazine exposure (1-10 ppm). Here we report the cloning and expression of a specific C tentans CYP4 gene that is responsive to atrazine induction with an open reading frame of 1678 bp which encodes a putative protein of 559 amino acid residues. Alignments of deduced amino acid sequences with other insect P450 genes and phylogenetic analysis indicated a high degree of similarity to other insect CYP4 genes. Northern blotting analysis employing a fragment of 1200 bp from the CYP4 gene as a probe indicated that the CYP4 gene was expressed in all developmental stages, but was expressed at highest levels in late instar larvae. Additionally, over-expression of CYP4 in C. tentans exposed to atrazine (10 mg/l) confirms the ability of atrazine to induce specific P450 genes and provides insight into potential consequences of atrazine exposure in aquatic organisms. (C) 2007 Elsevier Inc. All rights reserved.
A new cytochrome P450 gene, CYP4G25, was identified as a differentially expressed gene between the diapausing and post-diapausing pharate first instar larvae of the wild silkmoth Antheraea yamamai, using subtractive cDNA hybridization. The cDNA sequence of CYP4G25 has an open reading frame of 1674 nucleotides encoding 557 amino acid residues. Sequence analysis of the putative CYP4G25 protein disclosed the motif FXXGXRXCXG that is essential for heme binding in P450 cytochromes. Hybridization in situ demonstrated predominant expression of CYP4G25 in the integument of pharate first instar larvae. Northern blotting analysis showed an intensive signal after the initiation of diapause and no or weak expression throughout the periods of pre-diapause and post-diapause, including larval development. These results indicate that CYP4G25 is strongly associated with diapause in pharate first instar larvae. (c) 2008 Elsevier Ltd. All rights reserved.
A novel cytochrome P450, CYP4x1, was identified in EST databases on the basis of similarity to a conserved region in the C-helix of the CYP4A family. The human and mouse CYP4x1 cDNAs were cloned and found to encode putative cytochrome P450 proteins. Molecular modelling of CYP4x1 predicted an unusual substrate binding channel for the CYP4 family. Expression of human CYP4x1 was detected in brain by EST analysis, and in aorta by northern blotting. The mouse cDNA was used to demonstrate that the Cyp4x RNA was expressed principally in brain, and at much lower levels in liver; hepatic levels of the Cyp4x1 RNA were not affected by treatment with the inducing agents phenobarbital, dioxin, dexamethasone or ciprofibrate, nor were the levels affected in PPAR alpha-/- mice. A specific antibody for Cyp4x1 was developed, and shown to detect Cyp4x1 in brain; quantitation of the Cyp4x1 protein in brain demonstrated approximate to 10 ng of Cyp4x1 protein.mg(-1) microsomal protein, showing that Cyp4x1 is a major brain P450. Immunohistochemical localization of the Cyp4x1 protein in brain showed specific staining of neurons, choroids epithelial cells and vascular endothelial cells. These data suggest an important role for Cyp4x1 in the brain.
CYP1B1 is a cytochrome P450 enzyme implicated in autosomal recessive primary congenital glaucoma (PCG). The mechanism and function of CYP1B1 in the development of the PCG phenotype is unknown. Previously, investigators have reported detection of Cyp1b1 mRNA in the ciliary body and epithelium and neuroepithelium in the developing mouse eye, employing in situ hybridization techniques. Similarly, additional investigators have detected CYP1B1 mRNA in the iris, ciliary body, non-pigmented ciliary epithelial line, cornea, retinal-pigment epithelium, and retina in the human adult eye, using Northern blotting. This study was designed to immunolocalize CYP1B1 protein in the various ocular structures of normal, human fetal and adult eyes. Normal fetal and adult eyes were irrimunolabeled with a polyclonal antibody against human CYP1B1 using indirect immunofluorescence, and then compared with appropriate controls. The intensity of immunolabeling of the various ocular structures was assessed by qualitative and semi-quantitative techniques. In the anterior segment anti-CYP1B1 immunoreactivity (IR) was detected early in fetal development in the primitive ciliary epithelium. As well, the most intense CYP1B1 IR was in the non-pigmented ciliary epithelium. In addition, CYP1B1 IR was also present in the corneal epithelium and keratocytes, both layers of the iris pigmented epithelium, and retina. However, CYP1B1 IR was absent in the trabecular meshwork in all of the samples. In general, CYP1B1 immunolabeling in the human fetal eyes was more intense when compared to adult eyes. CYP1B1 IR was primarily immunolocalized to the non-pigmented ciliary epithelium and early in fetal development. In addition, CYP1B1 IR was not detected in the trabecular meshwork. These findings suggest that the abnormalities in the development of the trabecular meshwork in PCG may result from diminished or absent metabolism of important endogenous substrates in the ciliary epithelium due to non-functional CYP1B1 enzyme. (C) 2005 Elsevier Ltd. All rights reserved.
Objectives: The expression patterns of cytokeratin (CK) filaments in human epithelial neoplasms are complex and distinctive. The aims of this study were to analyze CK expression and to evaluate the diagnostic application of CKs in human non-small cell lung cancer (NSCLC). Methods: mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19 was analyzed by Northern blotting. Protein expression of CK5/6, CK7, CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue microarrays. Results: Northern blotting showed that CKs were highly expressed in human bronchial epithelial cells and/or small airway epithelial cells. In NSCLC cell lines, the expression pattern of CKs was heterogeneous. Regarding protein expression of CKs in 95 primary lung tumors, expression of CK5/6, CK14, and CK17 proteins was increased in squamous cell carcinomas compared to adenocarcinomas (ADC; p = 0.001, p = 0.030, and p = 0.001, respectively), and higher expression was significantly associated with lower grading (p = 0.006, p = 0.002, and p = 0.001, respectively), while increased expression of CK7 and CK18 was observed in ADC (p = 0.001, respectively). Conclusions: Our data suggest that CK5/6, CK7, CK14, CK17, and CK18 have diagnostic value in the subclassification of NSCLC. Copyright (C) 2011 S. Karger AG, Basel
Streptococcus mutans, the primary etiologic agent of dental caries, can gain access to the bloodstream and has been associated with cardiovascular disease. However, the roles of S.mutans in inflammation in cardiovascular disease remain unclear. The aim of this study was to examine cytokine production induced by S.mutans in human aortic endothelial cells (HAECs) and to evaluate the participation of toll-like receptors (TLRs) and cytoplasmic nucleotide-binding oligomerization domain (NOD) -like receptors in HAECs. Cytokine production by HAECs was determined using enzyme-linked immunosorbent assays, and the expression of TLRs and NOD-like receptors was evaluated by real-time polymerase chain reaction, flow cytometry and immunocytochemistry. The involvement of TLR2 and NOD2 in cytokine production by invaded HAECs was examined using RNA interference. The invasion efficiencies of S.mutans strains were evaluated by means of antibiotic protection assays. Five of six strains of S.mutans of various serotypes induced interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production by HAECs. All S.mutans strains upregulated TLR2 and NOD2 mRNA levels in HAECs. Streptococcus mutans Xc upregulated the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and NOD2 genes in HAECs invaded by S.mutans Xc led to a reduction in interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production. Cytokine production induced by invasive S.mutans via intracellular TLR2 and NOD2 in HAECs may be associated with inflammation in cardiovascular disease.
Background: TNF and its receptors TNF-Receptor 1 (TNFR1, CD120a) and TNF-Receptor 2 (TNFR2, CD120b) have been implicated in the rejection of transplanted cells and organs. Although pig TNFR1 (pTNFR1) is known to mediate the effects of human TNF in a xenogeneic setting, it is unclear whether pig TNFR2 (pTNFR2) could contribute to xenograft rejection. Methods: We have cloned the cDNA of various pTNFR2 variants by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. We have characterized the predicted proteins with bioinformatic tools and conducted expression, affinity, and functional studies to investigate their roles. Results: We have identified four isoforms of pTNFR2: one comprising the four cysteine-rich domains (CRD) conserved between species, a shorter variant (pTNFR2 Delta E7-10) encoding for a soluble isoform, another with only three CRD due to the lack of exon 4 (pTNFR2 Delta E4), and a fourth variant containing both modifications. Accordingly, multiple mRNA transcripts were observed by northern blotting. Quantitative RT-PCR determined high pTNFR2 expression in lung and immune cells and detected the two alternative splicings in all cells/tissues examined. The full receptor was moderately expressed on the surface of pig cells such as porcine aortic endothelial cells and PK-15 and was regulated by TNF. On the contrary, the membrane-bound pTNFR2 Delta E4 was located only intracellularly. Plasmon resonance studies showed that pTNFR2 binds pig and human TNF alpha with high affinity, but pTNFR2 Delta E4 interacts poorly with pig TNF alpha and does not bind to the human cytokine. Moreover, pull-down experiments with the two recombinant soluble isoforms consistently demonstrated that the two bound together and soluble pTNFR2 Delta E4 was able to modulate the TNF inhibitory activity of pTNFR2-GST in a cell-based assay. Conclusion: The pTNFR2 may participate in the process of xenograft rejection and other related events, as well as be used in soluble form to block TNF in this setting. In addition, we have discovered other pTNFR2 isoforms that may affect the pig immune responses and have an impact on rejection of xenografts.
Objectives To determine the effects of dental implant surface chemistry and energy on macrophage activation invitro. Materials and Methods Disks made from two clinically used implant materials (titanium [Ti], titanium zirconium alloy [TiZr]) were produced with two different surface treatments (sandblast/acid-etch [SLA], hydrophilic-SLA [modSLA]). Surface roughness, energy, and chemistry were characterized. Primary murine macrophages were isolated from 6- to 8-week-old male C57Bl/6 mice and cultured on test surfaces (Ti SLA, TiZr SLA, Ti modSLA, TiZr modSLA) or control tissue culture polystyrene. mRNA was quantified by quantitative polymerase chain reaction after 24h of culture. Pro- (IL-1, IL-6, and TNF-) and anti-inflammatory (IL-4, IL-10) protein levels were measured by ELISA after 1 or 3days of culture. Results Quantitatively, microroughness was similar on all surfaces. Qualitatively, nanostructures were present on modSLA surfaces that were denser on Ti than on TiZr. modSLA surfaces were determined hydrophilic (high-energy surface) while SLA surfaces were hydrophobic (low-energy surface). Cells on high-energy surfaces had higher levels of mRNA from anti-inflammatory markers characteristic of M2 activation compared to cells on low-energy surfaces. This effect was enhanced on the TiZr surfaces when compared to cells on Ti SLA and Ti modSLA. Macrophages cultured on TiZr SLA and modSLA surfaces released more anti-inflammatory cytokines. Conclusions The combination of high-energy and altered surface chemistry present on TiZr modSLA was able to influence macrophages to produce the greatest anti-inflammatory microenvironment and reduce extended pro-inflammatory factor release.
Background and ObjectiveOver the last 10 years, bioactive plant food compounds have received considerable attention in regard to their beneficial effects against periodontal disease. In this study, we investigated the effects of black tea theaflavins (TFs) on the virulence properties of Porphyromonas gingivalis and gingival keratinocyte tight junction integrity. In addition, the effects of black tea TFs on the nuclear factor-B (NF-B) signaling pathway and proinflammatory cytokine/matrix metalloproteinase (MMP) secretion by monocytes/macrophages were assessed. Material and MethodsVirulence factor gene expression in P. gingivalis was investigated by quantitative real-time PCR. A fluorescence assay was used to determine P. gingivalis adherence to, and invasion of, a gingival keratinocyte monolayer. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. Proinflammatory cytokine and MMP secretion by P. gingivalis-stimulated macrophages was quantified by ELISA. The U937-3xB-LUC monocyte cell line transfected with a luciferase reporter gene was used to monitor NF-B activation. Gelatin degradation was monitored using a fluorogenic assay. ResultsBlack tea TFs dose-dependently inhibited the expression of genes encoding the major virulence factors of P. gingivalis and attenuated its adherence to gingival keratinocytes. A treatment of gingival keratinocytes with black tea TFs significantly enhanced tight junction integrity and prevented P. gingivalis-mediated tight junction damage as well as bacterial invasion. Black tea TFs reduced the secretion of interleukin (IL)-1, tumor necrosis factor-, IL-6, chemokine (C-X-C) ligand 8, MMP-3, MMP-8 and MMP-9 by P. gingivalis-stimulated macrophages and attenuated the P. gingivalis-mediated activation of the NF-B signaling pathway. Lastly, black tea TFs inhibited gelatin degradation by MMP-9. ConclusionThis study provides clear evidence that black tea TFs represent promising multifunctional therapeutic agents for prevention and treatment of periodontal disease.
Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma. (C) 2017 Elsevier B.V. All rights reserved.
ObjectiveTo conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs). MethodThe PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models. ResultEighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I-2: 51.6-97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). ConclusionOur results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.
Objective: Interleukin-10 (IL-10) is a pleiotropic cytokine with either immunosuppressive or immunostimulative activities. It has been reported that in cancer, the promoter region polymorphism of IL-10 (-A592C) alters both the expression and serum levels of this cytokine. In the present study, we have addressed the question as to whether the single nucleotide polymorphisms (SNPs) at positions -592 A/C in the IL-10 gene promoter, could predispose an individual to oral squamous cell carcinoma (OSCC). Design: We analyzed the genotype of the IL-10 (-A592C) gene, in 250 histopathologically confirmed OSCC patients and similar number of healthy volunteers taken as controls, in an Indian population by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were analyzed by the Student's t-test and the chi-squared test, and strength of associations by the odds ratio (OR) with 95% confidence intervals. Results: The genotype and allele distribution of IL-10 (-A592C) gene polymorphism was significantly different between OSCC cases and controls (genotype AA vs AC: OR 2.87; 95 % CI 1.50-5.48; p = 0.0016 and AA vs CC: OR 4.08; 95 % CI 1.98-8.41; p = 0.0002). The -592 C alleles were found to be significantly different among OSCC cases and controls (OR: 1.44, 95% CI: 1.12-1.85, p < 0.0051). Conclusions: The IL-10 gene promoter region (-592) A/C polymorphism is significantly associated with reduced risk of OSCC. The OSCC group had a significantly greater frequency of genotype AA as compared to control group. (C) 2017 Elsevier Ltd. All rights reserved.
Mesangial re-modeling and mesangial cell (MC) migration are features of several glomerular diseases including mesangiocapillary glomerulonephritis. In vitro investigations have recently identified ADAM-15, a multidomain adamalysin, as central to the migration of MC. The current study used array technology to investigate the expression of other genes in migrating cells and identified pleiotrophin (PTN), platelet-derived growth factor alpha polypeptide chain, colony stimulating factor, and four members of the tumor necrosis factor-alpha superfamily as major genes that were upregulated. Transcriptional induction of PTN was confirmed by reverse transcription-polymerase chain reaction and Northern blotting and induction of the protein by Western blotting and immunohistochemical localization. PTN was observed associated with mesangial 'hillocks' in confluent MC cultures. In contrast, in models of migration, migrating cells had the highest expression of cell-associated PTN. PTN protein was less evident, however, in the conditioned medium of MCs. Treatment of MC with heparanase removed PTN from the cells suggesting that its localization was owing to an association with heparan sulfates on the cell surface or in the extracellular matrix. This is the first description of the expression of PTN by human MCs and the data suggest that it is rapidly induced in cells that are triggered to migrate. The result of this induction is currently under investigation.
The highly orchestrated transcriptional and metabolic reprogramming during activation drastically transforms the main functions and physiology of human macrophages across the polarization spectrum. Lipids, for example, can modify protein function by acting remotely as signaling molecules but also locally by altering the physical properties of cellular membranes. These changes play key roles in the functions of highly plastic immune cells due to their involvement in inflammation, immune responses, phagocytosis and wound healing processes. We report an analysis of major membrane lipids of distinct phenotypes of resting (M0), classically activated (M1), alternatively activated (M2a) and deactivated (M2c) human monocyte derived macrophages from different donors. Samples were subjected to supercritical fluid chromatography-ion mobility-mass spectrometry analysis, which allowed separations based on lipid class, facilitating the profiling of their fatty acid composition. Different levels of arachidonic acid mobilization as well as other fatty acid changes were observed for different lipid classes in the distinct polarization phenotypes, suggesting the activation of highly orchestrated and specific enzymatic processes in the biosynthesis of lipid signaling molecules and cell membrane remodeling. Thromboxane A2 production appeared to be a specific marker of M1 polarization. These alterations to the global composition of lipid bi-layer membranes in the cell provide a potential methodology for the definition and determination of cellular and tissue activation states. (C) 2016 Elsevier Inc. All rights reserved.
It is possible that during long lasting chronic infections such as tuberculosis (TB) and leprosy individuals who generate a stronger immune response will produce a chronic shift in the systemic levels of inflammatory proteins. Consequently, the systemic immunological shift could affect inflammatory responses against other persistent pathogens such as Porphyromonas gingivalis associated with periodontal disease (PD). ObjectiveTo determine if in vitro exposure to Mycobacterium tuberculosis or M. leprae lysates impacts subsequent immune responses to P. gingivalis; and to propose a new dialogue between experimental immunology and paleopathology. Material and methodsWe sequentially (2 days protocol) exposed peripheral blood mononuclear cells (PBMCs) from healthy donors to bacterial lysates either from M. tuberculosis, or M. leprae, or P. gingivalis. After collecting all supernatants, we measured the expression of immune proteins TNF and IFN using an enzyme-linked immunosorbent assay. ResultsEarly exposure (day 1) of PBMCs to M. leprae or M. tuberculosis lysates induces an inflammatory shift detected by the increase of TNF and IFN when the same cells are subsequently (day 2) exposed to oral pathogen P. gingivalis. DiscussionBy extrapolating these results, we suggest that chronic infections, such as TB and leprosy, could generate a systemic immunological shift that can affect other inflammatory processes such the one present in PD. We propose that the presence and severity of PD should be explored as a proxy for inflammatory status or competence when reconstructing the health profile in past populations.
Matrix metalloproteinases (MMPs) degrade collagen and mediate tissue remodeling. The novel cytokine IL-17 is expressed during various inflammatory conditions and modulates MMP expression. We investigated the effect of IL-17 on MMP-1 expression in primary human cardiac fibroblasts (HCF) and delineated the signaling pathways involved. HCF were treated with recombinant human IL-17. MMP-1 expression was analyzed by Northern blotting, RT-quantitative PCR, Western blotting, and ELISA; transcriptional induction and transcription factor binding by EMSA, ELISA, and reporter assay; and p38 MAPK and ERK1/2 activation by protein kinase assays and Western blotting. Signal transduction pathways were investigated using pharmacological inhibitors, small interfering RNA (siRNA), and adenoviral dominant-negative expression vectors. IL-17 stimulated MMP-1 gene transcription, net mRNA levels, protein, and promoter-reporter activity in HCF. This response was blocked by IL-17 receptor- Fc chimera and IL-17 receptor antibodies, but not by IL-6, TNF-alpha, or IL-1 beta antibodies. IL-17-stimulated type I collagenase activity was inhibited by the MMP inhibitor GM-6001 and by siRNA-mediated MMP-1 knockdown. IL-17 stimulated activator protein-1 [AP-1 (c-Fos, c-Jun, and Fra-1)], NF-kappa B (p50 and p65), and CCAAT enhancer-binding protein (C/EBP)-beta DNA binding and reporter gene activities, effects attenuated by antisense oligonucleotides, siRNA-mediated knockdown, or expression of dominant-negative signaling proteins. Inhibition of AP-1, NF-kappa B, or C/EBP activation attenuated IL-17-stimulated MMP-1 expression. IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-98059 blunted IL-17-mediated transcription factor activation and MMP-1 expression. Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK-dependent AP-1, NF-kappa B, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling.
We examined whether tumor necrosis factor-alpha (TNF-alpha) promotes postischemic inflammation and myocardial injury via activation of nuclear factor kappa B (NF kappa B) in an in vivo canine model. Isoflurane-anesthetized dogs underwent closed-chest balloon occlusion of the anterior descending coronary artery for 90 minutes, followed by reperfusion for 3 hours. Dogs randomly received a soluble TNF inhibitor (etanercept, 0.5 mg/kg intravenously) or saline before occlusion. Collateral blood flow and risk region size (RISK) were measured with radioactive microspheres, infarct size (INF) was measured by triphenyltetrazolium chloride staining, inflammation was measured by tissue mycloperoxidase (MPO) activity, intercellular adhesion molecular-1 (ICAM-1) messenger ribonucleic acid (mRNA) was measured by Northern blotting, and ICAM-1 protein expression was measured by Western blotting. NF kappa B activation was measured in nuclear extracts by electrophoretlic mobility shift assays. INF/RISK was significantly smaller in the etanercept group than in the saline control group after adjusting for collateral flow (P < 0.009 by analysis of covariance, mean reduction in INF/RISK = 40%, 0.32 +/- 0.09 versus 0.53 +/- 0.09). MPO activity, ICAM-1 mRNA and protein expression, and NF kappa B binding activity were all significantly reduced in the etanercept group. Administration of a soluble TNF-a inhibitor reduced NF kappa B activation, ICAM-1 upregulation, and myocardial injury following ischemia-reperfusion. TNF-a appears to play a significant role in vivo in the genesis of postischemic inflammation.
Purpose: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus (CMV) anterior uveitis in a tertiary uveitis referral center in Brussels, Belgium. Methods: A retrospective study of patients with a clinical diagnosis of CMV anterior uveitis/endotheliitis demonstrated by a positive polymerase chain reaction and/or Goldmann-Witmer coefficient (GWc). Results: We report a series of 15 patients presenting clinical characteristics of CMV anterior uveitis. Patients had a pretreatment follow-up of 13.00 +/- 12.78 months and a posttreatment follow-up of 42.64 +/- 31.23 months. The 14 non-Asian patients (93.3%) had clinical characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%) had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation, uveitis was unilateral in all patients, visual acuity (VA) was 0.91 +/- 0.25, and all patients had an increased intraocular pressure (IOP), with a mean IOP of 41.40 +/- 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had glaucoma, 2 needed glaucoma surgery (13.3%). The mean final VA was 0.93 +/- 0.11; 13 patients (86.5%) reached a final VA of 0.7 to 1. Patients had a significantly lower number of recurrences/year posttreatment (0.76 +/- 0.57) than in the pretreatment period (3.76 +/- 2.44) (P = 0.001). The mean time to recurrence increased from 4.03 months before treatment to 12.58 months after treatment (P = 0.003). Conclusion: Our results suggest that patients treated with 0.15% topical ganciclovir have a decreased frequency of CMV anterior uveitis recurrences, most preserve a relatively good central vision over time. However, glaucoma is a frequent and severe complication.
Background. Systemic reactivations of herpesviruses may occur in intensive care unit (ICU) patients, even in those without prior immune deficiency. However, the clinical relevance of these events is uncertain. Methods. In this study we selected patients admitted with septic shock and treated for more than 4 days from a prospectively enrolled cohort of consecutive adults in the mixed ICUs of 2 tertiary care hospitals in the Netherlands. We excluded patients who had received antiviral treatment in the week before ICU admission and those with known immunodeficiency. We studied viremia episodes with cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), and varicella zoster virus (VZV) by weekly polymerase chain reaction in plasma. Results. Among 329 patients, we observed 399 viremia episodes in 223 (68%) patients. Viremia with CMV, EBV, HHV-6, HSV1, HSV-2, and VZV was detected in 60 (18%), 157 (48%), 80 (24%), 87 (26%), 13 (4%), and 2 (0.6%) patients, respectively; 112 (34%) patients had multiple concurrent viremia events. Crude mortality in the ICU was 36% in this latter group compared to 19% in remaining patients (P < .01). After adjustment for potential confounders, time-dependent bias, and competing risks, only concurrent CMV and EBV reactivations remained independently associated with increased mortality (adjusted subdistribution hazard ratio, 3.17; 95% confidence interval, 1.41-7.13). Conclusions. Herpesvirus reactivations were documented in 68% of septic shock patients without prior immunodeficiency and frequently occurred simultaneously. Concurrent reactivations could be independently associated with mortality.
Background: Viruses and atypical pathogens can cause significant respiratory illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR) has improved the diagnostic yield of pathogens, and it is easier to identify the co-infections also. The present study was done to evaluate the performance of MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients. Methods: A total of 177 BAL specimens collected over a 19 months period from immunocompromised patients with respiratory illness were analyzed with the MPCR and aerobic culture. Patients were divided into four according to the pathogens. Category V (only viral), Category NV (nonviral, i. e., bacteria and atypical), Category M (mixed, i. e., both viral and nonviral pathogen), and Category UK (unknown etiology). Results: MPCR identified the causative pathogen in 59.3% of patients while culture could identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly higher in patients of Category M having mixed infections. Conclusion: MPCR is highly sensitive and rapid tool which can be considered in the routine diagnostic algorithm of respiratory illness in immunocompromised patients.
The transcriptional patterns of mitochondrial respiratory related genes were investigated in cytoplasmic male-sterile and fertile maintainer lines of stem mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel open reading frame, hereafter named orfB gene, was located at the downstream of mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220 gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified by primers of nad2F and nad2R from CMS) were found in the CMS line following Southern blotting digested with HindIII, but only a single copy in its maintainer line. Meanwhile, two transcripts were shown in the CMS line following Northern blotting while only one transcript was detected in the maintainer line, which were probed by specific fragment (amplified by primers of nad2F and nad2R from CMS). Meanwhile, the expression of nad2 gene was reduced in CMS bud compared to that in its maintainer line. We thus suggested that nad2 gene may be co-transcripted with CMS-associated orfB gene in the CMS. In addition, the specific fragment that was amplified by primers of nad2F and nad2R just spanned partial sequences of nad2 gene and orfB gene. Such alterations in the nad2 gene would impact the activity of NADH dehydrogenase, and subsequently signaling, inducing the expression of nuclear genes involved in male sterility in this type of cytoplasmic male sterility.
Purpose: To evaluate the effect of fractionated irradiation (FI) on tumor cells' sensitivity to ionizing radiation (IR) and antineoplastic drugs, and examine the potential of early growth response-1 (EGR-1) inhibition to sensitize tumor cells to IR. Materials and methods: PC3 and HepG2 cells were subjected 10 times to gamma-rays at 2 Gy. The surviving cells were named PC3/R and HepG2/R, respectively. The cells' sensitivity to irradiation and chemotherapeutic drugs, including cisplatin (PT), doxorubicin (DOX), mitomycin C (MMC) and 5-fluorouracil (5-FU), were identified by colony formation assay and MMT method, respectively. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis was utilized to compare the difference of gene expression between radioresistant cells and parental cells. The small interfering RNA system was implemented to inhibit endogenous EGR-1 expression in radiation-resistant cells. Western blot was employed to identify the possible mechanism by which EGR-1 regulates cells' radiosensitivity. Results: FI induced cross-resistant to IR and MMC in tumor cells. Along with the reduction of ovarian cancer-2/disabled homolog 2 (DOC-2/DAB2) interactive protein (DAB2IP) expression, EGR-1 gene was upregulated in FI-treated cells. On the other hand, downregulation of EGR-1 gene expression sensitized radioresistant cells to IR accompanied by DAB2IP overexpression and STAT3 inactivation. In addition, NF-kappa B inhibitor, BAY11-7082 enhanced resistant cells' radiosensitivity and chemosensitivity. Conclusions: Conventionally FI has a higher risk of forming acquired radioresistance (ARR) in vitro. EGR-1 gene-targeted drug design could be an effective strategy to overcome DAB2IP-dysregulation-induced ARR in tumor patients.
Tomato spotted wilt virus (TSWV) causes significant losses in the production of the ornamental plant Dahlia variabilis in Japan. The purpose of this study was to examine the distribution of TSWV in dahlia plants and identify plant parts that can be used in the selection of TSWV-free plants. The distribution of TSWV was investigated using reverse transcriptional polymerase chain reaction (RT-PCR) and tissue blot immunoassay. The detection rate of TSWV in latent infected compound leaves was the highest in the petiole, and it decreased from the veins and rachis to the lamina. The tissue blot immunoassays of the leaflets showed an uneven distribution of TSWV, especially along the edge of the leaf blade. In stems, the detection rate of TSWV was high partway up the stem compared to that in the upper and the lower parts of the stem during the vegetative growth stage. A highly uneven distribution was observed in the bulb. Our results indicated that middle parts of the stem as well as the petioles, rachis, and veins of compound leaves are suitable for detection of TSWV in dahlias. This study is the first to report uneven distribution of TSWV in dahlia plants.
Metabolic imbalance impairs fertility, because changes in concentrations of metabolites and hormones in the blood and follicular fluid create an unfavourable environment for early embryonic development. Insulin is a key metabolic hormone known for its effects on fertility: insulin concentrations are increased during energy balance disturbances in diabetes or metabolic syndrome. Still, insulin is frequently used at supraphysiological concentrations for embryo in vitro culture with unknown consequences for the developmental potential of the offspring. In the present study we investigated the effects of insulin exposure during in vitro bovine oocyte maturation on developmental rates, embryo quality and gene expression. Supplementation of the maturation media with insulin at 10 or 0.1 mu gmL(-1) decreased blastocyst rates compared with an insulin-free control (19.8 +/- 1.3% and 20.4 +/- 1.3% vs 23.8 +/- 1.3%, respectively; P<0.05) and led to increased cell numbers (nearly 10% more cells on Day 8 compared with control; P<0.05). Transcriptome analysis revealed significant upregulation of genes involved in lipid metabolism, nuclear factor (erythroid-derived 2)-like 2 (NRF2) stress response and cell differentiation, validated by quantitative polymerase chain reaction. To conclude, the results of the present study demonstrate that insulin exposure during in vitro oocyte maturation has a lasting effect on the embryo until the blastocyst stage, with a potential negative effect in the form of specific gene expression perturbations.
Background: A combined supplement of vitamins B9 and B12 was reported to increase milk and milk component yields of dairy cows without effect on feed intake. The present study was undertaken to verify whether this supplementation positively modifies the pathways involved in milk and milk component synthesis. Thus, by studying the transcriptome activity in these tissues, the effect of supplements of both vitamins on the metabolism of both liver and mammary gland, was investigated. For this study, 24 multiparous Holstein dairy cows were assigned to 6 blocks of 4 animals each according to previous 305-day milk production. Within each block, cows were randomly assigned to weekly intramuscular injections of 5 mL of either saline 0.9 % NaCl, 320 mg of vitamin B9, 10 mg of vitamin B12 or a combination of both vitamins (B9 + B12). The experimental period began 3 weeks before the expected calving date and lasted 9 weeks of lactation. Liver and mammary biopsies were performed on lactating dairy cows 64 +/- 3 days after calving. Samples from both tissues were analyzed by microarray and qPCR to identify genes differentially expressed in hepatic and mammary tissues. Results: Microarray analysis identified 47 genes in hepatic tissue and 16 genes in the mammary gland whose expression was modified by the vitamin supplements. Gene ontology (GO) categorizes genes in non-overlapping domains of molecular biology. Panther is one of the online GO resources used for gene function classification. It classifies the 63 genes according to Molecular Function, Biological Process and Protein Class. Most of the biological processes modulated by the vitamin supplements were associated to developmental process, protein metabolic process, transport and response to inflammation. In the liver, most of the genes modulated by the vitamin treatments involved protein metabolic process while developmental process appeared to be more affected by the treatments in mammary gland. Out of 25 genes analysed by qPCR, 7 were validated. Conclusion: The results indicate that several metabolic processes were modulated by the supplementation of vitamins in early-lactating dairy cows. In addition, the results suggest that the vitamin supplements promoted liver regeneration and reduced catabolism of lipids in early lactation.
In this study, we evaluated whether quantitative PCR (qPCR) and reverse transcription-qPCR (RT-qPCR) results could be affected by extracellular (free) DNA or RNA, respectively, obtained either from isolated bacteria or from fermented dairy foods manufactured with these microorganisms. These experimental set-ups involved two starter lactic acid bacteria (SLAB), Streptococcus thermophilus and Lactococcus lactis, as models across their most common technological environments: yoghurt, milk and cheese. The presence of free DNA modified qPCR results in levels sufficient to bias SLAB determinations, indicating that DNA may be a poor measure of cellular integrity. Furthermore, we showed for the first time that an order of magnitude more of free RNA than of DNA had to be used to modify RT-qPCR results. Importantly, the interference produced by free DNA and RNA was maintained across all the dairy matrices evaluated, independently of the SLAB and of the source of nucleic acids used, in both negative and positive samples. This study suggests that, contrary to DNA molecules, mRNA from dead microorganisms or from other extracellular sources may not be a determinant factor in skewing molecular quantifications. Therefore, our results support the potential use of mRNA as a molecular signature of cell integrity in dairy matrices. (C) 2017 Elsevier Ltd. All rights reserved.
Environmental managers in the United States and elsewhere are increasingly perceiving dam removal as a critical tool for river restoration and enhancing watershed resilience. In New England, over 125 dams have been dismantled for ecological and economic rationales. A surprising number of these removals, including many that are ongoing, have generated heated conflicts between restoration proponents and local communities who value their dammed landscapes. Using a comparative case study approach, we examine the environmental conflict around efforts to remove six dams in New England. Each of these removal efforts followed quite different paths and resultant outcomes: successful removal, stalled removal, and failure despite seemingly favorable institutional conditions. Lengthy conflicts often transpired in instances where removals occurred, but these were successfully arbitrated by paying attention to local historical-geographical conditions conducive to removal and by brokering effective compromises between dam owners and the various local actors and stakeholders involved in the removal process. Yet our results across all cases suggest that these are necessary, but not sufficient conditions for restoration through dam removal since a similar set of conditions typified cases where removals are continuously stalled or completely halted. Scholars examining the intersection between ecological restoration and environmental politics should remain vigilant in seeking patterns and generalities across cases of environmental conflict in order to promote important biophysical goals, but must also remain open to the ways in which those goals are thwarted and shaped by conflicts that are deeply contingent on historical-geographical conditions and broader institutional networks of power and influence.
DAMPE (DArk Matter Particle Explorer) is a scientific satellite which is mainly aimed at indirectly searching for dark matter in space. One critical sub-detector of the DAMPE payload is the BGO (bismuth germanium oxide) calorimeter, which contains 1848 PMT (photomultiplier tube) dynodes and 16 FEE (Front-End Electronics) boards. VA160 and VATA160, two 32-channel low power ASICs (Application Specific Integrated Circuits), are adopted as the key components on the FEEs to perform charge measurement for the PMT signals. In order to monitor the parameter drift which may be caused by temperature variation, aging, or other environmental factors, an onboard calibration circuit is designed for the VA160 and VATA160 ASICs. It is mainly composed of a 12-bit DAC (Digital to Analog Converter), an operational amplifier and an analog switch. Test results showed that a dynamic range of 0-30 pC with a precision of 5 fC (Root Meam Square, RMS) was achieved, which covers the VA160's input range. It can be used to compensate for the temperature drift and test the trigger function of the FEEs. The calibration circuit has been implemented for the front-end electronics of the BGO Calorimeter and verified by all the environmental tests for both Qualification Model and Flight Model of DAMPE. The DAMPE satellite was launched at the end of 2015 and the calibration circuit will operate periodically in space.
We investigated the effects of embryonic temperature (ET) treatments (22, 26 and 31 degrees C) on the life-time recruitment of fast myotomal muscle fibres in zebrafish Danio rerio L. reared at 26/27 degrees C from hatching. Fast muscle fibres were produced until 25 mm total length (TL) at 22 degrees C ET, 28 mm TL at 26 degrees C ET and 23 mm TL at 31 degrees C ET. The final fibre number (FFN) showed an optimum at 26 degrees C ET (3600) and was 19% and 14% higher than for the 22 degrees C ET (3000) and 31 C ET (3100) treatments, respectively. Further growth to the maximum TL of similar to 48mm only involved fibre hypertrophy. Microarray experiments were used to determine global changes in microRNA (miRNA) and mRNA expression associated with the transition from the hyperplasic myotube-producing phenotype (M(+), 10-12 mm TL) to the hypertrophic growth phenotype (M(-), 28-31 mm TL) in fish reared at 26-27 degrees C over the whole life-cycle. The expression of miRNAs and mRNAs obtained from microarray experiments was validated by northern blotting and real-time qPCR in independent samples of fish with the M(+) and M(-) phenotype. Fourteen down-regulated and 15 up-regulated miRNAs were identified in the M- phenotype together with 34 down-regulated and 30 up-regulated mRNAs (>2-fold; P<0.05). The two most abundant categories of down-regulated genes in the M- phenotype encoded contractile proteins (23.5%) and sarcomeric structural/cytoskeletal proteins (14.7%). In contrast, the most highly represented up-regulated transcripts in the M(-) phenotype were energy metabolism (26.7%) and immune-related (20.0%) genes. The latter were mostly involved in cell-cell interactions and cytokine pathways and included beta-2-microglobulin precursor (b2m), an orthologue of complement component 4, invariant chain-like protein 1 (iclp), CD9 antigen-like (cd9l), and tyrosine kinase, non-receptor (tnk2). Five myosin heavy chain genes that were down-regulated in the M- phenotype formed part of a tandem repeat on chromosome 5 and were shown by in situ hybridisation to be specifically expressed in nascent myofibres. Seven up-regulated miRNAs in the M- phenotype showed reciprocal expression with seven mRNA targets identified in miRBase Targets version 5 (http://microrna.sanger.ac.uk/targets/v5/), including asporin (aspn) which was the target for four miRNAs. Eleven down-regulated miRNAs in the M- phenotype had predicted targets for seven up-regulated genes, including dre-miR-181c which had five predicted mRNA targets. These results provide evidence that miRNAs play a role in regulating the transition from the M(+) to the M- phenotype and identify some of the genes and regulatory interactions involved.
1. Finding and developing inhibitors of catechol-O-methyltransferase (COMT) from natural products is highly recommended. Daphnetin, a naturally occurring catechol from the family thymelaeaceae, has a chemical structure similar to several potent COMT inhibitors reported previously. Here the potential of daphnetin and its Phase II metabolites as inhibitors of COMT was investigated with human liver cytosol (HLC). 2. Daphnetin and its methylated metabolite (8-O-methyldaphnetin) were found to inhibit COMT-mediated dopamine O-methylation in a dose-dependent manner. The IC50 values for daphnetin (0.51 similar to 0.53 mu M) and 8-O-methyldaphnetin (22.5 similar to 24.3 mu M) were little affected by changes in HLC concentrations. Further kinetic analysis showed the differences in inhibition type and parameters (K-i) between daphnetin (competitive, 0.37 mu M) and 8-O-methyldaphnetin (noncompetitive, 25.7 mu M). Other metabolites, including glucuronidated and sulfated species, showed negligible inhibition against COMT. By using in vitro-in vivo extrapolation (IV-IVE), a 24.3-fold increase in the exposure of the COMT substrates was predicted when they are co-administrated with daphnetin. 3. With high COMT-inhibiting activity, daphnetin could serve as a lead compound for the design and development of new COMT inhibitors. Also, much attention should be paid to the clinical impact of combination of daphnetin and herbal preparations containing daphnetin with the drugs primarily cleared by COMT.
The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf (AKV) has been noted for decades and the relationship between the 2 entities remains controversial. Although, it has been shown that both diseases are associated with mutations in ATPA2 gene, it is yet to be determined if they are the same disease, or separate but allelic, or interlinked in some other fashion. Herein, the authors report the case of a 13-year-old girl presenting with shiny flat-topped verruca plana-like papules, on the dorsal hands and feet and red-brown crusted papules on her forehead and along the sides of her neck. Histological evaluation of a wart-like lesion shows features of AKV, a verruca plana-like histopathology and focal acantholytic dyskeratosis. Forehead biopsy also demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD. Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression of the L1 capsid expression was seen in areas of hypergranulosis. The presence of productive betaPV infection in the setting of DD and AKV suggests a susceptibility to HPV infection.
There are significant differences between the DGIs and LGTs. Additionally, most of the characteristics indicate that the DGIs are more similar to recovered tissue and can resist viral attacks. Dark green islands (DGIs) surrounded by light green tissues (LGTs) are common leaf symptoms of plants that are systemically infected by various mosaic viruses. We performed cytological, physiological and molecular biological analyses of the DGIs and LGTs in cucumber mosaic virus-infected Nicotiana tabacum leaves. Our results indicated that the DGIs contained less virus than did the LGTs. Compared to the LGTs, the DGIs contained higher levels of the metabolites involved in plant defence. The contents of reduced glutathione and ascorbic acid were increased in the DGIs to reach levels that were even higher than those of control plants. Moreover, hormone measurements and quantitative real-time PCR analysis revealed that the endogenous salicylic acid, ethylene and defence genes mediated these elevations by playing positive roles in the regulation of the DGIs responses to viral infection. The accumulation of cytokinin was also much greater in the DGIs than in the LGTs. Finally, northern blotting analysis indicated that the accumulation of viral small interfering RNAs was decreased in the DGIs compared to the LGTs. Taken together, these results suggest that DGIs might represent leaf areas that have recovered from viral infection due to locally enhanced defence responses.
In this paper a new CMOS operational amplifier using a Darlington pair based gain boosted technique has been enunciated. The proposed Opamp shows high gain as well as high UGB using capacitor compensation technique and proper biasing circuit. It is operated on rail to rail power supply of +/- 900mV. This amplifier is highly useful for wireless communications due to low power consumption, high bandwidth, high gain and high noise immunity. The designed operational amplifier gain is 89dB, bandwidth is 4.40 GHz and phase margin is 67(O), and slew rate is 991.6V/mu S. This circuit is designed using Cadence analog & digital system design tools of gpdk45nm technology.
Diversity in major histocompatibility complex (MHC) genes can be correlated with the level of immunological fitness of an individual or group of individuals. This study tested published primer sets designed to amplify fragments of the MHC Class II DAB and DBB genes to amplify the equivalent gene fragments in red-tailed phascogales (Phascogale calura). Seventeen genomic DNA samples extracted from phascogale muscle tissue were used to amplify the initial DAB and DBB fragments; however, only DAB PCR proved successful. The fragments were 172 bp in length between the primers and had a high level of identity to other known marsupial MHC Class II DAB gene sequences (89-98%), including those of the koala (Phascolarctos cinereus), Tasmanian devil (Sarcophilus harrisii), commonbrushtail possum (Trichosurus vulpecula) and several wallaby species. Multiple sequence alignment revealed limited variability of MHC Class II genes between the individuals, but eight individual sequences in total. Genomic DNA was subsequently extracted from three fresh red-tailed phascogale scat samples and DAB fragments successfully amplified. The technique will allow for red-tailed phascogales to be sampled non-invasively in the wild and to determine the level of MHC diversity among individuals in the population.
In current industrial practice, thousands of industrial alarms generating millions of alarm events, are built into digital control systems typically found in power generation facilities, power grid and communication networks, oil refineries, petrochemical plants, and other manufacturing plants. Given the increasing complexity of such systems, an effective approach to managing alarms and the stream of data they generate becomes imperative. Hitherto, much of alarm management techniques are mostly rule-based with intensive engineering domain expertise requiring an understanding of the underlying physical processes and special skills on the part of the plant operator. This paper describes a novel graph-based data mining approach that can be used to analyze industrial alarm data. Our method leverages the availability of large timestamped historical alarm events datasets. Using these historical datasets, we developed a graph analytics model that identifies redundant alarms and the series of alarms associated with or leading to critical events. Our experiments using real-world (a power generation station and an oil refinery) industrial alarm datasets demonstrate that our proposed method is both scalable and efficient.
Neuroscience and molecular biology have been generating large datasets over the past years that are reshaping how research is being conducted. In their wake, open data sharing has been singled out as a major challenge for the future of research. We conducted a comparative study of citations of data publications in both fields, showing that the average publication tagged with a data-related term by the NCBI MeSH (Medical Subject Headings) curators achieves a significantly larger citation impact than the average in either field. We introduce a new metric, the data article citation index (DAC-index), to identify the most prolific authors among those data-related publications. The study is fully reproducible from an executable Rmd (R Markdown) script together with all the citation datasets. We hope these results can encourage authors to more openly publish their data.
This brief conceives a learning system for implementing self-optimization-based dynamic server resource provisioning (DSRP) of data centers under deregulated electricity markets. We formulate the DSRP problem as a constrained Markov decision process to minimize the electricity cost subject to a constraint on the queue delay. Instead of applying conventional Q-learning to solve this problem, a postdecision state learning-based DSRP algorithm having fast convergence is proposed by estimating and exploiting the workload arrival distribution. We further discuss the offline optimization of the DSRP problem, which is used as the performance benchmark of the proposed method. Finally, we evaluate the performance of the proposed scheme by using real workloads and electricity prices.
In this paper, the sensitivity of look-ahead economic dispatch in real-time power markets with respect to data perturbation is studied. In the look-ahead dispatch optimization problem, a small change in the data that are used for setting the interspatial and temporal equality/inequality constraints and the objective function may negatively affect normal operations, such as the calculation of real-time wholesale electricity prices and operating costs. This could lead to more distorted prices and larger operating costs with the look-ahead dispatch than with a static dispatch that use data for a single future time. We perturb Karush-Kuhn-Tucker conditions of the look-ahead dispatch optimization formulation and then, using them, derive a linear sensitivity matrix that assesses the impact of data corruption on look-ahead dispatch. This matrix illustrates the changing optimal solution of look-ahead dispatch subject to potential corruption in various types of spatial and temporal data-generator's bidding cost coefficients, capacity limits for generators and transmission lines, ramp rates and the estimate of initial generation output with ramp constraints, and multiple-time series of the forecast load for the look-ahead horizon. The results of the simulation are illustrated with numerical examples in the IEEE 14-bus system.
Achieving sustainable energy systems involves complex decision-making processes. This article addresses the combination of life-cycle (LC) approaches and Data Envelopment Analysis (DEA) for the sustainability assessment of energy systems. Through a literature survey of Multi-Criteria Decision Analysis (MCDA) tools for sustainability assessment of energy systems, the most commonly used criteria, data sources and tools are identified. Moreover, a review of the LC + DEA approaches available to date is performed in order to check their convenience to assess energy systems in terms of sustainability. In this sense, the central focus of the article is to explore and elucidate potentials of these combined approaches within sustainability-oriented MCDA in the field of energy. These potentials are mainly associated with the usefulness of sustainability benchmarks for decision-makers and the wide availability of DEA models and life-cycle approaches. Given the growing role of MCDA tools in energy scenario analysis and the innovative trends found in LC + DEA, a novel methodological framework is proposed: enriched energy systems modelling through (i) endogenous integration of life-cycle indicators and (ii) ranking and benchmarking of energy scenarios according to sustainability criteria using dynamic DEA. The LC + DEA concept emerges as a promising methodology to evaluate and rank prospective scenarios in energy planning, thus facilitating decision-making processes towards a sustainable energy future. (C) 2017 Elsevier Ltd. All rights reserved.
This paper explores the link between the presence of unions in the workplace, the adoption of decentralized labor agreements and technical efficiency, using a large sample of Italian manufacturing firms. We apply the Data Envelopment Analysis, and its robust version based on bootstrap theory, to get reliable estimates of technical efficiency at the firm level in a standard first stage. We devote particular attention to the specific technology adopted, by distinguishing 20 different sector frontiers, as well as to the presence of outliers. The obtained efficiency scores are analyzed in a second stage applying a truncated regression model estimated via Maximum Likelihood, following the Simar and Wilson (2007, 2011) methodology. Our results highlight that the presence of workplace unionization decreases the level of technical efficiency, while aspects limiting the unions' power such as a strong exposure to international markets, high debt levels or the prevalence of flexible assets partially reduce the negative effect. However, when firms adopt decentralized labor contracts agreements, the effect on efficiency is positive and partially compensates the negative unions' effect. (C) 2017 Elsevier B.V. All rights reserved.
AimThe primary aim of this study was to evaluate 23 pathogens associated with peri-implantitis at inner part of implant connections, in peri-implant and periodontal pockets between patients suffering peri-implantitis and participants with healthy peri-implant tissues; the secondary aim was to estimate the predictive value of microbiological profile in patients wearing dental implants using data mining methods. Material and MethodsFifty participants included in the present casecontrol study were scheduled for collection of plaque samples from the peri-implant pockets, internal connection, and periodontal pocket. Real-time polymerase chain reaction was performed to quantify 23 pathogens. Three predictive models were developed using C4.5 decision trees to estimate the predictive value of microbiological profile between three experimental sites. ResultsThe final sample included 47 patients (22 healthy controls and 25 diseased cases), 90 implants (43 with healthy peri-implant tissues and 47 affected by peri-implantitis). Total and mean pathogen counts at inner portions of the implant connection, in peri-implant and periodontal pockets were generally increased in peri-implantitis patients when compared to healthy controls. The inner portion of the implant connection, the periodontal pocket and peri-implant pocket, respectively, presented a predictive value of microbiologic profile of 82.78%, 94.31%, and 97.5% of accuracy. ConclusionThis study showed that microbiological profile at all three experimental sites is differently characterized between patients suffering peri-implantitis and healthy controls. Data mining analysis identified Parvimonas micra as a highly accurate predictor of peri-implantitis when present in peri-implant pocket while this method generally seems to be promising for diagnosis of such complex infections.
In recent years, electricity crisis still becomes noticeable in some countries due to a widening gap between demand and supply. Consequently, the future demand plays a significant role in efficient management and utilization of electricity. Pertaining to efficient supply handling to increase the power system reliability, an electricity demand forecasting is one of the most crucial tools. The forecasting technique is used by decision makers all over the world to predict the future demand as key information for a proper policy. In this research, the hybrid model consists of maximal overlap discrete wavelet transform (MODWT), support vector machine (SVM), and differential evolution (DE) optimization emphasizing on simplifying the complex structure in data pre-processing is proposed to forecast the thirty-two annual electricity consumptions and is compared with traditional forecasting models, hybrid model of MODWT and SVM, and combined model of SVM and DE optimization based on mean absolute error (MAE), mean absolute percentage error (MAPE) and symmetric mean absolute percentage error (sMAPE) measures as well as Friedman test and post hoc test. The empirical results indicate that the proposed model outperforms other forecasting models and provides more accurate forecasts than other candidate models at 0.05 significance levels and the nearly highest precision. Consequently, the proposed model is able to reduce the limitations of individual models regarding annual electricity consumptions and can be used as a promising tool in order to forecast annual electricity consumptions as well. (C) 2017 Elsevier B.V. All rights reserved.
It is shown that the problem of evaluation of states both object and controller arises at digital control. In multi-circuit embedded systems time intervals of residence of system in any state depends on both time complexity of control algorithm and dispatching discipline. Two simplest disciplines, of most common use are investigated: the cyclic dispatching and foreground (quasi-stochastic) one. With use the semi-Markov process as fundamental theory, models of functioning of control programs under investigated dispatching disciplines are worked out. Mathematical relationships for time of return to any state of semi-Markov process and time between switches are obtained. The parameters obtained are essential for working out of efficient regimes of data processing in embedded systems.
In a conventional electricity market, trading is conducted based on power forecasts in the day-ahead market, while the power imbalance is regulated in the real-time market, which is a separate trading scheme. With large-scale wind power connected into the power grid, power forecast errors increase in the day-ahead market which lowers the economic efficiency of the separate trading scheme. This paper proposes a robust unified trading model that includes the forecasts of real-time prices and imbalance power into the day-ahead trading scheme. The model is developed based on robust optimization in view of the undefined probability distribution of clearing prices of the real-time market. For the model to be used efficiently, an improved quantum-behaved particle swarm algorithm (IQPSO) is presented in the paper based on an in-depth analysis of the limitations of the static character of quantum-behaved particle swarm algorithm (QPSO). Finally, the impacts of associated parameters on the separate trading and unified trading model are analyzed to verify the superiority of the proposed model and algorithm.
Existing methods of measuring loop gain of digitally controlled DC/DC converters mainly fall into two categories, namely the analog signal disturbance method (ASDM) and the digital signal disturbance method (DSDM). However, the loop gains obtained from these methods do not totally agree with each other. Through rigorous theoretical analysis, this paper has derived the expressions of open-loop gains obtained from these two methods, whose accuracy has been verified by simulation. Also, this paper has put forward that the difference in signal that enters into the sampler results in the variation of the transfer function of the sampler, and further induces the difference between the open-loop gains obtained from the ASDM and the DSDM.
Spread spectrum is a technique introduced for mitigating electromagnetic interference (EMI) problems in many class of circuits. In this paper, with particular emphasis on switching DC/DC converters, we consider the most common and most efficient known spreading techniques, looking for spreading parameters that ensure the highest EMI reduction and the lowest performance reduction in the circuit where the spreading is applied. The result is an interesting tradeoff not only between EMI reduction and performance drop, but also on the EMI reduction itself when considering different EMI victim models. The proposed analysis is supported by measurements on two switching DC/DC converters: 1) based on pulse width modulation and 2) based on the resonant converter class.
This paper presents theoretical and practical results about dynamic analysis, frequency response, and control of a LLC resonant dc/dc converter operating under wide input voltage and load variations. A nonlinear model for the LLC resonant converter was developed using the extended describing function method; then, based on the derived model, a nonlinear observer-based controller was designed and implemented with a digital signal processor. Transient responses obtained under input voltage and output load variations show that the proposed controller is capable to stabilize the output effectively. Experimental results prove the superiority of the proposed observer-based controller over a conventional PID controller.
This paper presents finite-control-set modelpredictive control (FCS-MPC) for a three-phase quasi-Zsource (qZS) four-leg inverter under unbalanced load condition. The key novelty of the proposed control approach is eliminating the double-line frequency ripple in the inductor current with a simple and effective approach. The proposed four-leg qZS inverter with an output LC filter can handle buck/boost and dc/ac conversion features in a single stage. Furthermore, the FCS-MPC-based control algorithm helps in maintaining balanced point of common coupling voltages for stand-alone unbalanced loads. The behavior of the predictive controller has been investigated under different operating conditions, and its robustness with the qZS network and the LC filter parameter variations are also studied. Furthermore, the effect of double-line frequency ripple and its relation with the inductor current constraint have been tackled comprehensively. To verify the performance of the proposed approach, simulation and experimental studies were performed for balanced and unbalanced loads.
This paper introduces a high-frequency soft-switching pulse-width modulation DC-DC power converter with secondary active rectifier tested as a DC current source for arc welding applications. The soft-switching DC-DC converter consists of a high-frequency full-bridge inverter, high-frequency power transformer, and a controlled output rectifier with new secondary energy recovery turn-off snubber. Circulating currents in the converter are reduced by using active rectifier, and RMS values of the currents in primary and secondary switches are decreased by utilizing a novel control algorithm. The experimental results of a 4.5kW DC-DC converter working at switching frequency of 100kHz are presented.
A weighted controller structure for DC-DC converters is proposed to deal with large-signal operations. For wide range variations of input voltage and load conditions of DC-DC converters, we firstly divide the pre-defined global operation space into local subspaces where each local linear compensator is designed for the corresponding subspace, and then all the local linear compensators are weighted into single controller structure. By doing so, the weighted controller can automatically decide which local linear compensator regulates the dynamics of DC-DC converter according to the operation conditions, and thus has the capability of self-adaptation to wide range of operating point variations. Furthermore, the prominent feature underlying the weighted control scheme is also that the nonlinearities of DC-DC converters is easily to be handled by linear compensation approaches that can be easily implemented with analog or digital control circuitries. To demonstrate the effectiveness of this controller structure, a stand-alone DC-DC converter and a cascaded DC-DC converter system are taken as examples by simulation and experimental results.
The dc power feeding system has been attracted attention in recent years. Since the load is dynamically changed in this system, the stability of dc-dc converter is important. This paper presents the stability analysis and the transient response of digital integral gain changeable control dc-dc converter using small output capacitance. The proposed method changes the integral gain with a single logarithm function according to the load current. It is verified the proposed method can obtain a good transient response with high stability even when the output capacitance is small.
Stability of power converters has become more and more important in hybrid green energy systems because of its difficulties to maintain a stable dc-bus. This paper presents dynamic characteristics of a digital integral gain changeable control dc-dc converter to realize high stability with suppression of the output capacitance. The integral gain changeable control method uses a variable integral gain, which is changed by the value of load current. The stability analysis is conducted by Bode diagrams. It is shown that the transient response and stability of the integral gain changeable method are better than the conventional fixed integral gain control method even if the output capacitance is smaller than the conventional method. Simulation and experimental results show the effectiveness of our concept.
This paper presents a digital motion controller of an electric wheelchair by using a low-cost real-time microcontroller unit (MCU) and an own developed power electronic drive. The speed control of the wheels is implemented through a digital pulse-width modulation technique which is varying with the reference generated by a low-cost joystick. Voltage regulators and power converters are implemented to supply correct voltage levels to control cards and to the DC motors from batteries. Experimental results which have been obtained by using the MCU, the mechanical structure of a used electric wheelchair and the developed electronic drive demonstrate that the proposed digital controller meets the user requirements in terms of reliability, good driving and fair economic cost.
The aim of this paper is to propose a neural network based reference modified PID control which has a simple duration design method for transient characteristics improvement of digitally controlled dc-dc converters. In renewable energy network systems, various types of dc-dc converters are widely used for power conversion and such converters require a superior control method for a stable operation. Especially, transient characteristics should be improved since they heavily affect the stability of the system. For such purposes, designing of conventional control methods becomes a difficult task since the optimization of control parameters needs complicated analysis and it is affected from variations of circuit components of converters. Therefore, simple and easy design of control is widely required for a stable operation of power converters. The neural network can provide a suitable control methodology for such situation since it treats the plant as a black box and it can realize a non-linear control based on training of the input-output relation without complicated modelling and analysis. On the other hand, the neural network based method has a disadvantage caused from the fact that the neural network is trained with data obtained in advance and an overcompensation phenomenon occurs in the transient response. In this paper, the neural network control is adopted to control the dc-dc converter in coordination with a conventional PID control. The neural network predicts the output voltage of the converter and the reference value in the PID control is modified with the predictions to reduce the error of the output voltage. To avoid overcompensation, a simple duration design for the neural network control is also provided to improve the transient response effectively. From prototype testing in simulation and experiment, it is revealed that the proposed method contributes to obtain a superior transient performance compared with the conventional PID control.
The purpose of this paper is to analyze the dynamic characteristics of proposed digital peak current mode dc-dc converter. The waveforms of the output voltage and the reactor current are derived by the small signal analysis. They are compared with simulation results assuming an actual large amplitude operation. It is confirmed that the tendency of the transient response is indicated based on the analysis results. The experimental result of the proposed method shows the validity of the proposed method and a gradual response is obtained by an improvement of the stability of dc-dc converter. Consequently, the proposed method can be a solution of implementing the peak current mode control in digital.
In this paper, second-order sliding-mode (SOSM) control approach is applied to synchronous buck dc-dc converters. The proposed SOSM controller can stabilize synchronous buck dc-dc converters using a simple digital state-machine structure, without requiring current sensing or an integral term in the control loop. The SOSM controller results in fast step-load and start-up transient responses, and is robust against parameter uncertainties. Fast transients and current limitation during start up can be accomplished by adjusting one controller parameter. Furthermore, a hysteresis method is introduced to control the switching frequency. The proposed approach is verified by experimental results on a 1.25-V 10-A prototype.
We have proposed the sensorless model control based on the static model equation of the dc-dc converter that is able to change the bias value corresponding to changes of the load current, the input voltage and output voltage. The sensorless model control can regulate the output voltage. On the other hand, the transient response of output voltage is not improved. Therefore, an improvement of the transient response is carried out by adding the transient improvement function which changes a bias value drastically for a short time at the start of the transient state. The purpose of this paper is to indicate the parameter setting of the transient improvement function that improves the transient response by the simulation analysis under changing the circuit condition.
A fully integrated low-dropout-regulated step-down multiphase-switched-capacitor DC-DC converter (a.k.a. charge pump, CP) with a fast-response adaptive-phase (Fast-RAP) digital controller is designed using a 65-nm CMOS process. Different from conventional designs, a low-dropout regulator (LDO) with an NMOS power stage is used without the need for an additional step-up CP for driving. A clock tripler and a pulse divider are proposed to enable the Fast-RAP control. As the Fast-RAP digital controller is designed to be able to respond faster than the cascaded linear regulator, transient response will not be affected by the adaptive scheme. Thus, light-load efficiency is improved without sacrificing the response time. When the CP operates at 90 MHz with 80.3% CP efficiency, only small ripples would appear on the CP output with the 18-phase interleaving scheme, and be further attenuated at VOUT by the 50-mV dropout regulator with only 4.1% efficiency overhead and 6.5% area overhead. The output ripple is less than 2 mV for a load current of 20 mA.
This paper presents a novel control method based on predictions of a neural network in coordination with a conventional PID control to improve transient characteristics of digitally controlled switching dc-dc converters. Power supplies in communication systems require to achieve a superior operation for electronic equipment installed to them. Especially, it is important to improve transient characteristics in any required conditions since they affect to the operation of power supplies. Therefore, dc-dc converters in power supplies need a superior control method which can suppress transient undershoot and overshoot of output voltage. In the presented method, the neural network is trained to predict the output voltage and is adopted to modify the reference value in the PID control to reduce the difference between the output voltage and its desired one in the transient state. The transient characteristics are gradually improved as the training procedure of the neural network is proceeded repetitively. Furthermore, the timing and duration of neural network control are also investigated and devised since the time delay, which is one of the main issue in digital control methods, affects to the improvement of transient characteristics. The repetitive training and duration adjustment of the neural network are performed simultaneously to obtain more improvement of the transient characteristics. From simulated and experimental results, it is confirmed that the presented method realizes superior transient characteristics compared to the conventional PID control.
The aim of this paper is to present an overcurrent limitation for the digital peak current mode dc-dc converter. The proposed method can detect the overcurrent in real time and it also maintains arbitrary current in the overcurrent limitation mode. It is expected to provide an effective function to protect the renewable energy system. The effectiveness of proposed method is confirmed from both simulated and experimental results.
The purpose of this paper is to propose a flexible load-dependent digital soft-start control method for dc-dc converters in a 380 Vdc system. The soft-start operation is needed to prevent negative effects such as large inrush current and output overshoot to a power supply in the start-up process of dc-dc converters. In the conventional soft-start operation, a dc-dc converter has a very slow start-up to deal with the light load condition. Therefore, it always takes a long time in any load condition to start up a power supply and obtain the desired output. In the proposed soft-start control method, the speed of the start-up process is flexibly controlled depending on the load condition. To obtain the optimal speed for any load condition, the speed of the soft-start is determined from a approximated function of load current, which is estimated from experiment results in advance. The proposed soft-start control method is evaluated both in simulations and experiments. From results, it is confirmed that the proposed method has superior soft-start characteristics compared to the conventional one.
This paper describes a modular architecture based on the dual-active bridge (DAB) converter in input-series-output-parallel (ISOP) connection. This work is focused on the input voltage sharing to ensure a proper operation of each module by means of an active control of input and output voltages. A small-signal model of the modular architecture is proposed and a decoupled control loops' scheme is used to implement the control strategy. An experimental setup has been built in order to validate the model of the DAB converter in ISOP connection and the proposed control strategy, taking different operating conditions and constructive parameter values into account.
Dc-dc converters often exhibit undesirable oscillations due to their nonlinear dynamics. Digitally controlled converters have further degrees of nonlinearity in terms of quantization in the analog to digital converter and the digital pulse width modulator, giving rise to the well known phenomenon of limit cycle oscillations. In this study, a different and hitherto unreported class of oscillations in digitally controlled converters has been reported, and its origin has been traced to asymmetric saturation in the duty cycle. The study attempts to provide physical insights behind this phenomenon of saturation generated oscillation (SGO), and to identify the converter-system components responsible for it. The challenges in the traditional stability analysis of such a system are highlighted, followed by a simplified analysis leading to the calculation of the oscillation-free operating-zone, and some of the effects of system parameters on the SGO. The results have been used to show some potential ways in which the oscillation can be avoided by using SGO-immune designs. Simulation and experimental results have been provided to illustrate the points and substantiate the claims.
This study proposes a novel method to eliminate the limit cycle caused by low resolution analogue-to-digital converter (ADC) in digitally controlled DC-DC converter. The reduced state Kalman filter is proposed to get the optimum estimate of the output voltage from the noisy measurement provided by the low resolution ADC. The proposed scheme is simulated with 6 bit resolution of ADC and the validation is performed with different resolutions using a prototype model which is implemented in16 bit digital signal processor. The results show that the proposed scheme eliminates limit cycle oscillation completely and is computationally more efficient.
The loop-handover (LHO) technique is proposed to overcome the problem of close-loop performance in digitally controlled single-inductor multiple-output dc-dc boost converters during start-up. The presented technique utilises an existing clock source and requires only a small number of blocks. It also occupies a smaller silicon area, thus consuming low power and increasing efficiency. The presented technique is validated with proposed on-chip digital controller with multiple-output boost converter architecture using segmented delay line digital pulse width modulation. Experimental results show a successful close loop with reduced transients by using the simpler LHO technique.
This study presents an approach to system identification and adaptive control of a non-inverting buck-boost converter in the presence of large signal changes, uncertainty of converter components and effects of imperfect modelling. Feedback loops of DC-DC converters are typically designed conservatively so that the closed-loop regulation and stability margins are maintained over a pre-determined range of operating conditions. The proposed approach is able to keep a high-performance response without the instability issue of dynamic change of the converter. In the presence of uncertainty on the parameters of a DC-DC converter, a digital adaptive controller based on system identification and minimum degree pole placement is proposed. To verify the validity of the proposed digital controller, an experimental setup is constructed for a non-inverting buck-boost converter and the fully digital adaptive control is implemented by a micro controller. The experimental results show the capability of an adaptive controller during different operating points.
Centralised electricity systems are being integrated by a multitude of small distributed generation clusters, called nanogrids, capable of ensuring full utilisation of renewable energy sources, high flexibility, efficiency and improved reliability of the power grid due to redudancy. In this study, small photovoltaic plants combined with energy storage systems represent a promising solution for full exploitation of renewable energies and for effective development of electromobility. The purpose of this study is two-fold: first it deals with a DC nanogrid suitable for small energetic clusters such as residential or office buildings and consisting of photovoltaic arrays, fuel cells, electric vehicle charger stations, loads, then proposes a multifunctional full-bridge DC/DC LLC resonant converter building block. The latter, while accepting large input/output ranges is suitable for photovoltaic and fuel cells energy conversion, electric vehicle recharging stations and other DC applications available in the nanogrid. Proposed power system can be interconnected with conventional AC grid through voltage source converter. After description of proposed nanogrid, some analyses are performed on its core element, i.e. the DC converter building block.
This paper presents the stability analysis of dc distributed power systems with multiple converter-controlled loads. The load converters are tightly controlled, behaving as constant power loads with low-damped LC filters. The dynamic behavior of the system in high frequency range is often not studied with the classical tools based on conventional averaging techniques. However, dc power systems with the reduced size filter, and consequently, the high resonant frequency, are widely used in transportation applications. In this paper, the stability analysis of the system is established based on a discrete-time model of the system, taking into account the switching frequency and intrinsic nonlinearities of the system model. The impacts of the filter parameters and interactions among the constant power loads are investigated with the proposed discrete-time method. Moreover, an active stabilizer is developed and included in the dynamic model of the system, in order to extend the stability margin. The theoretical observations are then validated experimentally on a laboratory hardware prototype.
Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor I (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, this study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders.(C) 2017 Elsevier B.V. All rights reserved.
Soil salinity is a major environmental stress limiting plant growth and productivity. We have reported previously the isolation of an Apocynum yenetum DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here, we report that the overexpression of AvDH1 driven by a constitutive cauliflower mosaic virus 35S promoter in cotton plants confers salinity tolerance. Southern and Northern blotting analyses showed that the AvDH1 gene was integrated into the cotton genome and expressed. In this study, the growth of transgenic cotton expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant to salt than the wild-type plants when grown in a growth chamber. The lower membrane ion leakage, along with increased activity of superoxide dismutase, in AvDH1 transgenic lines suggested that these characteristics may prevent membrane damage, which increases plant survival rates. In a saline field, the transgenic cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed cotton yields compared with wild-type plants, especially at high soil salinity levels. This study indicates that transgenic cotton expressing AvDH1 is a promising option for increasing crop productivity in saline fields.
This paper proposes a new method of dead-time effect compensation. The proposed solution is based on additional phase current measurements realized by analog-to-digital converters. These measurements are carried out at the time instants specified by a pulsewidth-modulation (PWM) strategy. This makes it possible to estimate inverter currents at the commutation instants and, finally, to estimate the voltage error caused by dead time. This voltage error is compensated during the next switching period by modification of a reference voltage. The proposed solution can be used to compensate the voltage error in multilevel multiphase voltage source inverters. The experimental research studies were carried out on three-phase two-level and three-level neutral-point-clamped inverters supplying 55- and 160-kW motors, respectively. The results of the experimental investigations are presented in this paper.
By guiding our attention to the emotional responses of a little girl and her darkly lit surroundings, Jude's film explores human existence in the face of death. Informed by existential philosophy in the vein of Heidegger, this article investigates the difference between fear of death and fear of the dead.
The nature and quality of social work decision making have been highlighted in recent years by a number of high-profile child deaths. Recognising and assessing child abuse is beset with uncertainties and complexities that profoundly shape practice yet are often overlooked by more official and distanced accounts. This paper draws on ethnographic data from a study of social workers' decision making to uncover some of the issues they faced in gathering and assessing information. Workers faced problems with inaccurate or incomplete information, poorly defined situations, time pressures and heavy workloads. The paper draws attention to the ways in which the team organised itself to manage these issues which could provide a better understanding of how everyday decision making can be supported and improved.
The primate prefrontal cortex represents both past and future goals. To investigate its role in representing the goals of other agents, we designed a nonmatch-to-goal task that involved a human-monkey (H-M) interaction. During each trial, 2 of 4 potential goal objects were presented randomly to the left or right part of a display screen, and the monkey's (or human's) task was to choose the one that did not match the object goal previously chosen. Human and monkey trials were intermixed, and each agent, when acting as observer, was required to monitor the other actor's choice to switch the object goal choice in case it became the actor on the subsequent trial. We found neurons encoding the actor, either the monkey itself or the human, neurons encoding the agent future goal position and neurons encoding the agent previous goal position. In the category of neurons encoding the human future goal, we differentiated between those encoding the future goal of both agents and those encoding only the human agent future goal. While the first one might represent a covert mental simulation in the human trials, the other one could represent a prediction signal of the other's agent choice.
Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Nonmotor symptoms include cognitive deficits and impairment in emotions recognition ability associated with loss of dopaminergic neurons in the substantia nigra and with alteration in frontostriatal circuits. In this review, we analyzed the studies on social cognition ability in patients with PD. We searched on PubMed and Web of Science databases and screening references of included studied and review articles for additional citations. From initial 260 articles, only 18 met search criteria. A total of 496 patients were compared with 514 health controls, through 16 different tests that assessed some subcomponents of social cognition, such as theory of mind, decision-making, and emotional face recognition. Studies on cognitive function in patients with PD have focused on executive function. Patients with PD showed impairment in social cognition from the earliest stages of disease. This ability seems to not be significantly associated with other cognitive functions.
A monolithic integrated low-voltage deep brain stimulator with wireless power and data transmission is presented. Data and power are transmitted to the stimulator by mutual inductance coupling, while the in-vitro controller encodes the stimulation parameters. The stimulator integrates the digital control module and can generate the bipolar current with equal amplitude in four channels. In order to reduce power consumption, a novel controlled threshold voltage cancellation rectifier is proposed in this paper to provide the supply voltage of the stimulator. The monolithic stimulator was fabricated in a SMIC 0.18 mu m 1-poly 6-metal mixed-signal CMOS process, occupying 0.23 mm(2), and consumes 180 mu W on average. Compared with previously published stimulators, this design has advantages of large stimulated current (0-0.8 mA) with the double low-voltage supply (1.8 and 3.3 V), and high-level integration.
Literature studies showed the ability to treat neuropsychiatric disorders using H1 coil, developed for the deep Transcranial Magnetic Stimulation (dTMS). Despite the positive results of the clinical studies, the electric field (E) distributions inside the brain induced by this coil when it is positioned on the scalp according to the clinical studies themselves are not yet precisely estimated. This study aims to characterize the E distributions due to the H1 coil in the brain of two realistic human models by computational electromagnetic techniques and to compare them with the ones due to the figure-of-8 coil, traditionally used in TMS and positioned as such to simulate the clinical experiments. Despite inter-individual differences, our results show that the dorsolateral prefrontal cortex is the region preferentially stimulated by both H1 and figure-of-8 coil when they are placed in the position on the scalp according to the clinical studies, with a more broad and non-focal distribution in the case of H1 coil. Moreover, the H1 coil spreads more than the figure-of-8 coil both in the prefrontal cortex and medial prefrontal cortex and towards some deeper brain structures and it is characterized by a higher penetration depth in the frontal lobe. This work highlights the importance of the knowledge of the electric field distribution in the brain tissues to interpret the outcomes of the experimental studies and to optimize the treatments. (C) 2017 IPEM. Published by Elsevier Ltd. All rights reserved.
Narratives are an important component of culture and play a central role in transmitting social values. Little is known, however, about how the brain of a listener/reader processes narratives. A receiver's response to narration is influenced by the narrator's framing and appeal to values. Narratives that appeal to "protected values," including core personal, national, or religious values, may be particularly effective at influencing receivers. Protected values resist compromise and are tied with identity, affective value, moral decision-making, and other aspects of social cognition. Here, we investigated the neural mechanisms underlying reactions to protected values in narratives. During fMRI scanning, we presented 78 American, Chinese, and Iranian participants with real-life stories distilled from a corpus of over 20 million weblogs. Reading these stories engaged the posterior medial, medial prefrontal, and temporo-parietal cortices. When participants believed that the protagonist was appealing to a protected value, signal in these regions was increased compared with when no protected value was perceived, possibly reflecting the intensive and iterative search required to process this material. The effect strength also varied across groups, potentially reflecting cultural differences in the degree of concern for protected values.
Communication between cortical regions is necessary for optimal cognitive processing. Functional relationships between cortical regions can be inferred through measurements of temporal synchrony in spontaneous activity patterns. These relationships can be further elaborated by surveying effects of cortical lesions upon inter-regional connectivity. Lesions to cortical hubs and heteromodal association regions are expected to induce distributed connectivity changes and higher-order cognitive deficits, yet their functional consequences remain relatively unexplored. Here, we used resting-state fMRI to investigate intrinsic functional connectivity (FC) and graph theoretical metrics in 12 patients with circumscribed lesions of the medial prefrontal cortex (mPFC) portion of the Default Network (DN), and compared these metrics with those observed in healthy matched comparison participants and a sample of 1139 healthy individuals. Despite significant mPFC destruction, patients did not demonstrate weakened intrinsic FC among undamaged DN nodes. Instead, network-specific changes were manifested as weaker negative correlations between the DN and attentional and somatomotor networks. These findings conflict with the DN being a homogenous system functionally anchored at mPFC. Rather, they implicate a role for mPFC in mediating cross-network functional interactions. More broadly, our data suggest that lesions to association cortical hubs might induce clinical deficits by disrupting communication between interacting large-scale systems.
The symbiotic interaction between legume plants and rhizobia results in the formation of root nodules, in which symbiotic plant cells host and harbor thousands of nitrogen-fixing rhizobia. Here, a Medicago truncatula nodules with activated defense 1 (nad1) mutant was identified using reverse genetics methods. The mutant phenotype was characterized using cell and molecular biology approaches. An RNA-sequencing technique was used to analyze the transcriptomic reprogramming of nad1 mutant nodules. In the nad1 mutant plants, rhizobial infection and propagation in infection threads are normal, whereas rhizobia and their symbiotic plant cells become necrotic immediately after rhizobia are released from infection threads into symbiotic cells of nodules. Defense-associated responses were detected in nad1 nodules. NAD1 is specifically present in root nodule symbiosis plants with the exception of Morus notabilis, and the transcript is highly induced in nodules. NAD1 encodes a small uncharacterized protein with two predicted transmembrane helices and is localized at the endoplasmic reticulum. Our data demonstrate a positive role for NAD1 in the maintenance of rhizobial endosymbiosis during nodulation.
BackgroundThere is increasing popularity of high-power lasers for surgical debridement and antimicrobial therapy in the management of peri-implantitis and periodontal therapy. Removal of the noxious foci would naturally promote tissue healing directly. However, there are also anecdotal reports of better healing around routine high-power laser procedures. The precise mechanisms mediating these effects remain to be fully elucidated. This work examines these low-dose laser bystander effects on oral human epithelial and fibroblasts, particularly focusing on the role of human -defensin 2 (HBD-2 or DEFB4A), a potent factor capable of antimicrobial effects and promoting wound healing. Material and MethodsLaser treatments were performed using a near-infrared laser (810 nm diode) at low doses. Normal human oral keratinocytes and fibroblast cells were used and HBD-2 mRNA and protein expression was assessed with real time polymerase chain reaction, western blotting and immunostaining. Role of transforming growth factor (TGF)-1 signaling in this process was dissected using pathway-specific small molecule inhibitors. ResultsWe observed laser treatments robustly induced HBD-2 expression in an oral fibroblast cell line compared to a keratinocyte cell line. Low-dose laser treatments results in activation of the TGF-1 pathway that mediated HBD-2 expression. The two arms of TGF-1 signaling, Smad and non-Smad are involved in laser-mediated HBD-2 expression. ConclusionsLaser-activated TGF-1 signaling and induced expression of HBD-2, both of which are individually capable of promoting healing in tissues adjacent to high-power surgical laser applications. Moreover, the use of low-dose laser therapy itself can provide additional therapeutic benefits for effective clinical management of periodontal or peri-implant disease.
Specific defensive behaviors of rodents are shaped by features of the eliciting threat stimuli and situation. Threat scenarios confirmed these relationships in people, with results substantially replicated in 4 additional scenario studies. Subsequent human studies involve computer games measuring fear as flight from threat stimuli and anxiety as alternation between two threats. Stabilometric studies have shown reduction in sway (freezing) to inescapable (e.g. with gun pointed at subject) threatening photographs; but enhanced lateral sway (flight attempts) to escapable threats; (gun pointed away from subject). Relationships between threat ambiguity, risk assessment, and anxiety have been validated by identification of videos of facial expressions to ambiguous threats, as anxiety; and systematic biases toward threat stimuli by anxious individuals. Enhanced rumination, interpretable as unsuccessful risk assessment, is a dynamic component of both anxiety and depression, particularly in women. While there is less experimental work on defensive threat/attack, a transdiagnostic "Fear of Harm" phenotype of aggression associated with fear suggests that this is a component of pathological as well as normal human defensive behavior. (C) 2016 Published by Elsevier Ltd.
Background: The aim of the present study was to investigate the effects of the iron chelator deferiprone in diabetic nephropathy (DN) rats and the mechanisms involved. Methods: Thirty-two male Wistar rats (180-220 g, 6 weeks old) were randomly divided into a control group, a DN group and two DN groups treated with either 50 or 100 mg/kg per day deferiprone. The DN group was established by feeding of a high-carbohydrate-fat diet and injection of 35 mg/kg streptozotocin into the vena caudalis. The duration of deferiprone treatment was 20 weeks. Histopathological changes were detected by hematoxylin-eosin and Masson staining, as well as transmission electron microscopy. Levels of nuclear factor (NF)-kappa B, monocyte chemotactic protein (MCP)-1, matrix metalloproteinase (MMP)-9, tissue-specific inhibitor of metalloproteinase (TIMP)-1, cyclo-oxygenase (COX)-2, and nitrotyrosine were determined in kidney tissues using reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry. Results: Histopathological observations showed that deferiprone treatment alleviated inflammation infiltrates and collagenous fibrosis in DN rats. Results from RT-PCR and western blotting indicated that deferiprone inhibited the expression of NF-kappa B, MCP-1, COX-2, and nitrotyrosine, which were overexpressed in DN rats. Immunohistochemistry showed that the mechanism of deferiprone action may involve regulation of MMP-9 and TIMP-1. Decreased MMP-9 expression and increased TIMP-1 expression in DN rats were significantly promoted and inhibited by deferiprone, respectively. Conclusion: Iron chelation by oral deferiprone has a renoprotective effect in DN rats by relieving oxidative stress, inflammation, and fibrosis, which is related to the cytokines NF-kappa B, MCP-1, MMP-9, TIMP-1, COX-2, and nitrotyrosine.
Undocumented immigrant young adults growing up in the United States face significant challenges. For those qualified, the Deferred Action for Childhood Arrivals (DACA) program's protections may alleviate stressors, with implications for their mental health and wellbeing (MHWB). We conducted nine focus groups with 61 DACA-eligible Latinos (ages 18-31) in California to investigate their health needs. Participants reported MHWB as their greatest health concern and viewed DACA as beneficial through increasing access to opportunities and promoting belonging and peer support. Participants found that DACA also introduced unanticipated challenges, including greater adult responsibilities and a new precarious identity. Thus, immigration policies such as DACA may influence undocumented young adults' MHWB in expected and unexpected ways. Research into the impacts of policy changes on young immigrants' MHWB can guide stakeholders to better address this population's health needs. MHWB implications include the need to reduce fear of deportation and increase access to services.
Overpopulation and economic industrialization are two common explanations for deforestation. Political ecology, however, highlights that good governance and effective land management at the local level can offset the impact of population growth and development on environmental degradation. In this paper, we provide an innovative argument derived from political ecology to explain deforestation, but rather than pursing a "bottom up" approach to governance, we take a "top down" approach. We argue that the state can ease deforestation rates by weaning rural populations off of the consumption of biomass for their energy needs by expanding rural electrification access. Using a panel analysis of 158 countries for the years 1990, 2000, and 2010, we find that not only does rural electrification cause deforestation rates to decrease, but also that it is more robust in explaining deforestation than population growth or development. Our study provides two innovations to political ecology: it highlights that the state can help, rather than hinder, local populations with managing their local environments in a more sustainable way by providing them with (public goods-based) energy alternatives, and; it supplements political ecology's qualitative focus on environmental degradation with a generalized quantitative analysis of state-based initiatives on deforestation. Our results suggest that current global initiatives addressing deforestation specifically the Reduction of Emissions from Deforestation and Forest Degradation (REDD+) agenda of the United Nations' Framework Convention on Climate Change should not only assist local land managers, but also work with the state to ensure universal access to electricity. (C) 2017 Elsevier Ltd. All rights reserved.
Wiener processes have received considerable attention in degradation modeling over the last two decades. In this paper, we propose a generalized Wiener process degradation model that takes unit-to-unit variation, time-correlated structure and measurement error into considerations simultaneously. The constructed methodology subsumes a series of models studied in the literature as limiting cases. A simple method is given to determine the transformed time scale forms of the Wiener process degradation model. Then model parameters can be estimated based on a maximum likelihood estimation (MLE) method. The cumulative distribution function (CDF) and the probability distribution function (PDF) of the Wiener process with measurement errors are given based on the concept of the first hitting time (FHT). The percentiles of performance degradation (PD) and failure time distribution (FTD) are also obtained. Finally, a comprehensive simulation study is accomplished to demonstrate the necessity of incorporating measurement errors in the degradation model and the efficiency of the proposed model. Two illustrative real applications involving the degradation of carbon-film resistors and the wear of sliding metal are given. The comparative results show that the constructed approach can derive a reasonable result and an enhanced inference precision. (C) 2017 Elsevier Ltd. All rights reserved.
Advanced extraction and purification techniques were found to be essential tools for obtaining sufficient DNA from bones. However, in case of short tandem repeats (STRs) typing failure especially with old skeletal remains, mitochondrial DNA (mtDNA) analysis is the ultimate solution for individual and species identification. Thirty six bone samples were collected from human remains. DNA was extracted using the organic method after special sample preparations and quantified using a Real-time polymerase chain reaction (RT-PCR). Polymerase chain reaction (PCR) was done using Identifier Plus PCR Amplification Kit and amplified products were typed using a Genetic Analyzer for autosomal STR typing. Samples with DNA concentration above 0.04 ng were efficient in obtaining their complete STR profiles. MtDNA control region was also amplified and sequenced. MtDNA was more efficient than autosomal STR profiling in discriminating among human bone samples especially those which have low and/or degraded DNA content.
Dehydrins, a large family of abiotic stress proteins, are defined by the presence of a mostly conserved motif known as the K-segment, and may also contain two other conserved motifs known as the Y-segment and S-segment. Using the dehydrin literature, we developed a sequence motif definition of the K-segment, which we used to create a large dataset of dehydrin sequences by searching the Pfam00257 dehydrin dataset and the Phytozome 10 sequences of vascular plants. A comprehensive analysis of these sequences reveals that lysine residues are highly conserved in the K-segment, while the amino acid type is often conserved at other positions. Despite the Y-segment name, the central tyrosine is somewhat conserved, but can be substituted with two other small aromatic amino acids (phenylalanine or histidine). The S-segment contains a series of serine residues, but in some proteins is also preceded by a conserved LHR sequence. In many dehydrins containing all three of these motifs the S-segment is linked to the K-segment by a GXGGRRKK motif (where X can be any amino acid), suggesting a functional linkage between these two motifs. An analysis of the sequences shows that the dehydrin architecture and several biochemical properties (isoelectric point, molecular mass, and hydrophobicity score) are dependent on each other, and that some dehydrin architectures are overexpressed during certain abiotic stress, suggesting that they may be optimized for a specific abiotic stress while others are involved in all forms of dehydration stress (drought, cold, and salinity).
The thyroid gland has an exceptionally high selenium content, even during selenium deficiency. At least 11 selenoproteins are expressed, which may be involved in the protection of the gland against the high amounts of H2O2 produced during thyroid hormone biosynthesis. As determined here by in situ hybridization and Northern blotting experiments, glutathione peroxidases (GPx) 1 and 4 and selenoprotein P were moderately expressed, occurring selectively in the follicular cells and in leukocytes of germinal follicles of thyroids affected by Hashimoto's thyroiditis. Selenoprotein 15 was only marginally expressed and distributed over all cell types. GPx3 mRNA was exclusively localized to the thyrocytes, showed the highest expression levels and was down-regulated in 5 of 6 thyroid cancer samples as compared to matched normal controls. GPx3 could be extracted from thyroidal colloid by incubation with 0.5% sodium dodecyl sulfate indicating that this enzyme is (i) secreted into the follicular lumen and (ii) loosely attached to the colloidal thyroglobulin. These findings are consistent with a role of selenoproteins in the protection of the thyroid from possible damage by H2O2. Particularly, GPx3 might use excess H2O2 and catalyze the polymerization of thyroglobulin to the highly cross-linked storage form present in the colloid.
Airway exposure of lipopolysaccharide (LPS) is shown to regulate type I and type II helper T cell induced asthma. While high doses of LPS derive Th1- or Th17-immune responses, low LPS levels lead to Th2 responses. In this paper, we analyze a mathematical model of Thl/Th2/Th17 asthma regulation suggested by Lee et al. (S. Lee, H.T. Hwang, and Y. Kim, Modeling the role of TGF-8 in regulation of the Th17 phenotype in the LPS-driven immune system, Bull Math Biol., 76 (5), 1045-1080, 2014) and show that the system can undergo a Hopf bifurcation at a steady state of the Th17 phenotype for high LPS levels in the presence of time delays in inhibition pathways of two key regulators: IL-4/Th2 activities (H) and TCF-beta levels (G). The time delays affect the phenotypic switches among the Thl, Th2, and Th17 phenotypes in response to time-dependent LPS doses via nonlinear crosstalk between H and G. An extended reaction-diffusion model also predicts coexistence of these phenotypes under various biochemical and bio-mechanical conditions in the heterogeneous microenvironment.
Background. Deficiencies in lysosomal a-mannosidase (LAM) activity in animals, caused either by mutations or by consuming toxic alkaloids, lead to severe phenotypic and behavioural consequences. Yet, epialleles adversely affecting LAM expression exist in the honey bee population suggesting that they might be beneficial in certain contexts and cannot be eliminated by natural selection. Methods. We have used a combination of enzymology, molecular biology and metabolomics to characterise the catalytic properties of honey bee LAM (AmLAM) and then used an indolizidine alkaloid swainsonine to inhibit its activity in vitro and in vtvo. Results. We show that AmLAM is inhibited in vitro by swainsonine albeit at slightly higher concentrations than in other animals. Dietary exposure of growing larvae to swainsonine leads to pronounced metabolic changes affecting not only saccharides, but also amino acids, polyols and polyamines. Interestingly, the abundance of two fatty acids implicated in epigenetic regulation is significantly reduced in treated individuals. Additionally, swainsonie causes loco-like symptoms, increased mortality and a subtle decrease in the rate of larval growth resulting in a subsequent developmental delay in pupal metamorphosis. Discussion. We consider our findings in the context of cellular LAM function, larval development, environmental toxicity and colony-level impacts. The observed developmental heterochrony in swainsonine-treated larvae with lower LAM activity offer a plausible explanation for the existence of epialleles with impaired LAM expression. Individuals carrying such epialleles provide an additional level of epigenetic diversity that could be beneficial for the functioning of a colony whereby more flexibility in timing of adult emergence might be useful for task allocation.
Porcine-transmissible gastroenteritis virus (TGEV) is a pathogenic coronavirus responsible for high diarrhoea-associated morbidity and mortality in suckling piglets. We analysed the TGEV ORF3 gene using nested polymerase chain reaction and identified an ORF3a deletion in three field strains of TGEV collected from piglets in China in 2015. Eight TGEV ORF3 sequences were obtained in this study. Phylogenetic tree analysis of ORF3 showed that the eight TGEV ORF3 genes all belonged to the Miller cluster. CH-LNCT and CH-MZL were closely correlated with Miller M6, while CH-SH was correlated with Miller M60. These results thus indicate that the existence of Miller, as well as the Purdue cluster, in Chinese field strains of TGEV. Furthermore, we found the first evidence for a large deletion in ORF3 resulting in the loss of ORF3a, previously reported in porcine respiratory coronavirus, in three field strains (CH-LNCT, CH-MZL, and CH-SH) of TGEV. The results of the present study thus provide important information regarding the underlying evolution mechanisms of coronaviruses.
Modification of p53 expression levels and its principle apoptosis and cell cycle regulatory partners, mouse double minute 2 homolog (MDM-2) and p21, has been previously reported in various types of cancer. In the current study, the expression of Delta 133p53 isoforms was investigated in lung carcinomas with respect to the expression of the aforementioned genes. The expression of p53 full-length transcript and Delta 133p53 isoforms alpha, beta and gamma transcripts, MDM-2 and p21 transcripts were determined by reverse transcription-quantitative polymerase chain reaction, in total RNA isolated from 17 lung carcinoma specimens and 17 corresponding adjacent non-cancerous tissues. RNA expression analysis was performed according to the Pfaffl equation and Rest tool using beta-actin as a reference gene. Detection of the above proteins was additionally performed by western blotting. Significant overexpression of the Delta 133p53 mRNAs was observed in cancerous as compared with adjacent non-cancerous tissues (3.94-fold), whereas full-length p53 and MDM-2 expression exhibited a smaller, however significant, increase. The expression of the p21 transcript was significantly reduced in cancerous specimens. Delta 133p53 and p21 expression levels varied in parallel, however were not significantly correlated. p53 full-length protein expression observed by western blot analysis strongly varied from the Delta 133p53 isoforms, however MDM-2 protein isoforms were not detectable and p21 protein was more abundant in non-cancerous tissues. In conclusion, Delta 133p53 mRNA levels is suggested as a potentially useful marker of malignancy in lung cancer. The absence of Delta 133p53 protein in lung carcinomas, which overexpress Delta 133p53 transcripts, may indicate the role of the latter in post-transcriptional regulation through RNA interference in the cell cycle and apoptosis.
We propose an architecture that reduces the power consumption and active area of such a modulator through a reduction in the number of active components and a simplification of the topology. The proposed architecture reduces the power consumption and active area by reducing the number of active components and simplifying the modulator topology. A novel second-order loop filter that uses a single operational amplifier resonator reduces the number of active elements and enhances the controllability of the transfer function. A trapezoidal-shape half-delayed return-to-zero feedback DAC eliminates the loop-delay compensation circuitry and improves pulse-delay sensitivity. These simple features of the modulator allow higher frequency operation and more design flexibility. Implemented in a 130 nm CMOS technology, the prototype modulator occupies an active area of 0.098 mm(2) and consumes 5.23 mW power from a 1.2 V supply. It achieves a dynamic range of 62 dB and a peak SNDR of 60.95 dB over a 15 MHz signal bandwidth with a sampling frequency of 780 MHz. The figure-of-merit of the modulator is 191 fJ/conversion-step.
This paper discusses the use of a low gain amplifier and a passive switched-capacitor (SC) network to enable the SC integrator function. The method is applied to a delta-sigma modulator to achieve high resolution as proved by the 65-nm CMOS technology test vehicle. Compared with the conventional operational amplifier (op-amp)-based SC integrator, this solution utilizes a low-gain open-loop amplifier to drive a passive SC integrator with positive feedback. Since the open-loop amplifier requires a low dc gain and implements an embedded current adder, the power consumption is very low. Power reduction for single bit is obtained by using passive feed-forward with built-in adder to assist the first amplifier. The low swing obtained at the output of the active blocks relaxes the slew rate requirement and enhances the linearity. Implemented in 65-nm digital CMOS technology with an active area of 0.1 mm(2), the test chip achieves a dynamic range of 91 dB, peak signal-to-noise ratio of 88.4 dB, peak signal-to-noise-plus-distortion ratio of 88.2 dB, and a spurious free dynamic range of 106 dB while consuming 73.6 mu W in a 25-kHz signal bandwidth at 1 V supply, yielding a FoM(Walden) of 70 fJ/conv-step and FoM(Schreier) of 176 dB.
This paper presents a low voltage continuous-time delta-sigma modulator (DSM) intended for the receiver of an ultra-low-power radio. The DSM features a 2nd-order loop filter implemented with a single operational amplifier to reduce the power consumption. Furthermore, a 4-bit quantizer is used to achieve high resolution while keeping the sampling frequency low. The quantizer is realized using the successive approximation register architecture with asynchronous control which is more power efficient than the commonly used flash architecture. The DSM has been implemented in a 65 nm CMOS process. Simulation results show a peak SNDR of 65 dB over a 500 kHz signal bandwidth. The DSM consumes 69 W from a 800 mV power supply.
China is quickly installing advanced metering infrastructure (AMI), which could provide tremendous opportunities in developing and utilizing demand response resources. Demand response may potentially create a profitable industry and contribute to efficiency improvement, cost reduction, and pollution mitigation of the entire electricity sector. However, China lags behind the developed world in utilizing demand response. Institutional barriers, including the lack of competitive electricity market and the resistance by the state grid corporations, are preventing the commercialization of demand response. In order to fully realize the potential of smart grid, China needs to push forward the reforms toward establishing an open access electricity market so the pollution-free demand response resources may compete with power generators on leveled field. (C) 2015 Elsevier B.V. All rights reserved.
Understanding the contribution a resource can make to the power system could indicate where its value lies. This paper estimates the capacity value of a load-shifting resource which is capable of providing multiple services. The capacity value represents the contribution of a resource to generation adequacy and an understanding of this contribution is important to compare how different power system resources can assist power system operators and planners. Additionally, policy-makers and market operators need an appreciation of the capacity value of different resources in order to design capacity remuneration mechanisms. A building energy model coupled with a power system model, co-optimizing the supplyside and the demand-side, is employed in this paper to estimate the capacity value of a specific load shifting resource. The resource examined is electric thermal storage heating devices for space and water heating. Ireland is used as a test case. It was found that these load-shifting devices can provide an adequacy contribution to the power system and thus have a capacity value. The capacity value, for the Irish case, can be up to 26% for the DR resource in question for the given year but the values are typically much lower due to operational constraints (reserve provision) and due to occupancy profile impacts. The results highlight the need for holistic modeling of demand response resources, as well as the need for additional work for different load-shifting resources and more data. (C) 2017 Elsevier Ltd. All rights reserved.
We present an economic assessment of the impacts of Demand Response (DR) and pricing schemes on the conditions for distributed solar photovoltaics, with the focus on individual households. An optimization model has been developed that minimizes the electricity cost for individual households with the option of dispatching DR loads. DR of appliances and hydronic heating (electrical water heating for both space heating and hot water) are investigated, as well as the effects of applying a monthly, hourly or net metering pricing scheme for selling excess generated electricity and a tax reduction scheme for electricity sold to the grid. We show that for Swedish conditions a monthly net metering pricing scheme would result in the largest PV installations per household (median rated capacity of 4.21 Wpihousehold). The use of the tax reduction scheme reduces the installation per household (2.1 kWp/household), but with an installation being profitable for a larger fraction of the households. Furthermore, the tax reduction scheme retains an incentive for engaging in DR. The use of hydronic DR can support the same installations sizes as the tax reduction scheme, whilst Appliance DR is shown to have only a low impact on the profitability of a PV installation. (C) 2017 Elsevier Ltd. All rights reserved.
Power system reliability faces serious challenges when supply shortage occurs because of unexpected generation or transmission line outages especially during extreme weather conditions. Alternative to conventional approaches that solicit aids from the generation side, operators can now leverage the demand-side resources through a variety of electricity market mechanisms to balance the active power and enhance system reliability. The benefits of the demand response (DR) have long been recognized in many works and empirical cases. Systematic analyses, however, have never been addressed to assess the values of the market-based DR for supporting system reliability. In this paper, a case study on the performance of DR in PJM Interconnections during the 2014 North American Polar Vortex is provided to highlight the significant contributions to improving system reliability and maintaining grid stability from DR programs. The unique merits in technical, economic and environmental aspects exhibited by DR during this extreme event verse conventional system-reliability-improving approaches are also demonstrated accordingly. Furthermore, we reveal the difference of DR programs driven by various existing market mechanisms after describing the fundamental DR functions. Values of various DR programs are also highlighted. At last, challenges and opportunities facing China on the design and implementation of DR programs during the transform from the monopoly scheme to an open electricity market during the power industry restructuring in recent years are also discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Demand response, defined as the shifting of electricity demand, is generally believed to have value both for the grid and for the market: by matching demand more closely to supply, consumers could profit from lower prices, while in a smart grid environment, more renewable electricity can be used and less grid capacity may be needed. However, the introduction of residential demand response programmes to support the development of smart grids that includes renewable generation is hampered by a number of barriers. This paper reviews these barriers and categorises them for different demand programmes and market players. The case study for the Netherlands shows that barriers can be country specific. Two types of demand response programmes have been identified as being the most promising options for households in smart grids: price-based demand response and direct load control, while they may not be beneficial for market players or distribution system operators. (C) 2016 The Authors. International Journal of Energy Research Published by John Wiley & Sons Ltd.
This paper presents a novel approach to demand side management (DSM), using an "individualized" price policy, where each end user receives a separate electricity pricing scheme designed to incentivize demand management in order to optimally manage flexible demands. These pricing schemes have the objective of reducing the peaks in overall system demand in such a way that the average electricity price each individual user receives is non-discriminatory. It is shown in this paper that this approach has a number of advantages and benefits compared to traditional DSM approaches. The "demand aware price policy" approach outlined in this paper exploits the knowledge, or demand-awareness, obtained from advanced metering infrastructure. The presented analysis includes a detailed case study of an existing European distribution network where DSM trial data was available from the residential end-users.
Objective: To examine the effects of using cognitive reappraisal to find positive gains on caregivers' depressive symptoms, burden, and psychological well-being. Method: Ninety-six caregivers of persons with Alzheimer's disease were randomly assigned to receive a benefit-finding intervention or 1 of 2 treatment-as-usual conditions, namely, simplified psychoeducation (lectures only; SIM-PE) or standard psychoeducation (STD-PE). Each participant received 4 biweekly interventions of 3 hr each, over a 2-month period, at home. Results: Results showed that benefit-finding participants reported lower depressive symptoms after treatment, when compared with either SIM-PE (d = -0.46) or STD-PE (d = -0.50) participants. They also reported less role overload when compared with STD-PE participants (d = -0.46). Self-efficacy in controlling upsetting thoughts was a mediator for some of the treatment effects. Conclusion: Finding positive gains is an effective intervention to reduce depressive symptoms among Alzheimer caregivers.
Background: Cortical and subcortical cognitive impairments have been found in dementia with Lewy bodies (DLB). Roughly, they comprise visuoconstructive and executive dysfunction, whereas memory would remain relatively spared. However, the cognitive profile of patients with prodromal DLB remains poorly illustrated to date. Methods: We included 37 patients with prodromal DLB (age 67.2 +/- 8.6 years, 18 men, Mini Mental State Examination [MMSE] score 27.4 +/- 2) and 29 healthy control subjects (HCs; age 68.8 +/- 7.9 years, 15 men, MMSE score 29.0 +/- 0.9). They were presented with an extensive neuropsychological test battery to assess memory; speed of processing; executive function; visuoperceptual, visuospatial and visuoconstructive abilities; language; and social cognition. Results: Compared with HCs, patients had lower scores on a visual recognition memory test (Delayed Matching to Sample-48 items; p <= 0.021) and lower free recall (all p <= 0.035), but not total recall, performance on a verbal episodic memory test (Free and Cued Selective Reminding Test). Short-term memory (p = 0.042) and working memory (p = 0.002) scores were also lower in patients. Assessment of executive function showed no slowing but overall lower performance in patients than in HCs (all p <= 0.049), whereas assessment of instrumental function yielded mixed results. Indeed, patients had lower scores on language tests (p <= 0.022), apraxia for pantomime of tool use (p = 0.002) and imitation of meaningless gesture (p = 0.005), as well as weakened visuospatial abilities (p = 0.047). Visuoconstruction was also impaired in patients. However, visuoperceptual abilities did not differ between groups. Finally, theory of mind abilities were lower in patients than in HCs (p < 0.05), but their emotion recognition abilities were similar. Conclusions: This study presents the cognitive profile in patients with prodromal DLB. In line with the literature on DLB with dementia, our results show lower performance on tests of executive function and visuoconstruction. However, we found, from a prodromal stage of DLB, memory (free recall and visual recognition) and social cognition deficits, as well as weakened visuospatial and praxic abilities.
We herein report the case of a 75-year-old male who had shown many psychiatric symptoms, but whose autopsy disclosed the presence of dementia with Lewy bodies (DLB). When he was 70 years old, the patient had presented with stereotyped behavior, dietary changes, and a decline in social interpersonal conduct in clinical settings, and it was thought that these symptoms were consistent with a behavioral variant of frontotemporal dementia (bvFTD), and he lacked the core features of DLB. Nevertheless, this case was pathologically defined as the limbic type of DLB after he died at the age of 75 years. Looking retrospectively at the clinical course, it was considered that the following features were suggestive or supportive of DLB: neuroleptic sensitivity, autonomic symptoms, and psychiatric symptoms. It can be presumed that the bvFTD-like behavioral disturbances were caused by the severe Lewy pathology of the locus ceruleus (LC) and left anterior temporal region. The clinical symptoms of DLB might be more multifarious than has conventionally been thought, because the symptoms can be modified by the pathological spread of DLB within the brain. It is important to be aware of these possible symptoms of DLB so as not to overlook the diagnosis in the clinical setting.
Dementia is an ever-expanding problem facing an ageing society. Currently, there is a sharp paucity of treatment strategies. It has long been known that sex hormones, namely 17 beta-estradiol and testosterone, possess neuroprotective- and cognitive-enhancing qualities. However, certain lacunae in the knowledge underlying their molecular mechanisms have delayed their use as treatment strategies in dementia. With recent advancements in pharmacology and molecular biology, especially in the development of safer selective oestrogen receptor modulators and the recent discovery of the small-molecule brain-derived neurotrophic factor receptor agonist, 7,8-dihydroxyflavone, the exploitation of these signalling pathways for clinical use has become possible. This review aims to adumbrate the evidence and hurdles underscoring the use of sex hormones in the treatment of dementia as well as discussing some direction that is required to advance the translation of evidence into practise.
This cross-sectional study aimed to investigate the relationship between caregivers and care receivers, defined as home-dwelling family members with dementia. We used a self-rating questionnaire, the Felt Expressed Emotion Rating Scale (FEERS; 6 simple questions), to measure caregiver perceptions of the care receiver's criticisms (CCs) and emotional overinvolvement (EOI) toward the caregiver. We performed factor analyses to rank single items on the FEERS pertaining to CC and EOI. We included 208 caregiver/care receiver pairs. Logistic regression analyses tested associations between FEERS items and caregiver and care receiver variables. The main contributors to caregiver perceptions of CC were the caregiver's own distress and the amount of time spent with the care receiver. Socially distressed caregivers perceived the care receiver as emotionally overinvolved. When offering a psychosocial intervention, a tailored program should target the caregiver's perceived relationship with the family member and the caregiver's distress. The program should also endeavor to give the caretaker more opportunities for leisure time.
The objectives of the nuclear fusion power plant DEMO, to be built after the ITER experimental reactor, are usually understood to lie somewhere between those of ITER and a 'first of a kind' commercial plant. Hence, in DEMO the issues related to efficiency and RAMI (reliability, availability, maintainability and inspectability) are among the most important drivers for the design, as the cost of the electricity produced by this power plant will strongly depend on these aspects. In the framework of the EUROfusion Work Package Heating and Current Drive within the Power Plant Physics and Development activities, a conceptual design of the neutral beam injector (NBI) for the DEMO fusion reactor has been developed by Consorzio RFX in collaboration with other European research institutes. In order to improve efficiency and RAMI aspects, several innovative solutions have been introduced in comparison to the ITER NBI, mainly regarding the beam source, neutralizer and vacuum pumping systems.
This paper presents a demodulation algorithm based on the synchronous integrator circuit for the MEMS tuning fork gyroscope utilizing the digital processing technology. The synchronous integral demodulator (SID) is adopted to demodulate the drive-detection signal and sense-axis output signal separately. Combining with automatic gain control and phase-locked loop technology, the closed-loop control of drive mode has been implemented, and high precision output of the gyroscope has been achieved. The simulation results have verified the effectiveness of the synchronous integrator circuit, which is in good agreement with the theoretical analysis. Compared with other demodulation algorithms, the SID has the advantages of the lower noise level, a better ability to attenuate the harmonics, and the best hardware efficiency. The frequency characteristic of the synchronous integrator is also analyzed, which is vital to the bandwidth of gyroscope. The print circuit board based on field-programmable gate array digital circuit is manufactured and the corresponding experiment is carried out. The experimental results show that the SID algorithm of digital control system for the gyroscope developed in our laboratory has achieved a good performance. The bias instability of tested gyroscope is measured to be 0.2 degrees l/h with the angle random walk of 0.14 degrees/root h and the nonlinearity of the scale factor is < 60 ppm with the measurement range of +/- 100 degrees/s.
Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8(+) T-cells and Th1 helper CD4(+) T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103(+) DCs, which have been shown to be experts in cross-priming and the induction of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E-2 and beta-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized treatment regimens against cancer.
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8(+) T-cells, promoting their differentiation into cytotoxicT-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation. Our findings suggest that D3R in DCs constitutes a new therapeutic target to strengthen anti-tumor immunity. (C) 2016 Elsevier B.V. All rights reserved.
We introduce a versatile carrier system for in vitro and in vivo immune stimulation based on soft matter DNA nanoparticles (NPs). The incorporation of lipid-modified nucleotides into DNA strands enables the formation of micelles of uniform size. In a single self-assembly step, the micelles can be equipped with immune adjuvant (CpG) motifs and fluorescent probes. The immunological effects of CpG confined at the NP surface were studied in a comprehensive manner in animal experiments. Dose-dependent activation of spleen dendritic cells (DCs) by CpG-conjugated NP was observed, which was accompanied by the pronounced up-regulation of co-stimulatory molecule and cytokine production. (C) 2016 Elsevier Ltd. All rights reserved.
Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency of activated DCs have in the past been based on measurements of differentiation surface markers like HLA-DR, CD80, CID83, CD86, and CCR7 and the level of secreted cytokines like interleukin-12p70. However, the level of these markers does not provide a complete Picture of the DC phenotype and may be insufficient for prediction of clinical outcome for DC-based therapy. We therefore looked for additional biomarkers by investigating the differential expression of microRNAs (miRNAs) in mature DCs relative to immature DCs. A microarray-based screening revealed that 12 miRNAs were differentially expressed in the two DC phenotypes. Of these, four miRNAs, hsa-miR-155, hsa-miR-146a, hsa-miR-125a-5p, and hsa-miR-29a, were validated by real-time polymerase chain reaction and northern blotting. The matured DCs from 12 individual donors were divided into two groups of highly and less differentiated DCs, respectively. A pronounced difference at the level of miRNA induction between these two groups was observed, suggesting that quantitative evaluation of selected miRNAs potentially can predict the immunogenicity of DC vaccines. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Objective: To evaluate the trends in usage of dengue virus diagnostics in Pakistan. Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data for specimens tested for dengue virus from January 2012 to December 2015. Test for dengue virus ribonucleic acid by reverse transcription polymerase chain reaction, dengue virus antigen by immunochromatic assay and for human immunoglobulin M against dengue virus by enzyme-linked immunosorbent assay were reviewed. SPSS 17 was used for data analysis. Results: Overall, 33,577 specimens tested for dengue virus. Of them, 11,995 (35.7%) were positive. among them, 1,039(8.66%) were reported in 2012; 5,791(48.28%) in 2013; 1,027(8.56%) in 2014; and 4,138(34.49%) in 2015. In 2012, 966(93%) of the positive samples were diagnosed by immunoglobulin M-based method and 73(7%) by nonstructural protein-1 antigen. In 2013, 4,401(76%) samples were tested positive by immunoglobulinM, 1,332(23%) by antigen and 58(1%) by polymerase chain reaction. The trend continued in 2014, but in 2015, 2,111(51%) of all dengue positive tests were determined by antigen testing, 1,969(47.6%) by immunoglobulin M and 58(1.4%) by polymerase chain reaction. Conclusion: There was a shift in usage of direct virus identification for rapid diagnosis of dengue virus compared with host immunoglobulin M testing.
An upsurge of fever cases of unknown origin, but resembling dengue and leptospirosis was reported in Havelock, Andaman & Nicobar Islands, an important tourism spot, during May 2014. Investigations were carried out to determine the aetiology, and to describe the epidemiology of the outbreak. The data on fever cases attending Primary Health Centre (PHC), Havelock showed that the average number of cases reporting per week over the last 2 years was 461 (95% confidence interval 194-729). A total of 27 (435%) patients out of the 62 suspected cases were diagnosed as having DENV infection based on a positive enzyme immunoassay or reverse transcriptase-polymerase chain reaction. The overall attack rate was 94 cases/1000 population and it ranged between 28 and 188/1000 in different villages. The nucleotide sequencing showed that the virus responsible was DENV-3. DENV-3 was first detected in the Andaman & Nicobar Islands in 2013 among wharf workers in Port Blair and within a year it has spread to Havelock Island which is separated from South Andaman by 36 nautical miles.
BACKGROUND Despite the current global trend of reduction in the morbidity and mortality of neglected diseases, dengue's incidence has increased and occurrence areas have expanded. Dengue also persists as a scientific and technological challenge since there is no effective treatment, vaccine, vector control or public health intervention. Combining bibliometrics and social network analysis methods can support the mapping of dengue research and development (R&D) activities worldwide. OBJECTIVES The aim of this paper is to map the scientific scenario related to dengue research worldwide. METHODS We use scientific publication data from Web of Science Core Collection - articles indexed in Science Citation Index Expanded (SCI-EXPANDED) - and combine bibliometrics and social network analysis techniques to identify the most relevant journals, scientific references, research areas, countries and research organisations in the dengue scientific landscape. FINDINGS Our results show a significant increase of dengue publications over time; tropical medicine and virology as the most frequent research areas and biochemistry and molecular biology as the most central area in the network; USA and Brazil as the most productive countries; and Mahidol University and Fundacao Oswaldo Cruz as the main research organisations and the Centres for Disease Control and Prevention as the most central organisation in the collaboration network. MAIN CONCLUSIONS Our findings can be used to strengthen a global knowledge platform guiding policy, planning and funding decisions as well as to providing directions to researchers and institutions. So that, by offering to the scientific community, policy makers and public health practitioners a mapping of the dengue scientific landscape, this paper has aimed to contribute to upcoming debates, decision-making and planning on dengue R& D and public health strategies worldwide.
Background: Densoviruses (DVs) are highly pathogenic to their hosts. However, we previously reported a mutualistic DV (HaDV2). Very little was known about the characteristics of this virus, so herein we undertook a series of experiments to explore the molecular biology of HaDV2 further. Results: Phylogenetic analysis showed that HaDV2 was similar to members of the genus Iteradensovirus. However, compared to current members of the genus Iteradensovirus, the sequence identity of HaDV2 is less than 44% at the nucleotide-level, and lower than 36, 28 and 19% at the amino-acid-level of VP, NS1 and NS2 proteins, respectively. Moreover, NS1 and NS2 proteins from HaDV2 were smaller than those from other iteradensoviruses due to their shorter N-terminal sequences. Two transcripts of about 2.2 kb coding for the NS proteins and the VP proteins were identified by Northern Blot and RACE analysis. Using specific anti-NS1 and anti-NS2 antibodies, Western Blot analysis revealed a 78 kDa and a 48 kDa protein, respectively. Finally, the localization of both NS1 and NS2 proteins within the cell nucleus was determined by using Green Fluorescent Protein (GFP) labelling. Conclusion: The genome organization, terminal hairpin structure, transcription and expression strategies as well as the mutualistic relationship with its host, suggested that HaDV2 was a novel member of the genus Iteradensovirus within the subfamily Densovirinae.
Dental teams have been involved with child protection for over 40years. This brief review summarises their involvement in the detection of various types of child abuse and goes on to discuss the gap between the proportions of dental professionals who suspect child abuse or neglect in their paediatric patients and those who refer such cases on. Potential reasons for this discrepancy are discussed, and a glimpse of the future is given as to where further research may be necessary to tackle this existing gap.
According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA(human leukocyte antigen) antibodies was performed using methods such as the LAB Screen PRA Class I and Class II, LAB Screen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LAB Screen PRA) were further investigated to determine the specificity of the antibodies detected (LAB Screen Single Antigen) with a cutoff value of median fluorescence intensity >= 500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.
Objective: Pulp and periodontal tissues are well-known sources of mesenchymal stem cells (MSCs) that provide a promising place in tissue engineering and regenerative medicine. The molecular mechanisms underlying commitment and differentiation of dental stem cells that originate from different dental tissues are not fully understood. In this study, we have compared the expression levels of pluripotency factors along with immunological and developmentally-related markers in the culture of human dental pulp stem cells (hDPSCs), human dental follicle stem cells (hDFSCs), and human embryonic stem cells (hESCs). Materials and Methods: In this experimental study, isolated human dental stem cells were investigated using quantitative polymerase chain reaction (qPCR), immunostaining, and fluorescence-activated cell sorting (FACS). Additionally, we conducted gene ontology (GO) analysis of differentially expressed genes and compared them between dental stem cells and pluripotent stem cells. Results: The results demonstrated that pluripotency (OCT4 and SOX2) and immunological (IL-6 and TLR4) factors had higher expressions in hDFSCs, with the exception of the JAG-GED-1/NOTCH1 ratio, c-MYC and NESTIN which expressed more in hDPSCs. Immunostaining of OCT4, SOX2 and c-MYC showed cytoplasmic and nucleus localization in both groups at similar passages. GO analysis showed that the majority of hDFSCs and hDPSCs populations were in the synthesis (S) and mitosis (M) phases of the cell cycle, respectively. Conclusion: This study showed different status of heterogeneous hDPSCs and hDFSCs in terms of stemness, differentiation fate, and cell cycle phases. Therefore, the different behaviors of dental stem cells should be considered based on clinical treatment variations.
Fusarium Head Blight is a major disease of wheat and an important contributor to the reduced cultivation of wheat in South Africa, where the crop often is grown under irrigation. We collected Fusarium isolates from 860 Fusarium Head Blight-infected wheat heads in seven irrigated wheat-growing areas of South Africa. Six Fusarium species, i.e., F. chlamydosporum, F. crookwellense, F. culmorum, F. equiseti, F. graminearum and F. semitectum were recovered, three of which, i.e., F. chlamydosporum, F. equiseti and F. semitectum, were not previously associated with Fusarium Head Blight in South Africa. Fusarium graminearum occurred at high frequencies at all seven locations. Based on polymerase chain reaction (PCR) assays of diagnostic sequences, more isolates were predicted to produce deoxynivalenol than nivalenol. Fusarium graminearum (sensu lato) appears to be the primary causal agent of Fusarium Head Blight in irrigated wheat in South Africa, which may not be the case for wheat cultivated under rain-fed conditions. Rotations of irrigated wheat with other graminaceous crops and maize could increase fungal inoculum and disease pressure. The establishment of Fusarium Head Blight in the irrigated wheat region of the country means that resistant lines and alternative agronomic practices are needed to limit disease severity, yield losses and mycotoxin contamination.
Since the invention of polymerase chain reaction (PCR) in 1985, PCR has played a significant role in molecular diagnostics for genetic diseases, pathogens, oncogenes and forensic identification. In the past three decades, PCR has evolved from end-point PCR, through real-time PCR, to its current version, which is the absolute quantitive digital PCR (dPCR). In this review, we first discuss the principles of all key steps of dPCR, i.e., sample dispersion, amplification, and quantification, covering commercialized apparatuses and other devices still under lab development. We highlight the advantages and disadvantages of different technologies based on these steps, and discuss the emerging biomedical applications of dPCR. Finally, we provide a glimpse of the existing challenges and future perspectives for dPCR.
Deoxyribonucleic acid (DNA) plays an extremely important role in storing genetic messages that are used for cellular functions in living organisms. However, the process of replicating these messages is not free from errors as internal and external factors can contribute to the damages of DNA strands. These damages known as lesions are problematic since they can lead to mutagenesis and carcinogenesis after accumulation for a certain period of time. Thankfully, cells are able to synthesize various DNA glycosylases to target different lesions, repairing and restoring damaged DNA to its original state. This review article aims to explore the variety of assays used to evaluate the efficiency of these glycosylases, mainly focusing on uracil DNA glycosylase, thymine DNA glycosylase, and 8-oxoguanine DNA glycosylase since they are deployed to the sites of damages much more often than other repair enzymes. The progress in the development of DNA glycosylase assays is reviewed with an emphasis on the configuration and operating mechanism of the assays and with some discussion on challenges and prospects. It is hoped that this article will provide an introductory overview and the current standing of DNA glycosylase assays, opening up new perspectives towards the development DNA glycosylase assays for uses in molecular biology and at point-of-care. (C) 2016 Elsevier B.V. All rights reserved.
In a digital control system, the dependency model between the actions of operators differs from that in a conventional control room because information sharing and the main control room (MCR) operations are team operations. Dependencies between the actions of operators are more common in a digital control system compared with a conventional control room because operators share the same information and MCR operations are directed by team decisions. Therefore, assessing the dependencies between operators is an important aspect of human reliability analysis. In this study, we use a fuzzy logic-based approach to evaluate the dependencies among the actions of operators in the present study. First, the factors that influence the dependency levels among the actions of operators are identified by analyzing the characteristic human factors in a digital control system and an analytical model of the dependencies is then constructed. Second, a method for analyzing the dependencies between the actions of operators is established based on a fuzzy logic approach. This method can simulate vague and uncertain knowledge, but it also provides a clear explanation of the origins of results and their reasoning process by tracing the steps in reasoning. Therefore, traceability and repeatability are characteristics of the proposed method. Third, we present a case study to demonstrate the proposed approach. Finally, we demonstrate that the results obtained are reasonable and that the established model is stable based on validations that involve data comparisons and a sensitivity analysis of the model. (C) 2015 Elsevier B.V. All rights reserved.
BackgroundAdolescence is a period of increased risk for the development of depression. Epidemiological and clinical studies suggest that the phenomenology of depression may differ during childhood and adolescence. However, participants in these studies may not reflect depressed young people referred to routine clinical services. The aim of this paper was to describe referrals for depression to a UK routine public healthcare service for children and adolescents with mental health difficulties. MethodThis paper describes a consecutive series of adolescents (N=100, aged 12-17years), referred for depression to a routine public healthcare child and adolescent mental health service, in the south of England. Young people and their caregivers completed a structured diagnostic interview and self-report measures of anxiety and depression. ResultsFewer than half of young people referred for depression met diagnostic criteria for a depressive disorder. The key symptoms reported by those with depression were low mood or irritability, cognitive disturbances, sleep disturbances and negative self-perceptions. Suicidal ideation was common and was considerably higher than reported in other studies. Caregiver and young person's accounts of adolescent symptoms of depression and anxiety were uncorrelated. Caregivers also reported fewer symptoms of depression in their child than adolescents themselves. ConclusionsThese data have direct relevance to the design and delivery of public mental health services for children and adolescents. However, we do not know how representative this sample is of other clinical populations in the UK or in other countries. There is a need to collect routine data from other services to assess the needs of this group of high-risk adolescents.
Objective: Adjunctive antipsychotic therapy can be prescribed to patients with depression who have inadequate response to antidepressants. This study aimed to describe the use of adjunctive antipsychotics over a time period that includes the authorization in 2010 of prolonged-release quetiapine as the first adjunct antipsychotic to be used in major depressive disorder in the UK.Research design and methods: Adults with an episode of depression between January 1, 2005 and July 31, 2013 were identified from antidepressant prescriptions and depression diagnoses in the UK Clinical Practice Research Datalink. Patients with prior records of bipolar disorder, schizophrenia, or antipsychotic prescriptions were excluded.Main outcome measures: Rates of adjunct antipsychotic initiation and characteristics and management of patients with adjunct antipsychotics.Results: Of 224,353 adults with depression, 5,807 (2.6%) initiated adjunct antipsychotic therapy. Overall incidence of antipsychotic initiation was 7.4 per 1,000 patient-years (95% CI=7.2-7.6). Between 2005-2013, the overall rate did not change, although initiation of typical antipsychotic prescribing decreased (57.7% to 29.1%), while atypical antipsychotics, especially quetiapine (14.1% to 49.7%), increased. Of those who initiated antipsychotics, 59.4% were women (typical antipsychotics=62.8%, atypical antipsychotics=56.1%) and median age was 46 years (typicals=49 years, atypicals=44 years).Conclusions: Antipsychotics were rarely used to treat depression between 2005-2013 in UK primary care. The choice of adjunctive antipsychotic therapy changed over this time, with atypical antipsychotics now representing the preferred treatment choice. However, information on patients strictly cared for in other settings, such as by psychiatrists or in hospitals, potentially more severe patients, was unavailable and may differ. Nonetheless, the high off-label use in primary care, even after the authorization of quetiapine, suggests that there is a need for more licensed treatment options for adjunctive antipsychotic therapy in major depressive disorder.
Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1 beta, IL-2, IL-6 and tumor necrosis factor-alpha. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce IDO-1 leading to shift the balance of the Kynurenine/ serotonin toward the serotonin pathway.
Background: Collaborative Care is an evidence-based approach to the management of depression within primary care services recommended within NICE Guidance. However, uptake within the UK has been limited. This review aims to investigate the barriers and facilitators to implementing Collaborative Care. Methods: A systematic review of the literature was undertaken to uncover what barriers and facilitators have been reported by previous research into Collaborative Care for depression in primary care. Results: The review identified barriers and facilitators to successful implementation of Collaborative Care for depression in 18 studies across a range of settings. A framework analysis was applied using the Collaborative Care definition. The most commonly reported barriers related to the multi-professional approach, such as staff and organisational attitudes to integration, and poor inter-professional communication. Facilitators to successful implementation particularly focussed on improving inter-professional communication through standardised care pathways and case managers with clear role boundaries and key underpinning personal qualities. Limitations: Not all papers were independent title and abstract screened by multiple reviewers thus limiting the reliability of the selected studies. There are many different frameworks for assessing the quality of qualitative research and little consensus as to which is most appropriate in what circumstances. The use of a quality threshold led to the exclusion of six papers that could have included further information on barriers and facilitators. Conclusions: Although the evidence base for Collaborative Care is strong, and the population within primary care with depression is large, the preferred way to implement the approach has not been identified.
Objective: Depression screening should be increased when prevailing knowledge underscoring medication associated mental health risk is highest. Depression screening in primary care practices when medications with mental health risk were prescribed was estimated while considering the absence and presence of clinical decision support systems. Materials and methods: A cross-sectional, descriptive study using the National Ambulatory Medical Care Survey (NAMCS) data from 2008 to 2010 was conducted. Primary care physician visits were classified based on whether a medication prescribed had a contraindication, severe warning, moderate warning, adverse event only, or no documented mental health risk. Adjusted odds of depression screening for each risk warning level were estimated while controlling for important sociodemographic factors and presence of computerized systems for medication warnings and guideline recommendations. Results: Depression screening at primary care practice visits when medications were prescribed was 2.1% and increased to 2.8% or higher when medications had a moderate or severe mental health risk warning or medication-disease contraindication. Depression screening was increased at visits when at least one medication was prescribed that had a contraindication (AOR = 6.31, P < 0.001), severe warning (AOR = 2.04, P = 0.003), or moderate warning (AOR = 2.50, P = 0.012) for mental health risk, but not for mental health adverse event only warnings alone (AOR = 1.54, P = 0.074). Discussion: Depression screening is increased when medications were prescribed with a documented mental health risk. Presence of clinical decision support systems may help discern between minor and major medication-associated mental health risks. Conclusions: Appropriately, positioned warning systems with targeted content, workflow redesign, and health information exchange may improve depression screening in at-risk patients. (C) 2016 Elsevier Inc. All rights reserved.
ObjectiveTo test the association between recall for socially rewarding (positive) and/or socially critical (negative) information and depressive symptoms. MethodCohort study of people who had visited UK primary care in the past year reporting depressive symptoms (N=558, 69% female). Positive and negative recall was assessed at three time-points, 2weeks apart, using a computerised task. Depressive symptoms were assessed at four time-points using the Beck Depression Inventory (BDI). Analyses were conducted using multilevel models. ResultsConcurrently we found evidence that, for every increase in two positive words recalled, depressive symptoms reduced by 0.6 (95% CI -1.0 to -0.2) BDI points. This association was not affected by adjustment for confounders. There was no evidence of an association between negative recall and depressive symptoms (-0.1, 95% CI -0.5 to 0.3). Longitudinally, we found more evidence that positive recall was associated with reduced depressive symptoms than vice versa. ConclusionPeople with more severe depressive symptoms recall less positive information, even if their recall of negative information is unaltered. Clinicians could put more emphasis on encouraging patients to recall positive, socially rewarding information, rather than trying to change negative interpretations of events that have already occurred.
Aim: To evaluate the prevalence of recurrent falls and their risk factors among older men living in the Veterans Homes in Taiwan. Methods: This cross-sectional study enrolled 871 residents and all participants received the comprehensive geriatric assessment, including Barthel Index, Mini-Mental Status Examination (MMSE), Geriatric Depression Scale-5 questions (GDS-5), Mini-Nutrition Assessment Short Form (MNA-SF), the status of urinary incontinence, stool incontinence, polypharmacy, past history of falls, multimorbidity, and medication history. Results: Overall, 871 subjects (mean age: 85.5 +/- 5.2 years, all males) participated in this study, whereas 222(25.5%) of them had experienced falls in the past year, and 91 were recurrent fallers. Comparisons between non-fallers, single fallers and recurrent fallers disclosed that they were significantly different in the following characteristics: diabetes mellitus, chronic kidney disease, coronary artery disease, Charlson Comorbidity Index (CCI), Barthel Index, GDS-5, MNA-SF, polypharmacy, use of hypnotics, urinary incontinence, and stool incontinence (P for trend all <0.05). Multiple regression analysis identified that GDS-5 was significantly associated with single falls and recurrent falls (OR 1.256, 95% CI 1.094-1.441, P = 0.001 for single fallers; OR 1.480, 95% CI 1.269-1.727, P < 0.001 for recurrent fallers). Besides, urinary incontinence was the independently associated with recurrent fallers only (OR 2.369, 95% CI 1.449-3.817, P < 0.001), but not single fallers. Conclusion: Urinary incontinence and depressive symptoms were independent associated factors for falls among older men living in the retirement communities. However, urinary incontinence was associated with recurrent falls, but not single falls. Intervention study is needed to reduce recurrent falls through management of urinary incontinence. (C) 2017 Elsevier B.V. All rights reserved.
Sleep problems are common in patients with systemic lupus erythematosus (SLE). This study aimed to examine the following: (1) predictors of sleep quality and (2) fluctuations in sleep quality in patients with SLE. Patients with SLE were recruited from three rheumatology centers in Japan. We collected demographic and clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by administering the PSQI a second time after a 2-week interval. We used multiple linear regression analysis to predict sleep quality. Of 205 patients who completed the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep quality was for "waking in the middle of the night or early morning." "LupusPRO pain/vitality" was a major predictor of poor sleep. The other significant predictors were mostly LupusPRO subscales and clinical variables and SF-12 subscales were mostly non-predictive. The majority of the participants had poor sleep quality. A lupus-specific QoL scale is important for understanding poor sleep quality in SLE patients. Symptom management appeared to play a key role in improving sleep quality.
A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment. (C) 2016 Elsevier Inc. All rights reserved.
There is some evidence that lowered tryptophan and an activated tryptophan catabolite (TRYCAT) pathway play a role in depression, somatoform disorder, and postpartum blues. The aim of this study is to delineate the associations between the TRYCAT pathway and premenstrual syndrome (PMS) and perinatal depressive and physio-somatic symptoms. We examine the associations between end of term serum IgM and IgA responses to tryptophan and 9 TRYCATs in relation to zinc, C-reactive protein (CRP), and haptoglobin and prenatal physio-somatic (previously known as psychosomatic) symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depression and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Hamilton Depression Rating Scale (HAMD), and Spielberger's State Anxiety Inventory (STAI). We included pregnant females with (n = 24) and without depression (n = 25) and 24 non-pregnant females. There were no significant associations between the IgA/IgM responses to tryptophan and TRYCATs and prenatal and postnatal depression/anxiety symptoms, except for lowered IgA responses to anthranilic acid in prenatal depression. A large part of the variance in IgA responses to most TRYCATs was explained by PMS and haptoglobin (positively) and CRP (inversely) levels. The IgA responses to TRYCATs were significantly increased in PMS, in particular picolinic, anthranilic, xanthurenic and kynurenic acid, and 3OH-kynurenine. Variance (62.5%) in physio-somatic symptoms at the end of term was explained by PMS, previous depressions, zinc (inversely), CRP and haptoglobin (both positively), and the IgM responses to quinolinic acid (positively), anthranilic acid, and tryptophan (both negatively). The results suggest that mucosa-derived TRYCAT pathway activation is significantly associated with PMS, but not with perinatal depression/anxiety symptoms. Physio-somatic symptoms in pregnancy have an immune-inflammatory pathophysiology. Induction of the TRYCAT pathway appears to be more related to physio-somatic than to depression symptoms.
Major depressive disorder (MDD) is associated with disrupted relationships with partners, family, and peers. These problems can precipitate the onset of clinical illness, influence severity and the prospects for recovery. Here, we investigated whether individuals who have recovered from depression use interpersonal signals to form favourable appraisals of others as social partners. Twenty recovered-depressed adults (with >1 adult episode of MDD but euthymic and medication-free for six months) and 23 healthy, never-depressed adults completed a task in which the gaze direction of some faces reliably cued the location a target (valid faces), whereas other faces cued the opposite location (invalid faces). No participants reported awareness of this contingency, and both groups were significantly faster to categorise targets following valid compared with invalid gaze cueing faces. Following this task, participants judged the trustworthiness of the faces. Whereas the healthy never-depressed participants judged the valid faces to be significantly more trustworthy than the invalid faces; this implicit social appraisal was absent in the recovered-depressed participants. Individuals who have recovered from MDD are able to respond appropriately to joint attention with other people but appear to not use joint attention to form implicit trust appraisals of others as potential social partners.
BACKGROUND: Depression among patients with acute myocardial infarction (AMI) is prevalent and associated with an adverse quality of life and prognosis. Despite recommendations from some national organizations to screen for depression, it is unclear whether treatment of depression in patients with AMI is associated with better outcomes. We aimed to determine whether the prognosis of patients with treated versus untreated depression differs. METHODS: The TRIUMPH study (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) is an observational multicenter cohort study that enrolled 4062 patients aged >= 18 years with AMI between April 11, 2005, and December 31, 2008, from 24 US hospitals. Research coordinators administered the Patient Health Questionnaire-9 (PHQ-9) during the index AMI admission. Depression was defined by a PHQ-9 score of >= 10. Depression was categorized as treated if there was documentation of a discharge diagnosis, medication prescribed for depression, or referral for counseling, and as untreated if none of these 3 criteria was documented in the medical records despite a PHQ score >= 10. One-year mortality was compared between patients with AMI having: (1) no depression (PHQ-9<10; reference); (2) treated depression; and (3) untreated depression adjusting for demographics, AMI severity, and clinical factors. RESULTS: Overall, 759 (18.7%) patients met PHQ-9 criteria for depression and 231 (30.4%) were treated. In comparison with 3303 patients without depression, the 231 patients with treated depression had 1-year mortality rates that were not different (6.1% versus 6.7%; adjusted hazard ratio, 1.12; 95% confidence interval, 0.63-1.99). In contrast, the 528 patients with untreated depression had higher 1-year mortality in comparison with patients without depression (10.8% versus 6.1%; adjusted hazard ratio, 1.91; 95% confidence interval, 1.39-2.62). CONCLUSIONS: Although depression in patients with AMI is associated with increased long-term mortality, this association may be confined to patients with untreated depression.
Simultaneous relief of the pain from body and brain remains an ongoing challenge. The aim of the present study was to clarify whether plant-derived isoflavone puerarin could ameliorate comorbid depression and pain. We investigated the effects of puerarin on depressive-like behaviors and neuropathic pain in C57BL/6 N mice with spared nerve injury (SNI). After SNI surgery, mice were allowed to recover spontaneously for 7 days and subsequently treated with puerarin, anti-depressant citalopram, and analgesic ibuprofen, alone or in combination, for 8 or 14 days. Forced swim test and tail suspension test were used to assess depressive-like behaviors, whereas von Frey filament test was used to estimate the sensitivity to the mechanical stimulation. Our results suggested that puerarin effectively ameliorated depression and pain in SNI mice although citalopram exhibited anti-depressant activity. In contrast, ibuprofen showed lesser activities against SNI-induced depression and pain. Further mechanistic studies revealed the uniqueness of puerarin as follows: (1) puerarin did not recover SNI-induced depletion of reduced glutathione and loss of superoxide dismutase (SOD), whereas citalopram and ibuprofen showed somewhat antioxidant activities; (2) puerarin markedly promoted the activation of CREB pathway although puerarin and citalopram activated ERK pathway to the same extent; (3) puerarin rapidly and persistently induced brain-derived neurotrophic factor (BDNF) expression whereas citalopram only induced BDNF expression after a prolonged stimulation. Collectively, these results suggest that puerarin may ameliorate the SNI-induced depression and pain via activating ERK, CREB, and BDNF pathways. Puerarin may serve as new lead compound for the development of novel therapeutics for depression and pain comorbidity.
Aims: To assess the association between chronic tension-type headache coexistent with chronic temporomandibular disorder (TMD) pain and severe limitations in physical and emotional functioning. Methods: Sample size estimation was used to determine that this case-control study should include 126 subjects. Subjects suffering from chronic TMD who were aged between 18 and 68 were recruited in routine clinical practice. Of the 126 included subjects, 63 had TMD pain associated with chronic tension-type headache (cases) and 63 had TMD pain without a history of tension-type headache (controls). Clinical diagnosis of TMD was made according to the Research Diagnostic Criteria for TMD (RDC/TMD) Axis I criteria, and clinical diagnosis of headache was made according to the International Classification of Headache (ICHD-II). RDC/TMD Axis II criteria were applied to record the scores from the Graded Chronic Pain Scale (GCPS) and the Symptoms Checklist-90-Revised Depression (SCL-DEP) and Somatization (SCL-SOM) scales. A logistic regression analysis was used to assess the relationship between TMD pain with chronic tension-type headache and high levels of depression and somatization severity as scored on the SCL-DEP and SCL-SOM scales, respectively, and high pain-related disability (GCPS grade III or IV). Data were adjusted to take into account age, gender, time since TMD pain onset, chronic TMD pain intensity, and characteristic pain intensity. Results: The presence of chronic tension-type headache was significantly associated with severe SCL-DEP (odds ratio [OR] = 7.2; P <.001), severe SCL-SOM (OR = 13.8; P <.001), and high pain-related disability (OR = 9.7; P <.001). Conclusion: This study provides evidence of associations between the clinical diagnosis of chronic tension-type headache coexistent with chronic TMD pain and key aspects of physical and emotional functioning reflected in severe depression, severe somatization, and high pain-related disability.
Over the past decade, rates of depression and of suicide in adolescents have been increasing (Collishaw, Journal of Child Psychology and Psychiatry, 56, 2015, 370; Bor etal., The Australian and New Zealand Journal of Psychiatry, 48, 2014, 606). At the same time, there is some evidence that rates of diagnosis and, in the US at least, referral for depression in adolescents has been declining (Libby etal., Archives of General Psychiatry, 66, 2009, 633; John etal., Psychological Medicine, 46, 2016, 3315). These worrying statistics highlight the importance of disseminating accurate information about the risks and benefits of treatments for adolescent depression, in order to combat therapeutic nihilism. Extant controversy about the best ways to treat adolescent depression, and in particular with regards to the use of antidepressants, may have contributed to these trends. More specifically, we believe that some recent, high profile publications have incorrectly interpreted the benefit to risk ratio for the use of antidepressants in adolescent depression as unfavourable (e.g. Cipriani etal., The Lancet, 388, 2016, 881). In this editorial, we review clinical trial and pharmaco-epidemiological data that supports the retention of the use of antidepressants in the management of depressed adolescents.
Decades of research have shown that positive life events contribute to the remission and recovery of depression; however, it is unclear how positive life events are generated. In this study, we sought to understand if personality strengths could predict positive life events that aid in the alleviation of depression. We tested a longitudinal mediation model where gratitude and meaning in life lead to increased positive life events and, in turn, decreased depression. The sample consisted of 797 adult participants from 43 different countries who completed online surveys at five timepoints. Higher levels of gratitude and meaning in life each predicted decreases in depression over 3 and 6 months time. Increases in positive life events mediated the effects of these personality strengths on depression over 3 months; however, not over 6 months. Goal pursuit and positive emotions are theorized to be the driving forces behind gratitude and meaning in life's effects on positive life events. We used the hedonic treadmill to interpret the short-term impact of positive life events on depression. Our findings suggest the potential for gratitude and meaning in life interventions to facilitate depression remission.
Objective: Our objective was to determine whether a score of >11 on the Edinburgh postnatal depression scale (EPDS) at the initial prenatal visit was associated with an increased use of acute medical visits when compared to pregnant women with an initial EPDS score of 11.Methods: This was a retrospective cohort study comparing the utilization of acute medical care during pregnancy and the first eight weeks after delivery amongst 200 women with an EPDS score >11 at their initial prenatal visit compared with 200 women with an EPDS score 11. Super-utilization was defined as 4 acute or unscheduled medical visits during pregnancy and the first eight weeks after delivery (90th percentile). Logistic regression was used to control for confounders.Results: Women with an initial EPDS score >11 were significantly more likely to engage in super-utilization of acute medical care compared with those women scoring 11 (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI], 1.53-3.90).Conclusions: Pregnant women scoring >11 on the EPDS at their initial prenatal visit are more likely to super-utilize acute medical care in the perinatal period. This subset of patients at-risk for increased utilization can be identified early during prenatal care. Interventions to better meet the medical and psychosocial needs of these women warrant future research.
Background: The postpartum period represents a major transition in the lives of many women, a time when women are at increased risk for the emergence of psychopathology including depression and PTSD. The current study aimed to better understand the unique contributions of clinically significant postpartum depression. PTSD, and comorbid PTSD/depression on mother infant bonding and observed maternal parenting behavior (i.e., behavioral sensitivity, negative affect, positive affect) at 6 months postpartum. Methods: Mothers (n=164; oversampled for history of childhood maltreatment given parent study's focus on perinatal mental health in women with trauma histories) and infants participated in 6-month home visit during which dyads engaged in interactional tasks varying in level of difficulties. Mothers also reported on their childhood abuse histories, current depression/PTSD symptoms, and bonding with the infant using standardized and validated instruments. Results: Mothers with clinically significant depression had the most parenting impairment (self-report ant observed). Mothers with clinically significant PTSD alone (due to interpersonal trauma that occurred predominately in childhood) showed similar interactive behaviors to those who were healthy controls or trauma-exposed but resilient (i.e., no postpartum psychopathology). Childhood maltreatment in the absence of postpartum psychopathology did not infer parenting risk. Limitations: Findings are limited by (1) small cell sizes per clinical group, limiting power, (2) sample size and sample demographics prohibited examination of third variables that might also impact parenting (e.g., income. education), (3) self-report of symptoms rather than use of psychiatric interviews. Conclusions: Findings show that in the context of child abuse history and/or current PTSD, clinically significant maternal depression was the most salient factor during infancy that was associated with parenting impairment at this level of analysis.
Background: Universal screening of pregnant women for postpartum depression has recently been recommended; however, optimal application of depression screening tools in stratifying risk has not been defined. The current study examines new approaches to improve the ability of the Edinburgh Postnatal Depression Scale (EPDS) to stratify risk for postpartum depression, including alternate cut points, use of a continuous measure, and incorporation of other putative risk factors. Methods: An observational cohort study of 4939 women screened both antepartum and postpartum with a negative EPDS screen antepartum(i.e. EPDS < 10). The primary outcome was a probable postpartum major depressive episode(EPDS cut-off 10). Area under the receiver operating characteristics curve(AUC), sensitivity, specificity, and predictive values were calculated. Results: 287 women(5.8%) screened positive for postpartum depression. An antepartum EPDS cut-off95%) at all antepartum EPDS cut-off values from 4 to 8. Discrimination was improved(AUC ranging from 0.70 to 0.73) when the antepartum EPDS was combined with a prior history of major depressive disorder before pregnancy. Limitations: An inability to assess EPDS subscales and a relatively low prevalence of depression in this cohort. Conclusions: Though an antepartum EPDS cut-off score < 5 yielded the greatest discrimination identifying women at low risk for postpartum depression, the negative predictive value was insufficient to substitute for postpartum screening.
This study evaluated the efficacy of an interactive media based, computer-delivered depression treatment program (imbPST) compared to a no-treatment control condition (NTC) in a parallel-group, randomized, controlled trial conducted in an outpatient psychiatric research clinic. 45 adult participants with major depressive disorder or dysthymia were randomized to receive either 6 weekly sessions of imbPST or no treatment (No Treatment Control; NTC). The primary outcome measure was the Beck Depression Inventory II (BDI-II). There was a significant Group x Time interaction effect [F (1.73, 43)= 58.78; p <.001; eta 2 =.58, Cohens d = 1.94], such that the patients receiving imbPST had a significantly greater reduction in depressive symptoms compared to the patients in the NTC condition. Participants in the imbPST group improved their depression symptoms significantly from moderate (BDI-II = 21.9 +/- 4.20) to mild levels of depression (BDI-II = 17.9 +/- 4.0) after receiving 3 weekly sessions of imbPST (p <0.001), and progressed to still milder levels of depression after six weekly sessions (BDI-II = 14.5 +/- 3.7, p <0.001). NTC participants showed no significant reduction in BDI-II scores (BDI-II =21.8 +/- 4.2 pre, = 21.5 +/- 5.2 post, N.S.). Additionally, 40% of the imbPST group showed a clinically significant and reliable change in depression levels while none of the NTC group met this criterion. imbPST participants rated the program highly usable on the system usability scale (SUS) after the first session (SUS Session 1 = 74.6 +/- 7.2) and usability scores increased significantly by the last session (SUS Session 6 = 85.4 +/- 5.6). We conclude that imbPST is an effective, engaging, and easily used depression treatment program that warrants further evaluation with heterogeneous depressed populations in a stand-alone, self-administered fashion.
The aim of this cross-sectional study was to analyse quality of life, socio-demographic characteristics, family support, satisfaction with health services, and effect of integrative community therapy among non-institutionalised elderly adults with and without symptoms of depression in the state of Rio Grande do Norte, Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive symptoms were compared. The instruments used were the Mini-Mental State Examination, the short version of the Geriatric Depression Scale, a clinical socio-demographic questionnaire, the abbreviated version of the World Health Organisation Quality of Life questionnaire, the Family Assessment Device, and the Patient Satisfaction with Mental Health Services Rating Scale. Elderly adults with depressive symptoms had lower quality of life in the social relations domain than did those without depressive symptoms (p = 0.003). In addition, compared with those without depression, fewer elderly adults with depressive symptoms attended integrative community therapy (p = 0.04); they also reported a low degree of family involvement in problem solving (p = 0.04) and showed apathy regarding their satisfaction with health services (p = 0.007). These results have important implications in the decision-making process with regard to strategies for improving the health status of elderly adults with depressive symptoms.
BackgroundSleep disturbance is frequently comorbid with depression and sleep complaints are the most common residual symptoms after treatment among adolescents with depression. The present analyses investigated the effect of sleep disturbance in depressed adolescents treated with interpersonal psychotherapy for adolescents (IPT-A) versus treatment as usual (TAU) in school-based mental health clinics. MethodSixty-three adolescents participated in a randomized clinical trial of IPT-A versus TAU for adolescent depression. Participants were diagnosed with a DSM-IV depressive disorder and assessed for symptoms of depression, interpersonal functioning, and sleep disturbance. Measures were assessed at baseline, session 4 and 8 of treatment, and session 12 for postacute treatment follow-up. Hierarchical linear modeling was used to model change in depression, interpersonal functioning, and sleep disturbance. ResultsOngoing sleep disturbance was significantly associated with worse depression scores as rated by clinician (=1.04, SE=.22, p<.001) and self-report (=1.63, SE=.29, p<.001), as well as worse interpersonal functioning across the course of treatment (=0.09, SE=.02, p<.001). Treatment condition did not predict change in sleep disturbance (=-0.13, SE=.14, p=ns). ConclusionsFor all patients in the study, sleep disturbance was a predictor of depression and interpersonal functioning for depressed adolescents. Sleep disturbance predicted more depression and interpersonal stress across treatments and led to a slower improvement in depression and interpersonal functioning. These data suggest that sleep disturbance should be a target for future treatment development research among depressed adolescents.
Major depressive disorder is characterized by emotional dysfunction, but mood states in daily life are not well understood. This study examined complex explanatory models of daily stress and coping mechanisms that trigger and maintain daily negative affect and (lower) positive affect in depression. Sixty-three depressed patients completed perfectionism measures, and then completed daily questionnaires of stress appraisals, coping, and affect for 7 consecutive days. Multilevel structural equation modeling (MSEM) demonstrated that, across many stressors, when the typical individual with depression perceives more criticism than usual, he/she uses more avoidant coping and experiences higher event stress than usual, and this is connected to daily increases in negative affect as well as decreases in positive affect. In parallel, results showed that perceived control, less avoidant coping, and problem-focused coping commonly operate together when daily positive affect increases. MSEM also showed that avoidant coping tendencies and ongoing stress, in combination, explain why people with depression and higher self-critical perfectionism maintain daily negative affect and lower positive affect. These findings advance a richer and more detailed understanding of specific stress and coping patterns to target in order to more effectively accomplish the two predominant therapy goals of decreasing patients' distress and strengthening resilience.
Importance: Treatment augmentation is an important clinical decision in the pharmacotherapy for depression, yet few studies have examined the rates of treatment augmentation by medication class. Objective: The aim of this study was to examine which initial pharmacotherapies for depression are more likely than others to result in subsequent treatment augmentation. Methods: This study is a retrospective cohort analysis of administrative data of 214,705 privately insured US adults between the age of 18 and 64 years who were diagnosed with a new episode of depression in 2009. Propensity score-adjusted logistic regression and Cox regression were used to model the effect of the class of initial monotherapy on treatment augmentation. Risk adjustors included depression severity, comorbidities, provider type, insurance, and demographic characteristics. Exposure: The class of initial monotherapy and the health care provider type were the main independent variables of interest. Main Outcome: The outcome was the augmentation of monotherapy. Results: Thirty-four percent of individuals received treatment augmentation. Compared with selective serotonin reuptake inhibitor monotherapy, second-generation antipsychotics as the initial treatment were associated with significant increase in the likelihood of augmentation compared with the other classes (hazards ratio, 2.59; 95% confidence interval [CI], 2.51-2.68). This result was corroborated after propensity score adjustment (odds ratio, 2.85; 95% CI, 2.70-3.00) when comparing second-generation antipsychotics to the other classes of pharmacotherapy. The other significant predictor of treatment augmentation was the provider type. Mental health specialists were 27% more likely to augment a treatment compared with generalists (hazards ratio, 1.27; 95% CI, 1.25-1.30). Conclusions: The type of initial antidepressant therapy is associated with the chances of treatment augmentation. Second-generation antipsychotics progressed to augmentation more rapidly than the other classes.
Depressive symptomatology in IBD patients is known to predict disease activity, which, in turn, can increase depressive symptoms in perpetuating a cycle between depression and IBD symptomatology. The mechanisms that contribute to the relationship between disease activity and depressive symptoms are not clearly investigated yet. Since emotion regulation has been considered particularly relevant to define the impact of adverse experiences on different outcomes, the current study aimed to examine the longitudinal influence of two maladaptive emotion regulation processes, cognitive fusion and brooding, on the association between disease activity and depressed mood. This study was conducted over an 18-month period, using a sample of 116 IBD patients that completed self-report validated measures in three different waves. Correlation analyses and cross-lagged panel models were performed. The main result from this study discovered that the experience of IBD symptomatology at baseline, although positively linked to the manifestation of depressed mood 18 months later (r = 0.25; p < 0.01), does not directly predict depressive symptoms. This relationship is rather indirect, as it is explained by the engagement in cognitive fusion (p = 0.028) and brooding (p = 0.017). These maladaptive emotion regulation processes, that were revealed to be consistent over time, link IBD symptoms with subsequent depressed mood. These findings indicate that clinicians should be aware of the emotion regulation processes patients tend to use to handle difficult experiences. The inclusion of psychological assessments and interventions in the healthcare of IBD patients should be seriously considered. Further implications are discussed.
The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR and depressive symptoms with and without adjustment for genetic and family environmental factors. We conducted a cross-sectional study using twins and measured SFR and depressive symptoms as the outcome and explanatory variables, respectively. We also performed three-step regression analyses by first analysing the association between SFR and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed between-within analyses using monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs, and finally using only MZ twin pairs. These between-within analyses estimated the coefficients adjusted for genetic and family environmental factors. Furthermore, differences in the associations between individual-level and between-within suggest confounding by genetic and family environmental factors. We conducted 448 twins aged ae20 years. In individual-level analyses in males and between-within analyses using MZ and same-sex DZ male twin pairs, SFR associated with depressive symptoms. In between-within analyses using only MZ male twin pairs, SFR did not associate with depressive symptoms. In females, SFR did not associate with depressive symptoms in both individual-level and between-within analyses. The present study revealed that the association between SFR and depressive symptoms was affected by common genetic factors in males. Understanding this association between SFR and depressive symptoms with adjustment for genetic and family environmental factors could lead to an important consideration for the prevention and treatment of hyposalivation.
Objective: In adolescents and young adults, depressive symptoms are highly prevalent and dynamic. For clinicians, it is difficult to determine whether a young person reporting depressive symptoms is at risk of developing ongoing mood difficulties or whether symptoms form part of a transient maturational process. Trajectory analyses of longitudinally assessed symptoms in large cohorts have the potential to untangle clinical heterogeneity by determining subgroups or classes of symptom course and their risk factors, by interrogating the impact of known or suspected risk factors on trajectory slope and intercept and by tracing the interrelation between depressive symptoms and other clinical outcomes over time. Method: We conducted a systematic review of trajectory studies conducted in cohorts including people aged between 15 and 25years. Results: We retrieved 47 relevant articles. These studies suggest that young people fall into common mood trajectory classes and that class membership and symptom course are mediated by biological and environmental risk factors. Furthermore, studies provide evidence that high and persistent depressive symptoms are associated with a range of concurrent health and behavioral outcomes. Conclusion: Findings could assist in the formulation of novel concepts of depressive disorders in young people and inform preventive strategies and predictive models for clinical practice.
The gut microbiota has recently emerged as an important regulator of brain physiology and behaviour in animals, and ingestion of certain bacteria (probiotics) therefore appear to be a potential treatment for major depressive disorder (MDD). However, some conceptual and mechanistical aspects need further elucidation. We therefore aimed at investigating whether the habitual diet may interact with the effect of probiotics on depression-related behaviour and further examined some potentially involved mechanisms underlying the microbe-mediated behavioural effects. Forty male Sprague-Dawley rats were fed a control (CON) or high-fat diet (HFD) for ten weeks and treated with either a multi-species probiotic formulation or vehicle for, the last five weeks. Independently of diet, probiotic treatment markedly reduced depressive-like behaviour in the forced swim test by 34% (95% CI: 22-44%). Furthermore, probiotic treatment skewed the cytokine production by stimulated blood mononuclear cells towards IFN gamma, IL2 and IL4 at the expense of TNF alpha and IL6. In addition, probiotics lowered hippocampal transcript levels of factors involved in HPA axis regulation (Crh-r1, Crhr-2 and Mr), whereas HFD increased these levels. A non-targeted plasma metabolomics analysis revealed that probiotics raised the level of indole-3-propionic acid, a potential neuroprotective agent. Our findings clearly support probiotics as a potential treatment strategy in MDD. Importantly, the efficacy was not attenuated by intake of a "Western pattern" diet associated with MDD. Mechanistically, the HPA axis, immune system and microbial tryptophan metabolism could be important in this context. Importantly, our study lend inspiration to clinical trials on probiotics in depressed patients. (C) 2017 Elsevier Ltd. All rights reserved.
Nuclear power uprates are investments in generation capacity that enable reactors to operate beyond their original power limit. We find that owners of deregulated reactors are more likely to make investment in power uprates. Moreover, after deregulation owners of boiling water reactors are more likely to choose Extended Power Uprates (EPUs) that could add up to 20 percent of the original power, but owners of pressurized water reactors, another type of reactors for which EPUs are more technically challenging, tend to select other types of uprates that add less of reactor power. Deregulation incentivizes reactor owners to pursue profitable investments and propels them to make careful investment decisions more consistent with the technological nature of their plants.
High-performance phase-locked loops (PLLs) are critical for power control in grid-connected systems. This paper presents a new method of designing a PLL for single-phase systems based on derivative elements (DEs). The quadrature signal generator (QSG) is constructed by two DEs with the same parameters. The PLL itself is realized by using the DE-based QSG. It avoids errors due to the overlap and accumulation that are present in PLLs based on integral elements, such as a PLL based on a second-order generalized integrator. Additionally, frequency feedback is not needed which allows the proposed PLL to achieve high performance when the grid frequency changes rapidly. This paper presents the model of the PLL and a theoretical performance analysis with respect to both the frequency-domain and time-domain behavior. The error arising from the discretization process is also compensated, ensuring this PLL method is suitable for implementation in a digital control system. Simulation and experimental results show that the proposed PLL achieves good performance in both harmonic rejection and dynamic response.
Identification of fungi in dermatological samples using PCR is reliable and provides significantly improved results in comparison with cultures. It is possible to identify the infectious agent when negative results are obtained from cultures. In addition, identification of the infectious agent can be obtained in 1 day. Conventional and real-time PCR methods used for direct fungus identification in collected samples vary by DNA extraction methods, targeted DNA and primers, and the way of analysing the PCR products. The choice of a unique method in a laboratory is complicated because the results expected from skin and hair sample analysis are different from those expected in cases of onychomycosis. In skin and hair samples, one dermatophyte among about a dozen possible species has to be identified. In onychomycosis, the infectious agents are mainly Trichophyton rubrum and, to a lesser extent, Trichophyton interdigitale, but also moulds insensitive to oral treatments used for dermatophytes, which renders fungal identification mandatory. The benefits obtained with the use of PCR methods for routine analysis of dermatological samples have to be put in balance with the relative importance of getting a result in a short time, the price of molecular biology reagents and equipment, and especially the time spent conducting laboratory manipulations.
Neoscytalidium dimidiatum is an emerging fungus that causes a skin infection similar to dermatophytosis; it affects both immunocompetent and immunosuppressed individuals, and it may invade deeper tissues and organs and cause systemic disease. Little is known about the etiopathogenesis of the infection caused by this fungus, and no standard effective treatment is available. The aim of the present experimental study was to develop an animal model of skin infection with N. dimidiatum. BALB/c mice were inoculated with two fungal strains, and different routes of infection were tested. When challenged intradermally, N. dimidiatum strain HUPE164165 caused skin infection in 67% of the animals whereas strain HUPE115669 did it in 49%. Neoscytalidium dimidiatum was isolated from the skin of 25% of the animals inoculated via epidermal scarification and from 100% of the animals challenged via subcutaneous injection. Mice inoculated intradermally were followed-up during four weeks, and clinical samples were collected on days 3, 8, 15, and 29 after inoculation, corresponding to different stages of infection. The cutaneous infection rate, as measured by the recovery of N. dimidiatum strain HUPE164165 from skin biopsies of animals inoculated intradermally, revealed the presence of infection in 90% of the animals sacrificed at 3 days post-inoculation, 71% at 8, 85% at 15, and 33% at 29. Conidia and hyphae were observed in PAS-stained sections as well as a mild to moderate inflammatory infiltrate in haematoxylin-eosin, although it did not differ from animals inoculated either with T. quinckeanum or PBS. The intradermal route of inoculation was considered to be suitable for the study of skin infection with N. dimidiatum. The animal model developed in this preliminary study is the first to allow the study of cutaneous infection with N. dimidiatum and may contribute to further investigations of the aetiology, immunology, pathogenesis and treatment targeting this emerging mycosis.
Dermatophyte species, isolation and identification in clinical samples are still difficult and take a long time. The identification and molecular epidemiology of dermatophytes commonly isolated in a clinical laboratory in Turkey by repetitive sequence-based PCR (rep-PCR) were assessed by comparing the results with those of reference identification. A total of 44 dermatophytes isolated from various clinical specimens of 20 patients with superficial mycoses in Kayseri and 24 patients in Hatay were studied. The identification of dermatophyte isolates was based on the reference identification and rep-PCR using the DiversiLab System (BioMerieux). The genotyping of dermatophyte isolates from different patients was determined by rep-PCR. In the identification of dermatophyte isolates, agreement between rep-PCR and conventional methods was 87.8 % ( 36 of 41). The dermatophyte strains belonged to four clones (A -D) which were determined by the use of rep-PCR. The dermatophyte strains in Clone B, D showed identical patterns with respect to the region. In conclusion, rep-PCR appears to be useful for evaluation of the identification and clonal relationships between Trichophyton rubrum species complex and Trichophyton mentagrophytes species complex isolates. The similarity and diversity of these isolates may be assessed according to different regions by rep-PCR.
We report here the isolation, molecular cloning and initial characterization of the Trichophyton rubrum pacC gene, which encodes a putative protein that is homologous to the PacC/Rim101p family of pH signaling transcription regulators. The promoter region of the T. rubrum pacC gene contains four recognition sites 5'-GCCAAG-3' for the PacC protein, suggesting that the transcription of this gene itself could be induced under alkaline growth conditions. The enhanced expression profile of the T. rubrum pacC gene in an alkaline environment was confirmed by Northern blotting analysis. We also report that the disruption of pacC gene decreased both the secretion of keratinolytic proteases and the ability of the mutant pacC-1 to grow on human nail fragments as the sole source of nutrition, i.e., growth of the dermatophyte T. rubrum appear to be related to molecular events which depend on the action of protein PacC.
Despite their superficial localization in the skin, pathogenic dermatophytes can induce a complex but still misunderstood immune response in their hosts. The cell-mediated immunity (CMI) is correlated with both clinical recovery and protection against reinfection, and CD4+ T lymphocytes have been recognized as a crucial component of the immune defense against dermatophytes. Before the discovery of the Th17 pathway, CMI was considered to be only dependent of Th1 cells, and thus most studies on the immunology of dermatophytosis have focused on the Th1 pathway. Nevertheless, the fine comparative analysis of available scientific data on immunology of dermatophytosis in one hand and on the Th17 pathway mechanisms involved in opportunistic mucosal fungal infections in the other hand reveals that some key elements of the Th17 pathway can be activated by dermatophytes. Stimulation of the Th17 pathway could occur through the activation of some C-type lectin-like receptors and inflammasome in antigen-presenting cells. The Th17 cells could go back to the affected skin and by the production of signature cytokines could induce the effector mechanisms like the recruitment of polymorphonuclear neutrophils and the synthesis of antimicrobial peptides. In conclusion, besides the Th1 pathway, which is important to the immune response against dermatophytes, there are also growing evidences for the involvement of the Th17 pathway.
Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell sarcoma that typically occurs intra-abdominally in adolescents and young adults, and is characterized by a recurrent t(11;22)(p13;q12) translocation leading to generation of the EWSR1-WT1 fusion gene, which codes for a chimeric protein with transcriptional regulatory activity. DSRCT has a characteristic histologic appearance of nests of uniform small cells within prominent fibroblastic stroma and immunohistochemically it shows multidirectional differentiation, with expression of epithelial, neural, and muscle markers. We illustrate a case of DSRCT that presented as a large intra-abdominal mass, which harbored EWSR1 rearrangement by fluorescence in situ hybridization and EWSR1-WT1 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR), and which histologically had an entirely solid morphology, lacking evidence of desmoplastic stroma. This purely solid variant emphasizes that even when occurring at a typical location, DSRCT may be difficult to recognize when lacking nonclassical morphology. This is of clinical relevance, as DSRCT with this pattern could be misdiagnosed as Ewing sarcoma if RT-PCR is not performed, with resulting prognostic and therapeutic implications.
While attracting new tourists is an important issue in destination marketing, it is also imperative to manage tourists' experience post-trip, particularly in cases of unsatisfying experiences. Yet, the questions of how to rectify unsatisfying tourism experiences received little attention in tourism scholarship. In the present research, we investigated the effectiveness of different forms of marketing messages and the role of counterfactual thinking in the ability of a marketing message to improve tourists' attitudes towards the destination and intentions to recommend, when a tourism experience was not up to tourists' satisfaction. A scenario-based experiment was conducted with 480 respondents. The results showed that user-generated messages and the messages employing emotional appeal were more impactful than destination-generated or rational messages. Respondents who engaged in downward counterfactual thinking, that is imagining the situation in which their experience could have been worse, was shown to have a greater positive effect on unsatisfied tourists. (C) 2016 Elsevier Ltd. All rights reserved.
Bunch charge variations in Free Electron Lasers such as the Free Electron Laser in Hamburg (FLASH) or the European X-Ray Free Electron Laser (E-XFEL) impacts the longitudinal phase space distribution of the electrons resulting in different bunch peak currents, pulse duration and pulse shapes. The electron bunches are generated by short ultraviolet laser pulses impinging onto a photocathode inside a radio frequency (RF) accelerating cavity. At FLASH, bursts of bunches up to 800 pulses with an intra train repetition rate of 1 MHz are used and even higher repetition rates for the E-XFEL (up to 4.5 Mhz) are planned. Charge variations along these bunch-trains can be caused by variations of the laser pulse energies, instabilities of the accelerating fields in the RF cavity and time dependent effects in the photoemission process. To improve the intra bunch-train charge flatness and to compensate train-to-train fluctuations a dedicated digital control system, based on the Micro Telecommunication Computing Architecture (MicroTCA.4) standard, was designed, implemented and successfully tested at the FLASH. The system consists of a bunch charge detection module which analyzes data from toroid system and provides the input signal for the controller which drives a fast UV-Pockels Cell installed in the optical path of the photo-cathode laser. The Pockels cell alters the laser polarization and thus the transmission through a polarizer. The modulation of UV laser pulse energy with an iterative learning feed-forward minimizing the repetitive errors from bunch-train to bunch-train and a fast feedback algorithm implemented in a Field Programmable Gate Array (FPGA) allows for fast tuning of bunch charge inside the bunch-train. In this paper a detailed description of the system and first measurement results are presented.
Objective: To analyze the usefulness of rapid HIV testing in pregnant patients in the delivery room. Methods: This prospective study compared a rapid test and a fourth-generation enzyme-linked immunoassay (ELISA) for HIV screening among pregnant patients admitted in labor with an unknown HIV status at a university hospital in Mexico between July 2015 and February 2016. Pearson correlation analysis was performed, and the diagnostic accuracy of the two tests was assessed with HIV RNA polymerase chain reaction (PCR) as the reference method. Results: Overall, 534 patients were included. With a signal-to-cutoff (S/CO) value of 1.0 or more as a diagnostic criterion, 6 (1.1%) patients had a positive ELISA result. Three had a negative rapid test and three had a positive test (r=0.705). With an S/CO value of 2.0 or more as cutoff, 4 (0.7%) patients had a positive ELISA result. Three had a positive rapid test and one had a negative test (r=0.865). Only three of six patients with an S/CO of 1.0 or more were confirmed to have HIV by RNA PCR. Conclusion: The rapid test showed a strong correlation with the fourth-generation ELISA. Therefore, rapid testing is a useful tool in the delivery room for patients with unknown HIV status.
The purpose of this study was to determine the efficacy of a nucleic acid sequence-based amplification (NASBA) method of detecting noroviruses in artificially and naturally contaminated shellfish. We used 58 fecal samples that tested positive for noroviruses with electron microscopy (EM) to develop an NASBA assay for these viruses. Oligonucleotide primers targeting the polymerase coding region were used to amplify the viral RNA in an isothermal process that resulted in the accumulation of RNA amplicons. These amplicons were detected by hybridization with digoxigenin-labeled oligonucleotide probes that were highly specific for genogroup I (GI) and genogroup II (GII) of noroviruses. The expected band of 327 bp appeared in denaturing agarose gel without any nonspecific band. The specific signal for each amplicon was obtained through Northern blotting in many repeats. All fecal samples of which 46 (79.3%) belonged to GII and 12 (20.6%) belonged to GI were positive for noroviruses by EM and by NASBA. Target RNA concentrations as low as 5 pg/ml were detected in fecal specimens using NASBA. When the assay was applied to artificially contaminated shellfish, the sensitivity to nucleic acid was 100 pg/1.5 g shellfish tissue. The potential use of this assay was also confirmed in naturally contaminated shellfish collected from different ponds in Guangzhou city of China, of which 24 (18.76%) out of 128 samples were positive for noroviruses; of these, 19 (79.6 %) belonged to GII and 5 (20.4%) belonged to GI. The NASBA assay provided a more rapid and efficient way of detecting noroviruses in fecal samples and demonstrated its potential for detecting noroviruses in food and environmental samples with high specificity and sensitivity.
As direct-drive actuators, permanent-magnet linear synchronous motors (PMLSMs) are widely used in high velocity and high precision applications. The detent force, however, can deteriorate the performance and even excite the mechanical resonance. This paper focuses on a novel detent force compensation scheme for PMLSM systems through a combination of structural design and control method. First, due to the bandwidth constraint of the control system, eliminating high frequency ripples is unfeasible; skewed permanent magnets (PMs) considering an optimal skewing length are designed to suppress high order harmonic components. Second, based on the model of PMLSM with skewed PMs, a linearization observer is derived and applied independently to the velocity controller for further diminishing low-order harmonic components. To facilitate implementation in the digital control system, a discretization method taking account of estimated errors is designed. Through the online calculation, the estimated detent force is injected to the control system in a feedforward way. To tune the proposed scheme properly, the convergence of the algorithm is analyzed by utilizing Lyapunov stability theory. Simulation studies are performed to prove the effectiveness of the proposed method, and experiments are provided to confirm the theoretical analysis and simulation results.
This study examined the risk of deterioration/relapse in pregnant women who discontinued their antidepressant medications based on the discretion of the psychiatric specialists compared with those who performed self-interruption. We reviewed the obstetric records of all singleton deliveries beyond 22 weeks of gestation at Japanese Red Cross Katsushika Maternity Hospital from January 2009 through December 2015. Compared with the women continuing antidepressant medications throughout pregnancy, the incidence of deterioration/relapse was higher in the women who discontinued their antidepressant medications regardless of who made the decision (interruption based on the discretion of the psychiatric specialists: 61%, odds ratio (OR), 8.05; 95% confidence interval (CI), 2.4-27; p<0.01; self-interruption: 63%, odds ratio (OR), 8.79; 95% confidence interval (CI), 2.6-29; p<0.01 versus 16%). The continuation of medications and careful observation are required for pregnant women complicated by depressive disorders.
Compatibilism is the view that determinism is compatible with acting freely and being morally responsible. Incompatibilism is the opposite view. It is often claimed that compatibilism or incompatibilism is a natural part of ordinary social cognition. That is, it is often claimed that patterns in our everyday social judgments reveal an implicit commitment to either compatibilism or incompatibilism. This paper reports five experiments designed to identify such patterns. The results support a nuanced hybrid account: The central tendencies in ordinary social cognition are compatibilism about moral responsibility, compatibilism about positive moral accountability (i.e., about deserving credit for good outcomes), neither compatibilism nor incompatibilism about negative moral accountability (i.e., about deserving blame for bad outcomes), compatibilism about choice for actions with positive outcomes, and incompatibilism about choice for actions with negative or neutral outcomes.
This paper is devoted to the comparison of the numerically simulated Chua's circuit and the real circuit. The aim of the research was to figure out the factors affecting the computer simulation accuracy, and to find the ways to improve it. It was discovered that the most influence is exerted by an inaccuracy of the nonlinear Chua's diode characteristic measurement, a numerical integration method used for simulation and the operational amplifier properties. A possibility of an analog circuit application as a source of an accurate signal in order to find the most appropriate numerical method for the chaotic systems simulation is shown.
Multiple mutation combinations in the IgG Fc have been characterized to tailor immune effector function or IgG serum persistence to fit desired biological outcomes for monoclonal antibody therapeutics. An unintended consequence of introducing mutations in the Fc (particularly the C(H)2 domain) can be a reduction in biophysical stability which can correlate with increased aggregation propensity, poor manufacturability, and lower solubility. Herein, we characterize the changes in IgG conformational and colloidal stability when 2 sets of C(H)2 mutations "TM" (L234F/L235E/P331S) and "YTE" (M252Y/S254T/ T256E) are combined to generate an antibody format lacking immune receptor binding and exhibiting extended half-life. In addition to significantly lowered thermostability, we observe greater conformational flexibility for TM-YTE in C(H)2, increased self-association, and poorer solubility and aggregation profiles. To improve these properties, we dissected the contributions of individual mutations within TM-YTE on thermostability and substituted destabilizing mutations with new mutations that raise thermostability. One novel combination, FQQ-YTE (L234F/L235Q/K322Q/M252Y/S254T/T256E), had significantly improved conformational and colloidal stability, and was found to retain the same biological activities as TM-YTE (extended half-life and lack of antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activity). Our engineering approach offers a way to improve the developability of antibodies containing Fc mutations while retaining tailored biological activity. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Background: An extremely high percentage of children worldwide are exposed to stress from the first months of life. The aim of this review is to bring together the experimental results related to chronic early-life stress in both human and experimental models. Methods: We aimed to achieve our objective via a thorough review of the literature. Results: Early-life stress is a challenge for the developing organism and leads to negative effects in the medium and long term. The emotional, cognitive, and behavioral domains are compromised due to alterations produced in the nervous system, with some of the most important being related to the main neurotransmission systems. Conclusions: By using experimental models, it is possible to address the study of the structural and functional changes resulting from early-life stress and, thus, plan intervention and prevention alternatives.
Developmental Dyslexia (DD) is a neurodevelopmental disorder affecting reading acquisition. DD cannot be diagnosed before starting the primary school; thereby, one of the main challenges is to obtain an early DD identification even during preschool years. Achieving this goal could help children at risk for DD to limit the impact of this disorder. To this aim, we have created a digital system composed of various serious games designed for predicting the risk of DD in preschoolers and potentially training specific skills impaired in this learning disability. Our set of serious games are designed to be accessible from any device, a computer with mouse and keyboard, but also a tablet with touch interface for younger children.
Lentinula edodes (Shiitake mushroom) is a common edible mushroom that has high nutritional and medical value. Although a number of genes involved in the fruit of the species have been identified, little is known about the process of differentiation from dikaryotic mycelium to primordium. In this study, serial analysis of gene expression (SAGE) was applied to determine the gene expression profiles of the dikaryotic mycelium and primordium of L. edodes in an effort to advance our understanding of the molecular basis of fruit body development. A total of 6363 tags were extracted (3278 from the dikaryotic mycelium and 3085 from the primordium), 164 unique tags matched the in-house expressed sequence tag (EST) database. The difference between the expression profiles of the dikaryotic mycelium and primordium suggests that a specific set of genes is required for fruit body development. In the transition from the mycelium to the primordium, different hydrophobins were expressed abundantly, fewer structural genes were expressed, transcription and translation became active, different genes became involved in intracellular trafficking, and stress responses were expressed. These findings advance our understanding of fruit body development. We used cDNA microarray hybridization and Northern blotting to verify the SAGE results, and found SAGE to be highly efficient in the performance of transcriptome analysis. To our knowledge, this is the first SAGE study of a mushroom. (c) 2008 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
Although glucocorticoids are known to elicit functional maturation of the gastrointestinal tract, the molecular mechanisms of glucocorticoid action on the developing intestine have not been fully elucidated. Our previous microarray studies identified 66 transcripts as being rapidly induced in the jejunum following dexamethasone (Dex) administration to suckling mice. Now we report the specific cellular location of a subset of these transcripts. Mouse pups at P8 received Dex or vehicle and intestinal segments were collected 3-4 h later. Robotic-based in situ hybridization (ISH) was performed with digoxygenin-labeled riboprobes. Transcripts studied included Ndrg1, Sgk1, Fos, and two unknown genes (Gene 9 and Gene 36). As predicted, ISH revealed marked diversity of cellular expression. In small intestinal segments, Sgk1 mRNA was in all epithelial cells; Fos mRNA was confined to epithelial cells at the villus tip; and Ndrg1 and Gene 36 mRNAs were localized to epithelial cells of the upper crypt and villus base. The remaining transcript (Gene 9) was induced modestly in villus stroma and strongly in the muscle layers. In the colon, Ndrg1, Sgk1, and Gene 36 were induced in all epithelial cells; Gene 9 was in muscle layers only; and Fos was not detectable. For jejunal segments, quantitation of ISH signals in tissue from Dex-treated and vehicle-treated mice demonstrated mRNA increases very similar to those measured by Northern blotting. We conclude that glucocorticoid action in the intestine reflects diverse molecular mechanisms operating in different cell types and that quantitative ISH is a valuable tool for studying hormone action in this tissue.
Study objective: Administration of intranasal dexmedetomidine for sedation is comfortable and effective in children who are afraid of needles, and it offers efficient sedation similar to that of intravenous administration. We performed a systematic review and meta-analysis to evaluate the clinical effects of the pre-procedural administration of intranasal dexmedetomidine. Design: We identified randomized controlled trials (RCTs) that compared intranasal dexmedetomidine administration to other administration methods of various sedatives or placebo from MEDLINE, EMBASE, Cochrane, KoreaMed and hand searches of trial registries. Setting: Pediatrics who underwent interventional procedures and surgeries. Patients: Children under the age of 18. Interventions: Studies were included if they were compatible with the criteria that dexmedetomidine was administered intranasally. Measurements: We pooled data on the sedation status as the primary outcome and considered the behavioral score, blood pressure, heart rate and side effects to be secondary outcomes. Risk ratio (RR) and the standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated for dichotomous and continuous outcomes, respectively. Main results: This meta-analysis included 11 RCTs. The SMD for the sedative effects of intranasal dexmedetomidine was 2.45 (random, 95% CI; -3.33, -1.58) for continuous outcomes and RR of unsatisfactory patient outcome was 0.42 (M-H, random 95% CI; 026, 0.68 I-2 = 45%) for dichotomous outcomes compared to that of intranasal saline. The SMD for the sedative effects of intranasal dexmedetomidine was -0.41 (random, 95% CI; -1.09, 0.27 I-2 = 69%) for continuous outcomes and RR was 0.43 (M-H, random 95% CI; 0.32, 0.58 I-2 = 0%) for dichotomous outcomes compared to that of per os benzodiazepines. Conclusions: This review suggests that intranasal dexmedetomidine is associated with better sedative effects than oral benzodiazepines without producing respiratory depression, but it had a significantly delayed onset of effects. (C) 2017 Elsevier Inc. All rights reserved.
Dexmedetomidine is a highly selective 2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg (n = 6), 10 mg/kg (n = 6), and 100 mg/kg (n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via 2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine.
Advances in prenatal diagnosis, perioperative management, and postoperative care have dramatically increased the population of survivors of neonatal and infant heart surgery. The high survival rate of these patients into adulthood has exposed the alarming prevalence of long-term neuropsychological and psychiatric morbidities. Dextro-transposition of the great arteries (D-TGA) is one of the most extensively studied cyanotic congenital heart defect (CHD) with regard to neurodevelopmental outcomes. Landmark studies have described a common neurodevelopmental and behavioral phenotype associated with D-TGA. Children with D-TGA display impairments in key neurocognitive areas, including visual-spatial and fine motor abilities, executive functioning, processing speed, and social cognition. As they grow older, they may face additional challenges with a worsening of deficits in higher order cognitive skills, problems in psychosocial adjustment and a higher-than-expected rate of psychiatric disorders, such as attention-deficit hyperactivity disorder, depression, and anxiety. The aim of this review is to summarize the available recent data on neuropsychological and psychiatric outcomes in individuals with D-TGA after the arterial switch operation. We present findings within a life-span perspective, with a particular emphasis on the emerging literature on adolescent and young adult outcomes. Finally, we propose avenues for future research in the CHD adult neuropsychology field. Among these avenues, we explore the potential mechanisms by which pediatric neurodevelopmental impairments may have lifelong adverse effects as well as alternative interventions that could optimize outcomes.
The impedance-based model of doubly fed induction generator (DFIG) systems, including the rotor part (rotor side converter (RSC) and induction machine), and the grid part (grid side converter (GSC) and its output filter), has been developed for analysis and mitigation of the subsynchronous resonance (SSR). However, the high-frequency resonance (HFR) of DFIG systems due to the impedance interaction between the DFIG system and parallel compensated weak network is often overlooked. This paper, thus, investigates the impedance characteristics of DFIG systems for the analysis of HFR. The influences of the rotor speed variation, the machine mutual inductance and the digital control delay are evaluated. Two resonances phenomena are revealed, i.e., 1) the series HFR between the DFIG system and weak power grid; 2) the parallel HFR between the rotor part and the grid part of DFIG system. The impedance modeling of DFIG system and weak grid network, as well as the series HFR between DFIG system and parallel compensated weak network has been validated by experimental results.
Background/aim: An in-depth understanding of the early phase of type 1 diabetes (TID) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed TID compared to control neonates. Methods: The study is a case-control study with a 1:2 matching. The individuals were born between 1981 through 2002. Cases were validated using the National Patient Register and the Danish Childhood Diabetes Register. Interleukin(1)-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, interferon gamma, tumor necrosis factor alpha, transforming growth factor beta I (active form), leptin, adiponectin, c-reactive protein, mannose-binding lectin and soluble triggering receptor expressed on myeloid cells-1 were measured by using a flowmetric Luminex xMAP (R) technology. We tested two models both including a number of possible confounders. In the first model (model 1) we also adjusted for HLA-DQ beta 1) genotype. A total of 1930 groups of assay-matched cases and controls (4746 individuals) were included in the statistical analyses. Results: Adiponectin was negatively associated with later risk of TID in both models (relative change (RC), model 1: 0.95, P = 0.046 and model 2: 0.95, P = 0.006). IL-10 and IL-12 were both positively associated with T1D risk in the model 2 (RC, 1.19, P = 0.006 and 1.07, P = 0.02, respectively) these results were borderline significant in model 1, but showed the same direction as the results from model 2. Conclusions: Our results indicate that specific immunological signatures are already present at time of birth in children developing T1D before the age of 18 years. (C) 2016 Elsevier Inc. All rights reserved.
Background and ObjectiveNo previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. Material and MethodsGingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers ( 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes (glycated hemoglobin levels 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. ResultsThe MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). ConclusionUncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis.
Background: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. Methods: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 x 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-)Tregs. Results: The disease progressed and all patients were insulin-dependent 2 years after inclusion. The beta-cell function measured by c-peptide levels and the use of insulin were the best preserved in patients treated with two doses of Tregs (3/6 in remission), less so after one dose (1/6 in remission) and the worst in untreated controls (no remissions). Increased levels of Tregs could be seen in peripheral blood after their adoptive transfer together with the shift from naive CD62L(+)CD45RA(+) to memory CD62L(+)CD45RA(-)Tregs. Increasing serum levels of proinflammatory cytokines were found: IL6 increased in all subjects, while IL1 and TNF alpha increased only in untreated group. Therapeutic Tregs were dependent on IL2, and their survival could be improved by other lymphocytes. Conclusions: The disease progression was associated with changing proportions of naive and memory Tregs and slowly increasing proinflammatory activity, which was only partially controlled by the administered Tregs. The therapeutic cells were highly dependent on IL2. We conclude that the therapy should be administered at the earliest to protect the highest possible mass of islets and also to utilize the preserved content of Tregs in the earlier phases of T1DM.
Sleep problems are common in chronic disorders like diabetes and are the result of poor diet and unhealthy lifestyles. Comprehensive management of diabetes entails lifestyle management and restoration of good habits. Sleep hygiene maintenance helps persons living with diabetes enjoy a better quality of life by restoring normal sleep patterns and thereby improving glycaemic control.
Background: Calcium (Ca2+) handling proteins are known to play a pivotal role in the pathophysiology of cardiomyopathy. However little is known about early changes in the diabetic heart and the impact of insulin treatment (Ins). Methods: Zucker Diabetic Fatty rats treated with or without insulin (ZDF +/- Ins, n = 13) and lean littermates (controls, n = 7) were sacrificed at the age of 19 weeks. ZDF + Ins (n = 6) were treated with insulin for the last 6 weeks of life. Gene expression of Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a, further abbreviated as SERCA) and phospholamban (PLB) were determined by northern blotting. Ca2+ transport of the sarcoplasmatic reticulum (SR) was assessed by oxalate-facilitated 45Ca-uptake in left ventricular homogenates. In addition, isolated neonatal cardiomyocytes were stimulated in cell culture with insulin, glucose or triiodthyronine (T3, positive control). mRNA expression of SERCA and PLB were measured by Taqman PCR. Furthermore, effects of insulin treatment on force of contraction and relaxation were evaluated by cardiomyocytes grown in a three-dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5 days by insulin. By western blot phosphorylations status of Akt was determed and the influence of wortmannin. Results: SERCA levels increased in both ZDF and ZDF + Ins compared to control (control 100 +/- 6.2 vs. ZDF 152 +/- 26.6* vs. ZDF + Ins 212 +/- 18.5*# % of control, *p < 0.05 vs. control, #p < 0.05 vs. ZDF) whereas PLB was significantly decreased in ZDF and ZDF + Ins (control 100 +/- 2.8 vs. ZDF 76.3 +/- 13.5* vs. ZDF + Ins 79.4 +/- 12.9* % of control, *p < 0.05 vs control). The increase in the SERCA/PLB ratio in ZDF and ZDF +/- Ins was accompanied by enhanced Ca2+ uptake to the SR (control 1.58 +/- 0.1 vs. ZDF 1.85 +/- 0.06* vs. ZDF + Ins 2.03 +/- 0.1* mu g/mg/min, *p < 0.05 vs. control). Interestingly, there was a significant correlation between Ca2+ uptake and SERCA2a expression. As shown by in-vitro experiments, the effect of insulin on SERCA2a mRNA expression seemed to have a direct effect on cardiomyocytes. Furthermore, long-term treatment of engineered heart tissue with insulin increased the SERCA/PLB ratio and accelerated relaxation time. Akt was significantly phosphorylated by insulin. This effect could be abolished by wortmannin. Conclusion: The current data demonstrate that early type 2 diabetes is associated with an increase in the SERCA/PLB ratio and that insulin directly stimulates SERCA expression and relaxation velocity. These results underline the important role of insulin and calcium handling proteins in the cardiac adaptation process of type 2 diabetes mellitus contributing to cardiac remodeling and show the important role of PI3-kinase-Akt-SERCA2a signaling cascade.
Introduction: At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed.Areas covered: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD.Expert opinion: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation. One of the recent goals achieved by molecular biology is the development of monoclonal antibodies able to interfere with extracellular matrix accumulation and fibrosis. Other interesting therapies are under investigation and further studies with a greater number of patients will establish a better approach for diabetic nephropathy.
Wu D, Peng F, Zhang B, Ingram AJ, Kelly DJ, Gilbert RE, Gao B, Kumar S, Krepinsky JC. EGFR-PLC gamma 1 signaling mediates high glucose-induced PKC beta 1-Akt activation and collagen I upregulation in mesangial cells. Am J Physiol Renal Physiol 297: F822-F834, 2009. First published July 15, 2009; doi:10.1152/ajprenal.00054.2009.-Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We have recently shown that epidermal growth factor receptor (EGFR) transactivation mediates high glucose (HG)-induced collagen I upregulation through PI3K-PKC beta 1-Akt signaling in mesangial cells (MC). Phospholipase C gamma 1 (PLC gamma 1) interacts with activated growth factor receptors and activates classic PKC isoforms. We thus studied its role in HG-induced collagen I upregulation in MC. Primary rat MC were treated with HG (30 mM) or mannitol as osmotic control. Protein kinase activation was assessed by Western blotting and collagen I upregulation by Northern blotting. Diabetes was induced in rats by streptozotocin. HG treatment for 1 h led to PLC gamma 1 membrane translocation and Y783 phosphorylation, both indicative of its activation. Mannitol was without effect. PLC gamma 1 Y783 phosphorylation was also seen in cortex and glomeruli of diabetic rats. HG induced a physical association between EGFR and PLC gamma 1 as identified by coimmuno-precipitation. PLC gamma 1 activation required EGFR kinase activity since it was prevented by the EGFR inhibitor AG1478 or overexpression of kinase-inactive EGFR (K721A). Phosphoinositide-3-OH kinase inhibition also prevented PLC gamma 1 activation. HG-induced Akt S473 phosphorylation, effected by PKC beta 1, was inhibited by the PLC gamma inhibitor U73122. PLC gamma 1 inhibition or downregulation by small interference RNA also prevented HG-induced collagen I upregulation. Our results indicate that EGFR-PLC gamma 1 signaling mediates HG-induced PKC beta 1-Akt activation and subsequent collagen I upregulation in MC. Inhibition of EGFR or PLC gamma 1 may provide attractive therapeutic targets for the treatment of diabetic nephropathy.
BackgroundPrevious studies found that metformin provided some renoprotection for diabetic renal damage. In the present study, we evaluated the effects of different doses of metformin on the expression of renal tissue nephrin in type 2 diabetes mellitus (T2DM) model rats and the possible mechanism underlying its protective effect in kidney podocytes. MethodsA high-fat diet combined with a low dose of streptozotocin was used to induce T2DM model rats. Diabetic rats were treated with 150, 300, or 500mg/kg metformin for 8weeks. At the end of the study, urine and blood samples were collected for measurement of different indices. Light microscopy and transmission electron microscopy were used to identify morphological changes. Renal expression of nephrin protein was assayed by immunohistochemical staining, whereas real-time polymerase chain reaction was used to detect renal nephrin (Nphs1) mRNA expression. ResultsMetformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment. ConclusionMetformin protects kidney podocytes in T2DM model rats by dose-dependently adjusting renal nephrin expression.
AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in screening retinal endothelial injury and early diagnosis of proliferative diabetic retinopathy. METHODS: The study included 184 serum samples, 59 samples from healthy individuals, 44 samples from diabetes mellitus (DM) patients without diabetic retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR) patients and 39 samples from proliferative diabetic retinopathy (PDR) patients. The expression of miR-126 was evaluated using a real-time quantitative polymerase chain reaction. RESULTS: The serum content of miR-126 declined as the damage degree in the retina. There was significant difference between the two retinopathy groups (P0.05). Receiver operating characteristic curve (ROC) analyses indicated that serum miR-126 had significant diagnostic value for PDR. It yielded an area under the curve (AUC) of ROC of 0.976 with 81.21% sensitivity and 90.34% specificity in discriminating PDR from healthy controls, and an AUC of ROC of 0.919 with 84.75% sensitivity and 94.41% specificity in discriminating NDR and NPDR from healthy controls. When the diagnostic threshold was greater than or equal to 8.43, there was an increase in the possibility of NPDR. When the content of miR-126 was less than or equal to 5.02, the possibility of the occurrence of PDR increased. CONCLUSION: Serum miR-126 can serve as a non-invasive biomarker for screening retinal endothelial injury and early diagnosis PDR.
PURPOSE. Diabetic retinopathy is a leading cause of vision loss. Previous studies have shown signaling pathways mediated by Stat3 (signal transducer and activator of transcription 3) play a primary role in diabetic retinopathy progression. This study tested CLT-005, a small molecule inhibitor of Stat3, for its dose-dependent therapeutic effects on vision loss in a rat model of diabetic retinopathy. METHODS. Brown Norway rats were administered streptozotocin (STZ) to induce diabetes. CLT-005 was administered daily by oral gavage for 16 weeks at concentrations of 125, 250, or 500 mg/kg, respectively, beginning 4 days post streptozotocin administration. Systemic and ocular drug concentration was quantified with mass spectrometry. Visual function was monitored at 2-week intervals from 6 to 16 weeks using optokinetic tracking to measure visual acuity and contrast sensitivity. The presence and severity of cataracts was visually monitored and correlated to visual acuity. The transcription and translation of multiple angiogenic factors and inflammatory cytokines were measured by real-time polymerase chain reaction and Multiplex immunoassay. RESULTS. Streptozotocin-diabetic rats sustain progressive vision loss over 16 weeks, and this loss in visual function is rescued in a dose-dependent manner by CLT-005. This positive therapeutic effect correlates to the positive effects of CLT-005 on vascular leakage and the presence of inflammatory cytokines in the retina. CONCLUSIONS. The present study indicates that Stat3 inhibition has strong therapeutic potential for the treatment of vision loss in diabetic retinopathy.
IgE-associated allergic diseases belong to the most common inflammatory conditions. Their clinical manifestation ranges from mild symptoms to life-threatening episodes. Often patients experience a reduction in physical and psychologic well-being and suffer from a decreased quality of life due to disease activity. The continuously rising number of people that are affected by an allergic condition indicates an urgent need for better diagnostics and more efficient treatment options. Recent progress in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders has led to the identification of novel therapeutic targets and the development of drug candidates that are currently under evaluation. In this review, we highlight studies and clinical trials, which have helped to gain further insight in the etiology of IgE-associated allergic conditions as well as advances in the development of diagnostic tools and therapeutic approaches recently published in Allergy (European Journal of Allergy and Clinical Immunology).
Trichinellosis is a cosmopolitan zoonotic disease produced mainly by the consumption of poorly cooked swine meat. Several studies have probed the efficiency of immunotherapy as a method for the treatment of trichinellosis. In this work, a 45 kDa immunodominant antigen was characterized, and the presence of IgA, IgM and IgG anti-Trichinella spiralis antibodies was evaluated during the course of the infection. In addition, the differences between sublingual and parenteral administration of the 45 kDa T. spiralis antigen were determined. Long Evans rats were used both to purify the 45 kDa antigen and to evaluate the immune response produced in six different groups: healthy and infected controls; two groups of immunized murines (sublingually and parenterally) with four doses of the 45 kDa T. spiralis immunogen administered at days 0, 7, 14 and 21 and challenged with 500 T. spiralis infective larvae (IL) 7 days after the last immunization; and finally, two groups of murines infected with 500 IL of T. spiralis, immunized at week 4 post infection by the same two routes. The humoral response was evaluated by indirect immunofluorescence by confocal microscopyin order to determine the presence of IgA, IgM and IgG antibodies.
The detection of porcine reproductive and respiratory syndrome virus (PRRSV) in oral fluids (OF) by quantitative real-time polymerase chain reaction (qRT-PCR) is gaining increasing popularity. However, the different steps leading to a result have not been extensively evaluated. The aim of the present study was to examine the effect on the performance of qRT-PCR with different sampling materials, conditions of storage of the OF, the need for centrifuging OF, as well as to compare RNA extraction methods and PCR mixes. For the assays, pen-based oral fluids were used, which were pooled and spiked in a serial dilution (up to genotype 10(circle) TCID50/mL) of type 1 PRRSV isolate 3267. Centrifugation at 15,000g for 15 min resulted in an increase in sensitivity (1-2 PCR cycles) that was significant (P<0.05) at the lowest dilution tested. The TRIzol and MagMAX RNA extraction methods gave the maximum sensitivity, lowest threshold cycle (Ct), at equivalent virus concentrations. The AgPath-ID One-Step RT-PCR Kit PCR mix reagents were more sensitive for the detection of PRRSV using a purified plasmid as standard, but LSI VetMAX PRRSV EU/NA PRRSV reagents resulted in a slightly better sensitivity with OF (p <0.05). The present results may be useful to standardize protocols for optimizing detection of type I PRRSV in OF by qRT-PCR. (C) 2017 Elsevier B.V. All rights reserved.
Equine herpesvirus type 1 (EHV-1) is a double -stranded DNA virus occurring in all breeds of horses. It belongs to the Varicellovirus genus, Herpesviridae family and Alphaherpesvirinae subfamily. EHV-1 may cause epidemic respiratory disorders, abortions in pregnant mares, neonatal foal death, chorioretinopathy and also neurological disease, termed equine herpesvirus myeloencephalopathy (EHM). The infection spreads by inhalation of the aerosolised infectious virus or close contact with aborted fetuses, fetal membranes and fomites. Lifelong latency has been demonstrated especially in trigeminal ganglion, lymphatic tissues draining the respiratory tract and in peripheral blood leukocytes, from where the virus can be periodically reactivated. Both traditional serologic and virus isolation tests have been available for a long time, however, these assays have disadvantages, interfering with fast and reliable detection of EHV-1. Advances in molecular biology and the use of quantitative PCR system allow for more sensitive detection in a single genome copy range, higher analytical specificity and calculation of EHV-1 viral loads.
One of the main factors limiting molluscs production is the presence of pathogens and diseases. Disease agent transfer via transfers of live molluscs has been a major cause of disease outbreaks and epizootics. Because of that, the European Union has adopted several decisions and directives, the last in 2006 (2006/88/EC) to control movements of marine organisms over the European countries. Once the disease is established in a determined area its eradication is a complicated task because life cycle of pathogens are not completely known and only a good and early diagnosis of the disease could be the most appropriate way to deal with it. Besides, molluscs do not have an adaptive immune response and vaccination strategies are not possible. Molluscs listed diseases under EU legislation are mainly protozoan parasites, that's why histological techniques are recognized for their diagnosis. However, molecular techniques are being increasingly used primarily as confirmatory techniques of the presence of the pathogens but also in disease monitoring programs. Research perspectives are mainly focussed in the optimization, of the already described techniques to gain in sensitivity and sensibility and in the development of new molecular biology techniques (quantitative real time PCRs), that are faster and easier to apply and that allow a positive diagnosis even in early stages of infection. However, molecular tools detect DNA sequences of the pathogen which does not imply that pathogen is viable in the cell host and the infection is established. Consequently, it needs to be validated against other techniques, such as histology or in situ hybridization, so that its reliability can be determined.
Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumor-specific molecules can be found in exosomes isolated from biological fluids. We have previously analyzed the proteome of urinary exosomes by mass spectrometry, and identified proteins differentially expressed in prostate cancer patients compared to healthy males. Since mass spectrometry is so far not commonly used in clinical laboratories, we have here investigated whether antibody-based methods such as Western blot or ELISA can be used to validate the use of the identified proteins as prostate cancer biomarkers. Western blot experiments designed to detect flotillin 2, TMEM256, Rab3B and LAMTORI showed that the level of these proteins was higher in urinary exosomes from prostate cancer patients compared to healthy males. Furthermore, a receiver operating characteristic curve of flotillin 2 in samples from 16 controls and 16 patients showed an area under the curve of 0.91, and 88% sensitivity at a threshold set to give 94% specificity. In addition, ELISA-based detection of flotillin 2 and PARK7 showed that the combination of these proteins was able to distinguish prostate cancer patients and healthy controls with 68% sensitivity and 93% specificity. Several promising biomarkers identified by mass spectrometry could not be evaluated by Western blot or ELISA due to their low exosomal amount and/or lack of good antibodies. In conclusion, our results show that several urinary exosomal proteins identified as, prostate cancer biomarkers by mass spectrometry have a high diagnostic value also when analyzed by immunology-based methods, thus bringing these biomarkers closer to a potential clinical use. (C) 2016 Elsevier B.V. All rights reserved.
Purpose of review The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome. Recent findings Bacterial meningitis has been declining in incidence over recent years. Over a similar time period molecular diagnostics have increasingly been used. Because of both of these developments viral meningitis is becoming relatively more important. However, there are still many unanswered questions. Despite improvements in diagnostics many laboratories do not use molecular methods and even when they are used many cases still remain without a proven viral aetiology identified. There are also no established treatments for viral meningitis and the one potential treatment, aciclovir, which is effective in vitro for herpes simplex virus, has never been subjected to a clinical trial. Summary Viruses are in increasingly important cause of meningitis in the era of declining bacterial disease. The exact viral aetiology varies according to age and country. Molecular diagnostics can not only improve the rate of pathogen detection but also reduce unnecessary antibiotics use and length of hospitalization. Further research is required into treatments for viral meningitis and the impact in terms of longer term sequelae.
Background: Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management. Methods: Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis. Results: Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6months. Median duration of diarrheal symptoms was 4months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV. Conclusions: It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.
Background: There are multiple etiologies responsible for infectious gastroenteritis causing acute diarrhea which are often under diagnosed. Also acute diarrhea is one of the major causes of morbidity and mortality among children less than 5 years of age. Methods: In our study, fecal samples (n = 130) were collected from children (< 5 years) presenting with symptoms of acute diarrhea. Samples were screened for viral, bacterial, and parasitic etiologies. Rotavirus and Adenovirus were screened by immunochromatographic tests. Diarrheagenic Escherichia coli (EPEC, EHEC, STEC, EAEC, O157, O111), Shigella spp., Salmonella spp., Vibrio cholera, Cryptosporidium spp., and Giardia spp. were detected by gene-specific polymerase chain reaction. Results: Escherichia coli was detected to be the major etiological agent (30.07%) followed by Rotavirus (26.15%), Shigella (23.84%), Adenovirus (4.61%), Cryptosporidium (3.07%), and Giardia (0.77%). Concurrent infections with two or more pathogens were observed in 44 of 130 (33.84%) cases with a predominant incidence particularly in < 2-year-old children (65.90%) compared to children of 2-5 years age group (34.09%). An overall result showed significantly higher detection rates among children with diarrhea in both combinations of two as well as three infections concurrently (p = 0.004915 and 0.03917, respectively). Conclusion: Suspecting possible multiple infectious etiologies and diagnosis of the right causative agent(s) can aid in a better pharmacological management of acute childhood diarrhea. It is hypothesized that in cases with concurrent infections the etiological agents might be complementing each other's strategies of pathogenesis resulting in severe diarrhea that could be studied better in experimental infections.
We have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolated post-synaptic densities (PSDs), using methods of microRNA microarray, real time qRT-PCR, Northern blotting and immunopurification using anti-PSD95 antibody. The majority of brain microRNAs (especially microRNAs known to be expressed in pyramidal neurons) are detectably expressed in synaptic fractions, and a subset of microRNAs is significantly enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA precursors are also detectable in synaptic fractions at levels that are comparable to whole tissue. Whereas mature microRNAs are predominantly associated with soluble components of the synaptic fractions, microRNA precursors are predominantly associated with PSDs. For seven microRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature microRNA. These findings support the proposal that microRNAs are formed, at least in part, via processing of microRNA precursors locally within dendritic spines. Dicer is expressed in PSDs but is enzymatically inactive until conditions that activate calpain cause its liberation; thus, we propose that synaptic stimulation may lead to local processing of microRNA precursors in proximity to the synapse.
The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DECs). A PCR array analysis of Wnt pathway activation in DECs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DEC osteogenesis. By comparing DECs grown in normal growth and mineral-induction media for 4 weeks, the present study confirmed that DKK3 was a potential target gene of osteogenesis through reverse transcliption-quantitative polymerase chain reaction (RT-gPCR) and western blotting (WB). A short hairpin RNA (shRNA) was introduced into DECs using a lentiviral vector to inhibit DKK3 expression. An alkaline phosphatase (ALP) activity assay and Alizarin Red staining were performed to observe the DKK3-shRNA DECs. In addition, the osteogenic differentiation of DKK3-shRNA DECs was analyzed by RT-gPCR and WB. In vivo, DKK3-shRNA DECs seeded on hydroxyapatiteiP-tricalcium phosphate (HA/TCP) scaffolds were transplanted into the subcutaneous tissue of mice with severe combined immunodeficiency, followed by hematoxylin-eosin and Masson staining. The results confirmed that DKK3 expression was downregulated during mineral induction in rat DECs. Lentivirus-mediated expression of DKK3 shRNA in DECs promoted calcified-nodule formation, ALP activity and the expression of P-catenin, runt-related transcription factor 2 and osteocalcin, compared with control cells. In vivo, the implanted section presented the majority of newly formed osteoid matrices and collagen, with limited space between the HA/TCP scaffolds and matrices. In conclusion, DKK3 expression negatively regulates the osteogenic differentiation of DECs and, conversely, downregulation of DKK3 may enhance DEC osteogenesis.
The bewildering complexity of the relationship between genotype and phenotype in human mitochondrial diseases has delayed an understanding of the related cytopathological mechanisms. To explore the relationship between mitochondrial dysfunction in Dictyostelium discoideum and the related cytopathologies, we determined whether the phenotypic outcomes were similar regardless of which D. discoideum mitochondrial gene was targeted for disruption. The disruption of the mitochondrial genes resulted in a similar pattern of phenotypes to those caused by other mitochondrial defects. These include impairment of phototaxis, multicellular development and growth on plates and in liquid medium. As the reduced growth rates could have been due to defective phagocytic or macropinocytic nutrient uptake, these processes were tested but found to be unaffected. Since mitochondria have been associated with Legionella pathogenesis of human macrophages, it was also determined if mitochondrially diseased Dictyostelium strains were better or worse than healthy cells at supporting the growth of Legionella pneumophila. The results revealed that the mitochondrially diseased strains supported greater L pneumophila growth than the wild type Dictyostelium strain (AX2). Quantitative Northern blotting showed a significant reduction in the level of expression of the entire mitochondrial genome, regardless of which mitochondrial gene was targeted for disruption, suggesting a generalized deficiency in mitochondrial gene expression and function. The phenotypic outcomes were the same as those shown previously to result from chronic hyperactivity of the energy-sensing protein kinase, AMPK, after knockdown of mitochondrial chaperonin 60. (C) 2011 Elsevier Inc. All rights reserved.
Dielectric actuators are utilized to convert electrical power into mechanical strain with considerable potential in microrobotic applications. However, critical challenges that need to be addressed include high-voltage interface with high conversion ratio, light weight, small size, and high power density. This study proposes a high piezoelectric transformer-based high conversion ratio interface that is integrated with a direct current/direct current high conversion ratio boost stage and a direct current/alternating current high-voltage driving stage. A piezoelectric transformer-based class-E zero voltage switching direct current/direct current interface is controlled by a hybrid pulse frequency modulation and pulse width modulation control strategies to obtain the desired high step-up ratio in the direct current/direct current stage. A half-bridge converter with special digital control algorithm in the direct current/alternating current stage is designed to convert high direct current voltage into arbitrary unipolar signal driving dielectric actuators. A prototype 23.3 g and 4W interface has been fabricated for experimental validation to verify its ability to drive a 1 kV input dielectric actuator at 5 Hz in microrobotic applications.
A poly(vinylidene fluoride) (PVDF) nanocom-posite incorporated with polydopamine-coated reduced graphene oxide (rGO@PDOPA) nanosheets has been developed with high dielectric permittivity and low loss for electricity storage applications. Structural analysis indicates that PDOPA was successfully anchored onto rGOs through non-covalent linkage under mild conditions. The presence of PDOPA layer between rGO and PVDF can not only prevent the agglomeration and direct contact of original rGOs but also enhance the interaction between PVDF and rGO and microcapacitor formation. Compared to rGO/PVDF composites, higher dielectric permittivity and lower loss factor were achieved simultaneously in rGO@PDOPA/PVDF nanocomposites at low and moderate frequencies. The PDOPA interface layers are effective in modifying the dielectric characteristics of the composites to increase the dielectric permittivity without the introduction of loss mechanisms. This study demonstrates that PDOPA is an ideal interface layer for the development of new percolative dielectric composites with high dielectric permittivity and low loss.
This work describes an electrical interferometer for contactless permittivity measurements working at 120 GHz. It was fabricated in a 130 nm SiGe process featuring an ft and fmax of 240 and 330 GHz. The on-chip system contains a 120 GHz VCO with a tuning range of 7 GHz featuring a divide-by- 64 circuit to enable external PLL operation. The subsequent buffer provides 7 dBm of output power at 120 GHz. Additionally, the IC contains high-precision and high-resolution phase shifters based on a slow-wave transmission line approach with digital control for direct readout ability. A 120 GHz LNA with 17 dB gain and a power detector to provide DC output signals were realized on chip. It enables sample emulation capability by phase shift inducement in the measurement as well as a reference transmission line. In terms of phase detection, the system shows a sensitivity of 907.36 MHz/degrees.
Diencephalic defects underlie an array of neurological diseases. Previous studies have suggested that retinoic acid (RA) signaling is involved in diencephalic development at late stages of embryonic development, but its roles and mechanisms of action during early neural development are still unclear. Here we demonstrate that mice lacking enzymatic activity of the acetyltransferase GCN5 ((Gcn5(hat/hat))), which were previously characterized with respect to their exencephalic phenotype, exhibit significant diencephalic expansion, decreased diencephalic RA signaling, and increased diencephalic WNT and SHH signaling. Using a variety of molecular biology techniques in both cultured neuroepithelial cells treated with a GCN5 inhibitor and forebrain tissue from (Gcn5(hat/hat)) embryos, we demonstrate that GCN5, RAR alpha/gamma, and the poorly characterized protein TACC1 form a complex in the nucleus that binds specific retinoic acid response elements in the absence of RA. Furthermore, RA triggers GCN5-mediated acetylation of TACC1, which results in dissociation of TACC1 from retinoic acid response elements and leads to transcriptional activation of RA target genes. Intriguingly, RA signaling defects caused by in vitro inhibition of GCN5 can be rescued through RA-dependent mechanisms that require RAR beta. Last, we demonstrate that the diencephalic expansion and transcriptional defects seen in (Gcn5(hat/hat)) mutants can be rescued with gestational RA supplementation, supporting a direct link between GCN5, TACC1, and RA signaling in the developing diencephalon. Together, our studies identify a novel, nonhistone substrate for GCN5 whose modification regulates a previously undescribed, tissue-specific mechanism of RA signaling that is required to restrict diencephalic size during early forebrain development.
Pectinolytic bacteria from the genus Dickeya (former Erwinia chrysanthemi), belonging to Dickeya dianthicola and Dickeya solani species, are causative agents of blackleg and soft rot diseases in Europe. Recently, D. solani have been isolated most frequently from potato plants with the symptoms of blackleg and soft rot. D. solani strains were shown to cause more severe disease symptoms on potato plants than D. dianthicola especially at the higher temperature. They are also able to develop blackleg disease from lower inoculum levels. In the presented study we not only compared phenotypic features of fifteen D. solani strains isolated in countries having different climatic conditions, Poland, Finland and Israel, but also we examined three D. dianthicola strains. The comparison was performed to determine the influence of the strain origin and the temperature of incubation on the ability of the strains to macerate potato tissue and on their major virulence factors such as: pectinolytic, cellulolytic and proteolytic activities, siderophore production and motility. Polish D. solani strains showed higher activities of cell wall degrading enzymes than the Finnish and Israeli strains at all the tested temperatures: 18, 27, 37 A degrees C. This observation is correlated with the higher ability of Polish D. solani strains to cause soft rot. In addition, D. solani strains exhibited higher activity of the above mentioned enzymes and caused more severe potato tuber maceration in laboratory tests than the tested D. dianthicola strains. The collected results indicate that although D. solani strains from different climatic conditions have identical Pulse Field Gel Electrophoresis (PFGE) profiles in addition to the same fingerprint profiles obtained by the repetitive sequence-based polymerase chain reaction (REP, ERIC and BOX repetitive sequences), they differ in the examined phenotypic features, especially in the activities of pectinolytic, cellulolytic and proteolytic enzymes and their capacity to macerate potato tuber tissue.
This paper introduces a nonlinear control scheme based on the differential flatness approach for controlling the speed/torque of a permanent magnet synchronous motor (PMSM) drive. The differential flatness estimation is a model based approach. Then, two state-observers are proposed to estimate a load torque disturbance and a stator resistance (represent losses in an inverter and PMSM) by means of its voltage drop. It can help to improve the PMSM drive system and the efficiency. Using the flatness property, we propose simple solutions to dynamics and stabilization problems. The design controller parameters are autonomous of the operating point; moreover, high dynamics in disturbance rejection is achieved. To validate the proposed method, a hardware system is realized in a laboratory, and digital estimation is accomplished with a dSPACE controller DSll04 platform. Simulation and experimental results with a small-scale PMSM of 1000 W, 3000 rpm in a laboratory corroborate the excellent control scheme during a motor-drive cycles.
Exposure of watermelon fruit to ethylene leads to acute placental-tissue softening and watersoaking. mRNA differential display strategy was utilized to isolate and characterize genes associated with development of the disorder. Watermelon fruit were harvested at the full-ripe stage and exposed to 50 mu LL-1 ethylene for 12 h, and 1, 3, and 6 d at 20 degrees C. DNA-free total RNA (0.2 mu g) isolated from fruit treated with air or ethylene for 12 h was reverse transcribed using three different one-base-anchored oligo dT primers. High stringency PCR was performed using eight different 13-mer arbitrary primers in combination with the fluorescent-labeled one-base-anchored oligo dT primers. The PCR fluorescent-labeled products were separated-on a 6% polyacrylamide sequencing gel and differentially expressed bands were isolated. Confirmation of true positive bands was performed by reverse northern blotting. Comparison of mRNA profiles of ethylene- and air-treated fruit revealed that 78 genes were differentially expressed, of which 15 partial cDNAs were isolated and characterized. BLAST search results revealed significant homologies to ethylene biosynthesis and signal transduction pathway genes, lipid-metabolizing enzymes, proteins involved in plant defense responses, radical scavenging enzymes, exonucleases, and expansins. Northern blot analysis of RNA isolated from air- and ethylene-treated fruit stored for 1, 3, and 6d revealed an ethylene-dependent expression pattern of all corresponding genes. The data indicate that ethylene treatment of watermelon fruit results in a rapid up-regulation of oxidative and hydrolytic enzymes. (C) 2007 Elsevier B.V. All rights reserved.
Early metastasis and a poor five-year survival make lung cancer the leading cause of cancer related deaths worldwide. The clinical profile of lung cancer patients in India differs from the West as they present earlier, with squamous cell carcinoma being the commonest histological type. We compared gene expression profiles in primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA libraries containing differentially expressed genes in the tumors were constructed. Differential expression was confirmed by reverse Northern blot analysis. DNA of confirmed clones was sequenced and subjected to GenBank Blast searches. RNA expression levels were then analyzed by Northern blotting and validated by semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed gene cDNA fragments of LSCC were analyzed. The differentially expressed genes included those associated with cellular metabolism, cell-cycle, -structure, -adhesion, transcription, proliferation, apoptosis and signal transduction. The study provided first evidence that KLAA0767, a Death Inducing Protein, a novel p53 independent target of EM, and Geminin, an inhibitor of DNA replication are differentially expressed in LSCC. Identification of the differentially expressed genes in lung cancer in this study may serve as better molecular markers for early diagnosis and identifying novel intervention sites for anticancer therapy. (c) 2008 Elsevier Inc. All rights reserved.
Overselective stimulus control refers to discriminative control in which the number of controlling stimuli is too limited for effective behavior. Experiment 1 included 22 special-education students who exhibited overselective stimulus control on a two-sample delayed matching task. An intervention added a compound identity matching opportunity within the sample observation period of the matching trials. The compound matching functioned as a differential observing response (DOR) in that high accuracy verified observation and discrimination of both sample stimuli. Nineteen participants learned to perform the DOR and two-sample delayed matching accuracy increased substantially for 16 of them. When the DOR was completely withdrawn after 10 sessions, accuracy declined. In Experiment 2, a more gradual withdrawal of DOR requirements showed that highly accurate performance could be maintained with the DOR on only a proportion of trials for most participants. The results show that DOR training may lead to a general improvement in observing behavior.
This paper describes a distributed maximum power point tracking control scheme for photovoltaic (PV) systems at the submodule level. The system employs isolated differential power processing (DPP) converters that require no perturb and observe synchronization and little communication among power converters themselves. Design and benefits of this architecture with respect to control, communication, and converter efficiency are analyzed. Isolated dc-dc converter prototypes are constructed and employed within a string of series-connected PV submodules to experimentally validate the proposed control method. An experimental extraction efficiency of 99.12% is achieved for a three submodule connection with similar to 30% mismatch-a 10.19% improvement from the conventional, non-DPP architecture.
Differential response (DR) is a system reform that allows child protective services (CPS) agencies to divert low to-moderate risk families from an investigative track to an alternate track that does not require a maltreatment disposition or identification of an alleged perpetrator. Knowledge of how DR alters the flow of cases through CPS systems has been restricted by methodological limitations in prior research. This study uses cross-sectional and longitudinal data from the National Child Abuse and Neglect Data System (NCANDS) child file to examine the extent to which DR implementation affects the number and demographic composition of cases investigated for neglect. Results from multivariate, multilevel cross-sectional analysis of 2010 data indicated that investigations were 2.4 times more likely to be substantiated in DR counties than in non-DR counties. Children with a previous substantiated report were also more likely to have a current report substantiated and this difference was significantly greater in DR counties than in non-DR counties. Child race and ethnicity did not predict substantiation decisions. Results from a mixed-effect longitudinal analysis of 997,512 cases from 269 counties between 2001 and 2010 suggest that the rate of investigations fell sharply nationwide within three years of DR implementation. However, substantiation rates did not change as a result of DR implementation. Instead, analysis indicated differences between DR and non-DR counties emerged before the launch of DR. The findings highlight the benefit of using "big data" and longitudinal analysis to assess large-scale policy changes. (C) 2016 Elsevier Ltd. All rights reserved.
Using a simplified high-frequency small-signal equivalent circuit model for BSIM3 MOSFET, the fully differential two-stage folded-cascode CMOS operational amplifier is analyzed to obtain its small-signal voltage transfer function. As a result, the expressions for dc gain, five zero frequencies, five pole frequencies, unity-gain frequency, and phase margin are derived for op amp design using design equations. Then the analysis result is verified through the comparison with Spice simulations of both a high speed op amp and a low power op amp designed for the 0.13 mu m CMOS process.
Trifoliate orange (Poncirus trifoliata (L) Raf.) is extremely cold hardy when fully acclimated, but knowledge relevant to the molecular events underlying the acclimation is still limited so far. In this study, forward (4 degrees C over 25 degrees C) and reverse (25 degrees C over 4 degrees C) suppression subtractive hybridization (SSH) libraries were constructed in order to identify the genes involved in cold acclimation in trifoliate orange. After reverse northern blotting analysis and sequencing, a total of 105 and 117 non-redundant differentially expressed sequence tags (ESTs) were obtained from the forward and reverse libraries, respectively. Blast2go analysis revealed that 91 ESTs, 31 from the forward library and 60 from the reverse library, displayed significant sequence homology to the genes with known or putative functions. They were categorized into various functional groups, including catalytic activity, binding protein, structural molecule, enzyme regulator, molecular transducer, electron carrier, and transport activity/transcription regulation. Expression analysis of the selected ESTs by reverse transcriptase polymerase chain reaction was consistent with the results of differential screening. In addition, time-course expression patterns of the genes further confirmed that they were responsive to low temperature treatment. Among the genes of known functions, many are related to maintenance of cell wall integrity, adjustment of osmotic potential and maintenance of reactive oxygen species homeostasis, implying that these physiological processes might be of paramount significance in rendering protective mechanisms against the low temperature stress. The data presented here gain an insight into the molecular changes underlying the cold acclimation of trifoliate orange, and the results can be of reference for unraveling candidate genes that hold great potential for genetic engineering in an effort to create novel germplasms with enhanced cold stress tolerance. (C) 2011 Elsevier B.V. All rights reserved.
Work on standardising methods in the field of animal species differentiation has been intensified in Germany in recent years, not least due to the horsemeat scandal in 2013. Even though there are now hardly ever any positive findings any more in examinations to detect horse elements in foods such as lasagne, animal species differentiation altogether ranks high in detecting adulteration of foods. This article therefore summarises the current status of analysis techniques in Germany with a focus on standardisation. It has been established by the working group "Biochemical and Molecular Biological Analytics" of the Lebensmittelchemische Gesellschaft (Food Chemistry Society within the German Chemical Society) with support of experts in the working group "Molecular biology techniques for differentiating plant and animal species" [ 64 of the German Food and Feed Code - LFGBI and the "Immunology and molecular biology" task force of the Food hygiene and food of animal origin working group (ALTS), both from Germany.
Background: Major depressive disorder (MDD) and anxiety disorders are highly co-morbid. Research has shown conflicting evidence for white matter alteration and amygdala volume reduction in mood and anxiety disorders. To date, no studies have examined differences in structural connectivity between anxious depressed and non-anxious depressed individuals. This study compared fractional anisotropy (FA) and density of selected white matter tracts and amygdala volume between anxious depressed and non-anxious depressed individuals. Methods: 64- direction DTI and T1 scans were collected from 110 unmedicated subjects with MDD, 39 of whom had a co-morbid anxiety disorder diagnosis. Region of interest (ROI) and tractography methods were performed to calculate amygdala volume and FA in the uncinate fasciculus, respectively. Diffusion connectometry was performed to identify whole brain group differences in white matter health. Correlations were computed between biological and clinical measures. Results: Tractography and ROI analyses showed no significant differences between bilateral FA values or bilateral amygdala volumes when comparing the anxious depressed and non-anxious depressed groups. The diffusion connectometry analysis showed no significant differences in anisotropy between the groups. Furthermore, there were no significant relationships between MRI-based and clinical measures. Conclusion: The lack of group differences could indicate that structural connectivity and amygdalae volumes of those with anxious-depression are not significantly altered by a co-morbid anxiety disorder. Improving understanding of anxiety co-morbid with MDD would facilitate development of treatments that more accurately target the underlying networks. (C) 2017 Elsevier Ltd. All rights reserved.
Whereas a number of studies have examined relationships among brain activity, social cognitive skills, and autistic traits, fewer studies have evaluated whether structural connections among brain regions relate to these traits and skills. Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are white matter tracts that may underpin the behavioral expression of these skills because they connect regions within or provide sensory information to brain areas implicated in social cognition, and structural differences in these tracts have been associated with autistic traits. We examined relationships among self-reported autistic traits, mentalizing, and water diffusivity in UF and ILF in a nonclinical sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years; 15 women). We measured autistic traits using the Autism-Spectrum Quotient, and we measured mentalizing using the Dynamic Interactive Shapes Clips task. We used Tract-Based Spatial Statistics and randomize to examine relationships among fractional anisotropy (FA) values in bilateral ILF and UF, age, cognitive abilities, autistic traits, and mentalizing. Autistic traits were positively related to FA values in left ILF. No other relationships between FA values and other variables were significant. Results suggest that left ILF may be involved in the expression of autistic traits in individuals without clinical diagnoses.
The paper aims at explaining why large-scale energy-intensive industries-here the German iron and steel industry-had a period of slow uptake of major energy-efficient technologies from the mid 1990s to mid 2000s (Arens and Worrell, 2014) and why from the mid 2000s onwards these technologies are increasingly implemented again. We analyze the underlying factors and investment/innovation behavior of individual firms in the German iron and steel industry to better understand barriers and drivers for technological change. The paper gives insights on the decision-making process on energy efficiency in firms and helps to understand how policy affects decision-making. We use a mixed method approach. First, we analyze the diffusion of three energy-efficient technologies (EET) for primary steelmaking from their introduction until today (top-pressure recovery turbine (TRT), basic oxygen furnace gas recovery (BOFGR), and pulverized coal injection (PCI)). We derive the uptake of these technologies both at the national level and at the level of the individual firm. Second, we analyze the impact of drivers and barriers on the decision-making process of individual firms whether or not they want to implement these technologies. Economics and access to capital are the foremost barriers to the uptake of an EET. If the expected payback period exceeds a certain value or if the company lacks capital, investments in EET seem not to happen. But even if an EET is economically viable and the company has access to capital, investments in EET might not be realized. Policy-induced prices might have strengthened the recent diffusion of TRT. We found indications that in a limited number of cases, policy intervention was a driving factor. Technical risks and imperfect information are only marginal factors in our cases. Site-specific factors seem to be important, as site-specific factors shape the economics of the selected EET.
A digitally controlled operational amplifier (op-amp) with level-crossing-based approximation is proposed. A high gain is effectively obtained by means of a damping control without a stability problem occurring in the multiple gain stages. Compared to the previous version of the zero-crossing-based algorithmic approximation, the proposed scheme further improves the settling time with the class AB operation obtained by switching of multiple driving paths. For verification, the designed op-amp is applied to a 10-bit pipeline ADC and implemented in a 0.18 mu m CMOS technology. Measured results show that the designed op-amp successfully operates at 10-bit resolution, 10 MSample/s pipeline ADC and achieves an effective gain of more than 60 dB.
Inspiring by the advantages of digital peak voltage (DPV) control and digital average current (DAC) control, the digital average voltage (DAV) control for switching DC-DC converter is proposed and investigated. Taking buck converter as an example, DAV control algorithm is analyzed in detail. In order to explore the stability of system, the z-domain transfer function is deduced, by which the critical equivalent series resistance (ESR) of output capacitor is obtained. Finally, DAV controlled, DPV controlled and DAC controlled buck converter are compared by time-domain simulation. Results indicate that DAV control possesses better steady accuracy as well as DAC control. In addition, DAV controlled buck converter is in stable state during the whole duty ratio. Moreover, DAV control and DPV control have similar load transient performance but DAV control behaves lower overshoot voltage with load variation.
Brain-inspired circuits can provide an alternative solution to implement computing architectures taking advantage of fault tolerance and generalization ability of logic gates. In this brief, we advance over the memristive threshold circuit configuration consisting of memristive averaging circuit in combination with operational amplifier and/or CMOS inverters in application to realizing complex computing circuits. The developed memristive threshold logic gates are used for designing fast Fourier transform and multiplication circuits useful for modern microprocessors. Overall, the proposed threshold logic outperforms previous memristive-CMOS logic cells on every aspect, however, they indicate a lower chip area, lower total harmonic distortion, and controllable leakage power, but a higher power dissipation with respect to CMOS logic.
Loudspeakers line arrays are very common reproduction sound systems used in real environments (e.g., theaters, stadiums, cinemas, and conference halls) for synthesizing the directivity characteristics of a linear source. The sound field emitted by a vertical line array can be pointed in a particular direction by using digital signal processing techniques and avoiding any mechanical movements. The approach proposed in this paper to obtain the desired directivity behavior takes advantage of the reproduction of a virtual source with frequency-independent directivity characteristics using wave field synthesis theory and introducing a computational complexity reduction. A full investigation on the performance of the technique has been carried out making comparisons with other approaches proposed in the literature thus providing an overview of the results achievable with digital steering of line arrays. (C) 2015 Elsevier Ltd. All rights reserved.
This study demonstrates a new method for rapid and precise maximum power point tracking in photovoltaic (PV) applications using dithered PWM control. Constraints imposed by efficiency, cost, and component size limit the available PWM resolution of a power converter, and may in turn limit the MPP tracking efficiency of the PV system. In these scenarios, PWM dithering can be used to improve average PWM resolution. In this study, we present a control technique that uses ripple correlation control (RCC) on the dithering ripple, thereby achieving simultaneous fast tracking speed and high tracking accuracy. Moreover, the proposed method solves some of the practical challenges that have to date limited the effectiveness of RCC in solar PV applications. We present a theoretical derivation of the principles behind dithering digital ripple correlation control, as well as experimental results that show excellent tracking speed and accuracy with basic hardware requirements.
A rapid prototyping methodology for digital controllers is presented in this paper. Its main application is in the development, debugging, and test of microgrid inverter controllers. To fulfill the application requirements, these systems are characterized by complex multilayer architectures, extending from pulse width modulation (PWM) and current control loops up to global optimization and high level communication functions. The complexity and the wide variability of the different layer implementations make digital control mandatory. However, developing so complex digital controllers on conventional hardware platforms, like digital signal processors (DSPs) or even FPGAs, is not the most practical choice. This paper shows how multiplatform control devices, where software configurable DSP functions and programmable logic circuits are efficiently combined, represent the optimal solution for this field of application. Furthermore, this paper proposes hardware-in-the-loop real-time simulation as an effective means of developing and debugging complex hardware and software codesigned controllers. A case study is presented and used to illustrate the different design and test phases, from initial concept and numerical simulation to final experimental verification.
The article describes some of the features of the servo amplifier, developed in the NRU "MPEI" for use in multi-axis high-precision materials processing. Simplified structure of servo amplifier and some of the key components of servo drive digital control system are presented. Two ways of multi-axes control are compared: using the RS-232 interface and digital inputs/outputs, and using the CANopen standard based digital CAN protocol. The benefits of multi-axis control with the CANopen protocol are high-speed exchanges, reliability of data transmission, standardization and simple communication topology.
There are many industrial applications where precise delivery of fluid required such as ratio blending, delivery system, etc. One of such application is petroleum product delivery system. As the price of these petroleum products is increasing day by day, it is important to deliver the exact demanded quantity of product to the customer. For such delivery systems the digital control valve is used. This paper deals with the simulation of the digital control valve. The motivation behind this is, if we know the behavior of the digital control valve then we can develop different control strategies so that the fluid delivery can be done with accuracy and precision.
Purpose - The model for digitally controlled three-phase pulse width modulation (PWM) boost rectifiers is a sampled data model, which is different from the continuous time domain models presented in previous studies. The controller, which is tuned according to the model in continuous time domain and discretized by approximation methods, may exhibit some unpredictable performances and even result in unstable systems under some extreme situations. Consequently, a small-signal discrete-time model of digitally controlled three-phase PWM boost rectifier is required. The purpose of this paper is to provide a simple but accurate small-signal discrete-time model of digital controlled three-phase PWM boost rectifier, which explains the effect of the sampling period, modulator and time delays on system dynamic and improves the control performance. Design/methodology/approach - Based on the Laplace domain analysis and the waveforms of up-down-count modulator, the small signal model of digital pulse width modulation (DPWM) in the Laplace domain is presented. With a combination of state-space average and a discrete-time modeling technique, a simplified large signal discrete time model is developed. With rotation transformation and feed-forward decoupling, the large-signal model is decoupled into a single input single output system with rotation transformation. Then, an integrated small signal model in the Laplace domain is constructed that included the time delay and modulation effect. Implementing the modified z-transform, a small-signal discrete-time model is derived from the integrated small signal model. Findings - In a digital control system, besides the circuit parameters, the location of pole of open-loop transfer function is also related to system sampling time, affecting the system stability, and the time delay determines the location of the zero of open-loop transfer function, affecting the system dynamic. In addition to the circuit parameters discussed in previous literature, the right half plane (RHP) zero is also determined by the sampling period and the time delay. Furthermore, the corner frequency of the RHP zero is mainly determined by the sampling period. Originality/value - The model developed in this paper, accounting for the effect of the sampling period, modulator and time delays on the system dynamic, give a sufficient insight into the behavior of the digitally controlled three-phase PWM rectifier. It can also explain the effect of sampling period and control delay time on system dynamic, accurately predict the system stability boundary and determine the oscillation frequency of the current loop in critical stable. The experimental results verify that the model is a simple and accurate control-oriented small-signal discrete-time model for the digitally controlled three-phase PWM boost rectifier.
A simple method to aid in the design of digital compensators for DC-DC power switching converter is presented. From simple equations, feasible designs are determined, depending on the characteristics of the converter, sampling frequency and time delay restrictions. It allows to carry out sensitivity analysis of different parameters, obtaining an insightful assessment of their influence on the system performance
Recently, there has been an increase in the use of finite control set model predictive control (FCS-MPC) for power converters. Model predictive control (MPC) uses the discrete-time model of the system to predict future values of control variables for all possible control actions and computes a cost function related to control objectives. This control technique can provide fast dynamic response. However, MPC method implementation imposes a very high computational burden and causes significant hardware requirements for real-time implementation. In this paper, a fully field-programmable gate array (FPGA)-based real-time implementation of MPC is proposed for direct matrix converter (DMC). In the proposed method, all control calculations and the safe commutation scheme for DMC are fully implemented in the FPGA and the need for another digital control platform, such as digital signal processors (DSP) or dSPACE, is eliminated. The proposed scheme takes full advantages of the parallel computation capability of FPGAs.
A fundamental challenge in digital control arises when the controlled plant is subjected to a fast disturbance dynamics but is only equipped with a relatively slow sensor. Such intrinsic difficulties are, however, commonly encountered in many novel applications such as laser- and electron-beam-based additive manufacturing, human-machine interaction, etc. This paper provides a discrete-time regulation scheme for exact sampled-data rejection of disturbances beyond Nyquist frequency. By introducing a model-based multirate predictor and a forward-model disturbance observer, we show that the inter sample disturbances can be fully attenuated despite the limitations in sampling and sensing. The proposed control scheme offers several advantages in stability assurance and lucid design intuitions. Verification of the algorithm is conducted on a motion control platform that shares the general characteristics in several advanced manufacturing systems. (C) 2016 Elsevier B.V. All rights reserved.
In this paper, a new control structure is presented to extract maximum power from a wind regime. In this novel approach, a discrete-time higher order sliding-mode controller is designed as an observer to construct the reference value for the extractable power based on the condition that it operates. This is possible by tracking the optimal tip speed ratio with manipulating the voltages of the rotor in the doubly fed induction generator (DFIG) configuration. The presented structure improves the performance under abrupt changes in the wind speed and can be used for any type of optimum active power tracking algorithms. The simulations show the significant improvement in performance of the nonlinear discrete-time backstepping controller utilizing this technique.
A digital predictive peak current control (PPCC) employing the adaptive slope compensation is proposed in this paper. The PPCC precisely predicts the peak current reference with the adaptive slope compensation according to operation regions and load conditions. Thereby, the PPCC can control the peak inductor current, and it significantly reduces the total harmonic distortion compared to that of the conventional digital average current control with duty ratio feed-forward which is widely used. In addition, parts of the PPCC are implemented by utilizing the internal high-resolution ramp generator and comparator of a digital signal processor without external components. The principle and analysis of the PPCC are presented, and the performance and feasibility are verified by experimental results with universal input (90 V-rms similar to 260 V-rms) and 750 W - 400 V output laboratory prototype.
In order to make the dynamic voltage restorer (DVR) concurrently compensate for low-order harmonics and voltage sag, and eliminate the influence of digital control on system performance, we propose a novel double closed-loop digital control strategy, consisting of the fundamental proportional resonant (PR) control in a voltage loop and selective harmonic PR control in an inductance current loop. Then, we mainly analyse the discretization effects of the virtual LC method and the step response method, and further present a straightforward digital design method. Next, with this method, we design the parameters of the fundamental and selective harmonic PR controllers in the discrete domain, which inhibit the influence of sampling, calculation delay etc. on the steady-state error and the dynamic response performance. Finally, an 11-kVA DVR prototype is developed and tested. The experimental results indicate that the proposed control strategy satisfies the requirement of voltage quality for sensitive loads and achieves a good dynamic response performance.
Very-high-frequency (VHF) converters with the conventional driving scheme suffer from serious efficiency drop over entire input voltage range due to gate drive timing mismatch of the eGaN control and synchronous rectification (SR) HEMTs. A digital adaptive driving scheme is proposed to adjust the control and SR gate drive signals efficiently over input voltage range. A state-space model is derived to predict drive timing precisely according to different input voltage and adjust the gate drive signals correspondingly. A high time resolution circuit to improve time resolution by selecting cascaded high-speed buffers is proposed. With the proposed driving scheme, high-frequency switching loss and reverse conduction time of eGaN HEMTs are reduced significantly to maintain high efficiency over entire input voltage range. A 30-MHz VHF SR flyback with the printed circuit board (PCB) fabrication air-core transformer was built. With 18-V input and 5V/10-W output, the measured efficiency realizes 80.0%. With 24-V input and 5-V/10-W output, the proposed solution improves the efficiency from 72.9% using the conventional driver to 75.1% (an improvement of 2.2%).
This paper introduces a highly flexible multichannel output stage for battery-powered portable electric stimulators (ESs), based on novel power converter architecture. Compared with other solutions, the presented output stage for transcutaneous (surface) stimulations increases the number of applicable therapies, improves the battery operating time through reduced power consumption, and potentially results in more comfortable and shorter healing therapies. The new hybrid switch-mode power converter is a combination of flyback and switched-capacitor (SC) topologies. The flyback steps up the battery voltage and provides galvanic isolation. The following power-efficient SC stage replaces lossy linear current sources (CSs) of conventional solutions and produces pulses with a much higher slew rate, reducing the pulse energy needed to cause the stimulus. The SC also inherently produces pulses with zero-net charge, eliminating bulky blocking capacitors and/or dedicated discharging circuits. The regulation of the amplitudes of the pulses is performed with a new digital voltage-programmed current mode controller, forcing the output of the SC stage to behave as a CS. The flexible digital controller allows for creation of various types of pulses and also features several levels of patient protection. An experimental prototype of the output stage has undergone proof of principle tests with able-bodied individuals. The results show that the new output stage produces pulses with a 1-mA/ns slew rate, about two orders of magnitude higher than the other known solutions. The trials show that the faster slew rate pulses generate the same muscle contraction with 34% lower amplitudes, reducing energy consumption by 55%, allowing longer battery life of portable ES applications.
In order to meet the needs of modern intelligent agricultural detection, this paper designs and develops a novel energy-saving intelligent wireless agricultural detecting system combined with technologies green power supply, wireless transmission and digital control. This system can be powered by green energy resources such as solar energy or wind power and combined with digital control and wireless communication technologies it can achieve collection of a large amount of parameters in terms of modern agricultural cultivation, which will meet the needs of different application scenarios. Results of repeated experiments have shown that it has such advantages as being green and environmentfriendly, flexible and reliable.
The advantages of minimum-phase (MP) systems for control applications are well known. Prior research has shown that a non-MP (NMP) system can be discretized to an MP system using either a zero-order hold (ZOH) or a square-pulse sample-and-hold input (SHI). This paper investigates the MP characteristics of the discrete-time (DT) system obtained by discretizing a continuous-time single-input single-output NMP system using different SHIs. Two new SHIs (forward and backward triangular) are studied in addition to the square pulse. Numerical simulations were adopted for studying the MP property of the resulting DT system as a function of sample-and-hold parameters. The simulation results show that it is possible to find a smaller sampling period that results in an MP DT system using the proposed SHIs compared with the ZOH. The q-Markov cover system identification with pseudorandom binary signal was then used for a hardware-in-the-loop (HIL) simulation study. A resistor-capacitor filter was used to represent the implementation error of the SHI due to unmodeled actuator dynamics. The HIL simulation results show that the proposed SHI scheme is robust to actuator modeling error. The MP properties of the DT systems with three SHIs are compared. The results show that the forward triangle SHI has the best performance due to its robustness to unmodeled actuator dynamics and the capability of retaining the MP property of the discretized system at small sampling periods.
This paper presents a cycle efficient software frequency response analyzer (SFRA), which is integrated into the firmware of the digitally controller power converter to measure the frequency response of the plant and the open-loop gain of the closed-loop system. The algorithm uses the readily available measurements taken for the power stage control and does not require additional hardware. This enables periodic measurement of the frequency response which can be used to monitor changes in the power converter. The proposed technique can run on a conventional microcontroller without any host intervention, and adds no cost to the system, which is important for the cost-sensitive power converters. Both floating point and fixed point implementation are compared enabling widespread applicability of the technique. In order to validate the efficacy of the analyzer, a synchronous buck power converter is designed and its control transfer function is compared with the measured online frequency response. An algorithm is outlined to fit the measured SFRA data to a pole-zero format through intelligent cost function estimation. The correlation of zeros and poles identified using this method with the modeled plant transfer function is analyzed. A dual core approach is discussed to run SFRA on a high-switching-frequency converter, thus showing applicability of the technique in high-switching-frequency converters.
LCL filters have been widely used for grid-connected inverters. However, the problem that how time delay affects the stability of digitally controlled grid-connected inverters with LCL filters has not been fully studied. In this paper, a systematic study is carried out on the relationship between the time delay and stability of single-loop controlled grid-connected inverters that employ inverter current feedback (ICF) or grid current feedback (GCF). The ranges of time delay for system stability are analyzed and deduced in the continuous s-domain and discrete z-domain. It is shown that in the optimal range, the existence of time delay weakens the stability of the ICF loop, whereas a proper time delay is required for the GCF loop. The present work explains, for the first time, why different conclusions on the stability of ICF loop and GCF loop have been drawn in previous studies. To improve system stability, a linear predictor-based time delay reduction method is proposed for ICF, while a time delay addition method is used for GCF. A controller design method is then presented that guarantees adequate stability margins. The delay-dependent stability study is verified by simulation and experiment.
The "noise" induced by quantization in digitally controlled systems can be modelled as small amplitude chaotic behaviour described by a simple piecewise linear map, the micro-chaos map. The chaotic nature of certain micro-chaos maps was proved rigorously in the last 20 years. It was also pointed out that several disconnected strange attractors or repellers may coexist far from the desired state of the system. The control error is influenced by the number of these strange sets and the local behaviour of trajectories in their neighbourhoods. In the present paper we focus on the exploration of the possible attractor/repeller structures in the phase space of a PD-controlled system and estimate the expected control error by several methods.
Digital stabilization of unstable equilibria of linear systems may lead to small amplitude stochastic-like oscillations. We show that these vibrations can be related to a deterministic chaotic dynamics induced by sampling and quantization. A detailed analytical proof of chaos is presented for the case of a PD controlled oscillator: it is shown that there exists a finite attracting domain in the phase-space, the largest Lyapunov exponent is positive and the existence of a Smale horseshoe is also pointed out. The corresponding two-dimensional micro-chaos map is a multi-baker map, i.e. it consists of a finite series of baker's maps.
A new, small and efficient voltage regulator, realized using a resonant switched-capacitor converter technology, is introduced. Voltage regulation is implemented by means of simple digital pulse density modulation. It displays an ideal transient response with a zero-order nature to all disturbance types. The newly developed topology acts as a gyrator with awide range of voltage conversion ratios (below as well as above unity) with constant efficiency characteristics for the entire operation range. The operation of the voltage regulator is verified on a 20 W experimental prototype, demonstrating ideal transient recovery without over/undershoots in response to load and line transients. Simple design guidelines for the voltage regulation system are provided and verified by experiments.
In this paper, two discrete-time control schemes are presented for induction motors (IMs) based on the discrete-time sliding-mode technique. The first controller is designed using the equivalent control method. The second controller is based on a discrete-time equivalent of the super-twisting algorithm, in which the sliding-mode dynamics is robustified by adding an integral action. The non-measurable rotor fluxes are estimated by two observers. The first observer design is based on a simple copy of the rotor flux dynamics, whereas the second observer design is based on the sliding-mode technique. A simulation study was carried out for the evaluation of the closed-loop performance of the IM at different sampling periods and to compare results with other discrete-time control techniques. Moreover, the robust performance of the closed-loop IM is investigated under external and internal perturbations. The simulation study predicts that the IM, when in closed-loop with one of the proposed controllers, still performs well at a sampling time of 1250 mu s, whereas other control strategies start to lose accuracy. Real-time experiments were finally carried out, where the good performance of the proposed strategy is verified.
In this paper an adaptive rotor flux observer is developed. This observer performs a real-time correction of the mutual inductance and rotor resistance of the motor using data from the DC-link voltage sensor, the inverter state and the phase current and position sensors. The observer compares the behavior of two independent observers (sensorless and sensored observers) in order to correct the parameters of the sensored observer. The adaptation algorithm corrects the mutual inductance, which can vary due to change of the magnetization current, and the rotor resistance, which can change due to variation of the rotor temperature. Computer simulation results are presented to validate the proposed method.
This paper proposes an LED driving circuit with a digital controller, power factor correct (PFC) function, and low light flicker. The key topology of the proposed circuit is a conventional Flyback combined with a pre-stage. As a result, there will be less light flicker than with other one-stage PFC circuits. A digital controller, implemented using a low-cost microcontroller, dsPIC30F2020, will meet PFC and low light flicker. The experimental results validate the functionality of the proposed circuit.
A digital pulse-frequency-modulated controller is designed by discretizing an analog integral controller for an LLC resonant DC-DC converter using the so called IA-PIM digital redesign method. It regulates the output voltage by adjusting the frequency of the input switching, which in turn changes the gain of the LLC converter. Its performances to sudden changes in the load are evaluated though extensive simulations. These results show that the digital controller can realize the performance of an analog controller at a sampling frequency that can be much lower than those currently prevail, which may be advantageous in terms of reduced computational requirements and power consumption.
This paper presents a new algorithm for controlling the magnetic induction waveform in a specific measurement system for the magnetic characterization and modeling of silicon steel sheets. Experimental results show that, with this new control algorithm, the measurement system is able to characterize silicon steel sheets under sinusoidal or nonsinusoidal waveforms in wide frequency and amplitude range.
In order to get a thorough understanding of the total digital silicon micro-gyroscope, a novel system-level model with details of both the sense and circuit is presented in this paper. Unlike the traditional structures of the digital part of the digital gyroscope, a structure with programmable delay units (PDUs) instead of DPLLs gives a brief and robust character of the whole system. And the PDUs coordinating with the FIR filter could lead to a removal of the IF filters of the sigma delta DAC for feedback, which saves a lot of consumption. Two MASH sigma delta ADCs are designed to convert the output of the charge voltage converters to digital signals, which also bring a better stability. The ADCs achieve an SNR of 102.5 dB with a 10 kHz bandwidth. The stabilization of the closed drive mode has also been analyzed including how the noise caused by the quantization of the digital circuit is affecting the stabilization of both the amplitude and frequency of the driving signals. In the end, a final result of simulation of the gyroscope shows the correctness and accuracy of the whole model of the gyroscope.
In boost converters and other indirect energy transfer topologies, the fastest transient response usually does not coincide with the minimum possible output voltage deviation. This paper introduces a practical mixed-signal current programmed mode (CPM) controller that, compared to time-optimal solutions, provides a smaller deviation, lower current stress, and simpler controller implementation. To recover from transients, the controller passes through two phases. In the first phase, the inductor current is set in the proximity of its steady-state value, so that the initial transient-caused capacitor charging/discharging process is reversed. In the second phase, the voltage is gradually recovered. The controller implements a simple algorithm for setting up the inductor current and the output voltage peak/valley values during transients, based on the output current estimate, which is obtained through a self-tuning procedure. The operation of the controller is verified both through simulations and experimentally, with a boost-based 12 to 48 V, 100-W prototype, operating at 100-kHz switching frequency. A comparison with a time-optimal controller shows that the introduced programmable-deviation system results in up to 1.9 times smaller voltage deviation while limiting component stress.
A design of a new hybrid-type digital pulsewidth modulator (DPWM) with a wide frequency range of 1000 : 1, from 10 kHz to 10 MHz, is presented. The proposed DPWM has the maximum duty-cycle resolution of 11 bits and consumes the power of 17.5 mu W at 10 kHz and 2.36 mW at 10 MHz, respectively. The proposed DPWM realizes the upper 5-bit resolution using a programmable digital counter and the lower 6-bit resolution using a current-integrating-type phase interpolator, employing an M2M-ladder current-steering digital-to-analog converter for low power consumption. The operating clock is generated in on-chip using a relaxation oscillator. The prototype integrated circuit fabricated in a 0.25-mu m high-voltage complementary metal-oxide-semiconductor demonstrates that the proposed DPWM maintains a good linearity across the entire operating range.
The nonideal effects of the comparator and dead time in a synchronous controlled dc-dc converter adversely affect the stability of a four-switch noninverting-buck-boost (NIBB) converter. The pulse-skipping phenomenon occurs in the mode-transition region near the boundary between the step-down and step-up regions, and this phenomenon leads to an unstable output voltage and an unpredictable output voltage ripple. However, these two results may damage the entire power system and application system. This brief proposes an enhanced duty-cycle-overlap control technique for a digitally controlled NIBB converter. The proposed technique offers two duty cycle limitations for various conditions in the mode-transition region and ensures the stability of the digital controller and output voltage. Moreover, this technique involves combining the duty cycles of both step-down and step-upmodes for deriving an accurate value of the output voltage. The experimental results derived from a digital controller implemented through a field-programmable-gate-array-based platform revealed that the output voltage of the NIBB converter was stable throughout the transition region. The observed input voltage of the converter, provided by a Li-ion battery, was 2.5-4.5 V, and the output voltage was typically 3.3 V, which is suitable for communication systems, audio systems, and I/O pad power supplies. The switching frequency was 1 MHz, and the maximum load current was 500 mA.
In this technical note, we first present an adaptive distributed observer for a discrete-time leader system. This adaptive distributed observer will provide, to each follower, not only the estimation of the leader's signal, but also the estimation of the leader's system matrix. Then, based on the estimation of the matrix S, we devise a discrete adaptive algorithm to calculate the solution to the regulator equations associated with each follower, and obtain an estimated feedforward control gain. Finally, we solve the cooperative output regulation problem for discrete-time linear multi-agent systems by both state feedback and output feedback adaptive distributed control laws utilizing the adaptive distributed observer.
The aim of this paper is to present a superior transient response of a digital peak current mode dc-dc converter in order to address input voltage fluctuation. In the dc power feeding system, a quick response is important for not only load fluctuation but also input voltage fluctuation. Since the proposed peak current mode control method can detect the peak current in real time, the transient response can improve compared with the conventional digital voltage mode PID control. As a result, the convergence time and undershoot of output voltage is suppressed by more than 50%.
Phase-shift modulation (PSM) is a commonly used technique for controlling the active power flow in resonant dc-ac and dc-dc converters. Although traditionally developed as an analog modulation scheme, PSM is being increasingly implemented digitally in conjunction with advanced multivariable digital controllers and online efficiency optimization algorithms. While analog PSM is known not to introduce additional dynamics from a small-signal standpoint, the analysis disclosed in this study indicates that discrete-time, or uniformly sampled, PSM introduces a transport delay of small-signal nature. Furthermore, and in close analogy with the theory of uniformly sampled pulse width modulators, such delay depends on the modulator carrier type as well as on the converter operating point. This paper first clarifies the modeling procedure for describing the small-signal dynamics of uniformly sampled phase-shift modulators. Second, it provides an extension of the traditional phasor modeling to digital phase-controlled converters, allowing to account for the additional modulator dynamics in the design of the closed-loop compensation. Theoretical findings are validated via simulation and experimental results.
This paper explores the performance of a DC-DC converter based with current mode controller photovoltaic (PV) simulator which emulates the output characteristics of a real PV module. A portable PV simulator prototype of 85 W is examined in terms of its steady state IV curve matching capacity and the convergence time corresponding to step change in current source load, voltage source load, and insolation levels. The current voltage (IV) characteristics of the PV module are implemented as a look-up-table (LUT) which determines the reference output current from measured output voltage. A Thevenin Equivalent Method approach to PV arrays analysis is also included in order to model the small-signal linearized characteristics. Extensive simulation results obtained in MAT LAB are included to show that the PV simulator can work in most situations as a real PV module. Preliminary experimental results verify performance with current-source and voltage-source loads
How to control and monitor devices when I'm not at home? It is a question that until the last century did not have an overwhelming answer from the engineering field. The technological development of recent years has allowed us to perform this task by using software and hardware tools: monitoring different devices from our smart phone comes down to simply downloading an app or entering a website. This article presents an application that can be example of how to answer the aforementioned question.
This paper proposes a new approach of Field Programmable Gate Array (FPGA) controlled digital implementation of shunt active power filter (SAPF) under steady state and dynamic operations. Typical implementations of SAPF uses microprocessor and digital signal processor (DSP) but it limited for complex algorithm structure, absence of feedback loop delays and their cost can be exceed the benefit they bring. In this paper, the hardware resources of an FPGA are configured and implemented in order to overcome conventional microcontroller or digital signal processor implementations. This proposed FPGA digital implementation scheme has very less execution time and boosts the overall performance of the system. The FPGA controller integrates the entire control algorithm of an SAPF, including synchronous reference frame transformation, phase locked loop, low pass filter and inverter current controller etc. All these required algorithms are implemented with a single all-on chip FPGA module which provides freedom to reconfigure for any other applications. The entire algorithm is coded, processed and simulated using Xilinx 12.1 ISE suite to estimate the advantages of the proposed system. The coded algorithm is also defused on a single all-on-chip Xilinx Spartan 3A DSP-XC3SD1800 laboratory prototype and experimental results thus obtained match with simulated counterparts under the dynamic state and steady state operating conditions.
This paper describes the implementation of a second order sliding mode (SOSM) controller for a practical point-of-load (POL) power supply with realistic values of output capacitor equivalent series resistance (ESR) and equivalent series inductance (ESL). The SOSM control presented in this paper results in fast transient responses, has a current limiting feature, supports light load operation, and achieves constant frequency steady state operation. Experimental results are given for a 2.5 V - 5.5 V input, 0.6 V - 1.5 V output, 3 A prototype.
A new generator control unit (GCU) must be designed to work in a wide frequency range in order to obtain better control performance in variable frequency AC power system. Control algorithms make improvements in terms of determining the control parameters and analyze the influence of the controller parameters on system stability, and compensate for the loss of signals generated in the conditioning process. This paper compares the pros and cons of different RMS algorithms and determine the final RMS calculation scheme. Test results show a considerable performance improvement for the proposed design in dynamic performance and adjustment precision.
This paper discusses a discrete-time loop shaping algorithm for servo enhancement at multiple wide frequency bands. Such design considerations are motivated by a large class of practical control problems such as vibration rejection, active noise control, and periodical reference tracking; as well as recent novel challenges that demand new design in the servo technologies. A pseudo Youla-Kucera parameterization scheme is proposed using the inverse system model to bring enhanced control at selected local frequency regions. Design methodologies are created to control the waterbed amplifications that come from the fundamental limitations of feedback control. Finally, simulation and experimental verification are conducted in precision control and semiconductor manufacturing. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents the design and implementation of a digital control system for modular multilevel converters, based on digital signal processors. To achieve higher system control reliability and multi-functionality, the proposed architecture has been built with an effective split of the control tasks involved between a master controller and six slave controllers, one for each of the six arms of the converter. The master controller handles energy flow within the converter and user communication using Ethernet and universal serial bus. Each slave controller handles capacitors voltages balancing within the arm. Intercommunication between the different boards is achieved mainly through optical fiber and inter integrated circuit bus. Experiments have been carried out to verify the effectiveness of this architecture.
Digital micro-controllers/processors enable the costeffective control of grid-connected power converter systems in terms of system monitoring, signal processing (e.g., grid synchronization), control (e.g., grid current and voltage control), etc. Normally, the control is implemented in a micro-controller/processor with a fixed sampling rate considering the cost and complexity, where the number of unit delays that have been adopted should be an integer. For instance, in conventional digital control systems, a single-phase T/4 Delay Phase-Locked Loop (PLL) system takes 50 unit delays (i.e., in a 50-Hz system with a sampling frequency of 10-kHz) to create a 90 degrees-lagging voltage in order to achieve the grid synchronization with the orthogonal voltage system. However, in practice, the grid frequency is a time-variant parameter due to various eventualities, and thus rounding the number of the unit delays for the T/4 Delay PLL system should be done in its implementation. This process will result in performance degradation in the digital control system, as the exactly required number of delays is not realized. Hence, in this paper, a Virtual Unit Delay (VUD) has been proposed to address such challenges to the digital T/4 Delay PLL system. The proposed VUD adopts linear interpolation polynomial to approximate the fractional delay induced by the varying grid frequency in such a way that the control performance is enhanced. The proposed VUD has been demonstrated on a digitally controlled T/4 Delay PLL system. Experimental results have confirmed the effectiveness of the proposal.
Our planet is gradually moving towards an urbanized world. Modern urban agglomerations tend to turn nowadays into advanced information hubs supporting a smart management of dynamic urban systems. The currently popular notion of 'smart cities' aims to provide a new perspective for sustainable and high-performance strategies of city stakeholders in our 'urban century'. In this context, digital information technology provides a new tool for efficient and effective management and planning of urban space, inter alia in the field of transportation, environment, public facilities or advanced service provision to citizens. This paper aims to offer, first, a concise overview of the emerging opportunities of information and communication technology (ICT) for smart urban policy; digital technology in particular, appears to provide novel pathways for modern planning strategies in smart cities. Against this background, the paper sketches out the complex force field of global urbanisation phenomena and highlights the data and information needs for strategic planning of cities (using inter alia as a framework the so-called 'urban piazza' strategy framework). Secondly, various new decision support tools that are currently emerging and that offer a new promising scope for handling complex urban management issues (for instance, on accessibility, congestion, safety or sustainability) are briefly presented. And finally, the potential of such digital data systems for urban management and policy is concisely illustrated by means of some recent applications in the area of smartphone data systems. The paper concludes with a discussion of the challenges ahead for urban policy, inter alia by paying attention to institutional and governance aspects of 'big digital data' management in urban systems. (C) 2016 Elsevier Ltd. All rights reserved.
Various versions of a typical control panels are experimentally analyzed both from the effectiveness and efficiency point of view. The stimuli differed in objects' locations within a panel, and the type of the expected response to the presented stimuli. The results of users' performance are investigated using classical analyses of variance. Moreover, visual activity of all examined persons gathered by means of eye tracking system were presented and formally analyzed.
Quantitative PCR(qPCR) is an important tool in pathogen detection. However, the use of different qPCR components, calibration materials and DNA extraction methods reduces comparability between laboratories, which can result in false diagnosis and discrepancies in patient care. The wider establishment of a metrological framework for nucleic acid tests could improve the degree of standardisation of pathogen detection and the quantification methods applied in the clinical context. To achieve this, accurate methods need to be developed and implemented as reference measurement procedures, and to facilitate characterisation of suitable certified reference materials. Digital PCR(dPCR) has already been used for pathogen quantification by analysing nucleic acids. Although dPCR has the potential to provide robust and accurate quantification of nucleic acids, further assessment of its actual performance characteristics is needed before it can be implemented in a metrological framework, and to allow adequate estimation of measurement uncertainties. Here, four laboratories demonstrated reproducibility(expanded measurement uncertainties below 15%) of dPCR for quantification of DNA from human cytomegalovirus, with no calibration to a common reference material. Using whole-virus material and extracted DNA, an intermediate precision(coefficients of variation below 25%) between three consecutive experiments was noted. Furthermore, discrepancies in estimated mean DNA copy number concentrations between laboratories were less than twofold, with DNA extraction as the main source of variability. These data demonstrate that dPCR offers a repeatable and reproducible method for quantification of viral DNA, and due to its satisfactory performance should be considered as candidate for reference methods for implementation in a metrological framework.
Digital PCR (dPCR) is a powerful method for the absolute quantification and rare mutation detection of nucleic acids. However, the available dPCR platforms require either expensive instruments or complicated operation, which limit their extensive application. This paper describes a robust self-partition chip to perform dPCR in a very simple and inexpensive format. The chip is constructed by sandwiching a micromolded surfactant-doped PDMS layer between two glass slides, containing 10,000 reaction compartments (0.785 nL each). The two simple strategies, "glass-PDMS-glass" sandwich configuration and surfactant-doped surface modification, are used to enhance PCR compatibility and enable efficient amplification in the chip by minimizing water loss and nonspecific adsorption of protein. Furthermore, powered by pre-degassing of its PDMS substrate and an attached PDMS slab, the chip autonomously loads and partitions sample into a high-density array of microwells for performing dPCR analysis. We evaluated the quantitative capabilities of the dPCR chip by measuring a ten-fold serial dilution of genomic DNA from lung cancer cell line H1975. Finally, we also demonstrate its feasibility in the accurate measurement of small copy number variations, which exhibited better accuracy than real-time quantitative PCR (qPCR). Such simple and low-cost platform promises to accelerate the widespread use of dPCR. (C) 2017 Elsevier B.V. All rights reserved.
A wide-swing optical modulator driver is implemented in 0.13-mu m SiGe-BiCMOS using a three-stage distributed amplifier with a digital input line. Measurements demonstrate 6-Vp-p differential output, symmetric 6-ps (min) rise/fall times, 333-fs (rms) additive jitter, and better than 20-dB output return loss (S-11) below 58 GHz. Full output swing with adjustable (6-12 ps) rise/fall times is realized after a three-step calibration sequence facilitated by an on-chip energy detector and digital control. The circuit supports 28-48-Gb/s external data sources, or 2(11) -1 PRBS and 1-0 internal data generators for calibration and characterization respectively. The 3-mm(2) driver IC (1.8-mm(2) active area) consumes 1.92 W from + 5/-2.5-V supplies.
Proportional Integral Differentiator (PID) is widely used in industrial control applications; Digital PID is complicated and consists of many stages. This paper introduces the design of an analog PID controller by using single active element and implemented in 0.18 mu m CMOS technology. PID is tested by using three structures: Two stage Operational Amplifier with common source buffer stage; Folded cascade Operational Transconductance Amplifier and with a second generation Current Conveyer CCII+. The results taken from the three methods are compared by using both the frequency response and the transient response parameters.
A novel digital envelope modulator for envelope tracking radio frequency power amplifier is presented in this paper. The proposed modulator consists of a parallel combination of linear class AB and switching class D power amplifiers that are controlled digitally. In the previous analog architectures, the requirements needed for the AB operational amplifier such as high-current driving capability, high bandwidth and large output swing is usually obtainable at high overall static power dissipation. The digitally controlled power opamp presented here not only provides the aforementioned requirements but also reduces power dissipation compared with previous work. Furthermore, the digital control of the modulator makes it adaptive to the input signal variations in comparison with conventional analog parallel hybrid envelope modulators. The digital processor of the modulator is evaluated with a 45-nm complementary metal oxide semiconductor technology. The overall power consumption of the digital processor is around 142mW at 1.5-GHz clock frequency. As an application, the designed digital class AB is incorporated in a complete envelope modulator architecture. The overall efficiency of the modulator, including the digital processor power consumption, is around 82% at an average 32dBm output power for a 5-MHz input signal. Copyright (c) 2015 John Wiley & Sons, Ltd.
With the development of science and technology and the formation of a comprehensive multidisciplinary technology. The emergence of new permanent magnetic actuator and electronic operation of synchronous technology in the field of pressure to achieve a hardware basis. In order to meet the high reliability of the vacuum circuit breaker operation, our country is in-depth study, and gradually promote and electronic control systems match the permanent mechanism. In this article, we have the key technology of digital signal processing theory research motor and motor control. Experimental results show the effectiveness of the method, to better reflect the characteristics of the digital control system for digitizing motion brushless DC motor control engineering applications useful to explore and try.
This paper presents a novel control circuit that eliminates signal overshoot inherent to digital step attenuators (DSA) during state transitions. With the addition of digital delay elements, transitions from attenuation state to insertion loss state is delayed with respect to the transition from the insertion loss state to the attenuation state. This prevents unintended signal leakage to the output, eliminating possible signal overshoot. Since this novel technique achieves signal overshoot suppression with a simple addition to the digital control circuit, it is area efficient, and can be applied to any digital attenuator without degrading its RF performance. To present its effectiveness, the proposed technique is employed in a 6-bit DSA. The resulting reduced-overshoot DSA is manufactured in a commercial 0.18 mu m Silicon-On-Insulator (SOI) process. Measurement results show that this technique successfully suppresses the signal overshoot to less than 0.2 dB.
With the development of power electronic technology, the control technology of power electronic device is becoming more and more complicated. The switching power supply is a indispensable component in modern power electronic equipment. Its quality and size have a direct impact on the whole performance of electronic equipment. Digital control technology and the applications of FPGA have become a new research hotspot in the field of power electronics. Digital control can reduce the aging of the device and the impact of temperature drift on the accuracy of the convenient. This paper studies the digital switching power supply based on FPGA and points out the system structure of the system.
A novel integrated fault diagnosis method of 8 bit Digital to Analog Converter (DAC) circuit is presented in our paper. The circuit is based on the one presented in the IEEE 1997 International Test Conference (ITC'97). The gain waveforms of faulty and faults free (Golden) circuits as well as internal node voltages of two stage CMOS Operational Amplifier is used to detect the faults. An assembled fault detection procedure is introduced along with its localization and percentage of detectable faults estimation using HSPICE and MATLAB. This type of test is defined minutely accurate and effectiveness of it in detecting faulty circuit is evaluated.
For any wine estate, there is a need to demarcate homogeneous within-vineyard zones ('terroirs') so as to manage grape production, which depends on vine biological condition. Until now, the studies performing digital zoning of terroirs have relied on recent spatial data and scant attention has been paid to ancient geoinformation likely to retrace past biological condition of vines and especially occurrence of vine mortality. Is vine mortality characterized by recurrent and specific patterns and if so, are these patterns related to terroir units and/or past landuse? This study aimed at performing a historical and spatial tracing of vine mortality patterns using a long time-series of aerial survey images (1947-2010), in combination with recent data: soil apparent electrical conductivity EM38 measurements, very high resolution Pleiades satellite images, and a detailed field survey. Within a 6 ha-estate in the Southern Rhone Valley, landuse and planting history were retraced and the map of missing vines frequency was constructed from the whole time series including a 2015-Pleiades panchromatic band. Within-field terroir units were obtained from a support vector machine classifier computed on the spectral bands and NDVI of Pleiades images, EM38 data and morphometric data. Repeated spatial patterns of missing vines were highlighted throughout several plantings, uprootings, and vine replacements, and appeared to match some within-field terroir units, being explained by their specific soil characteristics, vine/soil management choices and the past landuse of the 1940s. Missing vines frequency was spatially correlated with topsoil CaCO3 content, and negatively correlated with topsoil iron, clay, total N, organic C contents and NDVI. A retrospective spatio-temporal assessment of terroir therefore brings a renewed focus on some key parameters for maintaining a sustainable grape production. (C) 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license.
This paper presents an innovative variable regulated high voltage power supply (VRHVPS). It has an output voltage ranging from 0V to 500V, for a maximum current of 0.25A. It consists of a switched mode power supply (SMPS) followed by a linear regulator with a power supply rejection ratio (PSSR) of 58dB. The digital control module consists of an 8bit microcontroller, a small digital display, an isolated inter-integrated-circuit ((IC)-C-2) interface with an isolated hall sensor as a current sensor and 12-bit analog to digital converters (ADC) to read the output voltage and current, also a 12bit digital to analog converter (DAC) which controls the linear regulator's output voltage.
Theorists of post capitalism have recently argued for a more or less inevitable end to capitalism. They assume that private accumulation is systematically blocked by the inability of capitalist corporations to create revenues by setting prices as they lose control over the reproduction of their commodities and that in this process, capitalist labour will eventually disappear. Drawing on a case study of Amazon and thoughts on the policies of other leading digital corporations, we challenge these assumptions. Key corporate players of digitization are trying to become powerful monopolies and have partly succeeded in doing so, using the network effects and scaling opportunities of digital goods and building socio-technical ecosystems. These strategies have led to the development of in part isomorphic structures, hence creating a situation of oligopolistic market competition. We draw on basic assumptions of monopoly capital theory to argue that in this situation labour process rationalization becomes key to the corporation's competitive strategies. We see the expansion of digital control and the organizational structures applied by key corporate players of the digital economy as evidence for the expansion of capitalist labour, not its reduction.
Digitally controlled oscillators are the main cores in all-digital phase-locked loops (ADPLL), which are important for determining the range of frequency and power consumption in ADPLLs. In the conventional digitally controlled oscillator (DCO) designs, one single band of operation is assigned to the DCO. The following paper presents a new approach in the design of DCOs, which works in dual-band and wide-band modes with a control unit. In dual-band mode, the DCO works in two different ranges of frequencies simultaneously via digital control bits. The wide-band DCO (WBDCO) works in one wider range of frequencies consecutively. It seems that in the wide-band DCO, the gap width for the dual-band DCO (DBDCO) is zero. The previously mentioned designs allow the designer to have standard frequencies with the help of direct or multiplied frequencies. So, we can have a trade-off between power and performance. This means that we can have low power consumption in low-frequency applications and vice versa. The proposed designs are based on using digitally controlled capacitors, current starving gates and Schmitt triggers in critical points of the DCO loop, while preserving coarse and fine tunings. The non-delay linearity factors are clearly investigated and resolved with the use of a new combined control unit. The simulations of the proposed designs are performed in Hspice with a voltage of v in 180 nm CMOS technology for 64- and 128-bit input coarse codes. Our simulation and evaluation results showed that in the dual-band DCO, a 14.8 ps jitter was calculated at 134 MHz with 1.2131 mW power consumption, while in the wide band with overlap mode, a 68.7 ps jitter was measured at 184.61 MHz with 1.604 mW power consumption. Our designs are proper for reconfigurable and multi-standard ADPLL designs.
Background: Dignity therapy is psychotherapy to relieve psychological and existential distress in patients at the end of life. Little is known about its effect. Aim: To analyse the outcomes of dignity therapy in patients with advanced life-threatening diseases. Design: Systematic review was conducted. Three authors extracted data of the articles and evaluated quality using Critical Appraisal Skills Programme. Data were synthesized, considering study objectives. Data sources: PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were 2002 (year of dignity therapy development) to January 2016. Dignity therapy' was used as search term. Studies with patients with advanced life-threatening diseases were included. Results: Of 121 studies, 28 were included. Quality of studies is high. Results were grouped into effectiveness, satisfaction, suitability and feasibility, and adaptability to different diseases and cultures. Two of five randomized control trials applied dignity therapy to patients with high levels of baseline psychological distress. One showed statistically significant decrease on patients' anxiety and depression scores over time. The other showed statistical decrease on anxiety scores pre-post dignity therapy, not on depression. Nonrandomized studies suggested statistically significant improvements in existential and psychosocial measurements. Patients, relatives and professionals perceived it improved end-of-life experience. Conclusion: Evidence suggests that dignity therapy is beneficial. One randomized controlled trial with patients with high levels of psychological distress shows DT efficacy in anxiety and depression scores. Other design studies report beneficial outcomes in terms of end-of-life experience. Further research should understand how dignity therapy functions to establish a means for measuring its impact and assessing whether high level of distress patients can benefit most from this therapy.
Background. After long-term treatment with continuous ambulatory peritoneal dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal mesothelial cells (PMCs) participate in the inflammatory reactions in the peritoneal cavity, and transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 beta (IL-1 beta) are involved in peritoneal fibrosis. Diltiazem is used frequently in patients with CAPD to treat hypertension. The objectives of this study were to examine the effects of diltiazem on collagen- and IL-1 beta-induced TGF-beta 1 production on human PMCs and the signalling pathway of diltiazem in this induction. Methods. Human PMCs were cultured from the enzymatic disaggregation of human omentum. Collagen synthesis was measured by [H-3]proline incorporation into pepsin-resistant, salt-precipitated collagen. The expression of collagen I and III, and TGF-beta 1 mRNA was evaluated by northern blotting. The production of TGF-beta 1 by human PMCs was measured by immunoassay. The changes of intracellular calcium level after adding Fura-2-AM were measured by fluorescence spectrophotometry. Western blotting was used to assess mitogen-activated protein kinase (MAPK) signalling proteins. Results. We found that diltiazem (< 0.2 mM) inhibited collagen I and III mRNA expression and collagen syntheses on a dose-dependent basis. Diltiazem (0.2 mM) suppressed IL-1 beta- (5 ng/ml) induced TGF-beta 1 production on human PMCs at both the protein and mRNA levels. Diltiazem (0.2 mM) also inhibited IL-1 beta- (5 ng/ml) induced collagen I and III mRNA expression. Intracellular calcium levels did not change after the treatment with diltiazem, IL-1 beta or both. The IL-1 beta-treated human PMCs increased phospho-JNK (stress-activated c-Jun N-terminal kinase) and phospho-p38 MAPK expression, while diltiazem could suppress this phenomenon. Conclusions. Diltiazem suppressed collagen synthesis of human PMCs and inhibited IL-1 beta-induced TGF-beta 1 production on human PMCs. This signalling transduction may be through p38 MAPK and JNK pathways instead of intracellular calcium. These results suggest diltiazem to be a potential therapeutic regimen in preventing peritoneal fibrosis and support further in vivo studies.
Recently, graph-based dimensionality reduction methods have attracted much attention due to their widely applications in many practical tasks such as image classification and data clustering. However, an inappropriate graph which cannot accurately reflect the underlying structure and distribution of input data will dramatically deteriorate the performances of these methods. In this paper, we propose a novel algorithm termed Locality Constrained Graph Optimization Dimensionality Reduction (LC-GODR) to address the limitations of existing graph-based dimensionality reduction methods. Firstly, unlike most graph-based dimensionality reduction methods in which the graphs are constructed in advance and kept unchanged during dimensionality reduction, our LC-GODR combines the graph optimization and projection matrix learning into a joint framework. Therefore, the graph in the proposed algorithm can be adaptively updated during the procedure of dimensionality reduction. Secondly, through introducing the locality constraints into our LC-GODR, the local information of high-dimensional input data can be discovered and well preserved, which makes the proposed algorithm distinct from other graph optimization based dimensionality reduction methods. Moreover, an effective updating scheme is also provided to solve the proposed LC-GODR. Extensive experiments on two UCI and five image databases are conducted to demonstrate the effectiveness of our algorithm. The experimental results indicate that the proposed LC-GODR outperforms other related methods. (C) 2017 Elsevier B.V. All rights reserved.
Dimethyl sulfoxide (DMSO) is an anti-inflammatory, antibacterial, analgesic drug widely used to treat several diseases as reported in the literature. It has a detractive effect on collagen deposition in the abnormal tissue. This study aimed to investigate the possible therapeutic effects of DMSO on hypertrophic scar formation in rabbits. Twenty-four New Zealand male albino rabbits were randomly divided into four groups: control, sham, DMSO, and TRA (triamcinolone acetonide). Except the control group, punch biopsy defects were created on each animal's right ear. Following the hypertrophic scar formation on day 28, intralesional DMSO and triamcinolone acetonide were administered once a week for 4 weeks into these scars of the DMSO and TRA groups, respectively. No therapeutic agent was administered to the control and sham groups. One week after the last injection, ear samples were collected for histopathological, immunohistochemical, and real-time polymerase chain reaction gene expression analyses. Histopathological examination revealed that the epithelium in the DMSO group was thicker than that in the control and TRA groups, but thinner than that in the sham group. Connective tissue thickness and vascularity level of the sham group were higher than those of the control, DMSO, and TRA groups. The collagen type I immunoreactivity level of the sham and TRA groups was higher than those of the control and DMSO groups. The collagen type III immunoreactivity level was higher in the sham group than in all other groups. Collagen type I/type III immunoreactivity ratios were lower in the DMSO group. The alignment of collagen fibers was normal in the DMSO group, but was irregular in the sham and TRA groups. The collagen type I gene expression levels of the DMSO and TRA groups were lower than that of the sham group. Collagen type III and IFN-gamma mRNA expression levels were almost similar among the groups. TGF-1 beta mRNA expression levels were higher in the DMSO and TRA groups than in the control and sham groups. On the basis of the results, it can be concluded that intralesional administration of DMSO decreases hypertrophic scar formation easily and safely. (C) 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.
Fresh fruit of longan (Dimocarpus longan Lour.) are susceptible to pericarp browning and aril breakdown. Aril breakdown in longan fruit is regarded as one of the most important factors reducing quality and shortening storage life of the fruit. To better understand the molecular mechanism of aril breakdown, the expression patterns of three expansin (EXP) and three xyloglucan endotransglucosylase (XET) genes in relation to the aril breakdown of longan fruit stored at room temperature (25 degrees C) or low temperature (4 degrees C) were investigated. The results showed that aril breakdown index increased progressively during storage at 25 and at 4 degrees C. Northern blotting analysis revealed that the accumulations of three EXP and three XET genes exhibited differential characteristics with the occurrence of aril breakdown. During storage at 25 degrees C, the accumulations of Dl-XET3 increased after 1 day, suggesting that Dl-XET3 correlated well with the early aril breakdown, while Dl-EXP3 together with Dl-XET1 and Dl-XET2 was involved in later aril breakdown. However, expression of Dl-XET1 and Dl-XET2 could be mainly involved in aril breakdown of longan fruit stored at 4 degrees C. In addition, Dl-EXP2, whose accumulation increased sharply when longan fruit were transferred from low temperature to room temperature within 12 hours, was related to the aril breakdown in this storage period. These data indicated that Dl-EXPs and Dl-XETs were closely related to aril breakdown in longan fruit.
A biofilm-forming strain of Pichia fermentans was found to be a very strong antagonist against brown rot and grey mold in artificially wounded apple fruit when co-inoculated with either Monilinia fructicola or Botrytis cinerea, respectively. The same strain of yeast, however, was an aggressive pathogen when inoculated on peach fruit, causing rot of fruit tissues, even in the absence of other pathogens. Optical and scanning electron microscopy showed that P. fermentans produces only yeast-like shaped cells during colonization of apple tissue, while exhibiting pseudohyphal growth on peach tissue. A rapid subtractive hybridization approach (RaSH) was used to identify differentially expressed genes in the pathogenic form of P. fermentans by comparing the cDNA of P. fermentans sampled after 24 hours growth on apple with the cDNA of the same strain grown 24 hours on peach fruit. A total of 450 clones were analysed by a reverse Northern Blotting technique, yielding some fragments which were significantly expressed on peach but less on apple tissue. These sequences were compared to the available genome sequences of another dimorphic yeast, Candida albicans, and homologous genes were identified. The relationship between these genes, dimorphism, and pathogenicity will be discussed.
During the domestication of canids, humans have selected for particular traits and selected against others. Wild canids and phylogenetically primitive breeds might then be expected to show less 'desirable' traits than more recently derived European breeds of dog. In order to examine this, we divided domestic dog breeds according to their apparent genetic relatedness to the wolf, and compared them to a wild canid, the dingo, using a validated behavioural assessment tool (C-BARQ). Our sample included 49 dingoes, 6935 modern dogs, and 673 ancient dogs. Overall, a number of differences were discovered between the breed groups, after accounting for demographic effects and variability between breeds. Dingoes were significantly less trainable than both ancient and modern dogs, and displayed greater stranger-directed fear and non-social fear than modern dogs. Dingoes were also more prone to escaping/roaming and urinating against objects than modern dogs, and tended to exhibit compulsive 'staring' and rolling in animal droppings more than both ancient and modern dogs. Using a multivariate test, we found that dingoes represented a significant outlier from the range of typical between-breed variation of domesticated dogs. Taken together, these results provide some evidence that (1) selective processes during domestication are reflected in the behaviour of dog breeds, and (2) primitive breed behaviour tends to reflect earlier and different selection pressures (natural rather that artificial selection). (C) 2016 Elsevier B.V. All rights reserved.
Karenia brevis is the Florida red tide dinoflagellate responsible for detrimental effects on human and environmental health through the production of brevetoxins. Brevetoxins are thought to be synthesized by a polyketide synthase ( PKS) complex, but the gene cluster for this PKS has yet to be identified. Here, eight PKS transcripts were identified in K. brevis by high throughput cDNA library screening. Full length sequences were obtained through 30 and 50 RACE, which demonstrated the presence of polyadenylation, 30-UTRs, and an identical dinoflagellate-specific spliced leader sequence at the 50 end of PKS transcripts. Six transcripts encoded for individual ketosynthase (KS) domains, one ketoreductase (KR), and one transcript encoded both acyl carrier protein (ACP) and KS domains. Transcript lengths ranged from 1875 to 3397 nucleotides, based on sequence analysis, and were confirmed by northern blotting. Baysian phylogenetic analysis of the K. brevis KS domains placed them well within the protist type I PKS clade. Thus although most similar to type I modular PKSs, the presence of individual catalytic domains on separate transcripts suggests a protein structure more similar to type II PKSs, in which each catalytic domain resides on an individual protein. These results identify an unprecedented PKS structure in a toxic dinoflagellate. Published by Elsevier GmbH.
Dinoflagellates are key species in marine environments, but they remain poorly understood in part because of their large, complex genomes, unique molecular biology, and unresolved in-group relationships. We created a taxonomically representative dataset of dinoflagellate transcriptomes and used this to infer a strongly supported phylogeny to map major morphological and molecular transitions in dinoflagellate evolution. Our results show an early-branching position of Noctiluca, monophyly of thecate (plate-bearing) dinoflagellates, and paraphyly of athecate ones. This represents unambiguous phylogenetic evidence for a single origin of the group's cellulosic theca, which we show coincided with a radiation of cellulases implicated in cell division. By integrating dinoflagellate molecular, fossil, and biogeochemical evidence, we propose a revised model for the evolution of thecal tabulations and suggest that the late acquisition of dinosterol in the group is inconsistent with dinoflagellates being the source of this biomarker in pre-Mesozoic strata. Three distantly related, fundamentally nonphotosynthetic dinoflagellates, Noctiluca, Oxyrrhis, and Dinophysis, contain cryptic plastidial metabolisms and lack alternative cytosolic pathways, suggesting that all free-living dinoflagellates are metabolically dependent on plastids. This finding led us to propose general mechanisms of dependency on plastid organelles in eukaryotes that have lost photosynthesis; it also suggests that the evolutionary origin of bioluminescence in nonphotosynthetic dinoflagellates may be linked to plastidic tetrapyrrole biosynthesis. Finally, we use our phylogenetic framework to show that dinoflagellate nuclei have recruited DNA-binding proteins in three distinct evolutionary waves, which included two independent acquisitions of bacterial histone-like proteins.
Two Keggin-type polyoxometalates (POMs) containing glycine, (HGly)(3)PW12O40 and (HGly)(4)SiW12O40, were synthesized and evaluated as mushroom tyrosinase inhibitors. The spectrophotometric method results showed that both (HGly)(3)PW12O40 and (HGly)(4)SiW12O40 could strongly inhibit the diphenolase activity of the tyrosinase and that their inhibition mechanisms were reversible. Their half-inhibition concentration values were estimated to be 1.55 and 1.39mmol/L, respectively. The inhibition kinetics analysis by Lineweaver-Burk plots indicated that (HGly)(3)PW12O40 was an uncompetitive inhibitor with K-IS=0.046mmol/L, whereas (HGly)(4)SiW12O40 was a noncompetitive inhibitor with K-I=K-IS=2.17mmol/L. This study may help to extend the application of POMs in the fields of medicine and food preservation. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Both cDNA and a genomic DNA fragment encoding a new potato proteinase inhibitor II were isolated from a diploid potato IVP101 (Solanum phurejia L.) and named PINII-2x. Nucleotide sequencing confirmed that the DNA fragment of PINII-2xwas 580 bp, including a 115-bp intron and two exons. The deduced PINII-2x protein contained an intact signal peptide and two active sites. The PINII-2x gene and its deduced PINII-2x protein had 88% and 93% homology with another tetraploid potato proteinase inhibitor II, respectively. Northern blotting analysis indicated that the mRNA of PINII-2x gene was wound induced in potato leaves. Binary vector pNAR301 and pNAR302 were constructed for rice transformation, in which the PINII-2x cDNA was driven, respectively, by rice actin I promoter (ActI) and maize ubiquitin promoter (UbiI). Via an Agrobacterium-mediated method, these two constructs were transferred into japonica rice cv. Xiushui 63. PCR and Southern blotting analysis for transgenic rice revealed the integration of the PINII-2x gene. Northern blotting analysis also confirmed transcripts of the PINII-2x gene in transgenic rice plants. Insect bioassays using stripe stem borer (Chilo suppressalis Walker) demonstrated that the average weight and body length of larvae in transgenic plants were only nearly 50% and 61% of those of larvae in control plants, respectively. These results indicate that the PINII-2x gene should be an effective insect-resistance gene and could be valuable for application in crop breeding for insect resistance.
While much research focuses on the causes and consequences of direct democracy and regime legitimacy, little attention has been paid to the potential relationship between them. In an attempt to fill this void, this paper focuses on the legal provisions for direct democracy and its use. The key argument is that possibilities for the public's direct involvement reflect high importance given to citizens, openness of the regime towards different modes of decision-making, and ways to avoid unpopular institutions. Consequently, citizens are likely to accept and support the regime, improving or maintaining its legitimacy. The cross-national analysis includes 38 European countries ranging from transition countries to established democracies. It uses bivariate statistical analysis and country-level data collected from legislation, secondary sources, and aggregate surveys.
Direct gaze is a salient social cue that affords rapid detection. A body of research suggests that direct gaze enhances performance on memory tasks (e.g., Hood, Macrae, Cole-Davies, & Dias, Developmental Science, 1, 67-71, 2003). Nonetheless, other studies highlight the disruptive effect direct gaze has on concurrent cognitive processes (e.g., Conty, Gimmig, Belletier, George, & Huguet, Cognition, 115(1), 133-139, 2010). This discrepancy raises questions about the effects direct gaze may have on concurrent memory tasks. We addressed this topic by employing a change detection paradigm, where participants retained information about the color of small sets of agents. Experiment 1 revealed that, despite the irrelevance of the agents' eye gaze to the memory task at hand, participants were worse at detecting changes when the agents looked directly at them compared to when the agents looked away. Experiment 2 showed that the disruptive effect was relatively short-lived. Prolonged presentation of direct gaze led to recovery from the initial disruption, rather than a sustained disruption on change detection performance. The present study provides the first evidence that direct gaze impairs visual working memory with a rapidly-developing yet short-lived effect even when there is no need to attend to agents' gaze.
Natural Gas Direct Injection (NGDI) engines have attracted attention of engine manufacturers because of low pollutant emissions and high efficiency. The jet structure and injector properties are control parameters for optimal mixture formation and stable combustion. Here, the jet characteristics are investigated experimentally. The natural gas jet, injected through a multi-hole injector, is visualized using Schlieren photography. The effects of injection and chamber pressures on macroscopic jet characteristics are examined. New correlations for tip speed and tip penetration are presented. Results show that reducing chamber pressure is more effective than injection pressure for increasing the jet axial penetration. Moreover, the linear relation between non-dimensional tip penetration and time is dependent on the chamber-toinjected gas density ratio. (C) 2017 Elsevier Ltd. All rights reserved.
The debate about direct perception encompasses different topics, one of which concerns the richness of the contents of perceptual experiences. Can we directly perceive only low-level properties, like edges, colors etc. (the sparse-content view), or can we perceive high-level properties and entities as well (the liberal-content view)? The aim of the paper is to defend the claim that the content of our perceptual experience can include emotions and also person impressions. Using these examples, an argument is developed to defend a liberal-content view for core examples of social cognition. This view is developed and contrasted with accounts which claim that in the case of registering another person's emotion while seeing them, we have to describe the relevant content not as the content of a perceptual experience, but of a perceptual belief. The paper defends the view that perceptual experiences can have a rich content yet remain separable from beliefs formed on the basis of the experience. How liberal and enriched the content of a perceptual experience is will depend upon the expertise a person has developed in the field. This is supported by the argument that perceptual experiences can be systematically enriched by perceiving affordances of objects, by pattern recognition or by top-down processes, as analyzed by processes of cognitive penetration or predictive coding.
Models of reciprocity imply that cheater detection is an important prerequisite for successful social exchange. Considering the fundamental role of memory in reciprocal exchange, these theories lead to the prediction that memory for cheaters should be preferentially enhanced. Here, we examine whether information of a partner's previous behaviour in an interaction is automatically retrieved when encountering the face of a partner who previously cheated or cooperated. In two studies, participants played a sequential prisoner's dilemma game with cheaters and cooperative partners. Alternating with the game blocks, participants were asked to classify the smiling or angry facial expressions of cooperators and cheaters. Both experiments revealed congruence effects, reflecting faster identification of the smiles of cooperators (Experiments 1 and 2) and faster identification of the angry facial expressions of cheaters (Experiment 2). Our study provides evidence for the automatic retrieval of the partner's behaviour in the game, regardless of whether partners cheated or cooperated, and thus provides further evidence against the cheater detection hypothesis.
The Low-level Radio Frequency (LLRF) control system for linear accelerator at Legnaro National Laboratories (LNL) of INFN is being upgraded by a new digital Radio Frequency (RF) controller. This controller is critical to keep phase, amplitude and frequency stability of the RF field in QuarterWave Resonator (QWR) cavities of the linear accelerator. These cavities work in superconducting condition. The resonance frequency of low beta cavities is 80 MHz, while medium and high beta cavities resonate at 160 MHz. Each RF controller can control at the same time eight different cavities. The RF signals picked-up from the cavities are sampled by RF ADCs. The digitized signals are fed into a field programmable gate array (FPGA) which implements the control loop. The signals processed by the FPGA are in-phase/quadrature modulated and sent to power amplifiers and hence to the cavities. The main feature of the new control system is an all-digital control loop that originates from direct sampling of the antenna RF signal. In-phase and quadrature components are obtained by a suitable choice of the undersampling frequency, while control of the field and phase in the cavity is based on a digital Complex Phase Modulator (CPM). This paper presents the FPGA firmware, the acquisition techniques and the performances of the new RF controller.
The problem of direction of arrival (DOA) estimation of non-circular (NC) signal for non-uniform linear array is investigated. A generalised-ESPRIT (GESPRIT) algorithm can be treated as an improvement of ESPRIT algorithm and the inter-elements spacing of the array geometry can be uniform or non-uniform within a half wavelength. The authors combine the GESPRIT algorithm and the NC property, and propose an NC-GESPRIT algorithm to obtain the DOAs of NC signals, which requires spectrum peak searching. Moreover, a computationally efficient search-free root NC-GESPRIT algorithm, which is based on polynomial rooting, is also proposed to depress the computational cost. The proposed NC-GESPRIT algorithms have much better estimation performance than the conventional GESPRIT algorithm and it can detect 2M-1 sources with only M sensors due to the NC property. Furthermore, the proposed algorithms can work well without estimating NC phase. The effectiveness and improvement of the proposed algorithms will be proved in the following simulation results.
Canine dirofilarioses are mosquito-borne zoonotic diseases with a continuous expansion of their geographical distribution, as a consequence of different climatic and ecological factors. Dirofilaria immitis, the aetiological agent of heartworm disease, has gained a major veterinary interest, mainly due to its severe clinical implication. In the last decades, D. repens, despite of being regarded as a less pathogenic species, regained attention due to its recognized zoonotic potential. Romania has been traditionally regarded as a non-endemic country, but recent epidemiological surveys are highlighting the presence of both D. repens and D. immitis. The present case report describes the clinical and pathological features of a natural co-infection with D. repens and D. immitis in 5 year old male Boxer from north-western Romania. Based on clinical and laboratory investigations, a diagnosis of kidney failure and chronical cystitis was established. The parasites were identified by morphology and confirmed by PCR and sequencing. To the best of our knowledge this is the first worldwide report of the ectopic presence of D. repens adults in the pelvic cavity and mesentery by natural infection and first report of the ocular localization of this parasite for Romania. The clinical and paraclinical findings suggest the implication of D. repens microfilariae in the aetiology of histopathological lesions. Further investigations are needed in order to establish the actual pathogenic potential of D. repens, a frequently neglected parasite. (C) 2017 Elsevier B.V. All rights reserved.
In the UK, child sexual exploitation (CSE) has received considerable attention in the last few years, with evidence pointing to an increased risk for young people with learning disabilities. However, no study has specifically focused on this and little is known about how best to protect, identify or support this group. This paper is based on a UK study which examined the identification of, and support for sexual exploited young people with learning disabilities. Data collection included surveys of all local authorities in the UK and of a sample of services supporting vulnerable or disabled children, in-depth interviews with 34 professional stakeholders and with 27 young people with-learning disabilities who were at risk of, or who had experienced CSE. This paper provides an overview of the study and identifies areas for improvement in policy and practice including the need for education, training and awareness raising amongst young people, their families and professionals; tackling social isolation, disempowerment and invisibility of young people with learning disabilities, and the need for full implementation of government guidance with a spotlight on this group of young people. (C) 2016 Elsevier Ltd. All rights reserved.
Children make many decisions about whether and how to disclose their performance to peers, teachers, parents and others. Previous research has found that children's disclosure declines with age and that older children and teenagers preferentially choose a peer audience for performance disclosure based on similar achievement. This research examines younger children's choice of a disclosure audience: whether young children predict that people will distinguish between peers at different achievement levels, and whether or not younger children expect preferential selections between those peers for their performance disclosure. One hundred and thirty-nine children, aged 3 to 6years, were asked about a character's disclosure of classroom performance information. At least until the age of 6years, children predicted significantly greater disclosure of failure to a high achieving peer who had been successful. When asked to predict the disclosure of success, however, children in all age groups did not discriminate between disclosing to the high-achieving or low-achieving peer. This evidence suggests that very young children may not show the same valence-matching preferences as older children and that early school ages are a critical time when children begin to adopt social norms around disclosure that impinge on possible help-seeking. Copyright (c) 2016 John Wiley & Sons, Ltd.
A discretization method is proposed for a rather general class of nonlinear continuous-time systems, which can have a piecewise-constant input, such as one under digital control via a zero-order-hold device. The resulting discrete-time model is expressed as a product of the integration-gain and the system function that governs the dynamics of the original continuous-time system. This is made possible with the use of the delta or Euler operator and makes comparisons of discrete and continuous time systems quite simple, since the difference between the two forms is concentrated into the integration-gain. This gain is determined in the paper by using the Riccati approximation of a certain gain condition that is imposed on the discretized system to be an exact model. The method is shown to produce a smaller error norm than one uses the linear approximation. Simulations are carried out for a Lotka-Volterra and an averaged van der Pol nonlinear systems to show the superior performance of the proposed model to ones known to be online computable, such as the forward-difference, Kahan's, and Mickens' methods. Insights obtained should be useful for developing digital control laws for nonlinear continuous-time systems, which is currently limited to the simplest forward-difference model.
In many wild animal populations, hosts are at risk of parasites and malnutrition and resource costs of defence may be difficult to afford. We postulate that proteins, important in homeostasis and immunity, play a complex but central role in condition dependence and resource costs of mammalian immune defence. To test this, we measured plasma concentrations of albumin, total proteins. Self-reactive antibodies and parasite-specific IgG in female Soay sheep. Using a principal component analysis, we found a new metric of condition reflecting individual variation in acquisition, assimilation and/or recycling of plasma proteins that predicted overwinter survival. Controlling for this metric, an age-dependent trade-off between antibody titres and protein reserves emerged, indicating costs of mounting an antibody response: younger individuals survived best when prioritising immunity while older individuals fared better when maintaining high-protein nutritional plane. These findings suggest fascinating roles for protein acquisition and allocation in influencing survival in wild animal populations.
Background: The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies. Methods: In this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists. The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center. Results: During the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0-5.0) years among patients assigned to disease management, and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure. Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up. Conclusions: This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care.
Wall-associated protein kinases (WAKs) are a new group of receptor-like kinases (RLK) recently identified in Arabidopsis. A cDNA encoding a novel WAK was isolated from rice and was named OsWAK1 (Oryza sativa WAK). The deduced amino acid sequence of OsWAK1 showed 27.6% identity to WAK2 from Arabidopsis. OsWAK1 not only has the ability of autophosphorylation but also can phosphorylate OsRFP1, a putative transcription regulator recently identified in rice. OsRFP1 strongly interacts with the kinase domain of OsWAK1. This demonstrated that OsWAK1 is a functional protein kinase. A fusion protein of OsWAK1 with GFP was found to be localized on the cell surface. Plasmolysis experiments further revealed OsWAK1 is associated with the cell wall. Northern blotting analysis showed that infection of the rice blast fungus, Magnaporthe oryzae significantly induced the OsWAK1 transcripts, and the accumulation of OsWAK1 mRNA occurred earlier and was more abundant in rice leaves infected with an incompatible race than with a compatible race of the blast fungus. OsWAK1 was also induced after treatment by mechanical wounding, SA and MeJA, but not by ABA. These results imply that OsWAK1 is a novel gene involved in plant defense. Furthermore, six transgenic rice lines with constitutive expression of OsWAK1 became resistant to the compatible race. However, OsWAK1 expression was undetectable in leaves, stems and flowers but very weak in roots under normal growth conditions. This provides functional evidence that induction of OsWAK1 as a novel RLK plays important roles in plant disease resistance.
Every cognitive process, including the conceptualization of some perceived facts, such as human disease states, entails both an emotional as an evaluative aspect. Regarding this, cross-cultural research has shown that there are common human value contents. Therefore, in a human phylogenetic context, it is plausible to argue that, along with the development of our language, both the hetero-perception and self-perception of some specific human states have been termed descriptively to communicate their adaptive significance. This is the case of those human states whose properties have been conceptualized, with the corresponding evaluative emotional component, as "disease". Since names are the symbols of a language that designate any type of object, either perceptual or conceptual, reviewing the etymology of terms related to "disease" could be a contribution to its elucidation. In consequence, some equivalent terms to the Spanish word enfermedad were reviewed in various Indo-European and non-Indo-European languages. From the analyzed denominations we can conclude that the different words have described the perception of human conditions as weak, evil, suffering states, etc. Therefore, there is a denotative concordance with the diseased human states in the revised cultures.
Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly transmissible vaccine poses substantial evolutionary risks, including reversion to high virulence as has been documented for the oral polio vaccine. An alternative, and far safer approach, is to rely on genetically engineered and weakly transmissible vaccines that have reduced scope for evolutionary reversion. Here, we use mathematical models to evaluate the potential efficacy of such weakly transmissible vaccines. Our results demonstrate that vaccines with even a modest ability to transmit can significantly lower the incidence of infectious disease and facilitate eradication efforts. Consequently, weakly transmissible vaccines could provide an important tool for controlling infectious disease in wild and domestic animal populations and for reducing the risks of emerging infectious disease in humans.
Lymphocyte-to-monocyte ratio (LMR) was associated with survival benefit in some types of cancer. The relationship between LMR and rectal cancer has not been investigated. We conducted a retrospective cohort study to assess the prognostic significance of LMR in patients with nonmetastatic rectal cancer. Patients with rectal cancer who underwent potentially curative resection between January 2009 and December 2013 were enrolled. The LMR was calculated from preoperative blood test by dividing the absolute lymphocyte counts by the absolute monocyte counts. The optimal cut-off value for LMR was calculated as the median value. On the basis of the cut-off value, patients were divided into 2 groups: low group and high group. A total of 543 patients with rectal cancer were eligible for this study. The median follow-up time for all patients was 55 months (range 6-85 months). The cut-off value of LMR was 5.13 and patients were divided into 2 groups: low group (LMR= 5.13). In the univariate and multivariate analysis, the LMR was not significantly associated with overall survival (OS) [hazard ratio (HR): 1.034, 95% confidence intervals (CIs): 0.682-1.566, P=0.876]. When disease-free survival (DFS) was compared, univariate and multivariate analysis also indicated that the LMR was not significantly associated with DFS (HR: 0.988, 95% CI: 0.671-1.453, P=0.950). In addition, in the subgroup analysis by tumor-node-metastasis stage, there existed no significance between LMR and OS and DFS. Although as an easy access and highly efficient laboratorial inflammatory marker, LMR cannot predict the prognosis of nonmetastatic rectal cancer patients.
The output stability of the displacement sensors is an important issue for safe operations in magnetic bearing supported high-speed rotor system. This paper proposes an effective postprocessing solution to the problems of temperature drift and synchronous measuring error for the axial displacement sensor in a 10-kW magnetically suspended motor. The proposed configuration of the axial displacement sensor consists of three probes: one pair is used to eliminate the synchronous measuring error, and the third probe is employed for the consideration of temperature drift. First, the generating mechanism of the synchronous measuring error caused by the improper assemble is presented, and an operational amplifier is proposed to obtain an accurate position of the axial center by adjusting the weights of sensing signals from one pair of probes. Then the scheme of temperature compensation using an auxiliary probe is presented. In order to obtain accurately the characteristics of temperature drift at the operating point, the detailed procedure is given to determine the temperature-drift ratio. Finally, the terms related to temperature drift and synchronous error in the final output of the displacement sensor are both eliminated. Experimental results on a magnetically suspended motor test rig show the effectiveness of the proposed solution.
1. Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein translation inhibitor approved by the US Food and Drug Administration for adult patients with chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. 2. The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72h after a single 1.25-mg/m(2) subcutaneous dose of C-14-omacetaxine in cancer patients. 3. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification. 4. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces very little unchanged omacetaxine was found and the pyrocatechol metabolite of omacetaxine, M534 and 4'-desmethyl homoharringtonine (4'-DMHHT) was the most abundant metabolites. 5. Omacetaxine was extensively metabolized, with subsequent renal and hepatic elimination of the metabolites. The low levels of the metabolites found in plasma indicate that the metabolites are unlikely to contribute materially to the efficacy and/or toxicity of omacetaxine.
Objective: This paper builds upon the analyses presented in three companion papers using data from the 2003 and 2008 cycles of the Canadian Incidence Study of Reported Child Abuse and Neglect (CIS-2003 and CIS 2008) and the Ontario Child Abuse and Neglect Data System (OCANDS) to examine disproportionality and disparity of child welfare involvement for Asian-Canadian children involved in the child welfare system. Methods: This study used CIS-2008 data adjusted by Census child population data to examine rates per 1000 and three disparity indexes (population-based disparity index [PDI], decision-based disparity index [DDI], and maltreatment-based disparity index [MDI]) to determine the representation of child maltreatment investigations for Asian-Canadian versus White-Canadian children involved in the child welfare system. Logistic regression analyses were conducted to determine the odds of case closure for substantiated child maltreatment investigations, and whether Asian ethnicity remained significant while controlling for child demographics and household composition, case characteristics, and clinical concerns. Results: This study found that Asian-Canadian children were underrepresented in the child welfare system compared to White-Canadian children (13.9 per 1000 Asian children in the Canadian population vs. 36.1 per 1000 White children in the Canadian population). Child welfare involvement for Asian-Canadian children are almost 2 times more likely to close after an investigation than White-Canadian children. The three disparity indexes (PDI, DDI, MDI) showed substantially different results with respect to the representation of child maltreatment investigations involving Asian-Canadian versus White-Canadian children for physical abuse, sexual abuse, neglect, emotional maltreatment, and exposure to domestic violence. Conclusions: Disproportionality and disparity are complex phenomena. The variation in results derived from different methods of calculating representation suggests the need for greater clarity and consistency in the definitions and methodology in examining racial disparity in child welfare research. Some methodological considerations for future child welfare research with Asian-Canadian populations were discussed. (C) 2016 Elsevier Ltd. All rights reserved
The modification of an energy-based approach called the dissipating energy flow (DEF) method is proposed, which uses data from phasor measurement units (PMUs) to trace the source of poorly damped natural and forced oscillations in power systems. The original energy-based approach (Chen et al., 2013) assumes the ability to determine steady-state values of variables measured by PMU during the transient process and that prevents the reliable use of the original method with actual PMU data. PMU data processing, proposed in the DEF method, is a key step in converting the energy-based method into a robust and automated tool for use with actual PMU data. The effectiveness of the proposed DEF method is demonstrated by testing multiple simulated cases of sustained oscillations, including both poorly damped natural and forced oscillations and more than 30 actual events in ISO New England (ISO-NE) and two events in Western Electricity Coordination Council (WECC) systems. The study also demonstrates the potential for using the DEF method to estimate the contribution of any generator to the damping of a specific oscillation mode. (C) 2016 Elsevier Ltd. All rights reserved.
Plunging water jets are used for oxygenation purposes due to their inherent advantages such as simplicity, energy efficiency, and low operational cost. Specifically, these provide an efficient gas-liquid interfacial area for dissolving oxygen in water. Oxygen transfer by plunging jets into stagnant water has received considerable attention; however, the oxygenation capacity of plunging water jets discharging into turbulent cross-flow has received limited attention. The flow characteristics such as volumetric oxygen transfer coefficient and standard oxygen transfer efficiency are evaluated considering water jet to cross-flow velocity ratio, jet fall height, cross-flow depth, and jet impact angle. Two equations are proposed for estimating the oxygen transfer rate for a single plunging jet in a turbulent cross-flow. Moreover, the dynamic behavior of the resulting two-phase air-water flow is investigated with the aid of flow visualization. (C) 2017 American Society of Civil Engineers.
Recently, wireless charging via magnetic resonance coupling has gained attention because it has the potential of efficient midrange wireless charging. Here, functions such as sensing at the transmitter and wireless communication from the target are the essential elements to realize a standard wireless charging system. Currently, the sensing and communication protocol of the hardware (i.e., the high-frequency power source and antenna configuration) compatible with wireless charging is gaining attention in terms of its cost and space reduction due to the use of common components for multiple functions. However, this protocol has the problem of narrow effective areas due to the fact that the sensing range depends on the fixed Q factor of the antenna. To overcome this problem, the concept of wide-area sensing based on a Q controllable antenna is proposed, and the effectiveness is verified through a theoretical analysis and an experiment. As a result, it is clarified that the effective area can be expanded up to a ratio of the distance g between the transmitting and receiving antennas to the inner diameter d of the antenna g/d = 5.0. (C) 2017 Wiley Periodicals, Inc.
Chongming's current energy system is highly import-dependent and the distributed energy system with high renewable energy penetration should be taken into consideration. In this paper, a simulation model based on EnergyPLAN software with 2014 as the reference year is developed to represent Chongming's present energy structure. Four future scenarios which propose different further energy constructions have been observed. Results show that reductions in primary energy consumption, electricity import, annual operating costs as well as CO2 emissions are realizable when switching to an energy system with a high share of renewable sources combining natural gas CHP (Combined Heating and Power). After preliminary discussions, the feasibility of different renewable sources penetration are analyzed through calculating the excess electricity production (CEEP). The estimated optimal combination is generated when the PV fraction is 20% while wind energy fraction is 80%. Moreover, the analyses have taken into account that several flexible techniques are needed in order to balance supply and demand and to ensure the grid voltage and frequency stabilities. As a result, through the recommended three techniques, the excess production can be avoided as far as a renewable energy input of up to nearly 60%. (C) 2016 Elsevier Ltd. All rights reserved.
Recent years, installation of photovoltaic (PV) system is active by the environmental problem and feed in tariff system. Due to PV's output fluctuation, the static var compensator (SVC) made by power electronics technology is planning to install in distribution system. The SVC is expected for maintain the voltage. But SVC differs in a theory of operation of the existing voltage controller load ratio control transformer (LRT) and step voltage regulator (SVR). Because the SVC operation makes the system impedance changes, the existing voltage controller may not operate effectively. In this study, the intelligent-control method which used the radial basis function (RBF) network is proposed. This method can reduce the effects of the SVC operation by including the performance characteristics of SVC in the conventional method. An advantage of unnecessary arrangement attention of the SVC setup node and easy cooperation with the existing equipment is obtained by applying this method.
This study examined mostly lower-middle-income Latino (37%) and African American (33%) adolescents'(N = 90, M-age = 15.90) conceptions of how U. S. wealth is and ought to be distributed, and whether these judgments are related to adolescents'views about societal and legal fairness and their immediate academic plans. Individually administered multipart interviews assessed conceptions regarding (a) actual and ideal U. S. wealth distribution and related "Rawlsian"judgments, (b) social system and legal fairness, and (c) adolescents'near-term life goals. Overall, adolescents underestimated actual levels of U. S. wealth inequality while also preferring a more egalitarian distribution than was believed to exist. Adolescents'wealth-related reasoning was mostly unrelated to other societal or personal judgments, whereas societal and legal fairness judgments were related to personal academic plans. Although adolescents had generally negative views of societal and legal fairness, having more positive fairness conceptions was related to a greater emphasis on academic plans. Compared with their younger peers, older adolescents preferred somewhat more wealth inequality for motivational and economic reasons and preferred living in a society with some inequality.
In this paper, a hypothetical district representing the typical urban districts in Hong Kong was considered and a district cooling system model was designed for this district. Mathematical models were tailor-designed for all the major district cooling system equipment to simulate the effects of changing the pumping station's configuration on the energy performance of the district cooling system. The measures included the use of multiple pumping stations and an unequal number of pumps in each station. In view of the vast number of pumping station combinations possible for analysis, a hydraulic gradient evaluation method was adopted to assist a quick assessment and exploration of those combinations that would be technically feasible. Furthermore, the energy performance of all these technically feasible combinations was evaluated to identify an optimum design that would lead to the lowest electricity consumption. Practical application: In a district cooling system where there is only one main pumping station for distributing chilled water to all the buildings in the district, the chilled water flow rate and pressure head are very high. Adding booster pumping stations can help to reduce pressure head, pump size and hence power demand of the main pumping station. In this paper, the effects of different pumping station configurations on the energy performance of a district cooling system were investigated. The configuration that could mitigate the impacts of a low delta-T on the energy performance of the district cooling system was also identified.
Pilots for the seasonal thermal energy storage of solar energy on a local basis are few in Finland, even if international demonstrations show that the utilization level of solar energy can exceed 50% of the annual local heat requirement in similar climate zones. This study presents options for heat and electricity generation based on local energy systems and utilizing seasonal thermal energy storages. Energy needs and production on Vartiosaari district in Helsinki in Finland were explored as a case area. The project studied the impacts of introducing solar thermal energy on local energy self-sufficiency and emissions from heating energy supply, if excess solar heat in the summer is stored using borehole thermal energy storage or tank storage for use in the winter. Around 60% self-sufficiency in heat production would have been achieved in the scenarios studied. In addition, carbon dioxide emissions could be reduced by around 50%, and sulphur dioxide and particulate emissions by up to 70% compared to the business-as-usual situation. (C) 2017 Elsevier Ltd. All rights reserved.
Ensemble weather predictions are introduced in the operation of district heating systems to create a heat load forecast with dynamic uncertainties. These provide a new and valuable tool for time-dependent risk assessment related to e.g. security of supply and the energy markets. As such, it is useful in both the production planning and the online operation of a modern district heating system, in particular in light of the low-temperature operation, integration of renewable energy and close interaction with the electricity markets. In this paper, a simple autoregressive forecast model with weather prediction input is used to showcase the new concept. On the study period, its performance is comparable to more complex forecast models. The total uncertainty of the heat load forecast is divided into a constant model uncertainty plus a time-dependent weather-based uncertainty. The latter varies by as much as a factor of 18 depending on the ensemble spread. As a consequence, the total forecast uncertainty varies significantly. The forecast model is applied to the operation of three heat exchanger stations. Applying an optimized temperature control can significantly lower supply temperatures compared to current operation. Improving the temperature control with dynamic time-dependent weather-based uncertainties can lower the supply temperature further and reduce heat losses to the ground. The potential benefit of using dynamic uncertainties is larger for systems with relatively smaller pumping capacities. (C) 2017 Elsevier Ltd. All rights reserved.
Wide bandgap semiconductors have been increasingly adopted to enhance the efficiency and reduce the volume of power converters, as these devices are able to switch at dozens of megahertz or even 100 megahertz with lower power losses. However, such a high frequency operation may impose a challenge to the digital control system, and the required clock frequency should be up to 100 gigahertz in high precision applications, which is difficult to realize in low-cost microprocessors such as field-programmable gate array (FPGA). Instead of using hardware-dependent high frequency clocks, an alternative solution is to utilize digital pulse-width-modulated (DPWM) dither techniques to enhance the DPWM resolution. Unfortunately, this is achieved at the expense of introducing low frequency harmonics, which may complicate the output filter and system controller design. In this paper, an optimal dither technique is proposed to enhance the resolution of DPWM power converters. The concepts of positive dither and negative dither are first proposed in this paper. Furthermore, vector diagram-based analysis indicates that with the combination of positive dithers, negative dithers and a carefully selected dither sequence, the lowest order harmonics can be completely eliminated when the dither period is multiples of six switching periods. In other cases, the proposed optimal dither technique can produce minimized lowest order harmonics. Finally, experimental results obtained from a synchronous buck converter validate the feasibility of the proposed technique.
Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness-eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep ( OR = 3.4, p < 0.0001), poor sleep quality ( OR = 2.9, p < 0.01) and daily tiredness ( OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale ( p < 0.05), Basic Nordic Sleep Questionnaire ( p < 0.0001) and Global Seasonality Score ( p < 0.01) and were also more often smokers, also during pregnancy ( p < 0.001) and reported poorer general health ( p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood ( OR = 1.5, p < 0.05) and adolescence ( OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.
The chief characteristic of Japan's postwar employment system, built around the needs of large corporations, is (a) a higher rate of lifetime employment and (b) 'deferred compensation', which is reflected in Japan's steeper age-wage profile, and relatively late-stage promotions and late-career tracking relative to comparable nations. However, a key attribute of regular employment in Japan-its 'indefinite' or 'unrestricted' nature'-has received less attention than it deserves. Companies make no guarantees regarding regular employees' duties, job locations, and working hours at the time of hiring. All are left indeterminate. The indefinite nature of regular employment is linked to the causes of many employment problems. The diversification of regular employment needs to progress to the point where 'job-specific' regular employment, in which employees' job contents are clearly defined, becomes the new 'norm'. This article presents some of the policies that must be put in place in order for this shift to occur.
Division-summation (D-Sigma) digital control has been successfully applied to the single-phase bidirectional inverter with an LC filter, which can coverwide inductance variation and achieve precise inverter current tracking. However, high frequency ripple current injection to the grid cannot be avoided, and an LCL filter is therefore required. Since there typically exist grid voltage harmonics, the injected grid current will contain harmonic components due to the effect of the LCL-filter capacitor. This paper presents an extended application of the D-Sigma digital control associated with a filter-capacitor-current compensation to reduce the injected grid-current harmonics. The control laws of the inverter with the D-Sigma digital control and compensation approach are derived in detail, and the reduction of grid-current harmonics is analyzed. With the proposed approaches, the phase margin between the output impedance of the inverter and grid impedance can be higher than 80 degrees from low to high frequencies, and the inverter can achieve high harmonic voltage rejection ratio up to 39th harmonic, which is relatively suitable for weak grid connection. Experimental results measured from a 5-kW single-phase bidirectional inverter have verified the feasible application of the D-Sigma digital control and proposed compensation.
The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis. Furthermore, the level of malondialdehyde and the activity of superoxide dismutase (SOD) paired with glutathione peroxidase (GPx) were restored in the NBP treatment group. NBP promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus markedly, increased the expressions of Nrf2-ARE pathway-related downstream factors, including hemeoxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and prevented the decline of antioxidant enzyme activities, including SOD and GPx. NBP enhanced the translocation of Nrf2 to the nucleus from the cytoplasm,verified by a western blot, immunofluorescence. Additionally, it upregulated the expression of the Nrf2 downstream factors such as HO-1 and NQO1 were also confirmed via a western blot and real-time quantitative polymerase chain reaction. In conclusion, NBP administration may increase the activities of antioxidant enzymes and attenuate brain injury in a TBI model, potentially via the mediation of the Nrf2-ARE pathway.
The present study was designed to compare the expression pattern of Dlx3 in four different mineralized tissues because of: 1-its role in skeleton patterning, 2-its expression in dental epithelium and mesenchyme during morphogenesis, 3-the membranous and endochondral bone and tooth phenotype of tricho-dento-osseous syndrome related to Dlx3 gene mutation and 4-recently emerging knowledge on Dlx family members in the bone field. Ameloblasts, odontoblasts, osteoblasts and chondrocytes were analyzed ill vitro and in vivo. Dlx3 transcripts were detected by RT-PCR in established model systems (microdissected dental epithelium and mesenchyme; primary cultures of rat chondrocytes), as recently performed in osteoblasts in vitro. A human 414-bp Dlx3 probe was generated. A 4.5-kb human Dlx3 sense RNA was identified in maxillo-facial samples by Northern blotting. Immunolabeling and in situ hybridization were performed in mice from Theiler stage E 14.5 until birth. In teeth, although Dlx3 was still expressed in differentiated ameloblasts, it was down regulated during odontoblast polarization. During endochondral bone formation, Dlx3 protein was detected in chondrocytes and was most strongly expressed in the prehypertrophic cartilage zone and in differentiating and differentiated osteoblasts of inetaphyseal periosteum. In vitro, real-time PCR studies supported this upregulation in prehypertrophic chondrocytes, closely Correlated with Ihh variations. In membranous bone, Dlx3 was present in preosteoblasts, osteoblasts and osteoid-osteocytes. The present data on Dlx3 and recently published functional studies show that this transcription factor may be instrumental during growth in the control of matrix deposition and biomineralization in the entire skeleton. (c) 2005 Elsevier Inc. All rights reserved.
Objectives: The purpose of this study was to investigate the role of a novel mutant DLX3 on the odontogenic differentiation of human dental pulp cells (hDPCs) in tricho-dento-osseous (TDO) syndrome. Design: hDPCs were obtained from the healthy premolars, stably-expressing wild-type DLX3 (WT), novel mutant DLX3 (Mu) and control vector (NC) cells were generated using recombinant lentiviruses. The proliferation rates of WT-hDPCs and Mu-hDPCs were measured by CCK8 assay. Odonto-differentiation of hDPCs was assessed by alkaline phosphatase (ALP) activity assay, and mineralization ability was assessed by Alizarin red staining. Odontogenic markers, including DMP-1, DSPP, Nes, ALP, and DLX5, were analyzed using real-time polymerase chain reaction (qPCR). DMP-1 and DSPP expressions were further confirmed by Western blotting. Results: CCK8 results showed that the novel mutant DLX3 decreased the proliferation rate of hDPCs compared with wild-type DLX3. qPCR showed that the novel mutant DLX3 weakened odontogenic differentiation by downregulating the expression of odontogenic genes. These results were further confirmed by Western blotting and ALP activity assay. Additionally, Alizarin red staining showed that the novel mutant DLX3 decreased the mineralization of hDPCs compared with wild-type DLX3. Conclusions: Novel de novo mutation of DLX3 significantly decreases the proliferation rate and inhibits the odontogenic differentiation and mineralization of hDPCs, suggesting that this novel mutation of DLX3 can influence the dentinogenesis in TDO syndrome. (C) 2017 Elsevier Ltd. All rights reserved.
The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play a role in tumorigenesis and pathogen defense. It encodes a protein with multiple scavenger receptor cysteine-rich (SRCR) domains, which are involved in recognition and binding of a broad spectrum of bacterial pathogens. The SRCR domains are encoded by highly homologous repetitive exons, whose number in humans may vary from 8 to 13 due to genetic polymorphism. Here, we characterized the porcine DMBTI gene on the mRNA and genomic level. We assembled a 4.5 kb porcine DMBT1 cDNA sequence from RT-PCR amplified seminal vesicle RNA. The porcine DMBT1 cDNA contains an open reading frame of 4050 nt. The transcript gives rise to a putative polypeptide of 1349 amino acids with a calculated mass of 147.9 kDa. Compared to human DMBT1, it contains only four N-terminal SRCR domains. Northern blotting revealed transcripts of similar to 4.7 kb in size in the tissues analyzed. Analysis of ESTs suggested the existence of secreted and transmembrane variants. The porcine DMBT1 gene spans about 54 kb on chromosome 14q28-q29. In contrast to the characterized cDNA, the genomic BAC clone only contained 3 exons coding for N-terminal SRCR domains. In different mammalian DMBT1 orthologs large interspecific differences in the number of SRCR exons and utilization of the transmembrane exon exist. Our data suggest that the porcine DMBT1 gene may share with the human DMBT1 gene additional intraspecific variations in the number of SRCR-coding exons. (c) 2006 Elsevier B.V. All rights reserved.
Penaeid shrimps represent the most economically important decapod group in the Egyptian capture fisheries. Up till now, the absence of proper morphological and genetic tools for species identification is negatively affecting the proper management of fisheries, especially when associated with the scarcity of data about fisheries of such species that have high economic value or the ones suffering from overfishing. In the present study, we sampled three penaeid species that prevail the Egyptian capture fisheries of the Mediterranean; Penaeus semisukatus, Metapenaeus monoceros and Trachypenaeus curvirostris. Morphological clues for the identification of these species were thoroughly recorded. Furthermore, the DNA was extracted from these species and partial fragments of the cytochrome oxidase subunit 1 (C01) and 16S rRNA genes were amplified using polymerase chain reaction (PCR) and sequenced. New barcodes of these species were added to the GenBank database as confirmed by the thorough morphological identification. Some discrepancies were detected between our samples and those in the Genbank database (whenever available). Hence, phylogenetic analyses ensued for proper placement of our samples with their closest relatives that were previously submitted to GenBank. Moreover, morphometric studies were conducted to provide the fundamental parameters which are important for fisheries management of the currently studied shrimp species. Through these parameters tested, the study provided a tool to select the appropriate stocks for successful hatcheries, and added more value to the growing sector of shrimp aquaculture in Egypt. This study is the first of its kind in Egypt as it provides both morphological and genetic clues for identifying such species, and also in assessing their fisheries in the Mediterranean supreme fishery in Egypt. (C) 2016 Elsevier B.V. All rights reserved.
Gold nanoparticles have proven to be promising for decentralized nucleic acid testing by virtue of their simple visual readout and absorbance-based quantification. A major challenge toward their practical application is to achieve ultrasensitive detection without compromising simplicity. The conventional strategy of thermocycling amplification is unfavorable (because of both instrumentation and preparation of thermostable oligonucleotide-modified gold nanoparticle probes). Herein, on the basis of a previously unreported co-precipitation phenomenon between thiolated poly(ethylene glycol)/11-mercaptoundecanoic acid co-modified gold nanoparticles and magnesium pyrophosphate crystals (an isothermal DNA amplification reaction byproduct), a new ultrasensitive and simple DNA assay platform is developed. The binding mechanism underlying the co-precipitation phenomenon is found to be caused by the complexation of carboxyl and pyrophosphate with free magnesium ions. Remarkably, poly(ethylene glycol) does not hinder the binding and effectively stabilizes gold nanoparticles against magnesium ion-induced aggregation (without pyrophosphate). In fact, a similar phenomenon is observed in other poly(ethylene glycol)- and carboxyl-containing nanomaterials. When the gold nanoparticle probe is incorporated into a loop-mediated isothermal amplification reaction, it remains as a red dispersion for a negative sample (in the absence of a target DNA sequence) but appears as a red precipitate for a positive sample (in the presence of a target). This results in a first-of-its-kind gold nanoparticle-based DNA assay platform with isothermal amplification and real-time monitoring capabilities.
Six different commercial methods were compared to evaluate their efficiency in recovering high quantity/quality PCR compatible microbial DNA from an agricultural biogas plant. Within the last two decades, biogas plants have been developed to produce energy from organic wastes and from devoted biomass. The complex biotransformations are performed by a diverse consortium of microorganisms that is an important reserve of genes and enzymatic activities with a huge range of applications in various commercial fields. In this respect, the ability to isolate DNA from a complex matrix is of high importance. Important parameters of the recovered DNA are good yield, purity, and quality. The methods examined showed considerable differences about quantity and quality of the recovered DNA and, usually, it was observed that a higher amount was accompanied by more degradation. DNA purity was determined by its PCR amplificability. Only two methods were able to provide DNA pure enough to be directly amplified. For the rest of the methods, a few intermediate steps such as dilution and/or the addition of polyvinylpyrrolidone were necessary to remove the inhibitors present and to amplify the DNA. Real-time PCR analysis evidenced that, as expected, prokaryotic DNA was much more abundant than eukaryotic DNA, but some methods were more suited to recovering prokaryotic or eukaryotic DNA. The digestion analysis of ribosomal DNA amplicons confirmed the influence of the methods on the final output, allowing the recovery of only a fraction of the present species as determined by sequencing a small prokaryotic and eukaryotic ribosomal library.
We present a label-free biosensor for the detection of nucleic acids from PCR amplicons based on the surface plasmon resonance (SPR) with novel DNA intercalators. These intercalators can specifically bind to double-stranded DNA (ds-DNA), allowing ds-DNA to be quantitatively monitored by angle shifts of SPR following mass changes on the SPR sensor surface. Pyrenyl intercalator compounds that were synthesized consisted of pyrenyl groups as intercalating moieties, ethylene glycol hexamer linkers that resist non-specific binding events and thiol groups that formed self-assembled monolayers (SAMs) on a gold substrate. Also, hydroxyl group terminated compound instead of pyrenyl group was synthesized to ensure adequate separation between adjacent pyrene groups. The molar concentration ratio of mixed SAMs on SPR sensor surface was selected for maximum mass sensitivity on the basis of experimental results from various mixed ratios. Finally, we investigated the sensor responses due to intercalations on various concentrations of applied pure ds-DNA and demonstrated the capability for the analysis of PCR amplicons in the reaction product mixtures without any purification process. These results show that the proposed label-free biosensor devised based on strong binding interactions between DNA intercalators and base pairs of any ds-DNA can quantitatively analyze ds-DNA in accordance. (C) 2016 Elsevier B.V. All rights reserved.
Stress plays an important role in major depressive disorder (MDD) and is one of the state dependent factors in suicidal behavior. A dysfunctional hypothalamic-pituitary-adrenal axis is a common feature in this disorder. The involvement of environmental factors has added additional complexity to understanding depression or suicidal behavior. In this regard, epigenetic regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network that may increase susceptibility to depression or suicidal behavior. The present study examined whether epigenetic modifications of stress related genes are associated with MDD and whether there are differences in these epigenetic marks between depressed individuals with and without serious suicidal ideation. Using MeDIP analysis in genomic DNA isolated from peripheral blood mononuclear cells (PBMC) of healthy controls (n = 20), MDD patients with (n = 14) or without serious suicidal ideation (n = 10), we studied methylation of the stress-associated genes, Brain Derived Neurotrophic Factor (BDNF), Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1), FK506 Binding Protein 5 (FKBP5), Corticotropin Releasing Hormone Binding Protein (CRHBP), and Corticotropin Releasing Hormone Receptor 1 (CRHR1). In addition, we determined their transcript levels in RNAs isolated from the same PBMC. We found that BDNF, FKBP5, CRHBP, and NR3C1 gene promoters were significantly hypermethylated in MDD patients with and without suicidal ideation. We also found concomitant reductions in expression of BDNF, FKBP5 transcript variants (1, 2 and 3), and NR3C1 genes in these patients, suggesting that promoter hypermethylation in these genes may functionally be associated with their observed downregulation in MDD patients. In a secondary analysis, methylation of these genes was compared between MDD patients with or without serious suicidal ideation and controls. The MDD with serious suicidal ideation were significantly different from controls while the MDD without were not, although MDD with or without suicidal ideation were not different from each other, likely owning to a relatively small sample size. Thus, our findings underline the importance of epigenetic modifications of stress-associated genes in depression and, possibly, suicidal behavior, which, in future, needs to be confirmed in a larger patient population. (C) 2017 Elsevier Ltd. All rights reserved.
Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up. Our analyses aimed to identify methylomic variation associated with exposure to five major types of childhood maltreatment. We found that: (i) maltreatment types differ in the extent to which they associate with methylomic variation, with physical exposures showing the strongest associations; (ii) many of the identified loci are annotated to genes previously implicated in stress-related outcomes, including psychiatric and physical disorders (e.g. GABBR1, GRIN2D, CACNA2D4, PSEN2); and (iii) based on gene ontology analyses, maltreatment types not only show unique methylation patterns enriched for specific biological processes (e.g. physical abuse and cardiovascular function), but also share a 'common' epigenetic signature enriched for biological processes related to neural development and organismal growth. A stringent set of sensitivity analyses were also run to identify high-confidence associations. Together, findings lend novel insights into epigenetic signatures of childhood abuse and neglect, point to novel potential biomarkers for future investigation and support a molecular link between maltreatment and poor health outcomes. Nevertheless, it will be important in future to replicate findings, as the use of cross-sectional data and high rates of polyvictimization in our study make it difficult to fully disentangle the shared vs unique epigenetic signatures of maltreatment types. Furthermore, studies will be needed to test the role of potential moderators in the identified associations, including age of onset and chronicity of maltreatment exposure. (C) 2016 Elsevier Ltd. All rights reserved.
DNA methylation is a fundamental means of epigenetic gene regulation that occurs in virtually all cell types. In many higher organisms, including humans, it plays vital roles in cell differentiation and homeostatic maintenance of cell phenotype. The control of DNA methylation has traditionally been attributed to a highly coordinated, linear process, whose dysregulation has been associated with numerous pathologies including cancer, where it occurs early in, and even prior to, the development of neoplastic tissues. Recent experimental evidence has demonstrated that, contrary to prevailing paradigms, methylation patterns are actually maintained through inexact, dynamic processes. These processes normally result in minor stochastic differences between cells that accumulate with age. However, various factors, including cancer itself, can lead to substantial differences in intercellular methylation patterns, viz. methylation heterogeneity. Advancements in molecular biology techniques are just now beginning to allow insight into how this heterogeneity contributes to clonal evolution and overall cancer heterogeneity. In the current review, we begin by presenting a didactic overview of how the basal bimodal methylome is established and maintained. We then provide a synopsis of some of the factors that lead to the accrual of heterogeneous methylation and how this heterogeneity may lead to gene silencing and impact the development of cancerous phenotypes. Lastly, we highlight currently available methylation assessment techniques and discuss their suitability to the study of heterogeneous methylation. (C) 2016 Published by Elsevier Ltd.
Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post-transcriptional mechanisms. We show that the CCR4-NOT complex, a post-transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long-lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post-transcriptional regulation involving specific alteration in the CCR4-NOT complex, whose modulation could control multiple aspects of the aging process.
Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.
With the intensification of human activities, fresh water resources are increasingly being exposed to contamination from effluent disposal to land. Thus, there is a greater need to identify the sources and pathways of water contamination to enable the development of better mitigation strategies. To track discharges of domestic effluent into soil and groundwater, 10 synthetic double-stranded DNA (dsDNA) 3 tracers were developed in this study. Laboratory column experiment and field groundwater and soil lysimeter studies were carried out spiking DNA with oxidation-pond domestic effluent. The selected DNA tracers were compared with a non-reactive bromide (Br) tracer with respect to their relative mass recoveries, speeds of travel and dispersions using the method of temporal moments. In intact stony soil and gravel aquifer media, the dsDNA tracers typically showed earlier breakthrough and less dispersion than the Br tracer, and underwent mass reduction. This suggests that the dsDNA tracers were predominantly transported through the network of larger pores or preferential flow paths. Effluent tracking experiments in soil and groundwater demonstrated that the dsDNA tracerswere readily detectable in effluent-contaminated soil and groundwater using quantitative polymerase chain reaction. DNA tracer spiked in the effluent at quantities of 36 mu g was detected in groundwater 37 mdown-gradient at a concentration 3-orders of magnitude above the detection limit. It is anticipated it could be detected at far greater distances. Our findings suggest that synthetic dsDNA tracers are promising for tracking effluent discharges in soils and groundwater but further studies are needed to investigate DNA-effluent interaction and the impact of subsurface environmental conditions onDNA attenuation. With further validation, synthetic dsDNA tracers, especially when multiple DNA tracers are used concurrently, can be an effective new tool to track effluent discharge in soils and groundwater, providing spatial estimation on the presence or absence of contamination sources and pathways. (C) 2017 Elsevier B.V. All rights reserved.
Introduction: Unlike other molecular biology studies, the analysis of ancient DNA (aDNA) requires special infrastructure and methodological conditions to guarantee the quality of the results. One of the main authenticity criteria is DNA quantification, where quantitative real-time PCR is often used given its sensitivity and specificity. Nevertheless, the implementation of these conditions and methodologies to fulfill authenticity criteria imply higher costs. Objective: To develop a simple and less costly method for mitochondrial DNA quantification suitable for highly degraded samples. Materials and methods: The proposed method is based on the use of mini-primers for the specific amplification of short fragments of mitochondrial DNA. The subsequent purification of these amplified fragments allows a standard curve to be constructed with concentrations in accordance to the state of degradation of the samples. Results: The proposed method successfully detected DNA from ancient samples including bone remains and mummified tissue. DNA inhibitory substances were also detected. Conclusion: The proposed method represents a simpler and cost-effective way to detect low amounts of aDNA, and a tool to differentiate DNA-free samples from samples with inhibitory substances.
DNA analysis of processed foods is performed widely to detect various targets, such as genetically modified organisms (GMOs). Food processing often causes DNA fragmentation, which consequently affects the results of PCR analysis. In order to assess the effects of DNA fragmentation on the reliability of PCR analysis, we investigated a novel methodology to quantify the degree of DNA fragmentation. We designed four real-time PCR assays that amplified 18S ribosomal RNA gene sequences common to various plants at lengths of approximately 100, 200, 400, and 800 base pairs (bp). Then, we created an indicator value, "DNA fragmentation index (DFI)", which is calculated from the Cq values derived from the real-time PCR assays. Finally, we demonstrated the efficacy of this method for the quality control of GMO detection in processed foods by evaluating the relationship between the DFI and the limit of detection. (C) 2017 Elsevier Ltd. All rights reserved.
Considering that mislabeled milk products have been widely reported throughout the world and that the authentication of food components is one of the key issues in food safety and quality, the aim of this study was to use DNA-based methods to investigate the prevalence of mislabeling among goat-milk products and, consequently, how far the ingredients matched the labels. The study reveals a high degree of species mislabeling in milk products (80%), underlining the need to enhance dairy traceability practices, so as to guarantee product authenticity, and provide reliable information to consumers. (C) 2017 Elsevier Ltd. All rights reserved.
The aim of this study was to develop an ultra-fast molecular detection method for meat identification using convection Palm polymerase chain reaction (PCR). The mitochondrial cytochrome b (Cyt b) gene was used as a target gene. Amplicon size was designed to be different for beef, lamb, and pork. When these primer sets were used, each species-specific set specifically detected the target meat species in singleplex and multiplex modes in a 24 min PCR run. The detection limit was 1 pg of DNA for each meat species. The convection PCR method could detect as low as 1% of meat adulteration. The stability of the assay was confirmed using thermal processed meats. We also showed that direct PCR can be successfully performed with mixed meats and food samples. These results suggest that the developed assay may be useful in the authentication of meats and meat products in laboratory and rapid on-site applications. (C) 2017 Elsevier Ltd. All rights reserved.
AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus. (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was analyzed by real-time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-kappa B (NF-kappa B) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-kappa B signaling was essential for DAI to elicit antiviral response in Huh7 cells. When the NF-kappa B signaling pathway was blocked by a NF-kappa B signaling suppressor (I kappa B alpha-SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-kappa B but independent of IRF3 and secreted cytokines. (C) 2012 Baishideng. All rights reserved.
To make the direct readout of loop-mediated isothermal amplification (LAMP) simpler and more reliable and to enhance the visual sensitivy of LAMP detection, we developed a facile cascade signal-on colorimetric DNAzyme LAMP (dLAMP) sensor that integrates the amplification power of LAMP and the inherent catalytic activity of the DNAzyme for the simple and ultrasensitive analysis of targets. First, a signal inner primer with a 17-nt DNAzyme complementary sequence (a signal precursor) in its middle insertable region was asymmetrically designed for the next amplification and colorimetric reaction. In the presence of target DNA, the target specifically initiated LAMP, and the signal precursor was amplified to a larger number of DNAzyme sequences during the target DNA amplification. With the addition of hemin, free DNAzyme fragments, which were released by ultrasonication and pPNA, formed G-quadruplex-hemin conjugates that act as a signal readouts for the direct colorimetric assay. Even less 0.5 pg genomic DNA were detected using the established one-step cascade signal amplification strategy without the need for gels or other apparatus. Moreover, the novel colorimetric strategy showed high fidelity in DNA detection and visual sensitivity of LAMP. This method may pave the way for the point-of-care detection and other PCR-based colorimetric analyses. (C) 2016 Elsevier B.V. All rights reserved.
Objectives: To investigate the expression, DNA methylation status and its regulatory mechanism of tissue factor pathway inhibitor 2 (TFPI-2) in human placenta tissues of preeclampsia (PE). Material and methods: We studied the mRNA and protein expression and the promoter methylation levels of TFPI-2 in the PE placentas compared with those in the normal pregnant (NP) women. Quantitative real-time polymerase chain reaction, immunohistochemistry, western blot, and Sequenom Mass ARRAY were used for placenta tissue detection. Results: The expressions of TFPI-2 mRNA and protein were significantly elevated in the PE placentas when compared with those in the NP ones (P<0.05). Hypomethylation of the TFPI-2 promoter was detected both in PE patients and NP women, with a significant decrease in PE placentas (P = 0.005). The methylation level was significantly decreased at CpG_6 (-168 to -167), CpG_15 (-98 to -97) and CpG_18.19 (-68 to -65) in PE patients than that in normal placentas (P0.05). Conclusion: Over-expression of TFPI-2 and aberrant promoter mythylation status presented in the PE placentas, suggesting that epigenetic mechanism might contribute to the pathogenesis of PE. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Methods: Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. Results: All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Conclusions: Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is associated with drug response. Although present, the link between apoptosis and RNA disruption is not completely understood. Evaluation of RNA disruption is thus proposed as a novel and effective biomarker to assess response to chemotherapy drugs in vitro and in vivo.
We explored the social shaping of science at the microlevel reality of face-to-face interaction in one of the traditional places for scientific activities-the scientific lab. We specifically examined how doctoral students ' perception of their: (i) interaction with doctoral mentors (MMI) and (ii) lab social environment (LSE) influenced productivity. Construed as the production of peer-reviewed articles, we measured productivity using total number of articles (TOTAL), number of articles with impact factor greater than or equal to 4.00 (IFGE4), and number of first-authored articles (NFA). Via face-to-face interviews, we obtained data from n=210 molecular biology Ph. D. students in selected universities in Japan, Singapore, and Taiwan. Additional productivity data (NFA) were obtained from online bibliometric databases. To summarize the original 13 MMI and 13 LSE semantic-differential items which we used to measure students ' perceptions, principal component (PC) analyses were performed. The results were smaller sets of 4 MMI PCs and 4 LSE PCs. To identify which PCs influenced publication counts, we performed Poisson regression analyses. Although perceived MMI was not linked to productivity, perceived LSE was linked: Students who perceived their LSE as intellectually stimulating reported high levels of productivity in both TOTAL and IFGE4, but not in NFA. Our findings not only highlight how students ' perception of their training environment factors in the production of scientific output, our findings also carry important implications for improving mentoring programs in science. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2): 130-144, 2017.
The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.
The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature.
Reasoning about physical properties of objects such as heaviness by observing others' actions toward them is important and useful for adapting to the environment. In this study, we asked whether domestic dogs (Canis familiaris) can use a human's action to infer a physical property of target objects. In Experiment 1, dogs watched an experimenter opening two differently loaded swinging doors with different corresponding degrees of effort, and then were allowed to open one of the doors. Dogs chose randomly between the two doors. In Experiment 2, we gave new dogs the same test as in Experiment 1, but only after giving them experience of opening the doors by themselves, so that they already knew that the doors could be either light or heavy. In this test the dogs reliably chose the light door. These results indicate that dogs are able to infer physical characteristics of objects from the latters' movement caused by human action, but that this inferential reasoning requires direct own experience of the objects. (C) 2017 Published by Elsevier B.V.
Babesiosis is a protozoal disease caused by Babesia spp. in mammals and humans worldwide. It is one of the most important tick-borne diseases, which affects livestock productions, reproductions, and accordingly failing economy. In this, systematic review and meta-analysis, study, the prevalence of babesiosis among domestic herbivores in Iran, between 1998 and 2015, was methodically reviewed. Nine databases including five English and four Persian databases were explored. A total of 49 articles, as regards the examination of 13,547 sheep, 1920 goats, 7167 cattle, and 940 horses, corresponding to prevalence of babesiosis from different regions of Iran were gathered for our qualifying criteria. The overall prevalence of babesiosis was expected to be 14% (95% CI 12%, 16%) in domestic herbivores. Our results showed the highest prevalence in Khorasan Razavi (18.6%) and West Azarbaijan (15.2%) and the lowest in Mazandaran (8.8%) and Isfahan provinces (9.6%), respectively. The high prevalence of Babesia infection in herbivores (mostly sheep and goats) confirms the established enzootic situation of babesiosis in Iran, particularly in western and northeastern regions of the country. Our data offered important and updated information on the epidemiology of babesiosis, for the first time, in domestic herbivores in Iran, and will likely be contributing to the expansion of the screening and control strategies to reduce health and economic impacts among farm animals.
Study Objective: To describe the clinical characteristics of patients referred for domestic minor sex trafficking (DMST) to improve identification and intervention. Design: Retrospective cohort study. Setting: The Lawrence A. Aubin, Sr Child Protection Center at Hasbro Children's Hospital where patients are evaluated by child abuse pediatricians in outpatient, emergency department, and inpatient settings. Participants: A total of 41 patients younger than the age of 18 years referred for the evaluation of DMST involvement between August 1, 2013 and March 30, 2015. Interventions and Main Outcome Measures: We collected demographic, social-environmental, medical, and psychiatric variables from the medical records of patients referred for evaluation who have self-disclosed, been reported with evidence, and/or have histories that place them at high risk for DMST involvement. Results: Children had frequent contact with medical providers, with 81% seen in the year before referral for DMST. Childhood maltreatment and family dysfunction were identified (sexual abuse, 21/37 or 57%; parental substance abuse, 22/37 or 60%) in the 41 patients. Children had medical problems (eg, sexually transmitted infection, 13/41 or 32%), psychiatric needs (eg, acute suicidality, 8/41 or 20%; at least 1 previous psychiatric admission, 19/41 or 46%), and substance use (36/41 or 88%). Although 26/41 (63%) had runaway and 17/41 (42%) lived in a group home placement, 28/41 (68%) currently lived at home and 29/41 (71%) presented with a parent/guardian or relative. Conclusion: Children referred for DMST present frequently to physicians and have complex medical and psychiatric needs. Medical providers' increased awareness of this health issue would inform victim identification and intervention.
This study aimed to identify and analyze the prevalence of physical and psychological family violence in a sample of children and adolescents with different categories of disabilities in a hospital in Rio de Janeiro, Brazil. This was a cross-sectional observational study based on application of the Parent-Child Conflict Tactics Scale in a sample of 270 parents or guardians. Prevalence was 83.7% for psychological aggression and 84.4% for physical maltreatment, while 96.5% of the children and adolescents with disabilities that suffered physical punishment were also victims of psychological aggression ( p < 0.01) and 100% of those who suffered severe physical maltreatment also suffered psychological aggression ( p = 0.01). Children and adolescents with disabilities showed increased risk of suffering family violence compared to those without disabilities. In conclusion, there is a need for greater awareness-raising and training of health teams for detection and notification of child abuse, and efforts should be made to support these families.
Victims of violence need special treatment in the emergency room, including exact documentation that can stand up in court. It may happen that the documentation must be made by the clinician if no forensic pathologist is on site The aim of this review is to provide clinicians a guide for documenting information from victims of violence and to identify potential victims of violence. Presentation of selected and typical cases, discussion of basic literature and expert opinions. Victims of violence can present a variety of injury patterns which the attending physician must recognize as being the result of violence. If urgent care is needed or no forensic pathologist is available, the documentation must be made by the clinician. Particular importance is attached to the exact photo documentation and description of injuries. Commonly physicians and nurses are not adequately trained in dealing with medicolegal situations. Continuing education in the field of wound documentation in words and pictures is necessary in order to provide proper documentation. Cooperation between clinicians and forensic medicine specialists should be intensified.
This research examined Children and Family Court Advisory and Support Service (Cafcass) reports prepared for private family court proceedings in domestic violence cases in England. The research found that in cases where children's accounts identified them as victims of violence, these disclosures regularly disappeared from report recommendations. Particular discourses regarding 'child welfare' and 'contact' were identified, which routinely impacted on the ways in which children's voices were taken into account. Whilst culturally there has undoubtedly been an influential move towards including children's perspectives in decision-making that affects them, how these views are interpreted and represented is subject to adult 'gate-keeping' and powerful cultural and professional ideologies regarding 'child welfare' and 'post-separation family relationships'. This research found that the unrelenting influence of deeply embedded beliefs regarding the preservation or promotion of relationships with fathers continues to have the effect of marginalising issues of safeguarding, including children's voiced experiences of violence, in all but the most exceptional of cases. Rather, safeguarding concerns in respect of domestic violence and child abuse were persistently overshadowed by a dominant presumption of the overall benefits of contact with fathers. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
Exposure of children to domestic violence and abuse (DVA) is a form of child maltreatment with short-and long-term behavioural and mental health impact. Health care professionals are generally uncertain about how to respond to domestic violence and are particularly unclear about best practice with regards to children's exposure and their role in a multiagency response. In this systematic review, we report educational and structural or whole-system interventions that aim to improve professionals' understanding of, and response to, DVA survivors and their children. We searched 22 bibliographic databases and contacted topic experts for studies reporting quantitative outcomes for any type of intervention aiming to improve professional responses to disclosure of DVA with child involvement. We included interventions for physicians, nurses, socialworkers and teachers. Twenty-one studiesmet the inclusion criteria: three randomised controlled trials (RCTs), 18 pre-post intervention surveys. There were 18 training and three system-level interventions. Training interventions generally had positive effects on participants' knowledge, attitudes towards DVA and clinical competence. The results from the RCTs were consistent with the before-after surveys. Results from system-level interventions aimed to change organisational practice and inter-organisational collaboration demonstrates the benefit of coordinating system change in child welfare agencies with primary health care and other organisations. Implications for policy and research are discussed. (C) 2015 The Authors. Child Abuse Review published by John Wiley & Sons Ltd.
The present study investigated the predictive utility of self-reported domestic violence perpetrators' exposure to violence in their family of origin and patterns related to this exposure through the use of longitudinal analyses on a sample of 228 men on probation in Lake County, Illinois. Differences in typology, recidivism, recidivism frequency, and violent behavior survival patterns in men with a history of domestic violence perpetration and with varying levels of family of origin violence exposure were examined. Findings suggest that those who witnessed interparental violence (either alone, or in combination with experiencing violence) were most likely to be classified as Generally Violent offenders (e.g., perpetrators who direct violence toward their family and others), compared to those who did not report experiencing or witnessing violence. In addition, results also indicate that men who experienced both witnessing interparental violence and receiving physical abuse in childhood were more likely to recidivate more frequently compared to those who did not report experiencing or witnessing violence. No significant findings for typology and recidivism were noted. Clinical and policy/practice implications are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
Aim: The dengue virus is responsible for a high worldwide incidence of infections, aggravated by late diagnosis, and often confused with other tropical diseases. Results/methodology: Oligonucleotide aptamers binding to the 5'-UTR from dengue virus selected after eight rounds by systematic evolution of ligands by exponential enrichment technology were analyzed by dot-blot assay and in silico prediction of secondary structures, demonstrating the presence of stem-loops that may have the potential for interaction with the viral genome, which can lead to loss of their original conformation. Conclusion: This is the first description of RNA aptamers against functional RNA elements of the dengue virus genome with implications for disease control, which may have potential as tools in the future of antiviral therapies and for diagnostics.
Based on the orthogonal superposition theorem of three alternating magnetic components, a universal uniform magnetic spin vector is superimposed using tri-axial Helmholtz coils, achieving successive digital control of the orientation, the rotational speed, and the magnetic flux density of the universal magnetic spin vector. For increasing the magnitude and orientation accuracy of the magnetic spin vector, this paper presents a mathematical model associated with the magnitude error and orientation error of the universal magnetic spin vector, along with a double error compensation method for the magnitude and orientation of the universal magnetic spin vector superimposed by three alternating magnetic components. The double error compensation method includes the current magnitude compensation by three different structural coefficients of tri-axial Helmholtz coils and the current phase compensation by two relative phase differences under linear polarization. The results have shown that the double compensation method can increase the magnitude and orientation accuracy of the rotating magnetic vector effectively, which would achieve an accurate posture adjustment and steering control on the capsule robots in curving environment.
Replacement of beef by buffalo and vice versa is frequent in global markets, but their authentication is challenging in processed foods due to the fragmentation of most biomarkers including DNA. The shortening of target sequences through use of two target sites might ameliorate assay reliability because it is highly unlikely that both targets will be lost during food processing. For the first time, we report a tetraplex polymerase chain reaction (PCR) assay targeting two different DNA regions in beef (106 and 120-bp) and buffalo (90 and 138-bp) mitochondrial genes to discriminate beef and buffalo in processed foods. All targets were stable under boiling, autoclaving and microwave cooking conditions. A survey in Malaysian markets revealed 71% beef curries contained buffalo but there was no buffalo in beef burgers. The assay detected down to 0.01 ng DNA and 1% meat in admixed and burger products. (C) 2016 Elsevier Ltd. All rights reserved.
Background: The double-blind, placebo-controlled food challenge (DBPCFC) is considered the definitive diagnostic test for food allergy. Nevertheless, validated recipes for masking the foods are scarce, have not been standardized, and differ between centers. Sensory evaluation techniques such as the triangle test are necessary to validate the recipes used for DBPCFC. Methods: We developed 3 recipes for use in DBPCFC with milk, egg white, and hazelnut and used the triangle test to validate them in a 2-phase study in which 197 volunteers participated. In each phase, participants tried 3 samples (2 active-1 placebo or 2 placebo-1 active) and had to identify the odd one. In phase 1, the 3 samples were given simultaneously, whereas in phase-2, the 3 samples of foods that failed validation in phase 1 were given sequentially. A visual analog scale (VAS) ranging from 1 to 10 was used to evaluate how much participants liked the recipes. Results: In phase 1, the egg white recipe was validated (n=89 volunteers, 38.9% found the odd sample, P=.16). Milk and hazelnut recipes were validated in phase 2 (for both foods, n=30 participants, 36.7% found the odd sample, P=.36). Median VAS scores for the 3 recipes ranged from 6.6 to 9.7. Conclusions: We used sensory testing to validate milk, egg white, and hazelnut recipes for use in DBPCFC. The validated recipes are easy to prepare in a clinical setting, provide the equivalent of 1 serving dose, and were liked by most participants.
This paper is concerned with the design of a self-scheduled current controller for doubly fed induction machines. The design is based on the framework of linear parameter-varying systems where the mechanical angular speed is considered to be a measurable time-varying parameter. The objective is to obtain robust dynamic performance for all variations of the mechanical rotor speed in a specified operating range. Employing the benefits of digital control, a continuous-to-discrete time transformation is utilized to replace the continuous-time current controller by an approximating discrete-time controller. Experimental results are provided to demonstrate the performance and robustness of the controlled system with respect to changes of the mechanical rotor speed and against stator voltage dips.
Some children with Down syndrome may experience difficulties in recognizing facial emotions, particularly fear, but it is not clear why, nor how such skills can best be facilitated. Using a photo-matching task, emotion recognition was tested in children with Down syndrome, children with nonspecific intellectual disability and cognitively matched, typically developing children (all groups N = 21) under four conditions: veridical vs. exaggerated emotions and emotion-labelling vs. generic task instructions. In all groups, exaggerating emotions facilitated recognition accuracy and speed, with emotion labelling facilitating recognition accuracy. Overall accuracy and speed did not differ in the children with Down syndrome, although recognition of fear was poorer than in the typically developing children and unrelated to emotion label use. Implications for interventions are considered.
Solar energy has an enormous potential to solve society energy needs in a sustainable way. Notably, photovoltaic systems (PV) permit to obtain electricity based on solar energy. However, some issues must be addressed to establish PV as a reliable source of electrical power, for example, its low energy density. One of the approaches to improve the performance of PV systems is to utilize the solar spectrum in solar cells efficiently. Downconversion (DC) is a process where a high energy photon is converted into two or more photons with lower energy. Trough downconversion is possible to use a wider portion of the solar spectrum raising the efficiency in different kinds of solar cells. The present paper reviews the state of the art of materials and methods used to take advantage of downconversion processes in solar cells. Here we discuss some of the pros and cons of different designs in solar cells as well as the main characteristics of the materials utilized.
Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool for cancer diagnosis and therapy. In the present study MCS nanogels were prepared by Myristate: Chitosan at 1: 9 ratio and were characterized by several techniques. A selected ssDNA aptamer (Apt) capable of detecting LNCaP cells was linked to Myristilated Chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded with Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the binding efficiency was estimated by flow cytometry. The binding affinity of the selected aptamers was above 70% compared to the initial library. The loading capacity of the nanogel was as high as 97% and up to 40% of DOX were released from MCS within 15 days. Cytotoxicity of nanodrug on LNCaP cells was determined by MTT assay. Apt-MCS- DOX was specifically binded to LNCaP cells whereas it didn't show any specificity to PC-3 cells as a negative control. Both MCS-DOX and Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an aptamer based simple and applicable technique for early diagnosis and treatment of cancerous cells.
Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-alpha. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy. (C) 2016 Published by Elsevier Inc.
Facile probing organic solvents is attracting intense attention due to the growing environmental issues. Herein, for the first time, we report a novel D-pi-A structured methanol responsive fluorescence molecule (TTO), synthesized by coupling triphenylamine (electron-donor) and p-toluenesulfonyl (electron-acceptor) via Cu (I) catalytic 1,3-dipolar cycloaddition (click chemistry) forming a triazole bridge. Density functional theory (DFT) calculations and X-ray single crystal structure reveal that TTO has a highly twisted conformation and unique D-pi-A structure which render it exceptional optical properties. TTO exhibits strong fluorescence in methanol (QE>0.67) but weak fluorescence in other organic solvents (QE<0.1) including various alcohols and can be used as a highly selective fluorescence probe for methanol identification. Notably, TTO is able to excellently probe methanol from its homologue ethanol in water with a detection limit of below 0.7% (volume concentration), which demonstrates the promise potential of TTO for practical applications. (C) 2017 Elsevier B.V. All rights reserved.
In this study, a specific and sensitive method for simultaneous detection of human astrovirus, human rotavirus, norovirus, sapovirus and enteric adenovirus associated with acute enteritis was developed, based on the specific dual priming oligonucleotide (DPO) system and the sensitive high-performance liquid chromatography (HPLC) analysis. The DPO system-based multiplex reverse transcription-polymerase chain reaction (RT-PCR) combined with HPLC assay was more sensitive than agarose gel electrophoresis analysis and real-time SYBR Green PCR assay, and showed a specificity of 100% and sensitivity of 96%-100%. The high sensitivity and specificity of the assay indicates its great potential to be a useful tool for the accurate diagnosis of enteric virus infections. (C) 2017 Elsevier B.V. All rights reserved.
Surface characteristics play a special role for the biological performance of implants and several strategies are available to this end. The OGI (Osteo Growth Induction) titanium surface is a surface, obtained by applying a strong acid onto the blasted surface. The aim of this in-vitro study is to evaluate in vitro the osteoproperties of OGI surfaces on Mesenchymal Stem cells derived from dental pulp. Our results confirm that this treatment exert a positive effect on mitochondrial homeostasis, as shown by a decrease in ROS production related to environmental stress on the mitochondria. Morphological and molecular biology analyses confirmed more over that the DPSC cultured on the OGI surfaces appeared more spread in comparison to those grown on control titanium surface and real time PCR and biochemical data clearly demonstrated the increase of osteoconductive properties of the OGI treatment. In conclusion, our results suggest that mesenchymal stem cells sensitively respond to surface properties related to OGI treatment enhancing their osteogenic activities. (C) 2016 Elsevier B.V. All rights reserved.
Duck plaque virus (DPV) belongs to the family Herpesviridae. The live attenuated vaccine is the only way to protect the ducks from DPV infection. The ineffectiveness of vaccine is one of the major causes of DPV outbreaks in the field condition. DPV is not well characterized for its pathogenicity and molecular biology in poultry. In the present study, we discuss briefly about the biology of DPV and its proteins under different conditions of temperature and pH in order to evaluate its infectivity under adverse physical conditions. Our results indicate that the DPV is non-infective above 42 degrees C and unstable above 65 degrees C. In addition, change in pH or salt concentrations significantly decreases the stability of the DPV. The study will be useful in estimating an optimum storage condition for DPV vaccines without causing any deterioration in its viability and effectiveness. (C) 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
While digital control has achieved success in various power electronic applications, data conversion remains a primary challenge and limitation compared to conventional analog methods. In particular, tradeoffs among resolution, switching frequency, and power consumption of digital pulse-width modulation (DPWM) blocks limit performance, particularly in high conversion-ratio applications. Analog-digital conversion is also challenging when line-voltage feedforward techniques are applied as it requires high speed, accuracy, and in some cases exposure to voltages exceeding the rating of deep-submicron CMOS technologies. This work explores tradeoffs in power consumption of counter/delay-line DPWM circuits, implemented in CMOS, and derives an optimization method to segment the bit allocation among the counter and delay line components. A method for line-voltage feedforward is also presented that can instrument and quantize transients on the supply voltage without direct exposure of low voltage devices to the supply. An automotive 48V:7V application is considered.
Development of effective monitoring systems of power exchange fluctuations and proportional alignment of loading on gas-diesel-generator units requires carrying out detailed researches both their own fluctuations, and exchange fluctuations in case of parallel work of several units. Carrying out such researches on real objects is limited to their considerable cost and can be given only at the final stage. Therefore it is very important for developers to have adequate models of the studied objects. The researches of output voltage frequency fluctuations for real objects executed by authors showed that in general they have casual character, and these fluctuations in all range of loadings represent non-stationary casual process with the changing population mean and dispersion. Authors developed mathematical model of the regulator stabilizing exchange fluctuations of power in the studied system. But there was a question of its hardware realization because it requires solving the problem of identification of the structure of this system and on-line monitoring of changes in its parameters and signals. The authors have proposed a candidate solution for such a problem through the example of identification and synthesis of the system of measuring system performance indicators required to appraise the electric power quality in this system and, as consequence, performance quality.
Biofilm detachment caused by flushing can result in secondary contamination in drinking water distribution systems (DWDSs). To evaluate the impact of flushing on biofilm detachment, actual water supply pipes including ductile cast iron pipes (DCIPs), gray cast iron pipes (GCIPs), and stainless steel compound pipes (SSCPs) were used in this study. Real-time quantitative polymerase chain reaction and 454 pyrosequencing were used to quantify bacteria and analyse microbial community composition, respectively. The results showed that the pipe material greatly influences the resistance of a biofilm to flushing. Biofilms attached to DCIPs were able to resist quite strong flushing, while those attached to GCIPs and SSCPs were sensitive to flushing. Both flush-resistant and flush-sensitive bacteria were present in all the biofilms, but their frequency differed among the different metal pipes. Thus, the resistance to flushing of bacteria is related not only to the nature of the bacteria, but also to the pipe material. Although flushing can remove some of the biofilm and may be a good way to clean the DWDS, the shear stress needed to remove the biofilm differs among different pipe types. The results of this study provide technical support for the management and operation of DWDS.
Vehicle driveability describes the complex interactions between the driver and the vehicle, mainly related to longitudinal vibrations. Today, a relevant part of the driveability process optimisation is realised by means of track tests, which require a considerable effort due to the number of parameters (such as stiffness and damping components) affecting this behaviour. The drawback of this approach is that it is carried on at a stage when a design iteration becomes very expensive in terms of time and cost. The objective of this work is to propose a light and accurate tool to represent the relevant quantities involved in the driveability analysis, and to understand which are the main vehicle parameters that influence the torsional vibrations transmitted to the driver. Particular attention is devoted to the role of the tyre, the engine mount, the dual mass flywheel and their possible interactions. The presented nonlinear dynamic model has been validated in time and frequency domain and, through linearisation of its nonlinear components, allows to exploit modal and energy analysis. Objective indexes regarding the driving comfort are additionally considered in order to evaluate possible driveability improvements related to the sensitivity of powertrain parameters.
With the development of economic globalization, the cultivation of minority secretary major should follow the principle of compound talents training mode and improve the overall quality of the talent of minority secretary major. Secretary major training plan has shortage of teaching content and lacks cross-cultural communication training program. Its teaching mission objectives is not new and secretary professional competence of teachers are not enough and the teaching method is too traditional and curriculum is unreasonable. Based on this situation, the paper does the digitization DRM solutions using the DRM digital control program based on multivariate intelligent teaching reform program of talent training. This paper establishes and develops the ODRL talent model and achieves the segmentation description and dynamic segmentation authorization of tasks and contents of minority secretary major secretary courses. It also achieves the secondary development of DRM under the ODRL control model and verifies the feasibility and reliability of the training mode using the teaching effect evaluation method of OpenAPI, which provides a reliable theoretical basis for the reform of minority secretary major training model.
Background: In many parts of the Old World, domesticated camels (genus - Camelus) are an essential resource, providing food, labor, commodities, and sport to millions of people Of the three extent species, two have been domesticated (single-humped dromedarius, Camelus dromedarius, and two humped Bactrian camels Camelus bactrianus) and one remains wild (two-humped wild Bactrian camels Camelus ferus). All three species possess a variety adaptations to harsh desert conditions, including mechanisms to tolerate of extreme temperatures, dehydration, and sandy terrain. People residing in harsh climate zones of the world are being benefitted by raising camels in terms of draft, milk, meat, hides and wool from centuries. There are different breeds of dromedary camels distributed in various parts of Pakistan; however there have been scarcity of research work on camels in Pakistan. Identification of novel link between Camel breeders with fatal neurodegenerative disorders is presence or not can be detect by a Prion gene and it was not carried out in Pakistan soil to date. Prion diseases which are a group of fatal neurodegenerative disorders affect both animals and humans. It is believed that the prions are infectious agents responsible for transmissible spongiform encephalopathies. In this study we report the first study on Prion protein gene in dromedary camels of Pakistan. Material, Methods & Results: Genes are the blueprint of life and determine the functional aspects of cellular mechanisms. Genomic DNA of the enrolled blood samples was extracted using the Nucleospin((R)) DNA extraction kit. Genomic DNA was run on Agarose gel electrophoresis, checked the Genomic DNA quality and amplified using prion region specific primer pair. Prion protein gene was amplified (770 bp) in 35 individuals of seven dromedary camel breeds from the province Balochistan and Punjab of Pakistan. Samples having required fragment size were selected and sent for sequencing through Sanger Sequencing. All the sequences were aligned through multiple sequence alignment and edited using Codon Code aligner and explored for phylogenetic analysis. A portion of 667 bp was finally selected for phylogenetic analysis of dromedary camels from Pakistan with 61 different mammalian species (drawn from GenBank) that revealed five different clades. We found 99.9% nucleotide sequence similarities among Dromedary camels (Germany), Dromedary camels (Iran), and Dromedary camels (Pakistan). We observed deletion in dromedary camels in codon region 66-69 except wild Bactrian camels that might be the causative factor for Prion protein gene resistance in camels. The Neighbor-Joining method with bootstrap analysis of 1000 replicates was used to draw phylogenetic tree. Discussion: This study documents the presence of 14 PrP polymorphisms and shows the relationship between different camel breeds. The deletion had not previously been examined PrP allelic variation, and was found to segregate in these breeds. However, additional data are necessary to demonstrate PrP and genetic approach will be ideal for the future studies and, more investigations are necessary to demonstrate PrP genetic resistance in camels. The utility of these techniques in identifying Prion genes and selecting superior animals and culling the weak animals and making them parents of the next generation that will lead to producing more meat and milk with fewer animals are well discussed and by slaughtering of high Prion incidence will eliminate human animal fatal neurodegenerative disorders.
Three novel small noncoding RNAs were identified from the conserved intronic regions of D. melanogaster by using comparative genomics method and molecular biology approach. One is a novel snoRNA in a combinated way, which displays structural features typical of C/D box snoRNA family and possesses a 10-nt-long rRNA antisense element for guiding the 2'-O-methylation of the D. melanogaster 28S rRNA at C2673. The other two are miRNAs whose predicted precursors adopt a stem-loop structure characteristic of known miRNA. The two miRNAs genes appear to have ubiquitous expression profiles with similar to 23-nt RNA transcripts detected by Northern blotting. Our study revealed 396 multi-species intronic conserved sequences (MCIS) that nested in the introns with a length from 100 to 500 bp. In addition to small RNA coding, the MCIS might function as cis-acting elements involved in gene transcription or post-transcriptional processing.
An H+-PPase gene, TsVP from Thellungiella halophila, was transferred into two cotton (Gossypium hirsutum) varieties (Lumianyan19 and Lumianyan 21) and southern and northern blotting analysis showed the foreign gene was integrated into the cotton genome and expressed. The measurement of isolated vacuolar membrane vesicles demonstrated that the transgenic plants had higher V-H+-PPase activity compared with wild-type plants (WT). Overexpressing TsVP in cotton improved shoot and root growth, and transgenic plants were much more resistant to osmotic/drought stress than the WT. Under drought stress conditions, transgenic plants had higher chlorophyll content, improved photosynthesis, higher relative water content of leaves and less cell membrane damage than WT. We ascribe these properties to improved root development and the lower solute potential resulting from higher solute content such as soluble sugars and free amino acids in the transgenic plants. In this study, the average seed cotton yields of transgenic plants from Lumianyan 19 and Lumianyan 21 were significantly increased compared with those of WT after exposing to drought stress for 21 days at flowering stage. The average seed cotton yields were 51 and 40% higher than in their WT counterparts, respectively. This study benefits efforts to improve cotton yields in arid and semiarid regions.
Drug courts were implemented nationwide during the 1990s to expand alternatives to incarceration for individuals with substance use disorders that were charged with nonviolent felonies or misdemeanors. Although these courts were publicized as a facilitator of treatment and alternative to incarceration, researchers and advocates have suggested that this approach may have unintentionally intensified law enforcement focus on casual drug users and individuals with minor substance dependency. The primary objective of this study was to determine whether there is evidence that drug courts systemically increased the arrest and punishment of misdemeanor drug use and possession by conducting a series of panel data analyses among more than 8,000 city and county jurisdictions while controlling for economic, demographic, and nationwide law enforcement trends. Analyses in this study provide evidence that local police increased their attention toward minor drug offenses in jurisdictions where drug courts were implemented across the nation.
Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules.
Background: Theory of mind concerns the sociocognitive ability to infer others' thoughts. It has been theorized to be impaired in substance use and abuse, as its alterations might explain negative social and interpersonal outcomes noted in the course of disorders. In addition, the brain structures involved in Theory of Mind (ToM) have been found to be disrupted in drug use conditions. Objective: We undertook a systematic review of ToM functioning in drug use conditions. Methods: Four electronic databases (MEDLINE, Web of Science, PsycINFO, and Embase) were searched to find studies that have addressed ToM and conditions related to actual or previous drug use. Results: The search found 147 papers, of which 14 fulfilled our review eligibility criteria. Different methods were used, but overall, results indicated that drugs are related to ToM deficits, particularly related to alcohol and amphetamines use. These impairments correlate with other clinical and cognitive functions. Conclusion: Despite the lack of studies and the methodological limitations of the existing ones Theory of Mind seems to play a role in drug use conditions, which requires further investigation.
Purpose of reviewTo highlight recent advances in the understanding of nutritional immunology and in the development of novel therapeutics for inflammatory bowel disease (IBD).Recent findingsWe highlight the variety of factors that contribute to the interaction of the immune system and nutrition including the microbiome and the nervous system stimulation of the gut. We describe the potential for therapeutic development in IBD. Further, we review the cellular metabolic effects on immune activation and promising therapeutic targets. Finally, we show how the progression of understanding the role of lanthionine synthetase C-like 2 has encompassed both nutritional and therapeutic advances and led to the development of novel oral small molecule therapeutics for IBD.SummaryNutritional immunology and drug development research centered around immunoregulatory pathways can provide safer and more effective drugs while accelerating the path to cures.
Protein-protein interactions are fundamental for virtually all functions of the cell. A large fraction of these interactions involve short peptide motifs, and there has been increased interest in targeting them using peptide-based therapeutics. Peptides benefit from being specific, relatively safe, and easy to produce. They are also easy to modify using chemical synthesis and molecular biology techniques. However, significant challenges remain regarding the use of peptides as therapeutic agents. Identification of peptide motifs is difficult, and peptides typically display low cell permeability and sensitivity to enzymatic degradation. In this review, we outline the principal highthroughput methodologies for motif discovery and describe current methods for overcoming pharmacokinetic and bioavailability limitations.
Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced self-renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-like properties of PANC-1 SP cells and metastatic potential by downregulating the expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR-200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Purpose of review Endometrial cancer incidence is increasing in North America and is a major cause of morbidity and mortality in women. We review recent literature published on treatment of endometrial cancer and highlight areas of active interest. Recent findings There has been movement toward minimal invasive surgery at diagnosis; lymph node staging remains controversial and continues to be investigated. Progress has been made to establish consensus on endometrial cancer risk classification to promote consistency for future trial design. Molecular characterization of endometrial cancer and its integration into clinicopathological profiling to develop predictive biomarkers for treatment selection are active areas of research. Optimal adjuvant treatment strategy in high-risk endometrial cancer remains to be defined with recognition of treatment-related toxicity. Despite encouraging results in drug development for treatment of advanced/recurrent endometrial cancer, no targeted therapies beyond hormonal therapy are approved. There is an urgent need for scientifically validated therapy with predictive biomarkers. Summary Our understanding of endometrial cancer has evolved through improvements in molecular biology, allowing improved definition of target-specific therapies. The precise role and sequence of conventional and targeted therapies, including immunotherapy, will require careful attention to the design of clinical trials with translational emphasis to allow the discovery, validation, and implementation of predictive biomarkers into clinical care.
PurposeTo investigate tear film stability and secretion according to serum 25-hydroxyvitamin D3 [25(OH)D] levels in dry eye patients. MethodsIn this retrospective observational study, the medical charts of 92 patients who visited the Department of Ophthalmology at Hallym University Kangnam Sacred Heart Hospital from April to August 2015 were reviewed. Serum 25(OH)D levels were measured. Subjects were divided into three groups according to serum 25(OH)D levels: sufficient, inadequate or deficient group. Eye discomfort was measured by ocular surface disease index (OSDI). Tear break-up time (TBUT), fluorescein staining score and Schirmer's tear secretion test were measured. ResultsThe mean age was 53.3813.69years. Mean serum 25(OH)D level was 14.41 +/- 5.98ng/ml. Tear break-up time (TBUT) and tear secretion were positively correlated with serum 25(OH)D levels (r=0.389, p=0.001; and r=0.428, p<0.001, Pearson correlation test). Tear break-up time (TBUT) and tear secretion were shorter in the vitamin D-deficient group compared to the sufficient group (p=0.022 and p=0.004). Fluorescein staining scores and OSDI scores were not different between the three groups. ConclusionTear break-up time (TBUT) and secretion were correlated with serum vitamin D levels. Vitamin D status may be an important factor for dry eye syndrome.
The division-summation (D-Sigma) current control and one-cycle voltage regulation (OCVR) of a 5-kW surface-mounted permanent-magnet synchronous generator (SPMSG) drive is developed. With the advancement of motor manufacturing, motor design, digital control units and power electronics converters, the permanent-magnet synchronous generator (PMSG) is broadly applied to electric vehicles, hybrid electric vehicles, flywheel energy storage system and wind power generators. Satisfactory current control scheme of a PMSG is significant to achieve desired generating performance. The D-Sigma current control is proposed and derived from the conventional space-vector modulation and two-phase modulation. A simplification of the complex self-and mutual inductances in a PMSG is demonstrated. The proposed current control can achieve the current waveform tracking through the simplification of winding inductances without parameter designing procedure of the feedback controller. The computation time of the microcontroller is reduced via the proposed current control scheme. The processing times of the conventional control and the D-Sigma control are compared. Moreover, the dc-link voltage can be well regulated by the proposed OCVR. This method can reduce the complexity of the voltage controller design. The merits of these two methods are easy to implement and the parameter designing procedure of the feedback controller is unnecessary. In addition, the system stability and the parameter sensitivity are analyzed and evaluated. Some measured waveforms verify the current tracking, torque ripple, dynamic performance and voltage regulation of the SPMSG drive. The reduction of the switching losses is verified by the calculation results.
This paper presents a three-phase transformerless uninterruptible power supply (UPS) with sinusoidal pulse width modulation (SPWM) based division-summation (D-Sigma) digital control. A transformerless UPS controls the power flow between dc link and utility grid, as well as tracks the ac reference voltage. The proposed control law derived with D-Sigma digital approach takes into account the effects of dc-link voltage fluctuation, grid-voltage distortion and inductance variation due to different current levels. Thus, distortion of input current and filter inductor core size can be reduced significantly. However, circulating current may flow through the common ground between the input power factor corrector (PFC) and the output three-phase four-wire inverter. The derived control law based on SPWM can suppress this circulating current and regulate output voltages tightly. Experimental results measured from a three-phase transformerless UPS have confirmed the analysis and discussion of the proposed control approach.
A division-summation (D-Sigma) digital control for three-phase inverters to achieve active and reactive power injection has been presented. It can overcome the limitation of abc to dq frame transformation. However, the D-Sigma control requires four sets of control laws to cover four quadrant operations, namely, grid connection (power factor (PF) 1 similar to +/- 0.866), rectification with PF correction, PF leading (0 similar to 0.866), and PF lagging (0 similar to-0.866). Moreover, the switching sequences for the four modes are also different from each other, increasing complexity of firmware programming. In this paper, improvement of the control law derivation and region selection for the D-Sigma digital control is presented. By selecting the zero-crossing points of phase voltages as region transitions, the control laws and the related parameter tables for the four modes can be unified to a general form. The switching sequences of the four modes are also unified to the switching pattern of the grid-connectionmode. Additionally, a D-Sigma transformation matrix is identified to simplify the derivation procedure of the division (D) and summation (Sigma), which can obtain the control law directly. Measured results from a 10-kVA 3 phi bidirectional inverter have been presented to confirm the improvement.
This paper presents a division-summation (D-Sigma) digital control based modular multilevel converter. Modular multilevel converters (MMC) have been applied to static synchronous compensators (STATCOM), high-voltage direct-current transmission (HVDCT), back-to-back power transfer systems, wind/solar power generation and battery storage systems. The D-Sigma digital control is adopted to track current reference, balance dc-bus capacitor voltage and regulate cell module capacitor voltage. The adopted D-Sigma digital control can accommodate wide filter inductance variation and take care of source voltage harmonics to achieve fast tracking response and low-distortion output current for the applications of active and reactive power injection and rectification with power factor correction. Based on power-balance principle, the combination of dc offset current and the ac current of each arm can be determined. According to charge-balance principle and with the D-Sigma digital control, dc-bus capacitor voltage balancing and cell voltage regulation can be achieved. To ensure the output current with low harmonics, a limitation factor for cell voltage regulation is discussed. In the paper, the MMC configuration is introduced first, and then the control laws for current tracking and voltage regulation are derived in detail. Simulated and experimental results obtained from a 54 kW MMC have verified the analysis and discussion.
Previous findings on the diagnostic validity and reliability of generalized anxiety disorder (GAD)-associated symptom criteria suggest need for further evaluation. The current study examined convergent validity and specificity of GAD-associated symptoms in a representative Singapore community sample. The Singapore of Mental Health Study a cross-sectional epidemiological survey conducted among 6166 Singapore residents aged 18 and older. The Composite International Diagnostic Interview version 3.0 was used to diagnose mental disorders. Associated symptoms in the GAD criteria and autonomic hyperactivity symptoms showed convergent validity with a GAD diagnosis. However, associated symptoms of GAD were also linked to major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder, suggesting lack of adequate specificity. The inability of the diagnostic criteria to differentiate GAD from symptoms of other conditions highlights the need to better define its associated symptoms criteria. The relationship of overlapping symptoms between GAD and MDD is also discussed.
The control of UPS inverters has a special importance in applications where a high quality output voltage is needed. Several control schemes have been proposed for the control of three-phase inverter. This paper presents a simple and powerful control scheme using model predictive control (MPC). It uses a discrete-time model of the system to predict the behaviour of the output voltage for all possible switching states generated by the inverter. Then, a cost function is used for selecting the optimal switching state that will be applied at the next sampling instant. The simulation results under linear and nonlinear loads are presented, using MATLAB/Simulink tools, verifying the feasibility and good performance of the proposed control scheme. Finally, experimental results are presented, using HIL simulation, to verify the feasibility and good performance of the proposed MPC under realistic conditions.
Design and implementation of a current controlled single stage single phase integrated AC/DC isolated Power Factor Correction (PFC) converter is -presented in this paper. With the integrated topology reduces the number control switches. The proposed converter has the advantage of low bulk capacitor voltage and only single control switch hence reduce in complexity in control and cost. Sub-harmonic oscillations which are produced in conventional current controller. By adding an external compensating signal effect of oscillations are reduced and performance of the converter is improved. The proposed scheme is implemented in real time by TMS320F2812 digital signal processor (DSP) board. The performance of converter is verified both experimentally and by simulation at different load and line conditions. The proposed converter is designed for 90-230 V, 50 Hz AC input, 48 V DC output and operating at 100 kHz switching frequency. The Experimental results shows that the DSP-based fuzzy controlled single phase single switch integrated PFC converter achieve high power factor and satisfies IEC-61000-3-2 and other European input current harmonic limits for Class-C & Class-D applications.
Viruses with segmented RNA genomes must package the correct number of segments for synthesis of infectious virus particles. Recent studies suggest that the members of the Reoviridae family with segmented double-stranded RNA genomes achieve this challenging task by forming RNA networks of segments prior to their recruitment into the assembling capsid albeit direct evidence is still lacking. Here, we investigated the capability of virus recovery by preformed complexes of ten RNA segments of Epizootic Haemorrhagic Disease Virus ( EHDV), a Reoviridae member, by transcribing exact T7 cDNA copies of genomic RNA segments in a single in vitro reaction followed by transfection of mammalian cells. The data obtained was further confirmed by RNA complexes generated from Bluetongue virus, another family member. Formation of RNA complexes was demonstrated by sucrose gradient ultracentrifugation, and RNA-RNA interactions inherent to the formation of the RNA complexes were demonstrated by electrophoretic mobility shift assay. Further, we showed that disruption of RNA complex formation inhibits virus recovery, confirming that recruitment of complete RNA networks is essential for packaging and consequently, virus recovery. This efficient reverse genetics system will allow further understanding of evolutionary relationships of Reoviridae members and may also contribute to development of antiviral molecules.
Rice false smut caused by Ustilaginoidea virens is a destructive disease in many rice-growing areas. Mycoviruses have been described in many fungal species, but there is little information regarding mycoviruses in U. virens. In this study, double-stranded (ds) RNA banding patterns were assessed in 198 wild-type isolates of U. virens obtained from different geographical regions in China. The presence of viral infections was unusually common in U. virens: 188 of the 198 isolates contained dsRNA elements with viral characteristics, and the presence of mixed infections with two or more related or unrelated mycoviruses was commonly detected. The GX-1 isolate contained four dsRNA mycoviruses: Ustilaginoidea virens RNA virus 1 (UvRV1) belonging to Totiviridae, Ustilaginoidea virens RNA virus 4 (UvRV4) belonging to an unclassified family which includes the Curvularia thermal tolerance virus, and the last two probably belonging to Partitiviridae. Biological comparisons of virus-free and infected fungal isolates revealed that UvRV1 strain GX-1 and UvRV4 were likely cryptic, since the infected strains did not show apparent symptoms or debilitation. Northern blotting experiments revealed that UvRV1 strain GX-1 and UvRV4 were frequently found in U. virens, irrespective of the place of origin, and similarly sized dsRNA bands were not always of similar sequence. Thus, our findings suggest that mycoviruses infecting U. virens in China are widespread and highly diverse. (C) 2014 Elsevier B.V. All rights reserved.
The dual active bridge (DAB) converter has been widely used in the distributed power systems and the energy storage devices. However, the inherent nonlinearity of the DAB converter can cause serious stability problem. In this paper, the dynamics of a digital controlled DAB converter with output voltage closed loop control is studied. Firstly, to accurately study the nonlinear dynamics and stability in a DAB converter, a full discrete-time model for the DAB converter is established. The model considers the ESR of the output capacitor and also considers the digital control delay and sample-and-hold process. Using this model, the stability of the DAB converter versus the parameter of the proportional controller is analyzed and the stability boundary is accurately predicted. Further, this paper also points out that the ESR of the output capacitor can bring a great effect to the stability of the system. Finally, simulation and experimental results verify the theoretical analysis.
The concepts expressed by social role terms such as artist and scientist are unique in that they seem to allow two independent criteria for categorization, one of which is inherently normative (Knobe, Prasada, & Newman, 2013). This study presents and tests an account of the content and structure of the normative dimension of these dual character concepts. Experiment 1 suggests that the normative dimension of a social role concept represents the commitment to fulfill the idealized basic function associated with the role. Background information can affect which basic function is associated with each social role. However, Experiment 2 indicates that the normative dimension always represents the relevant commitment as an end in itself. We argue that social role concepts represent the commitments to basic functions because that information is crucial to predict the future social roles and role-dependent behavior of others.
Neuroscience investigations of emotional influences on social cognition have been dominated by the somatic marker hypothesis and dual-process theories. Taken together, these lines of inquiry have not provided strong evidence that emotional influences on social cognition rely on neural systems which code for bodily signals of arousal nor distinguish emotional reasoning from other modes of reasoning. Recent findings raise the possibility that emotionally influenced social cognition relies on two stages of neural changes: once when emotion is elicited and a different set of changes at the time of social cognitive judgment. These findings suggest that affect infusion models may be a fruitful framework for bridging neuroscience and psychological understanding of the role of emotion in social cognition.
Since the decision of non-price feature such as product quality draws a little attention in the literature of dual-channel supply chains, this paper investigates price and quality decisions in dual-channel supply chains, in which a single product is delivered through a retail channel, a direct channel, or a dual channel with both retail and direct channels. Considering the supply chains can be centralized or decentralized, we demonstrate that quality improvement can be realized when a new channel is introduced. Moreover, we employ two themes in terms of channel-adding Pareto zone to characterize the impacts of channel structures on supply-chain performance, including the whole system's profit (for the centralized system), each player's profit (for the decentralized system), and consumer surplus. When price and quality decisions are considered, we find the supply chain performance could be improved due to a new channel augmented. Moreover, we show the effects of the quality sensitivity parameters of different channels on price and product quality, as well as profits and consumer surplus. (C) 2016 Elsevier B.V. All rights reserved.
Hepatitis A virus is one of five types of hepatotropic viruses that cause human liver disease. A similar liver disease is also identified in ducks caused by Duck Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be detected in urine. However, how those viruses enter into the urine is largely unexplored. To elucidate the potential mechanism, we used the avian hepatotropic virus to investigate replication strategies and immune responses in kidney until 280 days after infection. Immunohistochemistry and qPCR were used to detect viral distribution and copies in the kidney. Double staining of CD4+ or CD8+ T cells and virus and qPCR were used to investigate T cell immune responses and expression levels of cytokines. Histopathology was detected by standard HE staining. In this study, viruses were persistently located at scattered renal tubules. No CD4+ or CD8+ T cells were recruited to the kidney, which was only accompanied by transient cytokine storms. In conclusion, the extremely scattered infection was the viral strategy to escape host immunity and may persistently shed virus into urine. The deletion of Th or Tc cell responses and transient cytokine storms indeed provide an advantageous renal environment for their persistent survival.
Purpose of review The review intends to describe recent studies on the development of pancreatic cancer from a genetic, molecular, and microenvironment perspective. Recent findings Pancreatic cancer has been discovered to have distinct molecular subtypes based on transcriptome analyses that may have implications for treatment. Recent studies are also mapping the complex molecular biology of this cancer as it relates to the core signaling abnormalities inherent to this disease. There have been discoveries of novel modes of regulation of pancreatic cancer development, including alterations in key transcription factors, epigenetic modifiers, and metabolic pathways. Studies of the tumor-associated microenvironment continue to reveal its complex role in tumor development. Summary Pancreatic cancer development appears to depend on a multifaceted network of signals that are dynamic, involve multiple cell types, and are linked to spatiotemporal factors in tumor evolution. Understanding the development of pancreatic cancer in this context is key to identifying novel and effective targets for treatment.
Theileria spp. and Anaplasma spp., which are important tick-borne pathogens (TBP5), impact the health of humans and animals in tropical and subtropical areas. Theileria and Anaplasma co-infections are common in sheep and goats. Following alignment of the relevant DNA sequences, two primer sets were designed to specifically target the Theileria spp. 18S rRNA and Anaplasma spp. 16S rRNA gene sequences. Genomic DNA from the two genera was serially diluted tenfold for testing the sensitivities of detection of the primer sets. The specificities of the primer sets were confirmed when DNA from Anaplasma and Theileria (positive controls), other related hematoparasites (negative controls) and ddH2O were used as templates. Fifty field samples were also used to evaluate the utility of single PCR and duplex PCR assays, and the detection results were compared with those of the PCR methods previously published. An optimized duplex PCR assay was established from the two primer sets based on the relevant genes from the two TBPs, and this assay generated products of 298-bp (Theileria spp.) and 139-bp (Anaplasma spp.). The detection limit of the assay was 29.4 x 10(-3) ng per I, and there was no cross-reaction with the DNA from other hematoparasites. The results showed that the newly developed duplex PCR assay had an efficiency of detection (P >0.05) similar to other published PCR methods. In this study, a duplex PCR assay was developed that can simultaneously identify Theileria spp. and Anaplasma spp. in sheep and goats. This duplex PCR is a potentially valuable assay for epidemiological studies of TBP5 in that it can detect cases of mixed infections of the pathogens. (C) 2017 Elsevier Inc. All rights reserved.
The temporal pole (TP) has been associated with diverse functions of social cognition and emotion processing. Although the underlying mechanism remains elusive, one possibility is that TP acts as domain-general hub integrating socioemotional information. To test this, 26 participants were presented with 60 empathy-evoking film clips during fMRI scanning. The film clips were preceded by a linguistic sad or neutral context and half of the clips were accompanied by sad music. In line with its hypothesized role, TP was involved in the processing of sad context and furthermore tracked participants' empathic concern. To examine the neuromodulatory impact of TP, we applied nonlinear dynamic causal modeling to a multisensory integration network from previous work consisting of superior temporal gyrus (STG), fusiform gyrus (FG), and amygdala, which was extended by an additional node in the TP. Bayesian model comparison revealed a gating of STG and TP on fusiform-amygdalar coupling and an increase of TP to FG connectivity during the integration of contextual information. Moreover, these backward projections were strengthened by emotional music. The findings indicate that during social cognition, TP integrates information from different modalities and top-down modulates lower-level perceptual areas in the ventral visual stream as a function of integration demands.
Time-domain simulations are heavily used in today's planning and operation practices to assess power system transient stability, posttransient voltage/frequency profiles as well as oscillatory behavior following severe contingencies to comply with industry standards. Because of the increased modeling complexity, it is many times slower than real time for state-of-the-art commercial software packages to complete a dynamic simulation for a large-scale model. With the growing stochastic behavior introduced by emerging technologies, power industry has seen a growing need for performing security assessment in real time. This paper presents an innovative parallel implementation framework to speed up a single dynamic simulation by leveraging the existing stability model library in commercial tools through their application programming interfaces (APIs). Several high performance computing (HPC) techniques are explored and implemented such as parallelizing the calculation of generator current injection, identifying fast linear solvers for network solution, and parallelizing data outputs when interacting with APIs in the commercial package, TSAT. The proposed method has been tested on a Western Electricity Coordinating Council (WECC) planning base case with detailed synchronous generator models and it exhibits outstanding scalable performance with sufficient accuracy.
Conventional Organic Rankine Cycles (ORCs) using ambient air as their coolant cannot fully utilize the greater temperature differential available to them during the colder months. However, changing the working fluid composition so its boiling temperature matches the ambient temperature as it changes has been shown to have potential to increase year-round electricity generation. Previous research has assumed that the cycle pressure ratio is able to vary without a major loss in the isentropic efficiency of the turbine. This paper investigates if small scale ORC systems that normally use positive-displacement expanders with fixed expansion ratios could also benefit from this new concept. A numerical model was firstly established, based on which a comprehensive analysis was then conducted. The results showed that it can be applied to systems with positive-displacement expanders and improve their year-round electricity generation. However, such an improvement is less than that of the systems using turbine expanders with variable expansion ratios. Furthermore, such an improvement relies on heat recovery via the recuperator. This is because expanders with a fixed expansion ratio have a relatively constant pressure ratio between their inlet and outlet. The increase of pressure ratio between the evaporator and condenser by tuning the condensing temperature to match colder ambient condition in winter cannot be utilised by such expanders. However, with the recuperator in place, the higher discharging temperature of the expander could increase the heat recovery and consequently reduce the heat input at the evaporator, increasing the thermal efficiency and the specific power. The higher the amount of heat energy transferred in the recuperator, the higher the efficiency improvement.
Dysfibrinogenemia is characterized by blood coagulation dysfunction induced by an abnormal molecular structure of fibrinogen. Here, we describe a new case. A 32-year-old female was suspected of having dysfibrino-genemia during routine laboratory screening, based on her decreased functional fibrinogen level, normal fibrinogen antigen level, and prolonged thrombin time. We extracted DNA and performed polymerase chain reaction and DNA sequencing to identify genetic mutation. Fibrin polymerization, the kinetics of the fibrinopeptide release, scanning electron microscopy, mass spectrometric analysis, fibrin cross-linking, sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot were conducted. DNA sequencing identified a heterozygous point mutation, Gly13Arg in A alpha chain. Fibrin polymerization was markedly impaired (prolonged lag phase and decreased final turbidity). The rate and extent of fibrinopeptide A release from the patient were abnormal and reduced. The mass spectrometry analysis revealed the presence of mutant fibrinogen chains in the patient's circulation. Electron micro-graphs revealed abnormal fibrin clots. Fibrin cross-linking was normal. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot showed no difference. We report a new case with a mutation in the fibrinopeptide A region, A alpha Gly13Arg. These results indicated that the functional abnormalities were related to delayed and defective fibrinopeptide A cleavage and likely impaired thrombin binding.
Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis (n=15), uterine fibroid-induced moderate dysmenorrhoea (n=7) and tubal infertility with no pain (n=6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.
Dystonia musculorum (dt) is an inherited autosomal recessive neuropathy in mice. Homozygous animals display primarily sensory neuro degeneration resulting in a severe loss of coordination. Several dt strains exist, including spontaneous mutants dt-Alb (Albany), dt-J (Jackson Labs), and dt-Frk (Frankel), and a transgene insertion mutant, Tg4. They contain mutations in the gene encoding Bullous Pemphigoid Antigen 1 (BPAG1), or dystonin. BPAG1 is a member of the plakin family of cytolinker proteins. BPAG1 is alternatively spliced to produce several isoforms, including the major brain-specific isoform, BPAG1a. The neurological phenotype observed in dt-Alb mice is thought to result from the absence of BPAG1a protein in the developing nervous system. The goal of this study was to determine the precise molecular nature of the dt-Alb mutation and examine residual BPAG1 expression in homozygous dt-Alb mice. A combination of molecular biological strategies revealed that the dt-Alb lesion is a deletion-insertion eliminating a large part of the coding region of BPAG1a. The molecular lesion in the dt-Alb BPAG1 allele is expected to render it completely non-functional. Although transcripts corresponding to BPAG1 segments still remaining in homozygous dt-Alb mice could be detected by RT-PCR, there was no positive signal for BPAG1 in the brain of dt-Alb mice by Northern blotting. Western blotting with polyclonal anti-BPAG1 antibodies confirmed the absence of functional BPAG1 protein (full-length or truncated) in the dt-Alb brain. our identification of the 5' junction of the dt-Alb insertion makes it possible to genotype dt-Alb animals by standard PCR. (c) 2006 Elsevier B.V. All rights reserved.
Genetic findings of the past years have provided ample evidence for a substantial etiologic heterogeneity of dystonic syndromes. While an increasing number of genes are being identified for Mendelian forms of isolated and combined dystonias using classical genetic mapping and whole-exome sequencing techniques, their precise role in the molecular pathogenesis is still largely unknown. Also, the role of genetic risk factors in the etiology of sporadic dystonias is still enigmatic. Only the systematic ascertainment and precise clinical characterization of very large cohorts with dystonia, combined with systematic genetic studies, will be able to unravel the complex network of factors that determine disease risk and phenotypic expression.
ATR in EHEC 0157:H7 and the cross-protection effects thus induced lead to the uncertainty of food safety. This study aimed to identify factors that are associated with the ATR in EHEC 0157:H7 under stomach acidity using RNA-seq. In total, 223 DEGs in E. coil 0157:H7 and 110 DEG5 in E. coli after acid treatment were identified, including 118 upregulated and 105 downregulated in EHEC 0157:H7, and 89 upregulated and 21 downregulated in E. coil ATCC 25922. According to our results, when facing the ATR environment, protein Asr regulated the whole add resistance process. In E. coli ATCC 25922, cadA and cadB mediate the lysine decarboxylation consumed the extra protons inside and keep the neutral pH value in cytoplasm to protect the E. coli from death. In contrast, oxidation-reduction mediated by ahpC, which was activated by the depression of oxyR, and hydrogenation mediated by mhpA consumed the protons inside keeping the neutral pH value to protect the EHEC 0157:H7 from harm induced by a low pH environment. In addition, EHEC 0157:H7 expressed more anti-oxidation enzymes to repair damage caused by acid stress, which enhanced its resistance to acid compared to E. coli ATCC 25922. (c) 2017 Elsevier Ltd. All rights reserved.
Escherichia coli O157 related foodborne illnesses continue to be one of the most important global public health problems in the world. This study aims to determine E. coli O157 prevalence in 375 chicken meat parts and giblets. The samples were collected randomly from several supermarkets and butchers in Diyarbakir, a city in southeast Turkey. They were analyzed and confirmed using the immunomagnetic separation (IMS), Vitek (R) 2 microbial identification system and polymerase chain reaction (PCR) method. This study also aims to detect the presence of fliC(H7), eaeA, stx(1), stx(2) and hlyA genes by using PCR. The overall E. coli O157 prevalence in chicken meat parts and giblets was 1.3%. All of the E. coli O157 isolates carried rfbE(O157) and eaeA genes; but not any fliC(H7) and hlyA genes. The E. coli O157 isolates obtained from drumstick and breast meat carried either stx(1) or stx(2) genes, which were related to important virulence factors of the disease.
Phosphorylation and ubiquitination are pervasive post-translational modifications that impact all processes inside eukaryotic cells. The role of each modification has been studied for decades, and functional interplay between the two has long been demonstrated and even more widely postulated. However, our understanding of the molecular features that allow phosphorylation to control protein ubiquitination and ubiquitin to control phosphorylation has only recently begun to build. Here, we review examples of regulation between ubiquitination and phosphorylation, aiming to describe mechanisms at the molecular level. In general, these examples illustrate phosphorylation as a versatile switch throughout ubiquitination pathways, and ubiquitination primarily impacting kinase signalling in a more emphatic manner through scaffolding or degradation. Examples of regulation between these two processes are likely to grow even further as advances in molecular biology, proteomics, and computation allow a system-level understanding of signalling. Many new cases could involve similar principles to those described here, but the extensive co-regulation of these two systems leaves no doubt that they still have many surprises in store. (C) 2017 Elsevier Ltd. All rights reserved.
The European Academy of Allergy and Clinical Immunology (EAACI) Junior Members (JM) comprise the largest EAACI section with around 4000 clinicians and scientists under 35 years of age working in the field of allergy and clinical immunology. The Junior Member collaboration with Clinical and Translational Allergy Journal is a mutually beneficial relationship providing Junior Members of EAACI with excellent opportunities to publish their work in the Journal, enhance their visibility in their respective field, and get involved with Journal-related activities and processes. In the future, this collaboration will grow, not only by the consolidation of these activities, but also by the implementation of new initiatives, such as a platform for discussing and/or publishing Junior Members' dissertations in the Journal. From the CTA perspective, the collaboration presents an opportunity to promote a new generation of allergists with experience of conducting and presenting research, with improved skills in critical review.
Objective: Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGFbinding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. Design: 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real timereverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CFCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Results: Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho = 0361, p < 0.001) with each other, while presenting significant differences across age groups (all p values < 0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p = 0.558) or after completion (p = 0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p = 0.487) or after (p = 0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p = 0.499; OS: p = 0.220) or IGFBP-3 (DFI: p = 0.900; OS: p = 0.406) serum levels. Conclusions: IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer. (C) 2017 Elsevier Ltd. All rights reserved.
Home visitation programs are designed to provide comprehensive services that promote parent's abilities to create stable, nurturing care environments for their children. In order for program goals to be met, parents must participate actively and be engaged with the programs' mission. However, promoting engagement and participation are complex processes that have been understudied in research on home visitation. The current qualitative study examined how a national, federally funded home visitation program, Early Head Start (EHS), engaged and retained families so that potentially helpful preventative interventions could be delivered. The study also identified barriers to active engagement. Semistructured interviews were conducted with 10 parents of children enrolled in EHS. Findings suggest that engagement increased when EHS reduced social isolation by forming connections among parents and when the program focused on involving parents in fostering their children's meeting of important developmental milestones. Barriers to engagement identified included logistical and organizational challenges, as well as parental biases and differences in values and attitudes. Practice and policy recommendations for improving EHS and other programs that serve similar populations to increase engagement are discussed.
Background: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Methods: Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Results: Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Conclusions: Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.
Background: A number of mosquito vectors bite and rest outdoors, which contributes to sustained residual malaria transmission in endemic areas. Spatial repellents are thought to create a protective "bubble" within which mosquito bites are reduced and may be ideal for outdoor use. This study builds on previous studies that proved efficacy of transfluthrin-treated hessian strips against outdoor biting mosquitoes. The goal of this study was to modify strips into practical, attractive and acceptable transfluthrin treated sisal and hessian emanators that confer protection against potential infectious bites before people use bed nets especially in the early evening and outdoors. This study was conducted in Kilombero Valley, Ulanga District, south-eastern Tanzania. Results: The protective efficacy of hand-crafted transfluthrin-treated sisal decorative baskets and hessian wall decorations against early evening outdoor biting malaria vectors was measured by human landing catches (HLC) in outdoor bars during peak outdoor mosquito biting activity (19: 00 to 23: 00 h). Treated baskets and wall decorations reduced bites of Anopheles arabiensis mosquitoes by 89% (Relative Rate, RR = 0.11, 95% confidence interval, CI: 0.09-0.15, P < 0.001) and 86% (RR = 0.14, 95% CI: 0.11-0.18, P < 0.001), respectively. In addition, they significantly reduced exposure to outdoor bites of Culex spp. by 66% (RR = 0.34, 95% CI: 0.22-0.52, P < 0.001) and 56% (RR = 0.44, 95% CI: 0.29-0.66, P < 0.001), respectively. Conclusion: Locally hand-crafted transfluthrin-treated sisal decorative baskets and hessian wall decorations are readily acceptable and confer protection against outdoor biting malaria vectors in the early evening and outdoors: when people are resting on the verandas, porches or in outdoor social places such as bars and restaurants. Additional research can help support the use of such items as complementary interventions to expand protection to communities currently experiencing outdoor transmission of mosquito-borne pathogens.
Metacognition refers to a range of cognitive processes that allow one to form complex ideas of self and others and to use this information to navigate psychosocial challenges. Several studies in both early-phase and prolonged schizophrenia have demonstrated not only that significant deficits in metacognitive ability are present, but importantly that they are associated with significant functional impairment and decreased quality of life. In spite of the importance of metacognitive impairment in schizophrenia, relatively little is known about the biological substrates that may contribute to this dysfunction. In this study, we examined the relationship between resting state functional connectivity of the medial prefrontal cortex (mPFC), a structure shown in prior voxel-based morphometry studies to be associated with metacognition, with metacognitive function in an early phase psychosis cohort (n=18). Analyses revealed a positive association of resting state functional connectivity between the mPFC and precuneus and posterior cingulate structures and metacognitive ability. These results provide evidence of disrupted resting state connectivity in structures relevant to metacognitive dysfunction in early-phase psychosis, which may have implications for pathophysiological models of complex cognitive deficits in this illness.
The paper sets out to explore the possibility that citizen-led surveys provide a better coverage of populations and specifically of hard-to-reach poorer areas than the international standardized household surveys which are the basis for many of the estimates used in assessing progress toward meeting the MDGs and will be for the SDGs. This hypothesis is based on the argument that, the local volunteer enumerators of citizen-led surveys are likely to be more sensitive to the specificities of local population distribution and (recent) changes than those centrally trained; and may be more effective at reaching hard-to reach groups such as those nomadic groups and those in urban slums. To test the hypothesis, the results of UWEZO (meaning "capability") surveys have been compared at a regional level with those of contemporaneous DHS surveys in Kenya, Tanzania, and Uganda for estimates of access to water and electricity. Overall, at national level, we find that UWEZO estimates for access to clean water were lower at a statistically significant level than those of DHS and these differences were statistically significant at the 0.01% level; in particular, the DHS values were much higher in regions where there are high concentrations of nomads and of urban slums, implying that the UWEZO surveys "catch" more poverty. The suggestion therefore is that citizen surveys such as UWEZO provide better, and more accurate, coverage of the poorest of the poor. Using the lowest estimate of the percentage "missing" in urban slums and extrapolating to all developing countries, there are an estimated 369 million missing from the sampling frames of standardized household surveys worldwide. This has important implications for the "Leave no one behind" appeal of the UN Secretary General and for the UN's "Data Revolution". Some suggestions are made about how to progress improved population estimates. (C) 2017 Elsevier Ltd. All rights reserved.
Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight loss. Two groups of adolescent girls (AN-A, weight-recovered following AN) and (HC-A, healthy comparison) completed a functional magnetic resonance imaging task involving social evaluations, allowing comparison of neural activations during self-evaluations, friend-evaluations, and perspective-taking self evaluations. Although the two groups were not different in their whole-brain activations, anxiety and body shape concerns were correlated with neural activity in a priori regions of interest. A cluster in medial prefrontal cortex and the dorsal anterior cingulate correlated with the body shape questionnaire; subjects with more body shape concerns used this area less during self than friend evaluations. A cluster in medial prefrontal cortex and the cingulate also correlated with anxiety such that more anxiety was associated with engagement when disagreeing rather than agreeing with social terms during self evaluations. This data suggests that differences in the utilization of frontal brain regions during social evaluations may contribute to both anxiety and body shape concerns in adolescents with AN. Clinical follow-up was obtained, allowing exploration of whether brain function early in course of disease relates to illness trajectory. The adolescents successful in recovery used the posterior cingulate and precuneus more for friend than self evaluations than the adolescents that remained ill, suggesting that neural differences related to social evaluations may provide clinical predictive value. Utilization of both MPFC and the precuneus during social and self evaluations may be a key biological component for achieving sustained weight-recovery in adolescents with AN. (C) 2016 Elsevier Ltd. All rights reserved.
Background: By the end of the 2013-2016 West African Ebola Virus Disease (EVD) outbreaks, a total of 3814 cases (probable and confirmed) and 2544 deaths were reported in Guinea. Clearly, surveillance activities aiming at stopping human-to-human transmission have been the breakthrough of EVD outbreak management, but their application has been at times easier said than done. This article presents five confirmed or probable EVD cases that arose in Conakry towards the end of the Guinea epidemic, which demonstrate flaws in surveillance and follow-up. Case presentation: For case 1, safe burial requirements were not followed. For cases 1 and 2, negative Polymerase Chain Reaction (PCR) results were interpreted as no infection. For the first case, the sample may have not been taken properly while for the second the disease was possibly at its early stage. Case 3 was stopped at a border health checkpoint and despite her high temperature she was allowed to continue the bus journey. For case 4, an oral swab sample was supposedly taken after death but could not be found for retrospective testing. Despite characteristic symptomatology, case 5 was not identified as a suspect case for as long as 3 weeks. Conclusion: In epidemic contexts, health systems must be able to track all samples of suspect cases and deaths, regardless of their laboratory results. Social mobilization in communities and training in health care facilities must be strengthened at the tail of an outbreak, to avoid the natural slackening of disease surveillance, in particular for long-lasting and deadly epidemics.
The tragic West African Ebola epidemic claimed many lives, but would have been worse still if scientific insights from many disciplines had not been integrated to create a strong technical response. Epidemiology and modelling triggered the international response and guided where response efforts were directed; virology, engineering and clinical science helped reduce deaths and transmission in and from hospitals and treatment centres; social sciences were key to reducing deaths from funerals and in the community; diagnostic and operational research made the response more efficient; immunology and vaccine research contributed to the final stages of the epidemic and will help prevent future epidemics. These varied scientific contributions had to be integrated into a combined narrative, communicated to policymakers to inform decisions, and used by courageous local and international responders in the field in real time. Not every area of science was optimal, and in particular, clinical trials of simple interventions such as fluid management were slow to be adopted and sharing of data was initially poor. This Ebola epidemic demonstrated how science can respond to a major emergency, but also has lessons for better responses in future infectious emergencies. This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.
Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. The majority of ebolavirus species, most notably Zaire ebolavirus, can cause Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, in humans. EVD is associated with case-fatality rates as high as 90%, and there is currently no specific treatment or licensed vaccine available against EVD. Understanding the molecular biology and pathogenesis of ebolaviruses is important for the development of antiviral therapeutics. Ebolavirus encodes several forms of glycoproteins (GPs), which have some interesting characteristics, including the transcriptional editing coding strategy and extensive O-glycosylation modification, clustered in the mucin-like domain of GP1, full-length GP (GP(1,2)), and shed GP. In addition to the canonical role of the spike protein, GP(1,2), in viral entry, ebolavirus GPs appear to have multiple additional functions, likely contributing to the complex pathogenesis of the virus. Here, we review the roles of ebolavirus GPs in viral pathogenesis.
Infection with Epstein-Barr virus (EBV) usually leads to a latent state in B lymphocytes. The virus can be reactivated through two viral transactivators. Zta and Rta, leading to a cascade of gene expression. An EBV DNA array was generated to analyze the pattern of transcription of the entire EBV genome under various Conditions. Firstly, a complete set of temporal expression clusters of EBV genes was displayed by analyzing the array data of anti-IgG-induced Akata cells. In addition to assigning genes of unknown function to the various Clusters, increasing expression of latent genes, including EBNA2, EBNA3A and EBNA 3C, was observed during virus replication. Secondly, gene expression independent of viral DNA replication was analyzed in PAA blocked Akata cells and in chemically induced Raji cells. Several genes with presumed late functions were found to be expressed with early kinetics and independent of vital DNA replication, suggesting possible novel functions for these genes. Finally, the EBV array was used to identify Rta responsive gene expression in Raji cells, and in the EBV-positive epithelial cells NA, using a Zta siRNA strategy. The array data were confirmed by Northern blotting, RT-PCR and reporter assays. All the information here thus provides a better understanding of the control of EBV lytic gene expression. (c) 2005 Elsevier Inc. All rights reserved.
Unaccustomed exercise is known to produce strength loss, soreness, and myocellular disruption. With repeated application of exercise stimuli, the appearance of these indexes of muscle damage is attenuated, the so-called " repeated bout effect." No direct connection has been established between this repeated bout effect and exercise-induced increases in protein turnover, but it appears that a degree of tolerance is developed toward exercise for both. The present study sought to investigate markers of protein degradation by determining the expression of components related to the ubiquitin-proteasome system (UPS) with repeated exercise bouts. Healthy men carried out 30 min of bench stepping, performing eccentric work with one and concentric work with the other leg (n = 14), performing a duplicate exercise bout 8 wk later. A nonexercising control group was included (n = 6). RNA was extracted from muscle biopsies representing time points preexercise, + 3 h, + 24 h, and + 7 days, and selected mRNA species were quantified using Northern blotting. The exercise model proved sufficient to produce a repeated bout effect in terms of strength and soreness. For forkhead box O transcription factor 1 (FOXO1) and muscle RING finger protein-1 (MURF1), strong upregulations were seen exclusively with concentric loading (P < 0.001), while atrogin-1 displayed a strong downregulation exclusively in response to eccentric exercise (P < 0.001). For MURF1 transcription, the first bout produced a downregulation that persisted until the second bout (P < 0.01). In conclusion, the UPS is modulated differentially in response to varying loading modalities and with different time frames in a way that to some extent reflects changes in protein metabolism known to take place with exercise.
Echinococcus Granulosus (EG) is the major cause of cystic echinococcosis in humans and livestock in the world. In Chile is a zoonosis of great importance. The most frequently affected geographic areas are the Regions of Aysen, Los Rios, Los Lagos, Coquimbo and the Araucania. Hence, it was discovered that in endemic areas of hydatidosis there could be several strains and genotypes of EG. In addition, there is evidence that some strains and genotypes are more infectious for human beings than others. This interesting phenomenon of the biology of EG has been studied using molecular biology techniques based on polymerase chain reaction (PCR) and DNA sequence analysis, which has made it possible to characterize the cestode species complex called EG sensu lato (s l) as being comprised of EG sensu stricto (s. s.) (Genotypes G1-G3), E. equinus (G4), E. ortleppi (G5) and E. canadensis (G6-G10), which present an important phenotypic variation detectable in characteristics of the biological cycle, specificity of the intermediate host, pattern of development, pathogenicity, antigenicity, transmission dynamics and, consequently, in the measures needed to control the disease. The aim of this manuscript is to describe the different genotypes of EG described in humans and different livestock host reported in the literature.
Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and non-human animal models for many decades by the biomedical community, but ecological and evolutionary perspectives are lacking. Neuroendocrine-immune interactions can be conceptualized using a series of feedback loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can exert profound influences on these phenotypes, which can in turn reciprocally modulate behavior. For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors can impinge upon neuroendocrine-immune interactions. One classic example is the immunocompetence handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators of traits important for female choice while suppressing the immune system. Reciprocally, neuroendocrine-immune pathways can promote the development of altered behavioral states, such as sickness behavior. Understanding the energetic signals that mediate neuroendocrine-immune crosstalk is an active area of research. Although the field of psychoneuroimmunology (PNI) has begun to explore this crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus has been relatively underappreciated in comparative species. The field of ecoimmunology, while traditionally emphasizing the study of non-model systems from an ecological evolutionary perspective, often under natural conditions, has focused less on the physiological mechanisms underlying behavioral responses. This review summarizes neuroendocrine-immune interactions using a comparative framework to understand the ecological and evolutionary forces that shape these complex physiological interactions. (C) 2016 Elsevier Inc. All rights reserved.
Little research has been conducted specifically on the factors which have a bearing on a special education teacher's decision to report sexual victimization. The aim of this study is to determine what these factors are and the role they play amongst special education teachers in Taiwan. Individual interviews were conducted with eight female and four male special education teachers and thematic analysis was used to interpret the data. The relevant factors are categorized in accordance with the ecological system theory proposed by Bronfenbrenner. Microsystem factors include consequences of reporting, severity of victimization, and characteristics of students with disabilities. Mesosystem factors include relationship with student's family and colleagues, and support from school administration. Exosystem factors include paperwork load, rotation of social workers, and oppositional positions between school and government. Macrosystem factors include emphasis on maintaining harmonious relationships with colleagues and the student's family, and doubts about the applicability of mandatory reporting in cases involving students with disabilities. The results of this study indicate the need for clearer reporting standards for students with disabilities, more support and resources from school administration, and more comprehensive training on the mandatory reporting policy.
Citrus canker, caused by Xanthomonas citri pv. citri, is a serious disease of citrus plants worldwide. Earlier phylogenetic studies using housekeeping genes revealed that X. citri pv. citri is related to many other pathovars, which can be collectively referred as Xanthomonas citri pathovars (XCPs). From the present study, we report the genome sequences of 18 XCPs and compared them with four XCPs available in the public domain. In a tree based on phylogenomic marker genes, all the XCPs form a monophyletic cluster, suggesting their origin from a common ancestor. Phylogenomic analysis using the type strain further established that all the XCPs belong to one species. Clonal analysis of the core genome revealed the presence of two major lineages within this monophyletic cluster consisting of some clonal variants. Incidentally, the majority of these XCPs were first noticed in India, corroborating their clonal relationship and their common origin. Comparative analysis revealed an open pan-genome and the role of interstrain genomic flux of these XCPs since their diversification from a common ancestor. Even though there are wide variations in type III gene effectomes, we identified three core effectors which can be valuable in resistance-breeding programs. Overall, genomic examination of ecological relatives allowed us to dissect the tremendous genomic potential of X. citri species to rapidly evolve into specialized strains infecting diverse crop plants. IMPORTANCE Host specialization is one of the characteristic features of highly evolved pathogens such as the Xanthomonas group of phytopathogenic bacteria. Since the hosts involve staple crops and economically important fruits such as citrus, detailed understanding of the diversity and evolution of such strains infecting diverse plants is important for quarantine purposes. In the present study, we carried out genomic investigation of members of a phylogenetically and ecologically defined group of Xanthomonas strains pathogenic to diverse plants, including citrus. This group includes the oldest Xanthomonas pathovars and also recently emerged pathovars in a particular country where they are endemic. Our high-throughput genomic study has provided novel insights into the evolution of a unique lineage consisting of serious pathogens and their ecological relatives, suggesting the nature, scope, and pattern of rapid and recent diversification. Further, from the level of species to that of clonal variants, the study revealed interesting genomic patterns in diversification of a Xanthomonas lineage and perhaps will inspire careful study of the host range of the included pathovars.
While maps of solar irradiance are readily available, they do not represent the economic viability of a solar project in any particular location. This paper provides a financial analysis with different electricity tariffs and then maps the internal rate of return (IRR) of solar load displacement projects. We examine 25 locations in the southwestern USA and show that IRR maps differ substantially from irradiance maps. Our analysis includes 27 scenarios derived from the following combinations: three types of solar installations (concentrated photovoltaic (CPV), south-facing PV and PV oriented so as to optimize IRR); three project start dates (2016, 2018, 2020); and three price projections for grid-connected systems (optimistic, central, pessimistic). The variation of irradiance across these 25 locatibns is much lower than the variation of IRR. Direct normal irradiance is almost uncorrelated with the IRR from CPV projects, indicating that irradiance alone is a poor predictor of IRR. Tariff differences among the 25 locations, including time of use aspects, play a major role in determining economic viability and IRR varies considerably even within a single city. Orienting PV modules so as to optimize the IRR brings little benefit unless the optimized azimuth is greater than 20 west of south. (C) 2017 Elsevier Ltd. All rights reserved.
The Pharmacogenomics and Personalized Medicine group belongs to the Laboratory of Molecular Biology and Immunology, Department of Pharmacy and is active since 2009 mainly in the field of pharmacogenomics and personalized medicine. Herein, we describe the research interests, collaborations and accomplishments of the Pharmacogenomics and Personalized Medicine group together with the teaching activities of the group that greatly enhance the pharmacogenomics knowledge of graduate/postgraduate students and healthcare professionals.
This paper examines the current electrical generation expansion plan of Ghana and compares it with proposed expansion pathways with higher penetration of Renewable Energy Technologies. An adaptation of Schwartz's Scenario Methodology was used to develop the scenarios which were then analysed using the Long-range Alternatives Planning (LEAP) model. Each of the scenarios represents policy options for generation expansion in Ghana up to 2040. Energy, economic and environmental analysis of the three alternative scenarios compared to the base scenarios was undertaken. Sensitivity results show that, if the country were to follow the generation expansion path described in the renewable energy scenarios, it could reap economic benefits of 0.5-13.23% depending on the developments in fuel prices and renewable technology capital cost. The analysis further quantifies benefits to be derived from a reduction in Greenhouse gases of the scenarios. Policy implications for the generation system of Ghana based on the results are also discussed.
The soil organic carbon (SOC) stock is an important indicator in ecosystem service assessments. Even though a considerable fraction of the total stock is stored in the subsoil, current assessments often consider the topsoil only. Furthermore, mapping efforts are hampered by the limited spatial density of these topsoil measurements. The aim of this study was to assess the SOC stock in the upper 100 cm of soil in 30,556 ha of Low-Input High-Diversity systems, such as nature reserves, in Flanders (Belgium) and compare this estimate with the stock found in the topsoil (upper 15 cm). To this end, we combined depth extrapolation of 139 measurements limited to the topsoil with four digital soil mapping techniques: multiple linear regression, boosted regression trees, artificial neural networks and least-squares support vector machines. Particular attention was given to vegetation characteristics as predictors. For both the stock in the upper 15 cm and 100 cm, a boosted regression trees approach was most informative as it resulted in the lowest cross-validation errors and provided insights in the relative importance of predictors. The predictors of the stock in the upper 100 cm were soil type, groundwater level, clay fraction and community weighted mean (CWM) and variance (CWV) of plant height. These predictors, together with the CWM of specific leaf area, aboveground biomass production, CWV and CWM of rooting depth, terrain slope, CWM of mycorrhizal associations and species diversity also explained the topsoil stock. Our total stock estimates show that focusing on the topsoil (1.63 Tg OC) only considers 36% of the stock in the upper 100 cm (4.53 Tg OC). Given the magnitude of subsoil OC and its dependency on typical ecosystem characteristics, it should not be neglected in regional ecosystem service assessments. (C) 2017 Elsevier B.V. All rights reserved.
Two-component signal transduction system (TCS) is a common mechanism of signal transduction and exists in almost all bacterial species. The putative two-component genes SCO6421 (ecrE(1)) and SCO6422 (ecrE(2)) in Streptomyces coelicolor, which located in the vicinity of the red locus, could modulate the antibiotic undecylprodigiosin (Red) biosynthesis. In this study, the mutants of M145E1 (ecrE(1) knock-out) and M145E2 (ecrE(2) knock-out) were constructed using homologous recombination by double crossover. Red production of two mutants decreased dramatically compared with that of the wild-type strain. However, the production of actinorhodin (Act) of two mutants had not changed significantly. The results suggested that ecrE(1)/ecrE(2) participated in regulating the antibiotic Red synthesis. Northern blotting analysis indicated that ecrE(1)/ecrE(2) may regulate the biosynthesis of Red through influencing the transcription of redD and redZ during cell growth. Therefore, ecrE(1)/ecrE(2), as a specific pair of TCS, most likely regulates the red gene cluster positively.
Thyroid cancer is very common, but skull ectopic thyroid cancer has not been reported in 50 years of literatures in foreign countries. There are only four cases of the skull ectopic thyroid cancer reported in more than 30 years of domestic literature including the cases in this report. This paper aims to investigate the clinical characteristics and possible molecular mechanisms of this rare disease. Five keywords of "thyroid gland", "ectopic thyroid", "thyroid cancer", "ectopic thyroid cancer" and "metastatic thyroid cancer" were included and 50 years of literatures in the PubMed-MEDLINE and Wanfang database were reviewed. By combining the test data of 2 cases of surgical patient tissue microarray specimens-molecular immunology pathology, the possible molecular mechanisms were analyzed and molecular regulation network diagram was drawn. The skull ectopic thyroid cancer has not been reported in 50 years of literatures in foreign countries and there are only four cases of the skull ectopic thyroid cancer reported in more than 30 years of domestic literature including the cases in this report. The molecular expressions of skull ectopic thyroid cancer, orthotopic thyroid cancer, and metastatic thyroid cancer were not the same: (I) AKT (P=0.012, 0.002) and mTOR (P=0.002, 0.004) were highly expressed in the skull ectopic thyroid cancer; (II) BRAF (P=0.029, 0.014) and ERK (P=0.002, 0.001) were highly expressed in orthotopic thyroid cancer; (III) MMP-9 (P=0.023, 0.016) was highly expressed in metastatic thyroid cancer. According to the molecular information base, the PI3K is predicted to be a key crossing gene of the above three signaling pathways, which showed no significant differences in these three thyroid cancers (P=0.692, 0.388, 0.227), but PI3K has regulation roles in the three signaling pathways of Akt/mTOR, MAPK, and NF-kappa B. PI3K gene is an important starting gene of thyroid cancers. After the canceration starts, due to the fact that the local microenvironments of thyroid cancers in different parts are different, the thyroid cancers are regulated by different signaling pathways. The ectopic thyroid cancer was correlated with Akt/mTOR pathway high expression; orthotopic thyroid was related with MAPK/BRAF/ERK signaling pathway high expression; and the metastatic thyroid cancer was related with NFkB/MMP9 high expression.
In high-quality education, topics concerning the behavior and control of electrical machines and power electronics have to be taught not only theoretically but also in a practical manner. Hard-and software tools are necessary to fulfil this obligation. Nevertheless, commercial systems partially lack of functionality or full accessibility to implement custom solutions, which is obligatory in the research and education domain. Therefore, a digital signal processing system is presented, that allows full modification of every used device, both in hardware and in software.
Undergraduate medical curricula typically include forensic and legal medicine topics that are of a highly sensitive nature. Examples include suicide, child abuse, domestic and sexual violence. It is likely that some students will have direct or indirect experience of these issues which are prevalent in society. Those students are vulnerable to vicarious harm from partaking in their medical education. Even students with no direct or indirect experience of these issues may be vulnerable to vicarious trauma, particularly students who are especially empathetic to cases presented. Despite these risks, instruction relating to these topics is necessary to ensure the competencies of graduating doctors to respond appropriately to cases they encounter during their professional careers. However, risk can be minimised by a well-designed and thoughtfully delivered educational programme. We provide recommendations for the successful inclusion of sensitive forensic and legal medicine topics in undergraduate medical curricula. (C) 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
The power of local borders to resist and prevent transnational mobilities in education has received little attention in comparative education. In this article we explore the motif of border immunology' with reference to new history, a mobile paradigm of history teaching, and Greek-Cypriot and Turkish-Cypriot history textbooks as types of local borders that have been impermeable to new history. The overall argument we explore here is that ethnonational forms of collective identities that are imagined to be constitutive of textbook borders account for immunity to mobility and change.
The present research is aimed at analyzing the professional gestures of a museum educator in a specific situation: the demonstration of the Foucault Pendulum in the Arts et Metiers Museum in Paris. What professional gestures can give him the ability to present this object to a mixed audience in a museum space open to visitor circulation? How does he manage to capture the attention of his audience and make scientific knowledge accessible? Does the educator work like a teacher? Such are the questions that the research team had in mind and which allowed them to conceive the scientific museum educator's action from the point of view of professional gestures.
Background: Electroencephalography (EEG) is still a widely used imaging tool that combines high temporal resolution with a relatively low cost. Ag/AgCl metal electrodes have been the gold standard for non-invasively monitoring electrical brain activity. Although reliable, these electrodes have multiple drawbacks: they suffer from noise, such as offset potential drift, and usability issues, for example, difficult skin preparation and cross-coupling of adjacent electrodes. New method: In order to tackle these issues a prototype Electric Potential Sensor (EPS) device based on an auto-zero operational amplifier was developed and evaluated. The EPS is a novel active ultrahigh impedance capacitively coupled sensor. The absence of 1/f noise makes the EPS ideal for use with signal frequencies of similar to 10 Hz or less. A comprehensive study was undertaken to compare neural signals recorded by the EPS with a standard commercial EEG system. Results: Quantitatively, highly similar signals were observed between the EPS and EEG sensors for both free running and evoked brain activity with cross correlations of higher than 0.9 between the EPS and a standard benchmark EEG system. Comparison with existing method(s): These studies comprised measurements of both free running EEG and Event Related Potentials (ERPs) from a commercial EEG system and EPS. Conclusions: The EPS provides a promising alternative with many added benefits compared to standard EEG sensors, including reduced setup time and elimination of sensor cross-coupling. In the future the scalability of the EPS will allow the implementation of a whole head ultra-dense EPS array. (C) 2015 Elsevier B.V. All rights reserved.
Egocentric vs. allocentric perspective during observation of hand movements has been related to self-other differentiation such that movements observed from an egocentric viewpoint have been considered as self-related while movements observed from an allocentric viewpoint have been considered as belonging to someone else. Correlational studies have generally found that egocentric perspective induces greater neurophysiological responses and larger behavioral effects compared to an allocentric perspective. However, recent studies question previous findings by reporting greater (mu) suppression and greater transcranial magnetic stimulation(TMS)-induced motor-evoked potentials (MEPs) during observation of allocentric compared to egocentric movements. Furthermore, self-other differentiation has been generally related to activity within the inferior parietal lobe (IPL), but direct evidence for a causal and functional role of IPL in self-other differentiation is lacking. The current study was therefore designed to investigate the influence that IPL exerts on self-other differentiation. To this aim, we measured the impact of individually adjusted alpha-tuned transcranial alternating current stimulation (tACS) applied over IPL on it-suppression during hands movement observation from an egocentric and allocentric perspective. Electroencephalography (EEG) was recorded during movement observation before and immediately after tACS. Results demonstrated that tACS decreased it-reactivity over sensorimotor (but not visual) regions for egocentric (but not allocentric) movement observation providing direct evidence for a causal involvement of IPL in the observation of self- but not other-related hand movement. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Increased attention on what works' in education has led to an emphasis on developing policy from evidence based on comparing and combining a particular statistical summary of intervention studies: the standardised effect size. It is assumed that this statistical summary provides an estimate of the educational impact of interventions and combining these through meta-analyses and meta-meta-analyses results in more precise estimates of this impact which can then be ranked. From these, it is claimed, educational policy decisions can be driven. This paper will demonstrate that these assumptions are false: standardised effect size is open to researcher manipulations which violate the assumptions required for legitimately comparing and combining studies in all but the most restricted circumstances. League tables of types of intervention, which governments point to as an evidence base for effective practice may, instead, be hierarchies of openness to research design manipulations. The paper concludes that public policy and resources are in danger of being misdirected.
To foster the connection between biochemistry and the supporting prerequisite concepts, a collection of activities that explicitly link general and organic chemistry concepts to biochemistry ideas was written and either assigned as pre-class work or as recitation activities. We assessed student learning gains after using these activities alone, or in combination with regularly-integrated clicker and discussion questions. Learning gains were determined from student performance on pre-and post-tests covering key prerequisite concepts, biochemistry course exams, and stu-dent self-evaluation. Long-term retention of the material was assessed using a comprehensive exam given to a subset of the students. Our results show that using the preclass exercises in combination with integrative questions was effective at improving student performance in both the short and long term. Similar results were obtained at both a large research institution with large class enrollments and at a private liberal arts college with moderate enrollments. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2): 97-104, 2017.
Understanding the rationale for the generation of a pool of highly differentiated effector memory CD8(+) T cells displaying a weakened capacity to scrutinize for peptides complexed with major histocompatibility class I molecules via their T cell receptor, lacking the "signal 2" CD28 receptor, and yet expressing a highly diverse array of innate receptors, from natural killer receptors, interleukin receptors, and damage-associated molecular pattern receptors, among others, is one of the most challenging issues in contemporary human immunology. The prevalence of these differentiated CD8(+) T cells, also known as CD8(+)CD28(-), CD8(+)KIR(+), NK-like CD8(+) T cells, or innate CD8(+) T cells, in non-lymphoid organs and tissues, in peripheral blood of healthy elderly, namely centenarians, but also in stressful and chronic inflammatory conditions suggests that they are not merely end-of-the-line dysfunctional cells. These experienced CD8+ T cells are highly diverse and capable of sensing a variety of TCR-independent signals, which enables them to respond and fine-tune tissue homeostasis.
The trend toward a more fiercely competitive and strictly environmentally regulated electricity market in several countries, including China has led to efforts by both industry and government to develop advanced performance evaluation models that adapt to new evaluation requirements. Traditional operational and environmental efficiency measures do not fully consider the influence of market competition and environmental regulations and, thus, are not sufficient for the thermal power industry to evaluate its operational performance with respect to specific marketing goals (operational effectiveness) and its environmental performance with respect to specific emissions reduction targets (environmental effectiveness). As a complement to an operational efficiency measure, an operational effectiveness measure not only reflects the capacity of an electricity production system to increase its electricity generation through the improvement of operational efficiency, but it also reflects the system's capability to adjust its electricity generation activities to match electricity demand. In addition, as a complement to an environmental efficiency measure, an environmental effectiveness measure not only reflects the capacity of an electricity production system to decrease its pollutant emissions through the improvement of environmental efficiency, but it also reflects the system's capability to adjust its emissions abatement activities to fulfill environmental regulations. Furthermore, an environmental effectiveness measure helps the government regulator to verify the rationality of its emissions reduction targets assigned to the thermal power industry. Several newly developed effectiveness measurements based on data envelopment analysis (DEA) were utilized in this study to evaluate the operational and environmental performance of the thermal power industry in China during 2006-2013. Both efficiency and effectiveness were evaluated from the three perspectives of operational, environmental, and joint adjustments to each electricity production system. The operational and environmental performance changes over time were also captured through an effectiveness measure based on the global Malmquist productivity index. Our empirical results indicated that the performance of China's thermal power industry experienced significant progress during the study period and that policies regarding the development and regulation of the thermal power industry yielded the expected effects. However, the emissions reduction targets assigned to China's thermal power industry are loose and conservative. (C) 2017 Elsevier Ltd. All rights reserved.
We describe a spectrum splitting solar module design approach using ensembles of 2-20 subcells with bandgaps optimized for the AM1.5D spectrum. Device physics calculations and experimental data determine radiative efficiency parameters for III-V compound semiconductor subcells and enable modification of conventional detailed balance calculations to predict module efficiency while retaining computational speed for a wide search of the design space. Accounting for nonideal absorption and recombination rates due to realistic material imperfections allows us to identify the minimum subcell quantity, quality, electrical connection configuration, and concentration required for 50% module efficiency with realistic optical losses and modeled contact resistance losses. We predict a module efficiency of 50% or greater will be possible with 7-10 electrically independent subcells in a spectral splitting optic at 300-500 suns concentration, assuming a 90% optical efficiency and 98% electrical efficiency, provided the subcells can achieve an average external radiative efficiency of 3-5% and a short circuit current that is at least 90% of the ideal. In examining spectrum splitting solar cells with both series-connected and electrically independent subcells, we identify a new design trade-off independent of the challenges of fabricating optimal bandgap combinations. Series-connected ensembles, having a single set of electrical contacts, are less sensitive to lumped series resistance losses than ensembles where each subcells are contacted independently. By contrast, ensembles with electrically independent subcells can achieve lower radiative losses when the subcells are designed for good optical confinement. Distributing electrically independent subcells in a concentrating receiver module allows flexibility in subcell selection and fabrication, and can achieve ultra-high efficiency with conventional III-V cell technology.
Epigallocatechin-3-O-gallate (EGCG), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II)-induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II. Western blotting, Northern blotting, real-time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal-regulated kinase inhibitor SP600125 (JNK inhibitor), EGCG (100 M) and c-Jun N-terminal kinase (JNK) siRNA attenuated endoglin proteins following Ang II induction. In addition, pre-treated Ang II-induced endoglin with EGCG diminished the binding activity of AP-1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II-induced CFs by AP-1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have attenuated endoglin expression significantly in Ang II-induced CFs, as determined through confocal microscopy. Following in vivo acute myocardial infarction (AMI)-related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end-diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin-3-O-gallate (EGCG) attenuated the endoglin expression and myocardial fibrosis by anti-inflammatory effect in vitro and in vivo, the novel suppressive effect was mediated through JNK/AP-1 pathway.
A fish egg envelope is composed of several glycoproteins, called zona pellucida (ZP) proteins, which are conserved among vertebrate species. Euteleost fishes synthesize ZP proteins in the liver, while otocephalans synthesize them in the growing oocyte. We investigated ZP proteins of the Japanese eel, Anguilla japonica, belonging to Elopomorpha, which diverged earlier than Euteleostei and Otocephala. Five major components of the egg envelope were purified and their partial amino acid sequences were determined by sequencing. cDNA cloning revealed that the eel egg envelope was composed of four ZPC homologues and one ZPB homologue. Four of the five eel ZP (eZP) proteins possessed a transmembrane domain, which is not found in the ZP proteins of Euteleostei and Otocephala that diverged later, but is found in most other vertebrate ZP proteins. This result suggests that fish ZP proteins originally possessed a transmembrane domain and lost it during evolution. Northern blotting and RT-PCR revealed that all of the eZP transcripts were present in the ovary, but not in the liver. Phylogenetic analyses of fish zp genes showed that ezps formed a group with other fish zp genes that are expressed in the ovary, and which are distinct from the group of genes expressed in the liver. Our results support the hypothesis that fish ZP proteins were originally synthesized in the ovary, and then the site of synthesis was switched to the liver during the evolutionary pathway to Euteleostei.
MicroRNA (miRNA) is a highly conserved class of small noncoding RNA about 19-24 nucleotides in length that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Tissue miRNA expression studies have discovered a myriad of functions for miRNAs in various aspects, but a role for miRNAs in chicken ovarian tissue at 300 days of age has not hitherto been reported. In this study, we performed the first miRNA analysis of ovarian tissues in chickens with low and high rates of egg production using high-throughput sequencing. By comparing low rate of egg production chickens with high rate of egg production chickens, 17 significantly differentially expressed miRNAs were found (P < 0.05), including 11 known and six novel miRNAs. We found that all 11 known miRNAs were involved mainly in pathways of reproduction regulation, such as steroid hormone biosynthesis and dopaminergic synapse. Additionally, expression profiling of six randomly selected differentially regulated miRNAs were validated by quantitative real-time polymerase chain reaction (RT-qPCR). Some miRNAs, such as gga-miR-34b, gga-miR-34c and gga-miR-216b, were reported to regulate processes such as proliferation, cell cycle, apoptosis and metastasis and were expressed differentially in ovaries of chickens with high rates of egg production, suggesting that these miRNAs have an important role in ovary development and reproductive management of chicken. Furthermore, we uncovered that a significantly up-regulated miRNA-gga-miR-200a-3p- is ubiquitous in reproductionregulation- related pathways. This miRNA may play a special central role in the reproductive management of chicken, and needs to be further studied for confirmation.
To further the understanding of climate change adaptation processes, more attention needs to be paid to the various contextual factors that shape whether and how climate-related knowledge and information is received and acted upon by actors involved. This study sets out to examine the characteristics of forest owners' in Sweden, the information and knowledge-sharing networks they draw upon for decision-making, and their perceptions of climate risks, their forests' resilience, the need for adaptation, and perceived adaptive capacity. By applying the concept of ego-network analysis, the empirical data was generated by a quantitative survey distributed to 3000 private forest owners' in Sweden in 2014 with a response rate of 31%. The results show that there is a positive correlation, even though it is generally weak, between forest owner climate perceptions and (i) network features, i.e. network size and heterogeneity, and (ii) presence of certain alter groups (i.e. network members or actors). Results indicate that forest owners' social networks currently serve only a minimal function of sharing knowledge of climate change and adaptation. Moreover, considering the fairly infrequent contact between respondents and alter groups, the timing of knowledge sharing is important. In conclusion we suggest those actors that forest owners' most frequently communicate with, especially forestry experts providing advisory services (e.g. forest owner associations, companies, and authorities) have a clear role to communicate both the risks of climate change and opportunities for adaptation. Peers are valuable in connecting information about climate risks and adaptation to the actual forest property.
This research seeks to investigate the antecedents of e-Government adoption in a small island developing state. An extended model comprising of the unified theory of acceptance and use of technology 2 and the e-Government adoption model was employed. Results from a cross-sectional survey of 247 citizens show that performance expectancy, facilitating conditions, perceived value are positively related to behavioural intention. Computer self-efficacy is shown to have a significant negative relationship with behavioural intention and resistance to change. Our results further demonstrate that trustworthiness is inversely related to resistance to change. Small island developing states should engage in proper awareness campaigns of e-Government services offered and focusing their efforts on citizens aged 18-39 years old to obtain a critical mass of users. Website design and information quality should be improved paying particular attention to security and privacy, thereby increasing trust and reducing resistance to change. (C) 2017 Elsevier Ltd. All rights reserved.
E-government (E-Govt) services provide new opportunities to citizens by allowing them to use government services (paying electricity bill, e-filing, e-ticketing, get information about government policies & schemes etc.) anytime from anywhere irrespective of geographical location and releases citizens bound by government official hours. Experience plays an important role to change users' intention to adopt, that impacts their behavior and attitude too. The aim of this study was to investigate how citizens experience e-Gov services and how that experience influences their behavior. The study also investigates how users value e-Gov services. The study has used a qualitative approach involving 31 citizens of India, where e-Gov services are still at an early stage. The findings highlight the extent to which citizens are moving from traditional ways of using government services to using it electronically. The study also takes into account the effect of these technological innovations in government settings from a participant's perspective. The implications for researchers and practitioners are then discussed, with emphasis on government need to develop competent e-Gov services. (C) 2017 Elsevier Ltd. All rights reserved.
Unresolved experimental Lyme arthritis in C3H (5-LOX)(-/-) mice is associated with impaired macrophage phag-ocytosis of Borrelia burgdorferi. In the present study, we further investigated the effects of the 5-LOX metabolite, (LT)B-4, on phagocytosis of B. burgdorferi. Bone marrow-derived macrophages (BMDM) from 5-LOX-/- mice were defective in the uptake and killing of B. burgdorferi from the earliest stages of spirochete internali-zation. BMDM from mice deficient for the LTB4 high-affinity receptor (BLT1(-/-)) were also unable to efficiently phagocytose B. burgdorferi. Addition of exogenous LTB4 augmented the phagocytic capability of BMDM from both 5-LOX-/- and BLT1(-/-) mice, suggesting the low-affinity LTB4 receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB4-stimulated BLT1(-/-) BMDM, demonstrating a role for BLT2. However, the lack of a phagocytic defect in BLT2(-/-) BMDM suggested this was a compensatory effect. In contrast, 12-HHT, a natural BLT2-specific high-affinity ligand, and RvE1, a BLT1 agonist, were both unable to boost phagocytosis in BMDM from either 5-LOX-/- or BLT1(-/-) mice, suggesting a specific role for LTB4 in mediating phagocytosis in murine macrophages. This study demonstrates LTB4 promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfil this role in the absence of BLT1.
Peripheral neuronal activation by inflammatory mediators is a multifaceted physiological response that involves a multitude of regulated cellular functions. One key pathway that has been shown to be involved in inflammatory pain isGq/GPCR, whose activation by inflammatory mediators is followed by the regulated response of the cation channel transient receptor potential vanilloid 1 (TRPV1). However, the mechanism that underlies TRPV1 activation downstream of the Gq/GPCR pathway has yet to be fully defined. In this study, we employ pharmacological and molecular biology tools to dissect this activation mechanism via perforated-patch recordings and calcium imaging of both neurons and a heterologous system. We showed that TRPV1 activity downstream of Gq/GPCR activation only produced a subdued current, which was noticeably different from the robust current that is typical of TRPV1 activation by exogenous stimuli. Moreover, we specifically demonstrated that 2 pathways downstream of Gq/GPCR signaling, namely endovanilloid production by lipoxygenases and channel phosphorylation by PKC, converge on TRPV1 to evoke a tightly regulated response. Of importance, we show that only when both pathways are acting on TRPV1 is the inflammatory-mediated response achieved. We propose that the requirement of multiple signaling events allows subdued TRPV1 activation to evoke regulated neuronal response during inflammation.- KumarR., Hazan, A., Geron, M., Steinberg, R., Livni, L., Matzner, H., Priel, A. Activation of transient receptor potential vanilloid 1 by lipoxygenase metabolites depends on PKC phosphorylation.
This paper presents a harmonic instability analysis method using state-space modeling and participation analysis in the inverter-fed ac power systems. A full-order state-space model for the droop-controlled distributed generation (DG) inverter is built first, including the time delay of the digital control system, inner current and voltage control loops, and outer droop-based power control loop. Based on the DG inverter model, an overall state-space model of a two-inverter-fed system is established. The eigenvalue-based stability analysis is then presented to assess the influence of controller parameters on the harmonic instability of the power system. Moreover, the harmonic-frequency oscillation modes are identified, where participation analysis is presented to evaluate the contributions of different states to these modes and to further reveal how the system gives rise to harmonic instability. Based on the participation analysis, a reduced-order model for harmonic instability analysis is also proposed. The experimental results are presented for validating the theoretical analyses.
We studied the metallothionein (NIT) response in cadmium-exposed worms (Eisenia fetida) both at the protein level by Dot Immunobinding Assay (DIA) with a polyclonal antibody raised against the most immunogenic part of this protein and at the expression level by Northern blotting using a specific probe. NIT appeared as two close isoforms. DIA results clearly demonstrated significant differences in MT level of whole worm heat-treated supernatants between E. fetida exposed to Cd concentrations as low as 8 mg Cd kg(-1) of dry soil compared to controls. Northern blotting analysis performed on whole bodies of worms revealed that a single exposure to 8 mg Cd kg-1 of dry soil for I day resulted in the production of NIT mRNA. This response was maintained for exposure of at least I month. Clear differences of NIT gene expression were also observed between worms exposed to different Cd concentrations (8, 80 or 800 mg; Cd kg(-1) of dry soil). Immunocytochemistry demonstrated that NIT was located in the chloragogenous tissue surrounding the gut where metals are known to be accumulated. This work revealed that E. fetida NIT is a sensitive and relevant biomarker of Cd exposure and especially when considering gene expression response. Further experiments have now to prove its usefulness in natural metal-contaminated soil toxicity assessments. (c) 2006 Elsevier Inc. All rights reserved.
We studied metallothionein (NIT) response in the manure worm Eisenia fetida after exposures to cadmium (Cd), zinc (Zn) or cadmium and zinc spiked media. NIT was studied both at the protein level by Dot Immunobinding Assay, (DIA) and at the expression level by Northern blotting. Cd was highly accumulated by worms whereas Zn body concentration was regulated. In addition, Zn would limit Cd accumulation in worms exposed to low Cd concentrations (1 and 8 mg Cd kg(-1) of dry soil). Exposure to a mixture of Cd and Zn at high concentrations increased cytosolic NIT levels. This increase would allow worms to regulate body Zn concentrations and also to limit Cd toxicity. Cd exposures increased gene expression of Cd-binding MT isoform (MT 2A) whereas Zn did not. However, when both metals were at high concentrations in the exposure medium, this expression was further increased. Several hypotheses are proposed to explain the results and the best approach to estimate metal exposure of this earthworm species is given. Further experiments have now to be performed to evaluate the usefulness of these NIT responses for field contaminated soils toxicity assessment using this earthworm species. (C) 2007 Elsevier Inc. All rights reserved.
Chronic organochlorine (OC) exposure has been shown to cause immune impairment in numerous vertebrate species. To determine if elasmobranchs exhibited compromised immunity due to high OC contamination along the coastal mainland of southern California, innate immune function was compared in round stingrays (Urobatis halleri) collected from the mainland and Santa Catalina Island. Proliferation and phagocytosis of peripheral blood, splenic, and epigonal leukocytes were assessed. Percent phagocytosis and mean fluorescence intensity (MFI) were evaluated by quantifying % leukocytes positive for, and relative amounts of ingested fluorescent E. coli BioParticles. Total cell proliferation differed between sites, with mainland rays having a higher cell concentration in whole blood. Sigma PCB load explained significantly higher % phagocytosis in blood of mainland rays, while Sigma PCB and Sigma pesticide loads described increased splenic % phagocytosis and MFI in the mainland population. Data provides evidence of strong OC-correlated immunostimulation; however, other site-specific environmental variables may be contributing to the observed effects. (C) 2016 Elsevier Ltd. All rights reserved.
Instead of analog electronic circuits and components, digital controllers that are capable of active multi-resonant piezoelectric shunting are applied to elastic metamaterials integrated with piezoelectric patches. Thanks to recently introduced digital control techniques, shunting strategies are possible now with transfer functions that can hardly be realized with analog circuits. As an example, the `pole-zero' method is developed to design single-or multi-resonant bandgaps by adjusting poles and zeros in the transfer function of piezoelectric shunting directly. Large simultaneous attenuations in up to three frequency bands at deep subwavelength scale (with normalized frequency as low as 0.077) are achieved. The underlying physical mechanism is attributable to the negative group velocity of the flexural wave within bandgaps. As digital controllers can be readily adapted via wireless broadcasting, the bandgaps can be tuned easily unlike the electric components in analog shunting circuits, which must be tuned one by one manually. The theoretical results are verified experimentally with the measured vibration transmission properties, where large insulations of up to 20 dB in low-frequency ranges are observed.
Purpose: Emergency department assessment represents a critical but often missed opportunity to identify elder abuse, which is common and has serious consequences. Among emergency care providers, diagnostic radiologists are optimally positioned to raise suspicion for mistreatment when reviewing imaging of geriatric injury victims. However, little literature exists describing relevant injury patterns, and most radiologists currently receive neither formal nor informal training in elder abuse identification. Methods: We present 2 cases to begin characterisation of the radiographic findings in elder abuse. Results: Findings from these cases demonstrate similarities to suspicious findings in child abuse including high-energy fractures that are inconsistent with reported mechanisms and the coexistence of acute and chronic injuries. Specific injuries uncommon to accidental injury are also noted, including a distal ulnar diaphyseal fracture. Conclusions: We hope to raise awareness of elder abuse among diagnostic radiologists to encourage future large-scale research, increased focus on chronic osseous findings, and the addition of elder abuse to differential diagnoses.
Objectives: Physical activity may have positive effects on decreasing anxiety, stress and depression, maintaining mental health and ensuring psychological vitality. This study aimed to determine how a "Physical Activity Program" for elderly people in nursing homes affected their depressive symptoms and quality of life. Methods: We included 80 individuals aged >65 years (40 in the intervention group, 40 controls) in this experimental, randomized, controlled pretest-posttest study. Besides socio-demographic data, depressive symptoms and quality of life were assessed by standardized procedures (Beck Depression Scale [BDI], SF 36 Quality of Life Questionnaire) before and after a ten-weeks lasting "Physical Activity Program", consisting of 10 min warm-up activities, 20 mintes rhythmic exercices, 10 min cool-down exercises and a 30 mintes free walking period on four days of the week. Results: In contast to controls, individuals of the intervention group presented with a significant decrease in the BDI after the "Physical Activity Program". Likewise, eight-subscales and two sub-dimensions of the SF 36 Quality of Life Questionnaire significantly improved only in the experimental group (p < 0.05). Conclusions: Our results suggest that a structured physical activity program positively impacts depressive symptoms and quality of life in elderly individuals. (C) 2017 Elsevier B.V. All rights reserved.
Whether total joint replacement (TJR) patients are susceptible to postoperative cognitive dysfunction (POCD) remains unclear due to inconsistencies in research methodologies. Moreover, cognitive reserve may moderate the development of POCD after TJR, but has not been investigated in this context. The current study investigated POCD after TJR, and its relationship with cognitive reserve, using a more rigorous methodology than has previously been utilized. Fifty-three older adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6months). Forty-five healthy controls matched for age, gender, and premorbid IQ were re-assessed after an equivalent interval. Cognition, cognitive reserve, and physical and mental health were all measured. Standardized regression-based methods were used to assess cognitive changes, while controlling for the confounding effect of repeated cognitive testing. TJR patients only demonstrated a significant decline in Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive reserve only predicted change in TMT B scores among a subset of TJR patients. Specifically, patients who showed the most improvement pre to post surgery had significantly higher reserve than those who showed the greatest decline. The current study provides limited evidence of POCD after TJR when examined using a rigorous methodology, which controlled for practice effects. Cognitive reserve only predicted performance within a subset of the TJR sample. However, the role of reserve in more cognitively compromised patients remains to be determined.
Static VAR compensators (SVC) can improve some of the power quality (PQ) indices such as voltage flicker, unbalances, and power factors in power systems if properly controlled. Different nonlinear and time-varying loads generate these parameters. One of the great nonlinear loads is the electric arc furnace (EAF), which causes waveform distortions, voltage unbalances, and fluctuations. In this paper, a new digital and prediction-based control for thyristor switched capacitors (TSCs) was proposed to compensate an actual steel industrial plant. The digital control was based on generating adequate synchronous pulses, calculating required suitable susceptance, and measuring correct reactive power. The proposed TSC improved the PQ by means of the feedback from voltage and power factor. A predictive method based on time series and recursive least square with dynamic learning factor was then applied to estimate EAF reactive power in the future so that the TSC performance was enhanced by reducing the natural time delay. A band-pass harmonic filter was designed to compensate the load current harmonics and to protect the capacitor banks in the TSC. Finally, the suggested TSC was implemented in a steel industrial plant as an actual power system with 2 EAFs. The modeling and experimental results indicate the effectiveness of the proposed TSC.
This study presents control algorithms for a new unified power quality conditioner (UPQC) without the series transformers that are frequently used to make the insertion of the series converter of the UPQC between the power supply and the load. The behaviour of the proposed UPQC is evaluated in presence of voltage imbalances, as well as under non-sinusoidal voltage-and current conditions. The presented algorithms derive from the concepts involving the active and non-active currents, together with a phase-locked-loop circuit. Based on these real-time algorithms, and considering the proposed hardware topology, the UPQC is able to compensate the harmonic components of the voltages and currents, correct the power factor, and keep the load voltages regulated, all of this in a dynamic way, responding instantaneously to changes in the loads or in the electrical power system. The control algorithms were distributed in a two-DSP digital control architecture, without any communication between them. Consequently, can be increased the sampling frequency of the acquired voltages and currents and improve the UPQC performance. Furthermore, some constraints of the proposed UPQC are evidenced, particularly when the main voltages are imbalanced. Simulation and experimental results are presented to verify the UPQC performance under transient and steady state conditions.
Second-order generalised integrator or resonant integrator (RI) has wide range of applications. Forward and backward Euler's approximation based two integrator realisation of RI is an easily implementable frequency adaptive method. However, it suffers from resonant frequency deviation due to discretisation. The discretisation methods that lead to accurate realisation of RI require online calculation or lookup table of trigonometric functions to accommodate frequency variation. In this study, multi-rate computation-based implementation of two integrator-based RI has been proposed to minimise resonant frequency deviation. In this method, no additional logic elements are consumed to achieve accurate resonant frequency location. This along with down-sampling leads to lesser phase lag of RI. The effect of quantisation on resonant frequency deviation has been analysed for proper choice of calculation time. It is also shown that appropriate choice of down-sampling instants give a range of phase response characteristics around the nominal continuous time RI phase response. The accuracy of resonant frequency emulation has been experimentally verified by implementing a proportional-resonant controller as current controller.
This paper is a study on the real-time implementation of a position-control based electric elevator drive. The information contained within this paper serves as a framework to expand the usefulness of electric drives through the addition of digital control systems and switching power supplies. The tangible example of an elevator driven by a permanent-magnet DC motor with position control is used to relate to the work and apply it to various mechanical systems. The tasks to be accomplished to achieve an electric elevator drive with position control are as follows: determining the parameters of the motor, designing a control system to direct the motor as desired, and verifying the performance of the system through the use of computer simulations and real-time Hardware-In-The-Loop (HIL) experimental testing.
Electricity load demand estimation has a remarkable impact on the economic policies of power industry and business cycles. Forecasting the movements of load demand provides to know the tendency of the future and can lead to a clear decision in strategic, planning or investments. Besides the ability to know the fluctuations of the future values contributes to the management of daily/weekly and long term operations. This study aims to predict the electricity load demand using a hybrid method that incorporates Empirical Mode Decomposition (EMD) and Support Vector Regression (SVR) algorithms. The proposed EMD-SVR method integrates the EMD method to SVR algorithm by using EMD as a denoising step on the training data. Unlike the previous studies, the proposed algorithm is not dependent to a specific Intrinsic Mode Function (IMF) for denoising and model learning. Experimental results are conducted on 3 electricity load datasets from different countries and the proposed method is compared with SVR algorithm using different feature vectors as well. It is shown that the proposed algorithm outperforms the SVR and non-feature used denoised-SVR algorithm on electricity load forecasting. (C) 2017 Elsevier Ltd. All rights reserved.
As environmental issues become more prominent, electric vehicles (EV) have attracted an increasing amount of attention. However, the continuous cruising distance of an EV is limited to approximately 160 km, which is insufficient for everyday use. Battery capacity is the limiting factor in long-distance EV travel, because the vehicles need to stop at EV recharging stations multiple times. In Japan, there are more than 2,000 EV charge stations, but there are, at most, two rapid chargers. When multiple users converge at the station, a queuing (or waiting) condition is created, which may lead to a call-loss condition. In other words, an appropriate number of chargers must be installed at each station when planning the EV infrastructure. Therefore, the number of vehicles entering the station must be estimated. In this study, a mathematical model based on the supporting infrastructure for widespread EV use is proposed to estimate the number of vehicles arriving at each charge station.
In order to attain emissions reduction targets to improve air quality and reduce global warming, electric vehicles (EVs) arise as alternatives to conventional vehicles fueled by fossil fuels. In this context, this work presents a comparative study between an EV and its conventional version, a medium-duty, diesel engine powered vehicle, from road tests following a standard cycle in urban driving conditions. The performance parameters evaluated are EV electric energy consumption and carbon dioxide (CO2) emissions from electricity generation and, for the conventional vehicle, exhaust CO2 emissions and energy consumption calculated from fuel consumption and heating value. Five scenarios were built to conduct an economic viability study in terms of payback and net present value (NPV). Considering the conditions applied, the results from the environmental analysis showed that CO2 emissions from the EV was 4.6 times lower in comparison with the diesel vehicle. On the other hand, the economic analysis revealed that the viability of the EV is compromised, mainly due to the imported parts with unfavorably high exchange rates. In the best scenario and not considering revenue from commercial application, the calculated payback period of the EV is 13 years of operation. (C) 2017 Elsevier Ltd. All rights reserved.
State-of-energy (SoE) is an important index for batteries in electric vehicles and it provides the essential basis of energy application, load equilibrium and security of electricity. To improve the estimation accuracy and reliability of SoE, a novel multi-model fusion estimation approach is proposed against uncertain dynamic load and different temperatures. The main contributions of this work can be summarized as follows: (1) Through analyzing the impact on the estimation accuracy of SoE due to the complexity of models, the necessity of redundant modeling is elaborated. (2) Three equivalent circuit models are selected and their parameters are identified by genetic algorithm offline. Linear matrix inequality (LMI) based H-infinity state observer technique is applied to estimate SoEs on aforementioned models. (3) The concept of fusion estimation is introduced. The estimation results derived by different models are merged under certain weights which are determined by Bayes theorem. (4) Batteries are tested with dynamic load cycles under different temperatures to validate the effectiveness of this method. The results indicate the estimation accuracy and reliability on SoE are elevated after fusion. (C) 2016 Elsevier Ltd. All rights reserved.
The increasing demand for electricity caused by a growing number of electric vehicles (EV) might challenge future energy systems. For a smooth integration of the electricity demand from EV, a comprehensive knowledge of its characteristics is essential. The analysis of charging behavior patterns of EV and resulting load profiles become important premises for this crucial task. Three electric mobility studies in Germany's southwestern region (Get eReady, iZEUS, and CROME) deliver comprehensive data of EV use for this purpose. In this paper we analyze and discuss the mobility and charging characteristics of this data in detail. We derive empirical EV load profiles and show how they are affected by charging management. We present a model to simulate EV loads based on statistical characteristics of the conducted studies. The resulting charging load profiles show similar patterns as other EV studies. The developed simulation model and its results (see supplementary data available online) allow a realistic representation of EV demand in analyses of future energy systems. (C) 2017 Elsevier Ltd. All rights reserved.
This paper investigates the impact of plug-in electric vehicle (EV) integration on the power systems scheduling and energy cost. An intermediary entity, the EV aggregator, participates in the market on behalf of the EV owners by optimally self-scheduling under the price-taking approach. Through detailed rolling simulations for a year and different EVs' penetration scenarios at a large insular power system, this work highlights the different impact of direct and smart charging on power system scheduling and energy costs, the limitations of the price-taking approach, which is widely used in self-scheduling models, and the difference in system value and market value that smart charging adoption creates in restructured markets under the marginal pricing rule.
In this paper, we use the electricity consumption model for electric vehicular flow [H. Xiao, H. J. Huang and T. Q. Tang, Mod. Phys. Lett. B 30 (2016) 1650325] to study the effects of road conditions on the electricity consumption of electric vehicular flow during the evolutions of shock, rarefaction wave and small perturbation. The numerical results indicate that road conditions have negative influences on the electricity consumption during the evolutions of shock and rarefaction wave (i.e. the electricity consumption increases when road conditions become better) and positive impacts on the electricity consumption during the evolution of small perturbation when the traffic flow is unstable (i.e. the electricity consumption produces oscillation, but its amplitude decreases when road conditions become better).
This paper examines students' achievements in solving problems and their misunderstandings when using models. A mixed research methodology was applied. Quantitative research investigated how the performance of students with various levels of high school GPAs correlated with their rating of their lecturers' teaching proficiency. Four lecturers and 336 mechanical and electronics engineering students participated in the study. Achievement tests, consisting of problems to be solved by using models of a diode and an ideal operational amplifier, were implemented in introductory courses in electronics. Students taught by lecturers whom they rated as having high levels of teaching expertise achieved significantly higher grades on these tests than did students taught by lecturers receiving lower ratings for their teaching expertise. The tests investigated performance on three taxonomy levels, and the results were consistent on all three levels. The grades on the knowledge taxonomy level were higher than the grades on the routine level, and both were higher than the grades on the interpretation level, as expected. Qualitative research, based on analysis of students' written explanations and on face-to-face interviews, exposed three kinds of misunderstanding: 1) that the purpose of engineering models is just to simplify calculations, not to yield usable, reliable results; 2) that a nonlinear problem can be solved using linear concepts; and 3) that the accuracy of a solution is indicated by the number of decimal places in the result, rather than by its closeness to the actual value.
Electrical impedance spectroscopy usually requires a wide bandwidth current source with high output impedance. Non-idealities of the operational amplifier (op-amp) degrade its performance. This work presents a particle swarm algorithm for extracting the main AC characteristics of the op-amp used to design a mirrored modified Howland current source circuit which satisfies both the output current and the impedance spectra required. User specifications were accommodated. Both resistive and biological loads were used in the simulations. The results showed that the algorithm can correctly identify the open-loop gain and the input and output resistance of the op-amp which best fit the performance requirements of the circuit. It was also shown that the higher the open-loop gain corner frequency the higher the output impedance of the circuit. The algorithm could be a powerful tool for developing a desirable current source for different bioimpedance medical and clinical applications, such as cancer tissue characterisation and tissue cell measurements.
In this paper, a low-power and precise electrical stimulator is introduced in which no operational amplifier (OPAMP) is used. For electrical stimulations that have low pulse width, an OPAMP with high slew rate is needed which is power consuming. In this work, the OPAMP is substituted with a digital circuitry. A 100 KHz clock is also used to update the current of the stimulator in the stimulation phases in order to make the stimulator accurate enough. Producing such a clock needs only few micro watts. This stimulator is simulated in a 0.18 mu m CMOS process, as well. The simulation results shows that this stimulator has only 0.056% charge mismatch in 1 mA stimulation current with a pulse width of 32 mu s.
Gap junctions underlie electrical synaptic transmission between neurons. Generally perceived as simple intercellular channels, electrical synapses have demonstrated to be more functionally sophisticated and structurally complex than initially anticipated. Electrical synapses represent an assembly of multiple molecules, consisting of channels, adhesion complexes, scaffolds, regulatory machinery, and trafficking proteins, all required for their proper function and plasticity. Additionally, while electrical synapses are often viewed as strictly symmetric structures, emerging evidence has shown that some components forming electrical synapses can be differentially distributed at each side of the junction. We propose that the molecular complexity and asymmetric distribution of proteins at the electrical synapse provides rich potential for functional diversity. (c) 2016 Wiley Periodicals, Inc.
Studies on the implications of population density on energy consumption in small and medium-sized cities in low- and middle-income countries are limited. This paper estimates and analyses energy consumption, using a diverse set of methods, to compare two medium-sized cities in Thailand with similar urban forms and socioeconomic characteristics but different population densities - namely, the less dense city Chaiyaphum and denser city Roi Et. The results reveal that the annual household electricity consumption per capita of these two cities is similar, showing no implications of density. However, private transport energy consumption per capita in Chaiyaphum is 22 per cent higher, supporting the hypothesis that a less dense city will have higher transport energy consumption. The key factor identified is the greater distance travelled by households located in the peri-urban areas in the less dense city. This has important policy implications for urban planning and urban development practices in Thailand.
Since the reforming and opening up in 1978, China has experienced a miraculous development. To investigate the transformation and upgrading of China's economy, this study focuses on the relationship between economic growth and electricity consumption of the secondary and tertiary industry in China. This paper captures the dynamic interdependencies among the related variables using a theoretical framework based on a Vector Autoregressive (VAR)-Vector Error Correction (VEC) model. Using the macroeconomic and electricity consumption data, the results show that, for secondary industry, there is only a unidirectional Granger causality from electricity consumption to Gross Domestic Product (GDP) from 1980 to 2000. However, for the tertiary industry, it only occurs that GDP Granger causes electricity consumption from 2001 to 2014. All these conclusions are verified by the impulse response function and variance decomposition. This study has a great significance to reveal the relationship between industrial electricity consumption and the pattern of economic development. Meanwhile, it further suggests that, since China joined the World Trade Organization (WTO) in 2001, the trend of the economic transformation and upgrading has gradually appeared. (C) 2017 Elsevier B.V. All rights reserved.
Recently, several articles (Cullmann, 2012; Agrell et al., 2014; Filippini and Orea, 2014; Llorca et al., 2014) address the issue of benchmarking decision making units with different technologies by using latent class models. This method groups units that have similar technology for better comparison. Under this scheme, there are two implicit assumptions: First, that each class reflects a unique technology where its elements are not outliers. Second, classes are assumed to be stationary and fixed. If this assumption is violated, the classification is transient and time-dependent, inadequate for the regulatory use suggested in the seminal papers. We apply latent class models to classify Swedish electricity distributors under different specifications. In most of the models, we identify one large class with approximately 78.4% of the DMU's and two small classes with 7.4% and 14.2% respectively. Moreover, most of small classes elements switch between categories. We contrast our parametric results with nonparametric outlier detector methods and find a relationship between identified outliers and the elements of smaller residual classes. We believe that our work is an important caveat to the adoption of latent class modelling as an alternative or remedy for conventional models, relying on a homogeneous reference set.
The increasing limitations on available energy require use of new environmentally friendly resources and enhancement of utilization efficiency of available resources. Energy storage systems (ESSs) are a promising technology to realize such a goal; however, their application in networks requires an investment that must be economically justified. This study examined the effect of ESS use on energy generation costs in networks for a specific time period. This includes determining the best location for installation of the ESS and the best possible operation schedules for the ESS and power plants to achieve the greatest decrease in daily energy generation costs. The influences of all the factors affecting the final solution were studied under different scenarios. The effects of power plant cost functions, transmission line capacity, and network upgrades were compared. All scenarios were implemented in an IEEE standard 30-bus network. The best possible specifications of ESS can reduce daily energy generation cost by 3% for selected power plant cost functions. It was found that the use of ESS in a network uniformed stress on the transmission line and, in such a case, it would be possible to defer the network upgrade for 21 years.
Since 2009, Singapore has set about implementing mitigation and energy efficiency measures in key sectors to achieve unilaterally pledged reductions in greenhouse gas (GHG) emissions of 7-11% below business-as-usual (BAU) levels in 2020. Carbon dioxide (CO2) emissions from fossil fuel-fired power plants are a major focus for emissions abatement, with an expected reduction of 4 Mt CO2 from the electricity generation sector in 2020. In this paper, we explore Singapore's various strategies in the electricity generation sector to fulfil this target and use an EnergyPLAN optimization model to assess the impact of these strategies on CO2 emissions from Singapore's electricity generation sector through to 2020. A comparison of BAU scenario in 2020 (BAU 2020), 2020 target emissions reduction trajectory, and three emissions reduction alternative policy scenarios (denoted APS-I, APS-II, and APS-III) is carried out. The EnergyPLAN simulation results indicate that all three APS scenarios achieve the 2020 carbon emissions reduction target in Singapore's electricity generation sector. The results furthermore suggest that the 2020 electricity generation associated emissions reduction target can be met through measures that are already available. Vulnerabilities are identified in Singapore's electricity generation fuel mix, and emission reduction strategies beyond 2020 are outlined. (C) 2017 Elsevier Ltd. All rights reserved.
Currently, privatized state-owned Taiwan Power Company (Taipower) has a monopoly over energy production and vertically integrates the electricity market in Taiwan. Because of the geographical environments, economies of scales, social structures, and diverse political ideologies in Taiwan, the electricity market exhibits unique characteristics. To maximize the benefits of electricity liberalization, future market operations must not only involve conventional considerations for economic dispatch; overall social welfare should be included by incorporating the perspectives of fairness, responsibility, and the environment, and key electrical grid operations should be executed appropriately. We responded to the future market liberalization planning by including factors, such as, environmental effects and government policies, in addition to electrical line construction, and operation cost factors involved in the entire operational model planning. On the basis of responsibility sharing, this study used the simulated -responsibility three-phase pricing method. The proposed pricing method is expected to help attain the following policy goals: 1. Achieving reasonable power price allocations; 2. Simultaneously ensuring fair and efficient electric grid operation; 3. Changing the operation orientations of the power plants and electrical grid facilities; and 4. Increasing the rate of renewable energy use.
Countries are implementing policies to develop greener energy markets worldwide. In Europe, the "2030 Energy and Climate Package" asks for further reductions of green house gases, renewable sources integration, and energy efficiency targets. But the polluting intensity of electricity may be different in average than when considering market inefficiencies, in particular losses, and therefore the implemented policy must take those differences into account. Precisely, herein we study the importance in terms of CO2 emissions the extra amount of energy necessary to cover losses. With this purpose we use Spanish market and system data with hourly frequency from 2011 to 2013. Our results show that indeed electricity losses significantly explain CO2 emissions, with a higher CO2 emissions rate when covering losses than the average rate of the system. Additionally, we find that the market closing technologies used to cover losses have a positive and significant impact on CO2 emissions: when polluting technologies (coal or combined cycle) close the market, the impact of losses on CO2 emissions is high compared to the rest of technologies (combined heat and power, renewables or hydropower). To the light of these results we make some policy recommendations to reduce the impact of losses on CO2 emissions.
This paper addresses electricity transmission planning under the new industry and institutional structure of the Mexican electricity market, which has engaged in a deep reform process after decades of a state-owned vertically -integrated-non-competitive-closed industry. Under this new structure, characterized by a nodal pricing system and an independent system operator (ISO), we analyze welfare-optimal network expansion with two modeling strategies. In a first model, we propose the use of an incentive price-cap mechanism to promote the expansion of Mexican networks. In a second model, we study centrally-planned grid expansion in Mexico by an ISO within a power-flow model. We carry out comparisons of these models which provide us with hints to evaluate the actual transmission planning process proposed by Mexican authorities (PRODESEN). We obtain that the PRODESEN plan appears to be a convergent welfare-optimal planning process.
We study supply function competition among conventional power generators with different levels of flexibility and the impact of intermittent renewable power generation on the competition. Inflexible generators commit production before uncertainties are realized, whereas flexible generators can adjust their production after uncertainties are realized. Both types of generators compete in an electricity market by submitting supply functions to a system operator, who solves a two-stage stochastic program to determine the production level for each generator and the corresponding market prices. We aim to gain an understanding of how conventional generators' (in) flexibility and renewable energy's intermittency affect the supply function competition and the market price. We find that the classic supply function equilibrium model overestimates the intensity of the market competition, and even more so when more intermittent generation is introduced into the system. The policy of economically curtailing intermittent generation intensifies the market competition, reduces price volatility, and improves the system's overall efficiency. Furthermore, these benefits of economic curtailment are most significant when the production-based subsidies for renewable energy are absent.
We conduct a fractional integration and cointegration study of several Kenyan electricity price series in order to determine whether signs of persistence or mean reversion can eventually be discovered. Such features can be considered as relevant when considering the possibilities of shocks affecting the energy market of Kenya, which has recently been subjected to major debate. We conclude that electricity prices in Kenya contain unit roots, implying permanent shocks lasting forever. Among the factors affecting electricity prices, we find oil prices and interest rates have significant positive effects on electricity, and based on the fact that all the series are I(1), long run relationships are examined by means of fractional cointegration. The recently introduced FCVAR model is implemented, with results showing that the series under study are fractionally cointegrated, with oil price shocks affecting electricity prices. (C) 2017 Elsevier Ltd. All rights reserved.
Electricity customers who install solar panels often are paid the prevailing retail price for the electricity they generate. We demonstrate that this rate of compensation typically is not optimal. A payment for distributed generation (w) that is below the retail price of electricity (r) often will induce the welfare-maximizing level of distributed generation (DG) when the fixed costs of centralized electricity production and the network management costs of accommodating intermittent solar DG are large, and when centralized generation and DG produce similar (pollution) externalities. w can optimally exceed r under alternative conditions. The optimal DG compensation policy varies considerably as industry conditions change. Furthermore, a requirement to equate w and r can reduce aggregate welfare substantially and can generate pronounced distributional effects.
Electricity security, generally referring to a system's capability to provide electricity to its users, is a multi-faceted problem attracting mounting attention from policy makers and scientists around the world. Electricity security encompasses largely different properties based upon the time/geographical scales of the factors affecting electricity delivery; it is challenged by threats surfacing in spheres far beyond the physical one; it involves a myriad of stakeholders spanning manifold disciplines and with considerably different expectations from the electricity commodity or services; it can be studied as a complicated techno-economic problem or as a complex socio-economic problem. All the above reasons, in a framework of changing European Union (EU) and global energy scenarios, render electricity security ever more challenging to assess and critical to safeguard. Against this background, this work presents recommendations to bring science and policy making closer towards evaluating and handling EU electricity security. More in detail, this is done by: Characterising electricity security via features at the cross-roads of policy and science. Reviewing the electricity security modelling and assessment approaches across sectors. Proposing elements for a novel electricity security decision-analytic framework for the EU. Contextualising the proposed framework in EU's Energy Union grid design initiatives.
This paper accepts the widespread view that as electricity generation systems transition towards a greater proportion of renewables provision, there will be an increasing need for storage facilities. However, it differs from most such studies in contrasting the private incentives of a storage operator with the public desirability of bulk storage. A key factor in the context of a market such as Britain, where renewable energy largely means wind generation, is the nature of wind generation itself. The problem of wind's high variance and intermittent nature is explored. It is argued that not only is there a missing money and a missing market issue in providing secure energy supplies, there is also a missing informational issue. A key opportunity for new storage is participation in a capacity market, if the setting is right.
Liberalization policies, the challenges of integrating distributed generation resources, and the recent flattening of electricity demand due to the economic crisis and technological change have led to lower returns for European electricity suppliers. Innovative and sustainable business models are needed to serve electricity customers while reflecting the operational needs of the system and maintaining supplier financial viability. This paper describes a novel model of Integrated Energy Services that encompasses distributed generation (DG) and demand response (DR) resources for industrial customers. We further reflect on some of the market opportunities and regulatory drivers for the development of similar schemes across Europe. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents an integrated model for risk management of electricity traders. It integrates the Unit Commitment (UC) problem, which provides the power generation units' dispatch and the electricity price forecasting of a power system, with artificial neural network (ANN) models, which provide electricity price forecasting of a neighbouring power system by incorporating a clustering algorithm. The integrated model is further extended to estimate the traders' profitability and risk, incorporating risk provisions. The integrated model is applied in bi-directional trading between the Italian and Greek day-ahead electricity markets. The UC and neural network models provide forecasts of the wholesale electricity price in Greece and Italy respectively. The model attributes a confidence level of the price forecasts, depending on the data clustering and the forecasting performance of each model. The integrated model identifies periods with high price margins for trading for each power flow, aligned with a forecasting confidence and a risk level. The integrated model can provide price signals on the profitability of traders and useful insights into the risk of traders. (C) 2017 Elsevier Ltd. All rights reserved.
This paper introduces a panel threshold model to empirically estimate the main drivers of electricity performance. The empirical analysis is based on a panel data set including 30 OECD countries over the period 1975-2013. We argue that effective regulatory reforms have positive interaction with the electricity generated leading to a higher capacity utilization and an increase in the level of labor productivity of the sector. The threshold analysis suggests that for already economically liberalised countries the level of economic freedom does not affect electricity generation and subsequently the level of electricity performance. Finally, the results do not drastically change when the Renewable Energy Sources (RES) are taken into account.
In the last decade, the share of renewable energy sources in the energy mix has risen significantly in many countries, and the large-scale integration of these intermittent energy sources constitutes a major challenge to the power grid. A crucial building block of a successful transformation of today's energy systems is the use of energy storage, either co-located with renewable energy sources or on a grid-level. To this end, we present a model on the basis of a Markov Decision Process for the short-term trading of intermittent energy production co-located with energy storage. The model explicitly considers the time lag between trade and delivery of energy, which is characteristic for energy markets. Our storage representation includes asymmetrical conversion losses, asymmetrical power, and self-discharge. Stochastic production and market prices are represented by ARIMA processes, and the producer may also undertake price arbitrage by purchasing energy on the market when prices are comparatively low. Regarding the solution of our model, we develop several intuitive and easily interpretable decision rules that can be readily applied in practice. An extensive numerical study, based on real-world data, confirms the excellent performance of these rules in comparison to a sophisticated Approximate Dynamic Programming algorithm adapted from literature. (C) 2017 Elsevier Ltd. All rights reserved.
Resources scarcity and electricity demand have been dramatically increasing. Wastewater is recognized as one of resources for water, energy and plant fertilizing nutrients. Nevertheless, current wastewater treatment technologies have limitations due principally to their energy- and cost-intensive for achieving the conversion target of wastewater recovery. It is desired to develop a new technology to generate alternatives to conventional energy sources in a sustainable manner. An innovative technology based on the use of microbial fuel cells (MFCs) has been proved as a critical pathway for bioconversion processes towards electricity generation, then for addressing energy and environmental problems. Three special features including energy saving, less sludge production and less energy production make MFCs outstanding compared with the existing technologies. Multiform wastewaters could be efficiently degraded through advancing MFCs alone or integrating MFCs with other processing units. However, the low power density and the high operating cost of MFCs have greatly limited their applications on large-scale problems, and then result in some debates and doubts about their development and applications. Therefore, this paper objectively discussed the problems and applications of MFCs in wastewater treatment. Moreover, the integration of MFCs with other treatment processes was presented to verify the practicality and effectiveness of MFCs in contaminants removal. Furthermore, the primary challenges and opportunities for scaling-up and future applications of MFCs in wastewater were analyzed.
A digitally controlled sonar power amplifier for underwater transmitter is explained in this paper. It proposes a method of generating unipolar Sine Pulse Width Modulation (SPWM) signals for echo ranging sonar. This method can be effectively used in all kinds of inverters including high frequency inverters. A low cost digital signal controller was used to generate SPWM signals and used as gating pulses for a Controlled Full Bridge Circuit (CFBC). The power required, frequency, pulse-width and pulse repetition interval are given as the inputs to the digital controller and gating pulses for the CFBC are generated as output from the controller. A power transformer connected across CFBC boosts output voltage followed by power filter which removes unwanted harmonics present in the output. The output after the power filter is used to excite electro-acoustic transducer elements underwater. The voltage and current of the load were given as feedback to the same controller for voltage mode control loop implementation of the system. A prototype of 1kW Switch Mode Power Amplifier (SMPA) for echo ranging sonar has been designed and digital control has been implemented. Salient results are presented.
This paper introduces DNA-wrapped multi-walled carbon nanotube (MWCNT)-modified genosensor for the detection of Escherichia coli (E. coli) from polymerase chain reaction (PCR)-amplified real samples while Staphylococcus aureus (S. aureus) was used to investigate the selectivity of the biosensor. The capture probe specifically recognizing E. coli DNA and it was firstly interacted with MWCNTs for wrapping of single-stranded DNA (ssDNA) onto the nanomaterial. DNA-wrapped MWCNTs were then immobilised on the surface of disposable pencil graphite electrode (PGE) for the detection of DNA hybridization. Electrochemical behaviors of the modified PGEs were investigated using Raman spectroscopy and differential pulse voltammetry (DPV). The sequence selective DNA hybridization was determined and evaluated by changes in the intrinsic guanine oxidation signal at about 1.0 V by DPV. Numerous factors affecting the hybridization were optimized such as target concentration, hybridization time, etc. The designed DNA sensor can well detect E. coli DNA in 20 min detection time with 0.5 pmole of detection limit in 30 mu L of sample volume.
Electrochemical immunosensors have the potential to transform analytical procedures within the food industry by providing highly specific, rapid, and inexpensive determination of pathogens. In this paper, recent advances in this area are outlined. In particular, attention is paid to new methods that have been developed for the modification of working electrode surfaces. Many advances have been related to the use of novel nanomaterials such as carbon nanotubes, graphene, and metallic nanoparticles, often used in conjunction with each other or polymers. The use of these materials has generally provided superior sensor sensitivity. The application of immunosensors to the detection of a range of pathogens in real samples is then investigated to establish whether they provide solutions in practical applications.
A platform for electrochemical transduction suitable for miniaturised point-of-care diagnostic solutions with intuitive optical read-out was designed. Electrolytic current from electrochemical cell was transduced into the glow of a light-emitting diode. Its performance was optimised and several variants of transducing circuitry were tested. The circuit comprising field-effect transistor (FET) exhibited the sought abilities - absolute simplicity and high and tuneable sensitivity of the transducing device. Limit-of-detection, i.e. a signal readable by naked-eye without any additional instrumentation was as low as 4 mu M for direct assay of H2O2. The whole transducing system employing FET consisted of 4 off-the-shelf components and its price reached <0.3 (sic) even at small-scale experimental production. As our system was rather suitable for the semiquantitative "YES/NO" applications due to the steep response curve, an alternative circuitry for widening the linear range was also probed. Finally, rather higher initial voltage that was required in the electrochemical cell for FET-based transducer lead us to design a further simplified and more variable circuit employing the operational amplifier. (C) 2016 Elsevier Ltd. All rights reserved.
Electrochemistry coupled to liquid chromatography and mass spectrometry was used for simulating the biological and environmental fate of polycyclic aromatic hydrocarbons (PAHs) as well as for studying the PAH degradation behavior during electrochemical remediation. Pyrene and benzo[a]pyrene were selected as model compounds and oxidized within an electrochemical thin-layer cell equipped with boron-doped diamond electrode. Atpotentials of 1.2 and 1.6 V vs. Pd/H-2,H- quinones were found to be the major oxidation products for both investigated PAHs. These quinones belong to a large group of PAH derivatives referred to as oxygenated PAHs, which have gained increasing attention in recent years due to their high abundance in the environment and their significant toxicity. Separation of oxidation products allowed the identification of two pyrene quinone and three benzo[a]pyrene quinone isomers, all of which are known to be formed via photooxidation and during mammalian metabolism. The good correlation between electrochemically generated PAH quinones and those formed in natural processes was also confirmed by UV irradiation experiments and microsomal incubations. At potentials higher than 2.0 V, further degradation of the initial oxidation products was observed which highlights the capability of electrochemistry to be used as remediation technique. (C) 2017 Elsevier Ltd. All rights reserved.
ObjectiveElectroconvulsive therapy (ECT) remains underutilized because of fears of cognitive and medical risks, including the risk of death. In this study, we aimed to assess the mortality rate of ECT by means of a systematic review and pooled analysis. MethodThe study was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related mortality rate was calculated as the total number of ECT-related deaths reported in the included studies divided by the total number of ECT treatments. ResultsFifteen studies with data from 32 countries reporting on a total of 766 180 ECT treatments met the inclusion criteria. Sixteen cases of ECT-related death were reported in the included studies yielding an ECT-related mortality rate of 2.1 per 100 000 treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001 (covering 414 747 treatments), there was only one reported ECT-related death. ConclusionThe ECT-related mortality rate was estimated at 2.1 per 100 000 treatments. In comparison, a recent analysis of the mortality of general anesthesia in relation to surgical procedures reported a mortality rate of 3.4 per 100 000. Our findings document that death caused by ECT is an extremely rare event.
A novel driving method implemented with high frequency electromagnetic isolation is proposed in this paper. And the hardware designing schematic diagram and the software configuration method are presented. Then the corresponding operating principle is analyzed in detail based on digital control chip and analog circuits. The proposed driving method can be applied to real-time varying pulse width of the control signal and the duty-cycle ratio of this control pulse can be regulated in the range of 0-100 %. This novel driving method can achieve not only the advantages of high insulation and high common-mode suppression, but also the merits of low cost and fast dynamic response speed, and it is suitable for the isolation and amplification of high frequency switching control pulse signal. Finally, the experimental results show that the proposed driving method in this paper is effective.
Prior to 1950, the consensus was that biological transformations occurred in two-electron steps, thereby avoiding the generation of free radicals. Dramatic advances in spectroscopy, biochemistry, and molecular biology have led to the realization that protein-based radicals participate in a vast array of vital biological mechanisms. Redox processes involving high-potential intermediates formed in reactions with O-2 are particularly susceptible to radical formation. Clusters of tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O-2-reactive enzymes, raising the possibility that they play an antioxidant protective role. In blue copper proteins with plastocyanin-like domains, Tyr/Trp clusters are uncommon in the low-potential single-domain electron-transfer proteins and in the two-domain copper nitrite reductases. The two-domain muticopper oxidases, however, exhibit clusters of Tyr and Trp residues near the trinuclear copper active site where O-2 is reduced. These clusters may play a protective role to ensure that reactive oxygen species are not liberated during O-2 reduction.
In the neural network field, many application models have been proposed. Previous analog neural network models were composed of the operational amplifier and fixed resistance. It is difficult to change the connecting weight of a network. In this study, we used analog electronic multiple and sample hold circuits. The connecting weights describe the input voltage. It is easy to change the connection coefficient. This model works only on analog electronic circuits. It can finish the learning process in a very short time and this model will enable more flexible learning. However, the structure of this model includes only one input and one output network. We improved the number of unit and network layers. Moreover, we suggest the possibility of the realization the hardware implementation of the deep learning model. (C) 2015 The Authors. Published by Elsevier B.V.
In the neural network field, many application models have been proposed. Previous analog neural network models were composed of the operational amplifier and fixed resistance. It is difficult to change the connecting weight of network. In this study, we used analog electronic multiple and sample hold circuits. The connecting weights describe the input voltage. It is easy to change the connection coefficient. This model works only on analog electronic circuits. It can finish the learning process in a very short time and this model will enable more flexible learning. However, the structure of this model is only one input and one output network. We improved the number of unit and network layer. Moreover, we suggest the possibility of realization about the hardware implementation of the deep learning model.
The recommendation system is a useful tool that can be employed to identify potential relationships between items and users in electronic commerce systems. Consequently, it can remarkably improve the efficiency of a business. The topic of how to enhance the accuracy of a recommendation has attracted much attention by researchers over the past decade. As such, many methods to accomplish this task have been introduced. However, more complex calculations are normally necessary to achieve a higher accuracy, which is not suitable for a real-time system. Hence, in this paper, we propose a weight-based item recommendation approach to provide a balanced formula between the recommended accuracy and the computational complexity. The proposed methods employ a newly defined distance to describe the relationship between the users and the items, after which the recommendations and predictive algorithms are developed. A data analysis based on the MovieLens datasets indicates that the methods applied can obtain suitable prediction accuracy and maintain a relatively low computational complexity.
The performance for fuse electronic components may have degradation after long-term-storage. In order to as-certain the components which its performance has degradation, two fuse electronic parts, which have been stored for 10 years, are chosen as samples for an accelerated test. It shows that the white noise from the resistance and the interfering noise between different resistances may lead the performance degradation. The zero drift due to the brokenness of bonding wire may magnify the noise voltage when under storage, and influence the reliability of the operational amplifier. The result indicates that the resistances and operational amplifiers should be concerned more when test fuse electronic device after a long storage.
With growing Electronic Design Automation (EDA) industry, automated analog circuit design is now a feasible solution for the demand to exploit a span of nonlinear circuit behaviors from devices to circuits with the flexibility to optimize numerous competing continuous-valued performance specifications. In order to meet desired specifications, state-of art EDA tools are employed which depend upon more efficient and effective optimization techniques to suffice the cost of designing complex analog systems. In this paper, a hybrid metaheuristic based on PSO and SA is presented to design one of the most prominent design specifications, i.e. gains of a two-stage CMOS operational amplifier circuit and a simple operational transconductance amplifier circuit subject to a variety of design conditions and constraints. Here convergence of PSO is improved by advancing through local solutions using SA to achieve quality global optimum solution. Experimental results are compared with other standard optimization techniques to show performance of proposed hybrid metaheuristic in terms of optimization quality and robustness.
As silicon process geometry is reduced in scale with growing Electronic Design Automation (EDA) industry, the underlying circuitry on a chip has become more complex. The cost of designing such complex systems drives towards the path of employing automation in the field of analog circuit design. In this paper, a heuristic based on river formation dynamics (RFD) is presented to design analog circuits with user-defined specifications. Here search strategy of RFD scheme is employed to advance through stringent design requirements to evaluate an optimum solution for two-stage CMOS operational amplifier circuit. Experimental results show competent performance of RFD scheme in terms of quality of solution when compared with standard optimization techniques.
It is well known that electrostatic discharges can ignite mixtures of flammable gases with air and suspensions of combustible dust in air. For this reason, the prevention of electrostatic discharges is an essential part of measures to prevent explosions and fires. Incendive electrostatic discharges occurred in five cases in various chemical plants. The incidents involved were: 1. Spark type electrostatic discharges from a leaking steam pipe. 2. Spark type electrostatic discharges inside a charging chute for a solid. 3. A spark type electrostatic discharge whilst transferring a solid powder from a bin, which led to ignition of the powder. 4. A propagating brush discharge during pneumatic transfer of solid, which caused a severe electric shock to a process operator. 5. A brush discharge inside an electrostatic precipitator which caused ignition of an aerosol of hydrocarbon. To avoid explosions and fires it is important to prevent incendive electrostatic discharges from occurring in industrial facilities. To help managers of chemical plants to do this, the incidents above are presented in the form of learning lessons including: the mechanism of the generation and separation of electrical charges, the mechanism of the electrostatic discharge, the root causes of the incident, the safety measures which are necessary to avoid a repetition. (C) 2017 Published by Elsevier B.V.
Enzyme linked immunosorbent assay (ELISA) is one of the most popular and indispensable tools in molecular biology. Despite numerous advances in ELISA methods that markedly improve the sensitivity and throughput of detection, a hallmark of all ELISA continues to be repeated pipetting of fluids that is not only cumbersome but can easily introduce errors or contaminations. Robotics, despite obvious advantages, remains expensive. Here, we designed and produced cheap "pillar plates" using stereolithography-based 3D printing that can be readily inserted into conventional 96- and 384- well plates and serve as the substrate for ELISA. We demonstrate that ELISA using these "pillar plates" affords comparable specificity and sensitivity of detection of serum antibodies to traditional sandwich ELISA, while markedly reducing the time and efforts associated with fluid transfer. These results underscore "pillar plates" as an attractive platform for rapid yet robotics-free ELISA.
Recently, human leukocyte antigen-G (HLA-G) has been a focus in the field of reproductive immunology, tumor progression and transplantation, because of its inhibitory function as ligand to the inhibitory receptors leukocyte immunoglobulin-like receptors (LILR) B1 and LILRB2. The HLA-G is expressed in distinct mRNA isoforms, one of which encodes a soluble HLA-G (sHLA-G) protein, detectable by sandwich ELISA. Therefore, sHLA-G ELISAs have been used as a noninvasive diagnosis system. While a number of sHLA-G-specific ELISAs have been described, our prior studies showed that data obtained by the conventional ELISA system detecting sHLA-G in body fluids was not consistent with the data obtained from immunoprecipitation (IP)/immunoblotting (IB). Therefore, we established an optimized ELISA system described in this report, which yields results consistent with IP/IB analysis. Using this system, we determined sHLA-G protein in amniotic fluids, and found that sHLA-G levels at preterm (similar to 36 weeks) were clearly higher than those at term (37-41weeks). These data and supporting experiments showed that the ELISA system we established can be an useful tools for the detection of sHLA-G protein in body fluids than the conventional ELISA system.
Elongation factor (EF) is a key regulation factor for translation in many organisms, including plants, bacteria, fungi, animals and insects. To investigate the nature and function of elongation factor 1 beta' from Spodoptera exigua (SeEF-1 beta'), its cDNA was cloned. This contained an open reading frame of 672 nucleotides encoding a protein of 223 amino acids with a predicted molecular weight of 24.04 kDa and pI of 4.53. Northern blotting revealed that SeEF-1 beta' mRNA is expressed in brain, epidermis, fat body, midgut, Malpighian tubules, ovary and tracheae. RT-PCR revealed that SeEF-1 beta' mRNA is expressed at different levels in fat body and whole body during different developmental stages. In RNAi experiments, the survival rate of insects injected with SeEF-1 beta' dsRNA was 58.7% at 36 h after injection, which was significantly lower than three control groups. Other elongation factors and transcription factors were also influenced when EF-1 beta' was suppressed. The results demonstrate that SeEF-1 beta' is a key gene in transcription in S. exigua.
Single-phase inverters are widely used to connect small-scale distributed renewable energy sources to the grid. However, unlike a three-phase system, designing the vector control for a single-phase inverter is more challenging. This paper presents a neural network based vector control technique for a single-phase inverter, as well as how to develop and design an embedded digital control system to implement the neural network vector controller by using Texas Instruments TMS320F28335 chip. The paper addresses circuit design for effective interface between the high power inverter system and the embedded microcontroller as well as how to utilize built-in interrupts to achieve efficient digital control implementation, with user specified sampling time, and generation of high-quality pulse-width modulated driving pulses. Moreover, an embedded software design was developed to implement the neural network vector control for the single-phase inverter. A laboratory scale single-phase inverter system was built to test and evaluate the embedded neural network microcontroller. The hardware experiment assessment shows that the microcontroller works well using the novel neural network vector control mechanism in challenging, variable, and distorted hardware experiment conditions.
Psychological perspective-taking is a powerful social cognition that helps us to understand other people. It creates feelings of closeness and sympathy, motivates us to help others, and is important for positive social relationships. In contrast to the impressive knowledge about its consequences, relatively little is known about how exactly people achieve them. The present paper addresses this question from a grounded cognition perspective, drawing on recent findings on the embodiment of visuospatial perspective-taking. Visuospatial perspective-taking involves a mental transformation of one's body schema into the physical location of another person. We argue that when people psychologically "put themselves in another person's shoes,"this simulation of physical proximity happens, too, and is one source of perceived closeness. In five experiments (total N = 1067), participants completed a visuospatial perspective-taking task. During half of the trials, angular disparity between the target person and the participant was high and participants had to adopt the target's visual perspective (which involves an embodied simulation). During the remaining trials, angular disparity was low and participants could solve the task egocentrically. Taking another's perspective led participants to adopt the thoughts of the target person more strongly (Experiments 1-3) and increased the perceived similarity of that person to the self (Experiment 4) and participants' liking of that person (Experiment 5). These effects were independent of task difficulty (Experiment 2), and only present during trials where an embodied transformation happened (i.e., at high angular disparities; Experiment 3). Implications for psychological and visuospatial perspective-taking research and related phenomena are discussed.
Mammalian embryonic implantation requires reciprocal interactions between implantation-competent blastocysts and a receptive uterus. Some microRNAs might play a key role during embryo implantation in the mouse, but the let-7a expression profiles in the rat uterus during peri-implantation are unknown. In the study, the expression of let-7a in the uterus during early pregnancy, pseudopregnancy, artificial decidualization and activation of delayed implantation was detected by Northern blotting and in situ hybridization. The effect of steroid hormones on let-7a expression was also detected by Northern blotting and in situ hybridization. Here, we found that the expression level of let-7a was higher on gestation day 6-7 (g.d. 6-7) in rats than oil g.d.4-5 and g.d.8-9. Let-7a was specifically localized in glandular and luminal epithelia and decidua. The expression of let-7a was not significantly different in the pseudopregnant uterus and increased significantly in the uteri of rats subjected to artificial decidualization and activation of delayed implantation. Treatment with estradiol-17 beta or progesterone significantly increased let-7a expression. Thus, let-7a expression was significantly induced by the process of embryo invasion, and this increased expression level was mainly induced by active blastocysts and decidualization during the window of implantation, implying that let-7a may participate in endometrial decidualization. Steroid hormones, estradiol-17 beta or progesterone stimulated let-7a expression.
Somatic embryogenesis is an important biotechnological tool in breeding and conservation programmes for woody species. It exists an increasing interest in the improvement of somatic embryogenesis induction in commercial species such as Pinus radiata. One approach to obtain markers of successful somatic embryogenesis can be the study of protein profiling in a descriptive study. In order to accomplish this objective, 2-D and MALDI-TOF/TOF-MS analysis were used in the identification and quantification of proteins from Pinus radiata D. Don somatic embryos derived from 4 cell lines that were generated under different environmental conditions at initiation stage. Based on the Swiss-Prot database, among the 139 proteins detected, 25 of them appeared only in those cell lines with low initiation percentage at the initial stage of somatic embryogenesis. Only two proteins were detected differentially in cell lines with high initiation rates. Approximately 60% of the proteins identified were related to carbohydrate metabolic process and defence response. This study gives new insights about the proteomics in forest trees, as well as provides clues on the underlying causes of the mechanisms governing Pinus radiata somatic embryogenesis process, and can serve as a tool for facing the improvement ofthe breeding programmes.
The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways.
Digital Active EMI Filtering (DAEF) technique is a new direction of conductive EMI suppression technologies for switched-mode power converters. However, the conventional DAEF topology only suppresses EMI to ground on the AC (or DC) ports. It doesn't definitely aim to Common Mode (CM) or Differential Mode (DM) EMI. In this paper, a novel DAEF topology is proposed. It can flexibly suppress CM and DM EMI, and also effectively adjust EMI suppression ability as well as prevent interconversion between CM and DM EMI. On the other hand, because of the parasitic parameters of circuit and the time delay of controlling system, the traditional model of DAEF cannot describe the system behavior accurately. This paper proposes a precise model of DAEF system. The model not only considers the passive device parasitic parameters of sense circuit, injection circuit and decoupling circuit, but also considers the time delay of the digital control system. This model can accurately describe filter performance of DAEF. Finally, simulation and experimental results show that the proposed DAEF effectively suppress CM EMI. Moreover, the precise model can predict the system filter performance accurately.
Objectives: Emotion recognition impairments have been demonstrated in schizophrenia (Sz), but are less consistent and lesser in magnitude in bipolar disorder (BD). This may be related to the extent to which different face processing strategies are engaged during emotion recognition in each of these disorders. We recently showed that Sz patients had impairments in the use of both featural and configural face processing strategies, whereas BD patients were impaired only in the use of the latter. Here we examine the influence that these impairments have on facial emotion recognition in these cohorts. Methods: Twenty-eight individuals with Sz, 28 individuals with BD, and 28 healthy controls completed a facial emotion labeling task with two conditions designed to separate the use of featural and configural face processing strategies; part-based and whole-face emotion recognition. Results: Sz patients performed worse than controls on both conditions, and worse than BD patients on the whole-face condition. BD patients performed worse than controls on the whole-face condition only. Conclusions: Configural processing deficits appear to influence the recognition of facial emotions in BD, whereas both configural and featural processing abnormalities impair emotion recognition in Sz. This may explain discrepancies in the profiles of emotion recognition between the disorders.
Background and Objectives: Although humans have developed abundant strategies to down regulate their own negative emotions, at times of distress they frequently turn to significant others to seek comfort. In the present study we use a novel performance-based paradigm to evaluate the effectiveness of this interaction. Methods: Forty-seven couples in a long-term relationship volunteered to participate in the study. In each couple the two partners were randomly assigned as either target or regulator. The target viewed pictures with negative valance. In response to each picture he/she was then instructed to choose and apply a regulatory strategy (i.e., intrapersonal emotion regulation) or to apply a regulatory strategy chosen by his/her partner, the regulator (i.e., interpersonal emotion regulation). Results: We found that the outside perspective of the regulator helped reducing distress more effectively than intrapersonal emotion regulation. Moreover, the cognitive, but not the emotional, empathy of the regulator predicted the added value of interpersonal emotion regulation. Specifically, regulators with a better ability to understand their partners' point of view, selected regulatory strategies that reduced levels of distress more effectively. Limitations: While the present study examined possible effects of depression, anxiety and the ability to identify and describe feelings, a larger sample is needed in order to optimally address their potential moderating effect. Conclusions: The results illuminate the value of non-professional interventions and the importance of cognitive empathy in reducing distress. The study has significant clinical implications, providing a simple behavioral tool that can be used to decrease and prevent psychopathology. (C) 2016 Elsevier Ltd. All rights reserved.
It was recently proposed that the neural substrate mediating smile production might play a key role also in the recognition of others' smile. This hypothesis, however, has been challenged by difficulties in eliciting ecological smiling in standard laboratory settings. Here we report of a case where these difficulties were overcome by combining electrical stimulation and intracranial electroencephalogram recording in a patient with drug-resistant focal epilepsy. The stimulation of the pregenual anterior cingulate cortex (pACC) elicited a smiling facial expression. The same leads exploring pACC showed an increase of gamma band activity (50-100 Hz) during the observation of video-clips depicting actors laughing, relative to video-clips depicting actors crying or producing a neutral expression. These findings indicate that both smile production and recognition are encoded in pACC and further support the role of this region in social cognition.
The study examined third-party listeners' ability to detect the Hellos spoken to prevalidated happy, neutral, and sad facial expressions. The average detection accuracies from the happy and sad (HS), happy and neutral (HN), and sad and neutral (SN) listening tests followed the average vocal pitch differences between the two sets of Hellos in each of the tests; HS and HN detection accuracies were above chance reflecting the significant pitch differences between the respective Hellos. The SN detection accuracy was at chance reflecting the lack of pitch difference between sad and neutral Hellos. As expected, the SN detection accuracy positively correlated with theory of mind; participating in these tests has been likened to the act of eavesdropping, which has been discussed from an evolutionary perspective. An unexpected negative correlation between the HS detection accuracy and the empathy quotient has been discussed with respect to autism research on empathy and pitch discrimination.
Individuals with Autism Spectrum Disorder (ASD) are characterized by severe deficits in social communication, whereby the nature of their impairments in emotional prosody processing have yet to be specified. Here, we investigated emotional prosody processing in individuals with ASD and controls with novel, lifelike behavioral and neuroimaging paradigms. Compared to controls, individuals with ASD showed reduced emotional prosody recognition accuracy on a behavioral task. On the neural level, individuals with ASD displayed reduced activity of the STS, insula and amygdala for complex vs basic emotions compared to controls. Moreover, the coupling between the STS and amygdala for complex vs basic emotions was reduced in the ASD group. Finally, groups differed with respect to the relationship between brain activity and behavioral performance. Brain activity during emotional prosody processing was more strongly related to prosody recognition accuracy in ASD participants. In contrast, the coupling between STS and anterior cingulate cortex (ACC) activity predicted behavioral task performance more strongly in the control group. These results provide evidence for aberrant emotional prosody processing of individuals with ASD. They suggest that the differences in the relationship between the neural and behavioral level of individuals with ASD may account for their observed deficits in social communication.
Schadenfreude occurs when people feel pleasure at others' misfortunes. Previous research suggested that individuals feel such a malicious pleasure when the misfortune befalls social targets perceived as highly competent but lacking human warmth. Two experiments explored whether the two components of warmth (i.e., sociability and morality) have distinct roles in driving schadenfreude. Study 1 (N = 128) compared a competent but immoral individual to a competent but unsociable person and found that people felt more schadenfreude when a misfortune befell an individual lacking morality. Study 2 (N = 199) confirmed the primary role of morality in driving schadenfreude by manipulating not only morality and sociability, but also competence. Moreover, both experiments showed that social targets lacking moral qualities elicited higher levels of schadenfreude because their misfortunes were perceived as deserved. Overall, our findings suggest that morality has a primary role over other basic dimensions of person perception (i.e., sociability and competence) in driving schadenfreude.
Background: Functional brain imaging research has already demonstrated that patients with schizophrenia had difficulties with emotion processing, namely in facial emotion perception and emotional prosody. However, the moderating effect of social context and the boundary of perceptual categories of emotion attribution remain unclear. This study investigated the neural bases of emotional sentence attribution in schizophrenia. Methods: Twenty-one schizophrenia patients and 25 healthy subjects underwent an event-related functional magnetic resonance imaging paradigm including two tasks: one to classify sentences according to their emotional content, and the other to classify neutral sentences according to their grammatical person. Results: First, patients showed longer response times as compared to controls only during the emotion attribution task. Second, patients with schizophrenia showed reduction of activation in bilateral auditory areas irrespective of the presence of emotions. Lastly, during emotional sentences attribution, patients displayed less activation than controls in the medial prefrontal cortex (mPFC). Conclusions: We suggest that the functional abnormality observed in the mPFC during the emotion attribution task could provide a biological basis for social cognition deficits in patients with schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Background. Previous studies suggest that adults with Tourette syndrome (TS) can respond unconventionally on tasks involving social cognition. We therefore hypothesized that these patients would exhibit different neural responses to healthy controls in response to emotionally salient expressions of human eyes. Method. Twenty-five adults with TS and 25 matched healthy controls were scanned using fMRI during the standard version of the Reading the Mind in the Eyes Task which requires mental state judgements, and a novel comparison version requiring judgements about age. Results. During prompted mental state recognition, greater activity was apparent in TS within left orbitofrontal cortex, posterior cingulate, right amygdala and right temporo-parietal junction (TPJ), while reduced activity was apparent in regions including left inferior parietal cortex. Age judgement elicited greater activity in TS within precuneus, medial prefrontal and temporal regions involved in mentalizing. The interaction between group and task revealed differential activity in areas including right inferior frontal gyrus. Task-related activity in the TPJ covaried with global ratings of the urge to tic. Conclusions. While recognizing mental states, adults with TS exhibit greater activity than controls in brain areas involved in the processing of negative emotion, in addition to reduced activity in regions associated with the attribution of agency. In addition, increased recruitment of areas involved in mental state reasoning is apparent in these patients when mentalizing is not a task requirement. Our findings highlight differential neural reactivity in response to emotive social cues in TS, which may interact with tic expression.
It is known that children with mental and developmental problems are at risk of abuse and neglect. Attention-deficit/hyperactivity disorder is one of the most frequent neurodevelopmental disorders in children and adolescents. The purpose of this study is to examine whether children diagnosed with ADHD are under more risk in terms of child abuse and neglect compared to controls. In this case-control study, 104 children, who applied to Child and Adolescent Psychiatry Unit of Bursa Yuksek Ihtisas Training and Research Hospital between January and June 2015, were diagnosed with ADHD, and had no other psychiatric comorbidity except for disruptive behavior disorders, and 104 healthy children were compared. Abuse Assessment Questionnaire was applied to children after approval of the families was received. It was determined that the children diagnosed with ADHD were exposed to more physical (96.2%) and emotional abuse (87.5%) in a statistically significant way compared to controls (46.2%; 34.6%), they were exposed to physical and emotional neglect (5.8%) at a lower rate compared to healthy children (24.0%), and there was no difference between them and healthy children in terms of witnessing family violence (56.7%; 47.1%) and being exposed to sexual abuse (5.8%; 1.9%). The children diagnosed with ADHD were exposed to physical and emotional abuse at a higher rate; further studies should emphasize the role of parents in this topic and how parental education and treatment programs change the results. (C) 2016 Elsevier Ltd. All rights reserved.
This research analyses the emotional competence difficulties (measured through emotional intelligence and empathy) and social communication disorders of young victims of abuse. These minors are in residential care centres with protective measures after suffering maltreatment and/or neglect. The relation between their emotional competence and social communication is analysed, as well as the contribution of empathy and emotional intelligence in predicting their social communication. The results indicate that a lack of emotional competence is related to and can predict their difficulties in social communication. The study manifests a scarcity of emotional intelligence, affecting attention, emotional repair and clarity of feelings, as well as a deterioration in affective and cognitive empathy. The minors' scarce ability to put themselves in the place of others, to understand others' intentions and emotional states, limits their use of language in social interactions. The research stresses the need to set up intervention programmes aimed at training in interpersonal and intrapersonal emotional competences which can encourage social communication.
The deleterious effects of school burnout (academic-related stress) on academic, physiological, and cognitive outcomes have been previously established. However, school burnout's relationship to emotional and relationship outcomes as well as underlying factors contributing to their potential relationship are less understood. Therefore, three studies were conducted to fill this gap by examining the relationship between school burnout, self-control, emotional dysregulation, and intimate partner violence. In emerging adult samples, results demonstrate that school burnout is positively associated with emotional dysregulation, independent of anxiety and depression (Study 1), and that self-control moderates this relationship (Study 2) as well as the relationship between school burnout and intimate partner violence perpetration and victimization (Study 3). Specifically, the relationship between school burnout and emotional dysregulation (Study 2), as well as with both victimization and perpetration (Study 3), are stronger under lower levels of dispositional self-control. Findings from these studies identify school burnout as an important phenomenon of inquiry in relation to psychosocial outcomes among emerging adults. More importantly, findings suggest that self-control may serve as a potential point of intervention for ameliorating school burnout's damaging effects. Limitations and directions for future research are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Emotional processing (EP) is a complex cognitive function necessary to successfully adjust to social environments where we need to interpret and respond to cues that convey threat or reward signals. Ex-combatants have consistently shown atypical EP as well as poor social interactions. Available reintegration programs aim to facilitate the re-adaptation of ex-combatants to their communities. However, they do not incorporate actions to improve EP and to enhance cognitive-emotional regulation. The present study was aimed at evaluating the usefulness of an intervention focused on Social Cognitive Training (SCT), which was designed to equip ex-combatants enrolled in the Social Reintegration Route with EP and social cognition skills. A group of 31 ex-combatants (mean age of 37.2, 29 men) from Colombian illegal armed groups were recruited into this study. Of these, 16 were invited to take part in a SCT and the other continued with the conventional reintegration intervention. Both groups underwent 12 training sessions in a period 12-14 weeks. They were assessed with a comprehensive protocol which included Psychosocial, Behavioral, and Emotion Processing instruments. The scores on these instruments prior to and after the intervention were compared within and between groups. Both groups were matched at baseline. Ex-combatants receiving the SCT experienced significant improvements in EP and a reduction in aggressive attitudes, effects not observed in those continuing the conventional reintegration intervention. This is the first study that achieves such outcomes in such a population using SCT intervention. We discuss the implications of such results toward better social reintegration strategies.
Recognition of facial affect has been studied extensively in adults with and without traumatic brain injury (TBI), mostly by asking examinees to match basic emotion words to isolated faces. This method may not capture affect labelling in everyday life when faces are in context and choices are open-ended. To examine effects of context and response format, we asked 148 undergraduate students to label emotions shown on faces either in isolation or in natural visual scenes. Responses were categorised as representing basic emotions, social emotions, cognitive state terms, or appraisals. We used students' responses to create a scoring system that was applied prospectively to five men with TBI. In both groups, over 50% of responses were neither basic emotion words nor synonyms, and there was no significant difference in response types between faces alone vs. in scenes. Adults with TBI used labels not seen in students' responses, talked more overall, and often gave multiple labels for one photo. Results suggest benefits of moving beyond forced-choice tests of faces in isolation to fully characterise affect recognition in adults with and without TBI.
Relative to the general population, individuals with psychotic disorders have a higher risk of suicide. Suicide risk is also elevated in criminal offenders. Thus, psychotic-disordered individuals with antisocial tendencies may form an especially high-risk group. We built upon prior risk analyses by examining whether neurobehavioral correlates of social cognition were associated with suicidal behavior in criminal offenders with psychotic disorders. We assessed empathic accuracy and brain structure in four groups: (i) incarcerated offenders with psychotic disorders and past suicide attempts, (ii) incarcerated offenders with psychotic disorders and no suicide attempts, (iii) incarcerated offenders without psychotic disorders and (iv) community non-offenders without psychotic disorders. Established suicide risk variables were examined along with empathic accuracy and gray matter in brain regions implicated in social cognition. Relative to the other groups, offenders with psychotic disorders and suicide attempts had lower empathic accuracy and smaller temporal pole volumes. Empathic accuracy and temporal pole volumes were significantly associated with suicide attempts independent of other risk variables. The results indicate that brain and behavioral correlates of social cognition may add incremental value to models of suicide risk.
We hypothesized that distinct acute right hemisphere lesions disrupt separate components of valuation and emotional response to winning and losing money and of emotional empathy in observing a partner win or lose money. We measured skin conductance response (SCR) and ratings of emotions when acute right hemisphere stroke patients or healthy controls won or lost money in roulette, or when they watched a partner win or lose. Our results showed that percentage of damage after stroke to right anterior insula and frontal operculum negatively correlated with both SCR to winning and losing and difference between rating wins versus losses.
The concept of empathy has received much attention from philosophers and also from both cognitive and social psychologists. It has, however, been given widely conflicting definitions, with some taking it primarily as an epistemological notion and others as a social one. Recently, empathy has been closely associated with the simulationist approach to social cognition and, as such, it might be thought that the concept's utility stands or falls with that of simulation itself. I suggest that this is a mistake. Approaching the question of what empathy is via the question of what it is for, I claim that empathy plays a distinctive epistemological role: it alone allows us to know how others feel. This is independent of the plausibility of simulationism more generally. With this in view I propose an inclusive definition of empathy, one likely consequence of which is that empathy is not a natural kind. It follows that, pace a number of empathy researchers, certain experimental paradigms tell us not about the nature of empathy but about certain ways in which empathy can be achieved. I end by briefly speculating that empathy, so conceived, may also play a distinctive social role, enabling what I term 'transparent fellow-feeling'.
Inferring beliefs and social emotions of others has different neural substrates and possibly different roles in the pathophysiology of different clinical phases of schizophrenia. The current study investigated the neural basis for inferring others' beliefs and social emotions, as individual concepts, in 17 subjects at ultra-high risk for psychosis (UHR), 16 patients with schizophrenia and 20 healthy controls. Brain activity significantly differed from normal in both the left superior temporal sulcus (STS) and the inferior frontal gyrus (IFG) in the schizophrenia group while inferring others' beliefs, whereas those of UHR group were in the middle of those in the schizophrenia and healthy-control groups. Brain activity during inferring others' social emotions significantly differed in both the left STS and right IFG among individuals at UHR; however, there was no significant difference in the schizophrenia group. In contrast, brain activity differed in the left IFG of those in both the schizophrenia and UHR groups while inferring social emotion. Regarding the difference in direction of the abnormality, both the UHR and schizophrenia groups were characterized by hyper-STS and hypo-IFG activations when inferring others' beliefs and emotions. These findings might reflect different aspects of the same pathophysiological process at different clinical phases of psychosis.
Empathy for pain is often described as automatic. Here, we used implicit measurement and multinomial modeling to formally quantify unintentional empathy for pain: empathy that occurs despite intentions to the contrary. We developed the pain identification task (PIT), a sequential priming task wherein participants judge the painfulness of target experiences while trying to avoid the influence of prime experiences. Using multinomial modeling, we distinguished 3 component processes underlying PIT performance: empathy toward target stimuli (Intentional Empathy), empathy toward prime stimuli (Unintentional Empathy), and bias to judge target stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow) response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing imagine-self (vs. imagine-other) perspective-taking uniquely increased Unintentional Empathy. In Experiment 3, Intentional and Unintentional Empathy were stronger toward targets with typical (vs. atypical) pain outcomes, suggesting that outcome information matters and that effects on the PIT are not reducible to affective priming. Typicality of pain outcomes more weakly affected task performance when target stimuli were merely categorized rather than judged for painfulness, suggesting that effects on the latter are not reducible to semantic priming. In Experiment 4, Unintentional Empathy was stronger for participants who engaged in costly donation to cancer charities, but this parameter was also high for those who donated to an objectively worse but socially more popular charity, suggesting that overly high empathy may facilitate maladaptive altruism. Theoretical and practical applications of our modeling approach for understanding variation in empathy are discussed.
Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous theta burst stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and the dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects' prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high-SES players, while cTBS over DMPFC caused increased offers to low-SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans' prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized.
Introduction. Empathy is a sub-process of social cognition that is defined as the capacity to understand and share another person's thoughts, wishes and feelings, and is crucial in many forms of adaptive social interaction. It is a contextual, flexible and multidimensional phenomenon that is related with different neuronal networks and processes. Aims. To assess empathy in a sample of subjects diagnosed with conditions belonging to the category of severe mental disorders who were under treatment in a psychosocial rehabilitation programme. Subjects and methods. The sample consisted of 22 persons with severe mental disorders receiving treatment consisting in a psychosocial rehabilitation programme, and 22 healthy controls. A battery of tests, including the empathy quotient, Reading the Mind in the Eyes Test and the interpersonal reactivity index, was administered to each subject. Results. In the Reading the Mind in the Eyes Test, the experimental group scored significantly lower than the control group (t = 2.8; p < 0.05). No statistically significant differences were found on the other variables. Conclusions. Persons with a severe mental disorder do not display a generalised deficit of empathy. They do, however, have difficulty when it comes to recognising emotional states by looking, which suggests they process information about faces in a different way to subjects in the normal population.
Load demand forecasting is a critical process in the planning of electric utilities. An ensemble method composed of Empirical Mode Decomposition (EMD) algorithm and deep learning approach is presented in this work. For this purpose, the load demand series were first decomposed into several intrinsic mode functions (IMFs). Then a Deep Belief Network (DBN) including two restricted Boltzmann machines (RBMs) was used to model each of the extracted IMFs, so that the tendencies of these IMFs can be accurately predicted. Finally, the prediction results of all IMFs can be combined by either unbiased or weighted summation to obtain an aggregated output for load demand. The electricity load demand data sets from Australian Energy Market Operator (AEMO) are used to test the effectiveness of the proposed EMD-based DBN approach. Simulation results demonstrated attractiveness of the proposed method compared with nine forecasting methods. (C) 2017 Elsevier B.V. All rights reserved.
One of the most important issues in strategic management is enhancing employees' motivation to contribute in the implementation of strategies; because they usually do not pay necessary attention to strategies. Accordingly, it is required to consider and calculate their roles in implementing strategies. In terms of employees' role in the organization, they have managerial (goal setter) and/or non-managerial (non-goal setter) role. We are looking for a strategic performance measurement method to involve both roles. Since there was not a pervasive method in the literature to cover both roles properly, this research introduces a method that measures and calculates the strategic performance of employees based on two main parts: Project effectiveness (for managerial roles) and project efficiency (for non-managerial roles). This method tested on a sample of employees in Hormozgan Cement Company. Results show a significant difference between employees who participated and those who did not participate in implementation of strategies in their performance value. Achieved values are tangible and traceable; therefore, employees can have a proper sense and reaction to outputs of this method.
Job assistance programs are commonly recommended for parents of children who have been victimized by child maltreatment, particularly when illicit drugs are indicated. However, the relationship between employment factors, substance abuse, and risk of child maltreatment has received limited empirical attention. Therefore, the current study examines employment factors in a sample of 72 mothers, who were referred by child protective services for treatment of substance abuse and child neglect. Child maltreatment potential was found to be negatively associated with number of hours employed and self-reported happiness with employment. The association between child abuse potential and personal income of participants approached significance (p = .057), and the results were not influenced by social desirability. Employment satisfaction significantly contributed to the prediction of child maltreatment potential over and above other employment factors and control variables. These findings suggest that when mothers are involved in child protective services their risk of perpetrating child maltreatment may be reduced when they are assisted in gainful employment that is personally satisfying. Happiness with employment was the only employment factor correlated (inversely) with substance use (biological testing, self-report of participants). Future directions are discussed in light of the results, including the importance of considering employment satisfaction when conducting vocational assistance programs in this population.
This paper examines the long-run employment consequences of experiencing homelessness in childhood rather than later in life. We use novel panel data that link survey and administrative data for a sample of disadvantaged adults who are homeless or at risk of homelessness. Our estimation approach pays particular attention to the potential pathways linking childhood homelessness to adult employment. We find that those experiencing homelessness for the first time as children are less likely to be employed. For women, this relationship is largely explained by the lower educational attainment and higher welfare receipt (both in general and in the form of mental illness-related disability payments) of those experiencing childhood homelessness. Higher rates of high school incompletion and incarceration explain some of the link between childhood homelessness and men's employment; however, childhood homelessness continues to have a substantial direct effect on male employment rates.
The integration of multibarrel glass capillaries into a microfluidic co-flow configuration is demonstrated for parallel production of nanoliter scale droplets. The multibarrel system supports the generation of a continuous stream of single-phase or dual-phase droplets with digital control over droplet content, enabling the formation of dynamically-programmable and tunable emulsions. The multibarrel capillary method allows simultaneous generation of multiple droplets from parallel droplet generators, with controlled switching between selected dispersed phase or continuous phase compositions. Individual phases emerging from each capillary outlet may be selected to yield merged droplets combining continuous phase emitted from one or more neighboring droplet generators. Because the capillary emitters are configured in a two dimensional array, the multibarrel system provides greater flexibility toward producing controlled interactions between multiple solutions and phases than conventional planar microfluidic droplet generators. Using a 7-barrel capillary configuration, the ability to regulate droplet composition and particle size of individual as well as combined single and merged water-in-oil droplets is explored, together with the use of two-dimensional spatial control within the multibarrel array to generate higher order emulsions. (C) 2015 Elsevier B.V. All rights reserved.
We previously reported expression of a protein by enamel organ (EO) cells in rat incisors, originally isolated from the amyloid of Pindborg odontogenic tumors called Apin. The aim of the present study was to further characterize the Apin, gene and its protein in various species, assess tissue specificity, and clarify its localization within the EO. Northern blotting and RT-PCR revealed that expression of Apin was highest in the EO and gingiva, moderate in nasal and salivary glands, and lowest in the epididymis. The protein sequences deduced from the cloned cDNA for rat, mouse, pig, and human were aligned together with those obtained from four other mammal genomes. Apin is highly conserved in mammals but is absent in fish, birds, and amphibians. Comparative SIDS-PAGE analyses of the protein obtained from bacteria, transfected cells, and extracted from EOs all indicated that Apin is post-translationally modified, a finding consistent with the presence of predicted sites for phosphorylation and O-linked glycosylation. In rodent incisors, Apin was detected only in the ameloblast layer of the EO, starting at post-secretory transition and extending throughout the maturation stage. Intense labeling was visible over the Golgi region as well as on the apices of ameloblasts abutting the enamel matrix. Apin was also immunodetected in epithelial cells of the gingiva which bind it to the tooth surface (junctional epithelium). The presence of Apin at cell-tooth interfaces suggests involvement in adhesive mechanisms active at these sites, but its presence among other epithelial tissues indicates Apin likely possesses broader physiological roles.
Background: The aetiological spectrum of acute encephalitis shows inter- and intra-geographical variations. We aimed to identify the viruses that cause infectious encephalitis in Sri Lanka, which represents a South Asian population. Methods: A cross-sectional study was conducted among 99 patients with encephalitis/meningoencephalitis admitted to two tertiary-care hospitals in Colombo. Cerebrospinal fluid and serum were tested for conventional and emerging encephalitogenic viruses. Specific nucleic acid amplification and antibody assays were used to identify viruses. Plaque reduction neutralization test was done to confirm the diagnosis of West Nile virus (WNV). Results: Patients' age ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral aetiology was identified in only 27.3%. These included dengue virus (40.7%), Japanese encephalitis virus (25.9%), varicella zoster virus, WNV and probable Epstein Barr virus (11.1% each). None were positive for herpes simplex viruses or cytomegalovirus. Screening for bacterial aetiologies was negative for all patients. There were no distinguishable clinical or laboratory findings between the different viral aetiologies. The case fatality rate was 7%, which was higher among patients with an identified viral aetiology. Conclusions: A viral aetiology was identified in only about a quarter of patients with encephalitis. Dengue virus accounted for the majority.
Glycan conversion of glycoprotein via the transglycosylation activity of endo-beta-N-acetylglucosaminidase is a promising chemoenzymatic technology for the production of glycoproteins including bio-medicines with a homogeneous glycoform. Although Endo-M is a key enzyme in this process, its product undergoes rehydrolysis, which leads to a lower yield, and limits the practical application of this enzyme. We developed several Endo-M mutant enzymes including N175Q with glycosynthase-like activity and/or transglycosidase-like activity. We found that the Endo-M N175H mutant showed glycosynthase-like activity comparable to N175Q as well as transglycosidase-like activity superior to N175Q. Using a natural sialylglycopeptide as a donor substrate, N175H readily transferred the sialo-glycan onto an N-acetylglucosamine residue attached to bovine ribonuclease B (RNase B), yielding a nonnative sialoglycosylated RNase B. These results demonstrate that use of Endo-M N175H is an alternative glycoengineering technique, which provides a relatively high yield of transglycosylation product and avoids the laborious synthesis of a sugar oxazoline as a donor substrate. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 812-819, 2016
Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats. Newborn Wistar rats were treated daily with ETN, ALN, or sterile saline solution (control) for 21 days. Their femur and tibiae epiphyses were radiographed and analyzed by light, scanning and transmission electron microscopy. The expression of genes related to osteogenesis and to osteoclast differentiation and activity were analyzed by real-time quantitative polymerase chain reaction. The ETN group presented reduced body weight, disorganized growth plate and an extended area of cartilage in the ossification zone with little bone matrix; in the ALN group, this area was not altered. The ALN presented latent TRAP-positive cells, whereas in the ETN group, they were activated. The expression of NF kappa B1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. RANKL expression was reduced by ETN, whereas ALN decreased the expression of RANK. The results also indicated that, in addition to the anti-resorptive effect of the drugs, disturbances in bone deposition occurred concomitantly with the reduced expression of osteogenesis-related genes.
IntroductionWomen with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. Material and methodsA cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. ResultsThe body mass indices of women with polycystic ovary syndrome (29.282.91kg/m(2)) and controls (28.58 +/- 2.62kg/m(2)) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 +/- 5.70kg/m(2)). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p<0.0001). Sterol regulatory element binding protein-1 gene expression was positively correlated with body mass index (r=0.017, p=0.921) and waist-hip ratio (r=0.023, p=0.544) in polycystic ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r=0.643, p=0.06) and waist-hip ratio (r=0.096, p=0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p=0.028 and p=0.027, respectively). Quantitative serum sterol regulatory element binding protein-1 gene correlated with endometrial gene expression (p<0.05). ConclusionsSterol regulatory element binding protein-1 gene expression is significantly increased in the endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer.
The endoparasitoid wasp, Meteorus pulchricornis (Wesmael), introduces virus-like particles [M. pulchricornis VLP (MpVLP)] and venom into its lepidopteran host larvae upon oviposition. These wasp-associated factors are considered to help impair some host functions including immune defense. To obtain the major protein repertoire of the MpVLP and venom that might support successful parasitism, we constructed a conventional cDNA library of the venom gland filament that produces both of them, and sequenced cDNA clones arbitrarily in the 5' regions. The 5' expressed sequence tags obtained from 473 independent cDNA clones were grouped into 228 clusters. One hundred and five of these clusters were annotated with one or more gene ontology (GO) terms by Blast2GO analyses. While the major repertoire of the M. pulchricornis venom gland shared some constituents with those of the venom glands of other parasitoid wasp species, it was distinct from those encoded by polydnaviruses. Twenty clusters selected for further analyses were fully sequenced and characterized again. Among them, 17 factors were subjected to quantitative reverse transcription polymerase chain reaction analyses, and 12 factors were suggested to be highly adult specific. Among these 17 factors, ten were tested as RNA interference targets, and effective gene silencing was observed for five factors. These five factors included two components of MpVLP. The MpVLP deficient in the two factors prepared from the knockdown wasps was less effective than the wild-type MpVLP in terms of the inhibitory activity against host hemocyte spreading estimated in vitro.
Endophytes are microorganisms that inhabit plant tissues without causing disease. Some endophytes help their hosts to combat pathogens. Here we explored the hypothesis that the plant-derived foods consumed by humans and other animals host endophytes that also antagonize foodborne pathogens or food-rotting agents. Our laboratory previously cultured a library of bacterial endophytes from different members of the maize/corn family (Zea) including wild relatives. Here, 190 of these endophytes were screened for their ability to antagonize four foodborne pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Clostridium perfringens, and Salmonella enterica Newport) and a food spoiling agent (Pseudomonas fluorescens) using dual culture assays. Two Paenibacillus polymyxa endophytes (strains 3C6 and 3G11) were found to inhibit the growth of all five deleterious strains on agar. Using conserved polymerase chain reaction primers and sequencing, both beneficial endophytes were found to encode polymyxin genes, suggesting a potential antibacterial mechanism of action. Polymyxin production by both strains was confirmed using enzyme-linked immunosorbent assay. Strains 3C6 and 3G11 originated, respectively, from the seeds of the wild Central American maize species Zea diploperennis, and the wild ancestor of modern maize, Zea mays ssp parviglumis (Parviglumis). As the latter is the direct ancestor of modern maize, we discuss the role its endophyte(s) may have played in promoting crop domestication by suppressing foodborne pathogens and/or food-spoilage agents.
Taxol or paclitaxel, an approved drug by the Food and Drug Administration, is being used for the treatment of human cancers. This study aimed to isolate and determine different species of native endophytic fungi from Iranian Taxus baccata (yew) plants located in the northern forests of Iran. To do so, a novel molecular screening approach was performed for 50 isolated endophytic fungi through amplification of exon No. 1 of taxadine synthase as a key gene in taxol production pathway. We used effective colony-polymerase chain reaction technique for rapid screening of potent taxol-producing fungi instead of genomic DNA extraction. Production of taxol was performed in batch culture by selected fungi individually and produced taxol was assayed quantitatively by high-performance liquid chromatography using standard taxanes. We found that only six fungi could produce taxol and baccatin III. Interestingly, after 7 days of incubation, the highest level of taxol was found to be 129 and that of baccatin 139.2 mg/kg dw for two native isolated Cladosporium sp. named F1 and F3. The fungal taxols could decrease cell viability in MTT assay same as commercial taxol. The fungal taxols semi-quantitatively showed antimitotic effects on MCF-7 cells as human breast cancer cell line. The expression of bcl-2 anti-apoptotic gene, in contrast to bax pro-apoptotic gene, significantly decreased after treatment by standard and fungal taxols. As fungal taxol was produced simpler than other methods and could significantly affect viability and specific genes expression profile, it is recommended that using of taxol-producing fungi from Iranian yew could be a safe and confident procedure to overcome challenges of using other methods.
Since their discovery about 20 years ago, small RNAs have been shown to play a critical role in a myriad of biological processes. The greater availability of high-throughput sequencing has been invaluable to furthering our understanding of small RNAs as regulatory molecules. In particular, these sequencing technologies have been crucial in understanding the role of small RNAs in reproductive tissues, where millions of individual sequences are generated. In this context, high-throughput sequencing provides the requisite level of resolution that other procedures, like northern blotting, would not be able to achieve. Here, we describe a protocol for the preparation of small RNA libraries for sequencing using the Solexa/Illumina technology.
Background: Improving islet graft revascularization has become a crucial task for prolonging islet graft survival. Endothelial cells (ECs) are the basis of new microvessels in an isolated islet, and EC coating has been demonstrated to improve the vascularization and survival of an islet. However, the traditional method of EC coating of islets has low efficiency in vitro. This study was conducted to evaluate the effect of a polyglycolic acid (PGA) scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft. Methods: A PGA fibrous scaffold was used for EC coating of islet culture and was evaluated for its efficiency of EC coating on islets and islet graft angiogenesis. Results: In in vitro experiments, we found that apoptosis index of ECs-coating islet in PGA group (27% +/- 8%) was significantly lower than that in control group (83% +/- 20%, P < 0.05) after 7 days culture. Stimulation index was significantly greater in the PGA group than in the control group at day 7 after ECs-coating (2.07 +/- 0.31 vs. 1.80 +/- 0.23, P < 0.05). vascular endothelial growth factor (VEGF) level in the PGA group was significantly higher than the coating in the control group after 7 days culture (52.10 +/- 13.50 ng/ml vs. 16.30 +/- 8.10 ng/ml, P < 0.05). Because of a tight, circumvallated, adhesive and three-dimensional growth microenvironment, islet cultured in a PGA scaffold had higher coating efficiency showing stronger staining intensity of enzyme than those in the control group after 14 days of culture following ECs-coating. For in vivo study, PGA scaffold significantly prolonged the average survival time of EC-coated islet graft after transplantation compared with control group (15.30 +/- 5.60 days vs. 8.30 +/- 2.45 days, P < 0.05). The angiogenesis and area of survived grafts were more in the PGA group compared with the control group by measuring the mean microvessel density (8.60 +/- 1.21/mm(2) vs. 5.20 +/- 0.87/mm(2), P < 0.05). In addition, expression of VEGF and tyrosin-protein kinase receptor (Tie-2) gene increased in PGA scaffold group than that in control group by real-time reverse transcription-polymerase chain reaction analysis. Conclusions: These results demonstrate that the efficiency of EC coating of islets was successfully increased by culturing ECs on a PGA scaffold. This method enhances the function, survival, and vascularization of isolated islets in vitro and in vivo.
Aim: Existing evidence suggests that endothelial lipase (EL) plays an important role in high-density-lipoprotein (HDL) metabolism. Because rabbits are a useful animal model for the study of human lipid metabolism and atherosclerosis, we characterized rabbit EL (rEL) expression and investigated its relationship with plasma HDL levels in normal and hyperlipidemic rabbits. Methods: We cloned the rEL cDNA and analyzed the EL tissue expression using Northern blotting, real-time RT-PCR, Western blotting, and in situ hybridization. We evaluated the effects of rEL antisense on plasma HDL levels. Results: We found that rEL mRNA was highly expressed in cholesterol synthesis-related organs, including the liver, testis, and adrenal along with its expression in the lung, kidney, bone marrow, and small intestine. Interestingly, Watanabe heritable hyperlipidemic (WHHL) rabbits, a model of human familial hypercholesterolemia, had lower plasma levels of HDLs than normal rabbits. The plasma HDL levels in WHHL rabbits were inversely associated with high levels of plasma rEL proteins and hepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides into rabbits resulted in the elevation of plasma large HDLs. Furthermore, we demonstrated that rEL mRNA was expressed by both endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL rabbits. Conclusions: rEL is expressed in multiple tissues and may have many physiological and pathophysiological functions, such as in the regulation of cholesterol metabolism and atherosclerosis. Our results suggest that EL is an important regulator of plasma HDL levels in rabbits.
In the present study, we have investigated the effect of (i) ET-I (endothelin-1) and its precursor, big ET-1, on MMP (matrix metal loproteinase)-2 and MMP-9 synthesis and activity in osteosarcoma tissue, and (ii) ET-I receptor antagonists on cell invasion. Using Western blotting, zymography, RT-PCR (reverse transcription-PCR), immunohistochemistry, immunofluorescence and Northern blotting, we have shown that ET-I and ET-I receptors (ETA and ETB) were expressed in these cells. Additionally, we have demonstrated that ET-I markedly induced the synthesis and activity of MMP-2, which was significantly increased when compared with MMP-9. Furthermore, inhibition of NF-kappa B (nuclear factor kappa B) activation blocked MMP-2 production and activity, indicating the involvement of NF-kappa B, a ubiquitous transcription factor playing a central role in the differentiation, proliferation and malignant transformation. Since ET-I acts as an autocrine mediator through gelatinase induction and because inhibition of ETA receptor is beneficial for reducing both basal and ET-I-induced osteosarcoma cell invasion, targeting this receptor could be an attractive therapeutic alternative for the successful treatment of osteosarcoma.
Leptin, one of the adipocyte-secreted peptides, is involved in the control of appetite and body weight. Several studies have demonstrated that plasma leptin levels are elevated in obese subjects and are positively correlated with body weight. The arterial endothelin (ET) system plays an important role in the regulation of vascular tone, and ET-1 overexpression may be involved in the pathogenesis of the hypertension associated with insulin resistance. This study was performed to explore the regulatory effects of leptin on ET receptor expression and ET binding in A10 vascular smooth muscle cells (VSMCs) by use of Northern blotting, immunoblotting, and a I-125-labeled ET-1 binding assay. The effect of leptin on ET receptor-mediated cell proliferation was also tested. The results showed that leptin caused a significant increase in [I-125]-ET-1 binding, which was time- and dose-dependent. Immunoblotting showed that expression of the ET type A receptor (ETAR) in leptin (10(-7) M)-treated cells was increased by up to 2.3-fold compared with controls. Levels of ETAR mRNA measured by Northern blotting were also increased by up to 2.2-fold in leptin (10(-7) M)-treated cells. Pretreatment with an ERK inhibitor, PD-98059 (2.5 X 10(-5) M), blocked the leptin-induced increase in I-125-ET-1 binding. Finally, ET-1 (10(-7) M)-stimulated cell proliferation was enhanced by leptin (10(-7) M) pretreatment, with a maximal increase of twofold compared with controls. In conclusion, leptin increases ETAR expression in VSMCs in a time- and dose-dependent manner. This effect is ERK dependent and is associated with increased ET-1-stimulated cell proliferation. These findings provide support for roles for leptin and the ET system in the pathogenesis of obesity-associated hypertension.
Endothelin-1 (ET-1) is involved in the development of cardiac hypertrophy and heart failure. We investigated the effects of ET-1 on intracellular calcium transient and its mechanisms. Neonatal rat cardiomyocytes were prepared and calcium transient was measured using fura-2. Treatment with ET-1 for 48 h prolonged calcium transient decay. In the presence of thapsigargin, ET-1 did not alter calcium transient decay. On the other hand, the prolonged calcium transient decay was maintained even when sodium was removed from the bath solution. These results indicate that ET-1-induced prolongation of calcium transient decay is mainly due to the suppression of calcium uptake by sarcoplasmic reticulum, but not inhibition of the sodium/calcium exchanger. Northern blotting analysis revealed that sarcoplasmic reticulum ATPase (SERCA2) mRNA was decreased in ET-1-treated cardiomyocytes, and that this decrease was inhibited by BQ-123 but not by BQ-788. Moreover, pretreatment with chelerythrine partially restored the ET-1-induced decrease in SERCA2 mRNA, whereas phorbol 12-myristate 13-acetate markedly reduced SERCA2 gene expression. Real-time RT-PCR analysis showed abundant ETA receptor gene expression in cardiomyocytes. ET-1 reduces SERCA2 gene expression through the ETA receptor and PKC pathway, and prolongs intracellular calcium transient decay. Specific inhibition of the ETA receptor may be a possible therapeutic strategy for improving cardiac performance.
Leprosy triggers a complex relationship between the pathogen and host immune response. Endothelium plays an important role in this immune response by directly influencing cell migration to infected tissues. The objective of this work is to investigate the possible role of endothelium in M. leprae infection, correlating the characteristics of endothelial markers with the expression pattern of cytokines. Thirty-six skin biopsy samples were cut into 5-mu m thick sections and stained with hematoxylin-eosin and Ziehl-Neelsen for morphological analysis and then submitted to immunohistochemical analysis using monoclonal antibodies against ICAM-1, ICAM-2, VCAM-1, and VLA-4. Immunostaining for ICAM-1 showed a significantly larger number of stained endothelial cells in the tuberculoid leprosy (9.92 +/- 1.11 cells/mm(2)) when compared to lepromatous samples (5.87 +/- 1.01 cells/mm(2)) and ICAM-2 revealed no significant difference in the number of endothelial cells expressing this marker between the tuberculoid (13.21 +/- 1.27 cells/mm(2)) and lepromatous leprosy (14.3 +/- 1.02 cells/mm(2)). VCAM-1-immunostained showed 18.28 1.46/mm(2) cells in tuberculoid leprosy and 10.67 +/- 1.25 cells/mm(2) in the lepromatous leprosy. VLA-4 exhibited 22.46 +/- 1.38 cells/mm(2) in the tuberculoid leprosy 16.04 +/- 1.56 cells/mm(2) in the lepromatous leprosy. Samples with characteristics of the tuberculoid leprosy exhibited a larger number of cells stained with ICAM-1, VCAM-1 and VLA-4, demonstrating the importance of these molecules in the migration and selection of cells that reach the inflamed tissue. (C)2017 Elsevier Ltd. All rights reserved.
This paper uses data on the life satisfaction of more than 100,000 individuals in 21 European countries from 2002 to 2011, to study the relationship between subjective well-being and the affordability for households of electricity, heating oil and natural gas. We find that energy prices have statistically and economically significant effects on subjective well-being. The effect sizes are smaller than but comparable to the effects of important personal factors of well-being. Effects above average are found in individuals from the lowest income quartile. In addition, effects are strongest at times when required energy expenditures can be expected to be high. The empirical results are consistent with the prediction that greater fuel poverty implies a greater effect of energy prices on well-being.
Energy saving is a hot topic due to the proliferation of climate changes and energy challenges globally. However, people's perception about using smart technology for energy saving is still in the concept stage. This means that people talk about environmental awareness readily, yet in reality, they accept to pay the given energy bill. Due to the availability of electricity and its integral role, modulating consumers' attitudes towards energy savings can be a challenge. Notably, the gap in today's smart technology design in smart homes is the understanding of consumers' behaviour and the integration of this understanding into the smart technology. As part of the Paris Climate change agreement (2015), it is paramount for Singapore to introduce smart technologies targeted to reduce energy consumption. This paper focused on the perception of Singapore households on smart technology and its usage to save energy. Areas of current research include: (1) energy consumption in Singapore households, (2) public programs and policies in energy savings, (3) use of technology in energy savings, and (4) household perception of energy savings in smart homes. Furthermore, three case studies are reviewed in relation to smart homes and smart technology, while discussing the maturity of existing solutions.
As part of EU incentives, the UK government have set ambitious environmental targets relating to energy consumption including a reduction of carbon emissions of 80% by 2050. The use of various technologies can help meet these targets as well as providing a secure energy source for the UK in the future. This research took the UK as a case study and investigated where reduction measures are most suited to reduce energy consumption. This paper presents a review on the current state-of-the-art on the domestic technology available, in particular solar energy, heat pumps, phase changing materials (PCMs) and micro combined heat and power (micro-CHP) systems, aiming at identifying research and development opportunities for energy saving in these fields. Furthermore, the financial as well as environmental aspects are assessed as these are the two key considerations of typical household. A typical UK house design, including the floor plan, is created through the use of computer aided design (CAD) software. The house design gives a payback period between 8.7 years at best and 11.6 years at worst.
Climatic conditions are commonly considered the primary determinant of consumers' choices about energy use for heating. Besides, current regulations on the matter focus on the physical characteristics of the buildings, relying on a strict relationship between efficiency and savings. Nevertheless, the literature shows that energy demand determinants are difficult to be estimated with the accuracy required for predictive purposes, while the energy savings stemming from efficiency gains are partly outweighed by the consumers' behavior. We deal with these issues by analyzing spatial series data of natural gas consumptions for space heating and hot water production in the residential sector. The regression analysis takes four fields of covariates into account: climate, building characteristics, market aspects, and technological development. The estimation process is based on the following cornerstones: a spatially lagged dependent variable to deal with the problem of spatial autocorrelation, linear and logarithmic functional forms, and a two-stage interpolation strategy that is meant to provide unbiased estimates of both the dispersion matrix and the t-statistics by combining Ordinary Least Squares and Weighted Least Squares. The models turn out to be well specified, and their explanatory power is high, so the results are suitable for demand forecasting. Although the spatial autoregressive term does not appear among the significant regressors, we show that space does matter in shaping the natural gas consumption in different regions. Our analysis proves that heating gas demand is characterized by a positive elasticity to income. We use these results to provide estimates of the rebound effect. Nevertheless, the additional consumption directly attributable to an income effect is of moderate magnitude when the gas price does not vary. (C) 2017 Elsevier Ltd. All rights reserved.
This paper investigates the impact of stock market developments on oil and electricity demand of OECD member countries. We conduct different panel data methodologies and use annual data ranging from 1996 to 2011. The overall findings substantiate that income, real prices, size of the stock market and liquidity are important determinants for both oil and electricity demand. We also compute long-run elasticity coefficients by using a simple Partial Adjustment Model (PAM) and find that the long run elasticity coefficients are larger than the short run parameters. Moreover, our results show that the demand for oil and electricity is inelastic with respect to both own real price and real income over the short-run and the long-run. From a policy making perspective, the findings suggest that potential policy tools to reduce energy consumption may not be useful as the demand for energy is inelastic with respect to energy prices. Our results also manifest that although stock market deepening variables do not have a large effect on energy use as energy price and economic growth have, market size and liquidity significantly affect energy consumption. Therefore, energy demand estimations based on solely energy price and income may be inaccurate when some stock market development indicators are excluded. The empirical findings of this paper provide further insights for policy makers, energy companies and energy economists in terms of demand management policies and pricing decisions.
The empirical literature on the energy efficiency gap concentrates on demand inefficiencies in the energy-using durables markets and finds evidence that consumers underestimate future energy costs when purchasing a new appliance. We take a broader view and also consider the impact of imperfect competition. Using data on the UK refrigerator market (2002-2007), we find that the average energy consumption of appliances sold during this period was only 7.2% higher than what would have been observed under a scenario with a perfectly competitive market and non-myopic consumers. One reason for this small gap is that market power actually reduces energy use. (C) 2017 Elsevier B.V. All rights reserved.
The program administrator and total cost of saved energy allow comparison of the cost of efficiency across utilities, states, and program types, and can identify potential performance improvements. Comparing program administrator cost with the total cost of saved energy can indicate the degree to which programs leverage investment by participants. Based on reported total costs and savings information for U.S. utility efficiency programs from 2009 to 2013, we estimate the savings-weighted average total cost of saved electricity across 20 states at $0.046 per kilowatt-hour (kW h), comparing favorably with energy supply costs and retail rates. Programs targeted on the residential market averaged $0.030 per kW h compared to $0.053 per kW h for nonresidential programs. Lighting programs, with an average total cost of $0.018 per kW h, drove lower savings costs in the residential market. We provide estimates for the most common program types and find that program administrators and participants on average are splitting the costs of efficiency in half. More consistent, standardized and complete reporting on efficiency programs is needed. Differing definitions and quantification of costs, savings and savings lifetimes pose challenges for comparing program results. Reducing these uncertainties could increase confidence in efficiency as a resource among planners and policymakers.
This study presents an input-powered high-efficiency interface circuit for energy harvesting systems, and introduces a zero standby power design to reduce power consumption significantly while removing the external power supply. This interface circuit is composed of two stages. The first stage voltage doubler uses a positive feedback control loop to improve considerably the conversion speed and efficiency, and boost the output voltage. The second stage active diode adopts a common-grid operational amplifier (op-amp) to remove the influence of offset voltage in the traditional comparator, which eliminates leakage current and broadens bandwidth with low power consumption. The system supplies itself with the harvested energy, which enables it to enter the zero standby mode near the zero crossing points of the input current. Thereafter, high system efficiency and stability are achieved, which saves power consumption. The validity and feasibility of this design is verified by the simulation results based on the 65 nm CMOS process. The minimum input voltage is down to 0.3 V, the maximum voltage efficiency is 99.6% with a DC output current of 75.6 mu A, the maximum power efficiency is 98.2% with a DC output current of 40.4 mu A, and the maximum output power is 60.48 mu W. The power loss of the entire interface circuit is only 18.65 mu W, among which, the op-amp consumes only 2.65 mu W.
Fuel cell electric vehicles convert chemical energy of hydrogen into electricity to power their motor. Since cars are used for transport only during a small part of the time, energy stored in the on-board hydrogen tanks of fuel cell vehicles can be used to provide power when cars are parked. In this paper, we present a community microgrid with photovoltaic systems, wind turbines, and fuel cell electric vehicles that are used to provide vehicle-to-grid power when renewable power generation is scarce. Excess renewable power generation is used to produce hydrogen, which is stored in a refilling station. A central control system is designed to operate the system in such a way that the operational costs are minimized. To this end, a hybrid model for the system is derived, in which both the characteristics of the fuel cell vehicles and their traveling schedules are considered. The operational costs of the system are formulated considering the presence of uncertainty in the prediction of the load and renewable energy generation. A robust min-max model predictive control scheme is developed and finally, a case study illustrates the performance of the designed system. (C) 2016 The Authors. Published by Elsevier Ltd.
With the development of home area network, residents have the opportunity to schedule their power usage at the home by themselves aiming at reducing electricity expenses. Moreover, as renewable energy sources are deployed in home, an energy management system needs to consider both energy consumption and generation simultaneously to minimize the energy cost. In this paper, a smart home energy management model has been presented that considers both energy consumption and generation simultaneously. The proposed model arranges the household electrical and thermal appliances for operation such that the monetary expense of a customer is minimized based on the time-varying pricing model. In this model, the home gateway receives the electricity price information as well as the resident desired options in order to efficiently schedule the appliances and shave the peak as well. The scheduling approach is tested on a typical home including variety of home appliances, a small wind turbine, PV panel and a battery over a 24-h period. (C) 2017 Elsevier Ltd. All rights reserved.
In this work a photovoltaic energy station system is proposed. Power converters are designed to transfer energy between source, storage and underwater autonomous vehicle (AUV) load plus variable load station. Efficient regulation of the energy is achieved by linear control PI to track DC bus voltage. Energy management has a power configuration composed of DC-DC converters with digital-control using a Matlab software in order to do calculations. The mathematical formulation of system is analyzed to local stability and controlability. Gains of PI controllers are choice through two methods: Siso-tool of Matlab and stability gain analysis based on the transfer function. Stability proof analysis of converters is demonstrated by Routh Hurwitz even variation load station. Simulation evidence results of the performance improvement are shown.
Downhill conveyors are important potential energy sources within conveyor belt systems (CBSs). Their energy can be captured using regenerative drives. This paper presents a generic optimisation model for the energy management of CBSs that have downhill conveyors. The optimisation model is able to optimally schedule three configurations of a case-study CBS that is connected to the grid and operated under a time-of-use tariff. The three suggested drive configurations showcase potential energy savings/incomes that can be obtained from implementing: (a) variable speed control, (b) internal use of downhill conveyor energy and (c) the export of energy to the grid. The results show that a CBS with a daily energy consumption of 924 kWh can be reconfigured and controlled to reduce consumption by 53 or 100 % or be made to generate 1984 kWh, depending on the configuration. Analysis of the investment in each of the three configurations is assessed using a life-cycle cost and payback period (PBP). The daily operation simulation results show that the use of regenerative drives and variable speed control is able to provide energy savings in CBSs. The cost analysis shows that the configuration that enables sale of energy to the grid is the most profitable arrangement, for the case study plant under consideration. The sensitivity analysis indicates that the PBPs are more sensitive to the annual electricity price increases than changes in the discount rate. Combining regenerative drives and optimal operation of CBS generates energy savings that give attractive PBPs of less than 5 years.
This paper presents the system integration and hierarchical control implementation in an inverter-based Microgrid Research Laboratory (MGRL) at Aalborg University, Denmark. MGRL aims to provide a flexible experimental platform for comprehensive studies of microgrids. The structure of the laboratory, including the facilities, configurations, and communication network, is first introduced. The complete control system is based on a generic hierarchical control scheme including primary, secondary, and tertiary control. Primary control loops are developed and implemented in digital control platform, while system supervision, advanced secondary, and tertiary management are realized in a microgrid central controller. The software and hardware schemes are described. Several example case studies are introduced and performed to achieve power quality regulation, energy management, and flywheel energy storage system control. Experimental results are presented to show the performance of the whole system.
The Pacific white shrimp Litopenaeusvannamei is a euryhaline species with optimal salinity of 20-25 practical salinity unit (psu) for growth and survival, but has been cultured in inland water with salinity <5psu worldwide. In the past decade, much research progress has been made on the physiological and nutritional requirements of white shrimp at low salinity. This study reviews the recent findings in the aspects of growth, survival, energy metabolism, stress resistance and immunity of white shrimp at low salinity and synthesizes recent research outcomes in nutritional requirements in an attempt to improve the shrimp performance in aquaculture at low salinity. The white shrimp at low salinity usually show slow growth, low immunity, high susceptibility to pathogens and high energy demand. The diet containing 30-36% protein, 15-20% carbohydrate and supplementations of potassium, sodium, vitamin E and C, free amino acids (gly-cine, alanine, proline and taurine), antioxidants and probiotics can improve shrimp growth and immunity at low salinity. The white shrimp has demonstrated the ability to synthesize DHA and EPA from LNA at low ambient salinity, but further studies are needed to further confirm this finding. Future research should focus on the understanding of physiological mechanism and adaptation associated with salinity change and nutritional manipulation. The specific dietary requirements of essential fatty acids, essential amino acids, vitamins and minerals and the nutrition-mediated immune response also warrant further study on shrimp at low salinity.
When talking about energy conservation, "Rebound Effect" (RE) is always concerned, which defined as the increasing energy consumption relative to the counterfactual predicted by technological progress because of efficiency induced decrease in the real price of energy services. In this paper, we try to find a way to figure out the RE through calculating the substitution relations accord with the definition. Based on the trans-log cost function and considering the asymmetric impact on energy-cost share equation, the paper applies Allen-Uzawa substitution elasticity to establish the price-oriented analysis diagram of fossil-energy consumption RE. 'Using time series data, applying the joint method of the dynamic OLS (DOLS) and the seemingly unrelated regressions (SUR), the RE in China's electricity generation sector is estimated. The results showed that the RE is 11.6% in China's electricity generation sector if allowing for asymmetric price effects, which indicates that China's power generation sector generally displays a feature of energy saving.
In this paper, we propose novel techniques to reduce total cost and peak load of factories from a customer point of view. We control energy storage system (ESS) to minimize the total electricity bill under the Korea commercial and industrial (KCI) tariff, which both considers peak load and time of use (ToU). Under the KCI tariff, the average peak load, which is the maximum among all average power consumptions measured every 15 min for the past 12 months, determines the monthly base cost, and thus peak load control is extremely critical. We aim to leverage ESS for both peak load reduction based on load prediction as well as energy arbitrage exploiting ToU. However, load prediction inevitably has uncertainty, which makes ESS operation challenging with KCI tariff. To tackle it, we apply robust optimization to minimize risk in a real environment. Our approach significantly reduces the peak load by 49.9% and the total cost by 10.8% compared to the case that does not consider load uncertainty. In doing this we also consider battery degradation cost and validate the practical use of the proposed techniques.
The economic and environmental benefits brought by electric vehicles (EVs) cannot be fully delivered unless these vehicles are fully or partially charged by renewable energy sources (RES) such as photovoltaic system (PVS). Nevertheless, the EV charging management problem of a parking station integrated with RES is challenging due to the uncertain nature of local RES generation. This paper aims to address these difficulties by deploying an energy storage system (ESS) in parking stations and exploiting the charging and discharging scheduling of EVs to achieve better utilization of intermittent PVS for EV charging. A real-time charging optimization scheme is also formulated, using mixed-integer linear programming (MILP) to coordinate the charging or discharging power of EVs along with the power dispatches of power grid and ESS based on the vehicles' charging or discharging priorities and electricity price preferences. Extensive simulations show that the proposed approach not only maximizes the satisfaction of EV owners in terms of fulfilling all charging and discharging requests, but also minimizes the overall operational cost of the parking station by prioritizing the utilization of energy from PVS, ESS, and scheduling of every EV's charging and discharging.
Energy storage is unique in that it can provide multiple services. This feature raises cost-recovery issues for storage, due to the combination of competitive markets and ratebased cost recovery used in many power systems today. This hybrid regulatory paradigm relies on classifying assets as providing competitively prices or unpriced services and handling cost recovery based on that classification. Some recent regulatory precedents suggest that storage developers must choose between classifying their assets as providing competitively priced or unpriced services. In the former case, storage costs must be recovered through the market. If an asset is classified as providing only unpriced services, costs can be recovered through the ratebase. This regulatory design can hamper cost recovery for storage and may lead to inefficient storage investment and use. We propose an alternate solution whereby storage-capacity rights are auctioned to third parties that use their rights for priced or unpriced services. Storage-capacity rights disentangle storage cost recovery from the regulatory treatment of its end use. We formulate the storage-capacity auction model and demonstrate how to efficiently price storage-capacity rights. We show that the revenues earned by the storage owner through the auction equals the imputed marginal value of storage capacity, as revealed by the market bids.
In the transition to renewable energy systems, fluctuating renewable energy, such as wind and solar power, plays a large and important role. This creates a challenge in terms of meeting demands, as the energy production fluctuates based on weather patterns. To utilise high amounts of fluctuating renewable energy, the energy system has to be more flexible in terms of decoupling demand and production. This paper investigates two potential ways to increase flexibility. The first is the interconnection between energy systems, for instance between two countries, labelled as cross-border interconnection, and the second is cross-sector interconnection, i.e., the integration between different parts of an energy system, for instance heat and electricity. This paper seeks to compare the types of interconnectivity and discuss to which extent they are mutually beneficial. To do this, the study investigates two energy systems that represent Northern and Southern Europe. Both systems go through three developmental steps that increase the cross-sector interconnectivity. At each developmental step an increasing level of transmission capacities is examined to identify the benefits of cross-border interconnectivity. The results show that while both measures increase the system utilisation of renewable energy and the system efficiency, the cross-sector interconnection gives the best system performance. To analyse the possible interaction between cross-sector and cross-border interconnectivity, two main aspects have to be clarified. The first part defines the approach and the second is the construction of the two archetypes. (C) 2017 Elsevier Ltd. All rights reserved.
To alleviate environmental pollution and improve the efficient use of energy, energy systems integration (ESI)-covering electric power systems, heat systems and natural gas systems-has become an important trend in energy utilization. The traditional power flow calculation method, with the object as the power system, will prove difficult in meeting the requirements of the coupled energy flow analysis. This paper proposes a generalized energy flow (GEF) analysis method which is suitable for an ESI containing electricity, heat and gas subsystems. First, the models of electricity, heat, and natural gas networks in the ESI are established. In view of the complexity of the conventional method to solve the gas network including the compressor, an improved practical equivalent method was adopted based on different control modes. On this basis, a hybrid method combining homotopy and the Newton-Raphson algorithm was executed to compute the nonlinear equations of GEF, and the Jacobi matrix reflecting the coupling relationship of multi-energy was derived considering the grid connected mode and island modes of the power system in the ESI. Finally, the validity of the proposed method in multi-energy flow calculation and the analysis of interacting characteristics was verified using practical cases.
The EU dependence on imported gas is increasing, rising to 67% in the year 2014 with 30% of total gas consumption used for electricity generation that year. With such a dependence on imported gas, gas supply interruptions can have significant impacts on the EU energy system and economy. This points to the need for integrated electricity and gas modelling tools to fully explore the potential impacts of gas supply interruptions. This paper builds and applies a detailed publically available integrated electricity and gas model for the EU-28. We use this model to examine a number of hypothetical scenarios where gas supply routes are interrupted for yearly periods and the impacts on power system operation and gas flow in Europe observed. Model results show that interruption of Russian gas supply to the EU could lead to a rise in average gas prices of 28% and 12% in electricity prices. When supply from North Africa was removed all Southern European states were affected heavily, Spain in particular saw large increases of 30% in gas prices with a corresponding rise of 18% in electricity prices as a result. In addition to supply interruptions, all gas storages were removed from the model to examine the importance of gas storage infrastructure. This resulted in an average increase in power prices of 6% across Europe. These additional insights offer an increased understanding of the interplay between the gas and power systems and identify challenges which may arise when seeking to understand energy systems as a whole. (C) 2017 Elsevier Ltd. All rights reserved.
Drawing on basic physics, Kummel [24] and Beaudreau [4,5] attributed the productivity slowdown to the OPEC price-hike-led decrease in the rate of growth of energy consumption in the mid-1970s. The high post-WWII energy use growth rates observed in most OECD countries fell drastically, decreasing productivity and GDP growth. However since, considerable doubt has been cast on this view. For example, why did the rate of growth of energy use in manufacturing, specifically electricity use, fall when and where the price of electricity was either unaffected or increased slightly afterwards? Second, why did it fall instantaneously that is, without the usual lag? Third, why did energy consumption growth rates not return to their pre-1973 level once real energy prices had returned to their pre-1973 levels. Drawing from kinetics, this paper presents an alternative hypothesis, namely that energy demand-related factors, notably the physical limits to energy-based speed-ups, not energy supply-related factors, may have been behind this sudden decrease in productivity growth and hence behind the productivity slowdown. Specifically, in many industries and sectors, maximum machine speed/velocity may have been or was near to being reached in the late 1960s/early 1970s, making further increases physically impossible or not economically viable. (C) 2017 Elsevier Ltd. All rights reserved.
The global and UK drive for a low-carbon dioxide environment, as well as a secure and affordable energy supply, has encouraged nuclear power to play a core role in the UK energy mix: the UK landscape today houses eight large nuclear plants (15 reactors) reported to generate about 21% of UK electricity. By 2030, two-thirds of the UK's electricity generation capacity will have retired; it will need to be replaced with low-carbon dioxide and reliable power for the future to improve the UK's energy security and meet its commitments on carbon dioxide emissions targets. With 50% cumulative growth in nuclear capacity forecast between 2014 and 2035 (in comparison to coal at 10%, oil at 20% and gas at 44%) still leaving nuclear with only a 5% share of global capacity in 2035, there is considerable scope for nuclear in the long term.
Small modular reactors are a new generation of low-energy-output, low-hazard, compact and modular nuclear reactors, with an output of <300 MWe per unit. With the integration of inherent and passive safety measures, off-site construction and higher fuel burn-up rates, they promise a safer, lower-waste and reduced-risk venture, with earlier investment returns for investors compared with large-scale nuclear power plants. Moreover, non-proliferation is enhanced through the use of small quantities of non-weapons-grade nuclear fuel or the introduction of alternative potential fuels, such as thorium or fuel waste and actinides. This paper reviews the state of the art and discusses the economic feasibility of small modular reactors, with a focus on levelised cost of electricity, economy of scale and limitations for a country wishing to embark on nuclear energy through their deployment. Concerns regarding the integration of small modular reactors into the existing electrical grids of countries with various or no levels of nuclear-power production capability are also discussed. Suggestions on alternatively calculating the cost of small modular reactors and the legislation route are also provided, along with the pros and cons of the economics and safety of small modular reactor deployment in a country new to nuclear power.
More than two decades have passed since the start of the worldwide market-oriented electricity sector reforms. The reforms have varied in terms of structure, market mechanisms, and regulation. However, the passage of time calls for taking stock of the performance of the reforms in developing countries. This paper surveys the empirical literature on electricity sector reforms and draws some conclusions with a view to the future. Overall, the reforms have tended to improve the technical efficiency of the sector. The macroeconomic benefits of reforms are less clear and remain difficult to identify. Also, the gains from the reforms have often not trickled down to consumers because of institutional and regulatory weaknesses. In order to achieve lasting benefits, reforms need to adopt measures that align their pursuit of economic efficiency with those of equity and provision of access. Reforms can deliver more economic benefits and alleviate poverty when the poor have access to electricity. New technologies and institutional capacity building can help improve the performance of reforms.
Cloud computing has recently emerged as a dominant Internet service computing model due to its "payas-you-go" and "elastic service" features. Cloud computing systems are usually composed of distributed datacenters, which leverage virtualization technology to provide a scalable and reliable service. Optical networks are recognized as promising next-generation core networks for connecting these distributed datacenters due to their characteristics such as high bandwidth provisioning, low latency, low bit error rate, etc. However, concern about the ever-increasing energy consumption of cloud computing systems together with core networks has been raised due to high electricity bills as well as environmental pollution. In this paper, we study the Energy-aware Provisioning in Optical Cloud Networks (EPOCN) problem for both dynamic and static cases. When traffic requests arrive in an online fashion, we propose a polynomial-time energy-aware routing algorithm to solve the dynamic EPOCN problem. Simulations show that our energy-aware routing algorithm brings more energy savings in comparison to a shortest path-based routing algorithm and a traffic grooming algorithm. On the other hand, we show that the EPOCN problem in the static case (the traffic matrix is known in advance) is NP-hard. We further divide this problem into (1) the Energy-Aware Routing (EAR) problem in optical networks and (2) the Energy-efficient Server and Switch Allocation (ESSA) problem in datacenter networks. Considering these two (sub)problems are still NP-hard, we present an exact Integer Linear Program (ILP) and a heuristic to solve each problem. We also conduct simulations to compare the proposed ILPs and heuristics in terms of energy consumption and running time. (C) 2017 Elsevier B.V. All rights reserved.
In recent years, significant attention has been given to renewable energy integration within the context of global climate change. In the meantime, the energy-water nexus literature has recognized that the electricity & water infrastructure that enables the production, distribution, and consumption of these two precious commodities is intertwined. While these two issues may seem unrelated, their resolution is potentially synergistic in that renewable energy technologies not only present low CO2 emissions but also low water-intensities as well. Therefore, renewable energy integration has the potential to address both sustainability concerns. And yet, renewable energy integration studies have yet to methodologically consider an integrated energy-water infrastructure. Many of these works rely on a coupled unit commitment-economic dispatch simulation. Recently, a simultaneous co-optimization method has been contributed for the economic dispatch of networks that include water, power, and co-production facilities. This paper builds upon this foundation with the development of the corresponding unit commitment problem. It demonstrates the optimization on several case studies inspired by Singapore & the Middle East. It concludes that renewable energy simultaneously reduces CO2 emissions and water withdrawals. Furthermore, it shows how water storage can help alleviate binding co-production constraints, flatten production profiles and reduce production cost levels. (C) 2017 Elsevier Ltd. All rights reserved.
A facile, controllable, inexpensive and green electrochemical synthesis of IrO2-graphene nanohybrid thin films is developed to fabricate an easyto-use integrated paper microfluidic electrochemical pH sensor for resource-limited settings. Taking advantages from both pH meters and strips, the pH sensing platform is composed of hydrophobic barrier-patterned paper micropad (mu PAD) using polydimethylsiloxane (PDMS), screen-printed electrode (SPE) modified with IrO2-graphene films and molded acrylonitrile butadiene styrene (ABS) plastic holder. Repetitive cathodic potential cycling was employed for graphene oxide (GO) reduction which can completely remove electrochemically unstable oxygenated groups and generate a 2D defect-free homogeneous graphene thin film with excellent stability and electronic properties. A uniform and smooth IrO2 film in nanoscale grain size is anodically electrodeposited onto the graphene film, without any observable cracks. The resulting IrO2-RGO electrode showed slightly super-Nernstian responses from pH 2-12 in Britton-Robinson (B-R) buffers with good linearity, small hysteresis, low response time and reproducibility in different buffers, as well as low sensitivities to different interfering ionic species and dissolved oxygen. A simple portable digital pH meter is fabricated, whose signal is measured with a multimeter, using high input-impedance operational amplifier and consumer batteries. The pH values measured with the portable electrochemical paper-microfluidic pH sensors were consistent with those measured using a commercial laboratory pH meter with a glass electrode.
The construction of physical three-dimensional (3D) models of biomolecules can uniquely contribute to the study of the structure-function relationship. 3D structures are most often perceived using the two-dimensional and exclusively visual medium of the computer screen. Converting digital 3D molecular data into real objects enables information to be perceived through an expanded range of human senses, including direct stereoscopic vision, touch, and interaction. Such tangible models facilitate new insights, enable hypothesis testing, and serve as psychological or sensory anchors for conceptual information about the functions of biomolecules. Recent advances in consumer 3D printing technology enable, for the first time, the cost-effective fabrication of high-quality and scientifically accurate models of biomolecules in a variety of molecular representations. However, the optimization of the virtual model and its printing parameters is difficult and time consuming without detailed guidance. Here, we provide a guide on the digital design and physical fabrication of biomolecule models for research and pedagogy using open source or low-cost software and low-cost 3D printers that use fused filament fabrication technology.
Background: Various insect species have been added to genomic databases over the years. Thus, researchers can easily obtain online genomic information on invertebrates and insects. However, many incorrectly annotated genes are included in these databases, which can prevent the correct interpretation of subsequent functional analyses. To address this problem, we used a combination of dry and wet bench processes to select functional genes from public databases. Results: Enolase is an important glycolytic enzyme in all organisms. We used a combination of dry and wet bench processes to identify functional enolases in the silkworm Bombyx mori (BmEno). First, we detected five annotated enolases from public databases using a Hidden Markov Model (HMM) search, and then through cDNA cloning, Northern blotting, and RNA-seq analysis, we revealed three functional enolases in B. mori: BmEno1, BmEno2, and BmEnoC. BmEno1 contained a conserved key amino acid residue for metal binding and substrate binding in other species. However, BmEno2 and BmEnoC showed a change in this key amino acid. Phylogenetic analysis showed that BmEno2 and BmEnoC were distinct from BmEno1 and other enolases, and were distributed only in lepidopteran clusters. BmEno1 was expressed in all of the tissues used in our study. In contrast, BmEno2 was mainly expressed in the testis with some expression in the ovary and suboesophageal ganglion. BmEnoC was weakly expressed in the testis. Quantitative RT-PCR showed that the mRNA expression of BmEno2 and BmEnoC correlated with testis development; thus, BmEno2 and BmEnoC may be related to lepidopteran-specific spermiogenesis. Conclusions: We identified and characterized three functional enolases from public databases with a combination of dry and wet bench processes in the silkworm B. mori. In addition, we determined that BmEno2 and BmEnoC had species-specific functions. Our strategy could be helpful for the detection of minor genes and functional genes in non-model organisms from public databases.
Two bacterial strains isolated from root nodules of soybean were characterized phylogenetically as members of a distinct group in the genus Ensifer based on 16S rRNA gene comparisons. They were also verified as a separated group by the concatenated sequence analyses of recA, atpD and glnII (with similarities <= 93.9% to the type strains for defined species), and by the average nucleotide identities (ANI) between the whole genome sequence of the representative strain CCBAU 251167(T) and those of the closely related strains in Ensifer glycinis and Ensifer fredii (90.5% and 90.3%, respectively). Phylogeny of symbiotic genes (nodC and nifH) grouped these two strains together with some soybean-nodulating strains of E. fredii, E. glycinis and Ensifer sojae. Nodulation tests indicated that the representative strain CCBAU 251167(T) could form root nodules with capability of nitrogen fixing on its host plant and Glycine soja, Cajanus cajan, Vigna unguiculata, Phaseolus vulgaris and Astragalus membranaceus, and it formed ineffective nodules on Leucaena leucocephala. Strain CCBAU 251167(T) contained fatty acids 18:1 omega 9c, 18:0 iso and 20:0, differing from other related strains. Utilization of L-threonine and D-serine as carbon source, growth at pH 6.0 and intolerance of 1% (w/v) NaCI distinguished strain CCBAU 251167(T) from other type strains of the related species. The genome size of CCBAU 251167(T) was 6.2 Mbp, comprising 7,581 predicted genes with DNA G+C content of 59.9 mol% and 970 unique genes. Therefore, a novel species, Ensifer shofinae sp. nov., is proposed, with CCBAU 251167(T) (=ACCC 19939(T) = LMG 29645(T)) as type strain. (C) 2017 Elsevier GmbH. All rights reserved.
To investigate the microbial quality of retail pepper in Vietnam, the enumeration and detection of Enterobacteriaceae and the screening of cefotaxime (CTX)-resistant coliforms were performed by using 84 commercial samples. Although Enterobacteriaceae were isolated from 78 samples, the number of Enterobacteriaceae was lower than 1.0 log CFU/g in 46 samples. For the detection of Enterobacteriaceae with the International Organization for Standardization methods, Salmonella spp., Escherichia coli, Klebsiella pneumoniae, Cronobacter sakazakii, and Enterobacter cloacae complex were isolated from 5, 12, 36, 19, and 30 samples, respectively. During screening of CTX-resistant coliforms, K. pneumoniae, C. sakazakii, and E. cloacae complex were isolated from 8, 1, and 21 samples, respectively. Seven K. pneumoniae and seven E. cloacae complex isolates obtained in the screening of CTX-resistant coliforms were resistant to at least one of the three third-generation cephalosporins (CTX, ceftazidime, and cefpodoxime). Moreover, one E. cloacae complex cluster IV and all K. pneumoniae isolates were positive for extended-spectrum beta-lactamase genes or plasmid-mediated AmpC P-lactamase genes or both. Additionally, two extended-spectrum beta-lactamase-producing K. pneumoniae isolates and one AmpC beta-lactamase-producing E. cloacae complex cluster IV isolate were positive for the plasmid-mediated quinolone resistance determinants and also had amino acid alterations in the quinolone resistance-determining regions of GyrA and ParC. Furthermore, 10 E. cloacae complex isolates were positive for the plasmid-mediated fosfomycin resistance gene fosA. As pepper is often consumed without a heating process, the possible spread to humans of foodborne, opportunistic, and nosocomial infection pathogens or resistance genes from foods prepared or seasoned with pepper cannot be excluded. Therefore, it is necessary to handle pepper by using hygienic conditions during the cultivation, harvesting and processing steps.
Most studies of opportunistic infections focus on immunocompromised patients. However, there is a lack of information on microsporidiosis in healthy people (immunocompetent) worldwide. This study aimed to detect and identify microsporidia species in immunocompetent Orang Ash living in Pahang, Malaysia. Orang Ash is a collective term for a group of indigenous people that usually reside in the interior regions of Peninsular Malaysia. They comprise about 0.7% of the total population in Malaysia and 76% of them lived below the poverty line i.e., poor housing conditions with the lack of access to safe drinking water and adequate sanitation, contaminated environment, high illiteracy rate and unhygienic practices by these people. Stool samples were collected from 209 Orang Asli and analyzed for detecting the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis by polymerase chain reaction assay targeting small subunit ribosomal RNA gene. E. bieneusi was detected in 8 individuals (3.83%). This infection was commonly found in males than females (5.2% vs. 2.7%). All infected Orang Asli were adults, with a mean age of 44 years. Diarrhea and other gastrointestinal symptoms were reported in one case (12.5%) among individuals infected with this species. These findings clearly show that exposure to E. bieneusi may actually be common than reported. The accurate detection and identification of microsporidian species by molecular technique will improve therapy, clinical manifestations and prognosis of this infection, as no antiparasitic therapy has been approved for E. bieneusi. It is hoped that these findings will allow the formulation of better health management and disease prevention advisories, and improvement in the standards of health in similar communities. (C) 2017 Elsevier Ireland Ltd. All rights reserved.
BackgroundHuman enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. ObjectivesWe aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. Patients/MethodsStudy samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. Results8.2% (842/10260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44% (20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent. ConclusionsEV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.
Purpose of review Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. Recent findings HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. Summary Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.
Enterovirus (EV) belongs to the picornavirus family and is common pathogen in clinics. Early study regarding EV infection mainly utilized pathogen culture, but retarding diagnosis and treatment. Recent progress of molecular biology has made progress for pathogen diagnosis. This study thus investigated the expression of EV in cerebrospinal fluid (CSF) of children with central nervous infection, in an attempt to discuss the clinical significance of EV genotyping. 94 children with aseptic encephalitis (or meningitis) were enrolled in parallel with 37 controls. Fluorescent RT-PCR was used to screen EV from CSF, with positive results obtained from those samples with CT values less than 30. After primary screening of EV, amplification of VP1 and VP4 segment was then performed, followed by sequencing of positive fragments and genotyping. No EV RNA was detected in 37 control patients, while 69 out of 94 aseptic encephalitis patients had EV RNA expression. Among those 53 samples were positive for VP1 segment while 47 samples were VP4-positive. Sequencing of those segments showed more than 96% homology with Gen Bank EV standard viral strain. Fluorescent RT-PCR can detect EV RNA from CSF of central nervous infection children with efficiency and accuracy. The combined genotyping of VP4 sequence can further improve sensitivity of EV typing.
The entrepreneurial ecosystem (EE) literature has attracted much attention, especially in policy circles. However, the concept suffers from a number of shortcomings: (1) it lacks a clear analytical framework that makes explicit what is cause and what is effect in an EE; (2) while being a systemic concept, the EE has not yet fully exploited insights from network theory, and it is not always clear in what way the proposed elements are connected in an EE; (3) it remains a challenge what institutions (and at what spatial scale) impact on the structure and performance of EE; (4) studies have often focused on the EE in single regions or clusters, but lack a comparative and multi-scalar perspective and (5) the EE literature tends to provide a static framework taking a snapshot of EE without considering systematically their evolution over time. For each of these shortcomings, we make a number of suggestions to take up in future research on EE.
We describe the development and potential use of various designs of recombinant HIV-1 envelope glycoprotein trimers that mimic the structure of the virion-associated spike, which is the target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV-1 strains. Among the topics we address are the designs of various constructs; how native-like trimers can be produced and purified; the properties of such trimers in vitro and their immunogenicity in various animals; and the immunization strategies that may lead to the eventual elicitation of broadly neutralizing antibodies. In summary, native-like trimers are a now a platform for structure- and immunology-based design improvements that could eventually yield immunogens of practical value for solving the long-standing HIV-1 vaccine problem.
Envelope tracking (ET) and envelope elimination and restoration (EER) are techniques that have gained in importance in the last decade in order to obtain highly efficient radio frequency power amplifier that transmits signals with high peak-to-average power ratio. In this study, a multilevel multiphase buck converter is presented as a solution for the envelope amplifier used in ET and EER. The presented multiphase buck converter generates multilevel voltage using "node" duty cycles and nonlinear control. In this way, the multilevel is implemented using only one simple power stage. However, the complexity of the multilevel converter implementation has been shifted from complicated power topologies to complicated digital control. Detailed discussion regarding the influence of the design parameters (switching frequency, output filter, and time resolution of the digital control) on the performance of the proposed envelope amplifier is presented. The design of the output filter is conducted fulfilling the constraints of the envelope slew rate and minimum driver pulse that can be reproduced. In the cases when these two constraints cannot be fulfilled, they may be relieved by the modified control that is presented and experimentally validated. Finally, in order to validate the concept, a prototype has been designed and integrated with a nonlinear class F amplifier. Efficiency measurements showed that by employing EER, it is possible to save up to 15% of power losses, comparing to the case when it is supplied by a constant voltage. Additionally, adjacent channel power ratio has been measured. The obtained results showed the value higher than 30 dB for signals up to 5 MHz of bandwidth, without using a predistortion technique.
In this paper, a novel digital predistortion assisted supply modulator is presented. The proposed modulator is suitable for envelope tracking power amplifiers. In this topology, a digitally controlled linear power amplifier is used to compensate the switching noise ripples of the switching modulator. The proposed structure is evaluated with a 0.18 mu m CMOS process technology. The results show up to 9% static efficiency improvement in comparison with previous one-phase and two-phase architectures. It is shown that for a 5 MHz WiMAX signal with a 6.7 dB PAPR at 26.8 dBm output power, a maximum average efficiency of 73.5% is achieved in the proposed design. (C) 2015 Elsevier B.V. All rights reserved.
Purpose Knowledge regarding environmental impacts of agricultural systems is required. Consideration of uncertainty in life cycle assessment (LCA) provides additional scientific information for decision making. The aims of this study were to compare the environmental impacts of different growing cherry tomato cultivation scenarios under Mediterranean conditions and to assess the uncertainty associated to the different agricultural production scenarios. Materials and methods The burdens associated to cherry tomato production were calculated and evaluated by the LCA methodology. The functional unit (FU) chosen for this study was the mass unit of 1 t of commercial loose cherry tomatoes. This study included the quantitative uncertainty analysis through Monte Carlo simulation. Three scenarios were considered: greenhouse (GH), screenhouse (SH), and open field (OF). The flows and processes of the product scenario were structured in several sections: structure, auxiliary equipment, fertilizers, crop management, pesticides, and waste management. Six midpoint impact categories were selected for their relevance: climate change, terrestrial acidification, marine eutrophication, metal depletion, and fossil depletion using the impact evaluation method Recipe Midpoint and ecotoxicity using USEtox. Results and discussion The structure, auxiliary equipment, and fertilizers produced the largest environmental impacts in cherry tomato production. The greatest impact in these stages was found in the manufacture and drawing of the steel structures, manufacture of perlite, the amount of HDPE plastics used, and the electricity consumed by the irrigation system and the manufacture and application of fertilizers. GH was the cropping scenario with the largest environmental impact in most categories (varying from 18 and 37% higher than SH and OF, respectively, in metal depletion, to 96% higher than SH and OF, in eutrophication). OF showed the highest uncertainty in ecotoxicity, with a bandwidth of 60 CTUe and a probability of 100 and 99.4% to be higher than GH and SH, respectively. Conclusions The LCA was used to improve the identification and evaluation of the environmental burdens for cherry tomato production in the Mediterranean area. This study demonstrates the significance of conducting uncertainty analyses for comparative LCAs used in comparative relative product environmental impacts.
In Pisum sativum, the short-chain alcohol dehydrogenase-like protein (SAD) gene family consists of at least three members (SAD-A, -B, and -C). Expression of two of these genes (SAD-A and -C) in Escherichia coli or Pichia pastoris resulted in full-length soluble proteins. Purified SAD-A was used as antigen for antibody production in rabbits. With these antibodies the recombinant SAD-C protein (which was most highly expressed of the two isoforms) was shown to be a tetramer consisting of a dinner of dimers. The SAD genes are transiently expressed in plants by short exposures to ultraviolet-B radiation (UV-B), as judged by northern blotting. In turn, mRNA accumulation leads to formation of SAD protein in leaf and stem tissue upon prolonged UV-B irradiation. (c) 2008 Elsevier Inc. All rights reserved.
Lignin has recently attracted much attention due to their renewable nature. Here we focused on a simple self-assembly method for fabricating size and shape uniform enzymatic hydrolysis lignin (EHL) nanospheres, without chemical modification of lignin. EHL was dissolved in tetrahydrofuran at different initial concentrations and subsequently self-assembly with adding water under magnetic stirring for fabricating the nanospheres. The self-assembled structure, process parameters and formation mechanism of the nanospheres Were investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy (FTIR), and UV-vis absorption spectra. Results showed that the nanospheres were formed through a layer-by-layer self-assembly approach from inside to outside based on pi-pi interactions, which enabled the formation of nanospheres in the size range of 190-590 nm. Increasing the pre -dropping EHL concentration resulted in an increase of the average diameter and yield of the nanospheres. The nanospheres have good stability, and their average diameters had no significant change after 30 days. The chemical structural features of the nanospheres had not produced a significant change in the preparation process. High preparation temperature brought about the formation of the gaps at the surface of the nanospheres due to the effect of volatile speed of solvent. Moreover, the average diameter of the nanospheres decreased with an increase of stirring rate or the dropping speed of water. The proposed EHL nanospheres are eco-friendly, cost-effective and therefore a promising candidate for biomass based carrier. (C) 2017 Elsevier B.V. All rights reserved.
This study is the first comprehensive, report on the molecular cloning, structural characterization, sequence comparison between wild and mutant types, copy number in the genome, expression features and activities of a gene encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in Korean lawn grass (Zoysia japonica). The full length cDNA of the EPSPS from Korean lawn grass (zjEPSPS) obtained from a 3' and 5' RACE method was 1540 bp, containing a 1176 bp ORF, a 144 bp leader sequence (5' UTR) and a 220 bp 3' UTR, which was eventually decoded 391 amino acid residues with a molecular mass of 41.74 kDa. The Southern blot detection of the zjEPSPS showed that the gene exists as a single copy in the Korean lawn grass genome. Sequence comparison of the zjEPSPS gene demonstrated that the glyphosate-tolerant mutant (GT) having a Pro-53 to Ser substitution in the gene seems to have a preferred binding activity of the enzyme to phosphoenol pyruvate(PEP) over glyphosate, which allows the continuous synthesis of aromatic amino acids in the shikimate pathway. From the Northern blotting analysis, the zjEPSPS was found to be highly expressed, with continuous increase until 36 hours after 0.5% glyphosate treatment in both wild and mutant samples, but 1.5-fold higher EPSP synthase activity was observed in the tolerant mutant when exposed to the glyphosate treatment. The molecular information of the zjEPSPS gene obtained from this study needs to be further dissected to be more effectively applied to the development of gene-specific DNA markers and zoysiagrass cultivars; nevertheless, the glyphosate-tolerant mutant having the featured zjEPSPS gene can be provided to turfgrass managers for weed problems with timely adoptable management options.
A kinesthetic classroom activity was designed to help students understand enzyme activity and catalysis of reaction rate. Students served the role of enzymes by manipulating Pop-It Beads as the catalytic event. This activity illuminates the relationship between reaction rate and reaction progress by allowing students to experience first-hand the effect of substrate depletion on catalyzed reaction rate. Preliminary findings based on survey results and exam performance suggest the activity could prove beneficial to students in the targeted learning outcomes. Unique to previous kinesthetic approaches that model Michaelis-Menten kinetics, this activity models the effects of substrate depletion on catalyzed reaction rate. Therefore, it could prove beneficial for conveying the reasoning behind the initial rate simplification used in Michaelis-Menten kinetics. (C) 2016 by The International Union of Biochemistry and Molecular Biology, 45( 2): 179183, 2017.
Flat enzyme-based lactate biofuel cell (ELBC) integrated with power management system (PMS) was developed as a potential power supply for wearable sensors. Kinetic models of power output and chemical reagent concentration (lactate oxidase LOx and lactate) were developed to determine the limiting factor of the ELBC performance. Given the lactate concentration (0-40 mM) in human sweat, the optimum LOx amount coated on the anode ranged from 6U to 54U based on the experimental maximum power output. In the ELBC-PMS entity simulation test, power discharge recharge frequency was calculated for self-sustained sensing and data transmission, indicating that the ELBC could support wearable sensors (power requirement: 1-1350 mW; signal transfer frequency: 1-1320 times/h). The electrochemical activity of LOx coated anode was validated using the cyclic voltammetry (CV). The coefficient of variance and regression statistical analysis revealed the high stability and long lifespan (2 weeks) of ELBC without the need of lactate refill. Published by Elsevier Ltd.
BACKGROUND: Some patients with aspirin-exacerbated respiratory disease (AERD) and eosinophilia report angina-type chest pain that occurs at rest and responds to corticosteroid therapy. The frequency of eosinophilia-associated coronary artery vasospasm in patients with AERD, a disease characterized by blood and respiratory tissue eosinophilia, however, is unknown. OBJECTIVE: The objective of this study was to understand the cause of the chest pain described above and determine the most appropriate treatment for it. METHODS: A chart review of 153 patients with AERD who are followed at Brigham and Women's Hospital was performed. Patients who reported any type of chest pain were assessed for the presence of cardiac risk factors, eosinophilia, and response of chest pain to a variety of treatments. Two patients with AERD and eosinophilia who had recurrent chest pain due to suspected vasospasm are described in detail, and 8 other cases are also summarized. RESULTS: Of the 153 patients reviewed, 10 had a history of chest pain concerning for ischemia. Of the 10 patients with chest pain, 8 had undergone aspirin desensitization and initiated high-dose aspirin therapy; of these, 6 reported an increase in the frequency or severity of chest pain while on high-dose aspirin with improvement after aspirin discontinuation or dose reduction. Many patients had traditional cardiac risk factors, but none had any evidence of coronary atherosclerosis; almost all had significant eosinophilia. Their chest pain did not improve with typical antianginal treatments but did respond to corticosteroid therapy. CONCLUSIONS: Although uncommon, patients with AERD can develop eosinophilia-associated coronary artery vasospasm, which is occasionally worsened by high-dose aspirin. Patients with AERD who present with symptoms of ischemic chest pain should be screened for eosinophilia, as early treatment with corticosteroids can be life-saving. (C) 2016 American Academy of Allergy, Asthma & Immunology
AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 +/- 7.9 in the epithelium and 2.3 +/- 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 +/- 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 +/- 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.
Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016 classification, pathology is enriched by localization and molecular biology. Whatever the age, total removal by one or several looks when required remains a major prognostic factor. In children, focal radiation remains a standard, while the role of chemotherapy is matter of randomized studies. In infants, front line chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is encouraged. In case of relapse, further surgery and radiation are advised, while inclusion in innovative trials including re-irradiation, and phase I-II should be encouraged. A better understanding of underlying mechanisms of ependymoma cell will provide in the close future, the key to use targeted therapies at time of relapse, and very soon as first line therapy for some subgroups of patients.
Glaucoma is the second leading cause of blindness worldwide and is usually diagnosed in higher age groups. The goal was to survey how patient age influences the development of glaucoma. A web-based search on aging of the visual system and its influence on glaucoma was performed and the most important results are summarized. The prevalence of glaucoma rises with age. Aging processes of the trabecular meshwork and the uveoscleral outflow pathway lead to a rise in the intraocular pressure. Chronically elevated intraocular pressure leads to remodelling of the lamina cribrosa and narrowing of its pores through which ganglion cell axons leave the eye. Age-dependent glia cell, mitochondria and immune system alterations are discussed to influence glaucoma. Patient age and further age-related nonophthalmological systemic diseases also influence adherence and persistence to the prescribed therapy. Aging is an important risk factor for developing glaucoma and is a main factor which influences therapy and course of the disease. At this point in time it remains unclear to which extent additional factors determine the development of glaucoma.
Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for >= 9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.
Background: Germline mutations of the REarranged during Transfection (RET) proto-oncogene cause multiple endocrine neoplasia 2 (MEN2). It is unclear whether the distribution of RET mutations varies among populations. The first nationwide study of the distribution of RET mutations was conducted, and the results were compared to those of other populations. Methods: This retrospective cohort study included 1583 patients who underwent RET gene testing in one of three centers covering all of Denmark between September 1994 and December 2014. Primary testing method was Sanger sequencing, which included exons 8-11 and 13-16. Mutations were defined according to the ARUP database July 1, 2016. Results: RET mutations were identified in 163 patients from 36 apparently unrelated families. Among the 36 families 13 (36.1%) carried mutations in codon 611, four (11.1%) in codon 618, three (8.3%) in codon 620, one (2.8%) in codon 631, six (16.7%) in codon 634, one (2.8%) in codon 790, one (2.8%) in codon 804, one (2.8%) in codon 852, one (2.8%) in codon 883, and five (13.9%) in codon 918. Among the 13 families with codon 611 mutations, 12 had the p. C611Y mutation. Conclusions: The distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p. C611Y mutation. However, further studies are needed to find possible explanations for the skewed mutational spectrum in Denmark.
Objectives Sleep problems and deprivation are common during pregnancy, particularly in the third trimester. Previous studies are mostly descriptive or focused on specific clinical groups and late pregnancy. We aimed to identify sleep duration trajectories during the pregnancy period, their associated factors, and impact on pregnancy and birth outcomes. Methods We studied 200 women from a mother-child cohort recruited in 2009-2011 from the French general population. We used semi-parametric models to analyze data collected through questionnaires. Results We detected three sleep duration trajectories during pregnancy: short-decreasing (8h/night, 31.6%) trajectories. Factors associated with the short-decreasing trajectory relative to the medium-decreasing trajectory were older age (odds-ratio/year = 1.13 [95%Confidence-Interval 1.00-1.29]) and working >28 weeks of gestational age (odds-ratio = 0.30 [0.10-0.90]). Sleep duration during pregnancy in this trajectory group was modified by insomniac symptoms (regression coefficient/trimester = -0.74 [Standard-Error 0.12]) and naps (regression coefficient/trimester = 0.58 [0.25]). Restless legs syndrome was the only factor associated with the long-increasing trajectory and decreased sleep duration (regression coefficient/trimester = -0.88 [0.25]). Assisted delivery (i.e. cesarean section and/or instrumental delivery) and post-partum depression were more frequent among women with the short-decreasing and long-increasing trajectories whereas cesarean section alone was more prevalent among those with the short-decreasing trajectory. Proportion of premature births was higher in the short-decreasing trajectory group. Birth-weight-z-score was lower in the long-increasing trajectory group. Conclusion We identified sleep trajectories among pregnant women with specific risk factors that could affect both pregnancy and birth outcomes. Taking these into consideration could improve both maternal and child health.
Environmental epigenetics is the study of how environmental signals affect gene expression. Within this growing field of molecular biology, experiments on the epigenetic effects of 'maternal care' on offspring health have received much scientific and public attention and are often called upon to showcase how environmental epigenetics will create a new understanding of life as inherently 'biosocial.' While, on the one hand, this research is exciting and offers possible opportunities for collaboration between molecular biology and the social sciences, it is also necessary to consider its political dimensions. In this paper, we show how commonsense assumptions about sex, gender, sexuality, and class are present in the design, interpretation, and dissemination of experiments on the epigenetic effects of maternal care. As these experiments come to support claims about human motherhood through a dense speculative cross-traffic between epigenetic studies in rodents and psychological and epidemiological studies in humans, current research trends work to illustrate rather than interrogate existing stereotypes about maternal agency and responsibility. With this analysis, we offer a cautionary perspective regarding the potentials and challenges for new forms of collaborative biosocial knowledge practices emerging out of environmental epigenetics.
Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p < 0.001), but only reduced ToM in ASD-relatives (p < 0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. (C) 2017 Elsevier Ltd. All rights reserved.
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA). Recent preclinical research confirmed the anti-epileptiform activity of FA in homozygous scn1a mutant zebrafish larvae that mimic DS well. Here we explored the anti-epileptiform mechanisms of FA by investigating whether selective agonists/antagonists of specific receptor subtypes were able to counteract the FA-induced inhibition of seizures and abnormal brain discharges observed in the scn1a mutants. We show that antagonists of 5-HT1D and 5-HT2C receptor subtypes were able to do so (LY 310762 and SB 242084, respectively), but notably, a 5-HT2A-antagonist (ketanserin) was not. In addition, exploring further the mechanism of action of FA beyond its serotonergic profile, we found that the anti-epileptiform brain activity of FA was significantly abolished when it was administered in combination with a sigma(1)-agonist (PRE 084). Our study therefore provides the first evidence of an involvement of the sigma(1) receptor in the mechanism of FA. We further show that the level of some neurotransmitters [i.e., dopamine and noradrenaline (NAD)] in head homogenates was altered after FA treatment, whereas g-aminobutyric acid (GABA) and glutamate levels were not. Of interest, NAD-decreasing drugs have been employed successfully in the treatment of neurological diseases; including epilepsy and this effect could contribute to the therapeutic effect of the compound. In summary, we hypothesize that the anti-epileptiform activity of FA not only originates from its 5-HT1D and 5-HT2C-agonism, but likely also from its ability to block sigma(1) receptors. These findings will help in better understanding the pharmacological profile of compounds that is critical for their applicability in the treatment of DS and possibly also other drug-resistant epilepsies.
The red-spotted grouper, Epinephelus akaara, is a protogynous hermaphroditic fish that shows the characteristic of natural sex change. In this study, 2-year-old female groupers were successfully reversed to functional males by oral administration of 17 alpha-methyltestosterone (MT) for 42 days. The protein inhibitor of the neuronal nitric oxide synthase (PIN) gene was cloned from sex-reversed male gonads using modern suppression subtractive hybridization (SSH), cDNA synthesis and rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The full-length cDNA of PIN is 499 bp containing a 270 bp open reading frame (ORF) that encodes 89 amino acids. Virtual Northern blotting and reverse transcription-PCR (RT-PCR) analysis revealed that PIN was specifically transcribed in sex-reversed male gonads. Tissue-specific expression analysis showed that PIN gene was expressed in the brain, heart, liver, spleen, and kidney but not in the muscle tissue. Analyses of the expression pattern by RT-PCR and Western blotting indicated that transcription and the level of expression of PIN in the gonads increased gradually during the transformation from female to male. The results showed that PIN is strongly expressed in the sex-reversed male gonad but scarcely in the female gonad, and that its expression is upregulated as the change of sex proceeds. Taken together, these findings demonstrate that PIN is associated with the MT-induced sex transition of the red-spotted grouper, but the precise role of the gene in this process remains to be further investigated. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
The default mode network (DMN) has been identified reliably during rest, as well as during the performance of tasks such as episodic retrieval and future imagining. It remains unclear why this network is engaged across these seemingly distinct conditions, though many hypotheses have been proposed to account for these effects. Prior to generating hypotheses explaining common DMN involvement, the degree of commonality in the DMN across these conditions, within individuals, must be statistically determined to test whether or not the DMN is truly a unitary network, equally engaged across rest, retrieval and future imagining. To provide such a test, we used comparable paradigms (self-directed, uninterrupted thought of equal duration) across the three conditions (rest, retrieval, and future imagining) in a within-participant design. We found lower than expected pattern similarity in DMN functional connectivity across the three conditions. Similarity in connectivity accounted for only 40-50% of the total variance. Partial Least Squares (PLS) analyses revealed the medial temporal regions of the DMN were preferentially coupled with one another during episodic retrieval and future imagining, whereas the non-medial temporal regions of the DMN (e.g., medial prefrontal cortex, lateral temporal cortex, and temporal pole) were preferentially coupled during rest. These results suggest that DMN connectivity may be more flexible than previously considered. Our findings are in line with emerging evidence that the DMN is not a static network engaged commonly across distinct cognitive processes, but is instead a dynamic system, topographically changing in relation to ongoing cognitive demands. Hum Brain Mapp 38:1155-1171, 2017. (C) 2016 Wiley Periodicals, Inc.
Basement membranes maintain the epithelial phenotype and prevent invasion and metastasis. We hypothesized that expression of basement membrane laminins might be regulated by epithelial-mesenchymal transition (EMT), hallmark of cancer progression. As EMT is mediated by transcription factor Snail, we used oral squamous carcinoma cells obtained from a primary tumor (43A), from its EMT-experienced recurrence (43B) and Snail-transfected 43A cells (43A-SNA) displaying full EMT, as a model to study laminins and their receptors. Northern blotting, immunofluorescence, and immunoprecipitation showed a gradual loss of laminin-511 and its receptor Lutheran from 43A to 43B and 43A-SNA cells. In contrast, neoexpression of laminin alpha 4 mRNA was found congruent with synthesis of laminin-411. Chromatin immunoprecipitation disclosed direct binding of Snail to regions upstream of laminin alpha 5 and alpha 4 genes. Immunofluorescence and immunoprecipitation showed a switch from hemidesmosomal integrin alpha(6)beta(4) to alpha(6)beta(1) and neoexpression of alpha(1)beta(1) in 43A-SNA cells, and upregulation of integrin-linked kinase in both 43B and 43A-SNA cells. The cells adhered potently to laminin-511 and fibronectin, whereas adhesion to laminin-411 was minimal. In contrast, laminin-411 inhibited cell adhesion to other extracellular matrix proteins. In conclusion, EMT induces a switch from laminin-511 to laminin-411 expression, which may be directly controlled by Snail. Concomitant changes take place in laminin- and collagen-binding receptors. Laminin-411 reduces adhesion to laminin-511 and fibronectin, suggesting that tumor cells could utilize laminin-411 in their invasive behavior.
MicroRNAs (miRNAs) are involved in sequence-specific cleavage, translational repression or deadenylation of specific target mRNAs resulting in post-transcriptional gene silencing. Epstein-Barr Virus (EBV) infection induces cellular non-coding (nc)RNAs e.g., the "vault" RNAs or miRNAs such as miR-21, miR-155 or miR-146a. MiR-146a is upregulated in various tumours and plays a role in innate immunity. We show that the EBV-encoded latent membrane protein 1 (LMP1) induces the expression of miR-146a via NF kappa B. LMP1 activates the miR-146a promoter but not a promoter with a mutation of the NF kappa B-response elements. Conversely, a LMP1-mutant deficient in NF kappa B-activation failed to activate the promoter. The "CAO"-LMP1 variant which has an increased potential to induce NF kappa B also showed a higher ability to activate the miR-146a promoter as compared to standard B95.8-LMP1. Northern blotting revealed high levels of miR-146a and miR-155 in the Burkitt's lymphoma cell line Jiioye which expresses LMP1 while the LMP1-deficient P3HR1 mutant derived from Jiioye expresses less miR-146a or miR-155. Likewise, EBV-latency type I Burkitt's lymphoma cells with low LMP1 levels also contain low levels of either miR-146a or miR-155 while their levels are increased in LMP1-expressing EBV-latency type III BL cells. Expression of LMP1 in P3HR1 cells upregulates miR-146a levels. Neither miR-146a nor miR-155 are detectable in BCBL-1 cells transformed by the Kaposi-Sarcoma Herpes virus (KSHV/HHV8). It is possible that the induction of miR-146a plays a role in the induction or maintenance of EBV latency by modulating innate immune responses to the virus infected host cell.
Increase in power demand has required providing infrastructure, such as huge power plants and transmission lines. However, the recent trends in power system planning and operation are being toward maximum utilization of existing electricity infrastructure with tight operating margins because of new constraints placed by economic, political, and environmental issues. This might cause serious stability problems when a severe fault or a sudden outage of critical lines occurs. Therefore, the special protection scheme (SPS) has been used by generator tripping and successive load shedding to prevent a large-scale blackout by the cascading effect. If the number of tripping generators in the SPS operation is reduced, the enormous cost of power outage can be saved. This paper analyzes the enhancement of SPS via the transient stability improvement by the static synchronous compensator (STATCOM) applied to a generation side of Korea electric power system. First, its characteristic related to the SPS is described. Then, the proper capacity of STATCOM is determined with the equal area criterion to reduce the number of tripping generators. Also, the new control method for STATCOM is proposed for its full utilization. Finally, its effectiveness is verified by the case study with the practical data of Korea electric power system.
Invasive trophoblast from Day 34 horse conceptuses survives in extrauterine sites in allogeneic recipients that are immunologically naive to donor major histocompatibility complex class I antigens. The ectopic trophoblast retains its in utero characteristics, including similar lifespan, physiologic effect of its secreted product (equine chorionic gonadotropin) upon the recipient's ovaries, and induction of host immune responses. Immunologic memory has not been considered previously in this experimental system. We hypothesized that primary exposure to ectopic trophoblast would affect the recipient's immune status such that the survival time of subsequent transplants would be altered. Secondary transplant lifespans could be shortened by destructive memory responses, as has been observed in ectopic trophoblast studies in rodents, or lengthened, as occurs when male skin grafts follow multiple syngeneic pregnancies in mice. Eight mares received two closely spaced trophoblast transplants. Both grafts for each recipient were obtained from conceptuses sired by the same stallion to provide consistency in histocompatibility antigen exposure. Donor stallions were major histocompatibility complex class I homozygotes. Cytotoxic antibody production was tracked to monitor recipients' immune responses to the transplants. Detection of serum equine chorionic gonadotropin was used as a proxy for transplant lifespan. There was no significant difference between the distributions of primary and secondary transplant lifespans, despite evidence of immunologic memory. These data demonstrate that secondary ectopic trophoblast transplants in horses do not experience earlier destruction or prolonged survival following immune priming of recipients. Mechanisms responsible for the eventual demise of the transplants remain unperturbed by secondary immune responses or chronic antigenic exposure.
Although equine herpesvirus myeloencephalopathy (EHM) is a sporadic and relatively uncommon manifestation of equine herpesvirus-1 (EHV-1), it has the potential for causing devastating outbreaks in horses. Up till now, there were no reported EHM outbreaks in donkeys and mules. This study describes the isolation and molecular characterization of EHV-1 from clinically EHM-affected horses (n = 6), mules (n = 3) and donkeys (n = 82) in Ethiopia during outbreaks from May 2011 to December 2013. The incidence of EHM cases was higher from April to mid-June. EHM in donkeys was more severe and death without clinical signs of paralysis, and recumbency was frequently observed. The main age of affected equines ranged from 7 to 10 years (n = 51; 56.0%), and females (n = 58; 63.7%) were more affected than males. The incidence of neuropathogenic (D-752) and non-neuropathogenic (N-752) variants of EHV-1 from EHM-affected equines in Ethiopia was assessed by sequencing the DNA polymerase gene (ORF30) of the EHV-1 isolates. The results indicated that from the total of 91 clinically affected equines, 90 (98.9%) of them had an ORF30 D-752 genotype. An ORF30 N-752 variant was only found in one donkey. Analysis of ORF68 as grouping marker for geographical differences showed that the Ethiopian EHV-1 isolates belong to geographical group 4. Due to the fatal nature of EHV-1 in donkeys, it would be interesting to examine the pathogenesis of EHM in this species. At present, there is no vaccine available in Ethiopia, and therefore, outbreaks of EHV-1 should be controlled by proper management adaptations. In addition, it is important to test the efficacy of the commercial vaccines not only in horses, but also in donkeys and mules.
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells. In order to cope with ER stress, cancer cells and tumor-associated myeloid cells activate an integrated signaling pathway known as the Unfolded Protein Response (UPR), which promotes cell survival and adaptation under adverse environmental conditions. However, the UPR can also induce cell death under unresolved levels of ER stress. Three branches of the UPR have been described, including the activation of the inositol-requiring enzyme 1 (IRE1), the pancreatic ER kinase (PKR)-like ER kinase (PERK), and the activating transcription factor 6 (ATF6). In this minireview, we briefly discuss the role of ER stress and specific UPR mediators in tumor development, growth and metastasis. In addition, we describe how sustained ER stress responses operate as key mediators of chronic inflammation and immune suppression within tumors. Finally, we discuss multiple pharmacological approaches that overcome the immunosuppressive effect of the UPR in tumors, and that could potentially enhance the efficacy of cancer immunotherapies by reprogramming the function of tumor-infiltrating myeloid cells.
Anti-ErbB2 antibodies are used as convenient tools in exploration of ErbB2 functional mechanisms and in treatment of ErbB2-overexpressing tumors. When we employed the yeast Pichia pastoris to express an anti-ErbB2 single-chain antibody (scFv) derived from the tumor-inhibitory monoclonal antibody A21, the yield did not exceed 1-2 mg/L in shake flask cultures. As we considered that the poor codon usage bias may be one limiting factor leading to the inefficient translation and scFv production, we designed and synthesized the full-length scFv gene by choosing the P. pastoris preferred codons while keeping the G + C content at relatively low level. Codon optimization increased the scFv expression level 3- to 5-fold and up to 6-10 mg/L. Northern blotting further confirmed that the increase of scFv expression was mainly due to the enhancement of translation efficiency. Investigation of culture conditions revealed that the maximal cell growth and scFv expression were achieved at pH 6.5-7.0 with 2% casamino acids after 72 h methanol induction. Secreted scFv was easily purified (>95% homogeneous product) from culture supernatants in one step by using Ni2+ chelating affinity chromatography. The yield was approximately 10-15 mg/L. Functional studies showed that the A21 scFv could be internalized with high efficiency after binding to the ErbB2-overexpressing cells, suggesting this regent may prove especially useful for ErbB2-targeted immunotherapy. (c) 2005 Elsevier Inc. All rights reserved.
Background: Impaired function of endothelial nitric oxide synthase (eNOS) is involved in the pathologic processes of erectile dysfunction (ED), and three functional polymorphisms (G894T, T-786C, and a tandem repeat of 27 bp in intron 4) in the NOS3 gene, which encodes eNOS, are associated with the clinical characteristics of ED in several populations. Aim: To investigate the effect of these variations of NOS3 on ED phenotypes and the response to sildenafil in a Han Chinese population. Methods: This case-control study enrolled 112 patients with ED and 156 age-matched healthy men. Their medical history and laboratory data were collected. ED severity and response to sildenafil were assessed using the five-item International Index of Erectile Function (IIEF-5) score. Routine polymerase chain reaction and Sanger sequencing were used to genotype the three polymorphisms of NOS3. Outcomes: The frequencies of alleles, genotypes, and haplotypes of the loci in patients and controls; the IIEF-5 scores of patients carrying the risk and non-risk genotype; and the frequencies of risk and non-risk genotypes in patients with different ages at onset and responses to sildenafil were assessed. Results: The frequencies of drinkers and diabetic and hyperlipidemic patients in the ED group were higher than those in the age-matched control group (P<.05). The distributions of alleles (G894T, P<.005; T-786C, P<.015), genotypes (G894T, P<0.015; T-786C, P<.010), and haplotypes (G894T/T-786C, P<.015) of the NOS3 polymorphisms were significantly different between patients with ED and controls. An increased risk for earlier onset of ED was observed in the G894T risk genotype carriers (odds ratio = 3.572; P<.020). Patients with the risk genotype of T-786C exhibited lower IIEF-5 scores than patients with the non-risk genotype (8.2 +/- 4.5 vs 12.2 +/- 5.0; P<.015). The influence of the T-786C or G894T genotype on the response to sildenafil was not observed. Clinical Translation: The detectable effect of NOS3 functional polymorphisms on ED suggests their application potential as a molecular biomarker in predicting ED susceptibility and severity in the Han Chinese population. Strengths & Limitations: This study provides strong evidence that NOS3 functional variation is an independent risk factor for ED in the Han Chinese population, which should be confirmed in larger cohorts considering the limited number of subjects in this study. Conclusion: These results are the first to identify a clear association between NOS3 functional variation and ED susceptibility, age at onset, and severity in the Han Chinese population.
The paper presents an application of Hidden Markov Models (HMM) to fixations' sequences analysis. The examination concerns eye tracking data gathered during performing simple comparison and decision tasks for four versions of plain control panels. The panels displayed the target and current velocity either on a digital or analog (clock-face) speedometers. Subjects were to decide whether increase or decrease the current speed by pressing the appropriate button. The obtained results suggest that females, generally exhibit different covert attention patterns than men. Moreover, the article demonstrates the estimated four HMM with three hidden states for every examined control panels variant and provides discussion of the outcomes.
Infection of the freshwater Chinese mitten crab Eriocheir sinensis with hepatopancreatic necrosis disease (HPND) has been a major problem in the crab-cultivated Chinese Province of Jiangsu since 2015. To explore the etiology of HPND, meta-transcriptomic libraries of the hepatopancreata from crabs with and without HPND were constructed. Comparison analyses showed that there were no statistically significant differences in viral and microsporidial communities in the hepatopancreata of diseased and healthy crabs. Bacteroidetes, Proteobacteria, and Firmicutes were the most dominant bacterial phyla in the hepatopancreata of healthy crabs, with a combined prevalence of 93%. However, a decrease in bacterial diversity and a striking shift in the microbial composition were found in the hepatopancreata of crabs infected with HPND. Tenericutes was the most prevalent bacterial phylum in diseased crabs (31.82%), whereas its prevalence was low in healthy crabs (0.02%). By contrast, the prevalence of Bacteroidetes was significantly lower in crabs with HPND (3.49%) than in crabs without HPND (41.04%). We also found that the prevalence of Actinobacteria was higher in crabs with HPND (16.70%) than in crabs without the disease (4.03%). The major bacterial family within the Tenericutes phylum in crabs with HPND was detected by polymerase chain reaction and determined to be Mycoplasmataceae. In conclusion, there were striking changes in the microbiota of diseased and healthy crabs. Specifically, the prevalence of bacteria belonging to Tenericutes and Actinobacteria phyla increased, whereas the prevalence of bacteria belonging to the Bacteroidetes phylum decreased in crabs with HPND, clearly pointing to an association with HPND.
Molt-inhibiting hormone (MIH), a member of the crustacean hyperglycemic hormone (CHH) family, inhibits the synthesis of ecdysteroid in Y-organ (YO) and plays a significant role in the regulation of molting and growth of crustaceans. A complete cDNA sequence encoding MIH (Ers-MIH, GenBank Accession No.: DQ341280) was cloned from eyestalk of Chinese mitten crab (Eriocheir sinensis) by 5' and 3' RACEs and PCR cloning. The full-length cDNA consists of 1457 bp with a 330 bp open reading frame, encoding 110 amino acids, containing a 75 amino acid mature peptide. The deduced amino acid sequence contains a typical CHH domain. Transcripts of Ers-MIH mRNA were detected in eyestalk by Northern blotting. The production of purified recombinant Ers-MIH (rErs-MIH) expressed in Escherichia coli was 0.3 g/L. The LC-ESI-MS analysis showed that two peptide fragments of the recombinant protein were identical to the deduced amino acid sequence of Ers-MIH. By in vitro assay on E. sinensis YOs, a cGMP mediated suppression of rErs-MIH on ecdysteroidogenesis could be observed. Accumulation of cGMP in YOs showed a concentration-dependent manner within 0.01-1 nmol/mL of rErs-MIH; ecdysteroid secretion was inhibited significantly at the range of 0.01-100 nmol/mL rErs-MIH; furthermore, a significant inhibition effect on ecdysteroid releasing was shown when cGMP analog (8-Br-cGMP) concentration rose up to 100 nmol/mL. This study would facilitate to investigate the roles of MIH in molt cycle regulation. (C) 2011 Elsevier Inc. All rights reserved.
BACKGROUND. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lipid mediators that bind to G-protein-coupled receptors. In this study, signaling responses to 18:1 LPA and S1P were examined in parallel in three human prostate cancer cell lines: PC-3, Du145, and LNCaP. METHODS. Receptor expression was assessed by RT-PCR, Northern blotting, and immunoblotting. Cellular responses to mediators were studied by proliferation assays, phosphoprotein immunoblotting, and phospholipid metabolism assays. RESULTS. All cell lines express mRNA for both LPA and S1P receptors. PC-3 and Du145, but not LNCaP, proliferate in response to LPA and S1P. Epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), LPA, and S1P induce activation of Erks in PC-3 and Du145; only EGF and PMA activate Erks in LNCaP. In Du145 and PC-3, Akt is activated by EGF, LPA, and S1P. Akt is constitutively active in LNCaP; EGF but not LPA or S1P stimulates further phosphorylation. FAK is phosphorylated in response to both LPA and S1P in PC-3 and Du145, but not in LNCaP. LPA and S1P stimulate phospholipase D (PLD) activity to varying extents in the different cell lines. Notably, both lipid mediators activate PLD in LNCaP. In Du145, LPA, but not S1P, activates PLD and enhances cellular production of LPA. CONCLUSIONS. Although both LPA and S1P induce signal transduction in all prostate cancer cell lines studied, a proliferation response is observed only when the Erk, Akt, and FAK pathways are activated. Other responses to the lipid mediators, such as PLD activation, likely contribute to other cellular outcomes. Prostate 69: 1493-1506, 2009. (C) 2009 Wiley-Liss, Inc.
Bacteriorhodopsin is considered an important biomolecule for biochemical and technology-oriented studies. The modeling and functionality of bacteriorhodopsin sensors have been extensively studied, but the studies lack the analysis of the errors present in the measurements. Further, the impacts of these errors on photoelectric measurements are mostly unknown. In this paper, we discuss the errors caused by a transimpedance amplifier in the photocurrent measurements on a dry bacteriorhodopsin sensor. This information is especially useful when evaluating the reliability of photocurrent measurements.
With the rapid developments of computer technology and information technology, human-machine interfaces of aircrafts, ships, nuclear power plants, battlefield command system, and other complex information systems have evolved from the traditional control mode to digital control mode with visual information interface. This paper studies error factors of information interface in human-computer interaction based on visual cognition theory. A feasible error-cognition model is established to solve some design problems which result in serious failures in information recognition and analysis, and even in operation and execution processes. Based on Rasmussen, Norman, Reason and other error types as well as the HERA and CREAM failure identification models, we performed classification and cognitive characterization for error factors according to information search, information recognition, information identification, information selection and judgment as well as the decision-making process and obtained the comprehensive error-cognition model for complex information interface.
Erythema nodosum leprosum (ENL) is a painful inflammatory complication of leprosy occurring in 50% of lepromatous leprosy patients and 5-10% of borderline lepromatous patients. It is a significant cause of economic hardship, morbidity and mortality in leprosy patients. Our understanding of the causes of ENL is limited. We performed a systematic review of the published literature and critically evaluated the evidence for the role of neutrophils, immune complexes (ICs), T-cells, cytokines, and other immunological factors that could contribute to the development of ENL. Searches of the literature were performed in PubMed. Studies, independent of published date, using samples from patients with ENL were included. The search revealed more than 20,000 articles of which 146 eligible studies were included in this systematic review. The studies demonstrate that ENL may be associated with a neutrophilic infiltrate, but it is not clear whether it is an IC-mediated process or that the presence of ICs is an epiphenomenon. Increased levels of tumor necrosis factor-a and other pro-inflammatory cytokines support the role of this cytokine in the inflammatory phase of ENL but not necessarily the initiation. T-cell subsets appear to be important in ENL since multiple studies report an increased CD4(+)/CD8(+) ratio in both skin and peripheral blood of patients with ENL. Microarray data have identified new molecules and whole pathophysiological pathways associated with ENL and provides new insights into the pathogenesis of ENL. Studies of ENL are often difficult to compare due to a lack of case definitions, treatment status, and timing of sampling as well as the use of different laboratory techniques. A standardized approach to some of these issues would be useful. ENL appears to be a complex interaction of various aspects of the immune system. Rigorous clinical descriptions of well-defined cohorts of patients and a systems biology approach using available technologies such as genomics, epigenomics, transcriptomics, and proteomics could yield greater understanding of the condition.
Congenital causes of erythrocytosis are now more easily identified due to the improvement of the molecular characterization of many of them. Among these causes, hemoglobins with high oxygen affinity take a large place. The aim of this work was to reevaluate the diagnostic approach of these disorders. To assess the current practices, we sent a questionnaire to the expert laboratories in the diagnosis of hemoglobinopathies in France and Belgium. In parallel, we gathered the methods used for the diagnosis of the hemoglobins with high oxygen affinity indexed in the international database HbVar. Even though they remain a rare cause of erythrocytosis (1 to 5 positive diagnosis every year in each of the questioned specialized laboratories), hemoglobins with high oxygen affinity are increasingly suspected by clinicians. Phenotypic it enables the finding of 93% of them in the questioned laboratories (28 of the 30 variants diagnosed during the last 5 years). Among the 96 hemoglobin variants with high oxygen affinity indexed in the international database, 87% could be diagnosed with phenotypic techniques. A direct measure of the p50 with the Hemox-Analyzer is included in the diagnostic approach of half of the laboratories only, because of the poor availability of this apparatus. Comparatively, the estimation of p50 by blood gas analyzers on venous blood is a much more convenient and attractive method but due to the lack of proof as to its effectiveness in the diagnosis of hemoglobins with high oxygen affinity, it requires further investigations. Beta- and alphaglobin genes analysis by molecular biology techniques is essential as it either allows a quick and definite identification of the variant or definitely excludes the diagnosis. It is thus systematically performed as a first or second step method, according to the laboratory practice.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r) Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.
Testing for the presence of specific cell-surface receptors (such as EGFR or HER2) on tumor cells is an integral part of cancer care in terms of treatment decisions and prognosis. Understanding the strengths and limitations of these tests is important because inaccurate results may occur if procedures designed to prevent false-negative or false-positive outcomes are not employed. This review discusses tests commonly used to identify and characterize cell-surface receptors, such as the erythropoietin receptor (EpoR). First, a summary is provided on the biology of the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors and precursors in the bone marrow where it mediates red blood cell production in response to Epo. Second, studies are described that investigated whether erythropoiesis-stimulating agents could stimulate tumor progression in cancer patients and whether EpoR is expressed and functional on tumor cells or on endothelial cells. The methods used in these studies included immunohistochemistry, Northern blotting, Western blotting, and binding assays. This review summarizes the strengths and limitations of these methods. Critically analyzing data from tests for cell-surface receptors such as EpoR requires understanding the techniques utilized and demonstrating that results are consistent with current knowledge about receptor biology.
The present study investigated the correlation and significance of HOX transcript antisense RNA (HOTAIR) and epithelial-mesenchymal transition (EMT)-related factors in the occurrence and metastasis of esophageal squamous cell cancer (ESCC) progression. The mRNA and protein expression levels of HOTAIR and EMT-related factors were detected in 96 ESCC and para-carcinoma tissues using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The expression levels of these factors, and the correlation between these factors and clinicopathological characteristics were subsequently analyzed. HOTAIR mRNA expression levels were significantly higher in ESCC compared with in para-carcinoma tissues, and HOTAIR mRNA expression levels were significantly higher in the groups with lymph node involvement or organ metastasis compared with the group without. Furthermore, HOTAIR expression levels demonstrated a significant increasing trend from well-differentiated cancer to poorly differentiated cancer. The mRNA and protein expression levels of zinc finger protein SNAI1 (Snail) and beta-catenin in ESCC were significantly higher compared with para-carcinoma tissues, whereas E-cadherin mRNA and protein expression levels were lower in ESCC tissues compared with in para-carcinoma tissues. Snail mRNA and protein expression levels were also significantly higher in groups with lymph node involvement or organ metastasis compared with those without, and beta-catenin protein expression levels were significantly higher in the groups with lymph node involvement or organ metastasis compared with the group without. In the 96 ESCC tissues, HOTAIR mRNA expression levels were positively correlated with Snail mRNA and protein expression levels, and were negatively correlated with E-cadherin expression levels. HOTAIR mRNA expression levels were also positively correlated with beta-catenin mRNA expression levels. In conclusion, HOTAIR may be involved in carcinogenesis and metastasis, and may induce the expression of EMT-related factors; detection of these factors may assist in early diagnosis and prognostic prediction.
The Escherichia coli sequence type 648 complex (STc648) is an emerging lineage within phylogroup F-formerly included within phylogroup D-that is associated with multidrug resistance. Here, we designed and validated a novel multiplex PCR-based assay for STc648 that took advantage of (i) four distinctive single-nucleotide polymorphisms in icd allele 96 and gyrB allele 87, two of the multilocus sequence typing alleles that define ST648; and (ii) the typical absence within STc648 of uidA, an E. coli-specific gene encoding beta-glucuronidase. Within a diverse 212-strain validation set that included 109 STs other than STc648, from phylogroups A, B1, B2, C, D, E, and F, the assay exhibited 100% sensitivity (95% confidence interval [CI], 82% to 100%) and specificity (95% CI, 98% to 100%). It functioned similarly well in two distant laboratories that used boiled lysates or DNAzol-purified DNA as the template DNA. Thus, this novel multiplex PCR-based assay should enable any laboratory equipped for diagnostic PCR to rapidly, accurately, and economically screen E. coli isolates for membership in STc648.
Escherichia coli is able to utilize d-ribose as its sole carbon source. The genes for the transport and initial-step metabolism of d-ribose form a single rbsDACBK operon. RbsABC forms the ABC-type high-affinity d-ribose transporter, while RbsD and RbsK are involved in the conversion of d-ribose into d-ribose 5-phosphate. In the absence of inducer d-ribose, the ribose operon is repressed by a LacI-type transcription factor RbsR, which is encoded by a gene located downstream of this ribose operon. At present, the rbs operon is believed to be the only target of regulation by RbsR. After Genomic SELEX screening, however, we have identified that RbsR binds not only to the rbs promoter but also to the promoters of a set of genes involved in purine nucleotide metabolism. Northern blotting analysis indicated that RbsR represses the purHD operon for de novo synthesis of purine nucleotide but activates the add and udk genes involved in the salvage pathway of purine nucleotide synthesis. Taken together, we propose that RbsR is a global regulator for switch control between the de novo synthesis of purine nucleotides and its salvage pathway.
OBJECTIVES: Matrix metalloproteinases (MMPs) regulated by ets transcription factors facilitate carcinoma cell invasion. An ets family member, ESE-1, is expressed specifically in epithelial tissues, but its association with MMPs is obscure. In this study, we investigated whether ESE-1 regulates invasion of oral squamous cell carcinoma (SCC) via transcriptional activity of MMP-9. METHODS: HSC-3 and KB were used as human oral SCC lines. The expression of ESE-1 and MMP-9 was detected by in situ hybridization and immunohistochemistry. Invasion assay, gelatin zymography and Northern blotting were used to detect the invasion activity, the gelatinolytic activity and the expression of MMP-9 in the ESE-1 transfectants. Luciferase assays and mutation analysis were used for the transcriptional analysis of MMP-9 promoter region by ESE-1. RESULTS: ESE-1 was expressed in the intermediate layer but not in the invasive area, in which MMP-9 was expressed, in the oral SCC tissues. ESE-1 suppressed invasion activity and 92 kDa gelatinolytic activity in HSC-3 as a result of transfection. ESE-1 regulates MMP-9 expression in a negative manner and the ets binding site on the MMP-9 promoter contributed to suppression by ESE-1. CONCLUSIONS: These findings indicate that ESE-1 negatively regulates the invasion of oral SCC via transcriptional suppression of MMP-9.
Esophageal cancer (EC) is a highly malignant tumor, and the overall survival rate remains very low. Traditional treatment is not sufficiently effective, and thus, there is an urgent need for new and effective treatments. The advances in cancer immunotherapy have changed this situation because this type of therapy has a significant potential to eliminate tumors with little damage to normal tissue. This treatment primarily aims to enhance the ability of the immune system to eliminate tumors and prevent tumor immune escape, which is associated with immune surveillance. This review summarizes current cancer therapeutic strategies and immunotherapy studies to demonstrate the potential of immunotherapy for the treatment of EC.
Radiotherapy is a common therapeutic strategy used to treat esophageal squamous cell carcinoma (ESCC). However, tumor cells often develop radioresistance, thereby reducing treatment efficacy. Here, we aimed to identify the mechanisms through which ESCC cells develop radioresistance and identify associated biomarkers. Eca109 cells were exposed to repeated radiation at 2 Gy/fraction for a total dose of 60 Gy (Eca109R60/2Gy cells). MTT and colony formation assays were performed to measure cell proliferation and compare the radiation biology parameters of Eca109 and Eca109R60/2Gy cells. Cell cycle distributions and apoptosis were assessed by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were employed to analyze the expression of HOX transcript antisense RNA (HOTAIR), in addition to biomarkers of the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Eca109R60/2Gy cells exhibited increased cell proliferation and clone formation, with significantly higher radiobiological parameters compared with the parental Eca109 cells. The Eca109R60/2Gy cells also exhibited significantly decreased accumulation in G(2) phase and increased accumulation in S phase. Additionally, the apoptosis rate was significantly lower in Eca109R60/2Gy cells than in parental Eca109 cells. Finally, HOTAIR expression levels and SNAI1 and beta-catenin mRNA and protein expression levels were significantly higher, whereas E-cadherin levels were significantly lower in Eca109R60/2Gy cells than in Eca109 cells. Therefore, our findings demonstrated that radioresistance was affected by the expression of HOTAIR and biomarkers of the EMT and CSCs.
Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is an important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether serum HOTAIR is involved in the diagnosis of ESCC. Methods: In this study, we detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor resection and 8 without surgery) and 20 healthy volunteers to investigate the role of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction (qRT-PCR) method. Results: Clinical data indicated that serum HOTAIR were correlated with TNM stage. The expression level of serum HOTAIR (0.189 +/- 0.010) was significantly higher in ESCC patients compared with that of healthy controls (0.055 +/- 0.008, P < 0.01). The ROC curve analysis yielded an area under the ROC curve (AUC) value of 0.793 (95% CI: 0. 692 to 0.895, P < 0.01). Also, the serum HOTAIR expression level decreased obviously in postoperative samples (one month after the surgery) compared to preoperative specimens. Moreover, there was a significant correlation between serum HOTAIR expression and the expression of HOTAIR in ESCC tissue according to Pearson correlation analysis. Conclusions: Our study, for the first time, demonstrated that serum HOTAIR might serve as a potential biomarker for the diagnosis of ESCC.
The DNA mismatch repair (MMR) gene MutL homolog 1 (MLH1) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P= 0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR= 1.716; 95% CI= 1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.
The brown planthopper (BPH), Nilaparvata lugens (Stal), is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide resistance leading to frequent control failures in the field. The aim of the present study was to evaluate resistance in the field populations of N. lugens from major rice growing states of South India to various insecticides. We also determined the activity of detoxifying enzymes (esterases [ESTs], glutathione S-transferases [GSTs], and mixed-function oxidases [MFOs]). Moderate levels of resistance were detected in the field populations to acephate, thiamethoxam and buprofezin (resistance factors 1.05-20.92 fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively) as compared with susceptible strain while there were low levels of resistance to imidacloprid (resistance factor 1.23-6.70 fold) and complete sensitivity to etofenoprox (resistance factor 1.05-1.66 fold). EST activities in the field populations were 1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity was found to be correlated to acephate resistance (r = 0.999, P 0.001). The high selection pressure of organophosphate, neonicotinoid, and insect growth regulator (IGR) in the field is likely to be contributing for resistance in BPH to multiple insecticides, leading to control failures. The results obtained will be beneficial to IPM recommendations for the use of effective insecticides against BPH.
This work describes the co-fermentation to the simultaneous production of rhamnolipids and ethanol from exploded sugarcane bagasse (ESB) using Saccharomyces cerevisiae, Pseudomonas aeruginosa and crude enzyme complexes (CECs). The CECs were produced by Aspergillus niger in solid-state fermentation (SSF), using different levels of ESB, rice bran (RB) and corn cob (CC) as substrates. The best results for rhamnolipids (9.1 g/L, emulsification index of 84%, surface tension of 35 mN/m) and ethanol (8.4 g/L) were obtained after 86 h of fermentation of ESB (250 g/L, 30 degrees C), using CEC from SSF of ESB (20% wt/wt), RB (30% wt/wt) and water (50% wt/wt). It was also observed that the fermented bagasse had approximately the same calorific value of a bagasse in nature and could be used as a potential source of energy. These findings suggest that co-fermentation using P. aeruginosa, S. cerevisiae and ESB can be used in the successful co-production of rhamnolipids and ethanol, with the recovery of energy present in the fermented bagasse. (C) 2017 Elsevier Ltd. All rights reserved.
Responsible conduct in learning and research (RCLR) was progressively introduced into the pharmacology curriculum for undergraduate science students at The University of Western Australia. In the second year of this undergraduate curriculum, a lecture introduces students to issues such as the use of animals in teaching and responsible conduct of research. Third year student groups deliver presentations on topics including scientific integrity and the use of human subjects in research. Academic and research staff attending these presentations provide feedback and participate in discussions. Students enrolled in an optional capstone Honours year complete an online course on the responsible conduct of research and participate in an interactive movie. Once RCLR became established in the curriculum, a survey of Likert-scaled and open-ended questions examined student and staff perceptions. Data were expressed as Approval (% of responses represented by Strongly Agree and Agree). RCLR was found to be relevant to the study of pharmacology (69-100% Approval), important for one's future career (62-100% Approval), and stimulated further interest in this area (32-75% Approval). Free entry comments demonstrated the value of RCLR and constructive suggestions for improvement have now been incorporated. RCLR modules were found to be a valuable addition to the pharmacology undergraduate curriculum. This approach may be used to incorporate ethics into any science undergraduate curriculum, with the use of discipline-specific topics. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):53-59, 2017.
Ross Cheit's The Witch-Hunt Narrative raises a number of complex moral issues. Cheit's principal purpose is to challenge the belief that our society has overreacted to claims about the sexual abuse of children. Both directly and indirectly, Cheit's in-depth analysis broaches moral concerns pertaining to the integrity of child abuse allegations, investigations, civil litigation, and criminal prosecution, with an emphasis on the mixed motives of the parties involved in key cases. This article provides an overview of ethical questions pertaining to gathering information from very vulnerable individuals, informed consent, institutional review, protection of research participants, the use of deception and coercion, confidentiality and privacy, reporting research results, and conflicts of interest. In addition, the author discusses the phenomenon of whistle-blowing as it pertains to professionals' ethical judgments about disclosure of wrongdoing and misconduct. The author outlines key ethics-related concepts, applies relevant moral theory, and explores the implications of the moral issues raised by The Witch-Hunt Narrative for child sexual abuse victims, perpetrators, child welfare and law enforcement professionals, scholars and researchers, and the public at large.
Adding ethidium bromide (EtBr) at low concentrations to RNA samples before running formaldehyde-agarose gels affords the advantages of checking RNA integrity and evaluating the quality of size-separation at any time during electrophoresis or immediately after either electrophoresis or blotted the separated RNA onto the membrane without significantly compromising mobility, transfer, or hybridization. In this study, we systematically examined the factors that affect the sensitivity of RNA prestaining by heating RNA samples that include EtBr before electrophoresis under different denaturation conditions. We also examined the efficiency of the hybridization of EtBr-prestained RNA with heterologous DNA probes. The results showed that the fluorescent intensity of EtBr-prestained RNA was affected not only by the EtBr concentration as previously reported but also by the RNA amount, denaturation time, and denaturation temperature. Prior staining of RNA with 40 mu g/mL EtBr significantly decreased the efficiency of Northern blot hybridization with heterologous DNA probes. We propose that to best combine staining sensitivity and the efficiency of Northern blot hybridization with heterologous DNA probes, the concentration of EtBr used to prestain RNA should not exceed 30 mu g/mL. The efficiency of the hybridization of EtBr-prestained RNA was affected not only by factors that affect staining sensitivity but also by the type of probe used.
Little population-based work has been published about the mental health of adolescents with both sexual/gender (SG) and ethnic minority (i.e. double minority) status. This study aimed to provide an overview on their mental health. Analysis of data from a total of 17,607 high school students from New Zealand's 2007 and 2012 cross-sectional nationally representative Adolescent Health Surveys, including a total of 1306 (7.4%) SG minority participants, of whom 581 (3.3%) were also an ethnic minority. SG minority status, minority ethnicity, and female sex were associated with higher mental distress and poorer well-being. Generally speaking, double minority students reported poorer mental health than SG majority students of the same ethnicity, but reported better mental health than SG minority New Zealand European students. Explanations and future directions for research were suggested to further explore how double minority students negotiate mental health in the context of their communities/cultures in New Zealand.
This paper pursues an inquiry into the relationship between ethnicity and development in the largest authoritarian country in the contemporary world, the People's Republic of China. It engages the theoretical literature on ethnic diversity and development in general, but also pays special attention to political economy logics unique to authoritarian systems. Focusing on the western part of China over a decade since the launch of China's Western Development Program (xibu da kaifa) in 2000, this paper utilizes the data from two censuses (2000 and 2010) together with nighttime streetlight imagery data to analyze the overall relationship between ethnicity and development provision. It also analyzes changes in such a relationship during this period. The paper finds that ethnic minority concentration negatively correlates with economic development in both the years 2000 and 2010 across the western provinces. It also finds that counties in non-autonomous provinces, which are historically more integrated with the rest of China than autonomous provinces, have a positive and systematic correlation between changes in ethnic minority concentration and changes in development during the 10-year period. The counties in autonomous provinces, on the other hand, show the opposite trend. Using three case studies of Tibet, Inner Mongolia, and Xinjiang, the paper concludes that although there is in general a tendency for ethnic minority concentrated areas to be less developed, ultimately which groups prosper more or less depends upon specific economic development and which political control logics the Chinese state implements. (C) 2017 The Authors. Published by Elsevier Ltd.
Matrix metalloproteinase (MMP) is closely involved in the degradation of extracellular matrix and confers invasive and metastatic potential to malignant tumors. MMP-2 is a type-IV collagenase secreted as a proenzyme that is activated on the surface of the tumor cell by membrane-type I MMP (MT1-MMP). MT1-MMP plays a critical role during tumor progression and metastasis. We investigated the expression levels of E1AF and MT1-MMP in malignant melanoma cell lines and specimens from patients in order to clarify the mechanisms responsible for the invasion and metastasis of malignant melanoma. High levels of E1AF and MT1-MMP mRNA expression were observed in melanoma cells by Northern blotting and real-time PCR. The expression level was highly correlated with an invasive potential determined by an in vitro invasion assay. The down-regulation of MT1-MMP was identified when E1AF was knocked down by RNA interference. These results suggest that E1AF plays a crucial role in the invasion and metastasis of malignant melanoma through up-regulating the MT1-MMP expression.
The chenopodiaceae Suaeda salsa L. is a leaf succulent euhalophyte. Shoots of the S. salsa are larger and more succulent when grown in highly saline environments. This increased growth and water uptake has been correlated with a large and specific cellular accumulation of sodium. S. salsa does not have salt glands or salt bladders on its leaves. Thus, this plant must compartmentalize the toxic Na+ in the vacuoles. The ability to compartmentalize sodium may result from a stimulation of the proton pumps that provide the driving force for increased sodium transport into the vacuole. In this work, we isolated the cDNA of the vacuolar membrane proton-translocating inorganic pyrophosphatase (H+-PPase) from S. salsa. The SsVP cDNA contains an uninterrupted open reading frame of 2292 bp, coding for a polypeptide of 764 amino acids. Northern blotting analysis showed that SsVP was induced in salinity treated leaves. The activities of both the V-ATPase and the V-PPase in Arabidopsis overexpressing SsVP-2 is higher markedly than in wild-type plant under 200 mM NaCl and drought stresses. The Overexpression of SsVP can increase salt and drought tolerance of transgenic Arabidopsis.
Background: Jackals are medium-sized canids from the wolf-like clade, exhibiting a unique combination of ancestral morphotypes, broad trophic niches, and close phylogenetic relationships with the wolf and dog. Thus, they represent a potential host of several pathogens with diverse transmission routes. Recently, populations of the Eurasian golden jackal Canis aureus have expanded into the Western Palaearctic, including most of Europe. The aim of our study was to examine Eurasian golden jackals from Romania, Czech Republic and Austria for a wide spectrum of vector-borne protists and to evaluate the role of this species as a reservoir of disease for domestic dogs and/or humans. Results: Diagnostic polymerase chain reaction (PCR) DNA amplifications revealed 70% of jackals to be positive for Hepatozoon, 12.5% positive for piroplasms, and one individual positive for Leishmania infantum. Phylogenetic analyses of partial 18S rDNA sequences invariably placed sequenced isolates of Hepatozoon into the H. canis clade. For piroplasms, both the 18S and cox1 sequences obtained confirmed the presence of Babesia canis and "Theileria annae" in 5 and 2 individuals, respectively, providing the first records of these two piroplasmids in Eurasian golden jackals. A single animal from Dolj County (Romania) was PCR-positive for L. infantum, as confirmed also by sequencing of ITS1-5.8S. Conclusions: Apparently, expanding populations of jackals can play a significant role in spreading and maintaining new Babesia canis foci in Central Europe. The role of jackals in the epidemiology of " Theileria annae" and H. canis is probably similar to that of red foxes and should be taken into account in further research on these parasites. Also the presence of L. infantum deserves attention. Our study confirms that once established, the populations of Eurasian golden jackals constitute natural reservoirs for many canine vector-borne diseases, analogous to the role of the coyotes in North America.
This article reviews recent advances in the study of the European Court of Justice (ECJ) and its political impact at the European and member state levels. New quantitative as well as qualitative analyses show with great empirical precision that member state preferences guide the Court. The article summarises these findings, but argues that greater attention needs to be given to the (over-)constitutionalisation of EU law in order to fully capture the political impact of ECJ jurisprudence. Even if European judges are less activist than is often assumed and individual decisions are more restrained in the face of member state opposition, incrementally, case law evolves in a highly expansive fashion. And, exercising caution regarding unrealistic expectations about quasi-deterministic judicial law-making, it is found that the Court's constitutionalised jurisprudence impacts heavily on European and member state policy-making.
Events are temporal "figures", which can be defined as identifiable segments in time, bounded by beginnings and endings. But the functions and importance of these two boundaries differ. We argue that beginnings loom larger than endings by attracting more attention, being judged as more important and interesting, warranting more explanation, and having more causal power. This difference follows from a lay notion that additions (the introduction of something new) imply more change and demand more effort than do subtractions (returning to a previous state of affairs). This "beginning advantage" is demonstrated in eight studies of people's representations of epochs and events on a historical timeline as well as in cyclical change in the annual seasons. People think it is more important to know when wars and reigns started than when they ended, and are more interested in reading about beginnings than endings of historical movements. Transitional events (such as elections and passages from one season to the next) claim more interest and grow in importance when framed as beginnings of what follows than as conclusions of what came before. As beginnings are often identified in retrospect, the beginning advantage may distort and exaggerate their actual historical importance. (C) 2017 Elsevier B.V. All rights reserved.
The conglomerate layer at the upper section of the 4th member of the Shahejie formation(S-4(u)) of the Yongan district at the Donying depression is a well-developed sedimentation of several periods. It lacks stable muddy layers and sophisticated classification of the sedimentation periods and the proportion of sedimentary layering in each period has long been a difficult task for geologists. In addressing this problem, this paper attempts to introduce the theory of climatic cycles driven by astronomical periods from astronomical stratigraphy on the basis of the characteristics of the sedimentation under the turbidity current in the region of study. Through studying the conditions for the formation of the conglomerate layer and the factors of control, we pinpoint the formation of the layer in chronology and differentiate the cycle interface and correlation in the same formation period. Milankovitch analysis is conducted on the sedimentation of the conglomerate layer in the region of study to determine if the stratigraphy cycle of the region is primarily controlled by the eccentricity cycle and calculate MSC1 and MSC2 thicknesses of 189.3 m and 78.05 m, respectively. Milankovitch theory is the primary tool used in the analysis, in conjunction with petrographic analysis. The stratum at the S-4(u) is classified into four IV-grade sequences and 11 V-grade sequences. The information on the dominant cycle frequency is used for wave filtering of the well logs and to determine the significant Milankovitch wave log. With the data from this curve, we may compare the stratigraphy cycle with the characteristics of the standard cycle and classify and compare the sedimentation periods of the conglomerate layers in further detail.
Hostile attribution bias (e.g., tendency to interpret the intention of others as hostile in ambiguous social contexts) has been associated with impulsive aggression in adults, but the results are mixed and the complete sequence of hostile inferential processes leading to aggression has not been investigated yet. The goal of this event-related brain potentials (ERPs) study was to track the neural activity associated with the violation of expectations about hostile versus nonhostile intentions in aggressive and nonaggressive individuals and examine how this neural activity relates to self-reported hostile attributional bias and impulsive aggression in real life. To this end, scenarios with a hostile versus nonhostile social context followed by a character's ambiguous aversive behavior were presented to readers, and ERPs to critical words that specified the hostile versus nonhostile intent behind the behavior were analysed. Thirty-seven aggressive and fifty nonaggressive individuals participated in the study. The presentation of a critical word that violated hostile expectation caused an N400 response that was significantly larger in aggressive than nonaggressive individuals. Results also showed an enhanced late positive potential-like component in aggressive individuals when hostile intention scenarios took place in a nonhostile context, which is associated with impulsive aggression in real life even after having controlled for the effect of self-reported hostile attributional bias. The Hostile Expectancy Violation paradigm evaluated in this study represents a promising tool to investigate the relationship between the online processing of hostile intent in others and impulsive aggression. Aggr. Behav. 43:217-229, 2017. (c) 2016 Wiley Periodicals, Inc.
When we hear an event description, our mental construal is not only based on lexical items, but also on the message's syntactic structure. This has been well-studied in the domains of causation, event participants, and object conceptualization. Less studied are the construals of temporality and numerosity as a function of syntax. We present a theory of how syntax affects the construal of event similarity and duration in a way that is systematically predictable from the interaction of mass/count syntax and verb semantics, and test these predictions in six studies. Punctive events in count syntax (give a kiss) and durative events in mass syntax (give advice) are construed as taking less time than in transitive frame (kiss and advise). Durative verbs in count syntax (give a talk), however, result in a semantic shift, orthogonal to duration estimates. These results demonstrate how syntactic and semantic structure together systematically affect event construal. (C) 2016 The Author(s). Published by Elsevier Inc.
Event-triggered control aims at reducing the resource utilization, especially the communication over the feedback link, while guaranteeing a certain control performance. Although setpoint tracking problems are common in practice, the majority of the proposed approaches in literature focus on regulation problems. Therefore, an event-triggered PI control design strategy with guaranteed performance is proposed in this paper, where both the event-triggering condition and the PI controller are implemented periodically. Based on a quadratic cost function, the PI control design problem is introduced and formulated as an LMI optimization problem. Comparisons with other approaches in the literature are made by simulation and by experimental studies to demonstrate the effectiveness of the proposed strategy.
An effective approach in early intervention for children and families, including child maltreatment prevention, is home-based services. Although several evidence-based programs exist, they are often grouped or delivered together, despite having different foci and approaches. This article describes the development and pilot phases of a trial evaluating the systematic braiding of 2 evidence-based home-based models, SafeCare and Parents as Teachers. We describe the methodology for braiding model implementation and curriculum, specifically focusing on how structured qualitative feedback from pilot families and providers was used to create the braided curriculum and implementation. Systematic braiding of 2 models at the implementation and curriculum levels is a mechanism that has the potential to meet the more comprehensive needs of families at risk for maltreatment.
Despite their differences, human language and the vocal communication of nonhuman primates share many features. Both constitute forms of coordinated activity, rely on many shared neural mechanisms, and involve discrete, combinatorial cognition that includes rich pragmatic inference. These common features suggest that during evolution the ancestors of all modern primates faced similar social problems and responded with similar systems of communication and cognition. When language later evolved from this common foundation, many of its distinctive features were already present.
A complicated, almost conflicting situation exists in contemporary biology, i.e., there are two scientific concepts in existence that solve some phylogenetic problems in a different way. These concepts are evolutionary morphology and molecular biology. Modern biology urgently needs these contradictions to be examined and removed.
This paper presents an efficient approach for the optimal designs of two analog circuits, namely complementary metal oxide semiconductor) two-stage comparator with p-channel metal oxide semiconductor input driver and n-channel input and folded-cascode operational amplifier using a recently proposed meta-heuristic-based optimization algorithm named as colliding bodies optimization (CBO). It is a multi-agent algorithm that does not depend upon any internal control parameter, making the algorithm extremely simple. The main objective of this paper is to optimize the metal oxide semiconductor (MOS) transistors' sizes using CBO in order to reduce the areas occupied by the circuits and to get better performance parameters of the circuits. Simulation Program with Integrated Circuit Emphasis simulation has been carried out by using the optimal values of MOS transistors' sizes and other design parameters to validate that CBO-based design is satisfying the desired specifications. Simulation results demonstrate that the design specifications are closely met and the required functionalities are achieved. The simulation results also confirm that the CBO-based approach is superior to the other algorithms in terms of MOS area and performance parameters like gain, power dissipation, etc., for the examples considered. Copyright (c) 2016 John Wiley & Sons, Ltd.
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.
This paper presents a nonlinear power system stabilizer based on a pointwise min-norm control law and a third order state space mathematical model of the synchronous generator connected through transmission lines to the power system. Commonly, the mathematical model includes transient electromotive force as a state variable that cannot be measured. Therefore, the mathematical model is transformed in a form containing all measurable variables. Furthermore, the control law for the proposed stabilizer also considers voltage regulation. The proposed algorithm has been implemented in a digital control system and its performance experimentally verified on a 83 kVA synchronous generator connected to the power system. Experimental results referring to the change in voltage and mechanical power reference, for disconnection of the transmission line, three phase and two phase short circuit, and forced oscillations are presented and compared to a PSS2A stabilizer. The experimental results show better performance of the excitation system with the proposed stabilizer compared to the system with a conventional PI voltage controller and PSS2A stabilizer. Furthermore, the results show that the proposed stabilizer is robust to system changes in the case of small and large disturbances, as well as near the generator stability limit. (C) 2016 Elsevier B.V. All rights reserved.
A novel, optimized numerical method of modeling of an exciton polariton superfluid in a semiconductor microcavity was proposed. Exciton polaritons are spin-carrying quasiparticles formed from photons strongly coupled to excitons. They possess unique properties, interesting from the point of view of fundamental research as well as numerous potential applications. However, their numerical modeling is challenging due to the structure of nonlinear differential equations describing their evolution. In this paper, we propose to solve the equations with a modified Runge Kutta method of 4th order, further optimized for efficient computations. The algorithms were implemented in form of C++ programs fitted for parallel environments and utilizing vector instructions. The programs form the EPCGP suite which has been used for theoretical investigation of exciton polaritons. Program summary Program title: EPCGP Catalogue identifier: AFBQ_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AFBQ_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: BSD-3 No. of lines in distributed program, including test data, etc.: 2157 No. of bytes in distributed program, including test data, etc.: 498994 Distribution format: tar.gz Programming language: C++ with OpenMP extensions (main numerical program), Python (helper scripts). Computer: Modern PC (tested on AMD and Intel processors), HP BL2x220. Operating system: Unix/Linux and Windows. Has the code been vectorized or parallelized?: Yes (OpenMP) RAM: 200 MB for single run Classification: 7, 7.7. Nature of problem: An exciton polariton superfluid is a novel, interesting physical system allowing investigation of high temperature Bose Einstein condensation of exciton polaritons-quasiparticles carrying spin. They have brought a lot of attention due to their unique properties and potential applications in polariton-based optoelectronic integrated circuits. This is an out-of-equilibrium quantum system confined within a semiconductor microcavity. It is described by a set of nonlinear differential equations similar in spirit to the Gross Pitaevskii (GP) equation, but their unique properties do not allow standard GP solving frameworks to be utilized. Finding an accurate and efficient numerical algorithm as well as development of optimized numerical software is necessary for effective theoretical investigation of exciton-polaritons. Solution method: A Runge Kutta method of 4th order was employed to solve the set of differential equations describing exciton-polariton superfluids. The method was fitted for the exciton polariton equations and further optimized. The C++ programs utilize OpenMP extensions and vector operations in order to fully utilize the computer hardware. Running time: 6h for 100 ps evolution, depending on the values of parameters (C) 2017 Elsevier B.V. All rights reserved.
Objective: Interest continues in neuropsychological measures as cross-disorder intermediate phenotypes in understanding psychopathology. A central question concerns their specificity versus generalizability to particular forms of psychopathology, particularly for executive functioning (EF) and response speed. Three conceptual models examining these relationships were tested to clarify this picture at different levels in the diagnostic hierarchy. Method: Participants (total n = 641, age 18-60) yielded complete structured diagnostic interviews and a neuropsychological test battery comprising measures of executive function, processing speed, and IQ. Repeated measures multivariate analysis of variance, linear regression, and structural equation modeling (SEM) were used to test (a) a specificity model, which proposes that individual disorders are associated with component EF processes and speed; (b) a severity model, which proposes that the total number of comorbid disorders explain poor EF and/or slow speed; and (c) a higher-order dimensional model, which proposes that internalizing versus externalizing disorders are differentially related to EF or speed. Results: EF effects were best explained by a specificity model, with distinct aspects of EF related to attention deficit hyperactivity disorder versus antisocial substance use disorders. Speed, on the other hand, emerged as a general indicator of externalizing psychopathology in the dimensional model, as well as overall severity of psychopathology in the severity model. Conclusions: Granular approaches are likely to be most productive for linking EF to psychopathology, whereas response speed has underused potential as an endophenotype for psychopathology liability. Results are discussed in terms of an integrated conceptualization of neuropsychological processes and putative neural systems involved in general and specific aspects of psychopathology.
The Bangor Gambling Task (BGT, Bowman & Turnbull, 2004) is a simple test of emotion-based decision making, with contingencies varying across five blocks of 20 trials. This is the first study to characterise BGT performance in survivors of traumatic brain injury (TBI) relative to healthy controls. The study also aimed to explore sub-groups (cluster analysis), and identify predictors of task performance (multiple regression). Thirty survivors of TBI and thirty-nine controls completed the BGT and measures of processing speed, pre-morbid IQ, working memory, and executive function. Results showed that survivors of TBI made more gamble choices than controls (total BGT score), although the groups did not significantly differ when using a cut-off score for 'impaired'performance. Unexpectedly, the groups did not significantly differ in their performance across the blocks; however, the cluster analysis revealed three subgroups (with survivors of TBI and controls represented in each cluster). Findings also indicated that only age and group were significant predictors of overall BGT performance. In conclusion, the study findings are consistent with an individual difference account of emotion-based decision making, and a number of issues need to be addressed prior to recommending the clinical use of the BGT.
OBJECTIVE: To provide selectable microRNA for intervening diabetes mellitus diseases, NOD mice's expression of microRNA in pancreas tissues and blood under the exendin-4 intervention of was observed and the difference of microRNA target gene was screened. MATERIALS AND METHODS: Forty clean NOD mice were randomly divided into four groups (in each group, n = 10): One is blank control group D which is intervened with normal saline, and the other three groups were divided into low-dose group A, middle-dose group B, and high-dose group C according to the different exendin- 4 dosage 2, 4, and 8 mu g/kg.d. After the 8-week intervention, these four groups were killed, and the pancreatic tissue and blood were left to prepare specimens for morphology and molecular biology analysis. The specimen with differential expression microRNA in pancreas tissue and blood should be screened out after detected with the locked nucleic acid array system (LNATM) microRNA expression profile chip. The primers should be designed, and the ABI7500 real-time fluorescent quantitative PCR should be applied to amplify, analyze, and verify according to the screen results of the microRNA chip in order to screen out the significant differentially expressed microRNA. RESULTS: Histological detection showed that the pancreas of the mice in control group D was fibrosis gradually and the islet frame was relatively disordered and significantly atrophied. Groups A, B, and C have no islet hypertrophy or atrophy and the degree of fibrosis of the pancreas has reduced. According to the gene chip detection, there are four significantly differently expressed microRNAs in pancreas tissue and blood among the group A, B, and C, among which miR-19a, miR-19b, and miR-22 were down-regulated expressed while the miRNA-1 was upregulated expressed. Bioinformatics analysis showed that the target genes of 4 differentially regulated microRNA genes were related to cell proliferation, apoptosis, glucose metabolism, and angiogenesis. The expression of microRNA in pancreatic tissue and blood of NOD rats was highly consistent. CONCLUSIONS: MicroRNA expression file of pancreatic tissue and blood can be changed during the intervention of the NOD rat model with exendin-4. MicroRNA that indicates the differential expression may take part in the recovering process of the NOD pancreatic trauma. At the same time, the administration of exendin- 4 can protect NOD mice, reduce its pancreatic tissue fibrosis, and regulate molecular markers of pancreatic cells in size and pancreatic mast cells. This may be one of the main mechanisms of pancreatic injury in diabetes prevention.
Exercise immunology research has traditionally focussed on aerobic-exercise, however it has become apparent in more recent years that resistance-exercise can also considerably affect host immunobiology. To date however, no systematic process has been used to establish a dose-response relationship between resistance-exercise and the immune system. The present systematic review was thus conducted to determine the dose-response effects of a bout of resistance-exercise on acute leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature search was conducted in the electronic databases, PubMed, Web of Science, and Google Scholar, over the date range of 1989-2016. Following the PICO elements, eligibility criteria included: i) participants: healthy humans aged 18-40; ii) intervention: a single bout of resistance-exercise; iii) comparator: at least one comparator group; iv) outcome: acute measures of circulating leukocyte counts. Specific exclusion criteria were also applied. Risk of bias and quality of evidence was assessed using the PEDro scale. Due to the individual designs of the admitted studies, a qualitative analysis (systematic narrative synthesis) was employed in the present review. The results of the present review demonstrate that a single bout of resistance-exercise induces an acute monocytosis, neutrophilia, and lymphocytosis. It became apparent that the reviewed literature either does not consistently specify, or does not describe with sufficient detail, the time-course between the onset of exercise and the collection of blood. We recommend that researchers consider addressing this in future studies, and also collect blood measures during exercise to aid with comparison of temporal effects. Regarding the determination of a dose-response relationship, an acute neutrophilia, monocytosis and lymphocytosis appears to occur more rapidly and to a greater magnitude following a single bout of high-dose vs low-dose resistance-exercise. Mechanistically, exercise-induced cell trafficking changes are associated with mechanical, metabolic and endocrine factors. Physical aptitude of the host may also affect resistance-exercise-induced lymphocyte trafficking responses. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Background: Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. Methods: We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness. Subjects performed a brief maximal intensity cycling regimen and a longer less intense cycling regimen at separate visits. Leukocytes were measured by multi-parameter flow cytometry of more than 50 immunophenotypes for each collection sample. Results: We found a differential induction of leukocytosis dependent on exercise intensity and duration. Cytotoxic natural killer cells demonstrated the greatest increase (average of 5.6 fold) immediately post-maximal exercise whereas CD15(+) granulocytes demonstrated the largest increase at 3 h post-maximal exercise (1.6 fold). The longer, less intense endurance exercise resulted in an attenuated leukocytosis. Induction of leukocytosis did not differ in our limited study of active (n = 10) and sedentary (n = 5) subjects to exercise although we found that in baseline samples, sedentary individuals had elevated percentages of CD45RO(+) memory CD4(+) T cells and elevated proportions of CD4(+) T cells expressing the negative immune regulator programmed death-1 (PD-1). Finally, we identified several leukocytes whose presence correlated with obesity related fitness parameters. Conclusions: Our data suggests that leukocytes subsets are differentially mobilized into the peripheral blood and dependent on the intensity and duration of exercise. Pre-existing compositional differences of leukocytes were associated with various fitness parameters.
Purpose: The study aimed to investigate the effects of chronic moderate exercise on regulation of intracellular calcium signaling as an important link to proliferation capacity in murine splenic T lymphocytes. Methods: Male CD1 Swiss mice were randomly assigned either to a control group (CG) or an exercise training group (EG). EG mice performed voluntary exercise for 3 months. Lymphocytes were isolated from murine spleens and intracellular calcium was determined by using Fura-2(AM) and fluorescence spectrometry. The combination of flow cytometry and carboxy-fluorescein succinimidyl ester labeling technique was used for determination of cell proliferation. The expression levels of Ca2+-regulating genes were determined by quantitative polymerase chain reaction (qPCR) analysis. Results: Basal [Ca2+](i) was significantly higher in mice from the EG compared with mice of the CG (P < 0.001, n = 6). Similarly, [Ca2+](i) transients after stimulation with phytohemagglutinin, concanavalin A, and the anti-CD3 antibody induced were significantly increased in mice from the EG (P < 0.05, n = 5). However, no differences were found after stimulation with thapsigargin (P < 0.05, n = 5). CD3+ T cells from EG showed higher mitogen-induced proliferation levels than from CG (P < 0.05/0.01, n = 5). The mRNA expression of cellular Ca2+-regulating genes, such as STIM1, Cav2.3, TRPV4, IP3R2, ORAI1, MCU, TRPM5, and TRPC1, were significantly downregulated (P < 0.05/0.01, n = 5). Conclusion: This study suggests that chronic moderate exercise improves intracellular Ca2+ signaling in murine splenic lymphocytes. The enhanced availability of the second messenger Ca2+ is followed by an improved cellular function such as cell proliferation. The downregulation of Ca2+ homeostasis-related factor expression might be considered as a self-protective mechanism against elevated intracellular Ca2+ signals.
In this paper, a geothermal based multi-generation energy system, including organic Rankine cycle, domestic water heater, absorption refrigeration cycle and proton exchange membrane electrolyzer, is developed to generate electricity, heating, cooling and hydrogen. For this purpose, energetic, exergetic and exergoeconomic analysis are undertaken upon proposed system. Also, the effects of some important variables, i.e. geothermal water temperature, turbine inlet temperature and pressure, generator temperature, geothermal water mass flow rate and electrolyzer current density on the several parameters such as energy and exergy efficiencies of the proposed system, heating and cooling load, net electrical output power, hydrogen production, unit cost of each system products and total unit cost of the products are investigated. For specified conditions, the results show that energy and exergy efficiencies of the proposed multigeneration system are calculated about 34.98% and 49.17%, respectively. The highest and lowest total unit cost of the products estimated approximately 23.18 and 22.73 $/GJ, respectively, by considering that geothermal water temperature increases from 185 degrees C to 215 degrees C. (C) 2017 Published by Elsevier Ltd.
Exergy Life Cycle Assessment (ELCA) is proposed by literature to account for the exergy embodied in products of energy systems. In order to make results of ELCA comparable, supply chains that support the life cycle of the system should be analyzed through a unified model: this is one of the main concerns related to Life Cycle Assessment and Industrial Ecology disciplines. In this paper, Hybrid Input-Output analysis is proposed as the computational structure of ELCA: according to this method, national supply chains are modeled through the Monetary Input Output Tables (MIOTs) of national economies, a constantly updated and freely available data source. Then, the adopted national MIOT is expanded to include the detailed model of the considered energy system, hence defining a Hybrid Input-Output model. The (non-renewable) exergy embodied in electricity production and the Exergy Return on Investment (ExROI) are defined as the appropriate performance indicators based on ELCA. The introduced model is here adopted for the analysis of a Waste-to-Energy (WtE) power plant currently operating in the Italian context. It is found that the primary non-renewable exergy embodied in electricity produced by the analyzed WtE is non-negligible for both the construction (127.1 toe) and the operation phases (11.6 toe/y). Nonetheless, the plant is able to produce a net amount of electricity that pays back such primary non-renewable resources requirements about a hundred times. Finally, the joint application of Exergy Analysis and ELCA lead to improve the overall thermodynamic performances of the WtE system, increasing its exergy efficiency by 1%, and reducing the non-renewable exergy embodied in electricity production by 7938 toe. (C) 2016 Elsevier Ltd. All rights reserved.
Exfoliation syndrome (XFS) is a common age-related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worldwide. Recent developments in XFS genetics, cell biology and epidemiology have greatly improved our understanding of the etiology of this complex inherited disease. This review summarizes current knowledge of XFS pathogenesis, identifies gaps in knowledge, and discusses areas for future research. (C) 2016 Published by Elsevier Ltd.
Exosomes secreted from the cell to the extracellular environment play an important role in intercellular communication. Next-generation sequencing technology, which has achieved great development recently, allows us to detect more complete data and gain even deeper analyses of RNA transcriptomes. In our research, we extracted exosomes from different gastric cancer cell lines and immortalized normal gastric mucosal epithelial cell line and examined the amounts of exosomal proteins and RNAs. Our data showed that the secreted amount of cancer cell-derived exosomes, which contain proteins and RNAs, was much higher than that of normal cell-derived exosomes. Moreover, next-generation sequencing technology confirmed the presence of small non-coding RNAs in exosomes. Based on publicly available databases, we classified small non-coding RNAs. According to the microRNA profiles of exosomes, hsa-miR-21-5p and hsa-miR-30a-5p were two of the most abundant sequences among all libraries. The expression levels of the two microRNAs, miR-100 and miR-148a, in exosomes were validated through reverse transcription polymerase chain reaction. The reverse transcription polymerase chain reaction result, consistent with the trend of sequencing result, indicated a significant difference in exosomes between gastric cancer and gastric mucosal epithelial cell lines. We also predicted novel microRNA candidates but they need to be validated. This research provided an atlas of small noncoding RNA in exosomes and may make a little contribution to the understanding of exosomal RNA composition and finding parts of differential expression of RNAs in exosomes.
BACKGROUNDStereotactic body radiation therapy (SBRT) for localized prostate cancer involves high-dose-per-fraction radiation treatments. Its use is increasing, but concerns remain about treatment-related toxicity. The authors assessed the incidence and predictors of a global decline in health-related quality of life (HRQOL) after prostate SBRT. METHODSFrom 2008 to 2014, 713 consecutive men with localized prostate cancer received treatment with SBRT according to a prospective institutional protocol. Expanded Prostate Cancer Index Composite (EPIC-26) HRQOL data were collected at baseline and longitudinally for 5 years. EPIC-26 is comprised of 5 domains. The primary endpoint was defined as a decline exceeding the clinically detectable threshold in 4 EPIC-26 domains, termed multidomain decline. RESULTSThe median age was 69 years, 46% of patients had unfavorable intermediate-risk or high-risk disease, and 20% received androgen-deprivation therapy. During 1 to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had multidomain declines, respectively. On multivariable analysis, lower baseline bowel HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) and baseline depression (odds ratio, 5.7; 95% confidence interval, 1.3-24.3; P = .02) independently predicted for multidomain decline. Only 3% to 4% of patients had long-term multidomain declines exceeding twice the clinical threshold, and 30% of such declines appeared to be related to prostate cancer treatment or progression of disease. CONCLUSIONSProstate SBRT has minimal long-term impact on multidomain decline, and the majority of more significant multidomain declines appear to be unrelated to treatment. This emphasizes the importance of focusing not only on the side effects of prostate cancer treatment but also on other comorbid illnesses that contribute to overall HRQOL. Cancer 2017;123:1635-1642. (c) 2017 American Cancer Society. In a cohort of over 700 patients with prospective health-related quality-of-life information, prostate stereotactic body radiation therapy has minimal long-term impact on clinically detectable declines in global quality of life. Baseline poor bowel function and clinical depression are associated with an increased rate of multidomain decline.
An alpha-expansin (RiEXPA1) gene was cloned and sequenced from raspberry. Expression of RiEXPA1 in different ripening stages of raspberry fruits has been detected. Northern blotting showed that the level of RiEXPA1 transcript accumulation increased with fruit ripening and the highest level of expression appeared at the later stages of ripening. This indicates that expression of RiEXPA1 is closely correlated with the ripening and softening of raspberry fruits. In order to determine whether expression of the RiEXPA1 was regulated by ethylene, we cloned and sequenced a 1-aminocyclo-propane-1-carboxylic acid synthase cDNA (RiACS1) that encodes the rate-limiting enzyme for ethylene production. Transcript accumulation of RiACS1 was detected at a low level only in the later stage of fruit ripening. This reveals that ethylene is not a regulatory factor of RiEXPA1 expression in raspberry fruit. The results of this investigation suggest that the expression of RiACS1 gene during ripening resembles that of non-climacteric fruits. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
People who are high in victim-sensitivity a personality trait characterized by a strong fear of being exploited by others are more likely to attend to social cues associated with untrustworthiness rather than to cues associated with trustworthiness compared with people who are low in victim-sensitivity. But how do these people react when an initial expectation regarding a target's trustworthiness turns out to be false? Results from two studies show that victim-sensitive compared with victim-insensitive individuals show enhanced source memory and greater change in person perception for negatively labeled targets that violated rather than confirmed negative expectations (the "trustworthy trickster"). These findings are in line with recent theorizing on schema inconsistency and expectancy violation effects in social cognition and with research on the different facets of justice sensitivity in personality psychology.
Distinct explicit and implicit memory processes support weight predictions used when lifting objects and making perceptual judgments about weight, respectively. The first time that an object is encountered weight is predicted on the basis of learned associations, or priors, linking size and material to weight. A fundamental question is whether the brain maintains a single, global representation of priors, or multiple representations that can be updated in a context specific way. A second key question is whether the updating of priors, or the ability to scale lifting forces when repeatedly lifting unusually weighted objects requires focused attention. To investigate these questions we compared the adaptability of weight predictions used when lifting objects and judging their weights in different groups of participants who experienced size-weight inverted objects passively (with the objects placed on the hands) or actively (where participants lift the objects) under full or divided attention. To assess weight judgments we measured the size-weight illusion after every 20 trials of experience with the inverted objects both passively and actively. The attenuation of the illusion that arises when lifting inverted object was found to be context-specific such that the attenuation was larger when the mode of interaction with the inverted objects matched the method of assessment of the illusion. Dividing attention during interaction with the inverted objects had no effect on attenuation of the illusion, but did slow the rate at which lifting forces were scaled to the weight inverted objects. These findings suggest that the brain stores multiple representations of priors that are context specific, and that focused attention is important for scaling lifting forces, but not for updating weight predictions used when judging object weight. (C) 2017 Elsevier B.V. All rights reserved.
In applications involving digital control, the set of admissible control actions is finite/quantized. Coupled with state constraints and fast dynamics, explicit model predictive control (EMPC) provides an attractive control formalism. However, the design of data-driven EMPCs with finite admissible control sets is a challenging and relatively unexplored problem. In this paper, a systematic data-driven method is proposed for the design of quantized EMPCs (Q-EMPCs) for time-varying output tracking in nonlinear systems. The design involves: 1) sampling the admissible state space using low-discrepancy sequences to provide scalability to higher dimensional nonlinear systems; 2) at each sampled data point, solving for optimal quantized model predictive control actions and determining feasibility of the intrinsic mixed-integer nonlinear programming problem; and 3) constructing the Q-EMPC control surface using multiclass support vector machines (MC-SVMs). In particular, four widely used MC-SVM algorithms are employed to construct the proposed data-driven Q-EMPC. Extensive testing and comparison among the different MC-SVM algorithms is performed on 2-D and 5-D benchmark examples to demonstrate the effectiveness and scalability of the proposed methodology.
Background: The concept of well-being is multi-faceted by encompassing both positive and negative emotions and satisfaction with life. Measuring both positive and negative thoughts and emotions is highly relevant in maternity care that aims to optimise a woman's experience of pregnancy and childbirth, focussing on positive aspects of health and well-being, not just the prevention of ill health. Yet our understanding of well-being in pregnancy and childbirth is limited as research to date has focussed on negative aspects such as stress, anxiety or depression. The primary aim of this study is to describe the psychometric properties of a newly developed Well-being in Pregnancy (WiP) questionnaire.Methods: A cohort study of 318 women attending hospital antenatal clinics in Belfast completed a questionnaire including three general well-being measures (not pregnancy specific) and the newly developed WiP questionnaire. The psychometric properties of the questionnaire were analysed using correlations to explore the relationship between the WiP questionnaire with the generic well-being measures administered at the same time and exploratory factor analysis was conducted.Results: The overall Cronbach's alpha of the WiP was 0.73. Principal factor analysis was run on the WiP items and two factors were identified, one reflecting positive affect and satisfaction (Cronbach's alpha=0.718) and the other concerns (Cronbach's alpha=0.702). Both the overall WiP score and WiP sub-scale scores displayed significant correlations with the other well-being scales (r=0.235-0.527).Conclusions: Measuring well-being in pregnancy is an important step in understanding the potential physical, psychological and social benefits of pregnancy and in understanding how well-being can be enhanced for women and their families at this important life stage. The initial psychometric data presented for the WiP questionnaire are encouraging. Most importantly, the measure provides an opportunity for women to express positive and negative emotions and thoughts about their pregnancy thus reflecting the whole spectrum of well-being.
In screening for potent antimicrobial proteins (AMPs) from plant seeds, we had purified a heat-stable AMP, LJAMP2, from the seeds of a medicine herb, motherwort (Leonurus japonicus Houtt). In an in vitro assay, the protein can inhibit the growth of both fungi and bacteria. Then a cDNA encoding LJAMP2 was cloned by the rapid amplification of cDNA ends based on the N-terminal amino acid sequence determined. The deduced amino acid sequences of this cDNA show similarity to plant non-specific lipid transfer proteins. Northern blotting assay revealed that this nsLTP-like gene, designated LJAMP2, was expressed in seeds. Overexpression of LJAMP2 in tobacco enhanced resistance to the fungal pathogen Alternaria alternata and the bacterial pathogen Ralstonia solanacearum, significantly, while no visible alteration in plant growth and development. Our data confirm the antifungal and antibacterial function of LJAMP2 from motherwort seeds and suggest the potential of LJAMP2 in improving disease resistance in plants.
In mammals, 10 isoforms of fatty acid-binding protein (FABP) are expressed in various tissues. To understand the role of multiple FABP isoforms, we have quantitatively examined the transcript levels of individual FABP isoforms in each of various tissues by Northern blotting using synthesized RNAs corresponding to the mRNA of each isoform as external standards. As a result, absolute transcript levels of individual FABP isoforms expressed in each tissue were successfully determined. The 10 FABP isoforms were classified into three categories: (1) isoforms FABP7 and 12 were not markedly expressed in any tissue examined; (2) isoforms showing certain transcript levels in multiple tissues; and (3) isoforms FABP6, 8, and 9, expressed at certain levels in one particular tissue. Based on the expression profiles of the isoforms, individual tissues were also classified into three groups: (1) tissues in which high-level expression of FABP isoforms was not observed, (2) tissues in which multiple FABP isoforms were expressed at certain levels, and (3) tissues in which a single FABP isoform was dominantly expressed at a certain level. These results give a better understanding of the meaning of the presence of multiple FABP isoforms in mammals.
Superoxide dismutases (SODs) constitute the first line of cellular defense against oxidative stress in plants. SODs generally occur in three different forms with Cu/Zn, Fe, or Mn as prosthetic metals. We cloned the full-length cDNA of the Thellungiella halophila Cu/Zn-SOD gene ThCSD using degenerate RT-PCR and rapid amplification of cDNA ends (RACE). Sequence analysis indicated that the ThCSD gene (GenBank accession number EF405867) had an open reading frame of 456 bp. The deduced 152-amino acid polypeptide had a predicted molecular weight of 15.1 kDa, an estimated pI of 5.4, and a putative Cu/Zn-binding site. Recombinant ThCSD protein was expressed in Escherichia coli and assayed for SOD enzymatic activity in a native polyacrylamide gel. The SOD activity of ThCSD was inactivated by potassium cyanide and hydrogen peroxide but not by sodium azide, confirming that ThCSD is a Cu/Zn-SOD. Northern blotting demonstrated that ThCSD is expressed in roots, stems, and leaves. ThCSD mRNA levels increased by about 30-fold when plants were treated with sodium chloride (NaCl), abscisic acid (ABA), and indole-acetic acid (IAA) and by about 50-fold when treated with UVB light. These results indicate that ThCSD is involved in physiological pathways activated by a variety of environmental conditions.
The melanocortin 1 receptor (MCIR) gene is a candidate functional gene that controls the pigment production in melanocytes. The aim of this study was to identify polymorphisms and investigate the effect of the MCIR gene on plumage coloration in duck breeds, including Korean native ducks. Initially, 34 individuals from seven duck breeds were sequenced, obtaining 12 polymorphisms. Five single nucleotide polymorphisms (SNPs) in the coding region were non-synonymous, with mutations corresponding to amino acid changes. Among these, four SNPs were geno-typed using polymerase chain reaction-restriction fragment length polymorphism method in 264 individuals from same seven duck breeds. Fisher's exact test was conducted to identify possible relationships between the MCIR gene polymorphisms and plumage color variations. Four non-synonymous SNPs, c.52A>G (p.Lys18Glu), and c.376 A>G (p.Ile126Val), c.409G>A (p.Ala137Thr) and c.649C>T (p.Arg217Cys), were associated with the two deduced genotypes (i.e., E/E and e+ /e+) based on plumage color phenotypes. In addition, we reconstructed MCIR gene haplotypes, where the haplotype AAGC showed its highest frequency in Nageswari duck breed, which presents an extended black phenotype. Our results indicate that the identified polymorphisms by this study can be used to explore associations with plumage color variations in Asian duck breeds.
Background: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are resistant to several types of antibiotics excluding carbapenems. A transmissibility of ESBL-producing Enterobacteriaceae would be depending on each bacterial property, however, that has not been elucidated in clinical setting. In this study, we attempted to identify the source of an outbreak of ESBL-producing bacteria in a medical oncology and immunology care unit. Methods: An ESBL-producing Enterobacteriaceae (ESBL-E) outbreak observed between July 2012 and August 2012 in Kagawa University Hospital was surveyed using various molecular microbiology techniques. We used Pulsed-field gel electrophoresis (PFGE), PCR-based ESBL gene typing, and direct sequence of ESBL gene as molecular microbiology typing method to distinguish each strain. Results: The typical prevalence of ESBL-E isolation in the unit was 7.0 per month (1.7 per week). The prevalence of ESBL-E isolation during the target research period was 20.0 per month (5.0 per week). In total, 19 isolates (11 K. pneumoniae and 8 E. coli) were obtained from clinical samples, including four control strains (two each of both bacteria), that were physically different from those obtained from other inpatient units in our hospital. Pulsed-field gel electrophoresis (PFGE) for K. pneumoniae (digested by XbaI) produced similar patterns excluding one control strain. PCR classification of the ESBL gene for K. pneumoniae revealed that all strains other than the control strain carried SHV and CTX-M-9. This result was reconfirmed by direct DNA sequencing. Although the outbreak of K. pneumoniae was considered to be "clonal," PFGE and PCR classification of the ESBL genes for E. coli uncovered at least six different "non-clonal" strains possessing individual ESBL gene patterns. According to the result of an antibiogram, the pattern of antimicrobial susceptibility was more variable for K. pneumoniae than for E. coli. Conclusions: Typing by PFGE and ESBL gene PCR analysis is practical for discriminating various organisms. In our cohort, two outbreaks were concomitantly spread with different transmission strategies, namely clonal and non-clonal, in the same unit. This might represent clinical evidence that transmissibility differs according to the type of strain. We speculated that patient-to-patient transmission of ESBL-E occurred according to the properties of each individual strain.
Despite a substantial body of research examining the relationship between child maltreatment and externalizing, antisocial, and criminal behavior problems, theory is rarely applied in the current empirical research literature. The lack of theoretical application limits opportunities to understand the mechanisms explaining why maltreatment is associated with behavior problems, and the best strategies for intervening to interrupt this association. The purpose of this paper is to analyze relevant theoretical perspectives and develop a conceptual model explaining the relationship between maltreatment and behavior problems, and the intervening role of child welfare services. Six theoretical perspectives were selected for analysis: the ecological model, the transactional model, attachment theory, the life course perspective, the social learning perspective, and social-biological models. After applying these theories to understanding the maltreatment-behavior problem association and the role of child welfare services in intervening, insights from these theories were synthesized into a conceptual model. The policy and practice implications of this model are discussed, with a focus on the implications for child welfare workers, administrators, and policymakers. (C) 2016 Elsevier Ltd. All rights reserved.
ADAMTS-like 2 (ADAMTSL2), is a secreted protein resembling the ancillary domains of the ADAMTS proteases, but with distinct structural features. It has 7 thrombospondin type-1 repeats (TSRs), but an unusually long spacer module, which in both humans and mice, contains a novel insertion bearing six N-glycosylation sites. The ADAMTSL2 protein expressed in HEK293F and COS-I cells, is a cell-surface and extracellular matrix binding glycoprotein, with N-linked carbohydrate constituting similar to 20% by mass. The 4.0 kb Adamtsl2 mRNA is found most abundantly in adult mouse liver, lung and spleen by northern blotting. During mouse embryogenesis, Adamtsl2 was expressed most strongly in the third week of gestation. Adamtsl2 mRNA was detected by in situ hybridization in developing skeletal muscle, liver, bronchial and arterial smooth muscle, skin, intervertebral disc, perichondrium, pancreas and spinal cord. Immunohistochemical localization of ADAMTSL2 protein was similar to mRNA expression. Detection of Adamtsl2 mRNA and protein in developing skeletal myotubes, but not undifferentiated myogenic precursors led us to investigate its regulation during in vitro myogenic differentiation. In C2C12 and 23A2 myogenic cells, but not in 23A2 cells rendered non-myogenic by expression of G12V:H-Ras (9A2 cells), differentiation induced by serum starvation triggered expression of Adamtsl2 mRNA, coordinately with Myog, a marker of muscle differentiation. Furthermore, activation of the key myogenic determinant MyoD in 10T1/2 fibroblasts also triggered expression of Adamtsl2 mRNA. Collectively, the data suggest that induction of Adamtsl2 mRNA is an integral feature of myogenesis. (c) 2007 Elsevier B.V./International Society of Matrix Biology. All rights reserved.
The detection of exogenous plant microRNAs in human/animal plasma/sera lies at the foundation of exploring their cross-kingdom regulatory functions. It is necessary to establish a standard operation procedure to promote study in this nascent field. In this study, 18 plant miRNAs were assessed in watermelon juice and mixed fruits by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). C-T values, no-template controls and standard curves for each miRNA were used to evaluate the specificity and sensitivity of qRT-PCR and to obtain concentrations. Sixteen miRNAs were selected and measured in human plasma from volunteers after drinking juice. The CT values of 6 plant miRNAs in human plasma fell outside the linear ranges of their standard curves. The remaining 10 miRNAs were present at high basal levels, and 6 of them showed a dynamic physiological pattern in plasma (absorption rates of 0.04% to 1.31%). Northern blotting was used to confirm the qRT-PCR results. Critical issues such as RNA extraction and internal controls were also addressed. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate melanoma-derived extracellular vesicles (EVs) as potential mediators of the premetastatic niche through cargo-specific polarization of DCs. DCs matured in vitro in the presence of melanoma EVs demonstrated significantly impaired expression of CD83 and CD86 as well as decreased expression of Th1 polarizing chemokines FIt3L and IL15 and migration chemokines MIP-l alpha and MIP-1 beta compared to liposome-treated DCs. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo, which in vitro compromised DC maturation similar to melanoma EVs. Early evidence demonstrates that similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by which DC maturation is compromised warranting further study to consider this as a potential mechanism enabled by the primary tumor to establish the premetastatic niche in tumor-draining SLNs of patients.
Extracellular vesicles (EVs), including exosomes, play a key role in inter and intracellular communication, promoting the proliferation and invasion of recipient cells to support tumor growth and metastasis. Metastasis comprises multiple steps that first include the detachment of tumor cells through epithelial to mesenchymal transition (EMT), allowing the physical dissemination to distant organs. Thereafter, cancer-derived exosomes are still critical components for preparing the tumor microenvironment by (i) enabling tumor cells to escape from the immunological surveillance and (ii) arranging the pre-metastatic site for the engraftment of detached cancer cells. In this review, we discuss the multifaceted role of EVs in the multiple steps of metastasis. Future research directions draw attention to EVs as biological targets for cancer diagnosis, prognosis and therapy. However, due to their significant role in cell communication, they may become a valuable drug delivery system.
Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated soft tissue sarcoma with a high propensity for metastases. Using a clinical sequencing approach, we genomically profiled patients with metastatic EMC to elucidate the molecular biology and identify potentially actionable mutations. We also evaluated potential predictive factors of benefit to sunitinib, a multi-targeted tyrosine kinase inhibitor with reported activity in a subset of EMC patients. Between January 31, 2012 and April 15, 2016, six patients with EMC participated in the clinical sequencing research study. High quality DNA and RNA was isolated and matched normal samples underwent comprehensive next generation sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and capture transcriptome). The expression levels of sunitinib targeted-kinases were measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4. The previously reported EWSR1-NR4A3 translocation was identified in all patient tumors; however, other recurring genomic abnormalities were not detected. RET expression was significantly greater in patients with EMC relative to other types of sarcomas except for liposarcoma (p<0.0002). The folate receptor was overexpressed in two patients. Our study demonstrated that similar to other translocation-associated sarcomas, the mutational profile of metastatic EMC is limited beyond the pathognomonic translocation. The clinical significance of RET expression in EMC should be explored. Additional pre-clinical investigations of EMC may help elucidate molecular mechanisms contributing to EMC tumorigenesis that could be translated to the clinical setting.
Traditional cognitive assessment in neurological conditions involving physical disability is often prevented by the presence of verbal-motor impairment; to date, an extensive motor-verbal-free neuropsychological battery is not available for such purposes. We adapted a set of neuropsychological tests, assessing language, attentional abilities, executive functions and social cognition, for eye-tracking (ET) control, and explored its feasibility in a sample of healthy participants. Thirty healthy subjects performed a neuropsychological assessment, using an ET-based neuropsychological battery, together with standard "paper and pencil" cognitive measures for frontal (Frontal Assessment Battery-FAB) and working memory abilities (Digit Sequencing Task) and for global cognitive efficiency (Montreal Cognitive Assessment-MoCA). Psychological measures of anxiety (State-Trait Anxiety Inventory-Y-STAI-Y) and depression (Beck Depression Inventory-BDI) were also collected, and a usability questionnaire was administered. Significant correlations were observed between the "paper and pencil" screening of working memory abilities and the ET-based neuropsychological measures. The ET-based battery also correlated with the MoCA, while poor correlations were observed with the FAB. Usability aspects were found to be influenced by both working memory abilities and psychological components. The ET-based neuropsychological battery developed could provide an extensive assessment of cognitive functions, allowing participants to perform tasks independently from the integrity of motor or verbal channels. Further studies will be aimed at investigating validity and usability components in neurological populations with motor-verbal impairments.
Background: STAT3 signaling plays the pivotal role in tumorigenesis through EZH2 epigenetic modification, which enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. Here, another possible feedback mechanism and clinical significance of EZH2 and STAT3 were investigated in gastric cancer (GC). Methods: STAT3, p-STAT3 (Tyr 705) and EZH2 expression were examined in 63 GC specimens with matched normal tissues by IHC staining. EZH2 and STAT3 were also identified in five GC cell lines using RT-PCR and western blot analyses. p-STAT3 protein was detected by western blotting. In order to investigate whether EZH2 expression was directly regulated by STAT3, EZH2 expression was further detected using siRNA for STAT3 or IL-6 stimulation, with dual luciferase reporter analyses, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. The clinical significance of STAT3, p-STAT3 and EZH2 expression was evaluated by multi-factor COX regression and Kaplan-Meier analyses. Results: Hyper-activation of STAT3, p-STAT3 and EZH2 expression were observed in GC cells and tissues. STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 similar to-206). STAT3 was an independent signature for poor survival (P = 0.002). Patients with STAT3(+)/EZH2(+) or p-STAT3(+)/EZH2(+) had a worse outcome than others (P < 0.001); Besides, high levels of STAT3 and EZH2 was associated with advanced TNM staging (P = 0.017). Moreover, treatment with a combination of siSTAT3 and EZH2-specific inhibitor, 3-deazaneplanocin A (DZNEP), increased the apoptotic ratio of cells. It is benefit for targeting STAT3-EZH2 interplay in GC treatment. Conclusions: Our results indicate that STAT3 status mediated EZH2 upregulation, associated with advanced TNM stage and poor prognosis, suggesting that combination with knockdown of STAT3 and EZH2 inhibitor might be a novel therapy in GC treatment. Collectively, STAT3, p-STAT3 and EZH2 expression were provided for the precision medicine in GC patients.
The 1994 structure of a transition-state analogue with AlF4- and GDP complexed to G1 alpha, a small G protein, heralded a new field of research into the structure and mechanism of enzymes that manipulate the transfer of phosphoryl (PO3-) groups. The number of enzyme structures in the PDB containing metal fluorides (MFx) as ligands that imitate either a phosphoryl or a phosphate group was 357 at the end of 2016. They fall into three distinct geometrical classes: 1) Tetrahedral complexes based on BeF3- that mimic ground-state phosphates; 2) octahedral complexes, primarily based on AlF4-, which mimic "in-line" anionic transition states for phosphoryl transfer; and 3) trigonal bipyramidal complexes, represented by MgF3- and putative AlF30 moieties, which mimic the geometry of the transition state. The interpretation of these structures provides a deeper mechanistic understanding into the behavior and manipulation of phosphate monoesters in molecular biology. This Review provides a comprehensive overview of these structures, their uses, and their computational development.
A cDNA clone encoding an amphioxus fatty acid binding protein-like (AmphiFABPL) protein was isolated from a gut cDNA library of Branchiostoma belcheri. It contained a 423 bp open reading frame corresponding to a deduced protein of 140 amino acids with a predicted molecular mass of approximately 15.9 kDa. Phylogenetic analysis showed that AmphiFABPL fell outside the vertebrate clade of fatty acid binding proteins (FABPs), being positioned at the base of the chordate lineage, and was almost equally homologous to various vertebrate FABPs, suggesting that it may be the archetype of vertebrate FABPs. Both northern blotting and in situ hybridization analyses demonstrated that AmphiFABPL was expressed in the hepatic caecum and hind-gut, and although at a much lower level, it was also present in the endostyle, ovary and testis. In addition, whole-mount in situ hybridization revealed that AmphiFABPL was initially expressed in the posterior two thirds of the primitive gut, including the mid-gut where the hepatic caecum will form later, in 2-day larvae. The expression pattern is closely similar to that of the L-FABP and I-FABP genes in vertebrates, supporting the hypothesis that the hepatic caecum in the amphioxus is homologous to the vertebrate liver.
The confounded signal hypothesis maintains that facial expressions of anger and happiness, in order to more efficiently communicate threat or nurturance, evolved forms that take advantage of older gender recognition systems, which were already attuned to similar affordances. Two unexplored consequences of this hypothesis are (1) facial gender should automatically interfere with discriminations of anger and happiness, and (2) controlled attentional processes (like working memory) may be able to override the interference of these particular expressions on gender discrimination. These issues were explored by administering a Garner interference task along with a working memory task as an index of controlled attention. Results show that those with good attentional control were able to eliminate interference of expression on gender decisions but not the interference of gender on expression decisions. Trials in which the stimulus attributes were systematically correlated also revealed strategic facilitation for participants high in attentional control.
Individuals with moderate to severe traumatic brain injury (TBI) have been shown to experience significant problems in facial affect recognition (FAR). However, it is not known how these impairments relate to overall functioning and quality of life (QoL) following TBI. The aim of the current study was to test the hypothesis that worse performance on an FAR task would be associated with reduced QoL (related to social and emotional functioning), worse mood, and increased fatigue. Forty-seven individuals with TBI and 27 healthy controls (HCs) completed the facial emotion identification task (FEIT), as well as questionnaires assessing social and emotional QoL, mood, and fatigue. The TBI group performed significantly worse than HCs on the FEIT. A significant relationship between FAR and fatigue and QoL related to social and emotional functioning was documented, but in an unexpected direction: individuals who performed better on the FEIT reported poorer QoL and greater fatigue. Individuals who have better FAR may require increased effort to perform this task, and thus experience greater fatigue and poorer social and emotional QoL.
Schizophrenia patients have impaired performance and abnormal brain activation during facial emotion recognition, which may represent a marker of genetic liability to schizophrenia. However, it remains unclear whether the impairment is specific to recognizing emotion from faces or is instead attributable to more generalized dysfunction. The current study aimed to distinguish between specific and generalized neural dysfunction underlying impaired facial emotion recognition in schizophrenia and examine associations with genetic liability. Twenty-eight schizophrenia patients, 27 nonpsychotic first-degree relatives, and 27 community controls underwent functional magnetic resonance imaging while making judgments about either the emotion or age of emotional faces. Patients had performance deficits during the emotion and age discrimination conditions compared to relatives and controls, while relatives had intact performance. Patients had hypoactivation compared to controls across conditions, mainly in medial prefrontal cortex. Unlike controls, patients demonstrated a failure to recruit the dorsomedial prefrontal cortex, a region involved in social cognition and decision-making, and relatives had a pattern of recruitment intermediate between patients and controls. Compared to controls, relatives had greater deactivation of regions associated with the default mode network, and patients had similar findings during age discrimination. The common patterns of performance deficits and activation abnormalities during emotion and age discrimination in schizophrenia suggest that generalized cognitive impairment, notably in social cognition and decision-making, contributes to impaired facial emotion recognition. Similar functional activation patterns in relatives, despite intact performance, suggest that brain activation may represent a more sensitive marker of genetic liability than behaviour. Hyperdeactivation of default mode network regions in relatives may represent cognitive inefficiency, or compensatory mechanisms that help maintain intact performance.
Human adults automatically mimic others' emotional expressions, which is believed to contribute to sharing emotions with others. Although this behaviour appears fundamental to social reciprocity, little is known about its developmental process. Therefore, we examined whether infants show automatic facial mimicry in response to others' emotional expressions. Facial electromyographic activity over the corrugator supercilii (brow) and zygomaticus major (cheek) of four-to five-month-old infants was measured while they viewed dynamic clips presenting audiovisual, visual and auditory emotions. The audiovisual bimodal emotion stimuli were a display of a laughing/crying facial expression with an emotionally congruent vocalization, whereas the visual/auditory unimodal emotion stimuli displayed those emotional faces/vocalizations paired with a neutral vocalization/face, respectively. Increased activation of the corrugator supercilii muscle in response to audiovisual cries and the zygomaticus major in response to audiovisual laughter were observed between 500 and 1000 ms after stimulus onset, which clearly suggests rapid facial mimicry. By contrast, both visual and auditory unimodal emotion stimuli did not activate the infants' corresponding muscles. These results revealed that automatic facial mimicry is present as early as five months of age, when multimodal emotional information is present.
Globally, coastal waters have emerged into a pool of antibiotic resistance genes and multiple antibiotic resistant microorganisms, and pathogenicity of these resistant microorganisms in terms of serotypes and virulence genes has made the environment vulnerable. The current study underscores the presence of multiple antibiotic resistant pathogenic serotypes and pathotypes of Escherichia coli, the predominant faecal indicator bacteria (FIB), in surface water and sediment samples of famous recreational beaches (Juhu, Versova, Mahim, Dadar, and Girgaon) of Mumbai. Out of 65 faecal coliforms (FC) randomly selected, 38 isolates were biochemically characterized, serotyped (for 'O' antigen), antibiogram-phenotyped (for 22 antimicrobial agents), and genotyped by polymerase chain reaction (for virulence factors). These isolates belonged to 16 different serotypes (UT, O141, O2, O119, O120, O9, O35, O126, O91, O128, O87, O86, R, O101, O118, and O15) out of which UT (18.4%), O141 (15.7%), and O2 (13.1%) were predominant, indicating its remarkable diversity. Furthermore, the generated antibiogram profile revealed that 95% of these isolates were multiple antibiotic resistant. More than 60% of aminoglycoside-sensitive E. coli isolates exhibited resistance to penicillin, extended penicillin, quinolone, and cephalosporin classes of antibiotic while resistance to other antibiotics was comparatively less. Antibiotic resistance (AR) indexing indicated that these isolates may have rooted from a high-risk source of contamination. Preliminary findings revealed the presence of enterotoxin-encoding genes (stx1 and stx2 specific for enterohaemorrhagic E. coli and Shiga toxin-producing E. coli, heat-stable toxin enterotoxin specific for enterotoxigenic E. coli) in pathogenic serotypes. Thus, government authorities and environmental planners should create public awareness and adopt effective measures for coastal management to prevent serious health risks associated with these contaminated coastal waters.
A type III polyketide synthase (PKS) cDNA and the corresponding gene (FmPKS) were isolated from the rhizomes of Fallopia multiflora (Thunb.) (Polygonaceae). The full-length FmPKS cDNA was 1,228 bp, containing an open reading frame of 1,137 bp encoding a 378 amino acid residues long protein. The coding sequence of the gene was interrupted by three introns, a different gene structure from most of the type III PKS genes studied so far containing only one intron at a conserved site, except for the recently cloned gene PcPKS2 from Polygonum cuspidatum. Phylogenetic analysis revealed that it shares a close relationship with Rheum tataricum stilbene synthase and formes a group with functionally diverse chalcone synthase-like enzymes. Southern blotting showed that there are three to four copies of the FmPKS gene in the genome. The expression pattern of the FmPKS transcript was determined by Northern blotting and high expression levels were detected in rhizomes and old stems, while the lowest levels were found in old leaves, a pattern that strongly correlates with the accumulation of the major bioactive principles called 2,3,5,4'-tetra-hydroxy-stilbene-2-O-beta-D-glucoside, suggesting that FmPKS might play an important role in its biosynthesis.
Achieving false belief understanding is an important cognitive milestone that allows children to understand that thoughts and reality can differ. Researchers have found that low-income children score significantly lower than middle-income children on false belief understanding but have not examined why this difference exists. We hypothesized that children's language and parent discipline mediate the income-false belief relation. Participants were 174 3- to 6-year-olds. False belief understanding was significantly correlated with family income, children's vocabulary, parents' self reported discussion of children's behavior, discussion of emotions, and power assertion. Family income had a significant indirect effect on false belief understanding through children's vocabulary and parent discipline when examined independently, but only through children's vocabulary when using parallel multiple mediation. This study contributes to our knowledge of individual differences in false belief understanding. (C) 2017 Elsevier Inc. All rights reserved.
Recent studies suggest that by the second year of life, infants can attribute false beliefs to agents. However, prior studies have largely focused on infants' ability to predict a mistaken agent's physical actions on objects. The present research investigated whether 20-month-old infants could also reason about belief-based emotional displays. In Experiments 1 and 2, infants viewed an agent who shook two objects: one rattled and the other was silent. Infants expected the agent to express surprise at the silent object if she had a false belief that both objects rattled, but not if she was merely ignorant about the objects' properties. Experiment 3 replicated and extended these findings: if an agent falsely believed that two containers held toy bears (when only one did so), infants expected the agent to express surprise at the empty, but not the full, container. Together, these results provide the first evidence that infants in the second year of life understand the causal relationship between beliefs and emotional displays. These findings thus provide new evidence for false-belief understanding in infancy and suggest that infants, like older children, possess a robust understanding of belief that applies to a broad range of belief-based responses. (C) 2016 Elsevier B.V. All rights reserved.
Familial adenomatous polyposis (FAP; Mendelian of Inherintance in Man ID, 175100) is a rare autosomal dominant disorder characterized by the development of numerous adenomatous polyps throughout the colon and rectum associated with an increased risk of colorectal cancer. FAP is at time accompanied with certain extraintestinal manifestations such as congenital hypertrophy of the retinal pigment epithelium, dental disorders and desmoid tumors. It is caused by mutations in the adenomatous polyposis coli (APC) gene. The present study reported on a Chinese family with FAP. Polymerase chain reaction and direct sequencing of the full coding sequence of the APC gene were performed to identify the mutation in this family. A nonsense mutation of the APC gene was identified in this pedigree. It is a heterozygous G>T substitution at position 2,971 in exon 15 of the APC gene, which formed a premature stop codon at amino acid residue 991 (p.Glu991*). The resulting truncated protein lacked 1,853 amino acids. The present study expanded the database on APC gene mutations in FAP and enriched the spectrum of known germline mutations of the APC gene. Prophylactic proctocolectomy may be considered as a possible treatment for carriers of the mutation.
Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer.
Background: This research was conducted to investigate the effects of a nursing supportive program on anxiety and stress levels in the family members of patients admitted to the intensivee care unit (ICU) after cardiac surgery. Methods: This research was a quasi-experimental study. A control group and an intervention group (each = 35), both comprised of the family members of post-cardiac surgery patients admitted to the ICU, were studied. The intervention group received a nursing supportive program initially 2 hours after their patients entered the ICU (1st day) and thereafter on the 2nd and 3rd days. The control group received only the routine information. Demographic variables and an adjusted Depression Anxiety Stress Scales (DASS-21) were used to assess the anxiety and stress levels of the family members of the patients. Results: Demographic variables and the DASS scores had no statistically significant differences in stress levels between the 2 groups before the intervention. However, after the intervention, the mean score of the stress level in the intervention group dropped significantly in comparison with the control group (P = 0.0001). Anxiety levels in both groups were reduced after the intervention. However, although a statistically significant difference was observed between the 2 groups 2 hours after ICU admission and on the 2nd ICU day (P = 0.0001), there was no significant difference on the 3rd ICU day (P = 0.993). Conclusions: In light of the findings of the present study, our nursing supportive program, which was aimed at providing information, emotional and mental support, and reassurances to the family members of post-cardiac surgery patients hospitalized in the ICU, was able to decrease their stress levels and to some extent their anxiety levels.
Hegemonic masculinities (i.e., sets of socially accepted masculine behaviors and beliefs within a given time and culture) may affect the well-being of sexual minority men, yet quantitative relationships between these masculinities and well-being remain largely unexplored. Using data from a national cross-sectional survey of young sexual minority men (N = 1,484; ages 18-24 years), the current study examined the relationship between parental gender policing during childhood and adolescence and subsequent substance use and psychological distress. Over one third of the sample (37.8%) reported their parent(s) or the person(s) who raised them had policed their gender, including the use of disciplinary actions. Using multivariable regression, this study examined the relationship between parental gender policing and psychological well-being and substance use, after adjusting for age, race/ethnicity, educational attainment, and current student status. Gender policing during childhood and adolescence was associated with recent substance use behaviors and psychological distress in multivariable models. A linear association between substance use behaviors and psychological distress and the number of disciplinary actions experienced during childhood and adolescence was also observed. Parents' attempts to police their sons' gender expression were associated with markers of distress among young sexual minority men. The relationship between parental gender policing during childhood and adolescence and distress among young sexual minority men are discussed.
Clause 13 of the United Nations Convention on the Rights of the Child states that children have the right 'to seek, receive or impart information and ideas of all kinds, regardless of frontiers, either orally, in writing or in print, in art or in any other media of the child's voice'. However, there is one area in which this directive is constrained in various countries by domestic regulations curtailing children's access to information. That area is human sexuality. The arguments for and against children's access to sex education are well rehearsed. In this article, the author pursues a different angle, looking instead at the increasing restrictions placed upon young people's ability to imagine and communicate with each other about sexual issues, particularly in online settings. The advent of the internet and a range of social networking sites have not only enabled young people to access previously quarantined information about sexuality, but also to actively engage in forms of 'intimate citizenship' online. In this article, the author focuses on young people's online fan communities which use characters from popular culture such as Harry Potter or a range of Japanese manga and animation to imagine and explore sexual issues. 'Child abuse publications legislation' in Australia and elsewhere now criminalizes the representation of even imaginary characters who are or may only 'appear to be' under the age of 18 in sexual scenarios. Hence these children and young people are in danger of being charged with the offence of manufacturing and disseminating child pornography. Despite research into these fandoms that indicates that they are of positive benefit to young people in developing 'sexual literacies', there is increasingly diminishing space for young people under the age of 18 to imagine or communicate about sexuality, even in the context of purely fictional scenarios.
Introduction: There is limited evaluation of clinical and theoretical claims that sexual thoughts of children and coercing others facilitate sexual offending. The nature of these thoughts (what they contain) also is unknown. Aim: To examine the relation between child or coercive sexual thoughts and sexual offending and to determine the nature of these thoughts and any differences among sexual offending (SO), non-sexual offending (NSO), and non-offending (NO) men. Methods: In a cross-sectional computerized survey, anonymous qualitative and quantitative self-reported sexual thought and experience data were collected from 279 adult volunteers composing equal numbers of SO, NSO, and NO men recruited from a medium-security UK prison and a community sample of 6,081 men. Main Outcome Measures: Computerized Interview for Sexual Thoughts and Computerized Inventory of Sexual Experiences. Results: Three analytical approaches found child sexual thoughts were related to sexual offending; sexual thoughts with coercive themes were not. Latent class analyses identified three types of child sexual thought (primarily differentiated by interpersonal context: the reporting of own emotions, emotions of others, or both) and four types of sexual thoughts of coercing others (chiefly discriminated by the other person's response: no emotional states reported, consent, non-consent, or mixed). Type of child sexual thought and participant group were not significantly related. Type of coercive sexual thought and group were marginally related; the consensual type was more common for the NO group and the non-consensual type was more common for the SO group than expected statistically. Conclusion: Child sexual thoughts are a risk factor for sexual offending and should be assessed by clinicians. In general, sexual thoughts with coercive themes are not a risk factor, although thought type could be important (ie, thoughts in which the other person expresses an enduring lack of consent). Exploring the dynamic risk factors associated with each type of child and coercive thought could lead to more targeted treatment. Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of epilepsy phenotypes. Recent technological advances in molecular biology have also rapidly expanded the genotype of EOEE. Genes involved in diverse molecular pathways, including ion channels, synaptic structure, transcription regulation, and cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA synthetase, which plays a key role in mitochondrial protein synthesis by attaching 20 different amino acids to the tRNA tail, has been recently linked with the epilepsy phenotype. Here, we report a novel homozygous c.925G >A (G309S) missense mutation in the gene that encodes the human mitochondrial phenylalanyl-tRNA synthetase (FARS2) in four patients from two nonconsanguineous Korean families. All four patients suffered from intractable seizures that started at the age of 3 and 4 months. Seizure types were variable, including infantile spasms and myoclonic seizures, and often prolonged. Although their initial development seemed to be normal, relentless regression after seizure onset occurred in all patients. An etiologic investigation, including brain imaging and metabolic studies, did not reveal a specific etiology. We reviewed the epilepsy phenotypes of six additional FARS2 mutation-positive patients and suggest that FARS2 can be considered one of the genetic causes of EOEE. (C) 2016 Elsevier B.V. All rights reserved.
Background: Representatives of the trematode family Fasciolidae are responsible for major socio-economic losses worldwide. Fascioloides magna is an important pathogenic liver fluke of wild and domestic ungulates. To date, only a limited number of studies concerning the molecular biology of F. magna exist. Therefore, the objective of the present study was to determine the complete mitochondrial (mt) genome sequence of F. magna, and assess the phylogenetic relationships of this fluke with other trematodes based on the mtDNA dataset. Findings: The complete F. magna mt genome sequence is 14,047 bp. The gene content and arrangement of the F. magna mt genome is similar to those of Fasciola spp., except that trnE is located between trnG and the only non-coding region in F. magna mt genome. Phylogenetic relationships of F. magna with selected trematodes using Bayesian inference (BI) was reconstructed based on the concatenated amino acid sequences for 12 protein-coding genes, which confirmed that the genus Fascioloides is closely related to the genus Fasciola; the intergeneric differences of amino acid composition between the genera Fascioloides and Fasciola ranged 17.97-18.24 %. Conclusions: The determination of F. magna mt genome sequence provides a valuable resource for further investigations of the phylogeny of the family Fasciolidae and other trematodes, and represents a useful platform for designing appropriate molecular markers.
Background: Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica. Methods: The mice were immunised with synthetic peptides containing B-and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks. Results: Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from -2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes. Conclusion: The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.
Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment). We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M. tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.
The concepts of protein purification are often taught in undergraduate biology and biochemistry lectures and reinforced during laboratory exercises; however, very few reported activities allow students to directly gain experience using modern protein purification instruments, such as Fast Protein Liquid Chromatography (FPLC). This laboratory exercise uses size exclusion chromatography (SEC) and ion exchange (IEX) chromatography to separate a mixture of four different proteins. Students use an SEC chromatogram and corresponding SDS-PAGE gel to understand how protein conformations change under different conditions (i.e. native and non-native). Students explore strategies to separate co-eluting proteins by IEX chromatography. Using either cation or anion exchange, one protein is bound to the column while the other is collected in the flow-through. In this exercise, undergraduate students gain hands-on experience with experimental design, buffer and sample preparation, and implementation of instrumentation that is commonly used by experienced researchers while learning and applying the fundamental concepts of protein structure, protein purification, and SDS-PAGE. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):60-68, 2017.
this paper presents triple mode to optimize settling, current consumption and noise of a crystal oscillator (XTAL). The proposed XTAL driver has three mode. Fast settling mode is used to reduce settling time. To reduce the start-up time of a XTAL driver, internal noise booster (INB) and negative resistance booster (NRB) are proposed. The simulated start-up time of a 4.19403MHz XTAL Driver in 0.18um CMOS is reduced by 80% from 4ms to 800us. Retention mode is only operated in stand-by to reduce total power consumption. A Peak and Low detection (PLD) is proposed. The stand-by of the XTAL driver does not effect to load. Therefore, the PLD blocks input supply voltage until HVT signal goes to down. It reduces power consumption up to 60%. EMI reduction mode is proposed to reduce output spur noise. To reduce output spur noise, pseudorandom-number generator (PRNG) is used makes 4bits random signal to spread frequency up to -10dB. All mode is controlled by Digital Control block. An inverter amplifier driver is optimized to reduce power consumption to 30uA and gets +/- 100 ppm operation in changing temperature from -40 degrees C to 60 degrees C.
A novel folded-cascode operational amplifier (opamp) employing the nested gain-boosted technique is presented. The gain-booster in the signal path consists of two-level recursive folded-cascode amplifier to achieve high gain and high speed. The opamp is designed and simulated in 0.13 mu m CMOS technology, bode-plot results that an open-loop gain over 90dB and a unity-gain frequency up to 4.75G for loads of 1.6pF have been obtained. Settling measurements shows that the opamp has a settling time less than 2.5ns. So the proposed opamp can be employed in high speed and high resolution Analog-to-Digital converters (ADCs) such as pipelined ADC.
Background:Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status.Objective:The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula.Methods:Infants (N=89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined.Results:Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA.Conclusions:ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.
Biotechnological production of fatty alcohols, important raw materials in the chemical industry, has been receiving considerable attention in recent years. Fatty alcohols are formed by the reduction of fatty acyl-CoAs or fatty acyl-ACPs catalyzed by a fatty acyl reductase (FAR). In this study, we introduced genes encoding FARs from Arabidopsis thaliana (AtFAR5) and Simmondsia chinensis (ScFAR) into Crambe abyssinica hairy roots via Agrobacterium rhizogenes-mediated transformation. The efficiency of the transformation ranged between 30 and 45%. The fatty alcohols were only detected in the transgenic hairy root lines expressing ScFAR gene. In all tested lines stearyl alcohol (18:0-OH), arachidyl alcohol (20:0-OH), and behenyl alcohol (22:0-OH) were produced. The content of 18:0-OH varied from 1 to 3% of total fatty acids and fatty alcohols, while the amount of either 20:0-OH and 22:0-OH did not exceed 2%. The transgenic hairy root lines produced from 0.98 to 2.59nmol of fatty alcohols per mg of dry weight. Very low activity of ScFAR was detected in the microsomal fractions isolated from the selected hairy root lines. To our knowledge, this is the first report on the fatty alcohol production in the hairy root cultures. Biotechnol. Bioeng. 2017;114: 1275-1282. (c) 2016 Wiley Periodicals, Inc.
In response to overfeeding, geese develop fatty liver. To understand the fattening mechanism, mRNA differential display reverse transcription PCR was used to study the gene expression differences between French Landes grey geese and Xupu white geese in conditions of overfeeding and normal feeding. One gene was found to be up-regulated in the fatty liver in both breeds, and it has a 1797 bp cDNA with 83% identity to chicken SELENBP1. The sequence analysis revealed that its open reading frame of 1413 bp encodes a protein of 471 amino acids, which contains a putative conserved domain of 56 kDa selenium binding protein with high homology to its homologues of chicken (95%), rat (86%), mouse (84%), human (86%), monkey (86%), dog (86%), and cattle (86%). The function of this protein has been briefly reviewed based on published information. In tissue expression analysis, the expression of geese SELENBP1 mRNA was found to be higher in liver or kidney than in other tested tissues. The results showed that overfeeding could increase the mRNA expression level of geese SELENBP1.
In a medium-voltage power system, fault currents are subjected to uncertainties in lines and distributed generations. Uncertainties in fault currents in a power grid can introduce system protection problems. Superconducting cablewith fault current limiting capability can be used as means to meet the increasing electricity demand while resolving the issues involving system protection. In order to integrate the fault current limiting superconducting cable into a power grid, its impedance selection under fault conditions needs to consider the impact of power system uncertainties on system protection. In this paper, an expected regret-based method is proposed for determining the impedance of the fault current limiting superconducting cable incorporating the uncertainties in fault currents. The results of numerical simulations are presented to show the effectiveness of the proposed expected regret-based impedance selection method.
A novel observer-based fault accommodation technique for linear multi-input multi-output sampled-data systems affected by a general class of actuator faults in the presence of quantization errors is addressed in the paper. Only the output signal has been assumed to be available for direct measurement. A simulation study on a three-tank system supports theoretical developments. Copyright (c) 2014 John Wiley & Sons, Ltd.
This paper proposes a novel DC-side discrete-time voltage controller for grid-connected voltage-sourced converters during asymmetrical faults. The main objective is to eliminate the second-order voltage oscillation on the VSC's DC-side, as well as the positive sequence third-order harmonic current injection into the grid during asymmetrical faults. The compensator is designed based on the comprehensive discrete-time model of the DC-side dynamics. It is shown that DC-side average voltage can be controlled by the positive sequence direct axis current, while the oscillating component can be fully controlled by negative sequence dq-axes currents. The negative sequence current references are obtained using a discrete resonant controller plus a lead filter in order to achieve zero steady state error and asymptotically stability, without injecting harmonics currents into the grid. Simulation results showed the effectiveness of the proposed strategy under severe fault conditions. (C) 2016 Elsevier Ltd. All rights reserved.
Background and Objective: Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings. Material and Methods: 55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4 +/- 12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel-based SPM method at the single-subject level. Results: FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline. Discussion: Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes.
Recalling positive autobiographical memories is a powerful strategy to repair affect. Positive memory recall operates as a reparative strategy by enhancing positive affect, which facilitates the down-regulation of negative affect. There are individual differences, however, in the ability to use positive material to repair mood. Participants with elevated depression scores, for example, are less likely to profit from this strategy. Depression has been associated with elevated fear of positive emotion and the current study examined whether elevated fear of positive emotion is associated with depression-related difficulties in mood repair. Ninety-four participants first underwent a mood repair task in which a sad mood induction was followed by a cue to recall positive autobiographical memories. Subjective measures of state happiness and sadness were collected across the mood induction and positive memory recall procedures. Results revealed that greater fear of positive emotion was linked to less ability to enhance positive affect and down-regulate negative affect using positive memories. Results also provided preliminary support for a mediation model in which greater depressive symptoms predicted elevated fear of positive emotion, which in turn predicted less ability to repair positive affect. These findings highlight fear of positive emotion as a potential target for interventions aimed at improving affect regulation.
Integrated heat and electricity dispatch is crucial to exploit synergistic benefits from integrated energy systems. However, this requires information from both electricity systems and district heating systems (DHSs), which are managed by an electricity control center (ECC) and district heating control centers (DHCCs), respectively. For reasons pertaining to privacy, communication, dimension, and compatibility, it is not practical for DHCCs to send detailed models to the ECC. Therefore, a new feasible region method is proposed for formulation of new DHS models, which exploit the flexibility of DHSs with consideration of building thermal inertia. A greedy method is developed to solve the new modified feasible region models by calculating a series of linear programming problems efficiently. Then the new models are sent to the ECC to be used in central dispatch considering DHS operation constraints, i.e. integrated heat and electricity dispatch. The modified models are similar to conventional power plants and storages, and are thus compatible with current dispatch programs. Case studies verify the effectiveness of the method. Although some conservativeness exists, the total cost and wind energy curtailment are both decreased compared to conventional decoupled dispatch. (C) 2016 Elsevier Ltd. All rights reserved.
Biotreatment of feather wastes and utilization of the degraded products in feed and foodstuffs has been a challenge. In the present study, we have demonstrated the degradation of feather waste by Bacillus cereus DCUW strain isolated during a functional screening based microbial diversity study on East Calcutta Wetland Area. A high molecular weight keratinolytic protease from feather degrading DCUW strain was purified and characterized. Moreover, utilization of degraded products during feather hydrolysis was developed and demonstrated. The purified keratinolytic protease was found to show pH and temperature optima of 8.5 and 50 degrees C, respectively. PMSF was found to inhibit the enzyme completely. The purified enzyme showed molecular weight of 80 kDa (from SDS-PAGE). The protease was found to have broad range substrate specificities that include keratin, casein, collagen, fibrin, BAPNA and gelatin. The protease was identified as minor extracellular protease (Vpr) by RT-PCR and northern blotting techniques. This is the first report describing the characterization of minor extracellular protease (Vpr) and its involvement in feather degradation in B. cereus group of organisms.
Real numbermodeling of analog circuits in hardware description languages (HDLs) has become more common as a part of mixed-signal SoC validation. We propose two methods that both improve the fidelity and simulation speed, and make the event-driven, piecewise linear (PWL) analog functional models easier to write. First we use the accuracy set by users to dynamically determine when a new output segment should be emitted, which is computed without any iteration. This capability allows designers to trade accuracy for simulation speed of analog models without any time-consuming model calibration/error estimation, and creates models which generate events only when needed to maintain output accuracy. We next extend this method to eliminate limit-cycle oscillations that occur when simulating circuits with continuous-time feedback in a discrete-time event simulator. Handling this feedback efficiently allows the user to create the system model from simpler component models. The performance of this modeling approach is demonstrated on various analog filter models, an operational amplifier, and a high-speed, wireline transceiver system, and is 3.1x faster than an optimally-chosen, fixed-time step simulation for the transceiver.
In grid-connected converter control, grid voltage feedforward is usually introduced to suppress the influence of grid voltage distortion on the converter's grid-side AC current. However, owing to the time-delay in control systems, the suppression effect of the grid voltage distortion is seriously affected. In this paper, the positive effects of the grid voltage feedforward control are analyzed in detail, and the time-delay caused by the low-pass filter (LPF) in the voltage filtering circuits and digital control are summarized. In order to reduce the time-delay effect on the performance of the feedforward control, a voltage feedforward control strategy with time-delay compensation is proposed, in which, a leading correction of the feedforward voltage is used. The optimal leading step used in this strategy is derived from analyzing the phase-frequency characteristics of a LPF and the implementation of digital control. By using the optimal leading step, the delay in the feedforward path can be further counteracted so that the performance of the feedforward control in terms of suppressing the influence of grid voltage distortion on the converter output current can be improved. The validity of the proposed method is verified through simulation and experiment results.
Incentivizing development and deployment of renewable energy sources (RES), but also other low carbon technologies (LCT), has been a successful way of promoting new technologies by creating a feasible investment case and making them competitive with traditional energy sources. Although different incentive mechanisms exist, feed-in tariffs have shown to be the best model for accelerating LCT development guaranteeing producers preferential prices for the produced electricity over a period of time and enabling them access to the power network to sell/inject produced electricity. Due to these benefits, feed-in tariff models are the most common model for stimulating RES integration in southeast Europe. The paper reviews the current state of preferential tariffs for RES in countries of southeast Europe. While some countries already have significant installed RES capacity, others are still in the planning stage. The review shows that the amount of installed capacity of a specific technology has a strong impact on the support for the future projects for same technology. This comprehensive review of legislative development supporting RES, as well as technologies preferred in different countries of the region, is supported with feasibility assessment of investing in RES using the example of two different technology projects, wind and photovoltaic, analysing the impact of the current tariffs on the return on investment for each country of the region.
The present study evaluated the Response Bias scale (RBS), a symptom validity test embedded within the Minnesota Multiphasic Personality Inventory (MMPI)-2 Restructured Form (MMPI-2-RF) that assesses for feigned neurocognitive complaints, in a sample of pretrial incompetent to stand trial (IST) criminal defendants. Additionally, we examined the Improbable Failure (IF) scale, a performance validity test embedded within the Structured Interview of Reported Symptoms, Second Edition (SIRS-2), which similarly assesses for feigned cognitive impairment (FCI). Results indicated that both the RBS (area under the curve [AUC] = .76) and IF scale (AUC = .72) achieved moderate classification accuracy using the Test of Memory Malingering (TOMM) as the criterion. Further, the RBS and IF scale appeared to be most useful for screening out those defendants who presented as genuine (specificity = 99% and 88%, respectively), and less effective at classifying those defendants suspected of feigning according to the TOMM (sensitivity = 29% and 46%, respectively). In order to identify a significant proportion of IST defendants who may be feigning impairment, considerably lower cutoff scores than those recommended in each measure's manual were evaluated. An RBS T score of 63 (sensitivity = 86%; specificity = 37%), and IF scale raw score of 2 (sensitivity = 80%; specificity = 43%), was required to achieve >= 80% sensitivity; these alternate cutoff scores may therefore be useful when screening inpatient forensic psychiatric IST defendants. Further, the 2 scales effectively predicted TOMM classification in combination, although only the RBS significantly contributed to the model. Implications for the assessment of FCI in forensic psychiatric settings are discussed.
We describe the rationale and methods of a study designed to compare vaginal and urinary microbiomes in women with mixed urinary incontinence (MUI) and similarly aged, asymptomatic controls. This paper delineates the methodology of a supplementary microbiome study nested in an ongoing randomized controlled trial comparing a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone for MUI. Women in the parent study had at least "moderate bother" from urgency and stress urinary incontinence symptoms (SUI) on validated questionnaire and confirmed MUI on bladder diary. Controls had no incontinence symptoms. All participants underwent vaginal and urine collection for DNA analysis and conventional urine culture. Standardized protocols were designed, and a central lab received samples for subsequent polymerase chain reaction (PCR) amplification and sequencing of the bacterial16S ribosomal RNA (rRNA) gene. The composition of bacterial communities will be determined by dual amplicon sequencing of variable regions 1-3 and 4-6 from vaginal and urine specimens to compare the microbiome of patients with controls. Sample-size estimates determined that 126 MUI and 84 control participants were sufficient to detect a 20 % difference in predominant urinary genera, with 80 % power and 0.05 significance level. Specimen collection commenced January 2015 and finished April 2016. DNA was extracted and stored for subsequent evaluation. Methods papers sharing information regarding development of genitourinary microbiome studies, particularly with control populations, are few. We describe the rigorous methodology developed for a novel urogenital microbiome study in women with MUI.
Low-temperature NH3-SCR is an environmentally important reaction for the abatement of NOx from stationary sources. In recent years FeMnOx has attracted significant attention as a potential catalyst for this process, however its catalytic activity and SO2 resistance require further improvement. In this contribution FeMnOx has been modified to examine the effect of ceria on catalytic activity and SO2 resistance in the low temperature region. Preparation of catalysts via the citric acid method generate modified materials that exhibit enhanced NO turnover compared to FeMnOx. A reduction in NH3 adsorption (NH3-TPD) and a suitable ratio between NO sites (NO-TPD) and chemisorbed surface oxygen (XPS) are beneficial for the promotion of fast-SCR. A comparative SO2 resistance study of FeMnOx and Ce(12.5) showed that the latter exhibited improved stability in the presence of SO2, as indicated by the retention of pore volume (N-2 adsorption) and surface composition (XPS). In-situ DRIFTS demonstrated that chemisorbed N-containing species on Ce(12.5) were much more stable in the presence of SO2 compared to FeMnOx, which resulted in the formation of significantly less metal sulphates and NH4HSO4. Crown Copyright (C) 2017 Published by Elsevier B.V.All rights reserved.
Background: Ovarian tissue cryopreservation (OTC) is the only option available to preserve fertility in prepubertal females with neuroblastoma (NB), a childhood solid tumor that can spread to the ovaries, with a risk of reintroducingmalignant cells after an ovarian graft. Procedure: We set out to determine whether the analysis of TH (tyrosine hydroxylase), PHOX2B (paired-like homeobox 2b), and DCX (doublecortin) transcripts using quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) could be used to detect NB contamination in ovarian tissue. Analyses were performed on benign ovarian tissue from 20 healthy women between November 2014 and September 2015 at the University Hospital of Clermont-Ferrand. Pericystic benign ovarian tissues were collected and contaminated with increasing numbers of human NB cells (cell lines IMR-32 and SK-N-SH) before detection using RT-qPCR. Results: TH and DCX transcripts were detected in uncontaminated ovarian tissue from all the donors, hampering the detection of small numbers of tumor cells. By contrast, PHOX2B was not detected in any uncontaminated ovarian fragment. PHOX2B levels were significantly increased from 10 NB cells. Our study is the first to evaluate minimal residual disease detection using NB mRNAs in human ovarian tissue. Only PHOX2B was a reliable marker of NB cells contaminating ovarian tissue. Conclusions: These results are encouraging and offer hope in the near future for grafting ovarian tissue in women who survive cancer, whose fertility has been jeopardized by treatment, and who could benefit fromOTC without oncological risk.
Objective: To determine the role of Dkkl1 in mouse development, viability, and fertility. Design: Prospective experimental study. Setting: Government research institution. Animal(s): Mice of C57BL/6. B6D2F1/J, and 129X1/SvJ strains, as well as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies. Intervention(s): Expression of the Dkkl1 gene was characterized during early mouse development, and the effects of Dkkl1 ablation on reproduction and fertility were characterized in vitro and in vivo. Main Outcome Measure(s): Dkkl1 RNA expression was determined by Northern blotting hybridization as well as quantitative reverse transcriptase-polymerase chain reaction assays. In vitro fertilization assays were used to assess fertility of sperm from male mice lacking functional Dkkl1. Result(s): Dkkl1 is a gene unique to mammals that is expressed primarily in developing spermatocytes and its product localized in the acrosome of mature sperm. Here we show that Dkkl1 also is expressed in the trophectoderm/placental lineage. Surprisingly, embryos lacking DKKL1 protein developed into viable, fertile adults. Nevertheless, the ability of sperm that lacked DKKL1 protein to fertilize wild-type eggs was severely compromised in vitro. Because this defect could be overcome either by removal of the zona pellucida or by the presence of wild-type sperm. Dkkl1, either directly or indirectly, facilitates the ability of sperm to penetrate the zona pellucida. Penetration of the zona pellucida by Dkkl1 sperm was delayed in vivo as well as in vitro, but the delay in vivo was compensated by other factors during preimplantation development. Accordingly, Dkkl1 I males offer an in vitro fertilization model for identifying factors that may contribute to infertility. Conclusion(s): DKKL1 is a mammalian-specific, acrosomal protein that strongly affects in vitro fertilization, although the effect is attenuated in vivo. (Fertil Steril (R) 2010;93:1533-7. (C)2010 by American Society for Reproductive Medicine.)
Conditionally transformed human myocardial cell lines would be a valuable resource for studying human cardiac cell biology. We generated clonal human fetal cardiocyte cell lines by transfection of fetal ventricular cardiac cell clones with a plasmid containing a replication-defective mutant of the temperature-sensitive SV40 strain tsA58. Multiple resulting cell lines showed similar features, namely: (1) T antigen (TAg) expression at both permissive (34 degrees C) and restrictive (40.5 degrees C) temperatures; (2) extended growth capacity in comparison with parental wild type, when grown at the permissive temperature; (3) both temperature-dependent and serum-responsive growth, and; (4) an incompletely differentiated fetal phenotype which was similar at both permissive and restrictive temperatures and in the presence and absence of serum. The transformed myocyte phenotype was demonstrated using immunocytochemistry, Western and Northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR). Cell lines expressed skeletal alpha-actin, atrial natriuretic peptide (ANP), and keratins, but no sarcomeric myosin heavy chain or desmin. Immunoreactive sarcomeric actin was expressed predominantly as a truncated protein of approximately 38 kD. The phenotype of the transformed cells differs from that of the wild-type parental cells as well as from those reported by others who have used TAg to immortalize rodent or human ventricular myocytes. Our cell lines should provide a useful tool for study of the molecular mechanisms regulating growth and differentiation in human cardiac muscle cells.
Fibroblast growth factor 2 (FGF2) plays an important role in cortical development. However, the genes downstream of FGF2 that mediate its effect are largely unknown. We have performed a microarray screening of genes regulated by FGF2 using primary cortical neuron culture derived from embryonic day 14.5 (E14.5) mouse forebrains. In this study, we have analysed a previously uncharacterised gene encoding a 180-amino acid protein, hereby named 'coiled-coil protein 1 (ccp1)', that showed a modest up-regulation upon FGF2 stimulation. Northern blots and RT-PCR showed specific expression of ccp1 in multiple tissues including adult and embryonic brains. In situ hybridizations revealed that ccpl was expressed in the cortical plate between Reelin and Tbr1-positive layers in the dorsal cortex at E15.5. Furthermore, the expression pattern of ccp1 at E13.5-E14.5 reflected some of the aspects of tangential migration of cortical progenitors during the early phase. We observed that the expressed ccpl protein was localised to endo/lysosomal compartment in the cell body as well as to vesicles present in the processes of primary cortical neurons and oligodendrocyte cell line. (C) 2005 Elsevier B.V. All rights reserved.
FH98 digital scheduling system can realize the functions of centralized monitoring, remote maintenance, fault diagnosis, and environmental monitoring, etc. so that the remote equipment can be attended. In this way, railway scheduling, station and station communication can adapt to the future development of railway communication. This paper describes the common faults and processing methods of application of FH98 digital dispatching system.
The use of hybrid short fibers in a suitable combination as reinforcement for cement based materials has attracted widespread attention because of their benefits compared to mono fiber reinforcement in recent years. This paper provides a review of recent developments on the area of the cement-based composites reinforced by hybrid short fibers. The aim of paper is to represent the effects of hybridization by elaborating upon the chemical, physical and mechanical properties of fibers on the performance of fiber reinforced concretes (FRC). This provides a summary of the existing knowledge about the successful use of different hybrid forms such as combination of steel, polymer and natural fibers in cementitious composites. Different types of hybrid system depending on fiber type are classified and reviewed. Furthermore, the physical and mechanical properties of resultant composites are also presented. Generally, inclusion of fibers in concrete as hybrid forms, improves many of its engineering properties such as toughness, ductility, energy absorption capacity and durability performance in comparison with mono fiber reinforcement. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: The molecular mechanisms underlying fibrillation potentials are still unclear. We hypothesised that expression of the cardiac-type voltage-gated sodium channel isoform Nav1.5 in denervated rat skeletal muscle is associated with the generation of such potentials. Methods: Muscle samples were extracted and analysed biologically from surgically denervated rat extensor digitorum longus muscle after concentric needle electromyographic recording at various time points after denervation (4 h to 6 days). Results: Both nav1.5 messenger RNA (mRNA) signal on northern blotting and Nav1.5 protein expression on immunohistochemistry appeared on the second day after denervation, exactly when fibrillation potentials appeared. Administration of lidocaine, which has much stronger affinity for sodium channels in cardiac muscle than for those in skeletal muscle, dramatically decreased fibrillation potentials, but had no effect on contralateral compound muscle action potentials. Conclusions: Expression of Nav1.5 participates in the generation of fibrillation potentials in denervated rat skeletal muscle. Significance: We proposed an altered expression of voltage-gated sodium channel isoforms as a novel mechanism to explain the occurrence of fibrillation potentials following skeletal muscle denervation. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Research into regenerative dentistry has contributed momentum to the field of molecular biology. Periapical surgery aims at removing periapical pathology to achieve complete wound healing and regeneration of bone and periodontal tissue. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue-engineering product and has recently gained much popularity due its promising results in wound healing bone induction. The features of this product are an attribute of platelets which, after cellular interactions, release growth factors and have shown application in diverse disciplines of dentistry. This paper is intended to shed light onto the various prospects of PRF and to provide clinical insight into regenerative endodontic therapy.
Background: Aloe vera (A. v) have been used traditionally for topical treatment of wounds and burns in different countries for centuries, but the mechanism of this effect is not well understood. Various growth factors are implicated in the process of wound healing. Among the different growth factors involved in the process, TGF beta 1 and bFGF are the most importantly expressed in fibroblast cells. The aim of this study was to evaluate the effect of A. v on the expression of angiogenesis growth factors in mouse embryonic fibroblast cells. Methods: We exposed mouse embryonic fibroblast cells to different concentrations of A. v (50, 100 and 150 mu g/ml) at two different time of 12 and 24 h. Fibroblast cell without A. v treatment serves as the control. The expression of TGF beta 1 and bFGF was measured by real time-polymerase chain reaction (real-time-PCR) and enzyme-linked immunosorbent assay (ELISA) at the level of gene and protein. Results: We observed that A.v gel at first up-regulated the expression of TGF beta 1 and bFGF, but, these genes were later repressed after a particular time. Conclusion: Our results demonstrated that A. v was dose-dependent and time-dependent on the expression of bFGF and TGFb1 in fibroblast cell in vitro. This mechanism can be employed in the prospective treatment of physical lesion. (C) 2017 Elsevier Masson SAS. All rights reserved.
Background: Human skin shows various morphological characteristics, depending on the body site. As these distinct phenotypes have been explained on the basis of the variance in epidermal keratinocytes and the presence of skin appendages, the spatial distinction of the dermal components has not been fully elucidated. Objectives: To identify and characterize the profiles of mRNAs that are abundantly or specifically expressed by fibroblasts derived from trunk skin, but not from palmoplantar skin or oral mucosa. Methods: In order to identify the distinct mRNA expression by trunk skin fibroblasts, a subtraction cDNA screening was performed first, followed by Northern blotting, Western blotting and immunohistochemistry for cultured human and rat dermal fibroblasts and those skin tissues. Finally, whole mount in situ hybridization (WISH) was performed to examine the differences in the expression of the corresponding gene during the developmental stage of mouse embryos. Results: We identified three cDNA clones encoding fibronectin (FN), pregnancy-specific beta 1-glycoprotein 5 and beta-actin, respectively, whose mRNAs were abundantly or specifically expressed by trunk skin fibroblasts. FN and some integrins were further confirmed to be expressed more selectively in human and rat trunk skin fibroblasts, both in terms of the RNA and the protein levels, compared with the fibroblasts derived from plamoplantar skin and oral mucosa. WISH demonstrated that FN was localized around the hair follicles of mouse embryos. Conclusion: FN, one of most potent extracellular matrix molecules, was demonstrated to be spatially transcribed depending on the body sites. The distinct expression of FN was suggestive of the essential commitment in the process of cutaneous development and morphogenesis of appendages originated from hair germ. The paucity of FN in palmoplantar skin and oral mucosa might explain the characteristics of these skin phenotypes.
This descriptive study evaluates how dance movement psychotherapy (DMP) works in patients with fibromyalgia, analysing the psychotherapeutic process. As a second objective, we considered the effects of DMP on pain, stiffness, fatigue, anxiety, depression and lifestyle changes. The study includes 16 patients with a diagnosis of primitive fibromyalgia who were referred to individual DMP for psychological distress related to pain. Self-assessment questionnaires were administered before and after the intervention, and the data were analysed using a simple regression model and Student's test. Despite limitations, the study highlights changes in many areas of the relationship with Self and with Others. Some of the symptoms of fibromyalgia seem to have decreased, but the results were not statistically significant. The patients used the movement as a means of expression despite pain or other disabling symptoms. A low drop-out rate suggests that this approach could be useful when it is difficult to develop a therapeutic alliance.
This study explored the role of fibulin-4 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-4 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines, the normal osteoblastic cell line hFOB, and different invasive subclones were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real-time reverse transcriptase-polymerase chain reaction (real-time qRT-PCR). Using in vitro functional assays, we analyzed the invasive and proliferative abilities of different osteosarcoma cell lines and subclones with differing invasive potential. To assess the role of fibulin-4 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-4 small hairpin RNA (shRNA) and pLVX-fibulin-4 were constructed and used to infect the highly invasive and low invasive subclones and osteosarcoma cell lines. The effects of fibulin-4 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-4 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-4 was also found to be over-expressed in highly invasive cell lines and in the highly invasive subclones. Fibulin-4 could promote osteosarcoma cell invasion and metastasis by inducing EMT via the PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that fibulin-4 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.
Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and multifactorial process involving genetic and epigenetic events. The majority of HNSCC patients present with locoregional advanced stage disease and are treated with combined modality strategies that can markedly impair quality of life and elicit unpredictable results. A large fraction of those who undergo locoregional treatment and achieve a complete response later develop locoregional recurrences or second field tumors. Biomarkers that are thus able to stratify risk and enable clinicians to tailor treatment plans and to personalize post-therapeutic surveillance strategies are highly desirable. To date, only HPV status is considered a reliable independent predictor of treatment response and survival in patients with HNSCC arising from the oropharyngeal site. Recent studies suggest that telomere attrition, which may be an early event in human carcinogenesis, and telomerase activation, which is detected in up to 90 % of malignancies, could be potential markers of cancer risk and disease outcome. This review examines the current state of knowledge on and discusses the implications linked to telomere dysfunction and telomerase activation in the development and clinical outcome of HNSCC.
A 5-bit digital controlled switch-type passive phase shifter realised in a 40 nm digital CMOS technology without ultra-thick metals for the 60 GHz Industrial, Scientific and Medical (ISM) band is presented. A patterned shielding with electromagnetic bandgap structure and a stacked metals method to increase the on-chip inductor quality factor are proposed. To reduce the insertion loss from the transistors, the transistor switches are implemented with a body-source connection. For all 32 states, the minimum phase error is 1.5 degrees, and the maximum phase error is 6.8 degrees. The measured insertion loss is -20.9 +/- 1 dB including pad loss at 60 GHz and the return loss is >10 dB over 57-64 GHz. The total chip size is 0.24 mm(2) with 0 mW DC power consumption.
Newtonian fluid dynamics simulations were performed using the Navier-Stokes-Fourier formulations to elucidate the short time-scale (mu s and longer) evolution of the density and temperature distributions in an argon-gas-filled attenuator for an X-ray free-electron laser under high-repetition-rate operation. Both hydrodynamic motions of the gas molecules and thermal conductions were included in a finite-volume calculation. It was found that the hydrodynamic wave motions play the primary role in creating a density depression (also known as a filament) by advectively transporting gas particles away from the X-ray laser-gas interaction region, where large pressure and temperature gradients have been built upon the initial energy deposition via X-ray photoelectric absorption and subsequent thermalization. Concurrent outward heat conduction tends to reduce the pressure in the filament core region, generating a counter gas flow to backfill the filament, but on an initially slower time scale. If the inter-pulse separation is sufficiently short so the filament cannot recover, the depth of the filament progressively increases as the trailing pulses remove additional gas particles. Since the rate of hydrodynamic removal decreases while the rate of heat conduction back flow increases as time elapses, the two competing mechanisms ultimately reach a dynamic balance, establishing a repeating pattern for each pulse cycle. By performing simulations at higher repetition rates but lower per pulse energies while maintaining a constant time-averaged power, the amplitude of the hydrodynamic motion per pulse becomes smaller, and the evolution of the temperature and density distributions approach asymptotically towards, as expected, those calculated for a continuous-wave input of the equivalent power.
Background: The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia, Southeast Asia, Sri Lanka and India. However, the origin and evolution of the species in the Wuchereria-Brugia clade remain unclear. While investigating the diversity of filarial parasites in Malaysia, we discovered an undescribed species in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia). Methods: We examined 81 common treeshrews from 14 areas in nine states and the Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae that were found had been isolated, we examined their morphological characteristics and determined the partial sequences of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T vector, and the recombinant plasmids were used as templates for sequencing. Results: Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological characteristics of adults and microfilariae found in common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene sequences of the new species and W. bancrofti was 11.8%. Based on the three gene sequences, the new species forms a monophyletic clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes of the neck of common treeshrews. Conclusions: The newly described species appears most closely related to Wuchereria spp. and Brugia spp., but differs from these in several morphological characteristics. Molecular analyses based on the cox1 and 12S rRNA genes and the ITS1 region indicated that this species differs from both W. bancrofti and Brugia spp. at the genus level. We thus propose a new genus, Malayfilaria, along with the new species M. sofiani.
In this paper inlcjet-shaped barium-titanate thin films were examined by SEM, AFM and optical microscopy, along with XRD and Raman spectroscopy in order to study effects of drying chemical additives, ink concentration and printing parameters on microstructure and phase composition. Inkjet printing is a very attractive way of shaping functional materials. Simple setup, low-cost, digital control and the possibility of obtaining complex forms without post-processing make this technique highly competitive for application in microelectronics. The most common way of preparing inks via powder dispersion involves high-temperature treatment (900 degrees C and above) in order to achieve dense and uniform structure. Thus, we utilized an energy efficient sol gel approach where the final phase composition is achieved in situ on the substrate. (C) 2015 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
This paper deals with the application of the simulated inductor in the continuous-time allpass filters and group delay sensitivity analysis of the realized filter. The realization of filter pair based on the LCR resonator circuits employs a single generalized grounded impedance converter, which can be implemented with only one operational amplifier. A group delay sensitivity measure can be useful for comparison of the second order allpass filter cells, used for continuous-time filter pair design. It can be related to the well known pole Q factor- and pole frequency-sensitivities by a simple analytic expression. A design procedure is developed in which tuning can be achieved by trimming only resistors.
Little work has focused on the underlying mechanisms that may link financial strain and smoking processes. The current study tested the hypothesis that financial strain would exert an indirect effect on cognitive-based smoking processes via depressive symptoms. Three clinically significant dependent variables linked to the maintenance of smoking were evaluated: negative affect reduction motives, negative mood abstinence expectancies, and perceived barriers for quitting. Participants included 102 adult daily smokers (M-age = 33.0 years, SD = 13.60; 353% female) recruited from the community to participate in a self-guided (unaided; no psychological or pharmacological intervention) smoking cessation study. Results indicated that depressive symptoms explain, in part, the relation between financial strain and smoking motives for negative affect reduction, negative mood abstinence expectancies, and perceived barriers for quitting. Results indicate that smoking interventions for individuals with high levels of financial strain may potentially benefit from the addition of therapeutic tactics aimed at reducing depression. (C) 2017 Elsevier Ltd. All rights reserved.
Sparked by the conjunction of food, fuel, and financial crises, there has been an increasing awareness in recent years of the scarce and finite character of natural resources. Productive resources such as agricultural land have been touted by financial actors-such as merchant banks, pension funds, and investment companies-as providing the basis for a range of new "alternative" financial asset classes and products. While the drivers, motives, and rationales behind the increasing interest of turning farmland into a financial asset class have been traced by a number of scholars, the interpretations of, and interactions with, financial actors at the community level have received less attention. Based on qualitative research in rural Australia, this paper reveals the grounds on which finance-backed investments have been accepted and accommodated by communities in rural Australia and delineates the reasons that have led to feelings of unease or refusal. The paper thereby demonstrates that the financialization of farmland is neither abstract nor one-sided but rather a multidimensional process that not only includes financial actors but also the impacted rural populations in various ways. Positioning the activities of financial actors in Australia within the emerging research on the financialization of farmland, the paper endorses context-sensitive analyses to better interpret these recent transformations of the agri-food system.
This paper demonstrates a 0.8-V rail-to-rail operational amplifier (op-amp) for ultra-low-power Internet-of-Things (IoT) sensor nodes. To suppress the leakage current in the logic part, a FinFET technology with 0.4-V threshold voltage (V-t), is chosen. To realize the rail-to-rail operation in the small common-mode (CM) voltage headroom, V-DD - V-t, a 4-stage chopper-stabilized topology with high-pass filters, multi-path hybrid-nested Miller compensation, and a push-pull output stage are introduced. A near-V-t amplifier is also introduced to the second stage to boost the gain. The fabricated op-amp shows 1-MHz Gain-Bandwidth in whole of the CM voltage range.
In communication and computing devices, the growing demand for high performance, battery-operated portable equipments have transferred the concentration from staid constraints (such as area, performance and reliability) to power consumption. In the present scenario there is a cardinal requirement to diminish power consumption for non-portable systems where power dissipation and leakage current are censorious concerns. In VLSI circuits and systems, power dissipation is still censorious because the leakage occurs when device is in inactive mode. To reduce the leakage power and leakage current in FinFET based operational amplifier, a new circuit technique called low power state technique is adduced in this paper. This approach reduces significant amount of power during active mode and also has an endowment of conserving the state in state retention mode 1. The op-amp electrical characteristics are obtained by employing Cadence Virtuoso tool for circuit simulation at 0.7 V input supply voltage. The simulated DC gain thus obtained is 65.4 dB in the active mode. The proposed FinFET based operational amplifier performance traits are studied and compared with the existing CMOS technology at 45 nm scale. Here, the effect of temperature variation on electrical characteristics of op-amp at 45 nm technology regime has been reconnoitered. FUrthermore, by employing low power approach, the enhancement in slew rate has been significantly attained. The simulation results are given and concluded.
The operating voltages of low-voltage control circuits in power plants and substations have decreased with the installation of digital control equipment. This increases the susceptibility of control equipment to abnormal surges, which arise mainly from lightning. To protect control equipment from lightning, it is necessary to predict lightning surges invading power plants and substations and design effective lightning protection methodologies. Compared with conventional simulation techniques based on circuit theory, full-wave numerical approaches are advantageous in handling three-dimensional structures such as transmission line towers, grounding structures, nonhorizontal wires, such as incoming power lines to power plants and substations, and lightning-induced effects. In this study, to apply the finite-difference time-domain (FDTD) method to the lightning surge analysis of an air-insulated substation, we first propose techniques for simulating the nonlinear breakdown characteristics of short-air-gap arcing horns and transmission line surge arresters installed in 77 kV transmission lines for FDTD-based surge simulations, and compare the breakdown characteristics calculated using the proposed techniques with measured results for validation. Second, as an example of the application of the proposed techniques to practical surge analysis, it is confirmed that we can reproduce the measured results of lightning surges invading a 77 kV air-insulated substation in the case of a direct lightning strike to its nearby transmission line tower by taking into account lightning-induced voltages arising from the lightning current flowing through the lightning channel and transmission line tower, which are commonly ignored in conventional circuit-theory-based simulations, multiphase back-flashover phenomena, and the effect of applied AC voltages.
Empirical analysis of the price fluctuations of financial markets has received extensive attention because a substantial amount of financial market data has been collected and because of advances in data-mining techniques. Price fluctuation trends can help investors to make informed trading decisions, but such decisions may also be affected by a psychological factors the anchoring effect. This study explores the intraday price time series of Taiwan futures, and applies diffusion model and quantitative methods to analyze the relationship between the anchoring effect and price fluctuations during first passage process. Our results indicate that power-law scaling and anomalous diffusion for stock price fluctuations are related to the anchoring effect. Moreover, microscopic price fluctuations before switching point in first passage process correspond with long-term price fluctuations of Taiwan's stock market. We find that microscopic trends could provide useful information for understanding macroscopic trends in stock markets. (C) 2017 Elsevier B.V. All rights reserved.
Aim: Most studies on the determinants of psychosocial functioning in first-episode psychosis used few predictors. This study examines the effects of multiple cognitive domains and multiple symptoms on psychosocial functioning. Methods: A total of 162 patients with a first-episode psychosis were assessed within 3 months after referral to an early psychosis treatment department. Four psychopathological subdomains (positive and negative symptoms, depression and anxiety) and five subdomains of psychosocial functioning (work/study, relationships, self-care, disturbing behaviour and general psychosocial functioning) were measured. Neurocognitive and social cognitive factors were identified through principal component analyses (PCA) of a 15-measure cognitive battery. Stepwise backward regression models were computed to identify the determinants of psychosocial functioning. Results: The three neurocognitive and four social cognitive factors identified through PCA were largely independent of psychopathology. The strongest associations were between cognitive factors and anxiety. Higher levels of negative symptoms, poor general neurocognition and poor general social cognition showed strongest associations with impaired psychosocial functioning, followed by low verbal processing speed and low emotion processing speed. Together, these factors accounted for 39.4% of the variance in psychosocial functioning. Conclusions: The results suggest that negative symptoms, impaired neurocognition and poor social cognition are related to psychosocial problems in patients with first-episode psychosis. None of the affective or positive symptoms had a marked impact on psychosocial functioning.
To achieve higher engineering efficiency in solar cells, group-DT compound semiconductors, such as silicon (Si) or germanium (Ge), in the form of thin films containing carbon (C) and/or tin (Sn) atoms, are gaining attention as alternatives to poly-silicon crystals. Atomic configurations of C and Sn atoms near the (001) surface of a Si thin film were analyzed by first-principles calculation based on density functional theory (DFT). The results of the analysis are threefold. First, C and Sn atoms are most stable at the first atomic layer of the Si thin film, and the surface does not affect the stability of C or Sn atoms deeper than the fifth layer. Second, C and Sn atoms deeper than the fifth layer do not affect the stability of newly arrived C and Sn atoms at the surface during film growth. The effects of the (001) surface and interacting C and/or Sn atoms on the thermal-equilibrium concentrations of C and Sn in each layer of the Si thin film were evaluated in consideration of the degeneracy of the atomic configurations. Third, in the case of mono-doping, formation energy of C (Sn) at the (001) surface increases with increasing concentration of surface C (Sn). In the case of co-doping at C/Sn concentration ratio of 1:1, the formation energies of C and Sn decrease with increasing surface concentrations of C and Sn. It is concluded from these results that co-doping enhances the incorporation of C and Sn atoms in the Si thin film.
Laboratory sessions are designed to develop the experimental skills and the acquaintance with instruments that may contribute to a successful career in Biochemistry and associated fields. This study is a report on improving a traditional Biochemistry course by devising the laboratory sessions as an inquiry-based environment to develop the students' autonomy to plan, perform, and interpret experiments. We reformulated our Biochemistry laboratory to have three activities that sequentially increase regarding autonomy. We used an autonomy support structure consisting of varying levels of engagement by the student in such aspects as Organizational, Procedural, and Cognitive, gradually transferring to students the responsibility for their decisions within the laboratory. Our results show that students performed better on the less instructed worksheet activities, characterized by a more complex autonomy support, as compared to the activities tightly controlled by worksheet directions. A review of the group lab reports suggests that students showed skills required to work with different levels of autonomy. Thus, this approach has positively supported the students' autonomy, not only mapping their progress through the activities proposed but also encouraging them to make decisions during their experiments and stimulating their ability to think and to plan experiments themselves.
Diaz Encarnacion MM, Warner GM, Cheng J, Gray CE, Nath KA, Grande JP. n-3 Fatty acids block TNF-alpha-stimulated MCP-1 expression in rat mesangial cells. Am J Physiol Renal Physiol 300: F1142-F1151, 2011. First published March 2, 2011; doi:10.1152/ajprenal.00064.2011.-Monocyte chemoattractant protein 1 (MCP-1) is a CC cytokine that fundamentally contributes to the pathogenesis of inflammatory renal disease. MCP-1 is highly expressed in cytokine-stimulated mesangial cells in vitro and following glomerular injury in vivo. Interventions to limit MCP-1 expression are commonly effective in assorted experimental models. Fish oil, an abundant source of n-3 fatty acids, has anti-inflammatory properties, the basis of which remains incompletely defined. We examined potential mechanisms whereby fish oil reduces MCP-1 expression and thereby suppresses inflammatory responses to tissue injury. Cultured mesangial cells were treated with TNF-alpha in the presence of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA); equimolar concentrations of the n-6 fatty acids LA and OA served as controls. MCP-1 mRNA expression was assessed by Northern blotting, and transcriptional activity of the MCP-1 promoter was assessed by transient transfection. The involvement of the ERK and NF-kappa B pathways was evaluated through transfection analysis and the use of the MEK inhibitor U0126. DHA and EPA decreased TNF-alpha-stimulated MCP-1 mRNA expression by decreasing transcription of the MCP-1 gene. DHA and EPA decreased p-ERK expression and nuclear translocation of NF-kappa B, both of which are necessary for TNF-alpha-stimulated MCP-1 expression. Both NF-kappa B and AP-1 sites were involved in transcriptional regulation of the MCP-1 gene by DHA and EPA. We conclude that DHA and EPA inhibit TNF-alpha-stimulated transcription of the MCP-1 gene through interaction of signaling pathways involving ERK and NF-kappa B. We speculate that such effects may contribute to the salutary effect of fish oil in renal and vascular disease.
The Shi-Hang Belt is a Mesozoic tectonic zone and has always been regarded as the boundary between the Yangtze and Cathaysia blocks. It occupies a key tectonic location and attracts considerable attention due to its dynamic formation mechanism. However, its Cenozoic dynamic process is poorly constrained. The Cenozoic activation of the Shi-Hang Belt, as well as its cooling and exhumation, aids in dating the onset time of the formation of the mountain ranges and reveals the deformation process of the South China Block. To uncover the history of its Cenozoic cooling and denudation, apatite fission-track (AFT) thermochronology was applied to batholiths and strata spread across the Shi-Hang Belt in the Hunan Province. Twenty-three samples are dated with ages ranging from 23.6 +/- 1.5 to 45.8 +/- 3.0Ma. Except for two older ages (42.1 +/- 2.6 and 45.8 +/- 3.0Ma), the other ages range from 23 to 36Ma with less variation on both sides of the Chenzhou-Linwu fault. The thermochronological modelling of 15 measured samples demonstrates that rocks rapidly passed through the AFT partial annealing zone to the near surface at different onset times from 36 to 23Ma. The regional AFT cooling pattern is unrelated to the internal structures of the Shi-Hang Belt characterized by a Mesozoic fold-thrust feature. We attribute the Cenozoic exhumation of the Shi-Hang Belt to the dynamic topography of the South China Block, which is related to mantle downwellings and upwellings due to several episodes of quick subduction of the Pacific Plate underneath Eurasia during the Late Cretaceous-early Cenozoic and the Oligocene-early Miocene. The far-field effect of the India-Tibet collision may have contributed to the exhumation of the Shi-Hang Belt.
This paper presents a novel method for the design of analog integrated circuit, making use of fixator-norator pairs for the performance design and biasing design. Fixators are the distinctive tools for setting a critical design parameter at a desired value whereas the pairing norator renders these critical parameters into adequate supporting components, mainly resistors. For analog ICs, active loads and current mirrors serve as supporting components. Hence, the use of fixator-norator pairs may abbreviate as defining the dynamic and static resistance of active loads and current mirrors that should be affirmative with a given design. The proposed methodology is illustrated by the use of a common emitter amplifier, a BJT differential amplifier, a MOS operational amplifier and a three-stage CMOS operational amplifier.
FK506 binding protein (FBBP) 14 belongs to the family of FKBPs. Altered expression of FKBPs are observed in several malignancies. The present study aimed to explore the expression and biological function of FKBP14 in gastric cancer. FKBP14 expression levels in 40 gastric cancer samples and matched control samples were evaluated using quantitative polymerase chain reaction. Cell proliferation was evaluated using Cell Counting kit-8 assay. A cell adhesion and a Transwell assay were performed to detect cell adhesion and invasion. Protein expression was determined using western blot analysis. It was found that FKBP14 expression in gastric cancer tissues was elevated compared with normal tissues. Silencing of FKBP14 expression in the gastric cancer MKN-45 and AGS cell lines, which have a higher expression level of FKBP14 compared with four other gastric cancer cell lines, significantly inhibited cellular proliferation, adhesion and invasion. In addition, the protein levels of proliferating cell nuclear antigen, matrix metalloproteinase 2 and the epithelial-mesenchymal-transition (EMT) markers beta-catenin, Snail1 and Twist were repressed in gastric cancer cells with FKBP14 silenced. In conclusion, FKBP14 may act as an oncogene by suppressing cellular proliferation, adhesion and invasion and EMT in gastric carcinogenesis. FKBP14 may be a diagnosis marker and potential therapeutic target in gastric cancer.
We carried out molecular analyses of the novel flaky skin mutation, Ttc7(fsn-Jic) (a synonym for fsn(Jic)), which we found in a previous study. It was revealed that this mutation involved a genomic in-frame deletion including exons 9 and 10 of the Ttc7 gene, and that the genomic deletion in Ttc7(fsn-Jic) may disrupt the tetratricopeptide repeat-2B domain of the TTC7 protein. Based on a comparison of three Ttc7 mutations, including Ttc7(fsn-J) (a synonym for fsn) and Ttc7(fsn-hea) (a synonym for hea), it was suggested that either exon 9 or exon 10 or both may play a more important role than the other exons of the Ttc7 gene. Ttc7 gene expression analyses using Northern blotting revealed that Ttc7 mRNA is expressed in 11 tissues, except muscle. In conclusion, we confirmed that the Ttc7(fsn-Jic) mutation, as well as the Ttc7(fsn-J) and Ttc7(fsn-hea) mutations, is responsible for abnormal phenotypes observed in various tissues of mice with the flaky skin mutation.
A new microbent in-line microfiber interferometer (MI-MI) is proposed and demonstrated as a compact temperature and current sensor. The MI-MI is capable of generating interference fringes with a high extinction ratio of about 12.0 dB and a free spectral range of 1.9 nm at a wavelength of 1545 nm. When employed as a temperature sensor, a copper wire carrying a direct current is placed against the MI-MI sensor, and the interference fringes of the MI-MI sensor shifts toward the longer wavelength as the heat generated by the copper wire increases. As the temperature increase corresponds linearly to the current, thus the measurement of the current can be extrapolated as well. The sensor has a temperature responsivity of 33.0 pm/degrees C with a linearity of more than 0.97 as well as a current responsitivity of 1.46 degrees C/A(2), and has significant potential for application as a health and warning sensor for electricity generation and distribution grids.
Careful characterization and standardization of the composition of plant-derived food supplements is essential to establish a cause-effect relationship between the intake of that product and its health effect. In this review we follow a specific grape seed extract containing monomeric and oligomeric flavan-3-ols from its creation by Jack Masquelier in 1947 towards a botanical remedy and nutraceutical with proven health benefits. The preparation's research history parallels the advancing insights in the fields of molecular biology, medicine, plant and nutritional sciences during the last 70 years. Analysis of the extract's flavanol composition emerged from unspecific colorimetric assays to precise high performance liquid chromatography - mass spectrometry and proton nuclear magnetic resonance fingerprinting techniques. The early recognition of the preparation's auspicious effects on the permeability of vascular capillaries directed research to unravel the underlying cellular and molecular mechanisms. Recent clinical data revealed a multitude of favorable alterations in the vasculature upon an 8 weeks supplementation which summed up in a health benefit of the extract in healthy humans. Changes in gene expression of inflammatory pathways in the volunteers' leukocytes were suggested to be involved in this benefit. The historically grown scientific evidence for the preparation's health effects paves the way to further elucidate its metabolic fate and molecular action in humans.
Flavivirus genome encodes seven non-structural proteins (NSPs) and these NSPs are believed to be involved in their genomic RNA replication, of which the mechanism is unclear. We find that West Nile virus (WNV) NSPs were capable of self-assembling membranous vesicles in cells, which are composed of the host endoplasmic reticulum membrane integrated with viral NS1 and NS4A, and possibly NS2A. The vesicles can further organize into replication complex (RC)-associated vesicles which combine both the vesicle and predicted RC components. The authentic RC -associated vesicles were observed in cells transfected with infectious WNV cDNA as well as WNV replicon. Further mutational analysis showed that WNV/DENY heterologous NS polyproteins derived from lethal chimeric recombinants produced abnormal vesicles. Site-directed mutation of either NS2A or NS4A, which resulted in failure of viral RNA replication, caused immature vesicles too. These findings reveal molecular composition and assembly of the virus-specific nanomachine and confirm that these structures are used for the viral RNA replication.
Zika virus (ZIKV; family Flaviviridae, genus Flavivirus) is a rapidly expanding global pathogen that has been associated with severe clinical manifestations, including devastating neurological disease in infants. There are currently no molecular clones of a New World ZIKV available that lack significant attenuation, hindering progress toward understanding determinants of transmission and pathogenesis. Here we report the development and characterization of a novel ZIKV reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We generated a two-plasmid infectious clone system from which infectious virus was rescued that replicates in human and mosquito cells with growth kinetics representative of wildtype ZIKV. Infectious clone-derived virus initiated infection and transmission rates in Aedes aegypti mosquitoes comparable to those of the primary isolate and displayed similar pathogenesis in AG129 mice. This infectious clone system provides a valuable resource to the research community to explore ZIKV molecular biology, vaccine development, antiviral development, diagnostics, vector competence, and disease pathogenesis. IMPORTANCE ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barre syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with in vitro and in vivo characteristics similar to those of the primary isolate, providing a critical tool to study ZIKV infection and disease.
Geometric and electrostatic modeling is an essential component in computational biophysics and molecular biology. Commonly used geometric representations admit geometric singularities such as cusps, tips and self-intersecting facets that lead to computational instabilities in the molecular modeling. The present work explores the use of flexibility and rigidity index (FRI), which has a proved superiority in protein B-factor prediction, for biomolecular geometric representation and associated electrostatic analysis. FRI rigidity surfaces are free of geometric singularities. We proposed a rigidity based Poisson -Boltzmann equation for biomolecular electrostatic analysis. Our approaches to surface and electrostatic modeling are validated by a set of 21 proteins. Our results are compared with those of established methods. Finally, being smooth and analytically differentiable, FRI rigidity functions offer excellent curvature analysis, which characterizes concave and convex regions on protein surfaces. Polarized curvatures constructed by using the product of minimum curvature and electrostatic potential is shown to predict potential protein-ligand binding sites. (C) 2016 Elsevier B.V. All rights reserved.
This paper presents a flexible and low-power Read-Out Circuit (ROC) with tunable sensitivity, designed to interface a wide range of commercial resistive pressure sensors for robotic applications. The ROC provides contact detection, monitoring small capacitance variations at low pressure (<100 mbar), and encodes pressure measurement on 8 bit, evaluating resistive variations. Two all-digital circuits implement the conversion of the input resistance and capacitance-to-frequency, exploiting an on-chip ring oscillator as timing reference. A 130 nm RFCMOS prototype (with an active area of 428 x 159 mu m(2)) has a power consumption of 27.2 mu W, for VDD 1 V. Using digital control inputs, the ROC allows a wide range tuning of measurement sensitivity (6.7-46.4 mbar/LSB) and adjustable acquisition time (226.6-461.7 mu s and 648-890 mu s, for contact detection and pressure evaluation, respectively). The read-out time of similar to 1 ms is compatible with human response after touch.
Flexible Hybrid Electronics combine the best characteristics of printed electronics and silicon ICs to create high performance, ultra-thin, physically flexible systems. New static and dynamic tests are being developed to evaluate the performance of these systems. Dynamic radius of curvature and torsional test results are presented for a flexible hybrid electronics system with a FleX Silicon-on-Polymer operational amplifier manufactured in an 180nm CMOS process with 4-levels of metal interconnect mounted on a PET substrate.
In this paper, a new methodology for design of folded cascode (FC) and recycling folded cascode (RFC) OTAs based on 1/f noise reduction is presented. With a new formulation for input referred flicker noise based on Gm/Id characteristic in all operation regions significantly enhance of the noise performance is achieved. Also, this technique leads to the larger DC gain and gain-bandwidth, and phase margin degeneration. The amplifiers were simulated in the 0.18 mu m CMOS technology and the simulation results confirm the theoretical analyses. Proposed design methodology exhibits 50 % reduction of input voltage noise @ 1 Hz for RFC compared to the FC amplifier, without increasing the power consumption and silicon area.
This paper concerns automatic welding system with digital control and is directed to the improvement of certain drive and guide means for a relatively freely carried welding of wheel rim and wheel spider for continuous welding of a part resting on a freely rotatable table. The drive and guide means are carried on the welding head and impart drive to the part while maintaining the welding head properly positioned relative to the part. The system presented is a slightly simplified version of a real automobile wheel-welding system. Although system operation is explained in terms of wheel welding, the design of the system has much in common with other welding operations utilizing the basic industrial automatic welding sequence of Squeeze, Weld, Hold, Release, and Standby with digital control.
This work describes the practical implementation of a Floating-Interleaving Boost Converter (FIBC) for fuel cell applications. The paper aims to validate the concept of digitally-controlled from four-phases-FIBC for fuel cell applications. FIBC exhibits interesting performance in terms of magnetics, input, and output current ripple, part count and distributed power losses. A potential field of application is indeed medium and higher power fuel cell front-end converters, where minimizing input current ripple is significant but also redundancy and reliability are crucial. Actually, this approach covers all these aspects since provide module and device redundancy with real-time and flexible digital control reconfiguration. Relevant aspects related to design; modeling, simulation and experimental verification of 100W, Arduino-controlled, 4-phases-FIBC are treated in this paper.
Recent technological developments in high-dimensional flow cytometry and mass cytometry (CyTOF) have made it possible to detect expression levels of dozens of protein markers in thousands of cells per second, allowing cell populations to be characterized in unprecedented detail. Traditional data analysis by "manual gating" can be inefficient and unreliable in these high-dimensional settings, which has led to the development of a large number of automated analysis methods. Methods designed for unsupervised analysis use specialized clustering algorithms to detect and define cell populations for further downstream analysis. Here, we have performed an up-to-date, extensible performance comparison of clustering methods for high-dimensional flow and mass cytometry data. We evaluated methods using several publicly available data sets from experiments in immunology, containing both major and rare cell populations, with cell population identities from expert manual gating as the reference standard. Several methods performed well, including FlowSOM, X-shift, PhenoGraph, Rclusterpp, and flowMeans. Among these, FlowSOM had extremely fast runtimes, making this method well-suited for interactive, exploratory analysis of large, high-dimensional data sets on a standard laptop or desktop computer. These results extend previously published comparisons by focusing on high-dimensional data and including new methods developed for CyTOF data. R scripts to reproduce all analyses are available from GitHub (https://github.com/lmweber/cytometry-clustering-comparison), and pre-processed data files are available from Flow Repository (FR-FCM-ZZPH), allowing our comparisons to be extended to include new clustering methods and reference data sets. (C) 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.
Purpose of reviewThis review gives an overview of the systems-immunology single-cell proteomic and transcriptomic approaches that can be applied to study primary immunodeficiency. It also introduces recent advances in multiparameter tissue imaging, which allows extensive immune phenotyping in disease-affected tissue.Recent findingsMass cytometry is a variation of flow cytometry that uses rare earth metal isotopes instead of fluorophores as tags bound to antibodies, allowing simultaneous measurement of over 40 parameters per single-cell. Mass cytomety enables comprehensive single-cell immunophenotyping and functional assessments, capturing the complexity of the immune system, and the molecularly heterogeneous consequences of primary immunodeficiency defects. Protein epitopes and transcripts can be simultaneously detected allowing immunophenotype and gene expression evaluation in mixed cell populations. Multiplexed epitope imaging has the potential to provide extensive phenotypic characterization at the subcellular level, in the context of 3D tissue microenvironment.SummaryMass cytometry and multiplexed epitope imaging can complement genetic methods in diagnosis and study of the pathogenesis of primary immunodeficiencies. The ability to understand the effect of a specific defect across multiple immune cell types and pathways, and in affected tissues, may provide new insight into tissue-specific disease pathogenesis and evaluate effects of therapeutic interventions.
Angiosperms and gymnosperms are two major groups of extant seed plants. It has been suggested that gymnosperms lack FLOWERING LOCUS T (FT), a key integrator at the core of flowering pathways in angiosperms. Taking advantage of newly released gymnosperm genomes, we revisited the evolutionary history of the plant phosphatidylethanolamine-binding protein (PEBP) gene family through phylogenetic reconstruction. Expression patterns in three gymnosperm taxa and heterologous expression in Arabidopsis were studied to investigate the functions of gymnosperm FT-like and TERMINAL FLOWER 1 (TFL1)-like genes. Phylogenetic reconstruction suggests that an ancient gene duplication predating the divergence of seed plants gave rise to the FT and TFL1 genes. Expression patterns indicate that gymnosperm TFL1-like genes play a role in the reproductive development process, while GymFT1 and GymFT2, the FT-like genes resulting from a duplication event in the common ancestor of gymnosperms, function in both growth rhythm and sexual development pathways. When expressed in Arabidopsis, both spruce FT-like and TFL1-like genes repressed flowering. Our study demonstrates that gymnosperms do have FT-like and TFL1-like genes. Frequent gene and genome duplications contributed significantly to the expansion of the plant PEBP gene family. The expression patterns of gymnosperm PEBP genes provide novel insight into the functional evolution of this gene family.
Site specific recombinases are invaluable tools in molecular biology, and are emerging as powerful recorders of cellular events in synthetic biology. We have developed a stringently controlled FLP recombinase system in Escherichia coli using an arabinose inducible promoter combined with a weak ribosome binding site. (C) 2016 Elsevier B.V. All rights reserved.
Near-field thermophotovoltaic (NFTPV) devices have received much attention lately as an alternative energy harvesting system, whereby a heated emitter exchanges super-Planckian thermal radiation with a photovoltaic (PV) cell to generate electricity. This work describes the use of a grating structure to enhance the power throughput of NFTPV devices, while increasing the energy conversion efficiency by ensuring that a large portion of the radiation entering the PV cell is above the band gap. The device contains a high-temperature tungsten grating that radiates photons to a room-temperature In0.18Ga0.82Sb PV cell through a vacuum gap of several tens of nanometers. Scattering theory is used along with the rigorous coupled-wave analysis (RCWA) to calculate the radiation energy exchange between the grating emitter and the TPV cell. A parametric study is performed by varying the grating depth, period, and ridge width in the range that can be fabricated using available fabrication technologies. It is found that the power output can be increased by 40% while improving the efficiency from 29.9% to 32.0% with a selected grating emitter as compared to the case of a flat tungsten emitter. Reasons for the enhancement are found to be due to the enhanced energy transmission coefficient close to the band gap. This work shows a possible way of improving NFTPV and sheds light on how grating structures interact with thermal radiation at the nanoscale.
The reservoir diagenetic process and the petroleum charge histories of the Cretaceous Bashijiqike Formation (K(1)bs) in the Kuqa Depression, Tarim Basin were studied using an integrated petrographic, fluid inclusion, reservoir diagenesis and basin modeling approach. A suite of techniques were used in the investigation including optical microscopy, scanning, electron microscope (SEM), X-ray diffraction (XRD), fluorescence spectroscopy, microthermometry, and Laser Raman microspectroscopy. The workflow comprises petrographic characterization of the reservoir sandstone, identification of fluid inclusion assemblages, and construction of the diagenetic history of the reservoir sandstone with reference to the hydrocarbon charge and emplacement. Key diagenetic events identified include quartz overgrowths, early calcite cementation, dolomite cementation, alteration of kaolinite, bitumen emplacement, micro quartz and ankerite cementation. The first diagenetic event was characterized by quartz overgrowths and followed by calcite and dolomite cementation. Kaolinite and ankerite cementation were the last diagenetic events, coincided with hydrocarbon charge and emplacement. Three episodes of hydrocarbon charge and emplacement have been recorded by the diagenetic products and fluid inclusions in the K1bs Formations: (1) the first episode of oil charge was recorded in the early calcite cement, and were trapped around at 18 Ma; (2) the second and third episodes of hydrocarbon charge were recorded in the telo-diagenetic ankerite, and were trapped around at 4-6 Ma. The timing of oil emplacement determined from fluid inclusion homogenization temperature and basin modeling is consistent with the formation order of the diagenetic minerals. This study has thus demonstrated that integrated analysis of fluid inclusion and reservoir diagenesis can be an effective tool for determining hydrocarbon charge and emplacement history. (C) 2017 Elsevier B.V. All rights reserved.
The quantitative grain fluorescence and quantitative grain fluorescence on extract have become effective approaches in the analysis of hydrocarbon evolution in clastic reservoirs recently. The cutoff threshold for differentiating current/paleo-oil and water zones is crucial to reconstruct accurately hydrocarbon accumulation history. However, the absence of theoretical study on the cutoff threshold in the carbonate reservoir has precluded their application and development. In this paper, we attempted to investigate the cutoff threshold by analyzing the quantitative grain fluorescence and quantitative grain fluorescence on extract parameters and spectra of the cores and natural carbonate outcrop samples in known current/paleo-oil and water zones revealed by the frequency of oil inclusions, formation test, logging analysis, etc. Based on this, the hydrocarbon charging history of the Suqiao Buried-hill Zone, Bohai Bay Basin, eastern China was reconstructed using the gotten threshold. Results show that the carbonate minerals fluorescing will lead to a higher cutoff threshold of quantitative grain fluorescence index value in the carbonate reservoir, while the threshold of quantitative grain fluorescence on extract intensity value is coincident with the corresponding value in the clastic reservoir. The quantitative grain fluorescence and quantitative grain fluorescence on extract data have unraveled a complicated hydrocarbon accumulation history in Suqiao Buried-hill Zone including oil charging before gas and paleo-oil loss due to the tectonism. The ascertained cutoff threshold in this study is of great significance for reconstructing accurately and effectively the complicated hydrocarbon charging history in the carbonate reservoir, which provides significant models for future petroleum exploration.
The design of tailor-made gelators has attracted tremendous level of attention for the fabrication of novel nanogels with responsive characteristics. Exploiting the gel properties of nanocellulose (NC) because of its abundance, sustainability and renewability, we reported the fabrication of a fluorescent hydrogel based on S,N-codoped Graphene Quantum Dots (S,N-GQDs) acting as luminophore and sensitizer. The incorporation of the GQDs into the hydrogel resulted in a significant fluorescence intensity enhancement if compared to GQ.D solutions. In conjunction with recent efforts in the applicability of optical responsive gels, a simple method based on the selectively sensing ability of the GQD/NC hydrogel towards 2,4,5-trichlorophenol (TCP) through the fluorescence enhancement is disclosed. The validity of this strategy is demonstrated with the analysis of TCP in red wine and environmental water samples. (C) 2017 Elsevier B.V. All rights reserved.
A digital control method combining primary-side sensing, observer and model-predictive-control techniques is proposed. A conventional isolated Flyback converter is chosen for demonstrating the method. The only measured signal is the drain-source voltage over the switch. Following a procedure of signal processing, state estimation and constraint problem formulation, the controller determines the optimal duty cycle ratio. The advantages of the proposed method include minimal overshoot and fast stabilization, converter state restriction, and measurement network simplification.
The expression of antigens in transgenic plants has increasingly been used as an alternative to the classical methodologies for the development of experimental vaccines, and it remains one of the real challenges in this field to use transgenic plant-based vaccines effectively as feedstuff additives. We report herein the development of a new oral immunization system for foot and mouth disease with the structural protein VP1 of the foot and mouth disease virus (FMDV) produced in transgenic Stylosanthes guianensis cv. Reyan II. The transgenic plantlets were identified by polymerase chain reaction (PCR), Southern blotting, and northern blotting; and the production of VP1 protein in transgenic plants was confirmed and quantified by western blotting and enzyme-linked immunosorbent assays (ELISA). Six transformed lines were obtained, and the level of the expressed protein was 0.1-0.5% total soluble protein (TSP). Mice that were orally immunized using studded feedstuff mixed with desiccated powder of the transgenic plants developed a virus-specific immune response to the structural VP1 and intact FMDV particles. To our knowledge, this is the first report of transgenic plants expressing the antigen protein of FMDV as feedstuff additives that has demonstrated the induction of a protective systemic antibody response in animals. These results support the feasibility of producing edible vaccines from transgenic forage plants, and provide proof of the possibility of using plant-based vaccines as feedstuff additives.
Previous research has provided qualitative evidence for overlap in a number of brain regions across the subjective value network (SVN) and the default mode network (DMN). In order to quantitatively assess this overlap, we conducted a series of coordinate-based meta-analyses (CBMA) of results from 466 functional magnetic resonance imaging experiments on task-negative or subjective value-related activations in the human brain. In these analyses, we first identified significant overlaps and dissociations across activation foci related to SVN and DMN. Second, we investigated whether these overlapping subregions also showed similar patterns of functional connectivity, suggesting a shared functional subnetwork. We find considerable overlap between SVN and DMN in subregions of central ventromedial prefrontal cortex (cVMPFC) and dorsal posterior cingulate cortex (dPCC). Further, our findings show that similar patterns of bidirectional functional connectivity between cVMPFC and dPCC are present in both networks. We discuss ways in which our understanding of how subjective value (SV) is computed and represented in the brain can be synthesized with what we know about the DMN, mind-wandering, and self-referential processing in light of our findings.
In small, selected samples, an approach combining resting-state functional connectivity MRI and multivariate pattern analysis has been able to successfully classify patients diagnosed with unipolar depression. Purposes of this investigation were to assess the generalizability of this approach to a large clinically more realistic sample and secondarily to assess the replicability of previously reported methodological feasibility in a more homogeneous subgroup with pronounced depressive symptoms. Two independent subsets were drawn from the depression and control cohorts of the BiDirect study, each with 180 patients with and 180 controls without depression. Functional connectivity either among regions covering the gray matter or selected regions with known alterations in depression was assessed by resting-state fMRI. Support vector machines with and without automated feature selection were used to train classifiers differentiating between individual patients and controls in the entire first subset as well as in the subgroup. Model parameters were explored systematically. The second independent subset was used for validation of successful models. Classification accuracies in the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In the subgroup with higher depression severity, three out of 90 models performed significantly above chance (60.8-61.7% at independent validation). In conclusion, common classification methods previously successful in small homogenous depression samples do not immediately translate to a more realistic population. Future research to develop diagnostic classification approaches in depression should focus on more specific clinical questions and consider heterogeneity, including symptom severity as an important factor.
The present study used functional near-infrared spectroscopy (fNIRS) to measure 5- to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-month-old infants watched video clips of Peek-a-Boo (social signal) performed by an anime character (AC) or a human, and hand movements without social signal performed by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while behaviors including looking time were recorded simultaneously. NIRS data showed that infants hemodynamic responses in the PFC generally decreased due to these stimuli, and the decrease was most prominent in the frontopolar (FP), covering medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC. Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly, behavioral data revealed significantly longer looking times when Peek-a-Boo was performed by an AC than by a human. No significant difference between Peek-a-Boo and non-Peek-a-Boo conditions was observed in either measure. These findings indicate that infants at this age may prefer stimuli with more salient features, which may be more effective in attracting their attentions. In conjunction with our previous findings on responses to self-name calling in infants of similar age, we hypothesize that the dynamic function of the MPFC and its vicinity (as part of default mode network (DMN): enhanced by self-focused stimuli, attenuated by externally focused stimuli), which is consistently observed in adults, may have already emerged in 5- to 6-month-old infants.
Background: Foamy viruses (FVs) of the Spumaretrovirinae subfamily are distinct retroviruses, with many features of their molecular biology and replication strategy clearly different from those of the Orthoretroviruses, such as human immunodeficiency, murine leukemia, and human T cell lymphotropic viruses. The FV Gag N-terminal region is responsible for capsid formation and particle budding via interaction with Env. However, the critical residues or motifs in this region and their functional interaction are currently ill-defined, especially in non-primate FVs. Results: Mutagenesis of N-terminal Gag residues of feline FV (FFV) reveals key residues essential for either capsid assembly and/or viral budding via interaction with the FFV Env leader protein (Elp). In an in vitro Gag-Elp interaction screen, Gag mutations abolishing particle assembly also interfered with Elp binding, indicating that Gag assembly is a prerequisite for this highly specific interaction. Gradient sedimentation analyses of cytosolic proteins indicate that wild-type Gag is mostly assembled into virus capsids. Moreover, proteolytic processing of Gag correlates with capsid assembly and is mostly, if not completely, independent from particle budding. In addition, Gag processing correlates with the presence of packaging-competent FFV genomic RNA suggesting that Pol encapsidation via genomic RNA is a prerequisite for Gag processing. Though an appended heterogeneous myristoylation signal rescues Gag particle budding of mutants unable to form capsids or defective in interacting with Elp, it fails to generate infectious particles that co-package Pol, as evidenced by a lack of Gag processing. Conclusions: Changes in proteolytic Gag processing, intracellular capsid assembly, particle budding and infectivity of defined N-terminal Gag mutants highlight their essential, distinct and only partially overlapping roles during viral assembly and budding. Discussion of these findings will be based on a recent model developed for Gag-Elp interactions in prototype FV.
Mobile technologies are increasingly adopted by information intensive organizations such as public police corporations to support the tasks of its employees, for information management and innovation. However, because police organizations are government organizations, technology decisions are largely made by managers and politicians with budget being a key factor. Therefore, whether the technologies adopted are suitable for police tasks, and if they enhance performance, is generally not assessed. The aim of this research is to establish if mobile technologies support police tasks, and if Tablet PCs especially are suitable for specialist police tasks of the Criminal Investigators and Sexual Offence and Child Abuse Units. Guided by an interpretive paradigm and the theory of task technology fit, this research explores the use of Tablet PCs by the two police units for improved performance. Because information is critical for police tasks, data collected via focus groups establishes the impact of these technologies on case investigations, information management, and the performance of these units with the use of Tablet PCs. The contribution this study makes to mobile information systems is that if technology dimensions are suitable for information based tasks, the outcome is virtualization of processes through which improved performance is achieved due to reduced costs, transparency, teamwork, and quick and informed decisions. The findings of this research can be used by police organizations, as well as by other organizations, for effective implementation of mobile technologies.
Fiber optical gyro (FOG) is a kind of solid-state optical gyroscope with good environmental adaptability, which has been widely used in national defense, aviation, aerospace and other civilian areas. In some applications, FOG will experience environmental conditions such as vacuum, radiation, vibration and so on, and the scale-factor performance is concerned as an important accuracy indicator. However, the scale-factor performance of FOG under these environmental conditions is difficult to test using conventional methods, as the turntable can't work under these environmental conditions. According to the phenomenon that the physical effects of FOG produced by the sawtooth voltage signal under static conditions is consistent with the physical effects of FOG produced by a turntable in uniform rotation, a new method for the scale-factor performance test of FOG without turntable is proposed in this paper. In this method, the test system of the scale-factor performance is constituted by an external operational amplifier circuit and a FOG which the modulation signal and Y waveguied are disconnected. The external operational amplifier circuit is used to superimpose the externally generated sawtooth voltage signal and the modulation signal of FOG, and to exert the superimposed signal on the Y waveguide of the FOG. The test system can produce different equivalent angular velocities by changing the cycle of the sawtooth signal in the scale-factor performance test. In this paper, the system model of FOG superimposed with an externally generated sawtooth is analyzed, and a conclusion that the effect of the equivalent input angular velocity produced by the sawtooth voltage signal is consistent with the effect of input angular velocity produced by the turntable is obtained. The relationship between the equivalent angular velocity and the parameters such as sawtooth cycle and so on is presented, and the correction method for the equivalent angular velocity is also presented by analyzing the influence of each parameter error on the equivalent angular velocity. A comparative experiment of the method proposed in this paper and the method of turntable calibration was conducted, and the scale-factor performance test results of the same FOG using the two methods were consistent. Using the method proposed in this paper to test the scale-factor performance of FOG, the input angular velocity is the equivalent effect produced by a sawtooth voltage signal, and there is no need to use a turntable to produce mechanical rotation, so this method can be used to test the performance of FOG at the ambient conditions which turntable can not work.
This paper presents a novel CMOS folded cascode operational amplifier that leads to high PSRR and provides gain nearly equal to that of a two stage op-amp. The proposed design is implemented in GPDK 0.18 m CMOS technology. This op amp uses a folded cascode structure in the output stage combined with the differential amplifier having PMOS input transistors to achieve good input common mode range and lower flicker noise. It has an important feature that it allows the input common mode level close to supply voltage. The proposed topology improves the PSRR of op-amp which can be used for LDO applications. Simulations using Cadence under 1.8 V show a DC gain of 72.0404 dB and a phase margin of 62.4636 degree at a unity gain bandwidth of 13.33 MHz with the power consumption smaller than 0.13 mW along with a PSRR of 72.0966 dB. The layout of the design shows that the area acquired on the chip is approximately equal to 8897.27 mu m(2).
An amplifier and capacitor sharing technique with applications in a multiplying digital-to-analog converter (MDAC) of CMOS pipelined ACDC is presented. The amplifier used in this implementation is a recycling amplifier based on the folded cascode operational amplifier with gain improved using positive feedback. The operational amplifier designed in 0.35um CMOS process show a simulated gain of 75 dB, frequency bandwidth of 95 MHz, phase margin of 75 degree and power consumption of 0.75 mW on a 1.8V power supply. The simulation results in MDAC of 1.5 bits show that this configuration can be used in a implementation of a 10 bits 10 MSample/s CMOS pipelined ADC with 2.8 mW power consumption (analog part) on a 1.8V supply.
We screened the gene that encodes tetratricopeptide repeat domain 29 (Ttc29) in the maturing rat testis. Gene expression was determined by Northern blotting of 7-week-old rat testes, and a strong signal was detected close to the 18S rRNA band in addition to two weak high-molecular-weight signals. In situ hybridization revealed that Ttc29 was expressed primarily in the spermatocytes. We evaluated the effect of gonadotropin on Ttc29 expression using hypophysectomized rats. The pituitary was removed from 3-week-old rats, gonadotropin was injected at 5 weeks, and Ttc29 expression was determined at 7 weeks. Although testicular development and hyperplasia of interstitial cells were observed following chorionic gonadotropin treatment after hypophysectomy, Ttc29 expression was upregulated by treatment with follicle-stimulating hormone. Ttc29 encodes axonemal dynein, a component of sperm flagella. Taken together, these data indicate that axonemal dynein expression starts in the spermatocytes and is regulated by follicle-stimulating hormone.
Recent food safety scandals in Taiwan have caused panic among the Taiwanese public and have become a primary concern because foods were discovered containing a dangerous amount of illegal additives. The theory of planned behavior (TPB) model is extremely useful for predicting people's food choices and consumption habits. This study included an examination of the public attention to and perceived credibility of mass media food safety information and the perceived risk as background factors in the extended TPB model to predict public intention to take precautions to avoid consuming foods with additives. The empirical results of structural equation modeling analysis with 487 useful samples revealed that the extended TPB model has an increased explanatory power relative to the original model regarding the intention of the public in Taiwan to take precautions to avoid consuming foods that contain additives. In addition to attitudes toward and perceived behavioral control of the consumption of food with additives, the impact of risk perceptions plays an important role in determining an individual's intention to take precautions to avoid consuming foods that contain additives. The attention of an individual to food additive scandal news and their perceived risk determine their attitude toward consuming food with additives. An individual's perceived risk of consuming food with additives was determined through the attention paid to food additive scandal news and the perceived credibility of such news. (C) 2017 Elsevier Ltd. All rights reserved.
The diagnosis of food allergy is challenging due to different immunologic mechanisms and diversity of symptoms. An open or double-blinded oral food challenge (OFC) was performed on 391 children (aged 0.2-16.9 years) with suspected cow's milk (n = 266) or wheat allergy (n = 125) to characterize immediate, delayed, and transient symptoms, and to evaluate the role of earlier food-related symptoms and immunoglobulin E (IgE)-[pmediated sensitization for the OFC outcome. The OFC resulted in an immediate positive reaction in 38% (n = 148) and a delayed positive reaction in 21% (n = 81) of the 391 children. Transient reactions, the majority of which were localized skin reactions, were seen in almost third (n = 50) of the patients with a negative OFC result (n = 162/391). Immediate localized skin reactions were more common during the milk challenge (p = 0.010), whereas immediate lower respiratory tract symptoms (p = 0.001) were more common during the wheat challenge. Although 14% (n = 21) of those with an immediate reaction received i.m. adrenalin as a treatment of the reaction, there were no life-threatening events. Multivariate analyses revealed that independent risk factors for the immediate OFC outcome were earlier moderate-to-severe immediate food-related reactions, marked IgE-mediated sensitization to the suspected food, and in case of wheat, age <12 months. The accuracy of OFCs can be enhanced without increasing the risk of serious allergic reactions by taking into account earlier food-related symptoms and the level of IgE-mediated sensitization, by refining our knowledge of transient nonspecific reactions, and by applying standardized OFC protocols with over-one-day challenges.
This study examines the time to re-report following the close of a maltreatment investigation for cases involving food neglect. Data on families of children 0 to 17 involved in Child Protective Services (CPS) investigations from a merger of the 2010 cohort of the National Survey of Child and Adolescent Well-Being (NSCAW II) and the National Child Abuse and Neglect Data System (NCANDS) were used (n = 3580). More than half of the families had a history of CPS involvement, a third received CPS services, and one-in-ten families had their child place in out of-home care following an investigation. After controlling for other types of maltreatment allegations and multiple covariates, families investigated for food neglect had a greater chance of being re-reported for a subsequent CPS investigations in a shorter length of time than families without an allegation of food neglect. While only a small percentage of families had a food neglect allegation, problems adequately feeding a child - whether due to severe poverty, inattentiveness, or abusive negligence - placed a family at a higher risk of a future CPS investigation. (C) 2016 Elsevier Ltd. All rights reserved.
Food protein-induced enterocolitis (FPIES) is a non-IgE cell-mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
Recent attention to communities "localizing" food systems has increased the need to understand the perspectives of people working to foster collaboration and the eventual transformation of the food system. University Cooperative Extension Educators (EEs) increasingly play a critical role in communities' food systems across the United States, providing various resources to address local needs. A better understanding of EEs' perspectives on food systems is therefore important. Inspired by the work of Stevenson, Ruhf, Lezberg, and Clancy on the social food movement, we conducted national virtual focus groups to examine EEs' attitudes about how food system change should happen, for what reasons, and who has the resources, power, and influence to effect change. The institutions within which EEs are embedded shape their perceptions of available resources in the community, including authority and power (and who holds them). These resources, in turn, structure EEs' goals and strategies for food system change. We find that EEs envision working within the current food system: building market-centric alternatives that address inequity for vulnerable consumers and producers. EEs bring many resources to the table but do not believe they can influence those who have the authority to change policy. While these findings could suggest EEs' limited ability to be transformative change agents, EEs can potentially connect their efforts with new partners that share perceptions of food system problems and solutions. As EEs increasingly engage in food system work and with increasingly diverse stakeholders, they can access alternative, transformational frames within which to set goals and organize their work.
Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy. Published by Elsevier Inc on behalf of the American College of Allergy, Asthma & Immunology.
State statutes regarding the best interests of the child (BIC) in deciding disputed custody were reviewed and independently coded with respect to three issues (i) the child's preference and any limits (ii) parental alienation and (iii) psychological maltreatment. Results revealed that many states allowed for the child's preferences to be considered and none qualified that preference when undue influence has occurred; parental alienation as a term was not found in any state statutes but 70% of the states included at least one BIC factor relevant to its core construct of the parent supporting the child's relationship to the other parent; and many states included a history of domestic violence or child abuse but only three states explicitly mentioned psychological maltreatment. These findings highlight yet another way in which the BICS factors lack specificity in ways that could negatively impact children caught in their parents' conflict.
This review was prepared for the American Society of Mechanical Engineers Lissner Medal. It specifically discusses research performed in the Orthopaedic Biomechanics Laboratories on pediatric cranial bone mechanics and patterns of fracture in collaboration with the Forensic Anthropology Laboratory at Michigan State University. Cranial fractures are often an important element seen by forensic anthropologists during the investigation of pediatric trauma cases litigated in courts. While forensic anthropologists and forensic biomechanists are often called on to testify in these cases, there is little basic science developed in support of their testimony. The following is a review of studies conducted in the above laboratories and supported by the National Institute of Justice to begin an understanding of the mechanics and patterns of pediatric cranial bone fracture. With the lack of human pediatric specimens, the studies utilize an immature porcine model. Because much case evidence involves cranial bone fracture, the studies described below focus on determining input loading based on the resultant bone fracture pattern. The studies involve impact to the parietal bone, the most often fractured cranial bone, and begin with experiments on entrapped heads, progressing to those involving free-falling heads. The studies involve head drops onto different types and shapes of interfaces with variations of impact energy. The studies show linear fractures initiating from sutural boundaries, away from the impact site, for flat surface impacts, in contrast to depressed fractures for more focal impacts. The results have been incorporated into a "Fracture Printing Interface (FPI)," using machine learning and pattern recognition algorithms. The interface has been used to help interpret mechanisms of injury in pediatric death cases collected from medical examiner offices. The ultimate aim of this program of study is to develop a " Human Fracture Printing Interface" that can be used by forensic investigators in determining mechanisms of pediatric cranial bone fracture.
Rapid and progressive advances in molecular biology techniques and the advent of Next Generation Sequencing (NGS) have opened new possibilities for analyses also in the identification of entomological matrixes. Insects and other arthropods are widespread in nature and those found at a crime scene can provide a useful contribution to forensic investigations. Entomological evidence is used by experts to define the postmortem interval (PMI), which is essentially based on morphological recognition of the insect and an estimation of its insect life cycle stage. However, molecular genotyping methods can also provide an important support for forensic entomological investigations when the identification of species or human genetic material is required. This case study concerns a collection of insects found in the house of a woman who died from unknown causes. Initially the insects were identified morphologically as belonging to the Pediculidae family, and then, human DNA was extracted and analyzed from their gastrointestinal tract. The application of the latest generation forensic DNA assays, such as the Quantifiler (R) Trio DNA Quantification Kit and the HID-Ion AmpliSeq (TM) Identity Panel (Applied Biosystems (R)), individuated the presence of human DNA in the samples and determined the genetic profile. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
For more than two decades, conventional wisdom about the high-profile day care cases of the 1980s and early 1990s suggests all were modern-day witch hunts, based on false allegations made by highly suggestible children during an era when society was gripped by a "believe the children" hysteria. Author Ross Cheit refutes conventional wisdom by conducting an exhaustive examination of original data from dozens of cases bearing the witch hunt label. He concludes there was no witch-hunt epidemic, finding substantial evidence of sexual abuse in nearly every case he reviewed, contradicting the assertions made about those cases by what he calls the witch-hunt narrative. Cheit examines the legacy of the witch-hunt narrative and contends its exaggerated claims about the suggestibility of children have had a negative effect on the credibility of children today who allege being sexually abused. This writer examines Cheit's conclusions in light of her own experience as a career prosecutor of crimes against children as well as her involvement in a high-profile day care case encompassed by the witch-hunt narrative. Setting the record straight about these cases is important not only for the sake of historical accuracy and intellectual honesty but also because the witch-hunt narrative's unwarranted assertions about the suggestibility of children have had a negative effect on society's perception of their credibility. Bringing public attention to the fallacies of the witch-hunt narrative and shining a light on questionable tactics used by some in academia to support their contention that all children are highly suggestible will ultimately serve to strengthen society's ability to believe a child who discloses sexual abuse.
We comment on The Witch-Hunt Narrative (TWHN) by Cheit. As its first hypothesis, TWHN argues that most of the famous ritual child abuse cases of the 1980s and 1990s were not really witch-hunts at all. In response, we criticize the TWHN definition of a witch-hunt as overly narrow and idiosyncratic. Based on the scholarly literature, we propose 10 criteria for identifying a witch-hunt. We rate four well-known ritual child abuse cases with these criteria and show they were classic witch-hunts. As its second hypothesis, TWHN argues that most defendants in child ritual abuse cases were guilty or probably guilty. In response, we point out many instances in which TWHN has omitted or mischaracterized important facts or ignored relevant scientific information running contrary to its hypotheses. We conclude that TWHN is often factually inaccurate and tends to make strong assertions without integrating relevant scholarly and scientific information. Scholars should approach the book with caution.
Clinical forensic medicine (CFM), as a single discipline, encompasses a number of areas of medico-legal practice including injury interpretation, management of sexual and physical assault cases (both adult and child; alleged victim and offender), mental health issues, traffic medicine, custodial medicine and toxicology. The cases are usually alive but in some jurisdictions the forensic practitioner also engages in death investigation with some undertaking autopsies. During the last 20-30 years, the discipline has fragmented with areas being hived off to other medical specialist disciplines and, importantly, to nurses. Any user of forensic services wants the best value for money particularly when under financial pressure. To this end, governments have sought savings through privitisation of services and/or the utilisation of less qualified personnel to undertake some or all of the tasks. This places CFM at a crossroads. To ensure survival, the discipline needs to reconsider its direction and performance, convince stakeholders of its relevance and importance, and lift its profile within the legal, academic and medical world. It will need to think outside the square, place greater emphasis on the 'clinical' and relinquish those activities that are better undertaken by less expensive and qualified personnel. The establishment of meaningful research and academic centres are essential. The loss of and/or failure to grow CFM will result in the loss of a skills base and the subsequent potential for the miscarriages of justice. (C) 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Retinal hemosiderin deposition is a histologic indicator of sustained hemorrhage but cannot be used to precisely estimate the elapsed time since an episode of trauma. A 5-month-old male infant was admitted to hospital after acute deterioration. Examination revealed encephalopathy, subdural hematomas, and retinal hemorrhages consistent with abusive head trauma (AHT). At the age of 3, he was readmitted to hospital with spontaneous osteopenic fracture of the right femur. The patient deteriorated and died after unsuccessful resuscitation. Ophthalmopathological investigation showed atrophy of the retina and optic nerve and hemosiderin deposition in both eyes. Retinal hemosiderin deposition is currently generally assumed to disappear within 6-8 weeks after the occurrence of hemorrhage in AHT. This case report describes an infant with bilateral retinal hemosiderin depositions due to hemorrhages sustained from AHT occurring 32 months prior to death. Implications of this finding for the interpretation of retinal hemosiderin depositions in AHT are discussed.
Case files from the Cook County Medical Examiner's Office from 2007 to 2012 were reviewed to analyze homicides due to physical child abuse in children <3 years old. Fatal cases mostly involved younger subjects. Intracranial injuries were the leading cause of death, while death due to extracranial injuries was uncommon. Eyes were involved in most of the cases. Spinal cord was involved in about 1/3 of the cases, mostly in the thoracic area. In some cases, previous injuries were present. There were significant differences in the pattern of injuries between age groups. Subjects showing signs of impact to the head and subjects with no evidence of an impact showed no significant difference in internal injuries. The association of multiple injuries is highly suggestive of child abuse. In suspected child abuse, a postmortem examination including neuropathological, ophthalmological, and radiological information should be always evaluated, together with investigative reports and the medical history.
Since its introduction, colonoscopy has played an important role as a diagnostic, therapeutic, and screening tool. In general, colonoscopy is regarded as a safe procedure, but complications may occur. The most dreaded of these complications is colonic perforation. Bacteremia postprocedure may occur, and although it is not uncommon, it rarely results in clinically significant complications. Patients with IBD (inflammatory bowel disease) are a high-risk population for bacteremia, which may leads to bowel wall overstepping by the bacteria. With regard to that, we report a fatal case of gas gangrene complicating colonoscopy polypectomy without bowel perforation in a healthy adult. To the best of our knowledge, only two other cases of retroperitoneal gas gangrene associated with colonoscopy polypectomy without bowel perforation have been described in international literature, but none of which was completed by a molecular biology analysis.
Skull fracture characteristics are associated with loading conditions (such as the impact point and impact velocity) and could provide indication of abuse or accident-induced head injuries. However, correlations between fracture characteristics and loading conditions in infant and toddler are ill-understood. A simplified computational model representing an infant head was built to simulate skull responses to blunt impacts. The fractures were decided through a first principal strain-based element elimination strategy. Simulation results were qualitatively compared with test data from porcine heads. This simplified model well captured the fracture pattern, initial fracture position, and direction of fracture propagation. The model also very well described fracture characteristics found in studies with human infant cadaveric specimens. A series of parametric studies was conducted, and results indicated that the parameters studied had substantial effects on fracture patterns. Additionally, the jagged shapes of sutures were associated with strain concentrations in the skull.
The international prevalence of legal high drugs necessitates the development of a method for their detection and identification. Herein, we describe the development and validation of a tetraplex multiplex real-time polymerase chain reaction (PCR) assay used to simultaneously identify morning glory, jimson weed, Hawaiian woodrose, and marijuana detected by high-resolution melt using LCGreen Plus((R)). The PCR assay was evaluated based on the following: (i) specificity and selectivityprimers were tested on DNA extracted from 30 species and simulated forensic samples, (ii) sensitivityserial dilutions of the target DNA were prepared, and (iii) reproducibility and reliabilitysample replicates were tested and remelted on different days. The assay is ideal for cases in which inexpensive assays are needed to quickly detect and identify trace biological material present on drug paraphernalia that is too compromised for botanical microscopic identification and for which analysts are unfamiliar with the morphology of the emerging legal high species.
A verification methodology is described and evaluated to formally determine uncertain linear systems stability in digital controllers with considerations to the implementation aspects. In particular, this methodology is combined with the digital-system verifier (DSVerifier), which is a verification tool that employs Bounded Model Checking based on Satisfiability Modulo Theories to check the stability of digital control systems with uncertainty. DSVerifier determines the control system stability, considering all the plant interval variation set, together with the Finite Word-length (FWL) effects in the digital controller implementation; DSVerifier checks the robust non-fragile stability of a given closed-loop system. The proposed methodology and respective tool are evaluated considering non-fragile control examples from literature. Experimental results show that the approach used in this study is able to foresee fragility problems in robust controllers, which could be overlooked by other existing approaches due to underestimating of FWL effects.
This work outlines an equation-based formulation of a digital control program and transducer interacting with a continuous physical process, and an approach using the Coq theorem prover for verifying the performance of the combined hybrid system. Considering thermal dynamics with linear dissipation for simplicity, we focus on a generalizable, physically consistent description of the interaction of the real-valued temperature and the digital program acting as a thermostat. Of interest in this work is the discovery and formal proof of bounds on the temperature, the degree of variation, and other performance characteristics. Our approach explicitly addresses the need to mathematically represent the decision problem inherent in an analog-to-digital converter, which for rare values can take an arbitrarily long time to produce a digital answer (the so-called Buridan's Principle); this constraint ineluctably manifests itself in the verification of thermostat performance. Furthermore, the temporal causality constraints in the thermal physics must be made explicit to obtain a consistent model for analysis. We discuss the significance of these findings toward the verification of digital control for more complex physical variables and fields.
Catalytic oxidation at ambient temperature has drawn wide attention as a new promising method of air cleaning, converting hazardous materials into non-hazardous ones. However, limited information is available regarding catalytic filter performance/characteristics under real operating conditions, especially on service efficiency and byproducts. Also, no practical scale-up method/evidence for filter performance evaluation is currently available to scale-up laboratory results to real application conditions. These limitations and knowledge gaps prevent building owners/designers from adopting this new promising technique in their commercial/industrial applications. The present study conducted experiments from small-scale to full-scale chamber tests which challenged a developed catalytic filter under realistic conditions. Formaldehyde was selected for approach demonstration due to its indoor ubiquitousness and criticality for human health even at low-levels. Results showed that the competition level for reaction sites in filter media had a crucial role in the performance for formaldehyde abatement, a high initial (77%; under no competing pollutants) to a typical stable level (23-32%), depending on the coexistence of other pollutants and moisture in the air, that the employment of this type of filter might generate byproducts (opposite to previous literature reports), and that small-scale column tests represented a good indication for large-scale filter performance as a practical screening method. (C) 2017 Elsevier B.V. All rights reserved.
AIM: To study the expression of collagen I and transcription factor specificity protein 1 (Sp1), a transforming growth factor-beta 1 (TGF-beta 1) downstream target, and reveal the impact of the TGF-beta 1-Sp1 signaling pathway on collagen remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were randomly divided into normal control, form deprivation myopia (FDM), and self-control groups. FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment; then, changes in refractive power and axial length were measured. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia, and the relationship between collagen I and Sp1 levels was analyzed. RESULTS: In the FDM group, the refractive power was gradually changed (from 2.09 +/- 0.30 D at week 0 to -1.23 +/- 0.69 D, -4.17 +/- 0.59 D, -7.07 +/- 0.56 D, and -4.30 +/- 0.58 D at weeks 2, 4, 6, and 1wk after 4wk, respectively; P<0.05), indicating deepening of myopia. The axial length was increased (from 5.92 +/- 0.39 mm at week 0 to 6.62 +/- 0.36 mm, 7.30 +/- 0.34 mm, 7.99 +/- 0.32 mm, and 7.41 +/- 0.36 mm at weeks 2, 4, 6, and 1wk after 4wk; P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups (P<0.05), and the reduction was eye-coverage time-dependent. Furthermore, correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed. CONCLUSION: Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagen synthesis/degradation during myopic sclera remodeling, suggesting that TGF-beta 1 signaling plays a role in the development and progression of myopia.
Trinidad and Tobago is an oil exporting small island developing state (SIDS) with a 0.12% contribution to global emissions and with important socio-economic challenges. It has producer, electricity and transport fuel subsidies. It is at an interesting juncture in subsidy reform: the government faces the embeddedness of distributive justice norms that are contested by fiscal prudence and environmental stewardship norms. The value of the paper is twofold. First it develops a subsidy intractability framework to explain reform global narratives that highlights: the power of agents, the nature of contested economic, justice and environmental norms and the availability of mechanisms for reform. Second, this framework is used to explain reform narratives and trajectories in Trinidad and Tobago using data from public documents and from a unique elite survey of former and present heads of state, politicians, policy makers and stakeholders. Even in conditions of falling oil prices and national revenue and pressures to reduce emissions, where redistributive justice arguments are heavily embedded in public discourses, those aspects of the subsidy that have developmental or distributive justice goals are more intractable. The results of the study have implications for carbon emission reduction strategies in developing states with fossil fuel reserves.
The control system of moving mirror scanning is an important part of the Fourier transform spectrometer, and its dynamic and static performance determines the interference effect and the spectral resolution of the spectrometer. To meet the requirement of the uniform velocity of moving mirror scanning, a completely digital control scheme is proposed with FPGA as the key hardware, and this scheme is applied to the moving mirror movement in the spectrometer. According to the need of the current detection and the velocity detection, a dual closed loop control composed of current loop and velocity loop is realized, with current loop and velocity loop using PI control and fuzzy PID control respectively. The experiment results show that the current curve is smooth in the uniform scan phase of moving mirror, and that the peak current is 0.5 A in acceleration and deceleration period. Additionally, when the angular velocity of moving mirror is 30/s in the uniform section, the maximum relative error is less than 4%. From research results, it can be drawn that the digital control strategy can significantly improve the velocity stability of moving mirror, and meet the performance requirements of the control system. (C) 2016 Elsevier GmbH. All rights reserved.
The mechanism and characteristic of current oscillation of four-quadrant converter with predictive current controller caused by nonlinear characteristic of the system is analyzed in the paper. With the discrete model considering the digital control delay of the single-phase four-quadrant converter, the stability condition is derived. Using the describing function of saturation characteristic, the frequency and amplitude of the nonlinear oscillation is obtained. The simulation and experiment results verify the analyses.
This paper presents the flexibility of technology FPGA in the implementation of automatic control systems. A digital structure at level hardware of a regulator of PI action was designed and built by the VHDL standard. Also, a Java graphical interface was developed for monitoring and control. Experiments were performed on a mechanism for position control consisting of DC motors with encoder, checking an agile response to different reference values and graphing the results from the embedded Java application in real time.
A current fed push pull converters cascaded with a buck pre-regulator is proposed. Voltage stress of the push pull switches is reduced by buck pre regulation. Pulse width modulation is done only to the switch in buck stage. Output voltage and the buck inductor current is controlled using average current mode control. The closed loop simulation of a 20W, 100V, 0.2A cascaded buck push pull converter with analog control circuit is done using PSIM. Closed loop simulation using digital control circuit is done by using a SIMCOUPLER module which couples power electronic circuit in PSIM and digital control circuit in MATLAB. Further, hardware implementation of digital controllers on two platforms is explained. Switching pulses are generated using digital circuit are fed to the converter switches and the converter is tested for the open loop operation.
Chemokines are a family of small cytokines that share a typical key structure that is stabilized by disulfide bonds between the cysteine residues at the NH2-terminal of the protein, and they are secreted by a great variety of cells in several different conditions. Their function is directly dependent on their interactions with their receptors. Chemokines are involved in cell maturation and differentiation, infection, autoimmunity, cancer, and, in general, in any situation where immune components are involved. However, their role in postfracture inflammation and fracture healing is not yet well established. In this article, we will discuss the response of chemokines to bone fracture and their potential roles in postfracture inflammation and healing based on data from our studies and from other previously published studies.
Strawberry is an ideal model for studying the molecular biology of the development and ripening of non-climacteric fruits. Hormonal regulation of gene expression along all these processes in strawberries is still to be fully elucidated. Although auxins and ABA have been pointed out as the major regulatory hormones, few high-throughput analyses have been carried out to date. The role for ethylene and gibberellins as regulatory hormones during the development and ripening of the strawberry fruit remain still elusive. By using a custom-made and high-quality oligo microarray platform done with over 32,000 probes including all of the genes actually described in the strawberry genome, we have analysed the expression of genes during the development and ripening in the receptacles of these fruits. We classify these genes into two major groups depending upon their temporal and developmental expression. First group are genes induced during the initial development stages. The second group encompasses genes induced during the final maturation and ripening processes. Each of these two groups has been also divided into four sub-groups according their pattern of hormonal regulation. By analyzing gene expression, we clearly show that auxins and ABA are the main and key hormones that combined or independently are responsible of the development and ripening process. Auxins are responsible for the receptacle fruit development and, at the same timeA prevent ripening by repressing crucial genes. ABA regulates the expression of the vast majority of genes involved in the ripening. The main genes expressed under the control of these hormones are presented and their physiological rule discussed. We also conclude that ethylene and gibberellins do not seem to play a prominent role during these processes.
CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid autism. Unmethylated premutation (55-199 repeats) and FM alleles have been associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33-year-old male with FXS, with white matter changes and progressive deterioration in gait with cerebellar signs consistent with probable FXTAS; there was no evidence of any other cerebellar pathology. We show that he has tissue mosaicism in blood, saliva, and buccal samples for the size and methylation of his expanded alleles and a de novo, unmethylated microdeletion. This microdeletion involves a similar to 80 bp sequence in the FMR1 promoter as well as complete loss of the CGG repeat in a proportion of cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation and CGG sizing results are consistent with the diagnosis of concurrent FXS and probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain the manifestation of milder than expected cognitive and behavioral impairments and early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who manifest symptoms of FXTAS, may benefit from more detailed laboratory testing. (C) 2016 Wiley Periodicals, Inc.
Since the devastating 2011 tornado season, there has been renewed interest in understanding tornado wind loads and developing methodologies to reduce the risk of tornado damage. This study focuses on the assessment of the system-level performance of five different residential light-frame wood building archetypes subjected to tornado winds. The system-level performance considered three critical components along the vertical load path within each building, namely, the roof sheathing, roof-to-wall connection, and wall-to-foundation anchorage. Although there has been significant work on each of these components independently, combined uplift and lateral forces have received less attention. Therefore, a laboratory testing program for wood shear walls, reported herein, was performed to determine the wall-failure mechanisms and capacities when subjected to combined shear and uplift forces. Each building archetype was designed at varying locations across the United States based on the current residential building code and/or observed practice. Fragilities were developed, based on the assumption that failure of any component along the vertical load path results in failure of the system. Because the forces in each connection along the vertical load path arise from the same tornado wind load, the connection failures are not statistically independent, and Monte Carlo simulation was applied to perform the system reliability analysis. (C) 2017 American Society of Civil Engineers.
The antibody crystallizable fragment (Fc) is recognized by effector proteins as part of the immune system. Pathogens produce proteins that bind Fc in order to subvert or evade the immune response. The structural characterization of the determinants of Fc-protein association is essential to improve our understanding of the immune system at the molecular level and to develop new therapeutic agents. Furthermore, Fc-binding peptides and proteins are frequently used to purify therapeutic antibodies. Although several structures of Fc-protein complexes are available, numerous others have not yet been determined. Protein-protein docking could be used to investigate Fc-protein complexes; however, improved approaches are necessary to efficiently model such cases. In this study, a docking-based structural bioinformatics approach is developed for predicting the structures of Fc-protein complexes. Based on the available set of X-ray structures of Fc-protein complexes, three regions of the Fc, loosely corresponding to three turns within the structure, were defined as containing the essential features for protein recognition and used as restraints to filter the initial docking search. Rescoring the filtered poses with an optimal scoring strategy provided a success rate of approximately 80% of the test cases examined within the top ranked 20 poses, compared to approximately 20% by the initial unrestrained docking. The developed docking protocol provides a significant improvement over the initial unrestrained docking and will be valuable for predicting the structures of currently undetermined Fc-protein complexes, as well as in the design of peptides and proteins that target Fc.
Objective This study aimed to evaluate the efficacy of the Functional Independence Measure to assess preoperative frailty for elderly patients undergoing surgical aortic valve replacement. Methods Eighty-five patients >65 years who survived elective isolated aortic valve replacement from January 2008 to October 2015 were included. The mean age at the operation was 78 +/- 6 years old (n = 28 males, n = 57 females). The patients were divided into two groups according to their status at discharge: impossible to discharge home or hospitalization for >30 days (compromised group, n = 8), or unaffected (unaffected group, n = 77). Preoperative frailty was evaluated with the Functional Independence Measure, which comprises 18 items divided into six domains: self-care, sphincter control, mobility, locomotion, communication, and social cognition. Results The preoperative total Functional Independence Measure score was significantly lower in the compromised group (79 +/- 32) than in the unaffected group (120 +/- 9, p < 0.01). The preoperative motor Functional Independence Measure score was significantly lower in the compromised group (45 +/- 24) than in the unaffected group (85 +/- 9, p = < 0.01). The duration of postoperative intubation, intensive care unit stay, and postoperative hospitalization were significantly longer in the compromised group than in the unaffected group (48 +/- 67 vs 16 +/- 12 h, p < 0.01; 6.7 +/- 5.3 vs 3.4 +/- 2.0 days, p < 0.01; 34 +/- 27 vs 23 +/- 11 days, p = 0.02, respectively). Conclusions The preoperative Functional Independence Measure is effective for assessing preoperative frailty in elderly patients undergoing aortic valve replacement in terms of predicting operative morbidity.
Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. Francisella noatunensis subsp. orientalis is a Gram-negative, facultative intracellular bacterium that causes the disease francisellosis in fish. Francisellosis is commonly characterized as a chronic granulomatous disease with high morbidity and can result in high mortality depending on the host. In this study, we explored the potential of bacterial membrane vesicles (MVs) as a vaccine agent against F. noatunensis subsp. orientalis. Bacterial MVs are spherical structures naturally released from the membrane of bacteria and are often enriched with selected bacterial components such as toxins and signaling molecules. MVs were isolated from broth-cultured F. noatunensis subsp. orientalis in the present work, and proteomic analysis by mass spectrometry revealed that MVs contained a variety of immunogenic factors, including the intracellular growth proteins lgIC and lgIB, known to be part of a Francisella pathogenicity island (FPI), as well as outer membrane protein OmpA, chaperonin GroEL, and chaperone ClpB. By using flow cytometry and electron microscopy, we observed that F. noatunensis subsp. orientalis mainly infects myelomonocytic cells, both in vivo and in vitro. Immunization with MVs isolated from F. noatunensis subsp. orientalis protects zebrafish from subsequent challenge with a lethal dose of F. noatunensis subsp. orientalis. To determine if MVs induce a typical acute inflammatory response, mRNA expression levels were assessed by quantitative real-time PCR. Expression of tnfa, il1b, and ifng, as well as mhcii, mpeg1.1, and ighm, was upregulated, thus confirming the immunogenic properties of F. noatunensis subsp. orientalis-derived MVs.
To measure the nonlinear impedance of interdigital electrode-solution system, a novel method based on free damped oscillation is proposed. A high valued active inductance with adjustable negative resistance is constructed by an operational amplifier. A second order oscillation system for measurement is then set up by connecting the active inductance with the device under test. The active inductance is designed to be around 470H to meet the measurement requirements of low frequency. The negative resistor is utilized to adjust damping coefficient of the oscillation system in order to obtain enough number of ring-down oscillation cycles for parameter estimation. The free damped oscillation signal of the oscillation system is obtained under square wave voltage excitation. After processed by Hilbert transform, the instantaneous capacitance and resistance can be calculated simultaneously to implement nonlinear impedance measurement. The operational availability of the proposed method is verified by experimental results of commercial available resistors and capacitors. The impedance nonlinearity of a gold interdigital electrode immersed in KCl solutions of different concentration is tested and compared with that obtained by sweep-amplitude sinusoidal excitation methods. The results indicate that the proposed method can successfully obtain impedance nonlinearity in half of the square wave period.
Inferring the intentions and beliefs of another is an ability that is fundamental for social and affiliative interactions. A substantial amount of empirical evidence suggests that making sense of another's intentional and belief states (i.e. theory of mind) relies on exteroceptive (e.g. visual and auditory) and proprioceptive (i.e. motor) signals. Yet, despite its pivotal role in the guidance of behaviour, the role of the observer's interoceptive (visceral) processing in understanding another's internal states remains unexplored. Predicting and keeping track of interoceptive bodily states - which inform intentions and beliefs that guide behaviour - is one of the fundamental purposes of the human brain. In this paper, we will focus on the role of interoceptive predictions, prescribed by the free energy principle, in making sense of internal states that cause another's behaviour. We will discuss how multimodal expectations induced at deep (high) hierarchical levels - that necessarily entail interoceptive predictions - contribute to inference about others that is at the heart of theory of mind. (C) 2015 The Authors. Published by Elsevier Inc.
The light emitting diode (LED) based visible light communication (VLC) system can provide lighting and communication simultaneously. It has attracted much attenuation recently. As the photovoltaic cell (also known as solar cell) is physically flexible, low cost, and easily available, it could be a good choice for the VLC receiver (Rx). Furthermore, besides acting as the VLC Rx, the solar cell can convert VLC signal into electricity for charging up the Rx devices. Hence, it could be a promising candidate for the future internet-of-thing (IoT) networks. However, using solar cell as VLC Rx is challenging, since the response of the solar cell is highly limited and it will limit the VLC data rate. In this work, we propose and demonstrate for the first time using pre-distortion Manchester coding (MC) signal to enhance the signal performance of solar cell Rx based VLC. The proposed scheme can significantly mitigate the slow response, as well as the direct-current (DC) wandering effect of the solar cell; hence 50 times increase in data rate can be experimentally achieved.
Freedom is one of the central values in political and moral philosophy. A number of theorists hold that freedom (or, relatedly, opportunity) should either be the only or at least one of the central distribuenda in our theories of distributive justice. Moreover, many follow Mill and hold that a concern for personal freedom should guide, and limit, how paternalist public policy can be. For the most part, theorists have focussed on a person's freedom at one specific point in time but have failed to give proper attention to freedom across time. Given that we care about personal freedom now, we have reason to care about future freedom too. But what kind of distribution of freedom across a person's lifetime should we promote as a matter of legislation and public policy? I argue that none of the candidate principles for the distribution of freedom across time is plausible. Neither a starting gate view, nor a maximisation nor a sufficientarian view is satisfactory, because none adequately reflects our various reasons to value freedom. I show that this result presents a tough challenge for theories of distributive justice and paternalism that set great store by personal freedom.
A grid-connected inverter is indispensable for photovoltaic power generation and smart grid systems, and it must be designed for stable operation. The impedance method based on the Nyquist criterion is often utilized to analyze the stability of grid-connected inverter systems. The impedance method is based on the eigenvalues of the product of the inverter output admittance and the line impedance matrices in the frequency domain. However, the frequency characteristics have so far been derived only for inverters with analog control systems. A new frequency analysis method for inverters with digital control systems is proposed in this paper. First, a stability analysis example for a three-phase LCL-type inverter controlled digitally is shown and the results are compared and validated with those by simulation using a Saber simulator. Finally, they are also compared and validated with experimental results digitally controlled by a DSP-based system. (C) 2017 Wiley Periodicals, Inc.
Background and ObjectivesVariant RHD genes associated with the weak D phenotype can result in complete or partial D-epitope expression on the red cell. This study examines the genetic classification in Australian blood donors with a weak D phenotype and correlates RHD variants associated with the weak D phenotype against D-epitope profile. Materials and MethodsFollowing automated and manual serology, blood samples from donors reported as weak D' (n = 100) were RHD genotyped by a commercial SNP-typing platform and Sanger sequencing. Two commercial anti-D antibody kits were used for extended serological testing for D-epitope profiles. ResultsThree samples had wild-type RHD exonic sequences, and 97 samples had RHD variants. RHD*weak D type 1, RHD*weak D type 2 or RHD*weak D type 3 was detected in 75 donors. The remaining 22 samples exhibited 17 different RHD variants. One donor exhibited a novel RHD*c.939+3A>C lacking one D-epitope. Weak D types 11, 5, 15, 17 and 90 showed a partial D-epitope profile. ConclusionThe array of RHD variants detected in this study indicated diversity in the Australian donor population that needs to be accommodated for in future genotyping strategies.
Aims: This study explored the sex-specific associations between friendship trust and the psychological well-being of young Swedes from late adolescence to early adulthood. Methods: A random sample of native Swedes born in 1990 was surveyed at age 19 years and again at age 23 years regarding their own well-being and their relationships with a maximum of five self-named peers. The response rate was 31.3%, resulting in 782 cases to be analysed. We used sex-stratified structural equation models to explore the associations between trust and well-being. Psychological well-being was constructed as the latent variable in the measurement part. The structural part accounted for the autocorrelation of trust with respect to well-being over time and incorporated the cross-lagged effects between late adolescence and early adulthood. Results: It was found that trust increased while well-being decreased for young men and remained stable for young women from 19 to 23 years of age. The young women reported lower well-being at both time points, whereas no sex difference was found for trust. Based on model fit comparisons, a simple model without forward or reward causation was accepted for young men, whereas reversed causation from well-being to trust was suggested for young women. Subsequent analysis based on these assumptions confirmed the reversed effect for young women. Conclusions: The findings suggest that young people do not benefit from trustful social relations to the same extent as adult populations. Young women who express impaired well-being run a greater risk of being members of networks characterized by low friendship trust over time.
Background Friendships between people with and without intellectual disability remain elusive. Little is known about factors that support the development of such friendships and what services can do to promote the likelihood that contact will develop into friendship.Method A case study approach was used to explore the qualities and development of a long-term friendship between 2 women, 1 of whom has severe intellectual disability. Qualitative methods of data collection and analysis were used including interviews and field notes from participant observation.Findings The relationship progressed through 3 stages of introduction, consolidation, and autonomy supported by the working practices and culture of the disability support organisation. Individualised activity, the role of a connector, and a culture of positive expectations underpinned the growth of the friendship.Conclusions Friendships do not happen by chance but require thought, attention, dedicated resources, and commitment to long-term outcomes to be achieved.
Wood frogs (Rana sylvatica) are highly susceptible to infection with Frog virus 3 (FV3, Ranavirus, Iridoviridae), a cause of mass mortality in wild populations. To elucidate the pathogenesis of FV3 infection in wood frogs, 40 wild-caught adults were acclimated to captivity, inoculated orally with a fatal dose of 10(4.43) pfu/frog, and euthanized at 0.25, 0.5, 1, 2, 4, 9, and 14 days postinfection (dpi). Mild lesions occurred sporadically in the skin (petechiae) and bone marrow (necrosis) during the first 2 dpi. Severe lesions occurred 1 to 2 weeks postinfection and consisted of necrosis of medullary and extramedullary hematopoietic tissue, lymphoid tissue in spleen and throughout the body, and epithelium of skin, mucosae, and renal tubules. Viral DNA was first detected (polymerase chain reaction) in liver at 4 dpi; by dpi 9 and 14, all viscera tested (liver, kidney, and spleen), skin, and feces were positive. Immunohistochemistry (IHC) first detected viral antigen in small areas devoid of histologic lesions in the oral mucosa, lung, and colon at 4 dpi; by 9 and 14 dpi, IHC labeling of viral antigen associated with necrosis was found in multiple tissues. Based on IHC staining intensity and lesion severity, the skin, oral, and gastrointestinal epithelium and renal tubular epithelium were important sites of viral replication and shedding, suggesting that direct contact (skin) and fecal-oral contamination are effective routes of transmission and that skin tissue, oral, and cloacal swabs may be appropriate antemortem diagnostic samples in late stages of disease (>1 week postinfection) but poor samples to detect infection in clinically healthy frogs.
Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res2017, 10: 99-112. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Background: Anterior encephalocele (AE) is a rare congenital anomaly of the central nervous system which is thought to be associated with genetic defects in folate metabolism. Methods: This case-control study investigated the interactions of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-1958G>A (rs2236225) and the methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133) and 1298A>C (rs1801131) polymorphisms with the risk of AE in the Northeast Indian population. A total of 40 AE cases and 80 controls were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. Results: MTHFR 1298CC was significantly associated with AE risk (odds ratio [OR] 4.21; p = 0.01). The MTHFR haplotypes 677C-1298C/677T-1298A (OR, 2.50) and 677T-1298C (OR, 2.86) conferred risk in a progressive manner ((2) = 9.82; pA was not associated with disease susceptibility. Children with the rs2236225 GA and the rs1801131 CC genotypes were at an increased risk as compared to the reference genotype of rs2236225 GG and rs1801131 AA (OR, 14.4; p = 0.02). Children with the rs2236225 GG and rs1801133 CT genotypes were also at an elevated risk (OR, 4.76; p = 0.01). The MTHFD1 polymorphism together with the MTHFR haplotypes elevated risk in a progressive manner (chi(2) = 6.29; p = 0.01). Conclusion: The data support our hypothesis of gene-gene interaction between MTHFD1 and MTHFR and the risk of AE. Together with the MTHFR haplotypes, MTHFD1 elevates risk in a progressive manner. The minor allelic frequencies of the MTHFD1 1958G>A and MTHFR 1298A>C in our populations were similar to those reported from Southeast Asian population, suggesting a possible explanation for the prevalence of this malformation in these regions. (C) 2017 Wiley Periodicals, Inc.
Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical management of these patients. Purpose of the present article is to present and discuss available data about the pharmacological treatment of psychiatric symptoms in patients with FTD. A research in the main database sources has been conducted to obtain an overview of the pharmacological management of psychiatric symptoms in patients with FTD. The search strategy included the following termsFTD and psychiatry, FTD and behavioural disturbances, and FTD and treatment. Pathophysiology of psychiatric symptoms in FTD is different from other types of dementia. Although drugs for Alzheimer disease appear to be ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence supports a possible usefulness of serotonergic antidepressants for these patients. Data are too scanty to draw definitive conclusions, but antidepressant treatment, particularly with serotonergic compounds, may improve psychiatric symptoms in patients with FTD. Large observational studies are needed to confirm this preliminary evidence, and a lot of effort and collaboration between neurologists and psychiatrists will be definitely crucial for future research of effective treatments for FTD.
Frontotemporal dementia is a neurodegenerative disease affecting cognition and behavior in multiple devastating ways. This article highlights diagnostic features helpful in differentiating frontotemporal dementia from other dementias, most commonly Alzheimer disease.
Using structural MRI, we investigated the brain substrates of both affective and cognitive theory of mind (ToM) in 19 patients with semantic dementia. We also ran intrinsic connectivity analyses to identify the networks to which the substrates belong and whether they are functionally disturbed in semantic dementia. In line with previous studies, we observed a ToM impairment in patients with semantic dementia even when semantic memory was regressed out. Our results also highlighted different neural bases according to the nature (affective or cognitive) of the representations being inferred. The affective ToM deficit was associated with atrophy in the amygdala, suggesting the involvement of emotion-processing deficits in this impairment. By contrast, cognitive ToM performances were correlated with the volume of medial prefrontal and parietal regions, as well as the right frontal operculum. Intrinsic connectivity analyses revealed decreased functional connectivity, mainly between midline cortical regions and temporal regions. They also showed that left medial temporal regions were functionally isolated, a further possible hindrance to normal social cognitive functioning in semantic dementia. Overall, this study addressed for the first time the neuroanatomical substrates of both cognitive and affective ToM disruption in semantic dementia, highlighting disturbed connectivity within the networks that sustain these abilities.
An experimental study was conducted to investigate the influence of FRP confinement on the buckling behavior of longitudinal steel reinforcing bars (rebars) in RC columns subjected to monotonic and cyclic axial compression. Test results of 12 FRP-confined RC columns and 12 FRP-confined plain concrete columns (control specimens) are presented with particular attention to the evolution of strains in the longitudinal steel rebars and the FRP jacket as the load increases. For an FRP-confined RC column subjected to monotonic axial compression, the contribution of longitudinal steel rebars to the overall axial load carried by the column was deduced by subtracting the contribution of the FRP-confined plain concrete from the total axial load. The test results showed that the compressive stress-strain response of longitudinal steel rebars in FRP-confined RC columns follows that from tensile testing before the axial stress reduces gradually due to the onset of buckling deformation. Significant interactions were found to exist between FRP confinement and the buckling of longitudinal steel rebars. This interaction should be carefully considered when formulating constitutive laws for both the longitudinal steel rebars and the FRP-confined concrete for use in theoretical modeling. (C) 2017 Elsevier Ltd. All rights reserved.
The present study examines the moderating role of unconditional self acceptance and self esteem in relation to frustration intolerance beliefs and psychological distress. Participants were one hundred and fifty student (aged 18-25) studying at three universities (COMSATS Institute of Information Technology, University of Management Sciences, and University of Central Punjab) of Lahore, Pakistan. They completed a demographic information sheet, the Frustration Discomfort Scale (Harrington in Clin Psychol Psychother 12:374-387, 2005a), the Rosenberg Self-Esteem Scale (Rosenberg in Society and the adolescent self image. Princeton University Press, Princeton, 1965), the Unconditional Self Acceptance Questionnaire (Chamberlain and Haaga in J Ration Emotive Cogn Behav Ther 19:163-176, 2001a), and the General Health Questionnaire (Goldberg in Manual of the General Health Questionnaire. NFERNelson, Great Britain, 1972). The results demonstrated the moderating effects of unconditional self acceptance and self esteem in the relationship between frustration intolerance beliefs (entitlement, achievement, emotional intolerance, and discomfort intolerance) and psychological distress . The present findings highlight the importance unconditional self acceptance that reduces the emotional problems of students hindering their educational and personal growth.
Fucoidan, a sulfated marine polysaccharide, has many potential biological functions, including anticancer activity. Recently, fucoidan has been reported to target P-selectin expressed on metastatic cancer cells. Increasing research attention has been devoted to the developments of fucoidan-based nanomedicine. However, the application of traditional chitosan/fucoidan nanoparticles in anticancer drug delivery may be limited due to the deprotonation of chitosan at a pH greater than 6.5. In this study, a mutlistimuli-responsive nanoparticle self-assembled by fucoidan and a cationic polypeptide (protamine) was developed, and their pH-/enzyme-responsive properties were characterized by circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and zeta potential analysis. Enzymatic digestion and acidic intracellular microenvironment (pH 4.5-5.5) in cancer cells triggered the release of an anticancer drug (doxorubicin) from the nanoparticles. The protamine/fucoidan complex nanoparticles with P-selectin mediated endocytosis, charge conversion and stimuli-tunable release properties showed an improved inhibitory effect against a metastatic breast cancer cell line (MDA-MB-231). (C) 2017 Elsevier Ltd. All rights reserved.
Recent advances in thermoelectric technology have made exhaust-based thermoelectric generators (TEGs) promising for recovery of waste heat. Utilization of exhaust-based TEGs in heavy-duty vehicles was studied in this work. Given that the generated power is limited, the alternator is still indispensable. To improve the fuel economy, the generated electricity must be integrated into the automotive electrical system and consumed by electrical loads. Therefore, two feasible ways of integrating the generated electricity into the automotive electrical system are discussed: one in which the original alternator works only under certain conditions, i.e., the "thermostat" strategy, and another in which a smaller alternator is adopted and works together with the TEG, i.e., the "cooperative work" strategy. The overall performance and efficiency are obtained through simulation analysis. The simulation results show that both methods can improve the fuel economy, but the former provides better results. Moreover, if the electrical loads can be properly modified, the fuel economy is further improved. These simulation results lay a solid foundation for application of TEGs in vehicles in the future.
The ultrarapid underpass (URUP) tunneling method, in which a shield machine is launched and received at the ground surface level, has been developed for tunneling in congested areas. This paper reports monitoring results of a full-scale test conducted for the first URUP tunneling project in China. In the investigation, special attention was paid to tunneling phases in which the shield machine was buried super-shallowly or partially above the ground surface. The paper focuses on the tunneling-induced soil movements and on the grouting process. Measurement results indicated that surface settlements can be represented by the commonly used Gaussian function regardless of the cover depth, and that the load-factor approach provides a fair prediction of the volume loss. A contracting transverse soil-displacement field was identified as the dominating pattern, although an expanding displacement field was observed at several locations. Pressure measurements were used to identify a time-dependent response of the grouting process.
In this paper a novel high-frequency fully differential pure current mode current operational amplifier (COA) is proposed that is, to the authors' knowledge, the first pure MOSFET Current Mode Logic (MCML) COA in the world, so far. Doing fully current mode signal processing and avoiding high impedance nodes in the signal path grant the proposed COA such outstanding properties as high current gain, broad bandwidth, and low voltage and low-power consumption. The principle operation of the block is discussed and its outstanding properties are verified by HSPICE simulations using TSMC CMOS technology parameters. Pre-layout and Post-layout both plus Monte Carlo simulations are performed under supply voltages of to investigate its robust performance at the presence of fabrication non-idealities. The pre-layout plus Monte Carlo results are as; 93 dB current gain, phase margin, 137 dB CMRR, 13 input impedance, output impedance and 1.37 mW consumed power. Also post-layout plus Monte Carlo simulation results (that are generally believed to be as reliable and practical as are measuring ones) are extracted that favorably show(in abovementioned order of pre-layout) 88 dB current gain, phase margin and 96 dB CMRR, input impedance, output impedance and only 1.43 mW consumed power. These results altogether prove both excellent quality and well resistance of the proposed COA against technology and fabrication non-idealities.
This paper presents a dual band Digitally-Controlled-Oscillator (DCO) based on Ring-Oscillators (RO) topology with differential input/output at 1.45 GHz is proposed. The circuit has two frequency band which switches by a digital mode bit. Switching between two bands of DCO, will change delay path and power consumption during the run time. A new Source-Coupled-Logic (SCL) based reconfigurable delay element with Schmitt-Trigger (ST) characteristic is used in each stage and 6 bits digital code control their current tails. Power consumption profile with frequency in each band has a steady regime. The proposed designs are fully differential, which is appropriate for low jitter high performance applications. The proposed DCO is simulated by spice with CMOS standard 0.18 mu m @ 1.8 v supply. The frequency, power consumption and jitter in lower band are 455.2 MHz to 505.1 MHz, 1.98 mW (at 455 MHz), 6.04 ps (at 505.1 MHz) and for upper band are from 1.39 MHz to 1.45 MHz, 9.7 mW (at 1.39 GHz) and 3.48 ps (at 1.45 MHz), sequentially. In this paper also circuit analysis of proposed DCO, delay calculation and comparison and analytical equation for frequency bands are obtained. Also, Monte Carlo and PVT test shows acceptable frequency tolerance.
When interpreting results of a functional analysis, a clinician may conclude an automatic function either because problem behavior is elevated in the alone/ignore condition relative to other conditions or because problem behavior is elevated and undifferentiated across multiple conditions. In the latter, it is difficult to determine if problem behavior is maintained by automatic reinforcement alone or is multiply maintained. The current study tested for multiply-maintained self-injurious behavior exhibited by two participants by implementing functional analysis contingencies while controlling for automatic reinforcement through sensory extinction. Results suggest that self-injury was maintained by automatic reinforcement alone for one participant and both automatic reinforcement and physical attention for another participant. These results were then used to create function-based treatments for self-injury that were successfully generalized across settings and caregivers.
Multiferroic materials have attracted the attention of scientific community all over the world due to smart functionality and attractive applications such as in magnetoelectric memory and magnetoelectric sensors. In this paper, we report on the ferroelectric, magnetic and magnetoelectric properties of microwave sintered BiFeO3 (BFO) and Bi0.90La0.10Fe0.95Mn0.05O3 (BLFMO) ceramics. The ferromagnetic and paramagnetic components have been deconvoluted using standard magnetization equation. The ferromagnetic saturation and paramagnetic susceptibility for BFO are found to be 0.046 emu/g and 1.17 x 10(-5) emu/g.Oe respectively. The magnetization in BLFMO increases enormously as compared to BFO due to suppression of cycloid spin. The magnetoelectric voltage coefficient for BFO is 3.37 mV/cm.Oe, while for BLFMO it is 10.11 mV/cm.Oe. As compared to BFO, BLFMO exhibits improved ferroelectric, magnetic and magnetoelectric properties. (C) 2017 Elsevier B.V. All rights reserved.
Similarity search and related issues are current topic in databases. Over the last ten years more then 6500 papers dealing with similarity in databases were published according to Web of Science. The rising in the number of articles in the recent years shows that the research in this direction is still in its early stage. From the wide range of topics related with similarities in databases, one received a considerable attention already, namely functional dependencies which take similarities into account. Our main concern in this paper is to review and critically examine the existing work on this topic. (C) 2016 Elsevier B.V. All rights reserved.
Functional electrical stimulation has been widely used for the restoration of bladder functions after spinal cord injury or other neurological disorders. However, most of the neuroprostheses for bladder control are still imperfect due to lack of the feedback information about the state of the controlled bladder. The purpose of this study is to develop an implantable system which allows us to stimulate the nerves and record the nerve signals related to the condition of the bladder. The proposed stimulator consists of three parts: a digital-to-analog converter (DAC), a current driver, and a switch network. Using the same current source with a switch network eliminates the need for separate current sources for anodic and cathodic sections and reduce the need for interconnect lines of control signals which is an area-saved and power-efficient configuration. A symmetrical regulated cascode current driver is used to implement a high voltage compliance and a high output impedance which improves its ability with load. The amplitude, frequency and the pulse width of the stimulating current are adjusted by encoding the DAC and switch sequences, respectively. In addition, we also present two-stage fully differential capacitively-coupled amplifiers for neural recording. The neural amplifier's parameters are carefully chosen according to the characteristics of neural signal; meanwhile, we analyzed theoretically the main noise sources, especially the pseudo-resistor in the feedback path which gives little attention by previous studies. The integrated neural stimulating and recording frontend for bladder control prosthesis has been designed and simulated, using a TSMC's 0.18-mu m CMOS process. The proposed stimulator can provide a symmetrical cathodic-first biphasic current pulse with interphasic gap, a low headroom voltage of 0.168 V corresponding to 2.48 mA full-scale current, an adjustable pulse width of 100-500 mu s and frequency of 1-40 Hz. The recording amplifier with a low input-referred noise of 3.62 mu V, an NEF of 3.88 and a low power dissipation of 7.2 mu W has a gain of 61.6 dB and a frequency bandwidth from 300 Hz to 5.3 kHz. Both circuit analysis and simulations are presented to examine the performance of the proposed designs.
The transcript pool of a plant part, under any given condition, is a collection of mRNAs that will pave the way for a biochemical reaction of the plant to stimuli. Over the past decades, transcriptome study has advanced from Northern blotting to RNA sequencing (RNA-seq), through other techniques, of which real-time quantitative polymerase chain reaction (PCR) and microarray are the most significant ones. The questions being addressed by such studies have also matured from a solitary process to expression atlas and marker-assisted genetic enhancement. Not only genes and their networks involved in various developmental processes of plant parts have been elucidated, but also stress tolerant genes have been highlighted. The transcriptome of a plant with altered expression of a target gene has given information about the downstream genes. Marker information has been used for breeding improved varieties. Fortunately, the data generated by transcriptome analysis has been made freely available for ample utilization and comparison. The review discusses this wide variety of transcriptome data being generated in plants, which includes developmental stages, abiotic and biotic stress, effect of altered gene expression, as well as comparative transcriptomics, with a special emphasis on microarray and RNA-seq. Such data can be used to determine the regulatory gene networks, which can subsequently be utilized for generating improved plant varieties.
Psychopathological symptoms and cognitive impairment are related to psychosocial functioning. However, the nature of the association of cognitive impairment with psychosocial functioning still remains under scrutiny. We aimed to examine the relationships of premorbid adjustment, lifetime psychopathological dimensions, and cognitive performance with the typical level of psychosocial functioning during the previous year. We assessed ninety patients with schizophrenia spectrum disorders and affective disorders with psychotic symptoms to collect data on premorbid adjustment, lifetime psychopathological dimensions, cognitive performance and psychosocial functioning. Sixty-five healthy volunteers were included as controls. Pearson's correlations and hierarchical regression analyses were performed to ascertain to what extent the aforementioned variables predicted psychosocial functioning. Functional domains were significantly correlated with most of the premorbid features, lifetime psychopathological dimensions and cognitive domains. However, lifetime negative symptoms were the best predictors of psychosocial functioning in the hierarchical regression analyses (explaining between 47 and 64% of the variance). For psychosocial outcome in patients with psychoses, lifetime negative symptoms showed a stronger predictive validity than cognitive impairment or premorbid adjustment. (C) 2016 Elsevier B.V. All rights reserved.
The Cognitive Assessment Interview (CAI) is an interview-based instrument to assess cognition considering the impact of cognitive impairment on daily activities. We aimed to explore the associations of the Spanish version of the CAI (CAI-Sp) with a neuropsychological battery and a measure of psychosocial functioning in psychosis. The sample consisted of fifty-six first episode psychosis (FEP) patients and 66 non-FEP patients, who were assessed with a neuropsychological battery, the CAI-Sp and the Short Disability Schedule (DAS-S). Patients also underwent clinical assessment. Additionally, 37 controls were assessed with the neuropsychological battery and CAI-Sp, for normalization purposes. The results showed that CAI-Sp scores were overall correlated with the neuropsychological battery in non-FEP patients. In FEP patients, we found fewer significant correlations. Most associations were maintained after controlling for clinical symptoms. CAI-Sp rater scores contributed to the variance in the DAS-S scores in both groups, as did negative and disorganized symptoms. The CAI-Sp may be a good instrument to assess cognition in non-FEP patients. In FEP patients, it was less effective in capturing cognitive impairments and their functional consequences, probably because cognitive deficits have yet to become evident, due to the recency of illness onset, and no functional disturbances were observed due to these cognitive impairments. (C) 2016 Elsevier B.V. All rights reserved.
This paper pays attention to predicting the nonlinear bending behaviors of functionally graded materials (FGM) infinite cylindrical shallow shells with a two-parameter elastic foundation by using a two-step perturbation method. The shells are subjected to uniform temperature rise and temperature dependency of the constituents is also taken into account. Two ends of the shells are assumed to be clamped or pinned and in-plane boundary conditions are immovable. The governing equations are derived based on physical neutral surface concept and high order shear deformation theory. The explicit expressions between the transverse load and the deflection are obtained by perturbation method. In numerical examples, some comparisons are shown to verify the correctness of the present research and solution method. It can be concluded that FGM cylindrical shallow shells subjected to uniform bending loadings will bring about snap-through buckling and jump changes, and the foundation can enhance the stability of the shells. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: Social and role functioning are compromised for the majority of individuals at ultra-high risk of psychosis, and it is important to identify factors that contribute to this functional decline. This study aimed to investigate social cognitive abilities, which have previously been linked to functioning in schizophrenia, as potential factors that impact social, role and global functioning in ultra-high risk patients. Method: A total of 30 ultra-high risk patients were recruited from an established at-risk clinical service in Melbourne, Australia, and completed a battery of social cognitive, neurocognitive, clinical and functioning measures. We examined the relationships between all four core domains of social cognition (emotion recognition, theory of mind, social perception and attributional style), neurocognitive, clinical and demographic variables with three measures of functioning (the Global Functioning Social and Role scales and the Social and Occupational Functioning Assessment Scale) using correlational and multiple regression analyses. Results: Performance on a visual theory of mind task (visual jokes task) was significantly correlated with both concurrent role (r=0.425, p=0.019) and global functioning (r=0.540, p=0.002). In multivariate analyses, it also accounted for unique variance in global, but not role functioning after adjusting for negative symptoms and stress. Social functioning was not associated with performance on any of the social cognition tasks. Conclusion: Among specific social cognitive abilities, only a test of theory of mind was associated with functioning in our ultra-high risk sample. Further longitudinal research is needed to examine the impact of social cognitive deficits on long-term functional outcome in the ultra-high risk group. Identifying social cognitive abilities that significantly impact functioning is important to inform the development of targeted intervention programmes for ultra-high risk individuals.
The purpose of this study was to ascertain whether uses of music partially mediate the link between personality and music preference. Undergraduate students (N = 122) completed the following scales: The Brief Big Five Inventory, The Uses of Music Inventory, The Short Test of Music Preference, The Life Orientation Test Revised, The Beck Depression Inventory, and the Perceived Stress Scale. Openness to experience positively predicted preferences for reflective-complex (RC; e.g., jazz/blues) and intense-rebellious (IR; e.g., rock/metal) music and was inversely related to upbeat-conventional (UC; e.g., country/pop) music, whereas extraversion was positively related to preferences for energetic-rhythmic (ER; e.g., rap/soul) and UC genres. A link between trait optimism and ER music preference was fully mediated by the more prominent extraversion trait. The relationship between openness to experience and RC music preference was partially mediated by cognitive uses of music, with a marginally significant analysis indicating partial mediation of emotional uses of music for openness to experience and IR music preference. Trait neuroticism, perceived stress, and depression scores all correlated positively with emotional uses of music. The current findings support studying personality contextually alongside uses of music when investigating music preference and shed light on how negative affect may inform emotional uses of music.
Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.
P>Sucrose exuded by plants into the rhizosphere is a crucial component for the symbiotic association between the beneficial fungus Trichoderma and plant roots. In this article we sought to identify and characterize the molecular basis of sucrose uptake into the fungal cells. Several bioinformatics tools enabled us to identify a plant-like sucrose transporter in the genome of Trichoderma virens Gv29-8 (TvSut). Gene expression profiles in the fungal cells were analyzed by Northern blotting and quantitative real-time PCR (qRT-PCR). Biochemical and physiological studies were conducted on Gv29-8 and fungal strains impaired in the expression of TvSut. TvSut exhibits biochemical properties similar to those described for sucrose symporters from plants. The null expression of tvsut caused a detrimental effect on fungal growth when sucrose was the sole source of carbon in the medium, and also affected the expression of genes involved in the symbiotic association. Similar to plants, T. virens contains a highly specific sucrose/H+ symporter that is induced in the early stages of root colonization. Our results suggest an active sucrose transference from the plant to the fungal cells during the beneficial associations. In addition, our expression experiments suggest the existence of a sucrose-dependent network in the fungal cells that regulates the symbiotic association.
Pathogenic isolates of Fusarium oxysporum applied on a non-host plant species, as soil-borne nonpathogenic isolates, are able to protect this plant against pathogenic strains inducing wilts. Several modes of action contribute to the biocontrol activity of these protective strains; however the genetic basis of the biocontrol mechanisms is far from being understood. The aim of this study was to identify genes involved in biocontrol activity of F. oxysporum using an original model made of Fom24, a strain protective on tomato and its mutant rev157 which has lost its protective capacity. A Rapid Subtractive Hybridization (RaSH) approach was chosen to identify genes up-regulated in the protective or in the non-protective interaction when germinated conidia of either Fom24 or rev157 are confronted to tomato cell cultures. A total of 86 up-regulated sequences were generated, 42 and 44 from the protective and the non-protective interaction respectively. Homology searches led to identification of both plant and fungal genes that were grouped according to their putative functions. Among plant genes, those involved in plant response to stresses were the most abundant. Expression profiles of genes homolog to a basic endochitinase, a ferredoxine-NADP(H) reductase (FNR), an ATP synthase and the RPM1-interacting protein 4 (RIN4) were confirmed by Northern blotting. A large proportion of fungal sequences were encoding genes of unknown function; among other, those involved in response to oxidative stress and a gene putatively encoding an enolase are the most promising to further study their potential role in the protective interaction between F. oxysporum and tomato. (C) 2011 Elsevier Ltd. All rights reserved.
Fusarium head blight (FHB), mainly caused by Fusarium graminearum species complex (FGSC) and also by other species of this genus, is one of the most destructive cereal diseases with high yield losses and mycotoxin contamination worldwide. The aim of this study was to identify Fusarium species, characterize their virulence factors such as trichothecene genotypes and cell wall degrading enzymes (CWDEs), and also investigate virulence of the isolates obtained from wheat plants with FHB symptoms in Golestan province of Iran. Among 41 isolates tested, 24 were F. graminearum sensu stricto (s.s.), six were F. proliferatum, four were F. culmorum, three isolates belonged to each of F. subglutinans and F. meridionale species and one isolate of F. asiaticum was identified. Among Fusarium isolates, the nivalenol (NIV) genotype could be found more frequently, followed by 3-acetyl deoxynivalenol (3-ADON) and 15-acetyl deoxynivalenol (15-ADON) genotypes. Production of trichothecenes in autoclaved rice cultures was analyzed by gas chromatography (GC) and confirmed by GC-MS. The mean levels of NIV, 3-ADON and 15-ADON produced by Fusarium spp. were 824, 665 and 622 mu g kg(-1), respectively. All Fusarium isolates were capable of producing CWDEs, mainly cellulase and xylanase. Lipase and pectinase activities appeared later and at less quantities. In overall, the isolates FH1 of F. graminearum and FH8 of F. proliferatum showed the maximum activity of CWDEs, which was correlated with high level of their virulence and aggressiveness on wheat. On the other hand, correlation was observed between the level and type of trichothecene produced by each isolate and its virulence on wheat. Virulence of trichothecene producing isolates was higher than that of non-trichothecene producing isolates. Our results suggested that CWDEs and trichothecenes, as virulence factors, have considerable roles on virulence and aggressiveness of the pathogen. This is the first report on the effect of trichothecenes and CWDEs on virulence and aggressiveness of Fusarium spp. associated with FHB disease in wheat growing regions of Iran.
Fusarium wilts of strawberry, caused by Fusarium oxysporum f. sp. fragariae, is a serious soil-borne disease. Fusarium wilt causes dramatic yield losses in commercial strawberry production and it is a very stubborn disease to control. Reliable chemical control of strawberry Fusarium wilt disease is not yet available. Moreover, other well-known F. oxysporum have different genetic information from F. oxysporum F.. sp. fragariae. This analysis investigates the genetic diversity of strawberry Fusairum wilt pathogen. In total, 110 pathogens were isolated from three major strawberry production regions, namely Sukok, Hadong, Sancheong in Gyeongnam province in South Korea. The isolates were confirmed using F. oxysporum f. sp. fragariae species-specific primer sets. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were executed using the internal transcribed spacer, intergenic spacer, translation elongation factorl-alpha, and beta-tubulin genes of the pathogens and four restriction enzymes: AluI, HhaI and Hpy1I. Regarding results, there were diverse patterns in the three gene regions except for the beta-tubulin gene region. Correlation analysis of strawberry cultivation region, cultivation method, variety, and phenotype of isolated pathogen, confirmed that genetic diversity depended on the classification of the cultivated region.
IntroductionDetection of recurrent genetic abnormalities is of great significance for a refined diagnosis and assessment of prognosis in leukemia. Conventional nested reverse transcription PCR is labor intensive and time-consuming. MethodsWe have developed a novel dual-color TaqMan probe-based real-time PCR method for the simultaneous screening of 45 fusion transcripts in 12 parallel reactions. The method was tested and validated with cell lines carrying known fusion transcripts and patient samples. ResultsA multiplex real-time PCR method was successfully developed for rapid detection of 45 fusion genes and validated for 15 of the more commonly detected fusion genes. Intra-assay reproducibility assessed for the most frequent rearrangements ranged from 0.41% to 0.74% for the coefficient of variation (CV) of cycle threshold (Ct) and the interassay reproducibility ranged from 1.62% to 2.83% in five separate experiments. The lowest detection limit for the translocations tested ranged between 1 : 16 000 and 1 : 32 000. Validation of the method with 213 patient samples showed 100% specificity and excellent consistence with conventional nested RT-PCR. ConclusionOverall, we believe that this method is easily applicable, cost-effective, and clinically useful for a rapid screening of fusion genes in the initial diagnostic phase of leukemia. Its use can also be extended to the monitoring of minimal residual disease.
The gene Par -4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific proapoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5' AM\/) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SACPar-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes 0-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MU), apoptosis induction assays, and NF-KB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.
BACKGROUNDNovel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. METHODSRNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement. Next, the expression of NR5A2-KLHL29FT was measured by quantitative real-time polymerase chain reaction in colon cancers and matched corresponding normal epithelia. RESULTSThe authors identified the FT NR5A2-KLHL29FT in normal and cancerous epithelia. While investigating this transcript, it was unexpectedly found that it was due to an uncharacterized polymorphic germline insertion of the NR5A2 sequence from chromosome 1 into the KLHL29 locus at chromosome 2, rather than a chromosomal rearrangement. This germline insertion, which occurred at a population frequency of 0.40, appeared to bear no relationship to cancer development. Moreover, expression of NR5A2-KLHL29FT was validated in RNA specimens from samples with insertions of NR5A2 at the KLHL29 gene locus, but not from samples without this insertion. It is interesting to note that NR5A2-KLH29FT expression levels were significantly lower in colon cancers than in matched normal colonic epithelia (P =.029), suggesting the potential participation of NR5A2-KLHL29FT in the origin or progression of this tumor type. CONCLUSIONSNR5A2-KLHL29FT was generated from a polymorphism insertion of the NR5A2 sequence into the KLHL29 locus. NR5A2-KLHL29FT may influence the origin or progression of colon cancer. Moreover, researchers should be aware that similar FTs may occur due to transchromosomal insertions that are not correctly annotated in genome databases, especially with current assembly algorithms. Cancer 2017;123:1507-1515. (c) 2017 American Cancer Society. A novel fusion transcript identified by RNA sequencing, nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 fusion transcript (KLHL29FT), was generated from a polymorphism insertion at the KLHL29 locus instead of a chromosome rearrangement. The expression of NR5A2-KLHL29FT appears to be lower in colon cancers than in matched normal tissues, suggesting potential participation of NR5A2-KLHL29FT in the origin or progression of colon cancer.
Mushroom production is one of the biggest solid state fermentation industries in the world. The success in mushroom planting depends on how the control temperature, humidity and CO2 parameters. This paper presents a novel method for modeling an environment of mushrooms growth to comparing the performance of two controlling methods (fuzzy logic and digital (ON/OFF) control) for controlling mentioned parameters on production rate. The Controllers and other equipment were developed to data collection and analysis of these parameters was performed by using Simulink part of MATLAB software. Precise control of the parameters involved in the growth of mushrooms caused to improve product quality and reduced energy consumption. The results of tests and mean value obtained on two different methods showed that the fuzzy controlling with having least standard deviation, variance and error, is better than digital controlling. Fuzzy controlling system had the lowest fluctuation and lowest band pass. According to gradient of graph, maximum and minimum of results, can conclude that the fuzzy controlling has shown better response in controlling the process. Based on the number of actuators mode changing on both systems, it can be understood that in digital control system, downtime, and depreciation and energy consumption would be higher than the fuzzy control system. (C) 2016 Elsevier Ltd. All rights reserved.
This paper focuses on dynamic modeling, simulation and control of Advanced Automatic Pumping Station with Canal Level Remote Control System using ABB PLC (Programmable Logical Controller) based Fuzzy Logic Controller. The system is designed for the agricultural land where the water level (i.e. canals or rivers) is low and traditional system of irrigation is not working well. System is automated through two different controllers, first controller automate the water reservoir gate according to the upper and lower limits of reservoir level and second controller dealt with speed of two pumps with respect to the set point of water level in canal. For controlling, monitoring and real time visualization of a system, HMI (Humane Interface Machine -CP 405) is connected. The applied control method is based on Fuzzy Logic System, designed in MATLAB Simulink, which can communicate with PLC through OPC server by using gateway. Through GPRS based system communication is done between PLC and canal water level meter. A digital control unit PLC (AC500 PM556-ETH) gets data from the system, take the require actions and make decision to operate the pumping station. Simulation results show that system can effectively operate in both, automatic as well as manual conditions depending on selection switch.
In this paper, we illustrate a proposed method for control that combines the outputs of several individual controllers to improve global control of complex nonlinear plants. In the first part of this paper, we illustrate the proposed method that consists of two levels, where in the top level a fuzzy system represents a superior control that is designed for adjusting the behavior of the individual fuzzy controllers at the lower level. To test the approach, we consider the problem of flight control because it requires several individual controllers. Also a comparison is performed, where the hierarchical control strategy is compared with a simple control approach using the t student test. In this paper, we show that the proposed method outperforms the conventional fuzzy control approach. In the optimal design of the proposed control architecture a genetic algorithm was also applied to tune the parameters of the fuzzy systems in an optimal fashion. (C) 2015 Elsevier B.V. All rights reserved.
Galactose metabolism in the yeast Saccharomyces cerevisiae is carried out by a specialized GAL pathway consisting of structural and regulatory proteins. It is known that cells with unbalanced Gal proteins accumulate toxic metabolic intermediates and exhibit severe growth defects. Recently, we found that the molecular chaperone Hsp90 controls the abundance of multiple Gal proteins, possibly to prevent these defects. Hsp90 regulates various cellular processes including cell morphology in response to environmental cues. Yeast cells are known to resort to filamentous growth upon exposure to galactose or other environmental stresses. Our previous and current findings support the "Hsp90 titration model" of Hsp90 buffering, which links the cell morphology and galactose pathways. Our results suggest that, when a large proportion of Hsp90 molecules are used to help Gal proteins, the Hsp90 client proteins in cell morphology pathways are left unattended, leading to filamentous growth. It remains unclear whether this phenomenon serves any biological function or simply reflects a cellular constraint. Nonetheless, it provides an alternative explanation why the GAL pathway is degenerated in some yeast species.
Galactosemia, an inborn error of galactose metabolism, was first described in the 1900s by von Ruess. The subsequent 100 years has seen considerable progress in understanding the underlying genetics and biochemistry of this condition. Initial studies concentrated on increasing the understanding of the clinical manifestations of the disease. However, Leloir's discovery of the pathway of galactose catabolism in the 1940s and 1950s enabled other scientists, notably Kalckar, to link the disease to a specific enzymatic step in the pathway. Kalckar's work established that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible for the majority of cases of galactosemia. However, over the next three decades it became clear that there were two other forms of galactosemia: type II resulting from deficiencies in galactokinase (GALK1) and type III where the affected enzyme is UDP-galactose 4'-epimerase (GALE). From the 1970s, molecular biology approaches were applied to galactosemia. The chromosomal locations and DNA sequences of the three genes were determined. These studies enabled modern biochemical studies. Structures of the proteins have been determined and biochemical studies have shown that enzymatic impairment often results from misfolding and consequent protein instability. Cellular and model organism studies have demonstrated that reduced GALT or GALE activity results in increased oxidative stress. Thus, after a century of progress, it is possible to conceive of improved therapies including drugs to manipulate the pathway to reduce potentially toxic intermediates, antioxidants to reduce the oxidative stress of cells or use of "pharmacological chaperones" to stabilise the affected proteins. (C) 2015 Elsevier B.V. All rights reserved.
Aims: Understanding the metabolism of lactose and galactose and their regulation in Lactobacillus rhamnosus. Methods and Results: A gene cluster containing nine open reading frames (ORFs) involved in the metabolism of lactose and galactose in Lact. rhamnosus TCELL-1 was sequenced and characterized. The order of the ORFs was lacTEGF and galKETRM. Northern blotting experiments revealed that the gene cluster could be transcribed as one lacTEGF-galKETRM mRNA though three major transcripts (lacTEGF, galKETRM and galETRM) were detected for the gene cluster. The transcription of the lac or gal operon was independently induced in the presence of lactose or galactose. Northern blotting and primer extension experiments found the presence of four putative promoters upstream from the ORFs lacT (lacTp), galK (galKp1 and galKp2) and galE (galEp). The measurements of enzymatic activities of GalK, GalE and GalT suggested that the expression of the gal operon was subjected to a galactose activation and glucose repression mechanism. Conclusions: In Lact. rhamnosus TCELL-1, the galactose moiety of lactose could be metabolized by two alternative pathways (the Leloir and the tagatose 6-phosphate pathways) whereas galactose metabolism could be mediated by the Leloir pathway. Significance and Impact of the Study: This work provides important information about sugar metabolism in Lact. rhamnosus.
We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), alpha-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.
We study the role of environment in the evolution of central and satellite galaxies with the Sloan Digital Sky Survey. We begin by studying the size-mass relation, replicating previous studies, which showed no difference between the sizes of centrals and satellites at fixed stellar mass, before turning our attention to the size-core velocity dispersion (sigma(0)) and mass-sigma(0) relations. By comparing the median size and mass of the galaxies at fixed velocity dispersion, we find that the central galaxies are consistently larger and more massive than their satellite counterparts in the quiescent population. In the star-forming population, we find there is no difference in size and only a small difference in mass. To analyse why this difference may be present, we investigate the radial mass profiles and stellar metallicity of the galaxies. We find that in the cores of the galaxies there is no difference in mass surface density between centrals and satellites, but there is a large difference at larger radii. We also find almost no difference between the stellar metallicity of centrals and satellites when they are separated into star-forming and quiescent groups. Under the assumption that sigma(0) is invariant to environmental processes, our results imply that central galaxies are likely being increased in mass and size by processes such as minor mergers, particularly at high sigma(0), while satellites are being slightly reduced in mass and size by tidal stripping and harassment, particularly at low sigma(0), all of which pre-dominantly affect the outer regions of the galaxies.
Background: Functionalized nanoparticles (NPs) are one promising tool for detecting specific molecular targets and combine molecular biology and nanotechnology aiming at modern imaging. We aimed at ligand-directed delivery with a suitable target-biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising targets are galectins (Gal), due to their strong expression in and on PDAC-cells and occurrence at early stages in cancer precursor lesions, but not in adjacent normal tissues. Results: Molecular probes (10-29 AA long peptides) derived from human tissue plasminogen activator (t-PA) were selected as binding partners to galectins. Affinity constants between the synthesized t-PA peptides and Gal were determined by microscale thermophoresis. The 29 AA-long t-PA-peptide-1 with a lactose-functionalized serine revealed the strongest binding properties to Gal-1 which was 25-fold higher in comparison with the native t-PA protein and showed additional strong binding to Gal-3 and Gal-4, both also over-expressed in PDAC. t-PA-peptide-1 was selected as vector moiety and linked covalently onto the surface of biodegradable iron oxide nanoparticles (NPs). In particular, CAN-doped maghemite NPs (CAN-Mag), promising as contrast agent for magnetic resonance imaging (MRI), were selected as magnetic core and coated with different biocompatible polymers, such as chitosan (CAN-Mag-Chitosan NPs) or polylactic co glycolic acid (PLGA) obtaining polymeric nanoparticles (CAN-Mag@PNPs), already approved for drug delivery applications. The binding efficacy of t-PA-vectorized NPs determined by exposure to different pancreatic cell lines was up to 90%, as assessed by flow cytometry. The in vivo targeting and imaging efficacy of the vectorized NPs were evaluated by applying murine pancreatic tumor models and assessed by 1.5 T magnetic resonance imaging (MRI). The t-PA-vectorized NPs as well as the protease-activated NPs with outer shell decoration (CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac) showed clearly detectable drop of subcutaneous and orthotopic tumor staining-intensity indicating a considerable uptake of the injected NPs. Post mortem NP deposition in tumors and organs was confirmed by Fe staining of histopathology tissue sections. Conclusions: The targeted NPs indicate a fast and enhanced deposition of NPs in the murine tumor models. The CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac interlocking steps strategy of NPs delivery and deposition in pancreatic tumor is promising.
An analogue-digital circuit for thermal control of the resonance frequency of optical ring resonators is suggested. This approach is characterised by a low power dissipation of 209 mu W and needs only 2800 mu m(2) of chip area in 0.16 mu m CMOS technology. Therefore, it is well appropriate to be used to control each of the cells of large optical switch matrices. Compared with a purely analogue heater control approach the power dissipation is reduced to 7%.
During recent years, the practice of adding game design to non-game services has gained a relatively large amount of attention. Popular discussion connects gamification to increased user engagement, service profitability, goal commitment and the overall betterment of various behavioral outcomes. However, there is still an absence of a coherent and ample body of empirical evidence that would confirm such expectations. To this end, this paper reports the results of a 2 year (1 + 1 year - between- group) field experiment in gamifying a service by implementing a game mechanic called 'badges'. During the experiment a pre-implementation group (N = 1410) was monitored for 1 year. After the implementation, the post-implementation (the gamified condition) group (N = 1579) was monitored for another full year. Results show that users in the gamified condition were significantly more likely to post trade proposals, carry out transactions, comment on proposals and generally use the service in a more active way. (C) 2015 Elsevier Ltd. All rights reserved.
Gamification has become a focus of attention in an increasing number of fields including business, education, and health care. Through a wide range of applications and support functions, its potential for the tourism industry is significant. Gamification of tourism can contribute to a more rewarding interactions and higher level of satisfaction, as well as increase brand awareness and loyalty to the destination. As one of the first attempts to conceptualize gamification of tourism, this paper examines gaming in general terms and the application of it in specific tourism fields. It identifies game design elements that can contribute to a meaningful gamification. A few cases of best practices are presented to show how this innovative concept can benefit tourism marketing. Implications for tourism marketing and management are discussed as well as future research recommendations. (C) 2016 Elsevier Ltd. All rights reserved.
Human gamma delta T cells comprise a first line of defense through T-cell receptor (TCR) recognition of stressed cells. However, the molecular determinants and stress pathways involved in this recognition are largely unknown. Here we show that exposure of tumor cells to various stress situations led to tumor cell recognition by a V.8Vd3 TCR. Using a strategy that we previously developed to identify antigenic ligands of gamma delta TCRs, annexin A2 was identified as the direct ligand of V.8Vd3 TCR, and was found to be expressed on tumor cells upon the stress situations tested in a reactive oxygen species-dependent manner. Moreover, purified annexin A2 was able to stimulate the proliferation of a Vd2neg gamma delta T-cell subset within peripheral blood mononuclear cells and other annexin A2-specific Vd2neg gamma delta T-cell clones could be derived from peripheral blood mononuclear cells. We thus propose membrane exposure of annexin A2 as an oxidative stress signal for some Vd2neg gamma delta T cells that could be involved in an adaptive stress surveillance.
This paper presents an improved phase leg power loop design for enhance mode lateral structure Gallium Nitride (GaN) transistors. Static characterization results of a 650V/30A GaN transistor are presented to determine the design parameters of the gate driver circuits. The control of Common Mode (CM) noise current propagation is considered during the gate driver design by optimizing the power distribution and grounding structure of the gate driver and digital control circuits. By differentiating the propagation path impedance of digital control circuits and their power supply circuits, conductive CM noise can propagate through power supply path to protect the digital control circuits. In order to reduce current commutation loop inductance within the GaN phase leg, an improved power loop design with vertical structure is proposed for lateral structure GaN transistors which can significantly reduce power loop inductance compared with conventional lateral power loop design. The design is verified through experiments on a phase leg prototype which prove the performance of the proposed phase leg on the overvoltage reduction during current transition along with less cross-coupling between power loop and gate loop compared with conventional lateral power loop design. A full bridge voltage source inverter is implemented with the designed phase leg and tested with EMI noise measurement that verifies the effectiveness of the CM propagation path control.
This paper presents the first multi vector energy analysis for the interconnected energy systems of Great Britain (GB) and Ireland. Both systems share a common high penetratioh of wind power, but significantly different security of supply outlooks. Ireland is heavily dependent on gas imports from GB, giving significance to the interconnected aspect of the methodology in addition to the gas and power interactions analysed. A fully realistic unit commitment and economic dispatch Model coupled to an energy flow model of the gas supply network is developed. Extreme weather events driving increased domestic gas demand and low wind power output were utilised to increase gas supply network stress. Decreased wind profiles had a larger impact on system security than high domestic gas demand. However, the GB energy system was resilient during high demand periods but gas network stress limited the ramping capability of localised generating units. Additionally, gas system entry node congestion in the Irish system was shown to deliver a 40% increase in short run costs for generators. Gds storage was shown to reduce the impact of high demand driven congestion delivering a reduction in total generation costs of 14% in the period studied and reducing electricity imports from GB, significantly contributing to security of supply. (C) 2016 The Authors. Published by Elsevier Ltd.
The objective of this study is to analyze and optimize a solar assisted gas turbine system. Parabolic trough collectors are used in order to supply a part of the demanded heat input, reducing the natural gas consumption and leading to an environmental friendly system. Emphasis is given in the pressure losses in the collector field loop which reduce the pressure level in the turbine inlet, leading to lower electricity production. In the first part of this study, the gas turbine and the collector field are investigated separately and in the second part, the solar assisted gas turbine is investigated parametrically and it is optimized. In the optimization part, a multi-objective optimization is performed by setting as goals the minimization of the collector area, of the fuel consumption and of the inversed electricity production. The final results proved that 1050 collector modules lead to 0.3389 kg/s natural gas consumption and to electricity production equal to 14.81 MWel. This optimum solution leads to 64% fuel savings with a 2.8% penalty on the produced electricity. The system is analyzed in steady state conditions with the Engineering Equator Solver (EES). (C) 2017 Elsevier Ltd.
A comparative analysis of electricity and gas demand in the industrial sector over a long period of time appears to be absent in the literature. In fact, unlike electricity demand, natural gas demand in the industrial sector has not been well researched. Our paper aims to cover this gap. It analyses electricity and gas consumption patterns by the Spanish manufacturing sector, between 1995 and 2010. A novel and innovative quantitative approach based on, both, homogenous and heterogeneous estimators was used for this purpose. The results of the no-spurious estimations (the Augmented Mean Group Estimator) show that the price elasticity of gas demand is significantly negative and within the -0.44 to -0.48 range. In contrast, the price elasticity of electricity demand is not statistically significant. The income elasticities show the opposite pattern: those of natural gas are not statistically significant, whereas the income elasticities for electricity are statistically significant and within the 0.22 to 0.29 range. Compared to previous findings, our preferred estimation shows some variation regarding price elasticities of natural gas demand. (C) 2017 Elsevier Ltd. All rights reserved.
Small-scale thermal treatment of municipal solid waste (MSW) was investigated using mass and energy balances based on the assumption of thermodynamic equilibrium. A typical average MSW composition from the literature was used as basis for modelling of a one ton per day waste gasification facility (plant). Syngas production by pyrolysis, stoichiometric O-2 addition and auto-thermal (gasification with oxygen and/or air where no external heat input is required) combustion were considered. These cases were evaluated for production of electricity only, and steam. From purely thermodynamic considerations, it was observed that auto-thermal oxygen gasification produces the most electricity (47.00 kWe) and oxygen plasma gasification produces a positive net amount (4.07 kWe) on a 1 ton per day scale. Although auto-thermal air gasification also produces a net positive amount, the calorific value of the syngas is too low to fuel an internal combustion engine. As expected, the amount of steam generated by the different scenarios is high due to higher process efficiencies. The close-coupled auto-thermal oxygen process proved to be the most efficient. The cost of additional oxygen generation was however not taken into account, and may change the picture significantly.
Gasification is a promising alternative for polymeric waste valorization when mechanical recycling is unfeasible on account of its heterogeneity or partial contamination, or simply when it yields a product of lower quality than what the market requires. Apart from its application for electricity generation, the waste-derived syngas shows a great potential for chemical waste recycling for the synthesis of hydrogen, methane, natural gas or methanol. In spite of the effort devoted so far to the experimental demonstration of these processes to enable this technology to access commercial stage, it is still necessary to develop detailed models of the process that allow a precise prediction of the resulting syngas composition, as well as tar formation and global efficiency of the process. This research work presents the development of a polyolefin gasification model for fluidized bed reactors. The model details the behaviour of primary pyrolysis and homogeneous reactions of oxidation, steam reforming, aromatization and thermal cracking. To accomplish this, it adopts new modelling strategies for the definition of primary tar species in order to reflect their twofold nature (aliphatic and aromatic), as well as to describe kinetics and stoichiometry involved in thermal cracking processes of tar species. The model is able to successfully predict the generation, volume composition and heating value of the syngas, final tar generation and global efficiency of the process. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC). Methods: Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1. Results: In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression. Conclusions: Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2 axis acted as critical regulator pathway in GC tumorigenesis and progression, which provided a novel therapeutic target for gastric cancer.
Despite advances in molecular biology, imaging, and treatment, gastric neoplasms remain a significant cause of morbidity and mortality; gastric adenocarcinoma is the fifth most common malignancy and third most common cause of death worldwide (Brenner et al., Methods Mol Biol 472:467-477, 2009; Howson et al. Epidemiol Rev 8:1-27, 1986; Roder, Gastric Cancer 5(Suppl 1):5-11, 2002; Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, 2013). Because of both the frequency at which malignant gastric tumors occur as well as the worldwide impact, gastric neoplasms remain important lesions to identify and characterize on all imaging modalities. Despite the varied histologies and behaviors of these neoplasms, many have similar imaging features. Nonetheless, the treatment, management, and prognosis of gastric neoplasms vary by pathology, so it is essential for the radiologist to make every effort to differentiate between these lesions and raise the less common entities as differential diagnostic considerations when appropriate.
Circular RNAs are a special class of endogenous RNAs characterized by jointing 3' and 5' ends together via exon or intron circularization. Recent studies found that circular RNAs are involved in the development of some human diseases. However, little is known about their roles in human gastric cancer. In this study, we chose hsa_circ_0001895 as a targeted circRNA to investigate its clinical significances in gastric cancer patients. Hsa_circ_0001895 expression levels in five gastric cancer cell lines and 257 specimens of tissues were measured by real-time quantitative reverse transcription polymerase chain reaction. Then, the potential relationship between hsa_circ_0001895 expression levels and patients' clinicopathological factors was investigated. A receiver operating characteristic curve was constructed for evaluating the diagnostic value of hsa_circ_0001895. Hsa_circ_0001895 expression levels in five detected gastric cancer cell lines (AGS, BGC-823, HGC-27, MGC-803, and SGC-7901) were all significantly downregulated than those in normal gastric epithelial GES-1 cells. Besides, compared with healthy control tissues, it was downregulated not only in 69.8% (67/96) gastric cancer tissues but also in gastric precancerous lesions. Moreover, hsa_circ_0001895 expression levels were significantly correlated with cell differentiation, Borrmann type, and tissue carcino-embryonic antigen expression. Our results suggested that hsa_circ_0001895 may play crucial roles during gastric cancerogenesis and is a potential biomarker for clinical prognosis prediction.
Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.
O-GlcNAcylation is a monosaccharide modification by a residue of N-acetylglucosamine (GlcNAc) attached to serine or threonine moieties on nuclear and cytoplasmic proteins. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Increasing evidence suggests that O-GlcNAcylation is involved in a variety of human cancers. However, the exact role of O-GlcNAcylation in tumor progression remains unclear. Here, we show that O-GlcNAcylation accelerates oncogenic phenotypes of gastric cancer. First, cell models with increased or decreased O-GlcNAcylation were constructed by OGT overexpression, downregulation of OGA activity with specific inhibitor Thiamet-G, or silence of OGT. MTT assays indicated that O-GlcNAcylation increased proliferation of gastric cancer cells. Soft agar assay and Transwell assays showed that O-GlcNAcylation significantly enhanced cellular colony formation, migration, and invasion in vitro. Akt1 activity was stimulated by upregulation of phosphorylation at Ser473 mediated by elevated O-GlcNAcylation. The enhanced cell invasion by Thiamet-G treatment was suppressed by PI3K inhibitor LY294002. Although the cell invasion induced by Thiamet-G was reduced by Akt1 shRNA, it was still higher in comparison with that to the control (cells with Akt1 shRNA alone). And Akt1 overexpression promoted Thiamet-G-induced cell invasion. These results suggested that O-GlcNAcylation enhanced oncogenic phenotypes possibly partially involving PI3K/Akt signaling pathway. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 841-851, 2016
Background: Suitable diagnostic markers for cancers are urgently required in clinical practice. Long non-coding RNAs, which have been reported in many cancer types, are a potential new class of biomarkers for tumor diagnosis. Results: Five lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were validated to be increased in gastric cancer tissues. Furthermore, we found that plasma level of these five lncRNAs were significantly higher in gastric cancer patients compared with normal controls. By receiver operating characteristic analysis, we found that the combination of plasma lncRNAs with the area under the curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is a better indicator of gastric cancer than their individual levels or other lncRNA combinations. Simultaneously, we found that the expression levels of a series of MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of them higher than that in healthy control plasma samples. Materials and Methods: LncRNA gene expression profiles were analyzed in two pairs of human gastric cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer-associated lncRNAs were selected and assessed by quantitative real-time polymerase chain reaction in gastric tissues, and 5 of them were further analyzed in gastric cancer patients' plasma. Conclusions: Our results demonstrate that certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are enriched in human gastric cancer tissues and significantly elevated in the plasma of patients with gastric cancer. These findings indicate that the combination of these four lncRNAs might be used as diagnostic or prognostic markers for gastric cancer patients.
AIM To investigate the role of Delta 133p53 isoform in nuclear factor-kappa B (NF-kappa B) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells. METHODS The growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Delta 133p53, p53 beta, and the NF-kappa B p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose- dependent manner by co-treatment with PDTC (P < 0.01). RESULTS RT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Delta 133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P0.01). CONCLUSION Delta 133p53 isoform (not p53 beta) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-kappa B pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.
The protocadherin 7 is a member of the protocadherin family that expressed aberrantly in many types of human cancers. However, its expression, function, and underlying mechanisms are little known in gastric cancer. In this study, we detected protocadherin 7 expression in gastric cancer tissues and non-tumorous gastric mucosa tissues by realtime quantitative polymerase chain reaction and immunohistochemistry. The association of protocadherin 7 expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium))and transwell assays were performed to assess the effect of protocadherin 7 on proliferation, migration, and invasion in gastric cancer cell lines. Moreover, real-time quantitative polymerase chain reaction and western blot were used to detect the expression of epithelial-mesenchymal transition markers. Protocadherin 7 expression was decreased gradiently from normal tissue to gastric cancer, especially in gastric cancer tissue with lymph node metastasis. Low expression of protocadherin 7 was significantly associated with Lauren's classification (p = 0.0005), lymph node metastases (p = 0.0002), and tumor node metastasis stage (p = 0.0221), as well as poor prognosis (p < 0.05). Furthermore, down-regulation of protocadherin 7 in gastric cancer cell lines significantly increased their migration and invasion abilities (both p0.05). Additionally, our results demonstrated that E-cadherin expression was down-regulated in gastric cancer cells with protocadherin 7 depletion. Our data indicated that protocadherin 7 may play important roles in the invasion and metastasis of gastric cancer, and protocadherin 7 could suppress cell migration and invasion through E-cadherin inhibition. Protocadherin 7 can serve as a novel biomarker for diagnostic and prognosis in patients with gastric cancer.
Neuroendocrine (NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades probably due to the improvements in imaging and diagnosis. The recent advances in molecular biology have translated into an expansion of therapeutic approaches to these patients. Somatostatin analogs, which initially were approved for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Several new drugs such as antiangiogenics and others targeting mammalian target of rapamycin pathways have been approved to treat progressive pancreatic neuroendocrine tumors (NETs) although their role in nonpancreatic is still controversial. The treatment of NETs requires a coordinated multidisciplinary approach. The management of localized NETs primarily involves surgical resection followed by surveillance. However, the treatment of unresectable and/or metastatic disease may involve a combination of surgical resection, systemic therapy, and liver-directed therapies with the goal of alleviating symptoms of peptide release and controlling tumor growth. This article will review the current therapeutic strategies for metastatic gastroenteropancreatic NETs and will take a glimpse into the future approaches.
Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies. This understanding, although still limited, has the potential to enhance our ability to develop targeted therapies in conjunction with the ability to identify actionable gene mutations and perform genomic profiling to predict drug resistance. Several cell surface growth factor receptors have been found to play a prominent role in GE cancer cell signaling. This discovery has led to the approval of 2 agents within the last few years: trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody used in the first-line treatment of HER2-positive GE cancers, and ramucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody that is currently used in later lines of therapy. This review discusses the current state of molecular testing in GE cancers, along with the known molecular biology and current and investigational treatments. The development of trastuzumab and ramucirumab represents a significant advance in our ability to make use of GE tumor molecular profiles. As our understanding of the impact of molecular aberrations on drug effectiveness and disease outcomes increases, we anticipate improved therapy for patients with GE cancers.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (< 10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besancon between August 2005 and October 2014 were prospectively included in the present study. KIT, PDGFRA and KRAS-codons 12 and 13 as well as BRAF codon 600 mutations were analyzed by Sanger sequencing or SNaPshot. KIT and PDGFRA mutations were detected in 71.2 and 19.2% of the cases, respectively. A total of 43 different mutations were detected of which 13 had never been described. As expected, KIT exon 9 and PDGFRA exon 18 mutations were associated with small bowel and gastric localizations respectively. No mutation was found in KRAS and BRAF. Molecular studies are critical to improve the management of GISTs. Our study enhances the current knowledge by describing 13 new mutations in KIT. A common molecular pattern in all KIT exon 11 substitutions is also described for the first time in this study but its significance remains unknown since genetic and environmental risk factors favoring the development of GISTs such as DNA repair defects and exposure to carcinogens are not currently known.
This study tested whether including objects perceived as highly interesting by children with autism during a gaze following task would result in increased first fixation durations on the target objects. It has previously been found that autistic children differentiate less between an object another person attends to and unattended objects in terms of this measure. Less differentiation between attended and unattended objects in ASD as compared to control children was found in a baseline condition, but not in the high interest condition. However, typically developing children differentiated less between attended and unattended objects in the high interest condition than in the baseline condition, possibly reflecting reduced influence of gaze cues on object processing when objects themselves are highly interesting.
Biological functions of globo-series glycosphingolipids are not well understood. In this study, murine cDNAs of two glycosyltransferases responsible for the synthesis of globo-series glycolipids and mRNA expression of those genes were analyzed. Distribution of their products was also analyzed. Murine cDNAs for Gb3/CD77 synthase and Gb4 synthase predicted that both of them are type II membrane proteins with 348 and 331 amino acids, respectively. In northern blotting, Gb3/CD77 synthase gene was mainly expressed in kidney and lung but also detected in many other tissues. Gb4 synthase was expressed in brain, heart, kidney, liver, skin, and testis. In the immunohistological analysis, Gb3/CD77 was mainly expressed in the proximal tubules as revealed with coincidental expression with angiotensin-converting enzyme (ACE). In spleen, it was detected in pre-B cells in the peripheral region of the white pulp, as suggested with coincidental expression with CD10. It was also expressed on the endothelia of the alveolar capillaries in lung and on the sebaceous ducts aside of the hair follicles. Gb4 was also detected mainly on the proximal tubules in kidney and on the endothelia of the alveolar capillaries in lung as Gb3/CD77. But it was also detected on the epithelium of the bronchus, seminiferous tubules and tails of spermatozoa in testis, blood vessels of choroids plexus and endothelial cells in brain, and central and hepatoportal veins in liver. The expression patterns of two genes and their products almost corresponded with some exception. The results would provide essential information for the functional studies of globo-series glycolipids.
In this paper a high gain low noise Op-Amp has been designed. In designing of a high gain Op-Amp, for large values of coupling capacitor, gain will decrease. Since our requirement was to increase the gain, so we have designed a three stage Op-Amp. Our designed circuit provides gain of 78.4 dB, which is very much larger than two stage Op-Amp. There is a trade-off between various parameters like Phase margin, gain, slew rate etc. For example, to achieve larger values of GBW, PM will decrease. We have compared the results for two values of input common mode range. Improvement in the designed circuit is done to achieve the desired GBW by recalculating the transistor's W/L ratios and then simulating the results. Gain Bandwidth product of 176.9 MHz and Phase Margin greater than 60 degrees is achieved but at the cost of power dissipation and area. The Op-Amp is designed in gpdk 180 nm CMOS technology.
Microarrays can quantitatively measure the expression of thousands of genes simultaneously but they are also powerful tools to examine the expression of specific genes in different tissues and cell types. They complement other methods used to detect gene expression at the transcript level, including Northern blotting and RT-PCR. This study uses oligonucleotide microarray expression profiling to compare maize beta-tubulin (tub) gene expression at the transcript level in different tissues and during various stages of development and adds to what is known about maize beta-tubulin expression. In maize, at least nine beta-tubulin genes are expressed. The presence of multiple tub genes suggests that some could have evolved to provide fine control of expression or even have distinct biological or physiological properties in the plant. This is supported by the differential expression at the transcript level of the maize beta-tubulins in different tissues during development. The following work has added evidence of maize beta-tubulin gene differential expression and regulation. Based oil microarray data, some beta-tubulins exhibit statistically significant differences in transcript abundance in 11-day old seedling shoots, immature ears, 19-DAP embryos, 13-DAP endosperm and 19-DAP endosperm. There are also different expression patterns for many of the tubulin genes within the tissues Studied. As the plant develops it may use beta-tubulins in different amounts in specific tissues, and these tubulins may even interact differently with other proteins present at these developmental stages. In immature ears, tub1 and tub2 have higher transcript abundances. Comparisons of expression patterns indicate that tub3 and tub4 have very similar expression patterns, which may be a result of similar transcriptional regulation. The highest transcript abundance of these two genes occurs in developing seedling shoots. tub3 and tub4 transcripts have also been detected for the first time in maize endosperm. This chapter describes a variety of methods for array analysis of tubulin gene expression as well as important considerations before taking oil this type of work.
In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. While the role of GDNF in the testis stem cell niche is established, little is known about how this factor is regulated. Our previous studies on NOTCH activity in Sertoli cells demonstrated a role of this pathway in limiting stem/progenitor cell numbers, thus ultimately downregulating sperm cell output. In this study we demonstrate through a double-mutant mouse model that NOTCH signaling in Sertoli cells functions solely through the canonical pathway. Further, we demonstrate through Dual luciferase assay and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis that the NOTCH targets HES1 and HEY1, which are transcriptional repressors, directly downregulate GDNF expression by binding to the Gdnf promoter, thus antagonizing the effects of FSH/ cAMP. Finally, we demonstrate that testicular stem/progenitors cells are activating NOTCH signaling in Sertoli cells in vivo and in vitro through the NOTCH ligand JAG1 at their surface, indicating that these cells may ensure their own homeostasis through negative feedback regulation.
The beta-keratins constitute the hard epidermis and adhesive setae of gecko lizards. Nucleotide and amino acid sequences of beta-keratins in epidermis of gecko lizards were cloned from mRNAs. Specific oligonucleotides were used to amplify by 3'- and 5'-rapid amplification of cDNA ends analyses five specific gecko beta-keratin cDNA sequences. The cDNA coding sequences encoded putative glycine-proline-serine-rich proteins of 16.8-18 kDa containing 169-191 amino acids, especially 17.8-23% glycine, 8.4-14.8% proline, 14.2-18.1% serine. Glycine-rich repeats are localized toward the initial and end regions of the protein, while a central region, rich in proline, has a strand conformation (beta-pleated fold) likely responsible for the formation of beta-keratin filaments. It shows high homology with a core region of other lizard keratins, avian scale, and feather keratins. Northern blotting and reverse transcriptase-polymerase chain reaction (RTPCR) analysis show a higher beta-keratin gene expression in regenerating epidermis compared with normal epidermis. In situ hybridization confirms that mRNAs for these proteins are expressed in cells of the differentiating oberhautchen cells and beta-cells. Expression in adhesive setae of climbing lamellae was shown by RT-PCR. Southern blotting analysis revealed that the proteins are encoded by a multigene family. PCR analysis showed that the genes are presumably located in tandem along the DNA and are transcribed from the same DNA strand like in avian beta-keratins.
The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus.
Introduction: Tuberculous Meningitis (TBM) is the most severe form of Central Nervous System Tuberculosis (CNS- TB) and constitutes about 6% of all Extrapulmonary TB (EPTB) cases. Most guidelines for the diagnosis and management of TBM agree on the use of simple Cerebrospinal Fluid (CSF) analysis using molecular tools like Polymerase Chain Reaction (PCR). However, the sensitivity of PCR varies while using a CSF sample. In the present study, we have compared the diagnostic utility of PCR assay in both peripheral blood and CSF sample collected from TBM cases. Aim: To evaluate the application of the peripheral blood PCR assay as an alternate tool for TBM diagnosis compared to conventional CSF-PCR based system Materials and Methods: A total of 50 TBM patients were prospectively recruited from in patient department wards of Central India Institute of Medical Sciences (CIIMS) between January 2014 - Feburary 2015. Mycobacterium tuberculosis (MTB) specific IS6110 PCR and BactT liquid culture were performed in 20 of recruited cases classified as Stage 1, 2 and 3 based on British Medical Research Council (BMRC) contemporary clinical criteria for the severity of TBM. Clinical characteristics were summarised in terms of percentages for categorical variables, i.e., age groups, gender, signs and symptoms. All statistical analysis was carried out using MedCalc software version 11.6. Results: Overall IS6110 PCR positivity in CSF was around 80% (16/20), which was higher than culture (29.3%) and peripheral blood (39%). Out of 8 positive cases, stage wise positivity of peripheral blood PCR assay in three TBM stages was 0% (stage1) 50% (stage 2) and 67% (Stage 3) respectively. Positivity of peripheral blood PCR was significantly more (86%) in patients with CSF culture/IS6110 PCR positive for MTB infection with sensitivity and specificity of 50 and 100% respectively. Increased positivity rates of peripheral blood PCR was observed with decreased CSF/Blood sugar ratio in stage 3 cases, suggesting enhanced probability of mycobacterial blood dissemination in cases of TBM severity. Conclusion: Our results suggest that although the molecular diagnosis of TBM infection in CSF remains the method of choice, peripheral blood based PCR can be used as a good alternative to CSF in case of TBM severity where the repeated CSF collection may be needed. However, study demands further validation in large cohorts to justify the present hypothesis.
Northern blotting analysis is a classical method for analysis of the size and steady-state level of a specific RNA in a complex sample. In short, the RNA is size-fractionated by gel electrophoresis and transferred by blotting onto a membrane to which the RNA is covalently bound. Then, the membrane is analysed by hybridization to one or more specific probes that are labelled for subsequent detection. Northern blotting is relatively simple to perform, inexpensive, and not plagued by artefacts. Recent developments of hybridization membranes and buffers have resulted in increased sensitivity closing the gap to the more laborious nuclease protection experiments.
Several studies have demonstrated that women show a greater interest for social information and empathic attitude than men. This article reviews studies on sex differences in the brain, with particular reference to how males and females process faces and facial expressions, social interactions, pain of others, infant faces, faces in things (pareidolia phenomenon), opposite-sex faces, humans vs. landscapes, incongruent behavior, motor actions, biological motion, erotic pictures, and emotional information. Sex differences in oxytocin-based attachment response and emotional memory are also mentioned. In addition, we investigated how 400 different human faces were evaluated for arousal and valence dimensions by a group of healthy male and female University students. Stimuli were carefully balanced for sensory and perceptual characteristics, age, facial expression, and sex. As a whole, women judged all human faces as more positive and more arousing than men. Furthermore, they showed a preference for the faces of children and the elderly in the arousal evaluation. Regardless of face aesthetics, age, or facial expression, women rated human faces higher than men. The preference for opposite-vs. same-sex faces strongly interacted with facial age. Overall, both women and men exhibited differences in facial processing that could be interpreted in the light of evolutionary psychobiology. (C) 2016 Wiley Periodicals, Inc.
ObjectiveThere is evidence that some transgender people find aspects of the Standards ofCare (SOC) for theHealth ofTranssexual,Transgender, andGenderNonconformingPeople, and/or their implementation by health professionals, problematic and counterproductive to transitioning. This study evaluated the significance of this dissatisfaction to the transitioning and mental health of transgender people. Method161 self-identified transgender people responded to an online survey that assessed satisfaction with health services provided in accordance with SOC guidelines, satisfaction with health professionals assisting with their transition, personal hardiness, gender congruence, steps to transition, and depression, anxiety, and stress. ResultsAlthough results revealed dissatisfaction with the Standards of Care and with health professionals (particularly psychiatrists), subsequent path analyses conducted via structural equation modelling failed to reveal associations between this dissatisfaction and factors relevant to transitioning or mental health. However, personal hardiness was found to be associated with greater progress in transitioning and, by way of this, improved gender congruence, self-esteem, and mental health. ConclusionWhile the results reveal dissatisfaction with the Australian health system and its professionals, this does not appear to translate into poor mental health outcomes. Rather personal hardiness during transition is the important predictor of transitioning and mental health. This argues for greater emphasis to be placed on building and supporting personal resilience in transgender people.
The rapid advances in the field of computational genomics and bioinformatics have motivated the development of innovative engineering methods for data acquisition, interpretation, and analysis. With the help of the later methods, many processes in molecular biology can be modeled and further analyzed. Identification and discovery of the coding regions in the genomic structure using computational algorithms is a clear example of such processes. This work proposes a novel application of well-known principles and concepts from communications theory and digital signal processing for the detection of protein coding regions in prokaryotic genomes. The proposed algorithm employs a polyphase complex mapping scheme to provide a numerical representation of the genomic sequences involved in the analysis. It then utilizes concepts in communications theory such as correlation, the maximal ratio combining (MRC) algorithm, and filtering to generate a signal whose peaks and troughs signify coding and noncoding regions, respectively. The proposed algorithm is applied to several prokaryotic genome sequences. Two Bayesian classifiers are designed to evaluate the performance of the proposed algorithm. The obtained simulation results show that the algorithm is able to efficiently and accurately identify protein coding regions with sensitivity and specificity values comparable to well-known gene detection methods in prokaryotes such as GLIMMER and GeneMark. This further proves the relevance of using communications theory concepts for genomic sequence analysis. (C) 2016 Elsevier Ltd. All rights reserved.
The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) pathway is revolutionizing biological research. Modifications to this primitive prokaryotic immune system now enable scientists to efficiently edit DNA or modulate gene expression in living eukaryotic cells and organisms. Thus, many laboratories can now perform important experiments that previously were considered scientifically risky or too costly. Here, we describe the components of the CRISPR/Cas system that have been engineered for use in eukaryotes. We also explain how this system can be used to genetically modify cell lines and model organisms, or regulate gene expression in order to search for new participants in biological pathways. (c) 2017 American Society for Bone and Mineral Research.
Objective: Normalization of mRNA data, i.e., the calculation of mRNA expression values comparable in between different experiments, is a major issue in biomedical and orthopaedic/rheumatology research, both for single-gene technologies [Northern blotting, conventional and quantitative polymerase chain reaction (qPCR)] and large-scale gene expression experiments. In this study, we tested several established normalization methods for their effects on gene expression measurements. Method. Five standard normalization strategies were applied on a previously published data set comparing peripheral and central late stage osteoarthritic cartilage samples. Results: The different normalization procedures had profound effects on the distribution as well as the significance values of the gene expression levels. All applied normalization procedures, except the median absolute deviation scaling, showed a bias towards up- or down-regulation of genes as visualized in volcano plots. Of interest, the P-values were much more depending on the normalization procedure than the fold changes. Ten commonly used housekeeping genes showed a significant variability in between the different specimens investigated. The gene expression analysis by cDNA arrays was confirmed for these genes by qPCR. Conclusion: This study documents how much normalization strategies influence the outcome of gene expression profiling analysis (i.e., the detection of regulated genes). Different normalization approaches can significantly change the P-values and fold changes of a large number of genes. Thus, it is of vital importance to check every individual step of gene expression data analysis for its appropriateness. The use of global robustness and quality measures for analyzing individual outcomes can help in estimating the reliability of final microarray study results. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
This study presents the isolation and characterization of a novel nonsymbiotic Hb gene from sessile oak (Quercus petraea) seedlings, herein designated QpHb1. The cellular and tissue expression of QpHb1 was analysed by Northern blotting and in situ hybridization. The encoded protein was predicted to consist of 161 amino acid residues, and shares 71 and 51% amino acid sequence identity with the Arabidopsis class 1 and 2 nonsymbiotic Hb, respectively. Northern blot analysis revealed that QpHb1 was strongly expressed in roots. Spatial expression analysis of QpHb1 in the root apical region of sessile oak by in situ hybridization indicated that transcripts were mostly abundant in protoxylem cell initials, some cortical cells and the protoderm. In addition, when comparing the expression profile of QpHb1 in sessile and pedunculate oak (Quercus robur), two species with contrasted hypoxia tolerance, the transcript level of QpHb1 rose early in the most flood-tolerant species, pedunculate oak, during root submergence. The spatial-temporal expression of QpHb1 suggests that this gene could participate in perception and signalling during hypoxia.
Much effort has been devoted to the metabolic engineering of Klebsiella pneumoniae; however, our knowledge of the actual expression level of promoters used in K.pneumoniae is limited. In this study, the expression levels of three promoters were compared systematically by using the lacZ reporter gene with different carbon sources in K.pneumoniae. The results showed that, although promoters PT5 and Ptac designed for Escherichia coli were functional, PT5 appeared more efficient and the induction/repression ratio of Ptac was decreased extremely in K.pneumoniae. The basal level of Ptac for lacZ expression reached 396.5U/mg, which was 9.5-fold higher compared with PT5 in LB medium, indicating Ptac can be used as an efficient constitutive promoter as well as an efficient induced promoter in K.pneumoniae. In different carbon sources medium, a newly constructed endogenous constitutive Pbud proved to be a stable and weak promoter. On the basis of our data, a set of Pbud and Ptac promoters could meet the broad range (about 1,000 orders of magnitude) of gene expression needed for engineered K.pneumoniae in glycerol-based medium. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Lung cancer is the deadliest among all cancers in the US for both men and women. Early detection of premalignant lesions or tumors appears to be a promising approach to reducing the morbidity and mortality from lung cancer because the survival of early stage lung cancer patients is better than that of patients with advanced cancers. We approached the identification of early biomarkers of human lung carcinogenesis, by combining the use of cDNA array and an in vitro human lung carcinogenesis model that consists of normal (NHBE), immortalized (BEAS-2B and 1799), transformed ( 1198) and tumorigenic (1170-I) human bronchial epithelial (HBE) cells. We hypothesized that certain genes that are expressed differentially among these cells can serve as both biomarkers for early detection and targets for intervention. Nineteen genes were downregulated and six were upregulated in tumorigenic 1170-I HBE cells compared to normal HBE cells ( NHBE) using cDNA array. Downregulated genes encode cell-to-cell and cell-to-matrix adhesion-related proteins, calcium-binding proteins and some enzymes or growth factor-related proteins. The functions of upregulated gene were more variable. Similar expression of selected genes was found in different nonsmall cell lung cancer cell lines analyzed by Northern blotting. Furthermore, the differential expression of some genes was also observed by in silico analysis of database of human lung tumors. The differentially expressed genes encode calcium-binding proteins and cell-cell and cell-matrix adhesion proteins. Furthermore, Northern blotting analysis of RNA from different cell lines comprising an in vitro carcinogenesis model including normal, immortalized, transformed, and tumorigenic cells indicated that the expression of subsets of the identified genes changed at different stages of carcinogenesis. These data show that the in vitro carcinogenesis cell system could be useful for discovering potential biomarkers of early and late stages of lung carcinogenesis and targets for chemoprevention.
Zymoseptoria tritici, the causal agent of septoria tritici blotch, a serious foliar disease of wheat, is a necrotrophic pathogen that undergoes a long latent period. Emergence of insensitivity to fungicides, and pesticide reduction policies, mean there is a pressing need to understand septoria and control it through greater varietal resistance. Stb6 and Stb15, the most common qualitative resistance genes in modern wheat cultivars, determine specific resistance to avirulent fungal genotypes following a gene-for-gene relationship. This study investigated compatible and incompatible interactions of wheat with Z. tritici using eight combinations of cultivars and isolates, with the aim of identifying molecular responses that could be used as markers for disease resistance during the early, symptomless phase of colonization. The accumulation of TaMPK3 was estimated using western blotting, and the expression of genes implicated in gene-for-gene interactions of plants with a wide range of other pathogens was measured by qRT-PCR during the presymptomatic stages of infection. Production of TaMPK3 and expression of most of the genes responded to inoculation with Z. tritici but varied considerably between experimental replicates. However, there was no significant difference between compatible and incompatible interactions in any of the responses tested. These results demonstrate that the molecular biology of the gene-for-gene interaction between wheat and Zymoseptoria is unlike that in many other plant diseases, indicate that environmental conditions may strongly influence early responses of wheat to infection by Z. tritici, and emphasize the importance of including both compatible and incompatible interactions when investigating the biology of this complex pathosystem.
Microarray analysis was initially performed to screen for differentially expressed genes between nitrate-and ammonium-fed rice (Oryza sativa L.) leaves. In total, 198 genes were shown to have a unique expression response to each treatment and most of the genes for which function is known were involved in signal transduction, plant stress resistance, transcriptional regulation, and basic metabolism. Northern blotting analysis confirmed that expression of the MT and PCS genes was highly upregulated in ammonium-fed leaves compared with expression in nitrate-fed leaves and it was further revealed that ammonium-fed leaves accumulated more cysteine and glutathione. The upregulated expressions of the MT and PCS genes and the higher levels of cysteine and glutathione in ammonium-fed leaves indicate that ammonium may be able to accelerate sulfur assimilation metabolism in rice leaves. Unexpectedly, Northern blotting analysis showed that the expression of the two key enzymes in the sulfur assimilation pathway, namely adenosine 5'-phosphosulfate reductase and O-acetylserine(thiol)lyase, was not upregulated by ammonium treatment. It was found that the total content of free amino acids was much higher in ammonium-fed leaves compared with nitrate-fed leaves, mainly resulting from an increase in several amino acids such as serine, asparagine, glutamine, and arginine. The increased amino acids, in particular serine (as a central substrate for the synthesis of the thiol metabolites), may have promoted sulfur assimilation metabolism under conditions of ammonium nutrition.
Increasing evidence indicates an association between the concentration of systemic progesterone during the early luteal phase of the oestrous cycle and embryo survival rate in cattle. We examined the relationship between the concentration of systemic progesterone on Days 4 to 8 post-ovulation and expression of progesterone receptor (PGR), oestrogen receptor a (ESR1) and retinol-binding protein (RBP) mRNA in the bovine endometrium. Heifers were blood sampled from the day of ovulation (Day 0) to Day 8 post-ovulation. On Day 4, animals were divided into low progesterone control (LC) and high progesterone control (HC) groups based on their plasma progesterone concentrations. Half of each group was supplemented with exogenous progesterone resulting in two further groups, low progesterone supplemented (LS) and high progesterone supplemented (HS). Endometrial tissues were recovered from all groups on Day 6 or Day 8 and gene expression was analysed following Northern blotting. Increasing progesterone concentrations were associated with decreased PGR and ESR1 expression. Duration-dependent effects of progesterone supplementation on ESR1 were evident and there was an effect of systemic progesterone concentrations between Day 0 and Day 4 on the expression of RBP at Days 6 and 8. Such progesterone-responsive changes in uterine gene expression are likely to affect embryo development.
An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.
Quantitative real-time reverse transcription PCR (RT-qPCR) has been widely used in the detection and quantification of gene expression levels because of its high accuracy, sensitivity, and reproducibility as well as its large dynamic range. However, the reliability and accuracy of RT-qPCR depends on accurate transcript normalization using stably expressed reference genes. Amorphophallus is a perennial plant with a high content of konjac glucomannan (KGM) in its corm. This crop has been used as a food source and as a traditional medicine for thousands of years. Without adequate knowledge of gene expression profiles, there has been no report of validated reference genes in Amorphophallus. In this study, nine genes that are usually used as reference genes in other crops were selected as candidate reference genes. These putative sequences of these genes Amorphophallus were cloned by the use of degenerate prirners. The expression stability of each gene was assessed in different tissues and under two abiotic stresses (heat and waterlogging) in A. albus and A. konjac. Three distinct algorithms were used to evaluate the expression stability of the candidate reference genes. The results demonstrated that EF1-a, EIF4A, H3 and UBQ were the best reference genes under heat stress in Amorphophallus. Furthermore, EF1-a, EIF4A, TUB, and RP were the best reference genes in waterlogged conditions. By comparing different tissues from all samples, we determined that EF1-a, EIF4A, and CYP were stable in these sets. In addition, the suitability of these reference genes was confirmed by validating the expression of a gene encoding the small heat shock protein SHSP, which is related to heat stress in Amorphophallus. In sum, EF1-a and EIF4A were the two best reference genes for normalizing mRNA levels in different tissues and under various stress treatments, and we suggest using one of these genes in combination with 1 or 2 reference genes associated with different biological processes to normalize gene expression. Our results will provide researchers with appropriate reference genes for further gene expression quantification using RT-qPCR in Amorphophallus.
Background/Aims: Liver injury results in the activation of hepatic stellate cells (HSCs), which in turn produce matrix metalloproteinase (MMP) in response to pro-inflammatory cytokines for tissue remodelling. This study explored the transcriptional induction of the MMP-1 gene by tumour necrosis factor-alpha (TNF-alpha) in HSCs. Methods: The LI90 human HSC line was used in the present study. Gelatin zymography, enzyme-linked immunosorbent assay, Northern blotting and gene promoter-reporter assays were used to analyse the induction of MMP-1 protein, mRNA expression and gene transcription respectively. Deletional or site-directed mutations were introduced into the promoter region and transiently transfected into LI90 cells to determine the cis-acting elements necessary for TNF-alpha inducibility. Gel shift mobility assays were used to determine the transcriptional factors involved in the TNF-alpha responsiveness. Results: TNF-alpha upregulated MMP-1 protein and mRNA expression in a dose-dependent manner. A time-course experiment revealed a rapid induction of MMP-1 mRNA expression after TNF-alpha treatment. Mutation in a putative nuclear factor (NF)-kappa B-binding site at -2541 bp almost completely abolished the TNF-alpha response to MMP-1 gene-promoter activity, suggesting transcriptional regulation of MMP-1 expression by TNF-alpha via this site. Electrophoretic mobility shift assay and supershift assays indicated that this transcriptional regulation was regulated via the p50/p50 homodimer of NF-kappa B. Conclusions: MMP-1 gene expression might be induced by TNF-alpha via the p50/p50 homodimer of NF-kappa B in activated human HSCs.
At the end of June, over 120 microbiologists from 18 countries gathered in Dundee, Scotland for the fourth edition of the Young Microbiologists Symposium on 'Microbe Signalling, Organisation and Pathogenesis'. The aim of the symposium was to give early career microbiologists the opportunity to present their work in a convivial environment and to interact with senior world-renowned scientists in exciting fields of microbiology research. The meeting was supported by the Microbiology Society, the Society of Applied Microbiology and the American Society for Microbiology with further sponsorship from the European Molecular Biology Organisation and the Royal Society of Edinburgh. In this report, we highlight some themes that emerged from the many interesting talks and poster presentations, as well as some of the other activities that were on offer at this energetic meeting.
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Antitumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed death ligand 1 (anti-PDL-1) antibodies causes tumor regression in about 25% of patients with lung cancer. In another approach, the immune system is forced or accelerated to attack the tumor through augmentation of the antitumor response against mutations carried by each lung tumor. This latter approach has become feasible since the advent of next-generation sequencing technology, which allows identification of the specific mutations that each individual lung tumor bears. Indeed lung cancers are now known to have high mutation rates, making them logical targets for mutation-directed immune therapies. We review how sequencing of lung cancer mutations leads to better understanding of how the immune system recognizes tumors, providing improved opportunities to track antitumor immunity and ultimately leading to the development of personalized vaccine strategies aimed at unleashing the host immune system to attack mutations in the tumor.
Recent studies in our laboratories have shown that Protein Kinase C delta (PKC delta) is essential for insulin-induced glucose transport in skeletal muscle, and that insulin rapidly stimulates PKC delta activity skeletal muscle. The purpose of this study was to examine mechanisms of regulation of PKC delta protein availability. Studies were done on several models of mammalian skeletal muscle and utilized whole cell lysates of differentiated myotubes. PKC delta protein levels were determined by Western blotting techniques, and PKC delta RNA levels were determined by Northern blotting, RT-PCR and Real-Time RT-PCR. Insulin stimulation increased PKC delta protein levels in whole cell lysates. This effect was not due to an inhibition by insulin of the rate of PKC delta protein degradation. Insulin also increased 35 S-methionine incorporation into PKC delta within 5-15 min. Pretreatment of cells with transcription or translation inhibitors abrogated the insulin-induced increase in PKC delta protein levels. We also found that insulin rapidly increased the level of PKC delta RNA, an effect abolished by inhibitors of transcription. The insulin-induced increase in PKC delta expression was not reduced by inhibition of either P13 Kinase or MAP kinase, indicating that these signaling mechanisms are not involved, consistent with insulin activation of PKC delta. Studies on cells transfected with the PKC delta promoter demonstrate that insulin activated the promoter within 5 min. This study indicates that the expression of PKC delta may be regulated in a rapid manner during the course of insulin action in skeletal muscle and raise the possibility that PKC delta may be an immediate early response gene activated by insulin. (c) 2005 Elsevier Inc. All rights reserved.
Gene trapping is a powerful method for identifying novel genes and for analyzing their functions. It is, however, difficult to select trapped genes on the basis of their function. To identify genes regulated by transcription factors that are important in the mesodermal formation, we selected trapped ES clones by infection of adenoviral vectors expressing Pax1, Brachyury, and Foxa2. Among 366 trapped genes, seven seemed to be controlled by these transcription factors in the first screening. The trapped genes were identified by 5' RACE, and a Northern blotting revealed that expressions of three trapped genes were regulated by these transcription factors. Expression patterns of Cx43 and HPI gamma implicated their functional relationships to Foxa2 in the formation of the notochord and the neural tube. Furthermore, Wtap mutant mice derived from the trapped clone showed defects in the mesendoderm formation. Our results indicate that trapped ES clones could be selected effectively using transcription factors. (c) 2007 Elsevier Inc. All rights reserved.
Few studies have addressed likely gene x gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas. Single gene DISC1 mutants demonstrated a disruption in social cognition and nest-building, altered brain 5-hydroxytryptamine levels and hippocampal ErbB4 expression, and decreased cortical expression of the schizophrenia-associated microRNA miR-29b. Co-disruption of DISC1 and NRG1, indicative of epistasis, evoked an impairment in sociability and enhanced self-grooming, accompanied by changes in hypothalamic oxytocin/ vasopressin gene expression. The findings indicate specific behavioral correlates and underlying cellular pathways downstream of main effects of DNA variation in the schizophrenia-associated genes NRG1 and DISC1.
Differential display (DD) experiments were performed on drought-tolerant rice (Oryza sativa L.) genotype N22 to identify both upregulated and down-regulated partial cDNAs with respect to moisture stress. DNA polymorphism was detected between drought-stressed and control leaf tissues on the DD gels. A partial cDNA showing differential expression, with respect to moisture stress was isolated from the gel. Northern blotting analysis was performed using this, cDNA as a probe and it was observed that mRNA corresponding to this transcript was accumulated to high level in rice leaves under water deficit stress. At the DNA sequence level, the partial cDNA showed homology with psb A gene encoding for D1 protein.
Objective To test the phenotypic plasticity framework using a polygenic approach in a prospective depression cohort of primary care attendees with and without histories of severe childhood abuse. Methods Depressive symptoms were assessed at baseline and annually for 5 years post-baseline using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9) among 288 adult primary care attendees. Twelve polymorphisms in nine genes were genotyped and polygenic phenotypic plasticity allelic load (PAL) calculated. Linear mixed models assessed differences in depressive symptom severity over the 5-year follow-up period by PAL and history of severe childhood abuse. Results A higher PAL conferred greater depressive symptom severity among those with a history of severe childhood abuse but conferred significantly lower symptom severity among those without this history. Importantly, this interaction withstood adjustments for important covariates (e.g., antidepressant use, comorbid anxiety) and was stable over the 5 years of observation. Conclusions Aligned with the phenotypic plasticity framework, depressive symptom severity was dependent on the interaction between PAL and history of severe childhood abuse in a for better and for worse manner. Measures of polygenic phenotypic plasticity, such as ours, may serve as a trait marker of sensitivity to negative and potentially positive environmental influences.
Although intelligence should theoretically evolve to help animals solve specific types of problems posed by the environment, it is unclear which environmental challenges favour enhanced cognition, or how general intelligence evolves along with domain-specific cognitive abilities. The social intelligence hypothesis posits that big brains and great intelligence have evolved to cope with the labile behaviour of group mates. We have exploited the remarkable convergence in social complexity between cercopithecine primates and spotted hyaenas to test predictions of the social intelligence hypothesis in regard to both cognition and brain size. Behavioural data indicate that there has been considerable convergence between primates and hyaenas with respect to their social cognitive abilities. Moreover, compared with other hyaena species, spotted hyaenas have larger brains and expanded frontal cortex, as predicted by the social intelligence hypothesis. However, broader comparative study suggests that domain-general intelligence in carnivores probably did not evolve in response to selection pressures imposed specifically in the social domain. The cognitive buffer hypothesis, which suggests that general intelligence evolves to help animals cope with novel or changing environments, appears to offer a more robust explanation for general intelligence in carnivores than any hypothesis invoking selection pressures imposed strictly by sociality or foraging demands.
Generalized additive mixed models are introduced as an extension of the generalized linear mixed model which makes it possible to deal with temporal autocorrelational structure in experimental data. This autocorrelational structure is likely to be a consequence of learning, fatigue, or the ebb and flow of attention within an experiment (the 'human factor'). Unlike molecules or plots of barley, subjects in psycholinguistic experiments are intelligent beings that depend for their survival on constant adaptation to their environment, including the environment of an experiment. Three data sets illustrate that the human factor may interact with predictors of interest, both factorial and metric. We also show that, especially within the framework of the generalized additive model, in the nonlinear world, fitting maximally complex models that take every possible contingency into account is illadvised as a modeling strategy. Alternative modeling strategies are discussed for both confirmatory and exploratory data analysis. (C) 2016 Elsevier Inc. All rights reserved.
Some areas in China are facing pressing air pollution problems. Measures from the power sector can be taken to cope with air pollution issues, including reducing emission levels of thermal units and integrating wind and solar power. Social welfare, emission, and renewable integration are three major concerns in modern power system operations. This paper describes three stochastic scheduling models aiming at maximizing social welfare (SW), minimizing emission (EM) and maximizing renewable production (RE). A multi-objective scheduling model (MT) is also proposed that properly balances the above objectives. Wind power uncertainty and dispatchable loads are considered in the model. The outcomes of the three models are compared through an illustrative example and a 57-node case study. Results show that model EM results in 36% of the social welfare of model SW, 27% of its emissions, and 43% of its wind spillage, while model RE results in 55% of the social welfare of model SW, 56% of its emissions and 28% of its wind spillage. Additionally, we analyze how the optimal generation scheduling is affected by the weights in model MT. This work provides insight to policy makers on how to balance social welfare, emissions and renewable production. (C) 2017 Elsevier Ltd. All rights reserved.
High-temperature superconducting (HTS) generators for large-scale wind power generation systems attract much research attention. Excitation systems in HTS generators, particularly brushless HTS exciters, are a new challenge. To verify the possibility of a brushless HTS exciter in a large-scale wind power generator, we designed and fabricated HTS coils for a laboratory-scale wind power generator employing a brushless exciter. In order to supply dc current into the HTS coils, a brushless exciter was considered in the generator. All of the field coils were wound with an HTS coated conductor made of 2G GdBCO wire. The conduction cooling test was executed in a cryogenic test chamber to check the performances at 30 K. The detailed results of the operating performance of the HTS coils were discussed in detail.
A complete model of a thermionic generator has been developed in order to optimise the technology for application in the solar thermal generation of electricity. Steady state current densities predicted by the model have been shown to agree with published experimental thermionic data. Two separate genetic algorithm optimisations have been carried out for both power density and efficiency, in which electrode temperatures and work functions, external circuit resistance and electrode separation were varied. The result of these optimisations were two configurations separately exhibiting a maximum power density of 1.66 W/cm(2), and a Maximum efficiency of 7.69% for parameter ranges applicable to concentrating solar thermal power. Examination of the optimum simulation parameters indicated that future developments in lowering collector work functions, increasing emitter service temperature and decreasing attainable electrode separations will all positively impact device performance. (C) 2017 Elsevier Ltd. All rights reserved.
Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often 'weird' features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes. This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.
Modern biotechnology is one of the most important scientific and technological revolutions in the 21st century, with an increasing and measurable impact on society. Development of biotechnology curriculum has become important to high school bioscience classrooms. This study has monitored high school students in Taiwan on their knowledge of and attitudes towards biotechnology for nearly two decades. Not surprisingly, knowledge of biotechnology of current students has increased significantly (p<0.001) and most students have learned some definitions and examples of biotechnology. There was a positive correlation between biotechnology knowledge and attitudes toward biotechnology for current students who study Advanced Biology (AB). However, for current students who did not study AB, there was a negative correlation. The attitude results showed that students today expressed less favorable opinions toward agricultural biotechnology (p < 0.001) despite studying AB or not. However, there is no significant difference between students today and 18 years ago in opinions towards medical biotechnology. In addition, current students showed a greater concern involving environmental risks than former students. Interestingly, the high school curriculum did affect students' attitudes toward genetically engineered (GE) plants but not GE animals. Our current study also found that the students' attitude towards GE animals was influenced more by their limited knowledge than by their moral belief. On the basis of findings from this study, we suggest that more materials of emerging animal biotechnology should be included in high school curriculum and recommend that high school teachers and university faculty establish a collaborative framework in the near future. (C) 2016 by The International Union of Biochemistry and Molecular Biology
Aim of study - to estimate leptin gene (Arg223Gln) genotypes polymorphism in patients with coronary heart disease and obesity. Materials and Methods. 222 patients with the coronary heart disease (CHD) and obesity have been comprehensively examined. All patients were on treatment in cardiologic unit of KUZ of the Kharkiv city hospital. 27, which is the basic clinic of Department of Internal Medicine. 2 and Clinical Immunology and Allergology of the Kharkiv National Medical University of MH of Ukraine. The comparison group consisted of 115 ischemic heart disease patients with normal body weight. 35 practically healthy persons formed the control group. Groups were comparable in age and sex. The study didn't include the patients with the serious accompanying pathology of respiratory organs, digestion, kidneys and persons with oncological diseases. Results. In the control group there was the following distribution of leptin gene (Arg223Gln) alleles and genotypes polymorphism frequency: 15 people were allele A that made 42.86 %, allele G -20 people (57.14 %); genotypes G/G, A/A and G/G had 15 (42.86 %), 7 (20 %) and 13 (37.14 %) persons respectively. 42 patients with CHD were allele A, which made 36.52 %, allele G -73 patients (63.48 %). Genotypes G/G, A/A and G/G had 47 (40.87 %), 20 (17.39 %) and 48 (41.74%) patients with CHD respectively. In group of patients with combination of CHD and obesity 71 patients (31.98 %) were allele A, allele G -151 people (68.02 %); genotypes G/G, A/A and G/G -81 (36.49 %), 33 (14.87 %) and 108 (48.64 %) respectively. Comparison of leptin gene (Arg223Gln) alleles and genotypes polymorphism frequency of detection between groups showed the reliable differences of alleles A, G and a genotype G/G. In patients with CHD and obesity allele G was 10.88 % more and genotype G/G was 11.5 % more, than in the control group. Allele A was 10.88 % more in the control group, than in patients with CHD and obesity (p < 0.05). Reliable differences between group of CHD patients and the control group in distribution of detected alleles and genotypes frequency of leptin gene (Arg223Gln) polymorphism were not found (p < 0.05). Conclusions. By results of the study allele G and a genotype G/G of leptin gene (Arg223Gln) polymorphism in patients with CHD has been associated with obesity.
India is rich in genetic diversity of major pulse crops, but the productivity and the production of pulse crops remains low compared to the world and hence, there is a need to enhance the utilization for increasing the production. Major pulse species for which genetic diversity is occurring in India include Vigna, Cajanus, Cicer, Pisum, Lens, Phaseolus and few minor pulses such as Macrotyloma, Canavalia, Lathyrus, Vicia, Mucuna, Moghania and Rhynchosia etc. National Bureau of PInt Genetic Resources (NBPGR) is the nodal institute for the "management of plant genetic resources in India. It has assembled-70,000 accessions of different pulse crops majoring Cajanus cajan, Cicer arietinum, Phaseolus vulgaris, Pisum sativum, Vigna mungo, Vigna radiata, Vigna umbellata, Vigna unguiculata, Viceasp. and Lens sp. through collection and introduction from India and from >70 other countries of the world. Several pests of quarantine significance have been identified and salvaged from the exotic germplasm. The ex situ base collection at NBPGR conserve 64,744 accessions of 20 genera and 61 species of pulses. This germplasm has been characterized for agro-morphological, quality and biochemical traits, biotic and abiotic stresses for identifying trait-specific reference sets and 28 catalogues describing about 45,000 accessions of 14 pulse crops. A total of 121 accessions of various pulse crops have been registered as unique/potential donors. Core and mini cores have been developed in chickpea, pigeonpea, common bean, mungbean, adzuki bean, cowpea, lentil, moth bean and pea both nationally and internationally. Wild species of pulse crops have been utilized for transferring desirable traits into cultivated species. Application of modern tools and technologies of molecular biology will accelrate the process of gene transfer for improvement of pulse crops.
Background: A comprehensive evaluation of associations between the susceptibility to norovirus infections and histo-blood group antigens is not available in the Taiwanese population, in which the nonsecretor phenotype is absent. Methods: A 1: 1 matched case-control study was conducted in northern Taiwan from February 2013 to December 2014 when an epidemic of norovirus infection occurred. Cases were children <18 years old who were hospitalized because of diarrhea and were found to have laboratory-confirmed norovirus infections. Controls were healthy children matched to the cases by age and gender. The norovirus genotype was determined by polymerase chain reaction sequencing of the VP1 gene. The secretor status, Lewis antigen and ABO type were determined by characterization of genetic polymorphisms in the FUT2, FUT3 and ABO genes, respectively. Results: A total of 147 case-control pairs were included. GII. 4 Sydney strain was the major genotype and identified in 78.3% of the cases. The weak-secretor and Lewis-positive genotypes were less commonly identified in cases than in controls (5.4% vs. 23.1% and 79.6% vs. 89.8%, respectively). Multivariate analysis revealed that the secretor and Lewis-negative genotypes were both independent factors associated with increased risk of norovirus infections [matched odds ratio: 6.766, 95% confidence interval (CI): 2.649-17.285, P0.05). Conclusion: The weak-secretor genotype and the Lewis antigen-positive genotype were both protective factors against severe norovirus gastroenteritis during the GII. 4 Sydney strain epidemic in Taiwan.
The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.
Gene editing is a relatively recent concept in the molecular biology field. Traditional genetic modifications in animals relied on a classical toolbox that, aside from some technical improvements and additions, remained unchanged for many years. Classical methods involved direct delivery of DNA sequences into embryos or the use of embryonic stem cells for those few species (mice and rats) where it was possible to establish them. For livestock, the advent of somatic cell nuclear transfer platforms provided alternative, but technically challenging, approaches for the genetic alteration of loci at will. However, the entire landscape changed with the appearance of different classes of genome editors, from initial zinc finger nucleases, to transcription activator-like effector nucleases and, most recently, with the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas). Gene editing is currently achieved by CRISPR-Cas-mediated methods, and this technological advancement has boosted our capacity to generate almost any genetically altered animal that can be envisaged.
Genetically modified organisms are increasingly used in the production of feed and food, which has met with opposition from consumers. The aim of the study was the use of molecular biology methods with particular emphasis on techniques of real-time PCR in the research in the detection and identification of genetically modified feed. The research materials were samples of feed taken from feed produced and used in animal nutrition in Poland in the years 20042015. The applied research methods included PCR and real-time PCR techniques, and consisted in the detection and determination of the DNA content of genetically modified plants. Cascade methods used in this study included the screening method of detection of GMOs, the method of identifying the type of GMO, and methods of quantitative analysis of GMO content. As part of the research task in the years 20042015 a total of 1435 samples of feed towards GMOs were examined. A positive result was found in 559 cases (39%). Most frequently the positive samples were found the presence of genetically modified soybeans (531, 37%). Moreover, within the years 20142015 an increase in the number of positive GM rape samples was observed (56, 4%). GM maize contained the least positive samples (38, 2.6%). GMO content above the legislative threshold 0.9% was found in the vast majority of samples containing GM soy, while for maize and rapeseed the number of samples containing more than 0.9% GMO was respectively 12 and 8. Analysis of the feed market in Poland indicates that the soybean plant is the most common genetically modified crop. Analysis of the origin of sources of GM rapeseed showed that the reasons for this should be sought in batches of rapeseed imported from third countries. It has been observed with regard to the situation of GM maize for the feed market in Poland that from 2013 the situation changed radically as a result of the Decree of the Ministry of Agriculture issued prohibiting the cultivation of MON810 maize on Polish fields. The result of our study showed that the proportion of genetically modified feed on the feed market in Poland is very similar to other EU countries. The source of GMOs in feed on the Polish market is feed materials imported into Poland as a source of feed protein.
One novel standard reference plasmid, namely pUC-RICE5, was constructed as a positive control and calibrator for event-specific qualitative and quantitative detection of genetically modified (GM) rice (Bt63, Kemingdaol, Kefeng6, Kefeng8, and LLRice62). pUC-RICE5 contained fragments of a rice-specific endogenous reference gene (sucrose phosphate synthase) as well as the five GM rice events. An existing qualitative PCR assay approach was modified using pUC-RICE5 to create a quantitative method with limits of detection correlating to approximately 1-10 copies of rice haploid genomes. In this quantitative PCR assay, the square regression coefficients ranged from 0.993 to 1.000. The standard deviation and relative standard deviation values for repeatability ranged from 0.02 to 0.22 and 0.10% to 0.67%, respectively. The Ministry of Food and Drug Safety (Korea) validated the method and the results suggest it could be used routinely to identify five GM rice events. (C) 2017 Elsevier Ltd. All rights reserved.
Purpose of Review The ebb and flow of genetic influence relative to the understanding of craniofacial and dental disorders has evolved into a tacit acceptance of the current genetic paradigm. This review explores the science behind craniofacial and dental disorders through the lens of recent past and current findings and using tooth agenesis as a model of advances in craniofacial genetics. Recent Findings Contemporary studies of craniofacial biology takes advantage of the technological resources stemming from the genomic and post-genomic eras. Emerging data highlights the role of key genes and the epigenetic landscape controlling these genes, in causing dentofacial abnormalities. We also report here a novel Glu78FS MSX1 mutation in one family segregating an autosomal dominant form of severe tooth agenesis as an illustration of an evolving theme, i.e., different mutations in the same gene can result in a spectrum of dentofacial phenotypic severity. Summary The future of clinical therapeutics will benefit from advances in genetics and molecular biology that refine the genotype-phenotype correlation. Indeed, the past century suggests a continued convergence of genetic science in the practice of clinical dentistry.
The overarching theme of the 2016 Society of Toxicology Pathology's Annual Symposium was "The Basis and Relevance of Variation in Toxicologic Responses.'' Session 4 focused on genetic variation as a potential source for variability in toxicologic responses within nonclinical toxicity studies and further explored how knowledge of genetic traits might enable targeted prospective and retrospective studies in drug development and human health risk assessment. In this session, the influence of both genetic sequence variation and epigenetic modifications on toxicologic responses and their implications for understanding risk were explored. In this overview, the presentations in this session will be summarized, with a goal of exploring the ramifications of genetic and epigenetic variability within and across species for toxicity studies and disseminating information regarding novel tools to harness this variability to advance understanding of toxicologic responses across populations.
Introduction: Tumour necrosis factor-alpha (TNF alpha) gene -308G/A polymorphism (rs1800629) are associated with psoriasis in several populations worldwide. Presently, there is no literature on the status of this polymorphism in the South Indian population. Aim: To determine the profile of TNF alpha -308G/A polymorphism among psoriatic patients. Materials and Methods: This case-control study involved 74 patients with Psoriasis Vulgaris (PsV) and 74 age and gender matched healthy individuals. Patients were recruited from the Department of Dermatology of R. L. Jalappa Hospital and Research Center, Tamaka, Kolar, Karnataka, India, from March 2014 to March 2016. TNF alpha -308G/A polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: The frequency of TNF alpha -308A allele 7.4% among psoriatic and 8.8% among non-psoriatic individuals. The difference was not statistically significant (p=0.82). Conclusion: Our results indicate that TNF alpha gene -308G/A polymorphism is not a significant marker for the risk of developing PsV among South Indian (Karnataka) psoriatic patients.
The aim of this study was to analyze the influence of nucleotide transition (G/A) in position -2518 of the MCP-1 gene related to the susceptibility of developing RA. Two hundred twenty-three consecutive RA patients according to 2010 ACR/EULAR criteria were included; 120 healthy subjects were used as controls. MCP-1 -2518 A/G polymorphism (AG + GG) was present in 162 (72.6 %) RA patients and in 63 (52.5 %) healthy subjects [OR 2.44 (IC95% 1.53-3.88, p = 0.0002)]; associations for heterozygotes and homozygotes were OR 1.92 (IC95% 1.19-3.15, p = 0.001) and OR 5.19 (IC95% 2.34-11.51, p = 0.001), respectively. In Argentine patients, MCP-1 gene polymorphism confers susceptibility for developing RA.
Background: Several lines of evidence suggest that the dietary isoflavone genistein (Gen) has beneficial effects with regard to cardiovascular disease and in particular on aspects related to blood pressure and angiogenesis. The biological action of Gen may be, at Least in part, attributed to its ability to affect cell signalling and response. However, so far, most of the molecular mechanisms underlying the activity of Gen in the endothelium are unknown. Methods and results: To examine the transcriptional response to 2.5 mu M Gen on primary human endothelial cells (HUVEC), we applied cDNA array technology both under baseline condition and after treatment with the pro-atherogenic stimulus, copper-oxidized LDL. The alteration of the expression patterns of individual transcripts was substantiated using either RT-PCR or Northern blotting. Gen significantly affected the expression of genes encoding for proteins centrally involved in the vascular tone such as endothelin-converting enzyme-1, endothetin-2, estrogen related receptor a and atria[ natriuretic peptide receptor A precursor. Furthermore, Gen countered the effect of oxLDL on mRNA levels encoding for vascular endothelial growth factor receptor 165, types 1 and 2. Conclusions: Our data indicate that physiologically achievable levels of Gen change the expression of mRNA encoding for proteins involved in the control of blood pressure under baseline conditions and reduce the angiogenic response to oxLDL in the endothelium. (c) 2005 Elsevier B.V. All rights reserved.
Background. The mechanisms by which DNA sequences are expressed is the central preoccupation of molecular genetics. Recently, ourselves and others reported that in the diplomonad protist Giardia lamblia, the coding regions of several mRNAs are produced by ligation of independent RNA species expressed from distinct gnomic loci- Such trans splicing of introns was found to affect nearly as many genes in this organism as does classical cis-splicing of introns. These findings raised questions about the incidence of intron trans-splicing both across the G. lamblia transcriptome and across diplomonad diversity in general, however a dearth of transcriptomic data at the time prohibited systematic study of these questions. Methods. I leverage newly available transcriptornic data from G. lamblia and the related diplomonad Spironucleus salmonicida to search for trans-spliced introns. My computational pipeline recovers all four previously reported trans spliced introns in G. lamblia, suggesting good sensitivity. Results. Scrutiny of thousands of potential cases revealed only a single additional trans-spliced intron in G. lamblia, in the p68 helicase gene, and no cases in S. salmorticida. The p68 intron differs from the previously reported trans-spliced introns in its high degree of streamlining: the core features of G. lamblia trans-spliced introns are closely packed together, revealing striking economy in the implementation of a seemingly inherently uneconomical molecular mechanism. Discussion. These results serve to circumscribe the role of trails splicing in diplomonads both in terms of the number of genes effected and taxonomically. Future work should focus on the molecular mechanisms, evolutionary origins and phenotypic implications of this intriguing phenomenon.
The clustered, regularly interspaced, short palindromic repeat (CRISPR) and CRISPR associated protein 9 (Cas9) system discovered as an adaptive immunity mechanism in prokaryotes has emerged as the most popular tool for the precise alterations of the genomes of diverse species. CRISPR/Cas9 system has taken the world of genome editing by storm in recent years. Its popularity as a tool for altering genomes is due to the ability of Cas9 protein to cause double-stranded breaks in DNA after binding with short guide RNA molecules, which can be produced with dramatically less effort and expense than required for production of transcription-activator like effector nucleases (TALEN) and zinc-finger nucleases (ZFN). This system has been exploited in many species from prokaryotes to higher animals including human cells as evidenced by the literature showing increasing sophistication and ease of CRISPR/Cas9 as well as increasing species variety where it is applicable. This technology is poised to solve several complex molecular biology problems faced in life science research including cancer research. In this review, we highlight the recent advancements in CRISPR/Cas9 system in editing genomes of prokaryotes, fungi, plants and animals and provide details on software tools available for convenient design of CRISPR/Cas9 targeting plasmids. We also discuss the future prospects of this advanced molecular technology. Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved.
Volvariella volvacea is difficult to store fresh because of the lack of low-temperature resistance. Many traditional mutagenic strategies have been applied in order to select out strains resistant to low temperature, but few commercially efficient strains have been produced. In order to break through the bottleneck of traditional breeding and significantly improve low-temperature resistance of the edible fungus V. volvacea, strains resistant to low temperature were constructed by genome shuffling. The optimum conditions of V. volvacea strain mutation, protoplast regeneration, and fusion were determined. After protoplasts were treated with 1% (v/v) ethylmethylsulfonate (EMS), 40Sec of ultraviolet (UV) irradiation, 600 Gy electron beam implantation, and 750 Gy(60)Co- irradiation, separately, the lethality was within 70%-80%, which favored generating protoplasts being used in following forward mutation. Under these conditions, 16 strains of V. volvacea mutated by EMS, electron beam, UV irradiation, and Co-60- irradiation were obtained. The 16 mutated protoplasts were selected to serve as the shuffling pool based on their excellent low-temperature resistance. After four rounds of genome shuffling and low-temperature resistance testing, three strains (VF1, VF2, and VF3) with high genetic stability were screened. VF1, VF2, and VF3 significantly enhanced fruit body shelf life to 20, 28, and 28H at 10 degrees C, respectively, which exceeded 25%, 75%, and 75%, respectively, compared with the storage time of V23, the most low-temperature-resistant strain. Genome shuffling greatly improved the low-temperature resistance of V. volvacea, and shortened the course of screening required to generate desirable strains. To our knowledge, this is the first paper to apply genome shuffling to breeding new varieties of mushroom, and offers a new approach for breeding edible fungi with optimized phenotype. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Genome sequences nowadays play a central role in molecular biology and bioinformatics. These sequences are shared with the scientific community through sequence databases. The sequence repositories of the International Nucleotide Sequence Database Collaboration (INSDC, comprising GenBank, ENA and DDBJ) are the largest in the world. Preparing an annotated sequence in such a way that it will be accepted by the database is challenging because many validation criteria apply. In our opinion, it is an undesirable situation that researchers who want to submit their sequence need either a lot of experience or help from partners to get the job done. To save valuable time and money, we list a number of recommendations for people who want to submit an annotated genome to a sequence database, as well as for tool developers, who could help to ease the process.
A current goal of molecular biology is to identify transcriptional networks that regulate cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and cell types are mixed. To identify regulatory sites during sex determination, we subjected Sertoli cells from mouse fetal testes to DNaseI-seq and ChIP-seq for H3K27ac. DNaseI-seq identified putative regulatory sites around genes enriched in Sertoli and pregranulosa cells; however, active enhancers marked by H3K27ac were enriched proximal to only Sertoli-enriched genes. Sequence analysis identified putative binding sites of known and novel transcription factors likely controlling Sertoli cell differentiation. As a validation of this approach, we identified a novel Sertoli cell enhancer upstream of Wt1, and used it to drive expression of a transgenic reporter in Sertoli cells. This work furthers our understanding of the complex genetic network that underlies sex determination and identifies regions that potentially harbor non-coding mutations underlying disorders of sexual development.
Genomic DNA of good quality is a prerequisite in molecular biology studies involved in deciphering the information contained in the molecules that are chosen for studying the evolutionary interrelationships among taxa. Genomic DNA should be free of contaminants which may otherwise interfere while performing PCR. This is particularly essential while isolating genomic DNA from gastropods due to the presence of large amounts of mucopolysaccharides in their tissues. In the present study, we have developed a new method for obtaining high quality genomic DNA from a pulmonate snail Achatina fulica, which secretes a large amount of mucus. In this method, we have obtained good quality genomic DNA, compatible for downstream molecular biology applications like PCR and sequencing of 16S rDNA. The yield of the genomic DNA was 2790 mu g/ml. This method may be extended for isolating high quality genomic DNA from different gastropods native to Indian sub-continent, which serves as a starting point for studying their phylogenetic affinities.
Single nucleotide polymorphisms (SNPs) in DNA can result in phenotypes where the biochemical basis may not be clear due to the lack of protein structures. With the growing number of modeling and simulation software available on the internet, students can now participate in determining how small changes in genetic information impact cellular protein structure and function. We have developed a modular series of activities to engage lab or lecture students in examining the basis for common phenotypes. The activities range from basic phenotype testing/observation to DNA sequencing and simulation of protein structure and dynamics. We provide as an example study of the bitterness receptor TAS2R38 and PTC tasting, however these activities are applicable to other SNPs or genomic variants with a direct connection to an observable phenotype. These activities are modular and can be mixed to meet the student capabilities and infrastructure availability. The complete sequence of activities will demonstrate the direct connection between gene structure, protein structure and organism function. (C) 2016 by The International Union of Biochemistry and Molecular Biology
DNA microarrays are one of the new tools of genomics that have become quite commonplace in plant science research within the past decade. Essentially, DNA microarrays are an extension of the more traditional molecular biology technique of northern blotting. Unlike northern blotting, however, in which the expression of a single gene is monitored, DNA microarrays allow for the simultaneous monitoring of thousands of genes-or, in fact, potentially all of an organism's genes-in a single experiment. Most of the currently available plant microarrays are designed for crops species or the model plant, Arabidopsis; however, a microarray for at least one major weed species is currently available. Furthermore, CDNA-based microarrays prepared for one species can be used to investigate gene expression in related species. As the technology is maturing it is becoming much more accessible, and now is the time to begin utilizing microarrays in weed science research. Questions related to herbicide activity are particularly well suited for a microarray approach. Additionally, gene-expression profiling via microarrays can be used to address questions relating to weed biology, weed-crop competition, allelopathy, parasitic weeds, and biological control of weeds.
In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases.
High-grade osteosarcomas are the most common primary malignant tumors of bone. With complete surgical resection and multi-agent chemotherapy up to 70% of patients with high-grade osteosarcomas and localized extremity tumors can become long-term survivors. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Outcome is essentially unchanged for three decades. Herein, we describe selected novel insights into the genomics, biology and immunology of the disease and discuss selected strategies, which hold promise to overcome the current stagnation in the therapeutic success in childhood osteosarcoma.
Characterizing the immune response to pneumococcal proteins is critical in understanding this bacterium's epidemiology and vaccinology. Probing a custom-designed proteome microarray with sera from 35 healthy US adults revealed a continuous distribution of IgG affinities for 2,190 potential antigens from the species-wide pangenome. Reproducibly elevated IgG binding was elicited by 208 "antibody binding targets" (ABTs), which included 109 variants of the diverse pneumococcal surface proteins A and C (PspA and PspC) and zinc metalloprotease A and B (ZmpA and ZmpB) proteins. Functional analysis found ABTs were enriched inmotifs for secretion and cell surface association, with extensive representation of cell wall synthesis machinery, adhesins, transporter solute-binding proteins, and degradative enzymes. ABTs were associated with stronger evidence for evolving under positive selection, although this varied between functional categories, as did rates of diversification through recombination. Particularly rapid variation was observed at some immunogenic accessory loci, including a phage protein and a phase-variable glycosyltransferase ubiquitous among the diverse set of genomic islands encoding the serine-rich PsrP glycoprotein. Nevertheless, many antigens were conserved in the core genome, and strains' antigenic profiles were generally stable. No strong evidence was found for any epistasis between antigens driving population dynamics, or redundancy between functionally similar accessory ABTs, or age stratification of antigen profiles. These results highlight the paradox of why substantial variation is observed in only a subset of epitopes. This result may indicate only some interactions between immunoglobulins and ABTs clear pneumococcal colonization or that acquired immunity to pneumococci is an accumulation of individually weak responses to ABTs evolving under different levels of functional constraint.
MicroRNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in both plants and animals. A large number of miRNAs has been identified from various animals and model plant species such as Arabidopsis thaliana and rice (Oryza sativa); however, characteristics of wheat (Triticum aestivum) miRNAs are poorly understood. Here, computational identification of miRNAs from wheat EST sequences was preformed by using the in-house program GenomicSVM, a prediction model for miRNAs. This study resulted in the discovery of 79 miRNA candidates. Nine out of 22 miRNA representatives randomly selected from the 79 candidates were experimentally validated with Northern blotting, indicating that prediction accuracy is about 40%. For the 9 validated miRNAs, 59 wheat ESTs were predicted as their putative targets.
Between July 2009 and June 2014, a total of 1,546 fecal specimens were collected from children <5 years of age with acute gastroenteritis admitted to Kiambu County Hospital, Central Kenya. The specimens were screened for group A rotavirus (RVA) using ELISA, and RVA-positive specimens were subjected to semi-nested RT-PCR to determine the G and P genotypes. RVA was detected in 429/1,546 (27.5%) fecal specimens. RVA infections occurred in all age groups <59 months, with an early peak at 6-17 months. The infections persisted year-round with distinct seasonal peaks depending on the year. G1P[8] (28%) was the most predominant genotype, followed by G9P[8] (12%), G8P[4] (7%), G1P[4] (5%), G9P[4] (4%), and G12P[6] (3%). In the yearly change of G and P genotypes, a major shift from G9P[8] to G1P[8] was found in 2012. Phylogenetic analysis of the nucleotide sequences of the VP7 and VP4 genes of seven strains with unusual G8 or P[6] showed that the VP7 nucleotide sequences of G8 were clustered in lineage 6 in which African strains are included, and that there are at least two distinct VP4 nucleotide sequences of P[6] strains. These results represent basic data on RVA strains circulating in this region before vaccine introduction. (C) 2016 Wiley Periodicals, Inc.
Microtremor survey is a kind of passive-source methods which uses ambient ground tremors for geological investigation. Compared with traditional geophysical methods, it is more flexible, cost-efficient, and environmentally friendly. Most currently used geophones are expensive and bulky, and therefore inconvenient to large-scale deployment. In this study, a no-cable low-cost geophone was optimized to suit for large-scale microtremor survey. The method of optimization is based on the following four points: First, it selects a sensor through the analysis of the self-noise of to meet the needs of microtremor survey. Second, it chooses the right operational amplifier and AD conversion module. Third, it integrates design of the entire system without using external module. And fourth, it makes a low-cost design of the geophone system, including selection of low-cost hardware components and reducing the amount of software code. Finally, the optimized geophone was used in three areas with different geological conditions in order to verify the rationality of the improvement and the possibilities for large-scale microtremor survey. The purpose of optimization has been achieved in this research. The no-cable geophone wrights only 600 g, and the maximum average power cost does not exceed 0. 1 mW. The entire system costs less than 2000 RMB. The most important thing is the optimized geophone can record the microtremor signal from O. 5 to 20 Hz effectively. Experiments show that in different geological conditions the geophone can be setup quickly and work smoothly and reliably. The results of microtremor survey experiments are consistent with the existing geological data. Because the new geophone is much cheaper than the existing microtremor survey equipment, it is possible to use it in low-cost large-scale survey. The optimized geophone has a very small volume and light weight, and can be rapidly emplacedinto a variety of detector arrays. After the emplacement of large number of geophones, it can easily and quickly conduct survey to two-dimensional or three-dimensional velocity structure of the area. Such microtremor survey with environment-friendly and low-cost advantages has broad application prospects.
PurposeAlthough much has been written about Medicare Part D enrollment, much less is known about beneficiaries' personal experiences with choosing a Part D plan, especially among rural residents. This study sought to address this gap by examining geographic differences in Part D enrollees' perceptions of the plan decision-making process, including their confidence in their choice, their knowledge about the program, and their satisfaction with available information. MethodsWe used data from the 2012 Medicare Current Beneficiary Survey and included adults ages 65 and older who were enrolled in Part D at the time of the survey (n = 3,706). We used ordered logistic regression to model 4 outcomes based on beneficiaries' perceptions of the Part D decision-making and enrollment process, first accounting only for differences by rurality, then adjusting for sociodemographic, health, and coverage characteristics. FindingsOverall, half of all beneficiaries were not very confident in their Part D knowledge. Rural beneficiaries had lower odds of being confident in the plan they chose and in being satisfied with the amount of information available to them during the decision-making process. After adjusting for all covariates, micropolitan residents continued to have lower odds of being confident in the plan that they chose. ConclusionsPolicy-makers should pay particular attention to making information about Part D easily accessible for all beneficiaries and to addressing unique barriers that rural residents have in accessing information while making decisions, such as reduced Internet availability. Furthermore, confidence in the decision-making process may be improved by simplifying the Part D program.
Osmoprimed seeds increased the abundance of pGlcT proteins. Osmopriming together with heat shock increased the abundance of RBR proteins. NAD-ME increased when osmoprimed and heat-shocked seeds were imbibed at low temperature. The purpose of seed priming is to accelerate and synchronize germination and to increase stress tolerance through the activation of genes that function when seeds are exposed to unfavorable conditions. The objectives of this study were: (1) to evaluate the effects of osmopriming and heat-shock treatment on the germination of Eucalyptus urophylla seeds at different temperatures and (2) to analyze the seed proteome to elucidate the mechanisms of tolerance to thermal stress in primed and unprimed seeds. Untreated (control) seeds, osmoprimed (polyethylene glycol for 3 days) and redried seeds, and osmoprimed/heat-shocked (45 A degrees C for 1 h) and redried seeds were germinated for 14 days under constant light (2 x 40 W fluorescent daylight tubes) at 9, 16, 22, 24, or 31 A degrees C. Osmopriming, with or without heat-shock, led to a significant increase in the germination percentage at 9 A degrees C and induced the highest germination speed index at 31 A degrees C. According to proteomic analysis, osmoprimed seeds exhibited an increased abundance of several proteins, including sugar transport proteins, and this may have influenced the metabolic rate during germination. Osmopriming together with heat-shock treatment increased the abundance of proteins associated with regulation of the cell cycle suggesting that such proteins may be involved in protection against thermal stress. The Krebs cycle enzyme was increased when osmoprimed and heat-shocked seeds were imbibed at low temperature, possibly signifying increased synthesis of adenosine triphosphate. The results reported herein serve to explain some of the benefits of osmopriming/heat-shock treatment.
This study used Gestalt theory to examine the effects of colour similarity on blurring the boundary between banner advertising and web page content, as well as how colour similarity can elicit unconscious scanning behaviour and improve attitudes towards brands advertised using banner advertising at the pre-attention stage. An eye tracking device was used to record and analyse participants' eye movement, and a psychological scale was used to measure the participants' brand attitudes. The results suggested that using banner advertisements with background colours similar to those of the web page content increases the fixation time and fixation count. In addition, the results revealed that a longer fixation time and a higher fixation count increase positive attitudes towards a brand advertised in a banner advertisement. The results clarify the relationship between unconscious exposure and brand attitudes and provide physiological information relevant to e-commerce.
Viewing and manipulating three-dimensional (3D) structures in molecular graphics software are essential tasks for researchers and students to understand the functions of molecules. Currently, the way to manipulate a 3D molecular object is mainly based on mouse-and-keyboard control that is usually difficult and tedious to learn. While gesture-based and touch-based interactions are increasingly popular in interactive software systems, their suitability in handling molecular graphics has not yet been sufficiently explored. Here, we designed the gesture-based and touch-based interaction methods to manipulate virtual objects in PyMOL utilizing the motion and touch sensors in a mobile device. Three fundamental viewing controls-zooming, translation and rotation-and frequently used functions were implemented. Results from a pilot user study reveal that task performances on viewing controls using a mobile device are slightly reduced as compared to mouse-and-keyboard method. However, it is considered to be more suitable for oral presentations and equally suitable for education scenarios such as school classes. Overall, PyMOL mControl provides an alternative way to manipulate objects in molecular graphic software with new user experiences. The software is freely available at . (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):76-83, 2017.
According to the World Health Organization, mental distress and related illnesses are becoming leading causes of morbidity and mortality in developing countries. Despite the influence of food insecurity on mental health, empirical understanding of this relationship in sub-Saharan Africa, where incidence of food insecurity is relatively high, is almost non-existent. This study contributes to the literature by examining the association between food insecurity and mental health in the Upper West Region of Ghana. We used Ordinary Least Square (OLS) to analyze cross-sectional data collected on household heads (n = 1438) in 2014 using the Household Food Insecurity Access Scale and the DUKE Health Profile. The results show that heads of severely food insecure (beta= 0.934, p <= 0.001) and moderately food secure households (beta = 0.759, p <= 0.001) were more likely to report elevated mental distress compared to those from food secure households. We also found that female household heads were more likely to report elevated mental distress (beta= 0.164, p <= 0.05) compared to their male counterparts. Our findings suggest the need to improve food security as a strategy targeted at improving overall mental health in the Ghanaian context. (C) 2017 Elsevier Ltd. All rights reserved.
Flow cytometry has contributed to virology but has faced many drawbacks concerning detection limits, due to the small size of viral particles. Nonetheless, giant viruses changed many concepts in the world of viruses, as a result of their size and hence opened up the possibility of using flow cytometry to study them. Recently, we developed a high throughput isolation of viruses using flow cytometry and protozoa co-culture. Consequently, isolating a viral mixture in the same sample became more common. Nevertheless, when one virus multiplies faster than others in the mixture, it is impossible to obtain a pure culture of the minority population. Here, we describe a robust sorting system, which can separate viable giant virus mixtures from supernatants. We tested three flow cytometry sorters by sorting artificial mixtures. Purity control was assessed by electron microscopy and molecular biology. As proof of concept, we applied the sorting system to a co-culture supernatant taken from a sample containing a viral mixture that we couldn't separate using end point dilution. In addition to isolating the quick-growing Mimivirus, we sorted and re-cultured a new, slow-growing virus, which we named Cedratvirus. The sorting assay presented in this paper is a powerful and versatile tool for separating viral populations from amoeba co-cultures and adding value to the new field of flow virometry.
Ginger (Zingiber officinale Rosc.) is prone to photoinhibition under intense sunlight. Excessive light can be dissipated by the xanthophyll cycle, where violaxanthin de-epoxidase (VDE) plays a critical role in protecting the photosynthesis apparatus from the damage of excessive light. We isolated similar to 2.0 kb of ginger VDE (GVDE) gene promoter, which contained the circadian box, I-box, G-box and GT-1 motif. Histochemical staining of Arabidopsis indicated the GVDE promoter was active in almost all organs, especially green tissues. beta-glucuronidase (GUS) activity driven by GVDE promoter was repressed rather than activated by high light. GUS activity was altered by hormones, growth regulators and abiotic stresses, which increased with 2,4-dichlorophenoxyacetic acid and decreased with abscisic acid, salicylic acid, zeatin, salt (sodium chloride) and polyethylene glycol. Interestingly, GUS activities with gibberellin or indole-3-acetic acid increased in the short-term (24 h) and decreased in the long-term (48 and 72 h). Analysis of 5' flank deletion found two crucial functional regions residing in -679 to -833 and -63 to -210. Northern blotting analysis found transcription to be regulated by the endogenous circadian clock. Finally, we found a region necessary for regulating the circadian rhythm and another for the basic promoter activity. Key message A novel promoter, named GVDE promoter, was first isolated and analyzed in this study. We have determined one region crucial for promoter activity and another responsible for keeping circadian rhythms.
ObjectivesTo investigate the gene expression profile of human gingiva following surgical wounding. MethodsTen volunteers had one side of the palate wounded. Five days later, biopsies were harvested from both wounded (healing gingiva) and contra-lateral site (normal gingiva). Tissue samples were processed for gene expression (RNA-Seq, real-time PCR) and immunohistochemistry. Gene set enrichment/pathway analysis was also performed. ResultsSeven hundred genes were significantly differentially expressed in healing gingiva. Among genes with >twofold change (FC) in expression, 399 genes were up-regulated and 88 down-regulated, several not previously reported expressed in gingiva. Most increased in expression (30-FC) were MMP1, CCL18, SPP1, MUC21, CTHRC1, MMP10, and SERPINE1; most decreased (7-FC) were COCH, SIAH3, MT4, IGFL3, KY, and SYT16. Real-time PCR confirmed significantly changed mRNA levels for selective genes tested. Gene set enrichment analysis revealed several significantly enriched biological pathways. Immunohistochemistry confirmed protein expression of MUC21, CTHRC1, CTGF, and SYT16 in normal and healing gingiva. ConclusionsThis first comprehensive analysis of the human gingival transcriptome during surgical wound healing offers novel insights into the participating molecular and biological mechanisms. The present results could serve as basis for future investigations into gingival wound healing following surgical, traumatic, or other type of injury.
The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), fibroblast-like cells (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcriptionpolymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis. What's new? The emergence of drug resistance is a major problem in gastrointestinal stromal tumors (GISTs), where tumor cell escape appears in many instances to be associated with acquired resistance to apoptosis. Here, a protein known as FAM96A was found to bind to apoptotic peptidase activating factor 1 (APAF1) and to be profoundly reduced in most GISTs. When FAM96A expression was re-established in cells, tumor sensitivity to apoptosis increased. In xenograft and allograft murine models, tumor growth slowed with FAM96A re-expression. Hence, FAM96A may have a tumor-suppressive role in GISTs. Knowledge of its function could aid the development of novel GIST therapies.
Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of replacing the mutated gene causing the disease to the use of genes to control nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular biology and delivery systems has provided ways for targeting genes to the intended cell/ tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judging by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration.
Glioblastoma is the most common type of primary brain tumor in adults, and is usually fatal in a short duration. Acquiring a better understanding of the pathogenic mechanisms of glioblastoma is essential to the design of effective therapeutic strategies. Grb2-associated binding protein 2 (GAB2) is a member of the daughter of sevenless/Gab family of scaffolding adapters, and has been reported to be important in the development and progression of human cancer. Previously, it has been reported that GAB2 is expressed at high levels in glioma, and may serve as a useful prognostic marker for glioma and a novel therapeutic target for glioma invasion intervention. Elucidating why GAB2 is overexpressed in glioma, and investigating how to downregulate it will assist in further understanding the pathogenesis and progression of the disease, and to offer novel targets for therapy. The present study used in situ hybridization to detect microRNA (miR)-197 expression levels and Targetscan to predict that the 3'-UTR of GAB2 was targeted by miR-197. Northern blotting and reverse transcription-quantitative polymerase chain reaction were also conducted in the current study. miR-197 is downregulated in glioblastoma tissues, compared with adjacent normal tissues, however it involvement continues to be detected in the disease. The results of the present study demonstrated that miR-197, as a tumor suppressor gene, inhibited proliferation by regulating GAB2 in glioblastoma cells. Furthermore, GAB2 was not only upregulated in glioma, but its expression levels were also associated with the grades of glioma severity. In addition, overexpression of GAB2 suppressed the expression of miR-197 in glioblastoma cells. Therefore, restoration of miR-197 and targeting GAB2 may be used, in conjunction with other therapies, to prevent the progression of glioblastoma.
Activation of the AKT (serine-threonine kinase) pathway is a common feature in glioblastoma cells. Downstream factors of the AKT pathway are involved in cell proliferation, apoptosis, cellular migration and angiogenesis. Micro-RNAs (miRNAs) are highly conserved small non-coding RNAs that block targeted mRNA expression at the post-transcriptional level. The aim of this study was to investigate the role of the AKT pathway in regulating miRNA. The changes of miRNA expression profile in human glioblastome U251 cells after AKT small interfering RNA transfection were examined by a microarray, and confirmed by Northern blotting. Down-regulation of AKT expression by siRNA decreased the activity of AKT pathway in U251 cells. Interruption of AKT pathway suppressed the expression of NF-kappa B and c-Myc, furthermore, the expression of a set of miRNAs was also changed after AKT siRNA transfection. There are putative binding sites of NF-kappa B and c-Myc in the promoters of several up-regulated miRNAs, indicating these transcription factors may also be involved in the regulation of miRNA expression, thus affecting the activity of AKT pathway in tumorigenesis. We provide new components of the regulatory function of AKT pathway to better understand the regulatory network mediated by downstream transcription factors. The understanding of the regulatory function of AKT pathway is crucial in tailored therapy of gliomas.
Aberrant expression of microRNAs correlates with the development and progression of human cancers by targeting downstream proteins. MiR-1202 is downregulated in ovarian cancer and clear cell papillary renal cell carcinoma; however, its role in glioma remains unknown. The purpose of this study was to determine the expression and the role of miR-1202 and to elucidate its regulatory mechanism in glioma. We used quantitative real-time polymerase chain reaction to measure miR-1202 expression in both glioma tissues and cell lines. The findings showed that the miR-1202 expression decreased dramatically in clinical glioma tissues and cell lines, and miR-1202 expression was inversely correlated with the expression of Rab1A. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-1202. In vitro, overexpression of miR-1202 inhibited glioma cell proliferation and induced endoplasmic reticulum stress and apoptosis through targeting Rab1A, whereas suppression of miR-1202 promoted cell proliferation and inhibited endoplasmic reticulum stress and apoptosis. Similarly, silencing Rab1A with small interfering RNA also suppressed glioma cell growth and induced endoplasmic reticulum stress and apoptosis. Taken together, our data indicate that miR-1202 suppresses proliferation and induces endoplasmic reticulum stress and apoptosis through targeting and inhibiting Rab1A in glioma cells. These results suggest miR-1202 as a potential therapeutic target for the treatment of glioma patients.
Prolonged translation arrest correlates with delayed neuronal death of hippocampal CA1 neurons following global cerebral ischemia and reperfusion. Many previous studies investigated ribosome molecular biology, but mRNA regulatory mechanisms after brain ischemia have been less studied. Here we investigated the embryonic lethal abnormal vision/Hu isoforms HuR, HuB, HuC, and HuD, as well as expression of mRNAs containing adenine and rich uridine elements following global ischemia in rat brain. Proteomics of embryonic lethal abnormal vision immunoprecipitations or polysomes isolated from rat hippocampal CA1 and CA3 from controls or following 10min ischemia plus 8h of reperfusion showed distinct sets of mRNA-binding proteins, suggesting differential mRNA regulation in each condition. Notably, HuB, HuC, and HuD were undetectable in NIC CA1. At 8h reperfusion, polysome-associated mRNAs contained 46.1% of ischemia-upregulated mRNAs containing adenine and rich uridine elements in CA3, but only 18.7% in CA1. Since mRNAs containing adenine and rich uridine elements regulation are important to several cellular stress responses, our results suggest CA1 is disadvantaged compared to CA3 in coping with ischemic stress, and this is expected to be an important contributing factor to CA1 selective vulnerability. (Data are available via ProteomeXchange identifier PXD004078 and GEO Series accession number GSE82146).
Purpose of Review Globally, the majority of those who need mental health care worldwide lack access to high-quality mental health services. Stigma, human resource shortages, fragmented service delivery models, and lack of research capacity for implementation and policy change contribute to the current mental health treatment gap. In this review, we describe how health systems in low-and middle-income countries (LMICs) are addressing the mental health gap and further identify challenges and priority areas for future research. Recent Findings Common mental disorders are responsible for the largest proportion of the global burden of disease; yet, there is sound evidence that these disorders, as well as severe mental disorders, can be successfully treated using evidence-based interventions delivered by trained lay health workers in low-resource community or primary care settings. Stigma is a barrier to service uptake. Prevention, though necessary to address the mental health gap, has not solidified as a research or programmatic focus. Research-to-practice implementation studies are required to inform policies and scale-up services. Summary Four priority areas are identified for focused attention to diminish the mental health treatment gap and to improve access to high-quality mental health services globally: diminishing pervasive stigma, building mental health system treatment and research capacity, implementing prevention programs to decrease the incidence of mental disorders, and establishing sustainable scale up of public health systems to improve access to mental health treatment using evidence-based interventions.
Riboswitches are cis-acting mRNA elements that regulate gene expression in response to ligand binding. Recently, a class of riboswitches was proposed to respond to the molybdenum cofactor (Moco), which serves as a redox center for metabolic enzymes. The 5' leader of the Escherichia coli moaABCDE transcript exemplifies this candidate riboswitch class. This mRNA encodes enzymes for Moco biosynthesis, and moaA expression is feedback inhibited by Moco. Previous RNA-seq analyses showed that moaA mRNA copurified with the RNA binding protein CsrA (carbon storage regulator), suggesting that CsrA binds to this RNA in vivo. Among its global regulatory roles, CsrA represses stationary phase metabolism and activates central carbon metabolism. Here, we used gel mobility shift analysis to determine that CsrA binds specifically and with high affinity to the moaA 5' mRNA leader. Northern blotting and studies with a series of chromosomal lacZ reporter fusions showed that CsrA posttranscriptionally activates moaA expression without altering moaA mRNA levels, indicative of translation control. Deletion analyses, nucleotide replacement studies and footprinting with CsrA-FeBABE identified two sites for CsrA binding. Toeprinting assays suggested that CsrA binding causes changes in moaA RNA structure. We propose that the moaA mRNA leader forms an aptamer, which serves as a target of posttranscriptional regulation by at least two different factors, Moco and the protein CsrA. While we are not aware of similar dual posttranscriptional regulatory mechanisms, additional examples are likely to emerge. (c) 2012 Elsevier Ltd. All rights reserved.
Background: In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-gamma and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. Methods: Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: Control(TAK242), IgAN(TAK242), toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and Control(Pio), IgAN(Pio), Pio groups (rats were administrated with PPAR-y agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1 beta) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean +/- standard deviation. Differences between groups were analyzed by one-way analysis of variance. Results: Compared to normal rats, experimental rats showed higher ACR (4.45 +/- 1.33 mg/mmol vs. 2.89 +/- 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1 beta (48.28 +/- 13.49 pg/ml vs. 35.56 +/- 7.4 lpg/ml, P < 0.05), and renal expression of IL-1 beta and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1 beta, and serum IL-113 were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgAN(Pio) group (1.22 +/- 0.28 vs. 1.72 +/- 0.45, P < 0.01, and 0.12 +/- 0.03 vs. 0.21 +/- 0.05, P< 0.01). Conclusions: Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.
Background: Stem cell factor (SCF) has been implicated in many disease processes characterized by tissue remodelling and fibrosis. The growth factor (SCF) was evaluated in a rat model of nephrotoxic serum nephritis (NTN), characterized by early inflammation followed by later tissue fibrosis. Methods: NTN was induced in male Wistar Kyoto rats using rabbit anti-rat glomerular basement membrane antibodies. Animals were sacrificed at days 7, 15, 30 and 45 (n = 4-10 per group). Rats' kidneys were immunostained for ED1 as marker of inflammation, CD34, SCF, c-kit, mast cell tryptase and markers of fibrosis; collagens III and IV and alpha-SMA. Changes in SCF protein and mRNA content were evaluated by Western blotting and Northern blotting, respectively. Results: In the NTN kidney, levels of immunoreactive SCF and SCF receptor (c-kit) were significantly higher in glomerular, tubular and interstitial compartments. Mast cells were barely detectable in NTN and control rat sections. Double immunostaining showed the co-localization of SCF with alpha-SMA and of the SCF receptor with CD34 and ED1 positive cells. Immunostainable SCF protein in each of the 3 compartments, glomerular, tubular and interstitial, showed a positive linear correlation with serum creatinine, proteinuria, glomerulosclerosis score and interstitial fibrosis scores. Using multivariate analysis, immunostainable tubular SCF was a predictor of glomerular sclerosis and immunostainable glomerular SCF predicted tubular atrophy. Increased SCF immunostain was not a consequence of altered transcription as there was a fall in SCF mRNA determined by Northern blotting. Western blotting of NTN kidney homogenates revealed two bands for SCF, a 43-kDa band which decreased, and a 19-kDa band which increased throughout the study. Conclusion: These results highlight the potential role of SCF and its receptor in the remodelling process of the NTN kidney. Upregulation of SCF may involve a translational mechanism, with the soluble SCF protein KL-S1 (19 kDa) being derived from the transmembrane SCF protein KL-S1 (43 kD) by proteolytic cleavage. The immunohistochemical staining of few CD34+ cells in NTN kidneys warrants further evaluation of the nature of these cells in the context of the inflammatory as well as the fibrotic processes. Copyright (c) 2007 S. Karger AG, Basel.
Background and Objectives The mechanism of glucocorticoid -induced apoptosis is not fully understood and early predictive assays based on apoptotic markers for clinical outcome in acute lymphoblastic leukemia (ALL) are scarce. The aim of this study was to characterize the involvement of Bcl-2 family members and caspase activation in dexamethasone(Dex)induced apoptosis in ALL. Design and Methods Primary childhood ALL samples, the pre-B ALL cell line RS(4;11), and the T-ALL cell line CCRF-CEM were used. The involvement of Bcl-2 family members was evaluated by flow cytometry, immunocytochemistry, and western and northern blotting. Apoptosis was analyzed by annexin V and TMRE staining. Caspase activity was evaluated by a fluorometric assay. Results Dex induced significant down-regulation of the anti-apoptotic Bcl-2 family members Bcl-2 and Bcl-xL, differential activation of the pro-apoptotic Bak and Bax, loss of Delta psi m and cytochrome c release. Dex-induced apoptosis also involved early activation of caspases 2 and -3. Inhibition of caspase activity did not, however, protect against Dex-induced Bak/Bax activation, loss of Delta psi m or cell death. In 12 primary ALL samples Dex-induced apoptosis was associated with activation of Bax (p=0.045) and clown-regulation of Bcl-2 (p=0.016) and/or Bcl-xL (p=0.004). Furthermore, ex vivo Dex-sensitivity was associated with an early treatment response to polychemotherapy (p=0.026). Interpretation and Conclusions The differential regulation of pro- and anti-apoptotic Bcl-2 family members appears to be a key event in the execution of Dex-induced apoptosis in ALL cell lines, and also indicates a role for these proteins in primary ALL cells.
Experimental and epidemiological evidence suggests that consumption of hydrolyzable carbohydrate, hCHO (grain), by horses is an important risk factor for colic, a common cause of equine mortality. It is unknown whether the small intestinal capacity to digest hCHO and/or to absorb monosaccharides is limiting, or even if horses can adapt to increased carbohydrate load. We investigated changes in the brush-border membrane carbohydrate digestive enzymes and glucose absorptive capacity of horse small intestine in response to increased hCHO. Expression of the Na+/glucose co-transporter, SGLT1, was assessed by Western blotting, immunohistochemistry, Northern blotting, QPCR, and Na+-dependent d-glucose transport. Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses maintained on a hCHO-enriched diet compared to pasture forage. Activity of the disaccharidases was unaltered by diet. In a well-controlled study, we determined SGLT1 expression in the duodenal and ileal biopsies of horses switched, gradually over a 2-month period, from low (< 1.0 g/kg bwt/day) to high hCHO (6.0 g/kg bwt/day) diets of known composition. We show that SGLT1 expression is enhanced, with time, 2-fold in the duodenum and 3.3-fold in the ileum. The study has important implications for dietary management of the horse.
Reciprocal signalling and gene expression play a cardinal role during pathogen-host molecular interactions and are prerequisite to the maintenance of balanced homeostasis. Gene expression repertoire changes during rickettsial infection and glutathione-S-transferases (GSTs) were among the genes found up-regulated in Rickettsia-infected Dermacentor variabilis. GSTs are well known to play an important part in cellular stress responses in the host. We have cloned two full-length GSTs from D. variabilis (DvGST1 and DvGST2). Comparison of these two DvGST molecules with those of other species indicate that DvGST1 is related to the mammalian class theta and insect class delta GSTs, while DvGST2 does not seem to fall in the same family. Northern blotting analyses revealed differential expression patterns, where DvGST1 and DvGST2 transcripts are found in the tick gut, with DvGST2 transcripts also present in the ovaries. Both DvGST transcripts are up-regulated upon tick feeding. Challenge of fed adult ticks with Escherichia coli injection showed decreased transcript amounts compared with ticks injected with phosphate-buffered saline (sham) and naive ticks.
The addition of soybean protein materials to meat products is a common practice in the food industry, being a potential hidden allergenic commodity. This study aimed at proposing a novel specific and highly sensitive real-time PCR system for the detection/quantification of soybean as an allergenic ingredient in processed meat products. The method achieved a limit of detection of 9.8 pg of soybean DNA (8.6 copies), with adequate real-time PCR performance parameters, regardless of the soybean material (concentrate or isolate) and after thermal treatments. A normalised approach was also proposed in the range of 0.001-10% (w/w) of soybean material in pork meat, which was successfully validated and applied to processed meat products. Soybean was identified in more than 40% of tested samples of cooked ham and mortadella in the range of 0.1-4% (w/w), 3 samples not complying with labelling regulations as a result of undeclared soybean. (C) 2016 Elsevier Ltd. All rights reserved.
Glycogen and trehalose are important energy source and key regulation factors in the development of many organisms pass through energy metabolism, including bacteria, fungi, and insects. To study glycogen metabolism pathway in Spodoptera exigua, first cDNAs for glycogen synthase (SpoexGS) and glycogen phosphorylase (SpoexGP) were cloned from S. exigua. SpoexGS cDNA contains an open reading frame of 2,010 nucleotides encoding a protein of 669 amino acids with a predicted molecular mass of 76.19 kDa and a pI of 5.84. SpoexGP contains an open reading frame of 2,946 nucleotides, which encodes a protein of 841 amino acids with a predicted molecular mass of approximately 96.63 kDa and a pI of 6.03. Second, Northern blotting revealed that SpoexGS and SpoexGP mRNAs were expressed in brain, fat body, mid-gut, Malpighian tubules, spermary, and tracheae of S. exigua. Expression patterns for SpoexGS and SpoexGP mRNAs were similar in fat body, but differed in whole body at different developmental stages. The last, under starvation conditions, SpoexGS and SpoexGP transcript expression rapidly decreased with increasing starvation time. When the starvation stress was removed, SpoexGS and SpoexGP mRNA levels were lower in the groups starved for 6 and 12 h than in the 24-h starvation and control groups. Treatment with excessive sugar intake led to higher levels of SpoexGS and SpoexGP transcripts after 12 h compared to the control group. These findings provide new data on the tissue distribution, expression patterns, and potential function of glycogen synthase and glycogen phosphorylase proteins. (c) 2012 Wiley Periodicals, Inc.
The spermatogenic cell-specific variant of glyceraldehyde 3-phosphate dehydrogenase (GAPDS) has been cloned from a rat testis cDNA library and its pattern of expression determined. A 1,417 nucleotide cDNA has been found to encode an enzyme with substantial homology to mouse GAPDS (94% identity) and human GAPD2 (83% identity) isozymes. Northern blotting of rat tissue RNAs detected the 1.5 kb Gapds transcript in the testis and not in RNA from liver, spleen, epididymis, heart, skeletal muscle, brain, seminal vesicle, and kidney. The rat Gapds mRNA was first detected at day 29 of postnatal testis development, an age which coincides with the initial post-meiotic differentiation of round spermatids. When isolated rat spermatogenic cell RNA was probed for Gapds expression, transcripts were detected only in round spermatids and condensing spermatids, but not in pachytene spermatocytes, demonstrating haploid expression of the Gapds gene. However, immunohistochemical staining of rat testis sections with anti-GAPDS antisera did not detect GAPDS in round spermatids, but localized the protein only to stage XIII and later condensing spermatids as well as testicular spermatozoa, indicating that Gapds expression is translationally regulated. The current results are similar to those previously obtained for mouse GAPDS and human GAPD2, suggesting that reliable comparisons can be made between these species in toxicant screening and contraceptive development.
The gene encoding a cellobiohydrolase 7B (CBH7B) of the thermophilic fungus Thielavia terrestris was identified, subcloned, and expressed in Pichia pastoris. CBH7B encoded 455 amino acid residues with a molecular mass of 51.8 kDa. Domain analysis indicated that CBH7B contains a family 7 glycosyl hydrolase catalytic core but lacks a carbohydrate-binding module. Purified CBH7B exhibited optimum catalytic activity at pH 5.0 and 55 degrees C with 4-methylumbelliferryl-cellobioside as the substrate and retained 85% of its activity following 24 H incubation at 50 degrees C. Despite the lack of activity toward microcrystalline substrates, this enzyme worked synergistically with the commercial enzyme cocktail Cellic((R)) CTec2 to enhance saccharification by 39% when added to a reaction mixture containing 0.25% alkaline pretreated oil palm empty fruit bunch (OPEFB). Attenuated total reflectance Fourier transform infrared spectroscopy suggested a reduction of lignin and crystalline cellulose in OPEFB samples supplemented with CBH7B. Scanning electron microscopy revealed greater destruction extent of OPEFB strands in samples supplemented with CBH7B as compared with the nonsupplemented control. Therefore, CBH7B has the potential to complement commercial enzymes in hydrolyzing lignocellulosic biomass. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Interleukin-13 (IL-13) is a pleiotropic regulatory cytokine with the potential for treating several human diseases, including type-1 diabetes. Thus far, conventional expression systems for recombinant IL-13 production have proven difficult and are limited by efficiency. In this study, transgenic plants were used as a novel expression platform for the production of human IL-13 (hIL-13). DNA constructs containing hIL-13 cDNA were introduced into tobacco plants. Transcriptional expression of the hIL-13 gene in transgenic plants was confirmed by reverse transcriptase-polymerase chain reaction and Northern blotting. Western blot analysis showed that the hIL-13 protein was efficiently accumulated in transgenic plants and present in multiple molecular forms, with an expression level as high as 0.15% of total soluble protein in leaves. The multiple forms of plant-derived recombinant hIL-13 (rhIL-13) are a result of differential N-linked glycosylation, as revealed by enzymatic and chemical deglycosylation, but not of disulphide-linked oligomerization. In vitro trypsin digestion indicated that plant rhIL-13 was more resistant than unglycosylated control rhIL-13 to proteolysis. The stability of plant rhIL-13 to digestion was further supported with simulated gastric and intestinal fluid digestion. In vitro bioassays using a factor-dependent human erythroleukaemic cell line (TF-1 cells) showed that plant rhIL-13 retained the biological functions of the authentic hIL-13 protein. These results demonstrate that transgenic plants are superior to conventional cell-based expression systems for the production of rhIL-13. Moreover, transgenic plants synthesizing high levels of rhIL-13 may prove to be an attractive delivery system for direct oral administration of IL-13 in the treatment of clinical diseases such as type-1 diabetes.
Gnathostomiasis is a foodborne zoonotic parasitosis caused by Gnathostoma nematodes. It has caused significant public problems worldwide, but its molecular biology is limited. The purpose of this study was to decode the complete mitochondrial (mt) genomes of Gnathostoma nipponicum and Gnathostoma sp., and compare their mt sequences with other Gnathostoma species. The complete mt genome sequences were amplified by long-range PCR and determined by subsequent primer walking. The complete mt genomes of G. nipponicum and Gnathostoma sp. were 14,093 bp and 14,391 bp, respectively. Both of the two mt genomes contain 12 protein-coding genes (PCGs), 2 ribosomal RNA genes and 22 transfer RNA genes. The gene order and transcription direction are the same as G. spinigerum and G. doloresi. The sequence difference across the entire mt genomes varied from 14.4% to 18.2% between G. nipponicum, Gnathostoma sp., G. spinigerum and G. doloresi of Japan and China isolates. Phylogenetic analyses by Bayesian inference (BI) using concatenated amino acid sequences of 12 PCGs showed that G. nipponicum and Gnathostoma sp. are two distinctive species of Gnathostoma, and G. nipponicum are more closely related to Gnathostoma sp. than to G. spinigerum. The mtDNA datasets provide abundant resources of novel markers, which can be used for the studies of molecular epidemiology and diagnosis of Gnathostoma spp. (C) 2016 Elsevier B.V. All rights reserved.
Caseins are widely used for species identification of dairy products. Isoelectric focusing (IEF) of para-kappa-casein peptide is used as the official German method for the differentiation between caprine (isoform A) and ovine (isoform B) dairy products, based on their different isoelectric points. The discrimination between Greek goat and ewe dairy products using IEF has, however, been shown to he problematic because of the existence of the ewe isoform in milk from Greek indigenous dairy goats. This could be due to nucleotide polymorphisms within the goat kappa-casein gene of Greek indigenous breeds, which alter the isoelectric point of the para-kappa-casein peptide and lead to false positive results. Previous DNA analysis of the goat kappa-casein gene has shown high levels of polymorphism; however, no such information is available for Greek indigenous dairy goats. Therefore, 87 indigenous dairy goats were sequenced at exon IV of kappa-casein genie. In total, 9 polymorphic sites were detected. Three nonsynonymous point mutations were identified, which change the isoelectric point of the goat para-kappa-casein peptide so that it appears identical to that of the ewe peptide. Ten composite genotypes were reconstructed and 6 of them included the problematic point mutations. For the verification of genetic results, IEF was carried out. Both goat and ewe patterns appeared in the problematic genotypes. The frequency of these genotypes could be characterized as moderate (0.23) to high (0.60) within Greek indigenous breeds. However, this is not an issue restricted to Greece, as such genotypes have been detected in various non-Greek goat breeds. In conclusion, IEF based on the official German method is certainly inappropriate for ovine and caprine discrimination concerning Greek dairy goat products, and consequently a new method should be established.
Classical contagious caprine pleuropneumonia is one of the most fatal contagious disease of goats listed by World Organization for Animal Health that leads to major economic losses. It is caused by infection with Mycoplasma capricolum subspecies capripneumoniae. In order to isolate the causative agents of CCPP for the first time in the Kingdom of Saudi Arabia, fifteen flocks from Eastern region (Al Ahsa, Dammam and Hafr Albaten) and ten flocks from Riyadh and Al-Kharj regions were selected for this study. A total of 700 samples (400 nasal swabs, 300 pleural fluid samples and lung samples (from necropsied animals)) were collected from goats showing typical signs of CCPP. The clinical signs of diseased cases revealed serous to mucoid nasal discharge, coughing, dyspnea, frothy salivation, and fever (40-42 degrees C). Necropsied animals showed fibrinous pleuropneumonia and increased pleural fluid. Of 400 nasal swabs, 190 pleural fluid, and 110 lung samples, 26 (6.5%), 31 (16.3%) and 19 (17.3%) Mycoplasma isolates were recovered, respectively. Biochemically, all isolates were sensitive to digitonin and fermented glucose. Sixty seven of Mycoplasma isolates were belonged to Mycoplasma mycoides cluster based on detection of 16S rRNA. Polymerase chain reaction screening of Mycoplasma isolates using specific primer for M. capricolum subsp. capripneumoniae confirmed 55 isolates to be M. capricolum subsp. capripneumoniae. (C) 2017 Elsevier B.V. All rights reserved.
In view of the high biotoxicity and trace concentration of mercury (Hg) in environmental water, developing simple, ultra-sensitive and highly selective method capable of simultaneous determination of various Hg species has attracted wide attention. Here, we present a novel catalysis-reduction strategy for sensing inorganic and organic mercury in aqueous solution through the cooperative effect of AuNP-catalyzed properties and the formation of gold amalgam. For the first time, a new AuNP-catalyzed-organic reaction has been discovered and directly used for sensing Hg2+, Hg-2(2+) and CH3Hg+ according to the change of the amount of the catalytic product induced by the deposition of Hg atoms on the surface of AuNPs. The detection limit of Hg species is 5.0 pM (1 ppt), which is 3 orders of magnitude lower than the U.S. Environmental Protection Agency (EPA) limit value of Hg for drinking water (2 ppb). The high selectivity can be exceptionally achieved by the specific formation of gold amalgam. Moreover, the application for detecting tap water samples further demonstrates that this AuNP-based assay can be an excellent method used for sensing mercury at very low content in the environment.
Nanocarrier design combined with pulmonary drug delivery holds great promise for the treatment of respiratory tract disorders. In particular, targeting of dendritic cells that are key immune cells to enhance or suppress an immune response in the lung is a promising approach for the treatment of allergic diseases. Fluorescently encoded poly(vinyl alcohol) (PVA)-coated gold nanoparticles, functionalized with either negative (-COO-) or positive (-NH3+) surface charges, were functionalized with a DC-SIGN antibody on the particle surface, enabling binding to a dendritic cell surface receptor. A 3D coculture model consisting of epithelial and immune cells (macrophages and dendritic cells) mimicking the human lung epithelial tissue barrier was employed to assess the effects of aerosolized AuNPs. PVA-NH2 AuNPs showed higher uptake compared to that of their COOH counterparts, with the highest uptake recorded in macrophages, as shown by flow cytometry. None of the AuNPs induced cytotoxicity or necrosis or increased cytokine secretion, whereas only PVA-NH2 AuNPs induced higher apoptosis levels. DC-SIGN AuNPs showed significantly increased uptake by monocyte-derived dendritic cells (MDDCs) with subsequent activation compared to non-antibody-conjugated control AuNPs, independent of surface charge. Our results show that DC-SIGN conjugation to the AuNPs enhanced MDDC targeting and activation in a complex 3D lung cell model. These findings highlight the potential of immunoengineering approaches to the targeting and activation of immune cells in the lung by nanocarriers.
Gorham-Stout disease (GSD) is a rare condition of osteolysis with excessive lymphangiogenesis within bone tissue. The etiology of this condition remains unknown but seems to affect mainly children and young adults of both genders all over the world. Unfortunately, there is no standardized method for diagnosis; however, histopathology remains as the gold standard. This condition is often misdiagnosed due to its varying clinical presentations from case-to-case. Here, we report the case of an 8-year-old girl who presented with chronic mandibular pain during mastication and received multiple antibiotic treatment due to infectious origin suspicion. After integrating information from clinical manifestations, radiographic, laboratory, and histopathology information, she was diagnosed with GSD. Additionally, due to the lack of literature with respect to insights into biological mechanisms and standardized treatment for this condition, we underwent a literature revision to provide information related to activation of cells from the immune system, such as macrophages, T-cells, and dendritic cells, and their contribution to the lymphangiogenesis, angiogenesis, and osteoclastogenic process in GSD. It is important to consider these mechanisms in patients with GSD, especially since new studies performed in earlier stages are required to confirm their use as novel diagnostic tools and find new possibilities for treatment.
microRNAs (miRNAs) are 20-24 nucleotide non-coding small RNAs that play important roles in plant development. The stages of cotton fiber development include initiation, elongation, secondary wall thickening (SWT) and maturation. We constructed seven fiber RNA libraries representing the initiation, elongation and SWT stages. In total, 47 conserved miRNA families and seven candidate miRNAs were profiled using small RNA sequencing. Northern blotting and real-time polymerase chain reaction (PCR) analyses revealed the dynamic expression of miRNAs during fiber development. In addition, 140 targets of 30 conserved miRNAs and 38 targets of five candidate miRNAs were identified through degradome sequencing. Analysis of correlated expression between miRNAs and their targets demonstrated that specific miRNAs suppressed the expression of transcription factors, SBP and MYB, a leucine-rich receptor-like protein kinase, a pectate lyase, a-tubulin, a UDP-glucuronic acid decarboxylase and cytochrome C oxidase subunit 1 to affect fiber development. Histochemical analyses detected the biological activity of miRNA156/157 in ovule and fiber development. Suppressing miRNA156/157 function resulted in the reduction of mature fiber length, illustrating that miRNA156/157 plays an essential role in fiber elongation.
Kisspeptins and G protein coupled receptor (GPR54) play significant roles in regulating reproductive activity among seasonally reproductive animals; however, the mechanisms of KiSS-1 and GPR54 gene affecting the seasonal reproduction in striped hamster are still unknown. In this study, real-time quantitative polymerase chain reaction was employed to examine the expression profiles of KiSS-1 and GPR54 in the hypothalamus, ovaries, testes, uterus and epididymis of striped hamsters across 4 different seasons. Our results showed that, across different seasons, the KiSS-1 expression mode of male striped hamsters and the GPR54 expression mode of female striped hamsters were consistent with the seasonal photoperiod in the hypothalamus. Meanwhile, across different seasons, the expression profile of KiSS-1 in the testes and the GPR54 expression profile of male striped hamsters in the hypothalamus were consistent with the intensity of their seasonal reproductive activity. Among different tissues, the expression trend for GPR54 is consistent across 4 seasons, while that for KiSS-1 is tissue-dependent. The expression trend for GPR54 across 4 seasons is the same regardless of gender, while that for KiSS-1 is dramatically different and sex-dependent across different seasons. These results suggest that the expressions of KiSS-1 and GPR54 in the striped hamsters were regulated by complicated mechanisms, and the regulatory mechanisms in the striped hamsters are seasonal-dependent and sex-dependent. This research will provide a theoretical basis for studying how KiSS-1 and GPR54 affect seasonal reproduction and the mechanisms behind their influence.
AIM: To generate a Gpr128 gene knockout mouse model and to investigate its phenotypes and the biological function of the Gpr128 gene. METHODS: Bacterial artificial chromosome-retrieval methods were used for constructing the targeting vector. Using homologous recombination and microinjection technology, a Gpr128 knockout mouse model on a mixed 129/BL6 background was generated. The mice were genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a standard laboratory chow diet. Animals of both sexes were used, and the phenotypes were assessed by histological, biochemical, molecular and physiological analyses. Semi-quantitative reverse transcription-PCR and Northern blotting were used to determine the tissue distribution of Gpr128 mRNA. Beginning at the age of 4 wk, body weights were recorded every 4 wk. Food, feces, blood and organ samples were collected to analyze food consumption, fecal quantity, organ weight and constituents of the blood and plasma. A Trendelenburg preparation was utilized to examine intestinal motility in wild-type (WT) and Gpr128(-/-) mice at the age of 8 and 32 wk. RESULTS: Gpr128 mRNA was highly and exclusively detected in the intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in reduced body weight gain, and mutant mice exhibited an increased frequency of peristaltic contraction and slow wave potential of the small intestine. The Gpr128(+/+) mice gained more weight on average than the Gpr128(-/-) mice since 24 wk, being 30.81 +/- 2.84 g and 25.74 +/- 4.50 g, respectively (n = 10, P < 0.01). The frequency of small intestinal peristaltic contraction was increased in Gpr128(-/-) mice. At the age of 8 wk, the frequency of peristalsis with an intraluminal pressure of 3 cmH2O was 6.6 +/- 2.3 peristalsis/15 min in Gpr128(-/-) intestine (n = 5) vs 2.6 +/- 1.7 peristalsis/15 min in WT intestine (n = 5, P < 0.05). At the age of 32 wk, the frequency of peristaltic contraction with an intraluminal pressure of 2 and 3 cmH(2)O was 4.6 +/- 2.3 and 3.1 +/- 0.8 peristalsis/15 min in WT mice (n = 8), whereas in Gpr128(-/-) mice (n = 8) the frequency of contraction was 8.3 +/- 3.0 and 7.4 +/- 3.1 peristalsis/15 min, respectively (2 cmH(2)O: P < 0.05 vs WT; 3 cmH2O: P < 0.01 vs WT). The frequency of slow wave potential in Gpr128(-/-) intestine (35.8 +/- 4.3, 36.4 +/- 4.2 and 37.1 +/- 4.8/min with an intraluminal pressure of 1, 2 and 3 cmH(2)O, n = 8) was also higher than in WT intestine (30.6 +/- 4.2, 31.4 +/- 3.9 and 31.9 +/- 4.5/min, n = 8, P < 0.05). CONCLUSION: We have generated a mouse model with a targeted deletion of Gpr128 and found reduced body weight and increased intestinal contraction frequency in this animal model. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
In 2008, we established the Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) at Yale University. Our goal was to create a comprehensive graduate program to train a new generation of scientists who possess a sophisticated understanding of biology and who are capable of applying physical and quantitative methodologies to solve biological problems. Here we describe the framework of the training program, report on its effectiveness, and also share the insights we gained during its development and implementation. The program features co-teaching by faculty with complementary specializations, student peer learning, and novel hands-on courses that facilitate the seamless blending of interdisciplinary research and teaching. It also incorporates enrichment activities to improve communication skills, engage students in science outreach, and foster a cohesive program cohort, all of which promote the development of transferable skills applicable in a variety of careers. The curriculum of the graduate program is integrated with the curricular requirements of several Ph.D.-granting home programs in the physical, engineering, and biological sciences. Moreover, the wide-ranging recruiting activities of the IGPPEB serve to enhance the quality and diversity of students entering graduate school at Yale. We also discuss some of the challenges we encountered in establishing and optimizing the program, and describe the institution-level changes that were catalyzed by the introduction of the new graduate program. The goal of this article is to serve as both an inspiration and as a practical "how to" manual for those who seek to establish similar programs at their own institutions. (C) 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology
The efficacy of rabbit antithymocyte globulin (ATG) for the prevention of graft-versus-host disease (GVHD) has been evaluated in several randomized control trials, but the results show some discrepancies. Therefore, we performed a systematic review and meta-analysis covering the latest RCTs including six trials (total 845 patients). The incidence of acute and chronic GVHD was significantly lower in the ATG arms (risk ratio, 0.75 and 0.54, respectively). No significant differences were found regarding overall survival, the incidence of relapse, and non-relapse mortality; however, the incidence of cytomegalovirus and Epstein-Barr virus reactivation increased (risk ratio, 1.25 and 1.33), and neutrophil engraftment was significantly delayed (median, 2.66 days). In conclusion, rabbit ATG should be beneficial as a GVHD prophylaxis in addition to conventional regimens, with close monitoring of virus reactivation and enough attention to delayed engraftment. Studies comparing the timing and dosage of ATG are essential to determine the suitable prophylactic regimens.
Graft-versus-host disease (GVHD) is the major complication of hematopoietic stem cell transplantation and is associated with high mortality in severe cases. The skin is one of the major organs affected in both acute and chronic GVHD. This review aims to elucidate the basic characteristics of GVHD, and the role and contribution of dermatologists in the care of patients with this condition.
The aim of this study was to investigate the prevalence of fosfomycin resistance gene fosA3 and characterize plasmids harboring fosA3 among CTX-M-producing Escherichia coli from chickens in China. A total of 234 CTX-M-producing E. coli isolates collected from chickens from 2014 to 2016 were screened for the presence of plasmid-mediated fosfomycin resistance genes (fosA, fosA3, and fosC2). Clonal relatedness of fosA3-positive isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic environment of fosA3 was analyzed by polymerase chain reaction (PCR) mapping. Plasmids were studied by using conjugation experiments, PCR-based replicon typing and plasmid MLST. Sixty-four (27.4%) fosA3-positive E. coli isolates were identified in this study. The gene bla(CTX-M-55) (31/64) was predominant among these strains, followed by bla(CTX-M-14) (18/64) and bla(CTX-M-65) (14/64). Various PFGE patterns and sequence types (STs) indicated that these isolates were clonally unrelated. Seven different genetic environments of fosA3 were identified and two new combinations (ISEcp1-bla(CTX-M-65)-IS903D-IS26-fosA3-orf1-orf2-orf3-IS26 and IS26-ISEcp1-bla(CTX-M-3)-orf477-bla(TEM-1)-IS26-fosA3-orf1-orf2-orf3-IS26) were discovered for the first time. Conjugation experiments were successful for 47 isolates and 33 transconjugants harbored a single plasmid. Plasmids carrying fosA3 belonged to incompatibility group IncFII (17/33), IncI1 (2/33), IncHI2 (3/33), and IncB/O (1/33). F33:A-:B- plasmids carrying bla(CTX-M-55), IncHI2/ST3 plasmids carrying bla(CTX-M-65), and F2:A-:B-plasmids carrying bla(CTX-M-55) were found in E. coli isolates from different provinces. Our results revealed a considerable prevalence of fosA3 gene among CTX-M-producing E. coli with clonal diversity from chickens in China. The transmission of different kinds of plasmids is responsible for the dissemination of fosA3 in chicken farms in China.
Plasminogen is a major plasma protein and the zymogen of the broad spectrum protease plasmin. Plasmin activity leads to tissue degradation, direct and through activation of metalloproteinases. Infected tooth root canals, as a consequence of the inflammatory response and eventual necrosis, contain tissue fluid and blood components. These will coat the root canal walls and act as conditioning films that allow bacterial biofilms to grow and be a potential source of hematogenously spreading bacteria. We investigated the effect of in vitro surface conditioning with human plasminogen on the initial adhesion of bacteria. Four bacterial species, L. salivarius, E. faecalis, A. naeslundii, and S. gordonii, isolated from dental root canals, and three other oral streptococci, S. oralis, S. anginosus, and S. sanguinis, were grown in albumin- or plasminogen-coated flow chambers and studied by confocal laser scanning microscopy using the cell viability staining LIVE/DEAD and 16S rRNA fluorescence in situ hybridization (FISH). A. naeslundii, L salivarius and in particular S. gordonii showed a higher initial adhesion to the plasminogen-coated surfaces. E. faecalis did not show any preference for plasminogen. Four-species biofilms cultured for 96 h showed that streptococci increased their proportion with time. Further experiments aimed at studying different streptococcal strains. All these adhered more to plasminogen-coated surfaces than to albumin-coated control surfaces. The specificity of the binding to plasminogen was verified by blocking lysine-binding sites with epsilon-aminocaproic acid. Plasminogen is thus an important plasma component for the initial adhesion of oral bacteria, in particular streptococci. This binding may contribute to their spread locally as well as to distant organs or tissues. (C) 2016 Elsevier Ltd. All rights reserved.
Low-velocity impact cratering experiments are conducted in sloped granular targets to study the effect of the slope angle theta on the crater shape and its scales. We use two types of granular matter, sand and glass beads, former of which has a larger friction coefficient mu(s) = tan theta(r), where theta(r) is the angle of repose. Experiments show that as theta increases, the crater becomes shallower and elongated in the direction of the slope. Furthermore the crater floor steepens in the upslope side and a thick rim forms in the downslope side, thus forming an asymmetric profile. High-speed images show that these features are results of ejecta being dispersed farther towards the downslope side and the subsequent avalanche which buries much of the crater floor. Such asymmetric ejecta dispersal can be explained by combining the Z-model and a ballistic model. Using the topographic maps of the craters, we classify crater shape regimes I-III, which transition with increasing theta : a full-rim crater (I), a broken-rim crater (II), and a depression (III). The critical theta for the regime transitions are larger for sand compared to glass beads, but collapse to close values when we use a normalized slope (theta) over cap = tan theta / tan theta(r). Similarly we derive (theta) over cap -dependences of the scaled crater depth, length, width and their ratios which collapse the results for different targets and impact energies. We compare the crater profiles formed in our experiments with deep craters on asteroid Vesta and find that some of the scaled profiles nearly overlap and many have similar depth / length ratios. This suggests that these Vestan craters may also have formed in the gravity regime and that the formation process can be approximated by a granular flow with a similar effective friction coefficient. (C) 2017 Elsevier Inc. All rights reserved.
BackgroundThe incidence of cutaneous nontuberculous mycobacterial (NTM) infection has increased in recent decades because of widespread use of immunosuppressive therapy and better detection methods. The histopathology of cutaneous NTM infection is not pathognomic and the organisms are slow and difficult to culture, making diagnosis challenging. MethodsWe reviewed the clinical and histopathological features of 13 cases of cutaneous NTM infection, and performed panmycobacterial polymerase chain reaction (PCR) on the paraffin blocks. ResultsThe immunocompetent patients presented with localized lesions on the extremities, whereas the immunocompromised patients presented with disseminated cutaneous lesions. The histopathology in immunocompetent patients was characterized by pseudoepitheliomatous epidermal hyperplasia, intraepithelial abscesses, transepidermal elimination and dermal granulomatous inflammation accompanied by necrosis and suppuration. The immunocompromised patients showed suppurative inflammation with little granuloma formation and numerous acid-fast bacilli. Paraffin block PCR was positive in 4 of 13 cases (31%), whereas culture was positive in 11 of 13 cases (85%). ConclusionThe aforementioned histological features should help in diagnosing cutaneous NTM infection when combined with clinical and microbiological correlation. In our study, we did not find paraffin block PCR to be superior to conventional culture in detecting cutaneous NTM infection.
Purpose There is no information available about the IL-18 receptor in ovarian follicles, so the present study attempts to demonstrate the expression of IL-18 and its receptor in human granulosa cells (GCs). Methods To evaluate the concentration of IL-18 in serum and follicular fluid (FF), we collected serum and FF from 102 women undergoing oocyte retrieval. Also, to detect expression of IL-18 and its receptor by luteinized GCs, these cells were pooled six times from a total of twenty individual patients with 5-16 follicles each. The IL-18 concentration was determined by ELISA and the expression of IL-18 and its receptor by immunocytochemistry and reverse transcription polymerase chain reaction. Results Our results showed that the median IL-18 concentration in serum, 159.27 pg/ml (IQR 121.41-210.1), was significantly higher than in FF, 142.1 pg/ml (IQR 95.7176.5), p < 0.001. Moreover, we found that IL-18 and its receptor are expressed by GCs. Conclusion The presence of IL-18 in FF and the expression of IL-18 and its receptor by GCs suggest an important role for this cytokine in ovarian function.
Proanthocyanidins have been suggested as an effective antibiotic alternative, however their mechanisms are still unknown. The present study investigated the effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier using a weaned piglet model in comparison with colistin. Piglets weaned at 28 day were randomly assigned to four groups treated with a control ration, or supplemented with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut chyme and tissue samples were collected to test intestinal microbiota and barrier function, respectively. Proanthocyanidins treated piglets had better growth performance and reduced diarrhea incidence (P < 0.05), accompanied with decreased intestinal permeability and improved mucosal morphology. Gene sequencing analysis of 16S rRNA revealed that dietary proanthocyanidins improved the microbial diversity in ileal and colonic digesta, and the most abundant OTUs belong to Firmicutes and Bacteroidetes spp.. Proanthocyanidins treatment decreased the abundance of Lactobacillaceae, and increased the abundance of Clostridiaceae in both ileal and colonic lumen, which suggests that proanthocyanidins treatment changed the bacterial composition and distribution. Administration of proanthocyanidins increased the concentration of propionic acid and butyric acid in the ileum and colon, which may activate the expression of GPR41. In addition, dietary proanthocyanidins improved the antioxidant indices in serum and intestinal mucosa, accompanied with increasing expression of barrier occludin. Our findings indicated that proanthocyanidins with half-dose colistin was equivalent to the antibiotic treatment and assisted weaned animals in resisting intestinal oxidative stress by increasing diversity and improving balance of gut microbes.
Isolation of high quality RNA from plant tissues is one of the most critical steps for the successful application of diagnostic tests such as reverse transcription polymerase chain reaction (RT-PCR), northern blotting, microarray hybridization. The presence of inhibitors such as secondary metabolites, phenolic compounds and RNAses can cause inaccurate and undesirable results. Grapevine is rich in a wide range of metabolites which interfere with RNA isolation. From this point of view, we researched six different total RNA extraction methods on leaves of Vitisvinifera L. to find the best one that contribute the purity and high quality. The methods tested are silica-capture, modified silica-capture, commercial kit, the new combined, lithium chloride and citric buffer. RNA quality was analyzedspectrophotometrically by nanodrop, agarose gel electrophoresis and RT-PCR. As a result of all, it is clear that the most suitable TNA isolation protocol is the new combined method which experienced and named firstly by us, in terms of RNA purity, concentration, less time consuming of isolation step and achievement on detection of GYSVd-1.
Recent studies showed that a large amount of graphene oxide accumulated in kidney and liver when it injected intravenously. Evaluation of lethal and apoptosis gene expression in these tissues, which are under stress is very important. In this paper the in vivo dose-dependent effects of graphene oxide and reduced graphene oxide nanoplatelets on kidney and liver of mice were studied. Balb/C mice were treated by 20 mg/kg body weight of nanoplatelets. Molecular biology analysis showed that graphene nanoplatelets injected intravenously lead to overexpression of BAX gene in both kidney and liver tissues (P >= 0.01). In addition these nanoparticles significantly increase BCL2 gene expression in both kidney and liver tissues (P >= 0.05). Graphene significantly increase level of SGPT in groups 1 (220.64 +/- 13), 2 (164.44 +/- 9.3) in comparison to control group (P <= 0.05). Also in comparison with control group (148.11 +/- 10.4), (P <= 0.05), the level of SGOT in groups 1(182,01 +/- 12.6) and 2 (1782 +/- 22) significantly increased. (C) 2016 Published by Elsevier B.V.
Triboelectric generators, which can directly transform energy from our living environment into electricity, are self-powered component for wearable devices. Flexible and transparent triboelectric generators (FTTGs) with high output power densities are urgently needed for wearable electronics. By introducing graphene (G) and indium tin oxide (ITO) as transparent electrodes and optimizing the electrode structure, a FTTG with polyimide (PI) and polyethylene terephthalate (PET) as friction layers and graphene (ITO) as top (bottom) electrode was obtained and it has a large output power density of 10.1Wcm(-2), which is over four times larger than previously reported FTTGs ca. 2Wcm(-2). Moreover, the output voltage of the graphene-based FTTG is as large as 56V, and it exhibits excellent cycling behavior. The effects of electrode structure on the performance of FTTG have been analyzed and corresponding mechanism has been discussed. Light-emitting diodes (LED) can be easily powered by the FTTG, suggesting its potential application in harvesting electrical energy from human activities by using flexible and transparent devices.
How to preserve the structure integrity of graphene while enhance its dispersion and compatibility in matrix attracts the attention of researchers in graphene/polymer nanocomposite field. In this paper, methacryloxyethyltrimethyl ammonium chloride (DMC), a kind of ionic liquids, was first used to non-covalently functionalize graphene in the process of graphene oxide (GO) reduction. The as-modified graphene (DMC-rGO) was further incorporated into poly(vinyl alcohol) (PVA) matrix by solution casting technique to fabricate DMC-rGO/PVA composites. The structure and properties of the obtained DMC-rGO were investigated by X-ray diffraction analysis (XRD), X-ray Photoelectron Spectroscopy (XPS), Transmission Electron Microscope (TEM), Atomic force microscopy (AFM), and Raman test. The results showed that graphene could be successfully modified by DMC through ionic- interaction and the structure integrity of the graphene could be reserved by this non-covalently approach. Furthermore, after co-reduction process, some hydroxyl groups were introduced into DMC-rGO. In virtue of these intrinsic properties of DMC-rGO, the fabricated DMC-rGO/PVA composites exhibit considerable enhancements in mechanical properties and remarkable improvements in thermal stability, as well as the enhancement in electrical conductivity at low DMC-rGO loading. This simple modification approach gives a new opportunity to improve the performances of graphene/polymer composites. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45006.
We propose a multi-resolution scanning approach to identifying two-sample differences. Windows of multiple scales are constructed through nested dyadic partitioning on the sample space and a hypothesis regarding the two-sample difference is defined on each window. Instead of testing the hypotheses on different windows independently, we adopt a joint graphical model, namely a Markov tree, on the null or alternative states of these hypotheses to incorporate spatial correlation across windows. The induced dependence allows borrowing strength across nearby and nested windows, which we show is critical for detecting high resolution local differences. We evaluate the performance of the method through simulation and show that it substantially outperforms other state of the art two-sample tests when the two-sample difference is local, involving only a small subset of the data. We then apply it to a flow cytometry data set from immunology, in which it successfully identifies highly local differences. In addition, we show how to control properly for multiple testing in a decision theoretic approach as well as how to summarize and report the inferred two-sample difference. We also construct hierarchical extensions of the framework to incorporate adaptivity into the construction of the scanning windows to improve inference further.
Chemical fertilizers, especially nitrogen (N) and phosphorus (P), are used in grasslands to maximize plant biomass production for livestock. Despite a substantial body of work on how fertilization affects aboveground plant and belowground microbial communities, the short-term response of soil ammonia oxidizing microbial communities, which play the central role in nitrification, to fertilization is not well understood. The responses of ammonia-oxidizing microbial communities to short-term (3 years) N and/or P additions were investigated in an alpine grassland of the Qinghai-Tibetan Plateau. Quantitative polymerase chain reaction (qPCR) analysis of the amoA genes showed that ammonia-oxidizing archaea (AOA) dominated over ammonia-oxidizing bacteria (AOB) in non-amended soil. Short-term urea addition significantly increased the abundance of AOB, whereas AOA abundance remained unchanged, resulting in a shift from AOA to AOB dominance, which suggests that AOB are likely to be more important in the first step of the nitrification following urea amendment. Pyrosequencing demonstrated a significant shift in AOB but not AOA community composition within short-term N fertilizer plots, indicating that AOB community composition was more sensitive than AOA in response to urea amendment. This study demonstrated that the abundance and composition of AOA and AOB communities responded differently to 3 years of urea addition, suggesting that N fertilizer may be an important controller of ammonia oxidizing microbial communities in managed alpine grasslands, such as those of the Qinghai-Tibet Plateau.
The Great East Japan Earthquake (GEJE) and subsequent tsunamis that occurred in 2011 caused extensive and severe structural damage and interrupted numerous research activities; however, the majority of such activities have been revived, and further public health researches and activities have started to follow the population affected by the disaster. In this mini-review, we overview our recent activities regarding epidemiologic studies in Miyagi Prefecture, the region most affected by the GEJE. Through our study processes, we were able to identify the particular characteristics of vulnerable populations, and provide ideas that may help save lives and reduce the amount of damage caused by a future disaster. Long-term follow-up and care of survivors is essential in affected areas, and health professionals should pay particular attention to various diseases, e.g., cardiovascular complications and mental disorders. Furthermore, building up resilience and social relationships in the community is beneficial to survivors. Ongoing cohort studies conducted before disasters can help minimize biases regarding the survivors' pre-disaster information, and emerging cohort studies after disasters can find potential helpful novel indices. To identify characteristics of vulnerable populations, save lives, and reduce the amount of damage caused by a future disaster, constant research that is consistently improved by new data needs to be performed.
OBJECTIVES: The objectives of this study were to identify interrelations between matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients with aortic root/ascending aortic aneurysms and to describe comorbidities as possible biasing factors in the widely discussed correlation of serum MMP levels and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32 consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at the Heart Center University of Freiburg from May 2013 to January 2014. The influence of comorbidities and medication on serum MMP2 and MMP9 levels was studied. We took into account ascending aortic diameter (aAD), aortic valve configuration, hypertension, age and hyperlipidaemia as factors possibly altering serum MMP levels. The relation between serum MMP levels and aAD was examined by a correlation test based on ranks. RESULTS: Serum MMP2 levels and aAD correlated positively. Correlation was increased in patients without hyperlipidaemia (Spearman's rho = 0.62, P = 0.008 in patients without hyperlipidaemia;rho = 0.409, P = 0.020 in all patients). Serum MMP9 levels did not correlate with aAD and showed greater variation. Serum MMP9 levels were significantly associated with hyperlipidaemia (P = 0.037). CONCLUSIONS: The distinct correlation patterns in patients with and without hyperlipidaemia have to be considered when defining the potential of MMP2 as a biomarker in future studies. The relation between MMP9 and hyperlipidaemia has to be further investigated.
Rhodanese-domain proteins (RDPs) are widespread in plants and other organisms, but their biological roles are mostly unknown. Here we report on a novel RDP from Chlamydomonas that has a single rhodanese domain, and a predicted chloroplast transit peptide. The protein was produced in Escherichia coli with a His-tag, but lacking most of the N-terminal transit peptide, and after purification was found to have rhodanese activity in vitro. It was also used to elicit antibodies for western blot analysis, which showed that the native Chlamydomonas protein migrated slower on SDS gels (apparent M-r = 34 kDa) than its predicted size (27 kDa), and co-fractionated with chloroplasts. To assess function in vivo, the tandem-RNAi approach was used to generate Chlamydomonas strains that had reductions of 30-70 % for the mRNA and similar to 20-40 % for the 34-kDa protein. These strains showed reduced growth under all trophic conditions, and were sensitive to even moderate light; properties reminiscent of chloroplast translation mutants. Pulse-labeling in the presence of cycloheximide indicated that chloroplast protein synthesis was broadly reduced in the RNAi strains, and transcript analysis (by RT-PCR and northern blotting) indicated the effect was mainly translational. These results identify a novel rhodanese-like protein that we have named CRLT, because it is required to maintain chloroplast translation.
Green planning is critically important during the design phases of construction projects but continually gets less attention during construction. Project owners and planners need to understand how communication influences green implementation. To address a gap in the extant research, this paper presents the evaluation results on how sustainability awareness of field supervision personnel impacts the successful completion of school projects by proving that communicating sustainability goals with them is vital for decision-making during the construction stage of the project. This paper uses data collected from 162 new school construction projects to compare sustainability design goals with their successful incorporation into completed projects. Seventy-one project managers and inspectors were surveyed to assess their awareness of key high-performance sustainability requirements that were built into the designs. The responses from these two groups were compared to examine the positive or negative impacts. The analysis results show that early and continuous communication of sustainability design goals with field supervision personnel has a significant impact on whether those goals are realized when the project is turned over to the owner for occupancy. Successful implementation of sustainability goals not only provides economic benefits from fully exploiting life-cycle costs, but also holds the promise of providing a healthier working environment.
Several studies on sustainable technologies for the built environment (e.g., green roofs, green walls, etc.) have been carried out. Many of these focus on the technical performance of such technologies. Nonetheless, it also becomes necessary to examine how the public perceives such technologies. This understanding is clearly important to support their widespread use. More specifically, such perception can be incorporated into product design to increase people's acceptance. The contribution of this paper is twofold. First, it presents results of a survey examining the perception of people from a small city in the Southern region of Brazil (Feliz, RS) regarding three sustainable technologies: green roofs, green walls, and composting (or dry) toilets. Second, it proposes a set of preliminary design guidelines to improve acceptance of more sustainable technologies based on people's perception: (1) make the technology look good; (2) make visible the benefits provided by the technology; and (3) design the technology to avoid misunderstandings and concerns. (C) 2016 American Society of Civil Engineers.
Previous research focusing on rodent cells and animal models has demonstrated that gremlin-1 antagonizes bone morphogenetic proteins (BMPs) in order to suppress osteogenesis. However, the impact of gremlin-1 on osteogenesis in human bone marrow-derived mesenchymal stem cells (MSCs) remains unknown. The aim of the present study was to test the effects of gremlin-1 on viability and invitro BMP-2-induced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs). Gremlin-1-specific small interfering RNA (siRNA) inhibited gremlin-1 mRNA and protein expression in human MSCs. The mRNA expression levels of osteoblastic genes were analyzed using reverse transcription-quantitative polymerase chain reaction, and calcification and enzymatic alkaline phosphatase (ALP) activity assessed the BMP-2-induced osteogenic differentiation of human MSCs. The results indicated that gremlin-1 suppression significantly increased human MSC metabolism and DNA content. The expression levels of osteoblastic genes were also significantly increased by gremlin-1 inhibition. In the gremlin-1-inhibited group, enzymatic ALP activity was significantly increased. In addition, due to BMP-2-inducing osteoblasts, gremlin-1 inhibition increased calcium deposits. The present study indicated that gremlin-1 inhibited the cell viability and osteogenic differentiation of human MSCs and that the suppression of gremlin-1 expression suppressed can increase the cell viability and osteogenic differentiation of human MSCs induced by BMP-2.
Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium-to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M: 55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow- up. There was no association between baseline grey matter density and IQ or positive symptoms at followup. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions.
Background Blood parameters such as haematocrit or leucocyte counts are indicators of immune status and health, which can be affected, in a complex way, by exogenous as well as endogenous factors. Additionally, social context is known to be among the most potent stressors in group living individuals, therefore potentially influencing haematological parameters. However, with few exceptions, this potential causal relationship received only moderate scientific attention. Methods In a free-living and individually marked population of the highly social and long-lived Greylag goose, Anser anser, we relate variation in haematocrit (HCT), heterophils to lymphocytes ratio (H/L) and blood leucocyte counts to the following factors: intrinsic (sex, age, raising condition, i.e. goose- or hand-raised), social (pair-bond status, pair-bond duration and parental experience) and environmental (biologically relevant periods, ambient temperature) factors. Blood samples were collected repeatedly from a total of 105 focal birds during three biologically relevant seasons (winter flock, mating season, summer). Results We found significant relationships between haematological parameters and social as well as environmental factors. During the mating season, unpaired individuals had higher HCT compared to paired and family individuals and this pattern reversed in fall. Similarly, H/L ratio was positively related to pair-bond status in a seasonally dependent way, with highest values during mating and successful pairs had higher H/L ratio than unsuccessful ones. Also, absolute number of leucocytes tended to vary depending on raising condition in a seasonally dependent way. Discussion Haematology bears a great potential in ecological and behavioural studies on wild vertebrates. In sum, we found that HTC, H/L ratio and absolute number of leucocytes are modulated by social factors and conclude that they may be considered valid indicators of individual stress load.
Declining costs for solar photovoltaics (PV) and excitement about new technologies have led to speculation that self-sufficient PV/battery storage systems will soon become competitive with traditional electricity service. We compare a grid-tied residential solar system with an off-grid solar-plus-battery system at 1020 US locations, and calculate three effects of "grid defection" for each: the private net costs to the homeowner, the change in system generation costs, and change in system emissions. For the average US location, an off-grid solar system is almost double the price of grid-connected solar, is associated with higher system generation costs, and has no emissions benefit. (C) 2017 Elsevier Ltd. All rights reserved.
Power grid interconnection has gained attention in Northeast Asia (NEA) as a means to effectively utilize the abundant renewable resources in Mongolia. This paper quantifies the potential economic and environmental benefits of deploying massive wind turbines and solar PV in Mongolia for power exports. The author uses an NEA-wide multi-region power system model formulated as a linear programming problem. The analysis considers power systems characteristics, such as the seasonal and daily electric load curves of the NEA regions. The simulation results show that the large-scale Mongolian renewables contribute to significant CO2 reductions in NEA. China, in particular, benefits from a significant reduction in coal-fired generation. However, huge investments would be required for the massive renewables and cross-boundary transmission facilities, pushing up electricity supply cost. The relevant planning organizations need to carefully consider these environmental opportunities and economic barriers before implementation. This paper also investigates the economic impacts of transmission route circuity due to avoiding transmission through the Democratic People's Republic of Korea (DPRK). Our results imply modest effects of the circuity on the total system cost; availability of routes through the DPRK would not significantly increase the benefits to the NEA system of integrating massive renewables in Mongolia. (C) 2017 The Author(s). Published by Elsevier Ltd.
A systematic design method for 3-D grid multiscroll chaotic attractors by using staircase nonlinear functions (SNFs) is proposed in this paper. Equations of parameters for 3-D grid multiscroll chaotic attractors are derived in the consideration of the dynamic range for the active device and the number of multiscroll chaotic attractors. 5 x 4 and 4 x 3 of 3-D grid multiscroll chaotic attractors are generated by this method. A chaotic circuit is designed only using current feedback operational amplifiers (CFOAs). The circuit consists of three integrators and two nonlinear circuits. The parameters of the circuit are calculated by the parameters of 3-D grid multiscroll chaotic attractors. The circuit can generate 3-D grid multiscroll chaotic attractors. The central frequency of the circuit is higher with fewer active devices and simpler circuit construction for the good frequency characteristic and port characteristic of the CFOA. Numerical simulation results and the circuit simulation results show that the method is feasible and the designed circuit is correct.
In this paper, a method is proposed to realize the grid multi-scroll chaotic system with the current feedback operational amplifier (CFOA). Firstly, nonlinear circuit is designed based on the CFOA. Then the grid multi-scroll chaotic circuit is designed and relevant circuit parameters are calculated. Finally circuit simulation is conducted, and the results show that the circuit has a higher central frequency, needs less components, and possesses simpler circuit structure, good frequency characteristic and port characteristic of the CFOA.
A power distribution grid exhibits the characteristics of a weak grid owing to the existence of scattered high-power distributed power-generation devices. The grid impedance affects the robust stability of grid-connected inverters, leading to harmonic resonance, or even instability in the system. Therefore, a study of the stability of grid-connected inverters with high grid impedance based on impedance analysis is presented in this paper. The output impedance modeling of an LCL-type single-phase grid-connected inverter is derived, where the effects of the PLL loop and the digital control delays on the output impedance characteristics have been taken into account. To enhance the stability of grid-connected inverters with different grid impedance, a novel impedance-phased compensation control strategy is proposed by increasing the phase margin of the grid-connected inverters. Specifically, a detailed implementation and parameter design of the impedance-phased compensation control method is depicted. Finally, an impedance-phased dynamic control scheme combined with online grid impedance measurement is introduced and also verified by the experiment results.
In a distributed generation system, the stability of grid-connected inverters is directly related to the reliable operation of the grid-connected system. The impedance-based analysis method can be employed to effectively study the interaction stability between grid-connected inverters and grid, which means that it is necessary to obtain the impedance modeling of grid-connected inverters for the analysis of impedance stability. Based on the three-phase LCL-type grid-connected inverter, the harmonic linearization method was adopted in this paper to analyze the frequency characteristic of Phase-Locked Loop (PLL), and a design approach of PLL regulator parameters was proposed. Meanwhile, the impacts of the factors that include PLL and digital control delay on the impedance characteristic were considered, and the positive-sequence and negative-sequence impedance model of the gridconnected inverter was built by combining the harmonic linearization and symmetrical component methods. Then, the frequency characteristic of PLL was verified by the simulation results and the output impedance model of the grid-connected inverter was verified by the experimental results, which effectively proved the correctness of the theoretical analysis. Finally, based on the output impedance model of the grid-connected inverter, the impedance-based analysis method was adopted to make a theoretical analysis and experiment validation of the interaction stability of the grid-connected system.
Direct Model Predictive Power Control (DMPPC) has emerged as a viable alternative for grid-tied Active Front End (AFE) power converters. However, its one-switching-vectorper-sampling-interval character leads to big ripples in its control variables. This work proposes a Performance-Enhanced Direct Multiple-Vector Model Predictive Power Control (DMV-MPPC) solution for grid-tied AFEs directly implementable on an FPGA. The proposed control scheme is compared with the classical DMPPC. The presented experimental results illustrate that the control performance can be significantly improved by the proposed DMV-MPPC scheme.
One of the recent developments in personality psychology is the emergence of a new construct, Grit. Its emergence led to a proliferation of studies advancing Grit as a significant predictor of various positive outcomes. So far, little attention has been paid to testing its relevance for various work-related outcomes. The present paper unraveled Grit's validity in predicting a series of work-relevant outcomes, namely, organizational citizenship behavior, in-role performance, counter-productive work behaviors and job satisfaction over the Five-Factor Model (FFM) of personality. These constructs were assessed on a sample including 170 worldng adults. Grit had limited predictive validity over the FFM dimensions in predicting the focal outcomes. Consequently, its relevance in the workplace should be treated with caution. More research should be conducted before using Grit as a basis for personnel selection or for interventions focusing on various aspects of performance or job satisfaction. (C) 2017 Elsevier Ltd. All rights reserved.
The Gromov-Hausdorff distance of two compact metric spaces is a measure for how far the spaces are from being isometric and has been extensively studied in the field of metric geometry. In recent years, a lot of attention has been devoted to computational aspects of the Gromov-Hausdorff distance. One of the most prominent applications is the problem of shape matching, where the goal is to decide whether two shapes given as polygonal meshes are equivalent under certain invariances. Therefore, many methods have been proposed which heuristically estimate the Gromov-Hausdorff distance of metric spaces induced by the shapes. However, the computational complexity of computing the Gromov-Hausdorff distance has not yet been thoroughly investigated. We show that-under standard complexity theoretic assumptions-determining the Gromov-Hausdorff distance of two finite metric spaces cannot be approximated within any reasonable bound in polynomial time. Furthermore, we discover attributes of metric spaces which have a major impact on the complexity of an instance. This enables us to develop an approximation algorithm which is fixed parameter tractable with respect to corresponding parameters.
Transcriptional enhancers are DNA regulatory elements that are bound by transcription factors and act to positively regulate the expression of nearby or distally located target genes. Enhancers have many features that have been discovered using genomic analyses. Recent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs). GRO-seq, a method for identifying the location and orientation of all actively transcribing RNA polymerases across the genome, is a powerful approach for monitoring nascent enhancer transcription. Furthermore, the unique pattern of enhancer transcription can be used to identify enhancers in the absence of any information about the underlying transcription factors. Here, we describe the computational approaches required to identify and analyze active enhancers using GRO-seq data, including data pre-processing, alignment, and transcript calling. In addition, we describe protocols and computational pipelines for mining GRO-seq data to identify active enhancers, as well as known transcription factor binding sites that are transcribed. Furthermore, we discuss approaches for integrating GRO-seq-based enhancer data with other genomic data, including target gene expression and function. Finally, we describe molecular biology assays that can be used to confirm and explore further the function of enhancers that have been identified using genomic assays. Together, these approaches should allow the user to identify and explore the features and biological functions of new cell type-specific enhancers.
In this paper, two lossy grounded inductor simulators (GISs) and one lossless GIS including an inverting type current feedback operational amplifier (CFOA), two resistors and a capacitor are proposed. All the proposed GISs can be easily obtained with commercial available active devices such as AD844s. Also, they do not need any critical passive component matching conditions. Both of the proposed lossy GISs employ a grounded capacitor, whereas the lossless one has a floating capacitor. In order to show performance of the proposed GISs, a number of simulation and experimental test results are given.
In this paper a novel lossless grounded negative inductance simulator is proposed using only one operational transresistance amplifier (OTRA) as an active element and one capacitor and three or four resistors as passive elements. All the properties of the proposed negative inductance simulator are verified using both CMOS and current feedback operational amplifier (CFOA) based OTRA realization is PSPICE. The proposed circuit is also tested experimentally to verify the theoretical results. As an application, the cancellation of unwanted inductance is tested using the proposed inductance simulator.
Groundwater vulnerability assessment delineating areas that are susceptible to contamination from future scenarios has aroused worldwide attention. In this study, the authors (1)estimate future groundwater vulnerability in Hunan province, China, under urban-related land-use change and climate change scenarios; and (2)analyze the importance of related parameters to future groundwater vulnerability. The DRASTIC model [including seven parameters: depth to water table (D), net recharge (R), aquifer type (A), soil type (S), topography (T), impact of vadose zone (I) and conductivity (C)] together with an extra parameter, land-use patterns, was used to generate the map of groundwater vulnerability in future scenarios. The results indicated that vulnerability classes had an increasing trend from low to high vulnerability in the future scenarios. Hunan province may face high groundwater pollution risk in the future. The sensitivity analysis indicated that the depth-to-water table may be the dominant factor, and the land-use pattern was the most sensitive parameter on the predicted future groundwater vulnerability in Hunan province. Decision makers should identify the potential future groundwater vulnerability and take early steps to protect groundwater resources.
Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor gamma t, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR+ ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets.
This Reflection investigates some of the questions that arise when one attempts to write lives together'. What are the intellectual and theoretical implications of this mode of biographical writing? What might be its seductions? What are its creative possibilities? It considers the place of invisible figures in group biography, and argues that the genre enables the recovery of these figures in particularly productive ways. It does so because its focus rests not on individuals but on the interstices between them. Two women receive particular attention. The first is Elizabeth Kent, the sister-in-law of the radical Romantic journalist Leigh Hunt. The second is Virginia Edgar, a friend and correspondent of Mary Anne Disraeli. The Reflection explores what happens to the versions of the past we construct when such figures disappear from dominant cultural narratives, how group biography enables their recovery, and the theoretical pitfalls inherent in returning them to the foreground. Through a sustained focus on creative experience it suggests a way of deploying the possibilities of group biography in an act of resistance towards posthumous and anachronistic constructions of significance, and argues that such resistance has the potential to be creatively liberating.
Social groups aid human beings in several ways, ranging from the fulfillment of complex social and personal needs to the promotion of survival. Despite the importance of group affiliation to humans, there remains considerable variation in group preferences across development. In the current study, children and adolescents completed an explicit evaluation task of ingroup and out-group members during functional neuroimaging. We found that participants displayed age-related increases in bilateral amygdala, fusiformgyrus and orbitofrontal cortex (OFC) activation when viewing in-group relative to out-group faces. Moreover, we found an indirect effect of age on in-group favoritism via brain activation in the amygdala, fusiform and OFC. Finally, with age, youth showed greater functional coupling between the amygdala and several neural regions when viewing in-group relative to out-group peers, suggesting a role of the amygdala in directing attention to motivationally relevant cues. Our findings suggest that the motivational significance and processing of group membership undergoes important changes across development.
The operation of blood banks aims at the cost-efficient supply of uncontaminated human blood. Each unit of donated blood goes through multiple testing for the presence of various pathogens which are able to cause transfusion-transmitted diseases. The blood screening process is comprised of two phases. At the first phase, blood units are screened together in pooled groups of a certain size by the ELISA (Enzyme Linked Immuno-Sorbent Assay) test to detect various virus-specific antibodies. The second phase of the screening process is conducted by PCR (Polymerase Chain Reaction) testing of the individual blood units of the groups found clean by the initial ELISA phase. Thousands of units of donated blood arrive daily at the central blood bank for screening. Each screening scheme has associated testing costs and testing times. In addition, each blood unit arrives with an expiration date. As a result, the shorter the testing time, the longer the residual lifetime that is left for the blood unit for future use. The controller faces a natural and well-motivated operations management problem. He will attempt to shorten the testing period and reduce the testing costs without compromising too much on the reliability. To achieve these goals, we propose a new testing procedure that we term Recycled Incomplete Identification Procedure (RIIP). In RIIP, groups of pooled blood units which are found contaminated in the ELISA test are divided into smaller subgroups and again group-tested by ELISA, and so forth, until eventually the PCR test is conducted for those subgroups which are found clean. We analyze and optimize the performance of RIIP by deriving explicit formulas for the cost components of interest and maximize the profit associated with the procedure. Our numerical results suggest that it can indeed be profitable to do several cycles at ELISA. (C) 2016 Elsevier B.V. All rights reserved.
Purpose: The aim of this study was to provide the first formal evaluation of a unique 12-session group therapy programme developed by the UK-based National Association for People Abused as Children (NAPAC). Method: The therapy outcomes of this programme were assessed using the CORE-OM tool. Clients comprised 26 individuals (7 males and 19 females), with an age range of 19-67 (mean = 41; SD = 12.76). Clients were survivors of sexual, physical, emotional or neglectful childhood abuse, or a combination of these, and were from four different locations: London (n = 9), Bury (n = 4), Belfast (n = 8) and prison (n = 5). Findings: Across all CORE domains, improvements were shown from pre-to post-therapy. No gender or age differences were revealed, and improvements were shown across both community members and prison inmates. Implications: A person-centred approach to group therapy is beneficial to a wide range of adult clients within the community and prison settings that require therapy after historical sexual, physical, emotional or neglectful childhood abuse.
Group-focused moral foundations (GMFs) - moral values that help protect the group's welfare sharply divide conservatives from liberals and religiously devout from non-believers. However, there is little evidence about what drives this divide. Moral foundations theory and the model of motivated social cognition both associate group-focused moral foundations with differences in conflict detection and resolution capacity, but in opposing directions. Individual differences in conflict detection and resolution implicate specific neuroanatomical differences. Examining neuroanatomy thus affords an objective and non-biased opportunity to contrast these influential theories. Here, we report that increased adherence to group-focused moral foundations was strongly associated (whole-brain corrected) with reduced gray matter volume in key regions of the conflict detection and resolution system (anterior cingulate cortex and lateral prefrontal cortex). Because reduced gray matter is reliably associated with reduced neural and cognitive capacity, these findings support the idea outlined in the model of motivated social cognition that belief in group-focused moral values is associated with reduced conflict detection and resolution capacity. (C) 2017 Elsevier B.V. All rights reserved.
Embryo implantation involves a complex sequence of events, and a large amount of molecules have been postulated to be involved in the interaction of embryo and endometrium. This study evaluated the endometrial expression of -inhibin and -glycan in the mid-secretory phase of women scheduled to in vitro fertilization (IVF) and tested whether these markers are associated with implantation failure. We performed a nested case-control study including 52 women submitted to IVF and embryo transfer, divided into 2 groups: cases with implantation failure (n = 33) and controls with confirmed clinical pregnancy (n = 19). Endometrial -inhibin and -glycan gene expression was evaluated in the mid-secretory phase of the natural menstrual cycle immediately before IVF, using real-time polymerase chain reaction. We found a higher gene expression of -inhibin (fold increase = 2.14 +/- 0.32, P < .05) and -glycan (fold increase = 1.44 +/- 0.16, P < .05) in implantation failure patients compared to confirmed clinical pregnancy patients. The areas under the receiver operating characteristics curves for prediction of implantation failure in this context were 0.692 and 0.678 for -inhibin and -glycan, respectively. The present results suggest that high expression levels of -inhibin and -glycan transcripts in secretory phase endometrium are associated with a lower chance of achieving pregnancy with IVF.
The aim of this study was to investigate effects of two dietary medicinal herbs, Rose hip (Rosa canina) and Safflower (Carthamus tinctorius) supplementation on growth performance, haematological, biochemical parameters and innate immune response of in juvenile beluga, Huso huso. Fish (263 +/- 0.4 g) were allocated into 15 tanks (20 fish per tank) and triplicate groups were fed a control diet or diets containing 1% and 2% of medicinal herbs, respectively. Feed conversion ratio (FCR), specific growth rate (SGR) and condition factor (CF) did not show significant differences (P >0.05) in fish given herbal diets. Significant differences were observed in number of white blood cells (WBC) and haemoglobin (Hb) values among the dietary treatments. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly lower in supplemented diet groups compared with the control. Innate immune responses (lysozyme activity and ACH(50)) were significantly higher in 2% Safflower-fed fish compared with other groups (P < 0.05). These results indicate that medicinal herbs in diets can be considered as a beneficial dietary supplement for improving the physiological parameters and enhance the immune response of Persian sturgeon. (C) 2016 Elsevier Ltd. All rights reserved.
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8. Additionally, quantitative polymerase chain reaction and flow cytometry were used to detect the expression of the associated genes and proteins. The present study explores the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study showed that hBMSCs promoted the proliferation of TKI-resistant Ph+ ALL. This was shown by the increase in cells in the S+ G2-M phase of the cell cycle. It was also found that the expression of cyclins A, C, D1 and E was increased. Apoptosis was inhibited through upregulation of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2) and BCL-extra large] and downregulation of apoptotic genes (BCL-XS, BCL-2-associated X protein, and caspases 3, 7 and 9). Expression of the breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) gene, Wnt5a, and Wnt signaling pathway-associated genes (glycogen synthase kinase-3 beta, beta-catenin, E-cadherin and phosphoinositide 3-kinase) and transcription factors (c-myc, ephrin type-B2, fibroblast growth factor 20 and matrix metalloproteinase 7) was also increased. Furthermore, the expression of drug resistance genes (low-density lipoprotein receptor, multidrug resistanceasso-ciated protein and multi-drug resistance gene) was increased and the expression of anti-oncogenes (death-associated protein kinase and interferon regulatory factor-1) was decreased. It was concluded that hBMSCs promote the growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms. Therefore, targeting hBMSCs may be a promising approach for preventing the growth of TKI-resistant Ph+ ALL.
In the 21st century, systems biology is a holistic approach to understand life by the cross-talk study between the genome, Rnome and proteome of a cell. We describe a column-based rapid method for the simultaneous extraction of DNA, RNA, miRNA (microRNA) and proteins from the same experimental sample without prior fractionation, which allows a direct correlation between genomic, epigenomic, transcriptomic and proteomic data. This method provides a simple and effective way to analyse each of these biomolecules without affecting yield and quality. We also show that isolated biomolecules are of the highest purity and compatible for all the respective downstream applications, such as PCR amplification, RT-PCR (reverse transcription-PCR), real-time PCR, reverse Northern blotting, SDS/PAGE and Western blot analysis. The buffers and reagents used in this method are optimized extensively to achieve the cost effective and reliable procedure to separate the functional biomolecules of the cell.
Gamma-interferon-inducible lysosomal thiol reductase (GILT) is a key enzyme in the antigen processing and presentation pathway whereby it reduces disulfide bonds at an acidic pH. In this study, a homolog of GILT from guinea pigs (designated gpGILT) was identified and characterized using bioinformatic methods and bioactivity assays. The open reading frame of gpGILT is 705 bp in length and encodes 234 amino acids, with a putative molecular weight of about 25.85 kDa. The structure of gpGILT is similar to those of humans and zebrafish, containing six introns and seven exons. The deduced primary structure of the gpGILT protein includes all of the typical features of other known GILT proteins, including an active-site motif, CXXC, a GILT signature sequence, CQHGX(2)ECX(2)NX(4)C, three potential Asn-linked glycosylation sites, and six other conserved cysteines. The predicted tertiary structures of gpGILT, human GILT, and mouse GILT are quite similar in shape and positional arrangement of the key motifs modeled on the same template. Amino acid sequence-based alignment and phylogenetic analysis showed that gpGILT is most closely related to that from the rat, with an identity of 68.40%. Additionally, the constitutive expression and immune response to lipopolysaccharide (LPS) challenge of gpGILT were tested using real-time quantitative polymerase chain reaction. A tissue-specific expression pattern in selected tissues and remarkable up-regulation of gpGILT mRNA in spleen and blood within 12 h of LPS stimulation were observed, suggesting that GILT functions as an immunological surveillance-related factor in both innate and adaptive immunity. Soluble recombinant gpGILT produced in E. coli could reduce the interchain disulfide bonds of IgG in an acidic reaction system in vitro, suggesting thiol reductase activity in antigen processing. The results of this study provide a better understanding of the molecular characteristics of gpGILT and are a useful reference for further investigation of its involvement in antigen processing and immunological surveillance using the laboratory guinea pig. (C) 2016 Elsevier Ltd. All rights reserved.
Objectives:The aim of the study was to assess the effect of nutritional supplementation with lipid-based nutrient supplements (LNS) and corn-soy blend flour on Bifidobacterium and Staphylococcus aureus gut microbiota composition in Malawian infants. In addition, the microbiota changes over time were characterized in the study infants. Methods:Healthy 6-month-old Malawian infants were randomly assigned to 1 of 4 intervention schemes for a 6-month period. Infants in the control group were not provided with any supplementary food. Infants in other 3 groups received either micronutrient-fortified corn-soy blend, micronutrient-fortified LNS with milk protein base, or micronutrient-fortified LNS with soy protein base between 6 and 12 months of age. Fecal bifidobacteria and S aureus gut microbiota at 6 and 12 months of age were analyzed by quantitative real-time polymerase chain reaction method. Results:There was no difference in change in bacterial prevalence or counts between the intervention groups during the 6-month study period. When looking at the total study population, higher counts of total bacteria (P=0.028), Bifidobacterium genus (P=0.027), B catenulatum (P=0.031), and lower counts of B infantis (P<0.001), B lactis (P<0.001), B longum (P<0.001), and S aureus (P<0.001) were detected in the children's stools at 12 months rather than at 6 months of age. Conclusions:The dietary supplementation did not have an effect on the Bifidobacterium and S aureus microbiota composition of the study infants. The fecal bifidobacterial diversity of the infants, however, changed toward a more adult-like microbiota profile within the observed time.
Background: Up-regulation of P-gp is an adaptive survival mechanism of cancer cells from chemotherapy. Three new phytochemicals including two benzophenones, guttiferone K (GK) and oblongifolin C (OC), and a xanthone, isojacaruebin (ISO), are potential anti-cancer agents. However, the capability of these compounds to increase multidrug-resistance (MDR) through P-gp up-regulation in cancer cells has not been reported. Purpose: This study was to investigate the effects of GK, OC and ISO on P-gp up-regulation in colorectal adenocarcinoma cells (Caco-2 cells). In addition, the mechanisms underlying their inductive effect were also determined. Methods: The inductive effect of GK, OC and ISO on P-gp expression at transcription level was measured by real-time reverse transcription polymerase chain reaction. The reactive oxygen species production was determined by 2', 7'-dichlorofluorescin diacetate assay. The protein content of P-gp and involvement of mitogen-activated protein kinases (MAPK) pathway was evaluated by western blot analysis. Results: GK, OC and ISO (50 mu M, 24 h) were able to increase the amount of MDR1 mRNA and protein in Caco-2 cells. The presence of N-acetyl-l -cysteine significantly prevented the inductive effect of GK, OC and ISO on MDR1 mRNA level. Moreover, MAPK inhibitors including U0126 (an ERK1/2/MAPK inhibitor) and SB202190 (p38/MAPK inhibitor) suppressed an increase of MDR1 mRNA levels in the cells treated with benzophenones (GK, OC) and xanthone ISO, respectively. These findings were in agreement with the increase of phosphorylated form of either ERK1/2 (p-ERK1/2) or p38 (p-p38) upon treatment of the cells with these three compounds. In addition, OC and ISO, but not GK, increased mRNA of c-Jun level. Conclusion: The benzophenones GK, OC and xanthone ISO are likely MDR inducers through up-regulation of P-gp expression at transcription level. Their molecular mechanisms involve oxidative stress-mediated activation of MAPK signaling pathway. (C) 2017 Elsevier GmbH. All rights reserved.
The paper investigates the behavior of unidirectional two-port equivalent circuit composed of an electronic gyrator with Antoniou operational amplifier and a reciprocal two-port built by a transversal resistance (RT). From the analysis of two-port equations standpoint, by correct choice of circuit conductance, the two-port can operate as an ideal or a lossy gyrator. Due to the interest in practical aspects of energy transfer from one terminal to other, an analysis of the two-port parameters for the unidirectional circuit diagram is performed. The validity of the tested circuit results obtained analytically and through numerical simulation PSpice has been verified experimentally, in two cases, with equal and different transfer conductance.
In this study, we describe the complete mitochondrial genomes of Gyrodactylus brachymystacis and Gyrodactylus parvae infecting rainbow trout (Oncorhynchus mykiss) and the invasive topmouth gudgeon (Pseudorasbora parva), respectively. The two circular genomes have a common genome organization found in other Gyrodactylus species. Comparative analyses of mitochondrial genomes from six Gyrodactylus species were carried out to determine base composition, codon usage, transfer RNA and ribosomal RNA genes, major non-coding regions, and nucleotide diversity within the genus. We also provide the first universal models of the secondary structures of rrnS and rrnL for this group thereby promoting utilization of these genetic markers. Universal primers provided herein can be used to obtain more mitochondrial information for pathogen identification and may reveal different levels of molecular phylogenetic inferences for this lineage.
A 24 kDa protein is one of the important components in Haemonchus contortus (barber pole worm) excretory/secretory products (HcESPs), which was shown to have important antigenic function. However, little is known about the immunomodulatory effects of this protein on host cell. In the present study gene encoding 24kDa excretory/secretory protein (HcES-24) was cloned. The recombinant protein of HcES-24 (rHcES-24) was expressed in a histidine-tagged fusion protein soluble form in Escherichia coli. Binding activity of rHcES-24 to goat PBMCs was confirmed by immunofluorescence assay (IFA) and its immunomudulatory effect on cytokine secretion, cell proliferation, cell migration and nitric oxide production were observed by co-incubation of rHcES-24. IFA results revealed that rHcES-24 could bind to the PBMCs. The interaction of rHcES-24 increased the production of IL4, IL10, IL17 and cell migration in dose dependent manner. However, rHcES-24 treatment significantly suppressed the production of IFN gamma, proliferation of the PBMC and Nitric oxide (NO) production. Our findings showed that the rHcES-24 played important regulatory effects on the goat PBMCs.
Degradation of RNA as an intermediate message between genes and corresponding proteins is important for rapid attenuation of gene expression and maintenance of cellular homeostasis. This process is controlled by ribonucleases that have different target specificities. In the bacterial pathogen Helicobacter pylori, an exo- and endoribonuclease RNase J is essential for growth. To explore the role of RNase J in H. pylori, we identified its putative targets at a global scale using next generation RNA sequencing. We found that strong depletion for RNase J led to a massive increase in the steady-state levels of non-rRNAs. mRNAs and RNAs antisense to open reading frames were most affected with over 80% increased more than 2-fold. Non-coding RNAs expressed in the intergenic regions were much less affected by RNase J depletion. Northern blotting of selected messenger and non-coding RNAs validated these results. Globally, our data suggest that RNase J of H. pylori is a major RNase involved in degradation of most cellular RNAs.
As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win-win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model. With this model, we show that declining habitat, and thus declining biodiversity, can lead to either increasing or decreasing infectious-disease risk, measured as endemic prevalence. Whether larger habitats, and thus greater biodiversity, lead to a decrease (dilution effect) or increase (amplification effect) in infection prevalence depends upon the pathogen transmission mode and how host competence scales with body size. Dilution effects were detected for most frequency-transmitted pathogens and amplification effects were detected for density-dependent pathogens. Amplification effects were also observed over a particular range of habitat loss in frequency-dependent pathogens when we assumed that host competence was greatest in large-bodied species. By contrast, only amplification effects were observed for density-dependent pathogens; host competency only affected the magnitude of the effect. These models can be used to guide future empirical studies of biodiversity-disease relationships across gradients of habitat loss. The type of transmission, the relationship between host competence and community assembly, the identity of hosts contributing to transmission, and how transmission scales with area are essential factors to consider when elucidating the mechanisms driving disease risk in shrinking habitat. This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.
Background: Exercise is beneficial for depression, but less is known about its impact on post-intervention physical activity and sedentary behavior. The aim of this paper was to determine the extent to which participation in light-, moderate- and vigorous-intensity exercise intervention influenced habitual physical activity and sedentary behavior patterns in depressed adults. Methods: Accelerometer data was collected pre- and post-intervention from depressed participants randomized to one of three 12-week intervention groups: light (n = 21), moderate (n = 25) and vigorous (n = 22) exercise. Mixed models examined changes in time spent sedentary and in light and moderate to-vigorous physical activity (MVPA); time accumulated in sedentary and MVPA bouts; and, number of MVPA bouts and interruptions in sedentary time. Results: Overall sedentary time decreased while light activity time increased across all intervention groups but not significantly so. The light exercise intervention group reduced MVPA minutes (-8.22, 95% CI: -16.44, -0.01), time in MVPA bouts (-8.44, 95% CI: -14.27, -2.62), and number of activity bouts (-0.43, 95% CI: -0.77, -0.09). The moderate exercise intervention group reduced time in MVPA bouts (-6.27, 95% CI: -11.71, -0.82) and number of sedentary interruptions (-6.07, 95% CI: -9.30, -2.84). No changes were observed for the vigorous exercise intervention group. Conclusions: The exercise intervention led to an increase in overall light physical activity and decrease in sedentary time, though neither change was statistically significant. Participation in the light and moderate exercise intervention groups was associated with reductions of time in MVPA bouts, but this was not evident for the vigorous exercise intervention group. (C) 2017 The Authors. Published by Elsevier Ltd.
Ticks are blood-sucking ectoparasites of great medical and veterinary significance that can transmit bacteria, protozoa, fungi and viruses, causing a variety of human and animal diseases worldwide. In the present study, the intestinal bacterial flora associated with Haemaphysalis flava ticks in different developmental stages were analyzed using polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE). Eleven distinct DGGE bands were found using PCR-DGGE method. Sequences analyses indicated that they belonged to Bacillus cereus, Candidatus rickettsia, Erwinia sp., Klebsiella pneumoniae, Pectobacterium carotovorum, Pseudomonas aeruginosa, Rickettsia peacockii, Rickettsia helvetica, Rickettsia slovaca, Staphylococcus simulans and Uncultured bacterium clone. Our find that the K. pneumoniae and P. aeruginosa isolates were presented in all H. flava ticks in different developmental stages. The present results indicated that zoonotic pathogens are present in H. flava ticks in Henan province, China. To our knowledge, this is the first report on intestinal bacterial flora associated with H. flava ticks in China.
Objective The effect of polyomavirus infection in HSCT recipients is poorly understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by nested qualitative polymerase chain reaction (PCR) assays of urine. The risk factors for BK virus and JC virus were analysed. The kidney and liver functions of infected and uninfected patients were compared. Results BK virus, JC virus, and simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients respectively. HCMV infection was found to be an independent risk factor for JC virus infection (odds ratio (OR): 8.528), while transplants with mismatched HLA are more susceptible to BK virus infection (OR: 12.000). Liver function of JC virus-infected subjects was worse than that of uninfected subjects. Conclusion We must be vigilant for opportunistic polyomavirus infections in HSCT recipients, especially those with HCMV co-infection or a mismatched HLA transplant. When unexplained liver function deterioration is observed, JC virus infection should be considered.
We investigated the presence of ectoparasites and hemoparasites in side-blotched lizards (Uta stansburiana) across a large part of their range and measured how parasitic infection related to several key physiological indicators of health. Blood samples were collected from 132 lizards from central Arizona, southern Utah, and eastern Oregon. Hemoparasites were found in 22 individuals (3.2% prevalence in Arizona, 19.1% in Utah, and 6.3% in Oregon), and ectoparasites were found on 51 individuals (56.3% prevalence in Arizona, 56.1% in Utah, and 6.7% in Oregon), with 11 individuals infected with both. Hemoparasites and ectoparasites were found in all three states. Immunocompetence was higher in individuals infected with both hemoparasites and ectoparasites. Body condition, glucocorticoid levels, and reproductive investment were not related to infection status. Our study provides evidence that parasitic infection is associated with an active immune system in wild reptiles but may not impose other costs usually associated with parasites.
Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.
Semecarpus anacardium L. is a tree species which produces secondary metabolites of medicinal importance. Roots of the plant have been traditionally used in folk medicines. Different strains of Agrobacterium rhizogenes (A4, ATCC15834 and LBA 9402) were used for induction of hairy roots in in vitro grown tissues of the plant. Hairy root initiation was observed after 25-30 days of infection. Optimum transformation frequency of 61% was achieved on leaf explants with ATCC15834 strain. Infection time of 30 min resulted in greater transformation frequency compared to 10 and 20 min, respectively. The hairy roots cultured in growth regulator-free semi-solid woody plant medium differentiated into callus. Whole shoots infected with ATCC 15834 were found to produce more transformants upon co-cultivation for 4 (65%) and 5 (67%) days. Induction of hairy roots in stem explants infected with ATCC 15834 was lower (52%) compared to leaves (62%) after 4 days of co-cultivation. In A4 and LBA9402 strains transformation efficiency was 49 +/- 2.8% and 36 +/- 5.7% in shoots after 4 days of co-cultivation. Transformation frequency was higher in ATCC15834 strain, irrespective of explants. The hairy roots of S. anacardium elongated slowly upon transfer to half-strength liquid medium. After 3-4 passages in liquid medium slender hairy roots started differentiating which were separated from the original explants. Visible growth of the roots was observed in hormone-free liquid medium after 2-3 months of culturing. Polymerase chain reaction with gene-specific primers from rol A, B and C genes confirms the positive transformation events.
This paper presents the design and multivariable feedback control of a compact precision positioner. The moving stage that has a total mass of 1.52 kg can generate all 6-axis motions with a single frame. Aerostatic bearings levitate the positioner and three 3-phase synchronous permanent-magnet planar motors (SPMPMs) generate electromagnetic forces over the concentrated-field permanent-magnet matrix. Three Hall-effect sensors measure the magnetic flux to calculate the planar position and three laser-distance sensors detect the vertical displacement. Real Time Application Interface (RTAI) with Comedi on a Linux personal computer is used for real-time control. Single-input single-output (SISO) digital lead-lag controllers for each axis are designed, and a multi-input multi output (MIMO) model is developed for the positioner. Reduced-order linear-quadratic-Gaussian (LQG) controllers are applied in horizontal positioning. Several experimental results demonstrate the dynamic performance of the positioner.
The discrete-time robust disturbance attenuation problem for the n-degrees of freedom (dof) mechanical systems with uncertain energy function is considered in this paper. First, it is shown in the continuous time-setting that the robust control problem of n-dof mechanical systems can be reduced to a disturbance attenuation problem when a specific type of control rule is used. Afterwards, the robust disturbance attenuation problem is formulised as a special disturbance attenuation problem. Then, the discrete-time counterpart of this problem characterised by means of L-2 gain is given. Finally, a solution of the problem via direct-discrete-time design is presented as a sufficient condition. The proposed discrete-time design utilizes discrete gradient of the energy function of considered system. Therefore, a new method is also proposed using the quadratic approximation lemma to construct discrete gradients for general energy functions. The proposed direct-discrete-time design method is used to solve the robust disturbance attenuation problem for the double pendulum system. Simulation results are given for the discrete gradient obtained with the method presented in this paper. Note that the solution presented here for the robust disturbance attenuation problem give an explicit algebraic condition on the design parameter, whereas solution of the same problem requires solving a Hamilton-Jacobi-Isaacs partial differential inequality in general nonlinear systems.
The field of vascularized composite allotransplantation combining advances in reconstructive surgery, transplantation, and immunology offers great promise for patients with heretofore unsolvable problems. In the last 30 years, hand transplantation has progressed through the phases of being a research subject, a controversial clinical procedure, a more widely accepted and expanding field, and now a promising endeavor undergoing refined indications. Although many lessons have been learned, few procedures in the author's experience have been as life-transformative in restoring the body image, motor and sensory functions, activities of daily living, and personal autonomy as successful hand transplantation. Copyright (C) 2017 by the American Society for Surgery of the Hand. All rights reserved.)
A high-order curvature-compensated bandgap reference (BGR) with low temperature coefficient (TC) is proposed in this paper. The curvature compensation is maintained through the use of Pplus poly resistor and Nplus poly resistor to achieve temperature-dependent resistor ratios. A T-resistor structure is adopted which enables the BGR to work under low supply voltage or high MOSFET threshold voltage and to reduce the mismatches in transistors and resistors. The design is implemented in 65-nm CMOS technology with a 1.8-V supply. The output reference voltage is 550 mV and shows a TC of 0.22 ppm/degrees C in a temperature range from -20 degrees C to 80 degrees C. A high gain operational amplifier is used that enhances the power supply rejection ratio to -117.8 dB at DC and -75 dB at 1 kHz. The effect of mismatch is 4.3%. The proposed BGR achieves a line regulation of 0.8 mV/V and total power consumption of 20.8 mu W.
The MHC is a highly polymorphic genomic region that encodes the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. The MHC locus was first discovered in the mouse and for the past 50 years it has been studied most intensively in both mice and humans. However, in recent years the macaque species have emerged as some of the more important and advanced experimental animal models for biomedical research into MHC with important human immunodeficiency virus/simian immunodeficiency virus and transplantation studies undertaken in association with precise MHC genotyping and haplotyping methods using Sanger sequencing and next-generation sequencing. Here, in this special issue on 'Macaque Immunology' we provide a short review of the genomic similarities and differences among the human, macaque and mouse MHC class I and class II regions, with an emphasis on the association of the macaque class I region with MHC polymorphism, haplotype structure and function.
The alignment of many short sequences of DNA, called reads, to a long reference genome is a common task in molecular biology. When the problem is expanded to handle typical workloads of billions of reads, execution time becomes critical. In this paper we present a novel reconfigurable architecture for minimal perfect sequencing (RAMPS). While existing solutions attempt to align a high percentage of the reads using a small memory footprint, RAMPS focuses on performing fast exact matching. Using the human genome as a reference, RAMPS aligns short reads hundreds of thousands of times faster than current software implementations such as SOAP2 or Bowtie, and about a thousand times faster than GPU implementations such as SOAP3. Whereas other aligners require hours to preprocess reference genomes, RAMPS can preprocess the reference human genome in a few minutes, opening the possibility of using new reference sources that are more genetically similar to the newly sequenced data.
The optimal management of chronic hepatitis B virus (HBV) infections is known to be related with the genotype of HBV in order to prescribe the most appropriate treatment. In this study, including 19 chronic HBV patients from St. Parascheva Clinical Infectious Disease Hospital, Ia degrees i, we attempted to double test their samples for DNA/HBV detection and genotyping. DNA/HBV evidenced from19 patients known as being chronic infected by HBV were tested by two molecular techniques: Real Time PCR (Polymerase Chain Reaction) and genotyping by hybridization on strips. We obtained identical results from both methods. The most frequent genotype was D (47.4%), followed by genotype A (10,5%); 9 samples were negative, probably because of virus suppressed replication under treatment. The double testing is accurate, time and cost efficient, and for these reasons we propose this double testing like a possible algorithm for routine diagnostic, being time-efficient and accurate for HBV chronic infected patients' management cases.
Recently the performance of dual fuel strategy on multi-cylinder engines over the whole engine map has received increasing attention. This research focuses on the potential of Homogeneous Charge Induced Ignition (HCII) combustion fueled with gasoline and diesel meeting Euro V emission standard through the whole operating range using a simple after-treatment system. This combustion mode utilizes a port injection of high-volatile fuel (gasoline) to form a homogeneous charge and a direct injection of high ignitable fuel (diesel) near the Top Dead Center (TDC) to trigger combustion. In this paper, an experimental and numerical investigation of the combustion characteristics and emission formation of HCII on a multi-cylinder heavy-duty engine is conducted. The effects of gasoline ratio (R-g), one of the most important parameters in dual-fuel mode, are explored and analyzed in detail. A R-g of 70-80% is recommended for better combustion and emission performance at the operating condition in this paper. HCII also turns out to be an effective strategy to reduce NOx and soot emissions at the same time. Furthermore, the high THC and CO emissions of HCII combustion can be eliminated using Diesel Oxidation Catalyst (DOC). Then the HCII strategy was optimized through the whole operating range showing a great potential of meeting Euro V limitations only with DOC as an after-treatment device. The fuel consumption also reduced with dual fuel strategy. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Human Cytomegalovirus (HCMV) infections can be found throughout the body, especially in epithelial tissue. Animal model was established by inoculation of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into the ligated sacculus rotundus and vermiform appendix in living rabbits. The specimens were collected from animals sacrificed 1 and a half hours after infection. Results: The virus was found to be capable of reproducing in these specimens through RT-PCR and Western-blot. Severe inflammation damage was found in HCMV-infected tissue. The viral protein could be detected in high amounts in the mucosal epithelium and lamina propria by immunohistochemistry and immunofluorescense. Moreover, there are strong positive signals in lymphocytes, macrophages, and lymphoid follicles. Quantitative statistics indicate that lymphocytes among epithlium cells increased significantly in viral infection groups. Conclusions: The results showed that HCMV or HEV + HCMV can efficiently infect in rabbits by vivo ligated intestine loop inoculation. The present study successfully developed an infective model in vivo rabbit ligated intestinal Loop for HCMV pathogenesis study. This rabbit model can be helpful for understanding modulation of the gut immune system with HCMV infection.
The rapid advances in research on antisense transcripts are gradually changing our understanding of the expression of the Herpesviridae genome. In this study, the transcripts of the human cytomegalovirus (HCMV) UL83 antisense strand were investigated in three clinical isolates. Three cDNA clones containing sequences with an antisense orientation to the UL83 gene were identified in a late HCMV cDNA library. The UL83 antisense transcripts (UL83asts) were then shown to be transcribed only in the late infection phase of the three clinical HCMV strains, using rapid amplification of cDNA ends (RACE) and northern blotting. These UL83asts were identical at their 3 termini but different at 5 ends. Two open reading frames were predicted in the UL83asts. J. Med. Virol. 86:2033-2041, 2014. (c) 2014 Wiley Periodicals, Inc.
Background Hepatitis C virus (HCV) core protein, in addition to its structural role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by interfering in several cellular processes, including microRNA and mRNA homeostasis. The C-terminal truncated HCV core protein (C124) is intrinsically unstructured in solution and is able to interact with unspecific nucleic acids, in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs) in vitro. The specificity and propensity of C124 to the assembly and its implications on HCV pathogenesis are not well understood. Methods Spectroscopic techniques, transmission electron microscopy and calorimetry were used to better understand the propensity of C124 to fold or to multimerize into NLPs when subjected to different conditions or in the presence of unspecific nucleic acids of equivalent size to cellular microRNAs. Results The structural analysis indicated that C124 has low propensity to self-folding. On the other hand, for the first time, we show that C124, in the absence of nucleic acids, multimerizes into empty NLPs when subjected to a pH close to its isoelectric point (pH ? 12), indicating that assembly is mainly driven by charge neutralization. Isothermal calorimetry data showed that the assembly of NLPs promoted by nucleic acids is enthalpy driven. Additionally, data obtained from fluorescence correlation spectroscopy show that C124, in nanomolar range, was able to interact and to sequester a large number of short unspecific nucleic acids into NLPs. Discussion Together, our data showed that the charge neutralization is the major factor for the nucleocapsid-like particles assembly from C-terminal truncated HCV core protein. This finding suggests that HCV core protein may physically interact with unspecific cellular polyanions, which may correspond to microRNAs and mRNAs in a host cell infected by HCV, triggering their confinement into infectious particles.
Histone deacetylation, reciprocally mediated by histone deacetylases (HDAC) and acetyltransferases, represents one major form of post-translational modification. Previous research indicates that HDACs play an essential regulatory role in the development of various immune cells. However, the specific function of individual HDACs remains largely unexplored. HDAC4, a member of class II HDACs, profoundly investigated in the nervous system, while the expression profile and function of HDAC4 in T cells are barely known. For the first time, we report here that HDAC4 is expressed in the multiple T cell lineages. Using T-cell-specific HDAC4-deficient mice, we discovered that lack of HDAC4 did not alter the frequencies of conventional T cells, invariant NKT (iNKT) cells or regulatory T cells within both the thymus and secondary lymphoid organs. Moreover, conventional T cells and iNKT cells from wild-type and HDAC4-deficient mice displayed no significant difference in cytokine production. In conclusion, our results imply that under steady stage, HDAC4 is not required for the development and function of multiple T cell lineages, including conventional T cells and iNKT cells.
DNA damage response failure may influence the efficacy of DNA-damaging treatments. We determined the expression of 16 genes involved in distinct DNA damage response pathways, in association with the response to standard therapy. Twenty patients with locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric metabolic therapeutic response was determined by [18F]FDG-PET/CT. In the tumor and matched normal tissues collected before treatment, the gene expressions were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). The down-regulation of TP53 was apparently associated with a poor response to iChT, its up-regulation with complete regression in 2 cases. 7 cases with down-regulated REV1 expression showed complete regression after ChRT/RT, while 1 case with REV1 overexpression was resistant to RT. The overexpression of WRN was an independent predictor of tumor relapse. Our results suggest that an altered expression of REV1 predicts sensitivity to RT, while WRN overexpression is an unfavorable prognostic factor.
Background: HPV-16 modifies the overall survival (OS) of patients with oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC, but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients. Methods: HPV-16 infection was confirmed by amplification of E6 and E7 viral oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between HPV-16 status and clinicopathological parameters were performed using Fisher's exact test and x(2). Survival analysis was completed using Kaplan-Meier estimator and multivariate Cox regression analysis. Results: OS of HPV-16 positive patients was longer compared to HPV-16 negative patients (P = 0.002). HPV-16 positive tumors of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16 negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a better survival. Conclusions: HPV-16 status has a positive prognostic value in HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment in prognosis and guide treatment for HNSCC patients.
Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV-related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV-related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity.
Context: Pediatric abusive head trauma (AHT) can be defined as an injury to the skull or intracranial contents of a child under the age of 5 due to inflicted blunt impact or violent shaking. Evidence Acquisition: AHTis the most commoncause of traumatic death in children younger than 1 year, and it is the leading cause of death due to child abuse. Clinical presentation observed in children with AHT depends on the type of AHT and accompanying injuries. History and physical examination are important for diagnosing AHT and for distinguishing it from other conditions that can mimic shaken baby syndrome, such as accidental trauma, cancer, metabolic diseases, and others. Results: Progress in research on the medical diagnosis of AHT has been remarkable, while the development of treatment strategies has been limited. For these reasons, there is an urgent need to develop effective treatment strategies for AHT able to improve the outcomes. Conclusions: The construction of a nationwide database that supports clinical studies is required in the future.
Purpose Headache is a common presenting feature of patients with pituitary adenomas and other tumors of the sellar region. However, at present, it still is unclear whether the headache is actually caused by the tumor. To explore whether there is a relation, we examined in detail the headache types, their relationship to the underlying pathology, and if the headache responded to neurosurgery in a prospective study design. Methods One hundred twelve patients with tumors of the sellar region scheduled for neurosurgery in a single center were analyzed for presence and quality of headache before surgery and at least 3 months after surgery. Patients received headache and depression self-rating inventories, presented on a handheld computer (PainDetect(A (R))). Clinical variables thought to impact on headache were analyzed in conjunction with the inventories. Results Fifty-nine (53%) patients reported headache in the 3 months prior to neurosurgery, 49 (44%) had headache at the time of filling in the questionnaires. The four patients with pituitary apoplexy described thunderclap headache. In the other patients diverse headache types were encountered, most frequently migraine. Untreated gonadotroph deficiency was significantly associated with absence of headache, while none of the other clinical and morphological variables related to headache. Presence of headache and disability due to headache were not significantly reduced after surgery. Conclusion Apart from pituitary apoplexy we detected no specific headache type in our patient group and no significant improvement of headache after neurosurgery. Headache alone constitutes neither a valid diagnostic marker for the presence of tumors of the sellar region nor a sufficient indication for tumor removal.
This paper describes a provider-patient communication process, which although not new to health care in general, is new to the pharmacy profession. Health coaching is a technique that empowers patients to make lasting health behavior changes that improve overall well-being. It provides patients with health care implementation options that better suit their lifestyle and abilities. Health coaching programs have the potential to foster better health outcomes, especially with patients who are chronically ill or represent an at risk population for medication non-adherence (e.g. elderly, patients on psychotropic medications). Other health professions (e.g. nursing and medicine) have had success with the implementation of health coaching models. For example, nurse coaching is recognized by the American Nurse Association and recent statistics show 3.1 million nurses in the U.S.A are also trained in nurse coaching. The pharmacy profession has yet to tap the patient-related benefits of health coaching. This commentary will discuss (i) The theoretical foundations of health coaching (ii) Distinctions between health coaching, motivational interviewing and traditional medication therapy counseling (iii) Training necessary for health coaching; and (iv) How pharmacists can use health coaching in practice. (C) 2016 Elsevier Inc. All rights reserved.
Background Health care providers fill a central role in the prevention of both child abuse and neglect (CA/N) and unintentional childhood injury. Health communication interventions hold promise for promoting attitudes and behaviours among parents that increase positive parenting practices, which may be linked to decreased rates of intentional and unintentional childhood injuries. This manuscript describes the development of `RISE Up', an ambulatory clinic-based childhood injury prevention programme that provides tailored, injury prevention print materials to parents of children ages 0-5. Methods Fifteen semi-structured key informant interviews were conducted with clinic healthcare providers and staff to develop communication strategies and materials for caregivers. Cognitive response testing was then conducted with 20 caregivers of the priority population to assess all materials. Interviews were recorded, transcribed and analyzed using thematic coding methods. Results Formative research revealed that health care providers and caregivers were very responsive to messages and materials. Health care providers reported that abuse and neglect were particularly relevant to their patients and noted several benefits to implementing the RISE Up programme in a health care setting. Caregivers generally found messages on reducing the risks of injuries, as well as the graphics displayed in the RISE Up programme to be helpful. Conclusions Addressing the common determinants of both intentional and unintentional childhood injury through customized print materials may be a useful component of comprehensive prevention efforts to address childhood injury risk with greater impact. Providers and parents responded favourably to this communication strategy.
Background Low engagement in prenatal home visiting may limit programme effectiveness to improve birth outcomes. Multiple factors may influence engagement. Methods A retrospective cohort study of first-time mothers enrolled in home visiting prenatally in southwest Ohio from 2007 to 2010. The primary outcome was enrolment by 20weeks' gestation; a secondary outcome included home visit frequency. Two multilevel assessments were conducted using random intercept multilevel modelling; maternal covariates were nested first within the home visiting agency and then within the ZIP code. In the first model, variations attributable to individual agency and agency volume were assessed. In the second model nested within the ZIP code, violence rates by ZIP code and interaction terms between violence rates and maternal factors were evaluated. Results Of 837 women, 25.3% enrolled 20weeks and 7.4% enrolled early and received 75% of expected visits. The first model demonstrated a significant variation in early enrolment based on clustering by agency (p<0.001), however, agency volume was not a significant predictor. In the second model, violence rate was not associated with early enrolment (AOR 0.92, p=0.08), but an interaction term with maternal race was significant (p=0.02). The effect of increasing community violence disproportionately affected early enrolment among white women (AOR 0.80, p=0.005) compared with black women (AOR 0.95, p=0.30). In both the random intercept multilevel models, teenagers demonstrated a decreased likelihood of enrolling early (AOR 0.58, p=0.046 and AOR 0.49, p=0.004). Conclusions Prenatal home visiting engagement is related to maternal, agency and community factors, presenting multiple opportunities to optimise programme implementation.
There is wide variation in reported impact of caring on caregiver wellbeing, and often a negative appraisal of caregiving. Researchers are beginning to question the robustness of the evidence base on which negative appraisals are based. The present study aimed to draw on data from a population-representative sample to describe the health, quality of life and impact of caring of informal caregivers of people with an intellectual disability. Informal carers of people with intellectual disability (N = 260) were identified among 2199 carers in the English Survey of Carers in Households 2009/10. Generalised estimating equations explored the association between socio-demographic and caring profile with quality of life, physical health status, and impact on psychological health and personal life. Compared to other caregivers, providing care to a person with intellectual disability was not associated with reduced quality of life. There was an 82% increased risk of reporting poorer health status, even though poorer health was not likely to be attributed to caregiving. A higher risk of negative impact on personal life was seen in comparison with the wider group of caregivers, but not in comparison with more similar-sized caregiver groups (mental health or dementia). Carers of people with intellectual disability were more likely to be struggling financially and have a high caring load. These factors were systematically related to lower well-being. A uniformly negative appraisal of caring for people with intellectual disability was not supported by these English population-representative data. Poverty and long caregiving hours may make caregivers more susceptible to negative wellbeing. Support for caregivers of people with intellectual disability should focus on alleviating those two factors.
The health and well-being consequences of social isolation and loneliness in old age are increasingly being recognised. The purpose of this scoping review was to take stock of the available evidence and to highlight gaps and areas for future research. We searched nine databases for empirical papers investigating the impact of social isolation and/or loneliness on a range of health outcomes in old age. Our search, conducted between July and September 2013 yielded 11,736 articles, of which 128 items from 15 countries were included in the scoping review. Papers were reviewed, with a focus on the definitions and measurements of the two concepts, associations and causal mechanisms, differences across population groups and interventions. The evidence is largely US-focused, and loneliness is more researched than social isolation. A recent trend is the investigation of the comparative effects of social isolation and loneliness. Depression and cardiovascular health are the most often researched outcomes, followed by well-being. Almost all (but two) studies found a detrimental effect of isolation or loneliness on health. However, causal links and mechanisms are difficult to demonstrate, and further investigation is warranted. We found a paucity of research focusing on at-risk sub-groups and in the area of interventions. Future research should aim to better link the evidence on the risk factors for loneliness and social isolation and the evidence on their impact on health.
Objectives: This study aims to describe the dietary status of Turkish adults using two different versions of the Healthy Eating Index (HEI). Methods: In this cross sectional study, 494 healthy participants (311 females) with randomly selected and living in Ankara were included between September 2013 and March 2014. A questionnaire was completed and anthropometric measurements (weight and height) were performed. The 24-h dietary recall of individuals was collected. Diet quality was measured through HEI-2005 and HEI-2010 scores. Results: The mean age, body mass index (BMI), HEI-2005 and HEI-2010 scores of individuals were 32.9 +/- 10.8 years; 25.0 +/- 4.8 kg/m(2); 56.1 +/- 13.9 and 41.5 +/- 13.7 points, respectively. Significant differences were found between mean HEI-2005 and HEI-2010 scores (p < 0.05). The individual's whose diet quality needs to be improved according to mean HEI-2005 score, had poorer diet based on mean HEI-2010 scores. The highest mean HEI-2005 and HEI-2010 scores were stated in female, in subjects had low education levels, aged 51 years or older and in overweight groups (p < 0.05). Both versions of healthy eating indices were correlated positively with BMI and age Conclusion: Diet qualities of the individuals are associated with age, gender, education and BMI. Although the components and scores in HEI-2010 version were changed from the version of HEI-2005, the changes may encourage healthy choices of some food group. HEI-2010 gives more attention to food quality than HEI-2005. Thus, in the present study it was concluded that HEI-2010 provided more precise results about diet quality.
Background: Increased spiritual well-being is related to quality of life (QOL) in patients with heart failure (HF). However, consistent and deliberate integration of spirituality into HF patient care has received limited attention. Objective: The aim of this study was to evaluate the feasibility, acceptability, and preliminary evidence regarding the efficacy of a resource-sparing psychospiritual intervention to improve QOL in HF patients. Methods: A 12-week mail-based intervention addressing spirituality, stress, coping, and adjusting to illness was developed and tested using a mixed-methods, 1-group pretest-posttest pilot study design. A convenience sample of patients with HF completed prestudy and poststudy questionnaires, including the Kansas City Cardiomyopathy Questionnaire, Patient Health Questionnaire, Meaning in Life Questionnaire, and Functional Assessment of Chronic Illness Therapy-Spiritual. Research staff conducted semistructured interviews with program completers. Interviews were coded and analyzed using conventional content analysis. Results: Participants (N = 33; 82% male; mean age, 61 years) completed 87% of baseline data collection, an average of 9 intervention modules, and 55% of poststudy questionnaires. Participants rated all the modules as at least moderately helpful, and qualitative themes suggested that patients found the intervention acceptable and beneficial. Most participants believed spirituality should continue to be included, although they disagreed on the extent to which religion should remain. Participants who completed the intervention reported evidence suggesting increased QOL (Kansas City Cardiomyopathy Questionnaire; effect size [ES], 0.53), decreased depressive symptoms (Patient Health Questionnaire-9; ES, 0.62), and less searching for meaning (Meaning in Life Questionnaire; ES, 0.52). Conclusions: Results indicate that a module-based program integrating spirituality and psychosocial coping strategies was feasible and acceptable and may improve QOL. This preliminary study suggests that clinicians be open to issues of spirituality as they may relate to QOL in patients with HF. Future research will test a revised intervention.
Air pollution represented by haze in China has attracted great global attention in recent years. China has recently introduced a series of action plans to improve air quality and prevent air pollution. Remediation on small coal-fired boilers and the development of heat and power cogeneration (HPC) and centralized heat supply (CHS) are important measures for preventing air pollution. This paper introduces the above mentioned policies, An industrial park in Guangdong Province, China, is taken as an example to analyze the contributions of HPC-based industrial CHS to energy saving and environmental protection. The benefits to the heat supplier and user are also analyzed. Furthermore, this paper presents the difficulties and challenges in developing industrial CHS, including mismatching in the early phase, price dispute, measure dispute, and negative inter-effects. The reasons for these problems are analyzed and possible solutions are provided. (C) 2016 Elsevier By. All rights reserved.
To gain insight into the comparative function in stress response of HSPs in insects, three HSP cDNAs were cloned from the fat body of the beet armyworm Spodoptera exigua (Lepidoptera, Noctuidae). SexHSP70, SexHSP74 and SexHSP83 cDNAs encoding the protein of 667, 685 and 717 amino acids, with the pI of 5.52, 5.75 and 5.02, respectively. Northern blotting revealed that all three SexHSP mRNAs are expressed in the fat body, mid-gut, spermary and tracheae. SexHSP70, SexHSP74and SexHSP83 mRNAs were expressed in the fat body and whole body at different levels during different developmental stages. The three SexHSP transcripts were highly expressed in the fat body on the first day of fifth instar larvae, on the fourth and seventh days of the pupa stage, and in the whole body on the initial stages of larvae. Under heat and cold shock conditions, SexHSP70 and SexHSP83 mainly functioned during heat shock and cooling and SexHSP83 also had a function in the recovery stage. SexHSP74 had important functions in short-term heat shock and recovery, as well as long-term cooling. The results revealed that long-term shocking can affect SexHSP74 and SexHSP83 expression and long-term cooling can influence SexHSP83 expression during the recovery stage. Published by Elsevier Inc.
Heat shock transcription factor I (HSF1) regulates heat shock proteins (HSPs), which assist in protein folding and inhibit protein denaturation following stress. HSFI was firstly cloned from orange-spotted grouper and exists as two isoforms, one with (osgHSF1a) and one without (osgHSF1b) exon 11. Heat exposure increased the expression of osgHSFlb while cold exposure increased that of osgHSFla. Both isoforms were mainly expressed in the brains, eyes, and fins. Expression of osgHSF1b was higher than osgHSFla during development. Poly I:C and LPS could also induce osgHSF1 isoforms expression differentially. Exposure to nervous necrosis virus (NNV) increased the level of both osgHSF1 isoforms at 12 h. GF-1 cells with overexpression of osgHSF1 isoforms enhanced viral loads within 24 h, whereas both pharmacological inhibition and RNA interference of HSF1 reduced virus infection. This study shows that osgHSF1 can support the early stage of virus infection and provides a new insight into the molecular regulation of osgHSF1 between the influence of temperatures and immunity. (C) 2016 Elsevier Ltd. All rights reserved.
The common existence of heat transfer phenomena in energy utilization systems highlights the importance of appropriate design and optimization methods of heat transfer systems to an unprecedented level. In this contribution, we defined an alternative thermal resistance for heat exchangers based on the inlet temperature difference of hot and cold fluids, which was influenced by such two aspects as the finite heat capacity rates of hot and cold fluids and the entransy dissipation-based thermal resistance of heat exchangers. Meanwhile, the corresponding energy flow models are proposed to analyze the heat transfer performance of both individual heat exchangers and three basic heat exchanger networks, i.e. series, parallel and multi-loop by the thermo-electrical analogy method, which offer the solution for constructing the energy flow models of any heat transfer system. For validation, we constructed the energy flow model of a double-loop thermal management system. On this basis, the heat transfer characteristic was described on the system level and the overall system constraints were obtained by the Kirchhoffs Law without introducing any intermediate variables. With these system constraints, the optimization equations for the system were derived theoretically by applying the Lagrange multiplier method. Simultaneously solving these equations gave the optimal thermal conductances of each heat exchanger and the best allocations of heat capacity rate directly, which benefited energy conservation. That is, the energy flow model is reliable and convenient for the analysis and optimization of heat transfer systems. (C) 2016 Elsevier Ltd. All rights reserved.
In this study, we develop a novel system to recover the waste heat from the exhaust of a passenger car. A heat exchanger is therefore placed after the exhaust manifold of the vehicle. Thermoelectric generators (TEG) are installed on all pipes of the heat exchanger to generate electricity by the temperature difference between hot and cold sides of the TEG. The heat transfer of the TEG is analyzed numerically. Two configurations of TEG units are investigated for various exhaust flow rates and temperatures. The overall heat transfer rates from the exhaust gas to the TEG, the power capacity of the system and the overall heat transfer coefficients of the system are calculated. It is observed that the power capacity of the system is directly related to the inlet temperature and mass flow rate of the exhaust gas entering the system. The power generated by the system can be improved by 90% with an increase of the mass flow rate and temperature of the exhaust gas. Increasing the size of the TEG system by 66.7% rises the overall heat transfer rate of the system by 33.8%. (C) 2017 Elsevier Ltd. All rights reserved.
Physical treatments have gained great interest in recent years to control many postharvest diseases in fruits and vegetables because the total absence of residues in the treated product and minimal environmental impact. The present review shows the extensive research work conducted during many years and increased in the last 10 years, developing physical means for consistent disease control. The review include the use of cold storage as the main physical method for delaying or reducing biotic and abiotic diseases. Physical treatments, like heat, including hot water and hot air treatments, radio frequency and microwave, hypobaric and hyperbaric pressure and far ultraviolet radiation (UV-C light), are treated as promising control means, and controlled and modified atmospheres as complementary physical tools essential to reduce or delay the development of postharvest pathogens. A particular emphasis is given to the mode of action, which involve direct effect to the pathogen (lethal or sub-lethal) of spore germination and mycelial growth of fungi and the resistance induction in the host which is not well known but nowadays, with the new tools available in molecular biology will be easy to highlight other physiological and biochemical pathways on which the phenomenon are based. Besides benefits of treatment in different commodities, also limitations of use, including low persistence, risk of adverse effects and technological problems for commercial application are discussed. (C) 2016 Elsevier B.V. All rights reserved.
Microbially induced corrosion (MIC) has been identified as the main cause of the rupture of a key heat exchanger shell at a local refinery. The failure occurred at the 6 o'clock position, close to the girth weld, halfway along the length of the carbon steel shell. An ultrasonic survey revealed up to 90% wall thinning in the ruptured zone. Despite extensive crystallization at the external cooling seawater inlet of the cooling system tubing, there was no evidence of internal leakage of seawater into the shell compartment. The total dissolved solids in the condensate dropout sample were found to be 262 mg/L. The investigation also confirmed that the girth weld had been satisfactorily conducted, including post heat treatment, and that the failure occurred outside the heat affected zone (HAZ). Quantitative polymerase chain reaction (qPCR) analysis of the dry surface film from a crack in the ruptured area confirmed the suitability of the operating environment for prokaryotic growth and the presence of both groups of highly corrosive acid producing bacteria (APB) and denitrifying bacteria (DNB) in moderate numbers (1.92 x 10(3) APB/g and 1.81 x 10(5) DNB/g respectively). The colonization of different groups of corrosion-causing bacteria of a sour system resulted in the localized generation of highly aggressive metabolic by-products causing substantial loss of wall thickness of the heat exchanger shell. The localized wall thinning by over 90% of its original thickness led to the loss of pressure retention capacity of the shell and the rupture of the wall. (C) 2016 Elsevier Ltd. All rights reserved.
Transformation of DNA into microbial cells via heat-shock approach has been well established in the field of molecular biology for decades. Herein we described an unexpected finding that heat-shock may not play an essential role in the transformation process. This observation was verified via UV-Vis and fluorescence spectroscopies, and confocal microscopy images for various DNAs and bacterial cells. The non-heat-shock approach proposed in this study can be a convenient and beneficial modification for DNA transformation, especially for those laboratories lacking ice machine and heat-shock equipment.
Sunflower leaf spot caused by the necrotrophic pathogen Alternaria helianthi is one of the most important biotic constraints in sunflower production. The biochemical basis of resistance to infection by A. helianthi in sunflower is poorly elucidated. Differential activation of early defense responses like increased peroxidase activity predisposes the host plant resistance. In the present study, the active role of peroxidase in resistant and susceptible interactions of sunflower with the leaf spot pathogen was demonstrated using native PAGE analysis and Northern blotting. Differential time-dependent induction of peroxidase isoforms was evident in resistant and susceptible genotypes after pathogen inoculation. In the resistant interaction, three peroxidase (PO) isoforms (PO1, PO2, and PO3) were found to be expressed at 2 and 12 h after inoculation, but in susceptible interaction, PO2 was present at 24 and 48 h and PO3 was found only at 24 h after inoculation. However, in the susceptible genotype, expression intensity was lower than in the resistant interaction at all the time intervals. Molecular expression profiling by Northern blotting using heterologous cDNA probes showed rapid up-regulation of peroxidase at 2 and 12 h in resistant interaction. These results demonstrate that peroxidase isoforms are involved in defense against A. helianthi, and genetic regulation in the form of transcript accumulation is important for expression of disease resistance.
The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.
The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available culture-or molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.
Acyl-CoA-binding protein (ACBP), also known as the diazepam-binding inhibitor (DBI), has been identified in diverse species and is evolutionarily conserved in plants and animals. In a recent study, an ACBP cDNA (HaACBP) encoding 85 amino acids was isolated from the cotton bollworm Helicoverpa armigera. The isolated protein is highly homologous to the ACBP present in the Bombyx mori midgut, where it is highly expressed. Northern and Western blot analyses revealed that HACBP is expressed predominantly in the midgut. Moreover, Northern blotting revealed that HaACBP was probably stimulated by a high juvenile hormone titer at ecdysis and increased along with feeding at 12 h post-ecdysis. Immunohistochemistry of the midgut revealed that HaACBP is localized in columnar cells. Data from the Northern blotting and immunohistochemistry suggested that HaACBP was expressed during the larval period and is probably responsible for nutrition absorption. However, Western blot analysis of the midgut at different developmental stages indicated that HaACBP was upregulated during larval molting and metamorphosis, which suggested that HaACBP expression was posttranscriptionally regulated.
Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h) 1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity.
This study examined the services provided by one statewide warmline established to assist parents and caregivers of children from birth through adolescence. Warmlines offer telephone-based, non-crisis support for individuals experiencing diverse issues that include parenting questions and concerns. The University of Alabama Child Development Resources collaborated with the Alabama State Department of Child Abuse and Neglect Prevention to institute the Parenting Assistance Line to provide information and support to parents and caregivers of children, age birth through adolescence. Overall, the staff of the Parenting Assistance Line responded to 9487 calls during the 6 years of data reported here. Through a secondary data analysis of calls to the Parenting Assistance Line from June 2007 to July 2013, this study describes the concerns of callers in relation to the ages of the children about whom they are calling and also evaluates the perceptions of the helpfulness of the information and support provided by the warmline. We found that frequently calls involved parent support and parental stress for parents and caregivers of children from infancy through adolescence. The findings suggest that telephone assistance lines offer a viable choice for parents and caregivers seeking affordable and accessible resources when stressed by the responsibilities of caring for children and adolescents and/or seeking information related to parenting issues. The study identified the limitations of research involving secondary data collected for purposes other than research that program administrators and evaluators should consider when planning and implementing services of this nature.
A feeding trial was conducted to investigate the effects of different levels of dietary Lactobacillus plantarum on hemato-immunological parameters and resistance against Streptococcus iniae infection in juvenile Siberian sturgeon Acipenser baerii. Fish (14.6 +/- 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 x 10(7), 1 x 10(8) and 1 x 10(9) colony-forming units (cfu) g(-1)] and a control (non-supplemented basal) diet for 8 weeks. Innate immune responses (immunoglobulin (Ig), alternative complement activity (ACH50) and lysozyme activity) were significantly higher in fish fed the 1 x 10(8) and 1 x 10(9) cfu g(-1) L. plantarum diet compared to the other groups (P < 0.05). Furthermore, fish fed on various levels of L. plantarum significantly showed higher red blood cell (RBC), hemoglobin (Hb), white blood cell (WBC) and monocyte compared to those of the control group (P < 0.05). At the end of the feeding experiment, some fish were challenged with S. iniae to quantify the level of disease resistance. The mortality after S. iniae challenge was decreased in fish fed a probiotic. These results indicated that dietary supplementation of L. plantarum improved immune response and disease resistance of Siberian sturgeon juvenile.
Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence. However, their precise role in regulating B-cell commitment has been the subject of debate. In the present study we assessed the rescue of B-cell commitment in mice lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting in significant Ebf1 and Pax5 expression in Ly6D(+) CD135(+)CD127(+)CD19(-) precursors and subsequent generation of normal numbers of CD19(+) B-cell progenitors, therefore indicating that IL-7 can be dispensable for commitment to the B-cell lineage. Further analysis of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors in IL-7-or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive manner: FL by inducing proliferation of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors and IL-7 by providing survival signals to these progenitors.
Aging is associated with significant changes in hematopoiesis, including clonal dominance, anemia, myeloid malignancies, and reduced activation of signal transducer and activator of transcription 5 (Stat5). In previous studies, Stat5 deletion surprisingly amplified FLT3/ITD+ myeloid expansion or Myc-driven lymphoid expansion. Here we show that Stat5 deficiency has a strong impact upon transcriptional heterogeneity in single sorted c-Kit(+) Lin-Sca-1(+) (KLS) cells or CD150(+) CD48-KLS long-term repopulating hematopoietic stem cells (LT-HSC). Single cell polymerase chain reaction (PCR) was performed on selected regulators of multi-lineage hematopoiesis. At least two dominant sub-populations were identified by increased expression of cell cycle regulatory and leukemia-associated genes. Furthermore, in the top expressing quartile of cells, the majority of genes were proportionally overrepresented. In wildtype KLS cells, Stat5 mRNA levels were also strongly correlated with several genes. Since heterogeneity decreases with age or inflammatory or oncogenic stress, these results provide a potential mechanistic linkage to Stat5 expression.
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments.
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2(-/-) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho-and erythropoiesis, myelopoiesis was enhanced in Il2(-/-) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2(-/-) mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-gamma production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2(-/-) mice, preventing IFN-gamma activity could do the same even in the absence of Treg cells. Our study suggests that equilibrium in IL-2 and IFN-gamma activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-gamma treatment might help to restore hematopoiesis.
The diagnosis of hemophagocytic lymphohistiocytosis ( HLH) can be a difficult one, and the distinction between primary versus secondary HLH can be particularly challenging during the early stages of diagnosis. This distinction is important to make as primary HLH requires allogeneic hematopoietic cell transplantation for a definitive cure. Flow cytometric screening tests for many of the genetic forms of HLH are available. However, not all patients with primary HLH are captured by these screening tests, due to the fact that no screening test is 100% sensitive, and additionally, some patients with "primary" forms of HLH may have mutations in genes which are yet to be discovered. In this issue of the European Journal of Immunology, Ammann et al. [Eur. J. Immunol. 2017. 47: 364-373] compare T-cell phenotype patterns among patients with primary and secondary HLH, and find that assessment of T-cell activation and differentiation may assist with the diagnosis of HLH. Furthermore, this phenotypic analysis has the potential to help make the important distinction between primary and secondary HLH.
Heparin-induced thrombocytopenia (HIT) is a serious drug reaction that leads to a decrease in platelet count and a high risk of thrombosis. HIT patients produce pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet factor-4 (PF4) and heparin. HIT immune complexes crosslink Fc-receptors resulting in platelet and monocyte activation. These events lead to the release of procoagulant chemokines and tissue factor, which together create an intensely prothrombotic state. HIT represents an atypical immune response because it has features of both T cell-dependent and T cell-independent mechanisms. The disorder is characterized by newly formed anti-PF4/heparin IgG antibodies, which are characteristic of a T cell-dependent mechanism; however, re-exposure to heparin, months after HIT, does not lead to a memory response, which is consistent with a T cell-independent mechanism. In this review, we discuss the immunobiological events that can explain these features, including the role for T cell-dependent and T cell-independent mechanisms in HIT antibody generation, the immunogenic characteristics of the PF4/heparin antigen, and the concept of a temporary loss in immune regulation contributing to the onset of HIT. We also present a novel immunobiological model to explain the atypical immune response that is characteristic of HIT.
Tumor metastasis is a multistep process involving a number of genetic alterations so that the genetic diagnosis is got increasingly attentions today. The aim of this study was to use RNA-seq to screen the effective differential expression genes in the peripheral blood mononuclear cells for the hepatic carcinoma with metastasis. The results showed that hepatic carcinoma samples gathered according to different metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in inflammation mediated by chemokine and cytokine signaling pathway (P00031) in the hepatic carcinoma samples with metastasis, and subsequently confirmed by quantitative real-time polymerase chain reaction. In conclusions, CCL3, CCL3L1, JUN, IL8, and IL1B have the potential to be considered as candidates for future molecular diagnosis of the hepatic carcinoma with metastasis. This work may provide us with new visions into the metastasis process and potential efficient clinical diagnosis in the future.
Background: The sodium taurocholate co-transporting polypeptide, encoded by SLC10A1, was identified as a functional receptor for hepatitis B virus (HBV). The objective of this study was to determine if there was an association of the Ser267Phe variant (rs2296651) with HBV infection status in Moroccan patients. Methods: Using a TaqMan 5' allelic discrimination assay, the Ser267Phe variant was genotyped in 286 chronic hepatitis B patients, 135 individuals with spontaneous clearance from HBV infection and 109 healthy controls negative for hepatitis B serological markers. Results: In this cohort, we detected only wild-type genotype (S267S) in all groups. This polymorphism was not associated with the HBV infection status in Moroccan patients. Conclusions: The S267F variant is absent among Moroccans regardless of chronic HBV infection status.
The aim of this study was to compare the data obtained using the new LIAISON (R) XL chemiluminescence system to search for HBsAg, antiHCV, and anti-HIV1-2/p24 Ag with those obtained using the VITROS system currently adopted by the Microbiology Unit of the Hospital of Legnano. Routine samples of patients who were referred by practitioners for the determination of HBsAg (1,000 samples) and/or anti-HCV (1,002 samples) and/or anti-HIV1-2 (995 samples) were simultaneously analyzed using both systems. The concordant positive and discordant samples were re-examined for confirmation by means of an HBsAg neutralization assay, anti-HCV immunoblot, or anti-HIV1-2 Western blot; HBV-DNA, or HCV-RNA or HIV-RNA was also sought in the discordant samples. Samples of patients known to be positive were tested (100 HBsAg positive, 100 anti-HCV positive, and 100 HIV 1-2 positive) as well throughout treatment, with viremia levels becoming undetectable after treatment. The HBsAg, anti-HCV, and anti-HIV1-2 concordance between the two systems in routine series was respectively 99.8%, 98.5% and 99.7%, and 100% for all markers in samples known positive. The various molecular biology and confirmatory tests of the discordant samples were all negative (except for one anti-HCV positive sample). Measure of Cohen's kappa coefficient for HBsAg, anti-HCV, and anti-HIV gave K values of respectively 0.992, 0.946, and 0.980. In conclusion, the performance of the LIAISON (R) XL system in the routine laboratory determination for all three markers was comparable with that of the VITROS system. (C) 2016 Wiley Periodicals, Inc.
Hepatitis B virus (HBV) infection is one of the major risk factors leading to the development of hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg) plays a pivotal role in HBV-related HCC pathogenesis, and Toll-like receptor (TLR) 2 is also considered to mediate tumor progression. However, the interaction between HBsAg and TLR2 in HCC progression remains unclear. Thus, the aim of the study was to explore the effect of HBsAg-TLR2 pathway on growth and invasion of HBV-related HCC cells and examine the potential mechanisms been involved. The expression of TLR2 was measured in two different HCC cell lines (HepG2 and HepG2.2.15) with or without recombinant HBsAg by real-time reverse polymerase chain reaction and Western blot. Cellular proliferation, invasion, cytokine productions, and downstream signaling pathways were also measured in TLR2-silencing HepG2.2.15 cells in response to HBsAg stimulation. The mRNA and protein levels of TLR2 were significantly elevated in HepG2.2.15 cells than those in HepG2 cells. HBsAg simulation increased proinflammatory cytokine production and invasion of HepG2.2.15 cells, while this process was inhibited by TLR2 silence. However, TLR2 siRNA transfection alone did not affect the bioactivities of tumor cells. Moreover, HBsAg increased expression of MyD88 and phosphorylation of NF-kappa B p50 and p38MAPK. Downregulation of TLR2 inhibited HBsAg-induced MyD88 and p-NF-kappa B, but not p-p38MAPK in HepG2.2.15 cells. In conclusion, HBsAg stimulation promotes the invasion of HBV-related HCC cells. TLR2/MyD88/NF-kappa B signaling pathway may be involved in this procession by upregulation of cytokine production. The interaction between TLR2 and HBsAg may contribute to the poor prognosis of HBV-related HCC.
Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987-1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3.79%; 3.47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8.41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBspositive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55.13 mIU/ml and this declined after immunization. Fewer than 2.0% of participants had anti-HB levels 51000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.
Background MicroRNAs (miRNAs) are highly conserved small non-coding RNAs of 18-25 nucleotides (nt) that mediate post-transcriptional gene regulation. Hepatitis B virus (HBV) can cause either acute or chronic hepatitis B, and is a high risk factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses have been shown to modulate the expression of host cellular miRNAs. However, interactions between the HBV and the host cellular miRNAs are largely unknown. Methods miRNA microarray and Northern blotting analysis were used to compare the expression profile of cellular miRNAs of a stable HBV-expressing cell line HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda program were used to predict the miRNA targets. A flow cytometric assay was further used to investigate the expression of human leukocyte antigen (HLA)-A. Results Eighteen miRNAs were differentially expressed between the two cell lines. Among them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells. Northern blotting analysis confirmed that the expression of miR-181a, miR-181b, miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-regulated, which was in consistent with the results of the microarray analysis. Furthermore, some putative miRNA targets were predicted and verified to be linked with mRNA expression. The 3'-UTR of HLA-A gene had one partially complementary site for miR-181a and miR-181a might down-regulate the expression of HLA-A. Conclusion HBV replication modulates the expression of host cellular miRNAs, which may play a role in the pathogenesis of HBV-related liver diseases.
Hepatitis B virus (HBV) infection is a major global health challenge. HBV can cause significant morbidity and mortality by establishing acute and chronic hepatitis. Approximately 250 million people worldwide are chronically infected, and more than 2 billion people have been exposed to HBV. Since the discovery of HBV, the advances in our understanding of HBV virology and immunology have translated into effective vaccines and therapies for HBV infection. Although current therapies successfully suppress viral replication but rarely succeed in viral eradication, recent discoveries in HBV virology and immunology provide exciting rationales for novel treatment strategies aiming at HBV cure.
Aim: To investigate the action of isothiafludine (NZ-4), a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in vitro and in vivo. Methods: HBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interaction of pregenomic RNA (pgRNA) and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 (25, 50 or 100 mg.kg(-1).d(-1)) for 15 d. Results: NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC50 value of 1.33 mu mol/L, whereas the compound inhibited the cell viability with an IC50 value of 50.4 mu mol/L. Furthermore, NZ-4 was active against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 (5, 10, and 20 mu mol/L) concentration-dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks. Conclusion: NZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process, thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat HBV infection.
Vasculitis is a remarkable presentation of the extrahepatic manifestations of HCV. According to the presence or absence of cryoglobulins it is subdivided into two main types: cryoglobulinemic vasculitis and non cryoglobulinemic vasculitis based on the attribution of vasculitis to serum cryoglobulins as a pathogenic factor. The attribution of cryoglobulinemia to HCV represents a success story in the history of immunology, microbiology, and clinical medicine. HCV can bind to and invade lymphocytes, consequently triggering an immune response through different mechanisms. The epidemiology of the disease is well described and the clinical picture describes cutaneous, pulmonary, musculoskeletal, neurological, renal, endocrine, gastrointestinal, hepatic and cardiovascular manifestations. It may also be associated with sicca symptoms, an increased risk of lymphoma and serious catastrophic events. The pathology is well characterized. A classification criteria of the syndrome that was validated in 2014 is discussed. Management of CV is decided according to the presence and severity of its clinical presentation. It is divided into asymptomatic, mild, moderate, severe and life threatening disease. Recently introduced direct antiviral agents are proving safe and effective in the management of cryoglobulinemic vasculitis, and it is advocated that the two types of vasculitis be given prioritization in the Egyptian mass campaign to eradicate HCV. (C) 2016 Production and hosting by Elsevier B.V. on behalf of Cairo University.
Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.
Although rat hepatitis E virus (HEV) has been identified in wild rats, no cell culture systems for this virus have been established. A recent report suggesting the presence of antibodies against rat HEV in human sera encouraged us to cultivate rat HEV in human cells. When liver homogenates obtained from wild rats (Rattus rattus) in Indonesia were inoculated onto human hepatocarcinoma cells, the rat HEV replicated efficiently in PLC/PRF/5, HuH-7 and HepG2 cells, irrespective of its genetic group (G1-G3). The rat HEV particles released from cultured cells harbored lipid-associated membranes on their surface that were depleted by treatment with detergent and protease, with the buoyant density in sucrose shifting from 1.15-1.16 g/ml to 1.27-1.28 g/ml. A Northern blotting analysis revealed genomic RNA of 7.0 kb and subgenomic RNA of 2.0 kb in the infected cells. The subgenomic RNA of G1-G3 each possessed the extreme 5'-end sequence of GUAGC (nt 4933-4937), downstream of the highly conserved sequence of GAAUAACA (nt 4916-4923). The establishment of culture systems for rat HEV would allow for extended studies of the mechanisms of viral replication and functional roles of HEV proteins. Further investigation is required to clarify the zoonotic potential of rat HEV. (C) 2014 Elsevier B.V. All rights reserved.
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th) 1 inflammatory cells, characterized by interferon (IFN)-gamma and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-gamma-induced protein 10 (IP-10), monokine induced by IFN-gamma (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3). IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. IFN-gamma-induced chemokines, as MIG and IP-10, may promote lymphocyte recruitment to HCC playing important roles in cancer immunology. The production of CXC chemokines by HCC cell lines has been shown. It has been identified immune-gene signature that predicts patient survival including the chemokine gene IP-10. Inflammatory cytokines (tumour necrosis factor-alpha, IFN-gamma) and Toll-like receptor 3 ligands stimulate intratumoral production of these chemokines which drive T and Natural Killer cells tumor infiltration, leading to enhanced cancer cell death. Furthermore selective recruitment of CXCR3(+) B-cells that bridges proinflammatory IL-17 response and protumorigenic macrophage polarization in HCC has been shown, suggesting that blocking CXCR3(+) B-cell migration or function may help defeat HCC. It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment.
Hepatocellular carcinoma is an aggressive neoplasm and is one of the most common human cancers. Recently, long non-coding RNAs have been demonstrated to participate in pathogenesis of many diseases including the progression in several cancers. In this study, we found that the long non-coding RNA colon cancer-associated transcript 1 was upregulated in hepatocellular carcinoma tissues (p < 0.05), and high colon cancer-associated transcript 1 expression level was positively associated with tumor volume (p < 0.05) and American Joint Committee on Cancer stage (p < 0.05) in hepatocellular carcinoma patients. Luciferase reporter assays and RNA-pulldown assays showed that colon cancer-associated transcript 1 is a target of miR-490-3p. Real-time quantitative polymerase chain reaction and Western blot analysis indicated that colon cancer-associated transcript 1 regulated cyclin-dependent kinase 1 expression as a competing endogenous RNA by sponging miR-490-3p in hepatocellular carcinoma cells. Furthermore, colon cancer-associated transcript 1 silencing decreased hepatocellular carcinoma cells proliferation and invasion and overexpression promoted cell proliferation and invasion in vitro. These data demonstrated that the colon cancer-associated transcript 1/miR-490-3p/cyclin-dependent kinase 1 regulatory pathway promotes the progression of hepatocellular carcinoma. Inhibition of colon cancer-associated transcript 1 expression may be a novel therapeutic strategy for hepatocellular carcinoma.
Limited efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC) was observed in clinical trials, thus prompting investigation into combination therapy. Interleukin-6 (IL-6) has important roles in modeling immune responses in cancers. Here, we hypothesized that IL-6 blockade would enhance antitumor immunity of HCC and synergize with anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor in treating HCC. The sources and immune modulating effects of IL-6 were investigated in HCC models. Combination of anti-IL-6 and anti-PD-Ll was tested in HCC bearing mice. We found that IL-6 is mainly secreted by cancer associated fibroblast (CAFs), but not tumor cells in HCC. High IL-6 expression CAFs could induce strong immunosuppression in HCC microenvironment by recruiting immunosuppressive cells, such as myeloid derived suppressive cells. In addition, high IL-6 expression CAFs also impaired tumor infiltrating T-cell function via upregulating inhibitory immune checkpoints. Using IL-6 blockade could reverse anti-PD-LI resistance in HCC tumor model. In conclusion, our study indicates that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-Ll in HCC, providing a potential strategy to overcoming anti-PD-Ll resistance in HCC.(C) 2017 Published by Elsevier Inc.
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to regulate different tumorigenic processes, and a growing body of evidence indicates that Hippo kinase signaling is inactivated in many cancers. However, the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. Methods: Using a lncRNA microarray, we identified a novel lncRNA, uc.134, whose expression was significantly decreased in the highly aggressive HCC cell line HCCLM3 compared with MHCC97L cells. Furthermore, we evaluated uc.134 expression in clinical samples using in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The full-length transcript of uc.134 was confirmed using rapid amplification of cDNA ends (RACE) analyses. To investigate the biological function of uc.134, we performed gain-of-function and loss-of-function studies both in vitro and in vivo. The underlying mechanisms of uc.134 in HCC were investigated using RNA pulldown, RNA immunoprecipitation, ubiquitination assays, Western blotting, mRNA microarray analyses, and qRT-PCR analyses. Results: The ISH assay revealed that uc.134 expression was significantly decreased in 170 paraffin-embedded samples from patients with HCC compared with adjacent tissues and uc.134 expression directly correlated with patient prognosis. Furthermore, we defined a 1867-bp full-length transcript of uc.134 using 5'-and 3'-RACE analysis. The overexpression of uc.134 inhibited HCC cell proliferation, invasion, and metastasis in vitro and in vivo, whereas the knockdown of uc.134 produced the opposite results. Furthermore, we confirmed that uc.134 (1408-1867 nt) binds to CUL4A (592-759 aa region) and inhibits its nuclear export. Moreover, we demonstrated that uc.134 inhibits the CUL4A-mediated ubiquitination of LATS1 and increases YAPS127 phosphorylation to silence the target genes of YAP. Finally, a positive correlation between uc.134, LATS1, and pYAP(S127) was confirmed in 90 paraffin-embedded samples by ISH and immunohistochemical staining. Conclusions: Our study identifies that a novel lncRNA, uc.134, represses hepatocellular carcinoma progression by inhibiting the CUL4A-mediated ubiquitination of LATS1 and increasing YAPS127 phosphorylation. The use of this lncRNA may offer a promising treatment approach by inhibiting YAP and activating Hippo kinase signaling.
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. The high rate of diagnosis in non-curable stages and the lack of novel active treatments make it necessary to review all the possible sources of misleading results in this scenario. The incidence of HCC shows clear geographical variation with higher annual incidence in Asia and Africa than in Western countries; we aimed to review the literature to find if there are different trends in the main activated molecular pathways. Hyperactivation of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signalling and epithelial to mesenchymal transition (EMT) process are more prevalent in the Western population; however, fibroblast growth factor (FGF), transforming growth factor beta (TGF beta) and Notch pathways seems to be more relevant in Asian population. Whether these variations just reflect the distinct distribution of known causes of HCC or proper ethnical differences remain to be elucidated. Nevertheless, these clearly different patterns are relevant to regional or worldwide clinical trial design. If this information is neglected by sponsors and researchers the rate of failure in HCC trials will not improve. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Octamer 4 (Oct4), a member of the Pit-Oct-Unc transcription factor family required to maintain self-renewal and pluripotency of embryonic stem cells, has been previously identified to be associated with tumorigenesis and malignant transformation of numerous types of cancer including hepatocellular carcinoma (HCC). The present data shows that Oct4 enhances cancer stem cell properties and increases invasion ability in the Huh7 cell line. To increase understanding of the role of Oct4 in HCC, the present study used a functional genomics approach and analyzed the resulting transcriptional profiles to identify Oct4-dependent genes in Huh7. Affymetrix GeneChip Human genome U133 Plus 2.0 Arrays were used to determine differential gene expression profiles and then validated by quantitative polymerase chain reaction. The present study found that altered expression of 673 genes (fold-change >= 2) affected multiple signaling pathways linked with self-renew and metastasis. Among these differentially expressed genes, the present study noticed that the key component of the WNT signaling pathway lymphoid enhancer binding factor 1 (LEF1) and Twist Family BHLH transcription factor 1 were upregulated by Oct4, whilst cadherin 2 was downregulated. Additional studies found that the nuclear beta-catenin aggregation was increased in Oct4 overexpressed HCC cell lines. These results suggest that Oct4 regulates LEF1 to active LEF1/beta-catenin dependent WNT signaling pathway and promote epithelial-mesenchymal transition. The present findings provide novel mechanistic insight into an important role of Oct4 in HCC.
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined. STAT3 and HK2 expressions were evaluated by real-time polymerase chain reaction and Western blotting. The level of glycolysis metabolism was assessed by the determination of glucose consumption and lactate production. The results showed that transfection of HepG2 and Hep3B cells with pcDNA3.1(+)-EGFP-STAT3 significantly increased STAT3 mRNA and protein expression, glucose consumption and lactate production, and HK2 mRNA and protein expression. However, transfection of HepG2 and Hep3B cells with STAT3 siRNA significantly decreased glucose consumption and lactate production and HK2 mRNA and protein expression. Transfection of HepG2 and Hep3B cells with HK2 siRNA significantly decreased glucose consumption and lactate production. Treatment of HepG2 and Hep3B cells with rapamycin significantly reduced HK2 mRNA and protein expression and glucose consumption and lactate production. These results suggest that mTOR-STAT3-HK2 pathway is involved in the glycolysis of HCC cells and STAT3 may regulate HCC glycolysis through HK2 pathway, providing potential multiple therapeutic targets through intervention of glycolysis for the treatment of HCC.
Sphingosine kinase 1 (Sphk1) is an oncogenic kinase that is responsible for the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). Mounting evidence suggests that Sphk1 serves a crucial role in the proliferation and development of a variety of human cancer cells. However, the role of Sphk1 in hepatocellular carcinoma (HCC) has not been fully elucidated. Therefore, the expression of Sphk1 was examined in 127 formalin-fixed, paraffin-embedded HCC tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. As a result, the expression of Sphk1 in HCC tissue was revealed to be significantly higher than in normal tissue (P<0.01). In addition, Sphk1 expression was significantly associated with tumor size, tumor stage and histological differentiation (all P<0.05). The patients with low Sphk1 expression had higher overall survival and recurrence-free survival rates compared with patients with high Sphk1 expression. Furthermore, Sphk1-specific shRNA was used to downregulate the expression of Sphk1 in HCC cell lines, including hepatoblastoma G2 and HCC-9724. The CRISPR/Cas9 based transcription activation system was used to upregulate Sphk1 expression in the normal live cell, L02. Cell proliferation, mRNA expression and protein expression were measured using Cell Counting Kit-8, reverse transcription polymerase chain reaction and western blot analysis in the transfected cells. To the best of our knowledge, the present study provides the first evidence that Sphk1 promotes HCC cell proliferation and is involved in tumor progression. Notably, the data presented suggest that Sphk1 may be a potential independent prognosis biomarker for the treatment of HCC.
To date, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification represents the standard system for evaluation of prognosis in solid tumors. However, the clinical outcome can be significantly different in patients with the same TNM stage. Therefore, many efforts have been made aiming to define new prognostic parameters. Indeed, analyses conducted in large cohorts of colorectal cancer patients emphasized the prognostic value of tumor-infiltrating lymphocytes, leading to the development of a prognostic score referred to as "Immunoscore". In this commentary, we recapitulate the study by Gabrielson and colleagues, recently published in Cancer Immunology Research, addressing the role of intratumoral CD3(+) and CD8(+) T cells as well as as prognostic markers for hepatocellular carcinoma. The authors demonstrate that Immunoscore represents a valuable prognostic marker in patients with hepatocellular carcinoma who have undergone primary tumor resection, supporting its application in a tumor setting other than colorectal cancer.
The present study investigated ubiquitin specific peptidase 39 (USP39) gene knockdown on SMMC-7721 cells in vitro and in vivo, and the role of USP39 in regulating the growth of hepatocellular carcinoma (HCC). Two small interfering RNAs (siRNA) were constructed, which targeted the USP39 gene and control sequences were synthesized and inserted into a pGCSIL-GFP lentiviral vector. The full length of USP39 cDNA was amplified by polymerase chain reaction (PCR) and cloned into pEGFP-N2, and the recombinant plasmids were transfected into cells. Knockdown efficiency and upregulation of USP39 was determined by reverse transcription-quantitative PCR and western blotting. The impact of USP39 on the growth of SMMC-7721 cells in vitro was examined using an MTT assay, colony formation, flow cytometry (FCM) and immunohistochemical staining. The impact of USP39 on the growth of SMMC-7721 cells in vivo was examined by assessing tumorigenicity in nude mice. Western blotting was performed to examine the mechanism of USP39 regulation on SMMC-7721 cell growth. Recombinant vectors containing specific and scrambled USP39 siRNA sequences were constructed and transfected into SMMC-7721 cells. USP39 knockdown inhibited cell proliferation and colony formation in SMMC-7721 cells, while upregulation of USP39 promoted the growth of tumor cells. FCM indicated that USP39 knockdown led to G2/M arrest and induced apoptosis in SMMC-7721 cells. USP39 knockdown inhibited xenograft tumor growth in nude mice and led to the downregulation of the transcription factor Forkhead Box M1 (FoxM1). Gene expression of FoxM1 targets, including polo-like kinase 1, cyclin B1 and centromere protein A also decreased following USP39 knockdown. The results suggest that knockdown of USP39 inhibits the growth of HCC in vitro and in vivo, potentially through the induction of G2/M arrest by regulating the pre-mRNA splicing of FoxM1.
Background: Hepatocyte growth factor (HGF) was initially discovered as a mitogen for hepatocytes, but it is also known to be related to carcinogenesis in many other organs. However, the role of HGF in lung carcinogenesis is not fully-understood. In this study, we investigated the role of HGF in lung carcinogenesis using HGF transgenic mice. Materials and Methods: To elucidate the role of HGF in lung carcino genesis, 5 mu g/g body weight diethylnitrosamine (DEN) were administered intraperitoneally to HGF transgenic (TG) mice and wild-type (WT) mice at 15 days of age. The incidence and number of lung tumors, the expression of HGF and of its receptor (c-Met) were compared between HGF TG and WT mice. Results: HGF overexpression accelerated DEN-induced lung carcinogenesis. Seventy-six percent of TG mice (versus 50% of WT mice) developed malignant lung tumors by 48 weeks. The incidence of lung tumors was significantly higher in the TG mice in comparison with WT mice (p<0.05). Furthermore, the mean diameter and number of tumors in each mouse were significantly higher in the TG mice compared to the WT mice (p<0.01). The northern blotting analyses revealed that there was overexpression of the HGF trans gene in the lung tumors of TG mice in comparison with the surrounding non-tumorous lesions. The western blotting analyses of the tumor lesions revealed increased phosphorylation of c-Met. Conclusion: Our results suggest that HGF promotes lung carcino genesis through the autocrine activation of the HGF/c-Met signaling pathway. The HGF/c-Met signaling pathway appears to have vital roles in lung carcinogenesis.
Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. aEuro cent Expression of hepatocyte transporters is modified in rats with advanced liver fibrosis. aEuro cent Kinetic parameters at gadoxetate-enhanced MRI are correlated with hepatocyte transporter expression. aEuro cent Hepatocyte transport function can be assessed with compartmental analysis of gadoxetate-enhanced MRI. aEuro cent Compartmental analysis of gadoxetate-enhanced MRI might provide biomarkers in advanced liver fibrosis.
BACKGROUND: The anti-proliferative gene, PC3 (pheochromocytoma cell 3)/BTG2 (B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family. This study aimed to assess the effects of recombinant human hepatopoietin (HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma (HCC) at different stages of progression. METHODS: After a rat model of partial hepatectomy was established, we investigated gene expression within I hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system. The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile, the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization. RESULTS: The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation. HPO rapidly induced the expression of the genes c-fos, LRF-1, and PC3 in primary cultured rat hepatocytes, which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation. Positive BTG2 mRNA expression was detected in 71.19% (42/59) of the HCC samples and in 75% (3/4) of the normal liver tissue samples obtained from the region around the HCC tissues. PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation. CONCLUSIONS: Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/BTG2 gene. PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation. The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC, so PC3/BTG2 may play an important role in these processes. (Hepatobilimy Pancreat Dis Int 2009; 8: 288-293)
Background/Aims: Hepcidin is a liver-produced hormone that regulates systemic iron homeostasis. Hepcidin expression is stimulated upon iron overload or inflammation while iron deficiency, anemia and tissue hypoxia are negative regulators. We investigated the involvement of 2-oxoglutarate-dependent oxygenases, HIF-1 and other transcription factors in the hypoxic suppression of hepcidin. Methods: Northern blotting analysis and real time PCR were used to determine hepcidin mRNA levels in hepatoma cells and hepcidin promoter activity was measured using Huh7 cells transfected with suitable reporter constructs under various conditions. Results: Treatment of human cultured hepatoma cells with hypoxia or known inhibitors of 2-oxoglutarate-dependent oxygenases, such as the iron chelator desferrioxamine, cobalt or the 2-oxoglutarate analogue dimethyl-oxalylglycine significantly reduced hepcidin mRNA levels and down-regulated its gene promoter activity. This effect was not dependent on the HREs or other known putative response elements in the hepcidin promoter and was observed even under interleukin-6 treatment. Conclusions: 2-Oxoglutarate-dependent oxygenases are important to maintain high hepcidin mRNA expression in a HIF-1-independent manner. We suggest that modulation of oxygenase activity may be of therapeutic value in iron-related disorders. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
The anti-HER2 antibody trastuzumab (Herceptin (R)) has been used to treat patients with breast cancers that overexpress HER2. We have demonstrated that p27(Kip1) upregulation is one of the key events that cause G(1) arrest upon trastuzumab treatment. Here, we have examined the effect of trastuzumab on expression of CDK2, Rb, E2F, NPAT and histone H4 in breast cancer cells that overexpress HER2. Trastuzumab treatment dramatically inhibited the kinase activity and expression of CDK2, whereas the kinase activity and expression of CDK4 were not affected. Unlike the p27(Kip1) upregulation that occurs primarily through post-translational mechanisms, CDK2 was downregulated primarily at a transcriptional level as shown by Northern blotting and real-time RT-PCR analyses. With a decrease in CDK2 activity, trastuzumab decreased the kinase activity of cyclin E but had little effect on cyclin E protein level. Overexpression of wild-type cyclin E or its lower molecular weight forms did not influence the response to trastuzumab. Levels and activities of CDK6, cyclin A, and cyclin D1 were all suppressed by trastuzumab. As a result, trastuzumab inhibited Rb phosphorylation that associates with CDK2, cyclin E, CDK6, cyclin A, or cyclin D1. As predicted from these changes, trastuzumab decreased the DNA-binding activity of E2F, decreased the level of NPAT protein, and decreased the level of histone H4 mRNA. Blockade of the PI3K pathway with LY294002 produced similar effects to trastuzumab treatment on expression of each of these genes. Taken together, treatment of breast cancer cells that overexpress HER2 with the anti-HER2 antibody trastuzumab inhibits CDK2, Rb phosphorylation, E2F activity, NPAT, and histone H4 via PI3K signaling that are needed for both DNA and histone synthesis during progression from G1 phase to S phase of the cell cycle.
BACKGROUND. Men with biochemical recurrence of prostate cancer following local therapies often use natural supplements in an attempt to delay metastases and/or avoid the need for more aggressive treatments with undesirable side-effects. While there is a growing body of research into phytotherapeutic agents in this cohort, with some promising results, as yet no definitive recommendations can be made. This pilot study was undertaken to assess the feasibility of a fully-powered study to examine the effects of this phytotherapeutic intervention (containing turmeric, resveratrol, green tea and broccoli sprouts) on PSA doubling time in men with biochemical recurrence with a moderate PSA rise rate. METHODS. A double blind, randomized, placebo-controlled parallel trial was conducted with 22 men with biochemically recurrent prostate cancer and a moderate rise rate (PSA doubling time of 4-15 months and no evidence of metastases from conventional imaging methods). Patients were randomized to either the active treatment arm or placebo for 12 weeks. The primary endpoints were feasibility of study recruitment and procedures, and measurement of proposed secondary endpoints (prostate symptoms, quality of life, anxiety, and depression as measured on the EORTC QLQ-C30 and PR-25, the IPSS and HADS). Data were collected to estimate PSA-log slopes and PSA-doubling times, using a mixed model, for both the pre-intervention and post-intervention periods. RESULTS. Adherence to study protocol was excellent, and the phytotherapeutic intervention was well-tolerated, with similar numbers of mild-to-moderate adverse events in the active and placebo arms. Both the intervention and data collection methods were acceptable to participants. No statistical difference between groups on clinical outcomes was expected in this pilot study. There was between-subject variation in the PSA post treatment, but on average the active treatment group experienced a non-significant increase in the log-slope of PSA (pre-treatment doubling time = 10.2 months, post-treatment doubling time = 5.5 months), and the placebo group experienced no change in the log-slope of PSA (pre-treatment doubling time = 10.8 months, post-treatment doubling time = 10.9 months). CONCLUSION. The findings suggest that a fully powered study of this combination is feasible in men with biochemically recurrent prostate cancer and a moderate PSA rise rate. (C) 2017 Wiley Periodicals, Inc.
Hereditary fever syndromes (HFS) include a group of disorders characterized by recurrent self-limited episodes of fever accompanied by inflammatory manifestations occurring in the absence of infection or autoimmune reaction. Advances in the genetics of HFS have led to the identification of new gene families and pathways involved in the regulation of inflammation and innate immunity. The key role of several cytokine networks in the pathogenesis of HFS has been underlined by several groups, and supported by the rapid response of patients to targeted cytokine blocking therapies. This can be due to the direct effect of cytokine overproduction or to an absence of receptor antagonist resulting in dysbalance of downstream pro- and anti-inflammatory cytokine networks. The aim of this study was to present an overview and to discuss the major concepts regarding the cellular and molecular immunology of HFS, with a particular focus on their specific cytokine signatures and physiopathological implications. Based on their molecular and cellular mechanisms, HFS have been classified into intrinsic and extrinsic IL-1 beta activation disorders or inflammasomopathies, and protein misfolding disorders. This review integrates all recent data in an updated classification of HFS. (C) 2016 Elsevier Ltd. All rights reserved.
The virion host shutoff protein (vhs), encoded by the gene UL41, has RNase activity and is the key regulator of the early host shutoff response induced by type 1 herpes simplex virus. Despite low amino acid similarity, the vhs protein of the swine herpesvirus, pseudorabies virus (PrV), also exhibits RNase activity. However, the mechanism underlying the action of vhs remains undefined. Here, we report that the RNA degradation profile of PrV vhs is similar, but not identical, to that of type 1 herpes simplex virus vhs. Notably, the presence of a cap structure enhances both the degradation rate and the preferential targeting of the vhs protein towards the 3-end of the encephalomyocarditis virus internal ribosome entry site (IRES). Furthermore, type 1 herpes simplex virus vhs produces a simple degradation pattern, but PrV vhs gives rise to multiple intermediates. The results of northern blotting using probes recognizing various regions of the RNA substrate found that PrV vhs also cleaves downstream of the IRES region and this vhs protein overall shows 5 to 3 RNase activity. Moreover, addition of the translation initiation factors eIF4H and eIF4B significantly increased the RNase activity of recombinant PrV vhs against capped RNA. Nonetheless, these proteins did not fully reconstitute the IRES-directed targeting pattern observed for vhs translated in a rabbit reticular lysate system. The interaction between PrV vhs and eIF4H/eIF4B implies that the translation initiation machinery within the cell is able to stimulate the nuclease activity of PrV vhs. However, this process remains inefficient in terms of the IRES-targeting pattern.
Within Solanaceae, Nolana L. f. and Sclerophylax Miers are two genera that have deserved special attention because of their rare anatomical characteristics. However, they are poorly known from the cytogenetic perspective. In order to discuss their chromosome features in an evolutionary context, classical staining, chromomycin A(3)/4-6-diamidino-2-phenylindole (CMA/DAPI) fluorescent banding and in situ hybridisation (FISH) with probes for the 18-5.8-26S and the 5S rDNA loci were applied to root tips of germinating seeds. All the species presented the chromosome number 2n=24. Karyotypes were highly symmetric, with most chromosomes being metacentric and with a maximum of three submetacentric pairs in N. divaricata. The CMA/DAPI banding technique, assayed for the first time in Sclerophylax, showed CMA(+)/DAPI(-) bands associated with nucleolar organiser regions (NORs) in the first metacentric chromosome pair in each species. The FISH technique (applied to four species of Sclerophylax and, for the first time, in one species of Nolana) showed that the 18-5.8-26S loci coincide with CMA(+)/DAPI(-) bands. Three Sclerophylax species presented two pairs of 5S signals, whereas S. adnatifolia showed three. The rDNA loci resulted as asyntenic in Sclerophylax, but were localised in the same chromosome in N. divaricata. Despite the morphological peculiarities of Nolana and Sclerophylax, the chromosome number and karyotype features are consistent with the position of the two genera within the x=12 clade', while the number and position of rDNA loci established the chromosome rearrangements, suggesting different evolutionary pathways with respect to their closest relatives, Lycium and Jaborosa.
Novel hybrid nanostructures or nanocomposites are receiving increasing attention due to their newly evolved properties. In this work, alpha-Fe2O3 anchored to graphene oxide (GO) nanosheet (alpha-Fe2O3@GO) was synthesized through a facile hydrolysis process and its photo-catalytic performances and dtlrability in heterogeneous Fenton system were fully evaluated. The decolorization rates of methylene blue in alpha-Fe2O3@GO + H2O2 + UV system within a wide pH range were approximately 2.9-fold that of classical Degussa P25 TiO2 +UV and 2.4-fold that of alpha-Fe2O3 + H2O2 + UV. This enhanced decolorization of methylene blue (MB) in alpha-Fe2O3@GO + H2O2 + UV system were attributed to the unique incorporation of GO into the catalyst which not only mediated the morphology of active sites alpha-Fe2O3 nanoparticles but also offered high electron conductivity and electrostatic attraction between negatively charged GO with positively charged MB. High efficiencies of degradation were achieved on various surface charged organic pollutants (around 96-100%), such as cationic compounds of MB and rhodamine B (RhB), anionic compound Orange II (OII) and Orange G (OG), neutral compounds of phenol, 2-nitrophenol (2 -NP) and endocrine disrupting compound 17 beta-estradiol (E2). The dominant reactive oxygen species (ROS) responsible for decolorization, such as hydroxyl radicals ((OH)-O-circle) and superoxide anion radicals (O-2(circle-)) generated by activation of H2O2 on the surface of alpha-Fe2O3@GO were detected and quantified by free radical quenching methods. The possible degradation mechanism of MB involved the rupture of phenothiazine ring by desulfurization and the rupture of phenyl ring due to the attack of ROS, which was analyzed by LC/MS/MS. The reduction of MB and its intermediates was consistent with the decreasing trend of the acute toxicity towards luminous bacteria with the increasing irradiation time. The results lay a foundation for highly effective and durable photo-Fenton technologies for organic wastewater within wider pH ranges than the conventional photo-Fenton reaction.(C) 2017 Elsevier B.V. All rights reserved.
The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132male Sprague-Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP-9, MMP-2 and TIMP-1 levels and gene expression level were measured by ELISA and reverse transcription-quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP-9 levels of the experimental group were notably higher on postoperative days 5-7 compared with the control group. The MMP-9 gene expression of the experimental group was higher on postoperative days 3-7 compared with the control group. The TIMP-1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP-9 and the altered dynamic equilibrium between MMP-9 and TIMP-1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP-9 is a predictive marker of HO.
Human foamy virus (HFV) is a complex and unique retrovirus with the longest genomes among retroviruses that are used as vectors for gene therapy. Long non-coding RNAs (lncRNAs) are regarded as key regulators that are involved in diverse biological processes during viral infection. However, the role of lncRNAs in HFV infection remains unknown. In this study, we utilized next-generation sequencing to first characterize lncRNAs in 293T cells after HFV infection, evaluating length distribution, exon number distribution, volcano picture, and lncRNA class distribution. We identified 11,336 lncRNAs (4,729 upregulated lncRNAs and 6,588 down-regulated lncRNAs) and 61,367 mRNAs (30,133 upregulated mRNAs and 31,220 downregulated mRNAs), which were differentially expressed in the HFV-infected 293T cells. Subsequently, six differentially expressed lncRNAs characterized using RNA-seq were confirmed by quantitative real-time polymerase chain reaction assays. Interestingly, Gene Ontology (GO)/Gene Ontology Tree Machine (GOTM) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analyses indicated that positive regulation of interleukin 8 (IL8) production and cytokine-cytokine receptor interaction might be involved in the functional enrichment of lncRNAs. Moreover, cis-acting and trans-acting regulatory networks show that NR_028036 may target the fas gene in a cis-acting manner and that ENST00000354838 may target the IL18 gene in a trans-acting manner. Overall, these results not only provide novel insights into the relationship between HFV and lncRNAs in the host response to infection but also have implications for the future wider application of HFV as a vector.
A hydrokinetic smart grid (KSG) concept powered by modules of hydrokinetic microturbines arranged in rows is proposed in this work. A complete description of each module: mechanical design, hydropower characteristics, power electronics and control strategies have been included. A complete dynamic simulation of an example of a KSG has been performed. It considers microturbine modules, power loads, energy storage modules and a grid tie inverter that interface with the mains using a single connection. Additionally, the control and power stages of a hydrokinetic microturbine has been validated. The satisfactory technical results obtained in addition with the acceptable results of an investment analysis, encourage future implementations of KSGs.
This paper presents a computational platform for dynamic security assessment (DSA) of large electricity grids, developed as part of the iTesla project. It leverages high performance computing to analyze large power systems, with many scenarios and possible contingencies, thus paving the way for pan-European operational stability analysis. The results of the DSA are summarized by decision trees of 11 stability indicators. The platform's workflow and parallel implementation architecture is described in detail, including the way commercial tools are integrated into a plug-in architecture. A case study of the French grid is presented, with over 8000 scenarios and 1980 contingencies. Performance data of the case study (using 10 000 parallel cores) is analyzed, including task timings and data flows. Finally, the generated decision trees are compared with test data to quantify the functional performance of the DSA platform.
The invention of the microscope has been fundamental for the understanding of tissue architecture and subcellular structures. With the advancement of higher magnification microscopes came the development of various molecular biology tools such as Forster resonance energy transfer (FRET) and in situ proximity ligation assay (in situ PLA) to monitor protein interactions. Microscopy has become a commonly used method for the investigation of molecular events within the cell, for the identification of key players in signaling networks, and the activation of these pathways. Multiple approaches are available for functional analyses in single cells. They provide information not only on the localization of proteins at a given time point, but also on their expression levels and activity states, allowing us to pinpoint hallmarks of different cellular identities within tissues in health and disease. Clever solutions to increase the sensitivity of molecular tools, the possibilities for multiplexing, as well as image resolution have recently been introduced; however, these methods have their pros and cons. Therefore, one needs to carefully consider the biological question of interest along with the nature of the sample before choosing the most suitable method or combination of methods. Herein, we review a few of the most exciting microscopy-based molecular techniques for proteomic analysis and cover the benefits as well as the disadvantages of their use.
This study focuses on characterizing the effect of a high salt diet (HSD) on intestinal immunity and the risk of inflammatory bowel diseases (IBD). We found that mice on a HSD had an increased frequency of IL-17A producing cells in the intestinal lamina propria (LP) compared to mice on a normal diet (ND). Furthermore, most intestinal IL-17A producing cells were CD4(+)TCR beta(+) cells. A HSD increased the LP T helper 17 (Th17) responses in both the small and large intestines but did not increase the Th17 response of other gut-associated lymphoid organ. Although, HSD did not change the percentage of regulatory T (Treg) cells, HSD significantly inhibit secretion of IL-10 and the suppressive function of Treg cells. Moreover, we found that HSD exacerbates trinitrobenzenesulfonic acid (TNBS) induced colitis, and Th17 response was significantly increased in the colonic LP of HSD TNBS-treated mice compared with the ND TNBS-treated mice. This study demonstrates that HSD stimulates the intestinal Th17 response but inhibits the function of Treg cells. Moreover, HSD exacerbates TNBS induced mice colitis, suggesting that HSD disrupts the intestinal immunity and increases the risk of IBD.
The digital control of high speed Permanent Magnet Synchronous Motor (PMSM) is carried out as part of mass reduction for embedded systems. This paper focuses on improving the stability of high speed PMSM digital control. A study of the stability of the closed-loop system shows the importance of taking into account the constraints of digital control (delay and discrete characteristics) in the calculation of decoupling terms and inverse Park transformation. The proposed decoupling is done using the discrete model of the system and a prediction of the evolution of the currents during the delay. The voltage, calculated by vector control, is applied to the machine by a three-phase voltage-source Power Width Modulation PWM converter. This voltage is modified because the rotor reference d-q frame turns during the delay and the switching period. The voltage error caused by this rotation can be significant at high speeds and more generally when the ratio of the switching frequency over the electrical output frequency becomes too high. To stabilize the system, we suggest predicting the average electric angle that the motor will have during the application of the voltage vector. The efficiency is shown through a time simulation.
In sensor-node applications, the auxiliary power is drawn from the ac mains to supply the mixed-signal sensor components. There is therefore a need for low-cost, sub-1W, miniature non-isolated ac-dc down-converters. In this work, a new two-chip architecture is proposed to implement a high-voltage quasi-resonant buck converter with peak current-mode control. The current and voltage control loops are implemented in the high-side (HS) and low-side (LS) IC, respectively. Each IC includes a 700V power transistor, sensing and control circuits. The LS IC transmits the digital peak current command, along with mode selection information, to the HS IC using a low-power 20 MHz isolated communication interface. The architecture achieves a peak simulated efficiency of 85.6% when converting from 339 V to 12 V and allows the size of the input filter to be greatly reduced due to the current-mode operation. State-of-the- art UHV BCD technologies offer a unique opportunity to increase the level of integration and reduce the system cost in the targeted sensor node applications, despite the relatively poor figure-of-merit of the HV devices compared to discrete Silicon super-junction or GaN alternatives.
This paper describes the implementation of a load voltage observer into the control algorithms of a Rapid Capacitor Charger controlled by a digital signal controller (DSC) with a fast DSP core. A hybrid peak current mode control algorithm with digital control of the PWM signal and high speed analog current sensing is used to control the inverter of the charger. The DSC controller keeps the current loop stable using adaptive slope compensation. In addition to providing fast adaptive digital control of the current loop, the DSC can perform additional functions such as estimation of the voltage level of the load capacitor. This avoids the cost, bandwidth limitations and insulation challenges of a conventional HV-sensor. To evaluate the performance of the load voltage observer, we measured the output voltage with a laboratory grade HV probe to establish a reference to test the results of the digital algorithm.
This work presents a high-voltage (HV) operational amplifier (OPA). OPAs are widely used in signal conditioning circuits for industrial applications and integrated circuits (ICs). Particularly, in HV applications like BMS (battery management system), the signal conditioning circuits are always used to transfer voltage signal between HV domain and low voltage (LV) domain. Notably, the voltage from the HV domain could be as high as tens of volts, which might cause damages to regular silicon-based transistors. Nevertheless, since the resolution of the signal conditioning circuits depends on the output range and the operation range is determined by the input range, the input and output ranges of the signal conditioning circuits have been a key issue in the HV applications. We propose a rail-to-rail HV OPA to resolve these issues. The proposed design is implemented using 0.25 mu m 1-poly 3-metal 60 V BCD process. The core area is 0.809 x 0.303 mm(2). DC gain and unit-gain bandwidth of the proposed railto-rail HV OPA are measured to be 41 dB and 0.3 MHz, respectively. Finally, the proposed rail-to-rail HV OPA is proven on silicon to receive any signals between 0 and 30 V and transmit a signal in the range of [0.4, 29.6] V. (C) 2015 Elsevier Ltd. All rights reserved.
The multivariate location problem is addressed. The most familiar method to address the problem is the Hotelling test. When the hypothesis of normal distributions holds, the Hotelling test is optimal. Unfortunately, in practice the distributions underlying the samples are generally unknown and without assuming normality the finite sample unbiasedness of the Hotelling test is not guaranteed. Moreover, high-dimensional data are increasingly encountered when analyzing medical and biological problems, and in these situations the Hotelling test performs poorly or cannot be computed. A test that is unbiased for non-normal data, for small sample sizes as well as for two-sided alternatives and that can be computed for high-dimensional data has been recently proposed and is based on the ranks of the interpoint Euclidean distances between observations. Five modifications of this test are proposed and compared to the original test and the Hotelling test. Unbiasedness and consistency of the tests are proven and the problem of power computation is addressed. It is shown that two of the modified interpoint distance-based tests are always more powerful than the original test. Particularly, the modified test based on the Tippett criterium is suggested when the assumption of normality is not tenable and/or in case of high-dimensional data with complex dependence structure which are typical in molecular biology and medical imaging. A practical application to a case-control study where functional magnetic resonance imaging is used is discussed.
Higher education is understood as essential to enabling social mobility. Research and policy have centred on access to university, but recently attention has turned to the journey of social mobility itself - and its costs. Long-distance or extreme' social mobility journeys particularly require analysis. This paper examines journeys of first-in-family university students in the especially high-status degree of medicine, through interviews with 21 students at an Australian medical school. Three themes are discussed: (1) the roots of participants' social mobility journeys; (2) how sociocultural difference is experienced and negotiated within medical school; and (3) how participants think about their professional identities and futures. Students described getting to medical school the hard way', and emphasised the different backgrounds and attitudes of themselves and their wealthier peers. Many felt like imposters', using self-deprecating language to highlight their lack of fit' in the privileged world of medicine. However, such language also reflected resistance to middle-class norms and served to create solidarity with community of origin, and, importantly, patients. Rather than narratives of loss, students' stories reflect a tactical refinement of self and incorporation of certain middle-class attributes, alongside an appreciation of the worth their difference' brings to their new destination, the medical profession.
In this paper, a unified averaged modeling method is proposed to investigate the fast-scale period-doubling bifurcation of a full-bridge integrated buck-boost inverter with peak current control. In order to increase the resolution of the conventional classic averaged model to half the switching frequency, sample-and-hold effect of inductor current is absorbed into the averaged model, i.e. the proposed unified averaged model can capture the high-frequency dynamical characteristics of the buck-boost inverter, which is both an extension and a modification of conventional averaged model. Based on the unified mode, fast-scale bifurcation is identified, and the corresponding bifurcation point is predicted with the help of the locus movement of all the poles, and their underlying mechanisms are revealed. Detailed analysis shows that the occurrence of high-frequency oscillation means fast-scale bifurcation, while the occurrence of low-frequency oscillation leads to slow-scale bifurcation. Finally, it is demonstrated that the unified averaged model can provide not only a general method to investigate both the slow-and fast-scale bifurcations in a unified framework but also a quite straightforward design-oriented method which can be directly applicable.
ObjectivesMicroRNA-155 (miR-155) regulates T-cell differentiation and activation. It has also been associated with HIV infection. However, it remains unclear whether miR-155 is related to the T-cell response in HIV-infected individuals (e.g. T-cell activation and exhaustion). MethodsWe performed a cross-sectional study involving 121 HIV-1-infected patients on highly active antiretroviral therapy (HAART) and 43 HAART-naive patients. MiR-155 levels in the peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (PCR). T-cell immune activation, exhaustion, and homeostasis were measured by determining the expression of CD38, programmed death 1 (PD-1) and CD127 via flow cytometry. ResultsThe levels of miR-155 in total peripheral blood mononuclear cells, CD4 T cells and CD8 T cells from HIV-1-infected patients were increased (P < 0.01). Nonresponders and HAART-naive patients also exhibited a higher percentage of CD8(+)CD38(+) T cells and a lower percentage of CD4(+)CD127(+) and CD8(+)CD127(+) T cells (P < 0.05). We also found higher levels of PD-1 expression on the CD4(+) and CD8(+) T cells of HIV-1-infected patients (P < 0.05). ConclusionsOur findings suggest that miR-155 levels in the peripheral blood of HIV-1-infected patients are increased and associated with T-cell activation. Therefore, miR-155 is a potential biomarker of the immune response following HIV-1 infection.
A highly linear PGA with level shifter and class AB output stage for BLE receiver is reported in this paper. Both merits of degenerated PGA and operational amplifier based PGA are synthesized in proposed PGA. It is implemented in 0.18 mu m CMOS process and draws 290pA current from a supply of 1.8V when driving a capacitor load of 2p at the IF of 1MHz, while high SR up to 2.2 x 10(7) V/s is obtained. OIP3 of 40dBm is achieved under all gain modes due to the constant loop bandwidth. Proposed PGA has a gain range from 0dB to 14dB at the step of 2dB. The THD reaches 72.7dB at the frequency of 1MHz when proposed PGA outputs a 1.3Vpp differential voltage signal.
Conventional time series forecast models can hardly develop the inherent rules of complex non-linear dynamic systems because the strict assumptions they need cannot always be met in reality, whereas fuzzy time series (FTS) techniques can be used even the records of times series have uncertainty and instability since they do not need strict assumptions. In previous study of FTS, the process of aggregating the past observations and assigning proper weights of fuzzy logical relationship groups are ignored, which may lead to poor forecasting accuracy since they are important aspects in time series prediction and analysis where determination of future trends depends only on past observations. In this paper, a novel high-order FTS model is constructed to make time series forecasting. Specifically, by applying the harmony search intelligence algorithm, the optimal lengths of intervals are tuned. Moreover, regularly increasing monotonic quantifiers are employed on fuzzy sets to obtain the weights of ordered weighted aggregation. Simultaneously, the weights of right-hand side of fuzzy logical relationship groups are explored to compensate the presence of bias in the prediction. In the part of empirical analysis, the developed model was applied to predict three well-known time series: numbers of enrollment of Alabama University, TAIEX and electricity load demand of New South Wales and the results obtained were compared with several counterparts, including some old and recently developed models. Experimental results demonstrate that the developed model cannot only achieve higher accuracy of prediction, but also capture the fuzzy features and characters. (C) 2017 Elsevier B.V. All rights reserved.
Time-delays (dead time) are found in many processes in industrial practice. Time-delays are mainly caused by the time required to transport mass, energy and information. In many cases time-delay is caused by the effect produced by the accumulation of a large number of low-order systems. One of possibilities of control of such processes is their approximation by lower-order model with time-delay. The contribution is focused on the design of an algorithm for digital control of high order process that is approximated by a second-order model with time-delay. The controller algorithms use the digital modification of the linear quadratic (LQ) Smith predictor (SP). The LQ criterion was combined with pole assignment principle. These algorithms were applied to the control of a set of equal liquid cylinder atmospheric tanks.
Introduction: Emotion recognition, a social cognition domain, is impaired in people with schizophrenia and contributes to social dysfunction. Whether impaired emotion recognition emerges as a manifestation of illness or predates symptoms is unclear. Findings from studies of emotion recognition impairments in first-degree relatives of people with schizophrenia are mixed and, to our knowledge, no studies have investigated the link between emotion recognition and social functioning in that population.Methods: This study examined facial affect recognition and social skills in 16 offspring of parents with schizophrenia (familial high-risk/FHR) compared to 34 age- and sex-matched healthy controls (HC), ages 7-19.Results: As hypothesised, FHR children exhibited impaired overall accuracy, accuracy in identifying fearful faces, and overall recognition speed relative to controls. Age-adjusted facial affect recognition accuracy scores predicted parent's overall rating of their child's social skills for both groups.Conclusions: This study supports the presence of facial affect recognition deficits in FHR children. Importantly, as the first known study to suggest the presence of these deficits in young, asymptomatic FHR children, it extends findings to a developmental stage predating symptoms. Further, findings point to a relationship between early emotion recognition and social skills. Improved characterisation of deficits in FHR children could inform early intervention.
miRNAs have emerged as key regulators of gene expression in both plants and animals. These small (generally 21-22 nt) RNA molecules, originated from primary "hairpin" transcripts, can induce translational suppression or direct mRNA cleavage. Similar to regular mRNAs, the expression of miRNAs is highly regulated. Their expression pattern could provide critical clues to understanding miRNA functions. However, man), previously identified miRNA families have multiple paralogous loci. Within each family, different members are often closely related and sometimes give rise to identical miRNAs. This poses critical challenges in the analysis of individual miRNA genes. This chapter describes several methods that are commonly used for miRNA expression analysis, including high-throughput sequencing, microarrays, and briefly discusses qRT-PCR, northern blotting, and other approaches used for data validation.
The purposes of this study were to determine: (i) the extent of an acute session of high-intensity intermittent exercise (HIIE) followed by a concurrent strength session (Conc) on the increase of systemic inflammatory cytokines and chemokines, and (ii) whether eight weeks of high intensity interval training plus concurrent strength training alters the acute inflammatory response and immune status. Ten recreationally active males (aged 26.9 +/- 4.3 years) performed two experimental exercise sessions interspersed by eight weeks of HILT plus concurrent strength training. The experimental exercise session was composed of a 5-km run on a treadmill (1:1 at 100% of maximal aerobic speed (MAS)), and after 10 min of passive recovery, back squat exercises were performed (80% 1RM, four sets until exhaustion). Serum samples were collected after fasting, pre-HIIE, post-HIIE, Pre-Conc, Post-Conc, and 30 and 60 min postexercise session. The comparison between both concurrent exercise sessions was performed using repeated measure ANOVA, with the Bonferroni Post-hoc when necessary. Interleukin-6 (IL-6) presented a moment effect (F = 6.72; p < 0.05), with Post-Conc significantly higher than pre-HIIE, Post-HIIE, and 60 min, only a tendency was found between pre-HIIE and post-HIIE (difference =-5.99; p = 0.09). MCP-1 and IL-Ira did not present effects for condition, moment, or interaction. Interleuldn-10 (IL-10) presented both moment and interaction effects (F = 5.31 and 2.50; p = 0.005 and 0.036). Pre-Conc and Post-Conc were significantly higher than Pre-HIIE. The interaction between before and after eight weeks of concurrent training probably occurred at Post-Conc (11.42 +/- 3.09 pg mL(-1) and 8.88 +/- 1.29 pg mL(-1)). In addition, maintenance of immune function was observed. Therefore, HIIE and concurrent strength exercise lead to an increase in cytokines response, but eight weeks of training program promoted antiinflammatory response after an acute session of concurrent exercise. (C) 2016 Elsevier Ltd. All rights reserved.
Between the 24th of June and the 6th of July 2005, nine men came to Fort-deFrance emergency department (Martinique, French West Indies) with more or less pronounced pulmonary symptoms associated in two cases with skin lesions. Three weeks before these nine men performed work in a deserted house. The diagnosis of histoplasmosis was based on pulmonary sample mycological analysis (direct examination and culture), molecular biology and serological tests. Interrogatory and environmental investigations on the presumed place of exposition to H. capsulatum var. capsulatum spores allowed confirming how and where contamination took place. (C) 2016 Elsevier Masson SAS. All rights reserved.
Background: The planorbid snail Indoplanorbis exustus is the sole intermediate host for the Schistosoma indicum species group, trematode parasites responsible for cattle schistosomiasis and human cercarial dermatitis. This freshwater snail is widely distributed in Southern Asia, ranging from Iran to China eastwards including India and from the southeastern Himalayas to Southeast Asia southwards. The veterinary and medical importance of this snail explains the interest in understanding its geographical distribution patterns and evolutionary history. In this study, we used a large and comprehensive sampling throughout Indo-Malaya, including specimens from South India and Indonesia, areas that have been formerly less studied. Results: The phylogenetic inference revealed five highly divergent clades (genetic distances among clades: 4.4-13.9%) that are morphologically indistinguishable, supporting the assumption that this presumed nominal species may represent a cryptic species complex. The species group may have originated in the humid subtropical plains of Nepal or in southern adjacent regions in the Early Miocene. The major cladogenetic events leading to the fives clades occurred successively from the Early Miocene to the Early Pleistocene, coinciding with major periods of monsoonal intensification associated with major regional paleogeographic events in the Miocene and repeated climate changes due to the Plio-Pleistocene climatic oscillations. Our coverage of the Indo-Australian Archipelago (IAA) highlights the presence of a single clade there. Contrary to expectations, an AMOVA did not reveal any population genetic structure among islands or along a widely recognised zoogeographical regional barrier, suggesting a recent colonisation independent of natural biogeographical constraints. Neutrality tests and mismatch distributions suggested a sudden demographic and spatial population expansion that could have occurred naturally in the Pleistocene or may possibly result of a modern colonisation triggered by anthropogenic activities. Conclusions: Even though Indoplanorbis is the main focus of this study, our findings may also have important implications for fully understanding its role in hosting digenetic trematodes. The existence of a cryptic species complex, the historical phylogeographical patterns and the recent range expansion in the IAA provide meaningful insights to the understanding and monitoring of the parasites potential spread. It brings a substantial contribution to veterinary and public health issues.
OBJECTIVE: To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS: The study population consisted of patients met in an AIDS Outpatient Clinic in Sao Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS: Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B "e" antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B "e" antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B "e" antigen presented seroreversion or reactivation of this marker. CONCLUSIONS: Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.
The prevalence and associated factors of erectile dysfunction (ED) in Human Immunodeficiency Virus (HIV)-infected men remain controversial. The authors evaluated ED, clinical, and emotional variables in a group of 501 HIV-infected men in a cross-sectional 4-month observational study. ED was assessed using the International Index of Erectile Function-5 and emotional status using the Hospital Anxiety and Depression (HAD) questionnaire. Median age (interquartile range) was 42 (35, 48) years. Time since HIV diagnosis was 6.3 (2.6, 17.1) years, 92% were taking antiretroviral treatment and 81.8% had an HIV-RNA viral load <50 copies. The prevalence of ED was 58.5%. ED was mild in 30.1%, mild to moderate in 19.5%, moderate in 6.1%, and severe in 2.5%. ED medications were used by 19% of men. In the univariate analysis, the variables associated with all degrees of ED were older age, longer time since HIV diagnosis, higher scores in HAD, not taking efavirenz, taking etravirine, taking ritonavir, HIV/Hepatitis C Virus coinfection, and taking a protease inhibitor-containing regimen. For mild to moderate, moderate, and severe ED, the same variables were significant, as were lower nadir CD4 cell count, lower social support, taking atazanavir, concomitant conditions, and concomitant treatments. The variables that remained significant in the multivariate analyses, considering all degrees of ED or excluding mild ED were the following: older age and higher scores in HAD total. In summary, ED affected more than half of this cohort of well controlled HIV-infected men. Age and emotional status seemed to play a fundamental role in its presence.
Unlike in most of the world, HIV incidence in the former Soviet Union continues to rise. While international labor migration has been identified as a potentially important contributor to this trend, most attention has been focused on risks of male migrants themselves. This study uses recent household survey data to examine HIV-related perceptions and actions of migrants' left-behind wives in Armenia. Multivariate logistic regression analyses show that migrants' wives are significantly more likely to suspect their husbands of extramarital sex than are non-migrants' wives. The analyses detect greater worries about HIV infection and a higher likelihood of spousal communication on HIV matters among migrants' wives, compared to non-migrants' wives, but these differences are largely explained by the suspicion of husband's extramarital sex. Finally, no difference between the two categories of women in the probability of consistent condom use with husbands is found. These findings are interpreted within the context of patriarchal culture and unequal gender relations in Armenian society as they are further reinforced by male migration. Implications of these findings for policies to increase women's awareness of HIV risks associated with migration and their ability to reduce those risks are discussed.
This study investigated how HIV-related shame is associated with health-related quality of life (HRQoL) in older people living with HIV (PLHIV). Structural equation modeling tested whether HIV-related shame was associated with three dimensions of HRQoL (physical, emotional, and social well-being) and whether there were significant indirect associations of HIV-related shame with the three HRQoL dimensions via depression and loneliness in a sample of 299 PLHIV >= 50 years old. Results showed that depression and loneliness were key mechanisms, with depression at least partially accounting for the association between HIV-related shame and both emotional and physical well-being, respectively, and loneliness accounting for the association between HIV-related shame and social well-being. HIV-related shame appears to be an important correlate of HRQoL in older PLHIV and may provide a promising leveraging point by which to improve HRQoL in older PLHIV.
Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children. Methods: HIV-infected children500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen. Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm(3) (98-639), and HIV-RNA 5.2 log(10)copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with >= 1 PDR mutations, 30 children had a virus resistant to >= 1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 % CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to = 1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 % CI, 0.82-0.95; P < 0.001). Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.
Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by polymerase chain reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients. In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel mutations that display subtype-specific predominance or occurrence.
Prior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation. Caregivers discussed the effects of their own mental health on child well-being as primarily emotional and behavioral, and explained how looking after a child could bring distress, particularly when unable to provide desired care for sick children. Our findings suggest the need for investigation of the reciprocal effects of child sickness on caregiver wellness and for integrated programs that holistically address the needs of HIV-affected families.
Forkhead box O (FOXO)1, FOXO3, interferon regulatory factor (IRF)4, X-linked inhibitor of apoptosis protein (xIAP), and E74-like factor (ELF)4 have been described as important regulators of T cell functions and differentiation. However, whether these molecules are associated with HIV-1 disease progression is still unknown. In this study, we showed that the levels of FOXO3, IRF4, and xIAP mRNA in rapid progressors (RPs) were significantly higher than in HIV-negative healthy controls (HCs). Moreover, FOXO3 expression was positively correlated with HIV-1 viral load and CD4(+) T cell activation. Remarkably, increased CD4(+) and CD8(+) T cell activation was apparent in RPs compared with typical progressors and HCs. In addition, a profile of higher apoptosis, more CD8(+) T-EM cells, and fewer CD4(+) and CD8(+) Naive T cells were observed in early HIV infection patients with low CD4(+) T cell counts. Furthermore, in vitro, IRF4 and xIAP expression was enhanced in peripheral blood mononuclear cells from healthy people following T cell receptor stimulation. T cell activation was decreased by treatment with siRNA inhibiting FOXO3, IRF4, and xIAP. Our results show that significantly increased levels of FOXO3, IRF4, and xIAP mRNA in Chinese HIV-1-infected patients were related to T cell immune activation, implicating them as potential targets for developing new therapeutic avenues to slow down HIV-1 disease progression.
Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-based trajectory modeling followed by multinomial logistic regression was used to identify distinct trajectories and their association with baseline characteristics among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three trajectories were identified: (1) 72% never/sporadic opioid use (referent group), (2) 11% episodic use (associated with female sex, depression, drug-related diagnoses, antiretroviral therapy use, and undetectable HIV RNA), and (3) 16% chronic use (associated with older age, female sex, and mental health diagnoses). Overall, opioid prescription decreased substantially with longer time in HIV care among both episodic and chronic users.
CXCR4-using HIV-1 was previously shown to replicate more efficiently in a healthy donor-derived CD4(+) CD38(+) than in a CD4+ CD38(-) T-cell subset after stimulation with interleukin(IL)-4. Here, we identified 3 cellular genes, which were expressed to a higher level in an IL-4-stimulated CD38(-) subset. One of the 3 genes, RNF125/TRAC-1, was involved in the down-regulation of HIV-1 replication not only in cell lines, but also in peripheral blood mononuclear cells. RNFI25/TRAC-1 bears the RING finger domain, important for E3 ubiquitin protein ligase. Mutations in this domain of RNFl25/TRAC-1 led to the loss of HIV-1 down-modulatory activity, suggesting that E3 ligase activity is necessary. In addition, the results of Northern blotting and reporter gene analysis indicated that RNFl25/TRAC-1 function occurs at the viral transcription step. These results suggest that RNFI25/TRAC-1 could function to recruit host factor(s) controlling HIV-1 transcription to the ubiquitin-proteasome pathway. (C) 2007 Elsevier Inc. All rights reserved.
HLA-B*13:83 differs from HLA-B*13:01:01 by 2 nucleotide substitutions at positions 103 and 106.
HLA-B*52:01:27 differs from HLA-B*52:01:01 by a single nucleotide substitution at position 681 C>T.
HLA-C*01:109N differs from HLA-C*01:02:01 by a single nucleotide substitution at position 683 G >A.
Objective:The monitoring of septic shock induced immunosuppression has been proposed to identify patients who could benefit from specific immunoadjuvant therapies. Among potential biomarkers to monitor immunological status, functional testing remains the gold standard because it directly measures the capacity of a cell population to respond to an immune challenge. We investigated a new approach in intracellular staining for flow cytometry to measure tumor necrosis factor (iTNF) produced in vitro by monocytes in response to lipopolysaccharide.Design, Setting, Subjects, and Interventions:Observational study in intensive care unit and immunology laboratory of a university medical center. Sixteen septic shock patients and eight control subjects were included.Main Results:Monocyte iTNF was determined by flow cytometry in whole blood and completed in 2.5h according to a no-wash, no centrifuge procedure. Lipopolysaccharide challenge induced a tremendous expression of iTNF that was statistically more pronounced in controls than in patients. This was observed when results were expressed as medians of fluorescence intensity (median: 16.1 [IQR: 14.5-19.1] vs. 5 [4.0-8.0], P=0.0001) or as percentages of positive cells (99.7 [99.6-99.8] vs. 85 [74-97], P=0.0001). iTNF expression was correlated to monocyte HLA-DR expression in patients and controls.Conclusions:These preliminary results illustrate the feasibility of immune functional testing on a routine manner in septic shock patients. They now deserve to be widely assessed and validated in various intensive care unit conditions. This could be a major step to characterize the rapidly changing immune response overtime and thus permit personalized medicine.
Human leukocyte antigens (HLA) have been extensively studied as being antigen presenting receptors, but many aspects of their function remain elusive, especially their association with various autoimmune diseases. Here we discuss an illustrative case of the reciprocal relationship between certain HLA-DRB1 alleles and two diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly associated with HLA-DRB1 alleles that encode a five amino acid sequence motif in the 70-74 region of the DR beta chain, called the shared epitope (SE), while PV is associated with the HLA-DRB1*04:02 allele that encodes a different sequence motif in the same region. Interestingly, while HLA-DRB1*04: 02 confers susceptibility to PV, this and other alleles that encode the same sequence motif in the 70-74 region of the DR beta chain are protective against RA. Currently, no convincing explanation for this antagonistic effect is present. Here we briefly review the immunology and immunogenetics of both diseases, identify remaining gaps in our understanding of their association with HLA, and propose the possibility that the 70-74 DR beta epitope may contribute to disease risk by mechanisms other than antigen presentation.
Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy. Here, we investigated the impact of HLA-G on MDSCs accumulation and activation in pregnant women. We demonstrate that granulocytic MDSCs (GR-MDSCs) express receptors for HLA-G, namely immunoglobulin-like transcript (ILT) 2 and 4, and that ILT4-expression by GR-MDSCs is regulated during pregnancy. Stimulation with soluble HLA-G (sHLA-G) increased suppressive activity of GR-MDSCs, induced MDSCs from peripheral blood mononuclear cells (PBMCs) and led to phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and induction of indoleamine-2,3-dioxygenase (IDO) in myeloid cells. Effects of sHLA-G on MDSC accumulation were mediated through ILT4. These results suggest an interaction between MDSCs and HLA-G in humans as a potential mechanism for maintaining maternal-fetal tolerance. Modulating MDSC function during pregnancy via HLA-G might provide new opportunities for a therapeutic manipulation of immunological pregnancy complications.
Background: Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer. Methods: Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3 beta and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3 beta, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA. Results: HMBA increased p27(Kip1) expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3 beta in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3 beta. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3 beta inhibition. Conclusions: The results presented herein suggest that GSK-3 beta functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell differentiation.
Vitamin B-1 ( thiamine) is an essential cofactor for several key enzymes of carbohydrate metabolism. Mammals have to salvage this crucial nutrient from their diet to complement their deficiency of de novo synthesis. In contrast, bacteria, fungi, plants and, as reported here, Plasmodium falciparum, possess a vitamin B-1 biosynthesis pathway. The plasmodial pathway identified consists of the three vitamin B-1 biosynthetic enzymes 5-(2-hydroxy-ethyl)-4-methylthiazole (THZ) kinase (ThiM), 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP)/HMP-P kinase ( ThiD) and thiamine phosphate synthase (ThiE). Recombinant PfThiM and PfThiD proteins were biochemically characterised, revealing K-m(app) values of 68 mu M for THZ and 12 mu M for HMP. Furthermore, the ability of PfThiE for generating vitamin B1 was analysed by a complementation assay with thiE-negative E. coli mutants. All three enzymes are expressed throughout the developmental blood stages, as shown by Northern blotting, which indicates the presence of the vitamin B-1 biosynthesis enzymes. However, cultivation of the parasite in minimal medium showed a dependency on the provision of HMP or thiamine. These results demonstrate that the human malaria parasite P. falciparum possesses active vitamin B-1 biosynthesis, which depends on external provision of thiamine precursors.
The concept of functional neutrophil subsets is new and their clinical significance in malignancies is unknown. Our study investigated the role of CD16(dim) CD62L(high), CD16(high) CD62L(high) and CD16(high) CD62L(dim) neutrophil subsets in head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets may play different roles in immune-related activity in cancer, based on their profile, activation state and migration ability within a tumor site, which may be important in predicting cancer prognoses. Tumor biopsies and blood were obtained from newly diagnosed untreated HNSCC patients and healthy controls. Neutrophil subsets and their phenotype were characterized using flow cytometry. Isolated granulocytes were assessed for anti-tumor immune functions. Compared to controls HNSCC patients exhibited increased CD16(high) CD62L(dim) neutrophils in blood; this subset displayed a distinct phenotypes with high expression of CD11b and CD18. This subset was prone to migrate into the tumor facilitated by tumor-derived IL-8. Furthermore, IL-8 was also found to activate neutrophils and thereby promoting subset transition. Various assays demonstrated that activated CD16(high) CD62L(dim) neutrophils inhibited migration, proliferation and induced apoptosis of FaDu cancer cells. Neutrophil elastase detected in activated CD16(high) CD62L(dim) neutrophils and tumor biopsies suggested that CD16(high) CD62L(dim) neutrophils impart anti-tumoral activity via neutrophil extracellular traps. Furthermore, increased fraction of CD16(high) CD62L(dim) neutrophils was shown to correlate with an increased survival rate. Our study demonstrates the clinical relevance of the CD16(high) CD62L(dim) neutrophil subset, providing evidence for its increased migration capacity, its anti-tumor activity including increased NET formation and finally its correlation with increased survival in HNSCC patients. What's new? Evidence is growing for distinct neutrophil subsets with diverse roles in cancer immunology, but a clinical link remains to be established. Our study demonstrates the clinical relevance of the CD16(high) CD62L(dim) neutrophil subset in head and neck squamous cell carcinoma (HNSCC). Patients harbored an increased fraction of anti-tumorigenic CD16(high) CD62L(dim) neutrophils in the circulation compared to healthy controls. The subset had an enhanced capacity to elicit neutrophil extracellular traps (NETs) extrusion, and an increased fraction of CD16(high) CD62L(dim) neutrophils in the circulation correlated with increased survival. The findings demonstrate an anti-tumoral role of the CD16(high) CD62L(dim) neutrophil subset in HNSCC.
Home health care workers interventions have been implemented in western countries to improve health status of patients with respiratory diseases especially asthma and allergic illnesses. Twenty-six controlled studies dealing with prevention and control of these diseases through home environmental interventions were reviewed. After a comprehensive description of the characteristics of these studies, the effectiveness of each intervention was then evaluated in terms of participants' compliance with the intervention program, improvement of quality of the indoor environment, and finally improvement of health outcomes, in detailed tables. Limitations and biases of the studies are also discussed. Overall, this review aims at giving a toolbox for home health care workers to target the most appropriate measures to improve health status of the patient depending on his and/or her environment and disease. Only a case-by-case approach with achievable measures will warrant the efficacy of home interventions. This review will also provide to the research community a tool to better identify targets to focus in future evaluation studies of home health care workers action. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:66-79)
Substance use and depression are prevalent among mothers enrolled in home visiting programs and are significant risk factors for child maltreatment, yet most home visiting programs are staffed by workers who lack the training and clinical skills to address these risks. Emanating from one state network's interest in advancing its practice in this area, the current study surveyed 159 home visitors on their current practices, training, knowledge, and perceived self-efficacy, and perceived system- and client-level barriers regarding client substance use and depression. Home visitors reported managing maternal depression more extensively than substance use, though overall management of both risk areas was low. More training was associated with more extensive management of both risk domains, as was greater home visitor knowledge and self-efficacy. Implications for the development of strategies to improve home visitor management of client behavioral health risks, including enhanced skills-based training and supervision, are discussed.
This study examined the relationship between different areas of family need and the utilization of home-based, post-investigation services (HBPS) following a child protective services (CPS) investigation. The sample consisted of 2598 families with children who remained at home after an initial CPS investigation between July 2006 and April 2011. Family need was measured in three areas (concrete, clinical, and educational) using the Family Assessment Form (FAF), and families received one or more of the following HBPS: case management, concrete, educational, and clinical services. Pearson chi-square analyses were utilized to identify significant areas of needs to be included in a final multivariate logistic regression for each HBPS while controlling for demographic characteristics. Numerous areas of family need were associated with receipt of services intended to address those needs. Specifically, concrete need related to financial conditions was met with concrete services, educational need related to child development (an indicator of parenting need) was met with educational services, and clinical need related to interactions between caregivers (a potential indicator of domestic violence) was met with clinical services. In contrast, caregivers with concrete need related to living conditions were less likely to receive both educational and clinical services. Findings from the study highlight that matching concrete needs to related services is relatively straightforward but that the match between educational and clinical needs to respective services is more complex. We discuss the complexities of matching different areas of need and HBPS following a CPS investigation and the importance of "bridging services" to engage families at risk of maltreatment in additional prevention services. Published by Elsevier Ltd.
The aim of this review was to describe HIV prevalence in children and youth living on the street and subject to commercial sexual exploitation, and the studies' characteristics in terms of place, time, population, and sample design. This was a systematic review, not a meta-analysis, based on an article search in 10 electronic databases: Science Direct, MEDLINE, OVID, LILACS, Wiley InterScience, MD Consult, Springer Link, Embase, Web of Science, and Ebsco. A complementary search was also performed in the libraries of schools of public health and webpages of U.N. agencies, besides the reference lists from the selected articles. We selected observational studies focused on children and youth living on the street and subject to commercial sexual exploitation, ranging in age from 10 to 20 years, with the results for HIV prevalence rates. A total of 9,829 references were retrieved, of which 15 met the inclusion criteria and comprise this descriptive summary. Of these 15 articles, 12 were conducted in children and youth living on the street and three in children subject to commercial sexual exploitation. All 15 were cross-sectional studies. HIV prevalence in children and youth living on the street ranged from 0% in Dallas, USA and Cochabamba, Bolivia to 37.4% in St. Petersburg, Russia. In children and youth living subject to commercial sexual exploitation, prevalence ranged from 2% in Toronto, Canada to 20% in Kolkata, India. In conclusion, HIV infection is present in children and youth living on the street and subject to commercial sexual exploitation. Measures are needed for prevention, diagnosis, and treatment as a public health priority and an ethical responsibility on the part of governments and society.
The causes of homelessness are complex and poorly understood. This paper describes the homeless population in Santa Clara County, California in terms of Adverse Childhood Events, Traumatic Brain Injuries (TBIs), and family breakdown. Respondents reported severely traumatic childhoods; 78.7% grew up in a household with a person with drug or alcohol dependence and 64.6% endured psychological abuse as a child. Seventy-six percent of subjects recalled at least one TBI, 58.4% with loss of consciousness. Nineteen percent were in foster care as children and 40.2% reported having someone other than a parent as a primary caregiver. Fifty-three percent felt they had moved too much as children, and 37.5% had experienced homelessness as children. Santa Clara County has both the highest median income and the highest rate of unsheltered homelessness in the nation. Leaders and community members should work together to improve the lives of the homeless and to prevent another generation of homeless people.
The gender of the offender has been proved to be an important factor in judicial sentencing. In this study, we analyze the judgments of College students regarding perpetrators of familial homicides to evaluate the presence of these gender norms and biases in the larger society. The sample included 303 college students (54.8% female) enrolled in several social sciences and engineering courses. Participants were asked to read 12 vignettes based on real crimes taken from Portuguese newspapers. Half were related to infanticide, and half were related to intimate partner homicide. The sex of the offender was orthogonally manipulated to the type of crime. The results show that gender had an important impact on sentences, with males being more harshly penalized by reasons of perversity and women less penalized by reason of mental disorders. In addition, filicide was more heavily penalized than was intimate partner homicide. The results also revealed a tendency toward a retributive conception of punishment. We discuss how gender norms in justice seem to be embedded in society as well as the need for intervention against the punitive tendency of this population.
Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I (alpha 1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that honokiol may have therapeutic potential in mesangial proliferative GN.
BSMV (barley stripe mosaic virus) particles were obtained in a pure state from infected host plant tissues of Hordeum vulgare. The three genomic parities (alpha, beta and gamma) were amplified by PCR using specific primers for each particle; each was cloned. Partial sequence of the alpha, beta and gamma segments was determined for the Egyptian isolate of barley stripe mosaic virus (BSMV AE1). Alignment of nucleotide sequences with that of other known strains of the virus, BSMV type strains (CV17, ND18 and China), and the generation of phylogenetic trees was performed. A low level of homology was detected comparing 467 bp of the alpha and 643 bp of the segments to that of the other strains, and thus BSMV alpha and beta segments were in separate clusters. However, 1154 bp of the gamma segments of BSMV AE1 showed a high level of homology especially to strain BSMV ND18, as they both formed a distinct cluster. Northern blotting of pure BSMV AE1 virus and H. vulgare-infected tissue were compared using an alpha ND18 specific probe. Western blotting using antibodies specific for the coat protein (CP) and the triple gene block 1. (TGB1) protein, which are both encoded by the beta ND18 segment, still indicated a high level of similarity between proteins produced by BSMV ND18 and AEL We suggest that the BSMV AE1 isolate is a distinct strain of BSMV which reflects the genetic evolutionary divergence among BSMV strains and members of the Hordeivirus group.
Horizontal gene transfer (HGT) is pervasive in viruses and thought to be a key mechanism in their evolution. On the other hand, strong selective constraints against increasing genome size are an impediment for HGT, rapidly purging horizontally transferred sequences and thereby potentially hindering evolutionary innovation. Here, we explore experimentally the evolutionary fate of viruses with simulated HGT events, using the plant RNA virus Tobacco etch virus (TEV), by separately introducing two functional, exogenous sequences to its genome. One of the events simulates the acquisition of a new function though HGT of a conserved AlkB domain, responsible for the repair of alkylation or methylation damage in many organisms. The other event simulates the acquisition of a sequence that duplicates an existing function, through HGT of the 2b RNA silencing suppressor from Cucumber mosaic virus. We then evolved these two viruses, tracked the maintenance of the horizontally transferred sequences over time, and for the final virus populations, sequenced their genome and measured viral fitness. We found that the AlkB domain was rapidly purged from the TEV genome, restoring fitness to wild-type levels. Conversely, the 2b gene was stably maintained and did not have a major impact on viral fitness. Moreover, we found that 2b is functional in TEV, as it provides a replicative advantage when the RNA silencing suppression domain of HC-Pro is mutated. These observations suggest a potentially interesting role for HGT of short functional sequences in ameliorating evolutionary constraints on viruses, through the duplication of functions.
Current evidence is mixed on the role of progesterone and its metabolites in perinatal mood and anxiety disorders. We measured second and third trimester (T2 and T3) progesterone (PROG) and allopregnanolone (ALLO) levels by ELISA and postpartum depression (PPD) by clinician interview (DSM-IV criteria) in 60 pregnant women with a prior diagnosis of a mood disorder. Methods included multivariate and logistic regression with general linear mixed effect models. We found that, after adjustment, every additional ng/mL of T2 ALLO resulted in a 63% (95% CI 13% to 84%, p = 0.022) reduction in the risk of developing PPD. Our findings extend previous work connecting ALLO and depression within pregnancy, and indicate that the relationship between pregnancy ALLO and PPD is worth further exploration in a larger sample. (C) 2017 Elsevier Ltd. All rights reserved.
Some domestic animals are thought to be skilled at social communication with humans due to the process of domestication. Horses, being in close relationship with humans, similar to dogs, might be skilled at communication with humans. Previous studies have indicated that they are sensitive to bodily signals and the attentional state of humans; however, there are few studies that investigate communication with humans and responses to the knowledge state of humans. Our first question was whether and how horses send signals to their potentially helpful but ignorant caretakers in a problem-solving situation where a food item was hidden in a bucket that was accessible only to the caretakers. We then examined whether horses alter their behaviours on the basis of the caretakers' knowledge of where the food was hidden. We found that horses communicated to their caretakers using visual and tactile signals. The signalling behaviour of the horses significantly increased in conditions where the caretakers had not seen the hiding of the food. These results suggest that horses alter their communicative behaviour towards humans in accordance with humans' knowledge state.
C-reactive protein (CRP) is present at sites of inflammation including amyloid plaques, atherosclerotic lesions, and arthritic joints. CRP, in its native pentameric structural conformation, binds to cells and molecules that have exposed phosphocholine (PCh) groups. CRP, in its non-native pentameric structural conformation, binds to a variety of deposited, denatured, and aggregated proteins, in addition to binding to PCh-containing substances. In this study, we investigated the effects of H2O2, a prototypical reactive oxygen species that is also present at sites of inflammation, on the ligand recognition function of CRP. Controlled H2O2 treatment of native CRP did not monomerize CRP and did not affect the PCh binding activity of CRP. In solid phase ELISA-based ligand binding assays, purified pentameric H2O2-treated CRP bound to a number of immobilized proteins including oxidized LDL, IgG, amyloid peptide 1-42, C4b-binding protein, and factor H, in a CRP concentration- and ligand concentration-dependent manner. Using oxidized LDL as a representative protein ligand for H2O2-treated CRP, we found that the binding occurred in a Ca2+-independent manner and did not involve the PCh-binding site of CRP. We conclude that H2O2 is a biological modifier of the structure and ligand recognition function of CRP. Overall, the data suggest that the ligand recognition function of CRP is dependent on the presence of an inflammatory microenvironment. We hypothesize that one of the functions of CRP at sites of inflammation is to sense the inflammatory microenvironment, change its own structure in response but remain pentameric, and then bind to pathogenic proteins deposited at those sites.
Aggressive behavior is assumed to be associated with certain patterns of social information processing. While some theories link aggression to a tendency to interpret ambiguous stimuli as hostile (i.e., enhanced sensitivity to anger), others assume an insufficient ability to perceive emotional expressions, particularly fear. Despite compelling evidence to support both theories, no previous study has directly investigated the predictions made by these two accounts in aggressive populations. The aim of the current study was to test processing patterns for angry and fearful facial expressions in violent offenders (VOs) and healthy controls (CTLs) and their association with self-reported aggression and psychopathy scores. In Experiment 1, we assessed perceptual sensitivity to neutral-emotional (angry, fearful, happy) blends in a task which did not require categorization, but an indication whether the stimulus is neutral or emotional. In Experiment 2, we assessed categorization performance for ambiguous fearful-happy and angry-happy blends. No group differences were revealed in Experiment 1, while Experiment 2 indicated a deficit in the categorization of ambiguous fearful blends in the VO group. Importantly, this deficit was associated with both self-reported psychopathy and aggression in the VO, but not the CTL group. The current study provides evidence for a deficient categorization of fearful expressions and its association with self-reported aggression and psychopathy in VOs, but no support for heightened sensitivity to anger. Furthermore, the current findings indicate that the deficit is tied to categorization but not detection stages of social information processing.
The study of child abuse effects in conjunction with witnessing domestic violence has shown some influence of this dual exposure on the development of behavior problems in children. Thus, this study goal was to analyze the likely influence of dual exposure on adolescent drug use and antisocial behavior. The sample comprised 247 adolescents from juvenile offenders and foster care centers in the autonomous community of Galicia (Spain). Results showed that adolescents who have witnessed family violence had higher rates of aggressive and rule-breaking behaviors, theft and substance abuse, as well as more frequent use of alcohol, cannabis and cocaine, compared to: a) youths without history of family violence, b) adolescents maltreated in childhood, and c) those with dual victimization.
Hosts can utilize different types of defense against the effects of parasitism, including avoidance, resistance, and tolerance. Typically, there is tremendous heterogeneity among hosts in these defense mechanisms that may be rooted in the costs associated with defense and lead to trade-offs with other life-history traits. Trade-offs may also exist between the defense mechanisms, but the relationships between avoidance, resistance, and tolerance have rarely been studied. Here, we assessed these three defense traits under common garden conditions in a natural host-parasite system, the trematode eye-fluke Diplostomum pseudospathaceum and its second intermediate fish host. We looked at host individuals originating from four genetically distinct populations of two closely related salmonid species (Atlantic salmon, Salmo salar and sea trout, Salmo trutta trutta) to estimate the magnitude of variation in these defense traits and the relationships among them. We show species-specific variation in resistance and tolerance and population-specific variation in resistance. Further, we demonstrate evidence for a trade-off between resistance and tolerance. Our results suggest that the variation in host defense can at least partly result from a compromise between different interacting defense traits, the relative importance of which is likely to be shaped by environmental components. Overall, this study emphasizes the importance of considering different components of the host defense system when making predictions on the outcome of host-parasite interactions.
Background. Nasal colonization has gained attention as an effect modifier in Staphylococcus aureus vaccine trials, suggesting interference of carriage with T-cell immunity. Likewise, T-cell signals may be involved in regulating effectors of epithelial innate defense. Methods. Whole blood from 43 persistent carriers and 49 noncarriers was stimulated with viable S. aureus. T-helper type 1 (Th1), Th2, and Th17 cytokine expression was measured, compared between carrier groups, and linked with data on human beta-defensin 3 (hBD-3) messenger RNA (mRNA) in skin while adjusting for transcriptionally relevant promoter haplotypes. Results. Compared with carriers, stimulated whole blood from noncarriers contained on average 60% more interferon gamma mRNA (P = .031) and 19% less interleukin 17A (IL-17A) mRNA (P = .11), resulting in, on average, a 90% higher IFN-gamma to IL-17A mRNA ratio (P = .003). In a multivariable model, per duplication of the mRNA template, the risk of being a carrier increased by 93% for IL-17A (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.10-3.41; P = .023) and decreased by 35% for IFN-gamma (OR, 0.65; 95% CI, 0.47-0.91; P = .01). Independent of carriage and DEFB promotor haplotype, a 1-unit increase in the IFN-gamma to IL-17A mRNA ratio (mean +/- SD, 5.93 +/- 1.60) led to a 24% increase in hBD-3 transcription in experimentally wounded human skin (P = .003). Conclusions. A low Th1 to Th17 mRNA ratio increases the propensity for persistent S. aureus nasal colonization, with down-regulated hBD-3 transcription providing a potential link.
Protein-protein interaction is a vital process which drives many important physiological processes in the cell and has also been implicated in several diseases. Though the protein-protein interaction network is quite complex but understanding its interacting partners using both in silico as well as molecular biology techniques can provide better insights for targeting such interactions. Targeting protein-protein interaction with small molecules is a challenging task because of druggability issues. Nevertheless, several studies on the kinetics as well as thermodynamic properties of protein-protein interactions have immensely contributed toward better understanding of the affinity of these complexes. But, more recent studies on hot spots and interface residues have opened up new avenues in the drug discovery process. This approach has been used in the design of hot spot based modulators targeting protein-protein interaction with the objective of normalizing such interactions. (c) 2016 The Authors. Production and hosting by Elsevier B. V. on behalf of King Saud University. This is an open access article under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Housekeeping genes are widely used as internal controls for gene expression normalization for western blotting, northern blotting, RT-PCR, etc. They are generally thought to be expressed in all cells of the organism at similar levels because it is assumed that these genes are required for the maintenance of basic cellular function as constitutive genes. However, real-time RT-PCR experiments revealed that their expression may vary depending on the developmental stage, type of tissue examined, experimental condition, and so on. To date, no histological data on their expression are available for embryonic development. In the present study, we compared the histological expression profile of two commonly used housekeeping genes, GAPDH and beta-actin, in the developing chicken embryo by using section and whole mount in situ hybridization supplemented by RT-PCR. Our results show that neither GAPDH mRNA nor beta-actin mRNA is expressed in all cell types or tissues at high levels. Strikingly, expression levels are very low in some organs. Moreover, the two genes show partially complementary expression patterns in the liver, the vascular system and the digestive tract. For example, GAPDH is more strongly expressed in the liver than beta-actin, but at lower levels in the arteries. Vice versa, beta-actin is more strongly expressed in the gizzard than GAPDH, but it is almost absent from cardiac muscle cells. Researchers should consider these histological results when using GAPGD and beta-actin for gene expression normalization in their experiments.
Background/Aims: Sexual differences in the transcript levels of various genes including the hepatic isoforms of cytochrome P450 have been extensively studied. Expression of these sexual dimorphic genes have been quantified by Northern blotting, nuclear run on assays and reverse transcriptase-polymerase chain reaction (RT-PCR) methods using numerous housekeeping genes to normalize results. Earlier reports apparently assumed that these internal controls were sex-independent. We have studied sex differences in the expression levels of seven different commonly used housekeeping genes. Methods: We have used quantitative and semiquantitative RT-PCR to monitor the levels of hepatic mRNAs in intact and hypophysectomized male and female rats. Results: We have observed sex-dependent expression of the commonly used housekeeping genes tubulin, cyclophilin, tyrosine aminotransferase, beta-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S and one unconventional housekeeping gene, that is, hypoxia inducing factor-1 alpha, in the livers of intact male and female rats. With the exception of glyceraldehyde-3-phosphate dehydrogenase and 18S which were female-predominant (P < 0.01), the five other genes were found to be expressed at significantly (P < 0.01) higher concentrations in the livers of intact male rats. Similar to findings in which hypophysectomy eliminates sexual dimorphisms in cytochromes P450 expression, of the five housekeeping genes examined, cylophilin, tyrosine aminotransferase, glyceraldehyde-3-phosphate dehydrogenase, beta-actin, and 18S, all lost their sex-dependent expression following pituitary ablation. Conclusionds: Our data suggest that expression levels of these commonly measured housekeeping genes (structural and metabolic) are not constant, but rather are directly or indirectly regulated by sex-dependent hormones, compromising their application as normalizing controls. (c) 2005 Blackwell Publishing Asia Pty Ltd.
Current sources with Howland topology made with operational amplifier are often used for sensors that requires constant current polarization, for bioimpedance measuring, actuators driving systems and so on. Theoretical determination of overall performances for this circuits is generally known. This paper presents a practical method for real output impedance determining of such current sources based on performing two simple measurements. The results is according with the measurements on the practical circuit. Using the TL084 circuit the frequency cut-off was 250 KHz but using one other circuit as THS3201 the cut-off frequency was 20MHz.
MicroRNAs (miRNA), small noncoding RNAs, affect a broad range of biological processes, including tumorigenesis, by targeting gene products that directly regulate cell growth. Human polynucleotide phosphorylase (hPNPase(old-35)), a type I IFN-inducible 3'-5' exoribonuclease, degrades specific mRNAs and small noncoding RNAs. The present study examined the effect of this enzyme on miRNA expression in human melanoma cells. miRNA microarray analysis of human melanoma cells infected with empty adenovirus or with an adenovirus expressing hPNPase(old-35) identified miRNAs differentially and specifically regulated by hPNPase(old-35). One of these, miR-221, a regulator of the cyclin-dependent kinase inhibitor p27(kip1), displayed robust down-regulation with ensuing up-regulation of p27(kip1)by expression of hPNPase(old-35), which also occurred in multiple human melanoma cells upon IFN-beta treatment. Using both in vivo immunoprecipitation followed by Northern blotting and RNA degradation assays, we confirm that mature miR-221 is the target of hPNPase(old-35). Inhibition of hPNPase(old-35) by shRNA or stable overexpression of miR-221 protected melanoma cells from IFN-beta-mediated growth inhibition, accentuating the importance of hPNPase(old-35) induction and miR-221 down-regulation in mediating IFN-beta action. Moreover, we now uncover a mechanism of miRNA regulation involving selective enzymatic degradation. Targeted overexpression of hPNPase(old-35) might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma.
Background: The highly pathogenic porcine reproductive and respiratory syndrome virus (HP- PRRSV) continues to pose one of the greatest threats to the swine industry. M protein is the most conserved and important structural protein of PRRSV. However, information about the host cellular proteins that interact with M protein remains limited. Methods: Host cellular proteins that interact with the M protein of HP- PRRSV were immunoprecipitated from MARC145 cells infected with PRRSV HuN4-F112 using the M monoclonal antibody (mAb). The differentially expressed proteins were identified by LC-MS/MS. The screened proteins were used for bioinformatics analysis including Gene Ontology, the interaction network, and the enriched KEGG pathways. Some interested cellular proteins were validated to interact with M protein by CO-IP. Results: The PRRSV HuN4-F112 infection group had 10 bands compared with the control group. The bands included 219 non-redundant cellular proteins that interact with M protein, which were identified by LC-MS/MS with high confidence. The gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway bioinformatic analyses indicated that the identified proteins could be assigned to several different subcellular locations and functional classes. Functional analysis of the interactome profile highlighted cellular pathways associated with protein translation, infectious disease, and signal transduction. Two interested cellular proteins-nuclear factor of activated T cells 45 kDa (NF45) and proliferating cell nuclear antigen (PCNA)-that could interact with M protein were validated by Co-IP and confocal analyses. Conclusions: The interactome data between PRRSV M protein and cellular proteins were identified and contribute to the understanding of the roles of M protein in the replication and pathogenesis of PRRSV. The interactome of M protein will aid studies of virus/host interactions and provide means to decrease the threat of PRRSV to the swine industry in the future.
Dysregulated expression of oncogenic types of E6 and E7 is necessary for human papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ hybridization (ISH) assay covering 18 common high-risk types ("HR-RISH,"aka HR-HPV RNA18 ISH) has not been extensively studied in the anogenital tract or validated on automated technology. We herein compare HR-RISH to DNA polymerase chain reaction (PCR), p16 immunohistochemistry, and a previously available HPV DNA ISH assay in HPV-related anogenital and head and neck (H&N) neoplasia. A total of 102 squamous intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3, 9 VIN3)/invasive squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well as 10 normal and 15 reactive cervix samples were collected. HRRISH, DNA ISH, and p16 immunohistochemistry were performed on whole formalin-fixed, paraffin-embedded sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed. RNA and DNA ISH assays used automated systems. HR-HPV PCR was performed on morphology-directed formalin-fixed, paraffin-embedded punches. HR-RISH was Z97% sensitive for PCR+and p16+neoplasia, as well as morphologically defined anogenital high grade squamous intraepithelial lesion/invasive squamous cell carcinoma. HR-RISH was also positive in 78% of anogenital low grade squamous intraepithelial lesion, including 81% of CIN1. Furthermore, a subset of PCR-negative/invalid and p16-negative lesions was positive for HR-RISH. Only 1 problematic reactive cervix sample and no normal cervix samples stained. These results demonstrate that HR-RISH is a robust method for the detection of HR-HPVrelated neoplasia and provides insight into HPV pathobiology.Performance meets or exceeds that of existing assays in anogenital and H&N lesions and may play a role in resolving diagnostically challenging CIN1 versus reactive cases.
Decentralized energy supply is a frequently discussed topic in German industry, caused by continuously rising energy prices. This study assesses configurations of hybrid renewable energy systems (HRES) with regard to their ability to decrease a company's energy supply costs. We apply mixed-integer linear programming (MILP) to optimize an electricity and heat supply system with the aim of minimizing annual costs and perform energy system optimizations for a sample of three case studies and 363 virtual companies. Our results show that systems consisting of grid supply, combined heat and power plants (CHP), heat storage facilities and, in some cases, photovoltaics can lower the sample companies' annual energy costs by an average of 8.3%, including annualized investments. For a time frame of 20 years, the average internal return rate of the HRES investments is 29.8%. This work expands the body of literature on HRES optimizations by shifting the research focus from household to industrial supply. Our model can support corporate investment decisions on decentralized supply facilities. (C) 2017 Published by Elsevier Ltd.
Heat shock factor 1 (HSF1) is the major heat shock transcription factor and plays an essential role in mediating the cellular response to physiological and environmental stress. We found that LPS-induced expression of the granulocyte-colony stimulating factor (G-CSF) gene was upregulated in HSF1 knock-out (HSF1(-/-)) mice using a gene array. In order to determine whether and how HSF1 regulates the induced expression of G-CSF, mRNA, and protein levels of G-CSF were detected by Northern blotting and ELISA, the promoter of G-CSF was analyzed with an online transcription element search system and the transcriptional activity of the G-CSF promoter was analyzed by EMSA and a reporter gene assay. The results showed that transcription and protein secretion of G-CSF induced by LPS are both inhibited by HSF1. Three high affinity binding sites for NF-IL6/CCAAT enhancer binding protein beta, but no heat shock element, were identified in the core promoter of G-CSF. The DNA-binding capability of NF-IL6 to the G-CSF promoter was reinforced by LPS but not influenced by heat shock or HSF1. However, HSF1 was observed to bind to the binding sites of NF-IL6 in the G-CSF promoter. The transcriptional activity of the G-CSF promoter was enhanced by LPS or NF-IL6 and inhibited by HSF1 in a dose dependent manner. We conclude that HSF1 regulates expression of G-CSF through binding to the NF-IL6-binding element.
The cDNA of Crassostrea gigas HSP70 was cloned and rapid amplification of cDNA (RACE) techniques were used. The full length of HSP70 cDNA was 2045 bp, consisting of a 5' terminal untranslated region (UTR) of 80 bp, a 3' terminal UTR 146 bp, and an open reading frame (ORE) of 1829 bp encoding deduced 620 amino acids. The HSP70 cDNA contained HSP70 family signatures, ATP-GTP binding site motif, tetrapeptide (GGMP) and conserved carboxyl terminal region (EEVD) at C-terminal of deduced amino acid sequence. BLAST analysis revealed that the HSP70 gene has an extreme similarity of 98.9% with C. gigas (AF144646). Northern blotting was used to examine the expression of HSP70 mRNA in the gill tissue of the oyster obtained from surface, middle and bottom layers. The HSP70 mRNA observed the samples taken from middle and bottom layers in September and February, but samples from the surface layer did not find a signal intensity of HSP70 mRNA transcript. Consequently, it seems that the oyster occurring middle and bottom layer have been stressed during the period of summer and winter, which is associated with the massive mortality in Gamak bay.
Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h; P < 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported < 4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h; P < 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h; P = 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.
AIM: To investigate the effect of HtrA1 on the proliferation, migration and apoptosis of human retinal pigment epithelium (RPE) cells in the light injured model, as well as the expression of the apoptosis related molecules. METHODS: The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1 expression. Subsequent expression of HtrA1 was determined by real-time polymerase chain reaction (RTPCR) and Western blot, respectively. Changes in cell proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue-light-irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were significantly reduced both at mRNA and protein levels (P<0.05) after siRNA treatment. Bcl-2 expression significantly increased in blue-light irradiated ARPE-19 cells after siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may inhibit the proliferation, migration and apoptosis of ARPE-19 cells in light injured model. Moreover, HtrA1 suppression in blue-light irradiated ARPE-19 cells may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3, and up regulation of Bcl-2 expression.
Surface characteristics and cellular response to titanium surfaces that had been implanted with calcium and magnesium ions using plasma immersion ion implantation and deposition (PIIID) were evaluated. Three different titanium surfaces were analyzed: a resorbable blast media (RBM) surface (blasted with hydroxyapatite grit), a calcium ion-implanted surface, and a magnesium ion-implanted surface. The surface characteristics were investigated by scanning electron microscopy (SEM), surface roughness testing, X-ray diffraction (XRD), and Auger electron spectroscopy (AES). Human bone marrow derived mesenchymal stem cells were cultured on the 3 different surfaces. Initial cell attachment was evaluated by SEM, and cell proliferation was determined using MTT assay. Real-time polymerase chain reaction (PCR) was used to quantify osteoblastic gene expression (i.e., genes encoding RUNX2, type I collagen, alkaline phosphatase, and osteocalcin). Surface analysis did not reveal any changes in surface topography after ion implantation. AES revealed that magnesium ions were present in deeper layers than calcium ions. The calcium ion- and magnesium ion-implanted surfaces showed greater initial cell attachment. Investigation of cell proliferation revealed no significant difference among the groups. After 6 days of cultivation, the expression of RUNX2 was higher in the magnesium ion-implanted surface and the expression of osteocalcin was lower in the calcium ion-implanted surface. In conclusion, ion implantation using the PIIID technique changed the surface chemistry without changing the topography. Calcium ion- and magnesium ion-implanted surfaces showed greater initial cellular attachment.
Objective: To review contemporary knowledge of the hCG molecule, its isoforms and the importance of glycosylation. Biologic variants and glycoforms of hCG have different biological activities and functions related to the control of menstrual cycle, conception, gestation as well as gynaecologic and non-gynaecologic malignancies. Design: A review. Setting: Department of Obstetrics and Gynaecology, University Hospital Olomouc. Methods: To present own experience and an overview of recent literature in molecular biology, clinical biochemistry and clinical practice. Conclusion: Recent knowledge of the role of hCG glycosylation in physiologic and pathologic events in female organism will provide a better understanding of regulation of processes like ovulation (co-operation of pituitary hCG with LH), implantation and hemochorial placentation (invasivity of hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important for the prediction of certain pathologies of pregnancy, prenatal screening of inborn errors (free beta hCG) as well as in the treatment of infertility.
Background. DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. Methods. A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. Results. A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P=.01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P=.04), although no association was found at 6 months of age. Conclusions. A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.
Background: It has been predicted that the UL31 gene originates from the positive strand of the human cytomegalovirus (HCMV) genome, whereas the UL30 and UL32 genes originate from the complementary strand. Except for the UL32 gene, the transcription of this gene region has not been investigated extensively. Methods: Northern blotting, cDNA library screening, RACE-PCR, and RT-PCR were used. Results: At least eight transcripts of the antisense orientation of UL31 were transcribed from the UL30-UL32 region during the late phase of HCMV infection. The 3' coterminus of these transcripts was located within the predicted UL30 gene. The longest 6.0-kb transcript was initiated upstream of the predicted UL32 gene. Other transcripts were derived from the predicted UL30 and UL31 gene region. Except for the previously predicted UL32 open reading frame (ORF), three novel ORFs, named UL31anti-1, UL31anti-2 and UL31anti-3, were located in the transcripts from the UL31anti-UL32 transcription unit. No transcription was found in UL31. Conclusion: A family of novel 3' coterminal transcripts was transcribed from the UL30-UL32 gene region.
Objective: To study the mRNA expression of the two leucine-rich repeat-containing G-protein-coupled receptors LGR-4 and LGR-5 and the mRNA and protein expression of LGR-7, the relaxin receptor, in the human cyclic endometrium. Design: Retrospective study. Setting: Department of Anatomy and Reproductive Biology, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Germany. Method(s): LGR-4, -5, and -7 mRNA expression was assessed by semiquantitative and real time reverse transcription-polymerase chain reaction in the endometrium of premenopausal women (n = 26) and cultured primary endometrial epithelial cells and fibroblasts (n = 3). Transcript size was determined by Northern blotting. LGR-7 protein expression was assessed by immunohistochemistry. Result(S): The mRNA of LGR-4, LGR-5, and LGR-7 was expressed constitutively throughout the menstrual cycle in the endometrium, and characterized by substantial differences in expression levels of individual women. LGR-7 immunostaining was detected in the epithelium of the functional layer throughout the cycle, with lowest staining in the midproliferative phase. Furthermore, individual stromal cells of the functional layer and the stroma of the basal layer showed LGR-7 immunostaining. Conclusion(S): Endometrial expression of the mRNA of orphan receptors LGR-4 and LGR-5 implies that the endometrium is potentially influenced by as yet unknown mediators, which are possibly involved in fertility control. Furthermore, we confirmed constitutive endometrial mRNA expression of LGR-7, the classical relaxin receptor, and demonstrated specific LGR-7 immunostaining of different endometrial cell types, which suggests a physiological role of relaxin in the human endometrium.
Background. Seasonal influenza is responsible for high annual morbidity and mortality worldwide, especially in elderly patients. The aim of the study was to analyse the epidemiological, clinical and prognostic features of influenza in octogenarians and nonagenarians admitted to a general hospital, as well as risk factors associated with mortality. Methods. Retrospective, cross-sectional, descriptive study in patients admitted and diagnosed with influenza by molecular biology in the General University Hospital of Alicante from 1 January to 31 April 2015. Results. A total of 219 patients were diagnosed with influenza in the study period: 55 (25.1%) were= 90 years. Most flu episodes were caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80 or over (adjusted odds ratio [ORa] 9.2, 95% confidence interval [CI] 1.65-51.1), those who had acquired the flu in a long-term care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00). Conclusions. Seasonal influenza is a serious problem leading to elevated mortality in octogenarian and nonagenarian patients admitted to a general hospital.
Background: The human leukocyte antigen (HLA) system plays critical roles in regulating immune responses to various vaccines. This study aimed to evaluate the association of HLA class II gene polymorphisms and the long-term duration of anti-HBs response in children vaccinated against hepatitis B during infancy. Methods: Totally 297 children 5-7 years after the completion of primary vaccination against hepatitis B in infancy, without booster immunization or natural resolved infection, were enrolled. Of them, 86 children with anti-HBs= 10 mIU/ml were defined as long-term responders. Ten alleles in HLA-DR and -DQ subregions were detected by polymerase chain reaction with sequence-specific primers. Results: The frequency of HLA-DQB1*0401 was 15.1% in the long-term non- or hypo-responder group, relatively higher than 7.6% in the long-term responder group (OR = 2.17, 95% CI 1.01-4.73), however, the difference had no statistical significance after Bonferroni correction (P = 0.470). The frequencies of seven HLA-DRB1 alleles, including (*)01, (*)03, (*)04, (*)07, (*)08, (*)11, and (*)1301/1302, and two HLA-DQB1 alleles, including (*)0201 and (*)0501, were each similarly distributed in the long-term non- or hypo responders and responders respectively. Conclusion: None of the ten HLA class II gene alleles previously reported to be related with short-term antibody response to hepatitis B vaccine is associated with the long-term antibody response after vaccination during infantile. (C) 2017 Elsevier Ltd. All rights reserved.
A sensitive and rapid sandwich immunoassay (IA) was developed for human lipocalin-2 (LCN2) by functionalizing a KOH-treated polystyrene microtiter plate with multiwalled carbon nanotubes (MWCNTs) dispersed in 3-aminoproyltriethoxysilane (APTES). The significantly increased surface area due to the presence of MWCNTs led to a high immobilization density of 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide (EDC) activated anti-LCN2 capture antibodies (Ab). The anti-LCN2 Ab-bound MTPs were stable for 6 weeks when stored in 0.1 M PBS, pH 7.4 at 4 degrees C. The IA detects LCN2 from 0.6 to 5120 pg mL(-1) with a limit of detection (LOD) and limit of quantification (LOQ) of 0.9 pg mL(-1) and 6 pg mL(-1), respectively. The assay offered similar to 50-fold lower LOD and similar to 3-fold faster IA, compared to a commercial sandwich enzyme-linked immunosorbent assay kit. (C) 2016 Elsevier B.V. All rights reserved.
The profound influence of ATP-binding cassette (ABC) transporters on the disposition of numerous drugs has led to increased interest in characterizing their expression profiles in various epithelial and endothelial barriers. The present work examined the presence and functional activity of five ABC efflux proteins, i.e., MRP 1-5, in freshly isolated human nasal epithelial cells and two in vitro models based on the human RPMI 2650 cell line. To evaluate the expression patterns of MRP1, MRP2, MRP3, MRP4, and MRP5 at the mRNA and protein levels in the ex vivo model and the differently cultured RPMI 2650 cells, reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and indirect immunofluorescence staining were used. The functionality of the MRP transporters in the three models was assessed using efflux experiments and accumulation assays with the respective substrates and inhibitors. The mRNA and protein expression of all selected ABC transporters was detected in excised human nasal mucosa as well as in the corresponding cell culture models. Moreover, the functional expression of the MRP transport proteins was demonstrated in the three models for the first time. Therefore, the potential impact of multidrug resistance-associated proteins 1-5 on drug disposition after intranasal administration may be taken into consideration for future developments. The specimens of human nasal turbinate exhibited slightly lower efflux capacities of MRP1, MRP3, and MRP5 in relation to the submerged and ALI-cultured RPMI 2650 cells, but showed a promising comparability to both in vitro models concerning the activity of MRP2 and MRP4. In this regard, the different RPMI 2650 cell culture models will be able to provide useful experimental data in the preclinical phase to estimate the interaction of particular efflux transporters with drug candidates for nasal application.
A novel approach for stem cell generation is the attempt to induce conversion of the adult somatic cells into pluripotent stem cells so called induced pluripotent stem cells (iPSCs) by introducing specific transcription factors. iPSCs have two essential cell characteristics, they are pluripotent and posses long term cell-renewal capacity. Additionally, iPSCs can be derived from patient-specific somatic cells, thus bypassing ethical and immunological issues. The aim of our study was to reprogram long-term cryopreserved human neonatal fibroblasts by new method using lipid nano-particle technology (Lipofectamine 3000 reagent transfection system) in combination with Epi 5 reprogramming vectors. Obtained iPSCs were characterized by several sophisticated methods of molecular biology and microscopy. Distinct colonies of iPSCs started to appear by day 20 after reprogramming. The presence of iPSCs colonies was proved by alkaline phosphatase (AP) live staining. After manual picking the colonies and their subsequent passaging, they did not lose ability to form embryoid bodies, they were positive for AP, Tra-1-60, and SSEA-5. Moreover, obtained iPSCs expressed pluripotency markers Oct4, Sox2 and Nanog, and the expression levels of chondrogenic, osteogenic and adipogenic markers were significantly higher in comparison to control (p < 0.05). In summary, we have demonstrated that long-term cryopreserved human neonatal fibroblasts can be reprogrammed into iPSCs and after further analysis concerns on their biological safety they may be used as patient-specific cells in regenerative medicine.
Rapid methods for the detection and clinical treatment of human norovirus (HuNoV) are needed to control foodborne disease outbreaks, but reliable techniques that are fast and sensitive enough to detect small amounts of HuNoV in food and aquatic environments are not yet available. We explore the interactions between HuNoV and concanavalin A (Con A), which could facilitate the development of a sensitive detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange (HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine alanine residues (mCon AM), the affinity for HuNoV (GII.4) diminishes, demonstrating that this Ca2+ and Mn2+ coordinated region is responsible for the observed virus-protein interaction. The mutated carbohydrate binding region of Con A (mCon A(CBR)) does not affect binding affinity significantly, indicating that MCR of Con A is a major region of interaction to HuNoV (GII.4). The results further contribute to the development of a HuNoV concentration tool, Con A-immobilized polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I and II (GI and GII). This method offers many advantages over currently available methods, including a short concentration time. HuNov (GI and GII) can be detected in just 15 min with 90% recovery through Con A-PAB application. In addition, this method can be used over a wide range of pH values (pH 3.0 - 10.0). Overall, this rapid and sensitive detection of HuNoV (Cl and GII) will aid in the prevention of virus transmission pathways, and the method developed here may have applicability for other foodborne viral infections. (C) 2017 Elsevier Ltd. All rights 'reserved.
TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs. (C) 2017 Elsevier Inc. All rights reserved.
Background: Human papillomavirus (HPV) infection is linked to cervical cancer. With the technological development of molecular biology and epidemiology, detection and treatment of HPV has become an important mean to prevent cervical cancer. Methods: A simple, rapid, and sensitive colorimetric loop-mediated isothermal amplification (LAMP) method was established herein to detect 23 HPV genotypes. The sequences of the primers for the LAMP reaction were located in the L1 gene of the HPV genome. As it is a fluorescent dye, calcein was added before the reaction. The reaction was run under isothermal conditions at 65 degrees C for 40 minutes. A positive reaction was indicated by a color change from yellow to fluorescent green. The fluorescence curve diagram represents the monitoring of real time quantitative instrument. 450 cervical swab samples from patients with single infections of 23 different HPV genotypes were examined to evaluate the specificity. Results: The results revealed no cross-reaction with other HPV genotypes. A serial dilution of a cloned plasmid containing 23 HPV L1 gene sequences was employed to evaluate the sensitivity. Different HPV subtypes have different detection capability. The sensitivity of different HPV subtypes tested by LAMP assay was in the range from 1.0 x10 to 4.0 x 10(3) copies per reaction. The LAMP assay and the RDB (reverse dot blot) were compared for detecting and genotyping HPV among the 450 clinical samples. There were 385 (85.6%) and 375 (83.3%) HPV positive specimens detected by LAMP and RDB, respectively, as well as 306 (68.0%) and 296 (65.8%) for HR-HPV positive specimens. The agreement between the LAMP and RDB assays was 93.3% (kappa = 0.75) for HPV positivity and 94.7% (kappa = 0.88) for HR-HPV positivity. Conclusions: It was concluded that this colorimetric LAMP assay had potential application for the rapid screening of the HPV infection in resource-limited hospitals or rural clinics.
BackgroundHuman papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. MethodsE6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. ResultsAll HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. ConclusionHPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. (c) 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017
Cervical cancer, which is the second most common female malignancy, is characterized by the consistent presence of human papillomavirus. Inappropriate activation of Notch signaling has been associated with various types of cancer; however, the role of Notch in cervical cancer remains unclear. The present study aimed to investigate the role of Notch in cervical cancer. The methods used included the generation of plasmids, viability assays, polymerase chain reaction and western blotting The present findings demonstrated that cervical cancer samples also consistently exhibit abnormal activation of the Notch pathway. The data also indicated that different Numb isoforms may have opposite effects on the proliferation of cervical cancer cells. As a result, the activated Notch signaling pathway regulates the alternative splicing of the Numb gene, which affects the proliferation of the cervical cancer cells. These findings suggest that activated Notch signaling may lead to the development of cervical cancer by regulating Numb splicing. Thus, Numb splice variants may be a potential clinical marker for indicating cervical cancer genesis and development.
Many epidemical and biological studies have proposed that human papillomavirus (HPV), primarily high-risk HPV16/18, is an etiological factor for a subset of head and neck (HN) cancers. On that premise, we systematically reviewed relevant articles and improved the understanding of HPV-related cancers. This article comprehensively described the characteristics of HPV-associated HN tumors according to demography, histopathology, molecular biology, and prognosis. Meta-analyses were conducted to combine the studies that reported the association between HPV status and these variables using Rev Man 5.0. The pooled results showed that HPV-positive tumors were not only poorly differentiated (OR = 2.77, 95% CI: 2.3-3.32) and smaller (OR = 2.21, 95% CI: 1.75-2.8) but were also strongly associated with oropharynx (OR = 5.8, 95% CI: 4.01-8.38) and node involvement (OR = 2.77, 95% CI: 2.3-3.32). HPV-related tumors showed significantly more p16 overexpression (OR = 34.55, 95% CI: 20.91-57.09) and less TP53 mutations (OR = 0.27, 95% CI: 0.18-0.41) than HPV-negative tumors. The patients with HPV-positive cancers had different clinical behaviors, such as a reduced risks of death (HR = 0.32, 95% CI: 0.29-0.36). This study supported the view point that HPV is a favorable indicator of prognosis and that HPV-related HN tumors are distinct from traditional tumors. This etiological relationship could impact future strategies of diagnosis, prevention, therapy, and prognosis for this subset of patients. (C) 2016 Wiley Periodicals, Inc.
Objectives/HypothesisThe human papillomavirus (HPV) is known to infect the tissues of the oropharynx as demonstrated in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV has also been shown to induce benign lymphoid hypertrophy. We sought to investigate an association between obstructive sleep apnea (OSA) and the presence of HPV in palatine and lingual tonsillar oropharyngeal tissue. Study DesignCase series with chart review. MethodsThis retrospective laboratory-based study of oropharyngeal tissue from patients with OSA included patients >18 years old who underwent surgical treatment for OSA at a single institution between January 2012 and May 2014. Surgical specimens of adequate size were analyzed for HPV6, 11, and 16 using real-time quantitative polymerase chain reaction from DNA extracted from formalin-fixed paraffin-embedded tissue blocks. Student t test, Pearson (2) test, and linear logistic regression were used to assess comparisons of body mass index (BMI), apnea-hypopnea index (AHI), age, and gender between HPV-positive and HPV-negative groups. ResultsOf 99 cases included in the study, six were positive for HPV: two with HPV16 and four with HPV6. BMI, AHI, age, and gender showed no significant differences between the HPV-positive and HPV-negative groups. Logistic regression to predict HPV positivity accounting for each variable and multivariate analysis were not statistically significant. ConclusionsOur study did not show HPV to have a statistically significant association with OSA. None of the covariates analyzed (BMI, AHI, gender, age) predicted HPV positivity in surgically resected oropharyngeal tissue from OSA patients. Level of Evidence4 Laryngoscope, 127:1231-1234, 2017
Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti-B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti-B19 antibodies during pregnancy is limited. To investigate the possible roles of anti-B19 antibodies during pregnancy, the present study examined the effects of anti-B19-VP1 unique region (VP1u), anti-B19-VP2 and anti-B19-nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with purified IgG against B19-VP1u, B19-VP2 and B19-NS1. Subsequently, the expression of surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using flow cytometry, ELISA and western blotting. The expression levels of human leukocyte antigen (HLA)-G were significantly increased on BeWo trophoblasts treated with rabbit anti-B19-VP1u IgG, and were unchanged in those treated with rabbit anti-B19-NS1 and anti-B19-VP2 IgG, as compared with the control group. Furthermore, the expression levels of globoside (P blood group antigen) and cluster of differentiation (CD) 29 (beta 1 integrin) were significantly increased in BeWo trophoblasts treated with rabbit anti-B19-NS1 and anti-B19-VP2 IgG, whereas only CD29 was also significantly increased in cells treated with anti-B19-VP1u IgG. In addition, the number of cells at sub-G(1) phase; caspase-3 activity; and the expression of intrinsic and extrinsic apoptotic molecules, including Fas-associated death domain protein, activated caspase-8, activated caspase-3, B-cell lymphoma 2-associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and activated caspase-9, were significantly increased in BeWo trophoblasts treated with anti-B19-VP1u and anti-B19-NS1 IgG. In conclusion, the present study demonstrated that antibodies against B19 may have a crucial role in pathological processes during pregnancy. These findings may help to elucidate the mechanisms underlying transmission of the B19 virus during pregnancy.
Objective: Potassium channels of the ATP-sensitive family (K-ATP channel) are inhibited by increase in intracellular ATP. Electrophysiological studies have demonstrated that the kinetics and pharmacological properties of KAT? channels vary among different tissues, suggesting structurally and functionally distinct types. There are studies showing human periodontal ligament (PDL) cells respond to mechanical stress by increasing ATP release, which participates in bone resorption or bone homeostasis. So, in this study we investigated the existence of KAT? channel subunit and their single channel properties in human periodontal ligaments. Materials & method: The human PDL cells were isolated from healthy erupted third molar. For patch clamp experiments, human PDL fibroblasts were seeded on 3.5 cm plastic dishes. The inside-out patch clamp recordings were performed under voltage clamp mode. Reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to identify the channel subunits. All pair-wise comparisons were performed by Paired t-test. A P value < 0.05 was considered significant. Results: We observed mRNA transcripts for Kir6.1, Kir6.2 and Sur2B subuits in the human PDL cells. In inside-out patch mode, the single channel conductance was 163 pS at symmetrical K+ concentration of 140 mM and inward rectification was seen in ATP-free bath solution. The reversal potential of the currents was found to be 0 mV at symmetrical concentration (140 mM) of K+ in bath solution. The single channel currents were almost blocked by adding 5 mM ATP in the bath solution. However, the currents were not blocked by 100 mu M glibenclamide, a subunit specific K-ATP channel blocker. Conclusions: These results indicate that human PDL cells express K-ATP channels subunit including Sur2B and Kir6.1 and Kir6.2 which are sensitive to ATP but insensitive to glibenclamide. (C) 2017 Elsevier Ltd. All rights reserved.
Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially compared gene expression profiles between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and 127 genes were down-regulated. Next, a subset of genes, twofold differentially expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor formation in subcapsule of kidney and lung metastasis. On the other hand, induction of caveolin-1 gene affected the production of lung metastasis under anti-cancer drug treatment: the incidence of pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules decreased significantly (p = 0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis.
The necessity for schools to implement human resources management (HRM) is increasingly acknowledged. Specifically, HRM holds the potential of increasing student outcomes through the increased involvement, empowerment and motivation of teachers. In educational literature, however, little empirical attention is paid to the ways in which different HRM practices could be bundled into a comprehensive HRM system (content) and how HRM could best be implemented to attain positive teacher and student outcomes (process). Regarding the content, and following the AMO theory of performance', it is argued that HRM systems should comprise (A) ability-, (M) motivation- and (O) opportunity-enhancing HRM practices. Regarding the process, and based on HRM system strength' literature, it is argued that when teachers perceive HRM as distinctive and consistent, and if they perceive consensus, this will enhance teachers' and schools' performance. By combining insights from educational studies on single HRM practices with HRM theories, this paper builds a conceptual framework which can be used to design HRM systems and to understand the way they operate.
Background: The administration of cisplatin is limited due to its nephrotoxic side effects, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury. In this study, we demonstrated that the pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent the development of cisplatin-induced renal toxicity by activation of autophagy in vitro and in vivo. Methods: In vitro, rat renal tubular epithelial (NRK-52E) cells were pre-incubated with exosomes from hucMSC or HFL1 (human lung fibroblast cells; as control) for 30 min, and 3-methyladenine (an autophagic inhibitor) and rapamycin (an autophagic inducer) for 1 h before cisplatin treatment for 8 h, respectively. Cells were harvested for apoptosis assay, enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, we constructed cisplatin-induced acute kidney injury rat models. Prior to treatment with cisplatin for 0.5 h, hucMSC-Ex or HFL1-Ex were injected into the kidneys via the renal capsule. 3-methyladenine and rapamycin were injected under the kidney capsule before hucMSC-Ex. All animals were sacrificed at 3 days after cisplatin injection. Renal function, Luminex assay, tubular apoptosis and proliferation, and autophagy response were evaluated. Results: hucMSC-Ex inhibited cisplatin-induced mitochondrial apoptosis and secretion of inflammatory cytokines in renal tubular epithelial cells in vitro. hucMSC-Ex increased the expression of the autophagic marker protein LC3B and the autophagy-related genes ATG5 and ATG7 in NRK-52E cells. Rapamycin mimicked the effects of hucMSC-Ex in protecting against cisplatin-induced renal injury, while the effects were abrogated by the autophagy inhibitor 3-methyladenine in the animals. Conclusions: Our findings indicate that the activation of autophagy induced by hucMSC-Ex can effectively relieve the nephrotoxicity of cisplatin. Therefore, pre-treatment of hucMSC-Ex may be a new method to improve the therapeutic effect of cisplatin.
Objective: Ulinastatin reduces the high permeability of vascular endothelial cells induced by tumor necrosis factor alpha (INF-alpha). This study investigated the molecular mechanism behind this effect, with the aim of understanding the action of ulinastatin in sepsis therapy and exploring novel therapeutic strategies for sepsis patients. Methods: A TNF-alpha treated human umbilical vein endothelial cell line (EA.hy926) was employed as an inflammation model. Horseradish peroxidase permeability assays and an epithelial voltmeter method were used to measure the permeability of EA.hy926 cells. Immunocytochemistry was used to assay the expression of p-MYPT1 and the distribution and morphology of F-actin; the expression of the key molecules related to vascular endothelial permeability. (RhoA, ROCK2, MYPT1, p-MYPT1 and VE-cadherin) was detected by immunocytochemistry assays, western blotting and quantitative real-time polymerase chain reaction. Results: After incubation with TNF-a or septic serum, the transendothelial electrical resistance of EA.hy926 cells decreased and the permeability of the cells increased significantly (all P < 0.05). The expression of p-MYPT1 was higher and VE-cadherin was lower compared with the control group, and F-actin was redistributed, with the formation of additional stress fibers in the cells. Ulinastatin treatment moderated these phenomena. The immunocytochemistry assays and western blots showed that the expression of RhoA and ROCK2 was significantly upregulated in cells treated with TNF-alpha (P < 0.05); however, ulinastatin could inhibit the high expression of these two proteins. Under treatment with TNF-alpha and ulinastatin, compared with normal EA.hy926 cells, overexpression of RhoA upregulated expression of RhoA, ROCK2 and p-MYPT1, downregulated expression of VE-cadherin, and restored the hyperpermeability of vascular endothelial cells due to TNF-alpha treatment (P < 0.05). Conclusions: Ulinastatin inhibited the hyperpermeability of vascular endothelial cells induced by TNF-alpha. This inhibitory effect of ulinastatin may be related to the RhoA/ROCK signaling pathway. (C) 2017 Elsevier B.V. All rights reserved.
Helminths and their products can suppress the host immune response to escape host defense mechanisms and establish chronic infections. Current studies indicate that macrophages play a key role in the immune response to pathogen invasion. They can be polarized into two distinct phenotypes: M1 and M2. The present paper examines the impact of the adult Hymenolepis diminuta (HD) tapeworm and its excretory/secretory products (ESP) on THP-1 macrophages. Monocytes were differentiated into macrophages and cultured with a living parasite or its ESP. Our findings indicate that HD and ESP have a considerable impact on human THP-1 macrophages. Macrophages treated with parasite ESP (with or without LPS) demonstrated reduced expression of cytokines (i. e., IL-1 alpha, TNF alpha, TGF beta, IL-10) and chemokines (i. e., IL-8, MIP-1 alpha, RANTES, and IL-1ra), while s-ICAM and CxCL10 expression rose after ESP stimulation. In addition, inflammatory factor expression rose significantly when macrophages were exposed to living parasites. Regarding induced and repressed pathways, significant differences were found between HD and ESP concerning their influence on the phosphorylation of ERK1/2, STAT2, STAT3, AMPKa1, Akt 1/2/3 S473, Hsp60, and Hck. The superior immunosuppressive properties of ESP compared to HD were demonstrated with lower levels of IL-1 beta, TNF-alpha, IL-6, IL-23, and IL-12p70 following stimulation. The presence of HD and its ESP were found to stimulate mixed M1/M2 macrophage phenotypes. Our findings indicate new molecular mechanisms involved in the response of human macrophages to tapeworm infection, this could be a valuable tool in understanding the mechanisms underlying the processes of immune regulation during cestodiasis.
The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies. To circumvent this critical limitation, we have developed a method to quickly propagate established BLT mice. Through secondary transfer of bone marrow cells and human thymus implants from BLT mice into NSG (NOD/SCID/IL-2R gamma(-/-)) recipient mice, we were able to expand one primary BLT mouse into a colony of 4-5 proBLT (propagated BLT) mice in 6-8 weeks. These proBLT mice reconstituted human immune cells, including T cells, at levels comparable to those of their primary BLT donor mouse. They also faithfully inherited the human immune cell genetic traits from their donor BLT mouse, such as the HLA-A2 haplotype that is of special interest for studying HLA-A2-restricted human T cell immunotherapies. Moreover, an EGFP reporter gene engineered into the human immune system was stably passed from BLT to proBLT mice, making proBLT mice suitable for studying human immune cell gene therapy. This method provides an opportunity to overcome a critical hurdle to utilizing the BLT humanized mouse model and enables its more widespread use as a valuable preclinical research tool.
Although Small Hydropower Projects (SHPs) are encouraged as sources of clean and green energy, there is a paucity of research examining their socio-ecological impacts. We assessed the perceived socio-ecological impacts of 4 SHPs within the Western Ghats in India by conducting semi-structured interviews with local respondents. Primary interview data were sequentially validated with secondary data, and respondent perceptions were subsequently compared against the expected baseline of assured impacts. We evaluated the level of awareness about SHPs, their perceived socio-economic impacts, influence on resource access and impacts on human-elephant interactions. The general level of awareness about SHPs was low, and assurances of local electricity and employment generation remained largely unfulfilled. Additionally most respondents faced numerous unanticipated adverse impacts. We found a strong relationship between SHP construction and increasing levels of human-elephant conflict. Based on the disparity between assured and actual social impacts, we suggest that policies regarding SHPs be suitably revised.
Affective "Theory of Mind" (ToM) is the specific ability to represent own and others' emotional states and feelings. Previous studies examined affective ToM ability in patients with Huntingtons disease (HD), using the "Reading the Mind in the Eyes test" (RMET). Results were consistent in showing difficulties in inferring complex mental states from photographs of people even in the early stage of HD. However, there has been no agreement as to whether or not cognitive impairments in HD population might have contributed to poor performance on the RMET test. The aim of the present study was to assess whether the affective ToM ability was impaired in the mild to moderate stages of HD, and whether there was an association between compromised ToM ability and the presence of cognitive impairment. We evaluated ToM by means of RMET and global cognitive functioning by means of the MoCA questionnaire in 15 HD patients and 15 healthy subjects (HS). Both groups were matched for age and level of education. Our study showed that the ability to judge a persons mental states from a picture of their eyes was impaired in HD patients compared to normal population. Indeed, HD subjects gave the 34% of correct responses on RMET, whereas healthy control subjects percentage of correct responses was 71%. Furthermore, this impairment was not correlated with global cognitive functioning except for the visuospatial task. These results show that RMET might represent a valid instrument to assess affective ToM ability in HD patients in the mild to moderate stages of the disease, independently from their cognitive status. Since it is known that HD patients, in addition to motor symptoms, suffer from cognitive deficits, including memory and executive impairments, it is important to have an instrument, which is not influenced by cognitive abilities. It is possible therefore to use RMET to assess important aspects of HD patients such as their ability to recognize others emotions and feelings even when patients suffer from cognitive decline.
Purinergic signaling maintains local tissue homeostasis in blood vessels via the regulation of vascular tone, blood platelet aggregation, cell proliferation, and differentiation as well as inflammatory responses. Extracellular purines are important signaling molecules in the vasculature, and both purine-hydrolysing as well as -phosphorylating enzymes are considered to selectively govern extracellular nucleotide/nucleoside metabolism. Recent studies have provided some evidence for the existence of these enzymes in a soluble form in human blood and their secretion into the extracellular space under physiological and pathological conditions. However, the comprehensive analysis of endothelium-derived enzymes involved in purine metabolic pathways has received no attention so far. In the presented study, in vitro cultured human umbilical vein endothelial cells (HUVEC) are shown to be an abundant source of exo-nucleotidases comprising 5-nucleotidase (exo-5-NT), and nucleoside triphosphate diphosphohydrolases (exo-NTPDase) as well as phosphotransferases, represented by nucleoside diphosphate kinase (exo-NDPK) and adenylate kinase (exo-AK). An attempt is also made to demonstrate that, in contrast to the metabolic pattern determined on the endothelial cell surface, exo-phosphorylating activities markedly predominate over exo-hydrolytic ones. We present for the first time the expression profiles of genes encoding isoenzymes belonging to distinct nucleotide kinase and nucleotidase families. The genes encoding NDPK1, NDPK2, AK1, and AK2 phosphotransferases have been shown to be expressed at the highest level in HUVEC cells. The data indicate the coexistence of secreted and cell-associated factors of endothelial origin mediating ATP-consuming and ATP-generating pathways with the predominance of exo-phosphotransferases activity. The described enzymes contribute to the regulation of purinergic signal duration and extent in the venous vasculature. J. Cell. Biochem. 118: 1341-1348, 2017. (C) 2016 Wiley Periodicals, Inc.
The paper postulates the feasibility and optimization of HVAC systems using programmable controllers. HVAC (heating, ventilating and air conditioning) systems are used for controlled maintenance of indoor ambient characteristics in optimal manner; with regards to outdoor ambient characteristics. The paper includes a simplified sequence of diagrams to represent the architecture of the system. Further, it also comprises of the systems and software's used for the same. Also, the paper gives an insight of the advantages of using programmable controllers, and the challenges which are overcome by it. For the ease of understanding a case study of a pharmaceutical company is given who is currently using the system. The main purpose of this project was to create a regulated monitoring system, integration of the utilities like electricity and water, creating a general report of the system for the given or needed time span, also to create a graphical visualization of the real time data and system.
this paper presents a column-level 14-bit two-stage analog-to-digital converter (ADC) based on pseudo-differential operational amplifier, which is designed for the readout circuit of X-ray sensor array. This low-power hybrid ADC employs an incremental sigma-delta ADC and a cyclic ADC, achieving a good trade-off between accuracy and conversion speed. The two stages share the same analog circuit to reduce area and power consumption. A test chip is fabricated in 0.18 mu m CMOS technology. The hybrid ADC in each column is performed in parallel with power consumption of 218.813 mu W. The simulation result reveals the effective number of bits (ENOB) is 13.775 bits.
this paper presents a low-power 14-bit hybrid incremental Sigma-Delta/cyclic analog-to-digital converter (ADC) based on pseudo-differential operational amplifier, which is designed for the readout circuit of infrared focal plane array detector. This two-stage hybrid ADC employs an incremental sigma-delta ADC and a cyclic ADC, achieving a good trade-off between accuracy and conversion speed. The two stages share the same analog circuit to reduce area and power consumption. A common-mood feedback module is used to suppress the influence of charge injection, and the effectiveness is demonstrated by detailed theoretical analysis and simulation result. A test chip is fabricated in 0.18 mu m CMOS technology. The hybrid ADC in each column is performed in parallel with power consumption of 218.813 mu W. The simulation result reveals the effective number of bits (ENOB) is 13.775 bits.
This paper proposes a method for three-phase state estimation (SE) in power distribution network including on-load tap changers (OLTC) for voltage control. The OLTC tap positions are essentially discrete variables from the SE point of view. Estimation of these variables in SE presents a formidable challenge. The proposed methodology combines discrete and continuous state variables (voltage magnitudes, angles, and tap positions). A hybrid particle swarm optimization (HPSO) is applied to obtain the solution. The method is tested on standard IEEE 13-and 123-bus unbalanced test system models. The proposed algorithm accurately estimates the network bus voltage magnitudes and angles, and discrete tap values. The HPSO-based tap estimation provides a more accurate estimation of losses in the network, which helps in fair allocation of cost of losses in arriving at overall cost of electricity.
The current increase in the deployment of new renewable electricity generation systems is creating new challenges in balancing electric grids. Solutions including energy storage at small and large scales are becoming of paramount importance to guarantee and secure a stable supply of electricity. This paper presents a study about a hybrid solution including a large scale energy storage system coupled with power generation and fast responding energy storage systems. The hybrid plant is able to deliver the energy previously stored by using an air liquefaction process either with or without the contribution of additional energy from combustion. The paper also highlights how such hybrid plants may offer the chance of providing the grid with fast control services. An ideal energy storage technology should have a high power rating, a large storage capacity, high efficiency, low costs and no geographic constraints. The use of air as energy carrier has been studied since the 20th century with the first compressed air energy storage (CAES) systems. This technology is still considered to have a potential but it is geographically constrained, where suitable geological reservoirs are available, unless compressed air is stored in pressurized tanks with significant costs. Liquid Air Energy Storage (LAES) represents an interesting solution due to its relatively large volumetric energy density and ease of storage. Different process schemes for hybrid plants were modeled in this study with Aspen HYSYS (R) simulation software and the results were compared in terms of equivalent round-trip and fuel efficiencies. Equivalent round-trip efficiencies, higher than 80%, have been calculated showing that the proposed configurations might play an important role for power systems balancing in the near future. (C) 2016 Elsevier Ltd. All rights reserved.
Off-grid electricity generation using renewable energy technologies has become a more reliable source to fulfill the needs of rural areas at limited level without considering conventional resources. The main purpose of this study was to propose an economical and optimized design for electricity generation using hybrid energy source PV/Biomass for an agricultural farm and a residential community centered in a small village of district Layyah in the Punjab province of Pakistan. The electric load data was collected for the irrigation and residential needs. Hybrid Optimization Model for Electric Renewable (HOMER) was used to design and perform techno-economic analysis to meet the load requirements using PV/biomass hybrid configuration. The solar irradiance data and the available biomass potential on the farm was used in the HOMER software to perform the analysis. Total net present cost (NPC) and cost of electricity (COE) were obtained as a solution by the HOMER analysis and then these results were refined further by performing sensitivity analysis. Sensitivity parameter such as biomass potential, biomass price, solar irradiance and variations in loads were used in the sensitivity analysis. This analysis compares the performance of the system and shows that system is techno-economically viable based on the net present cost and cost of energy. (C) 2017 Elsevier Ltd. All rights reserved.
The paper presents a real-time open software simulation framework, dedicated to the analysis of control systems deployed over distributed execution resources and wireless links. It is able to consistently simulate in parallel the numerical devices (real-time tasks and communication links) and the evolution of the controlled continuous time plant. It is applied to foresee future enhancements of a Functional Electrical Stimulation (FES) system used in therapy for rehabilitation or substitution for disabled people. It is a distributed control system using electrodes to interface a digital control system with livings. Hence the whole system gathers continuous-time (muscles and nerves) and discrete-time (controllers and wireless links) components. During the design process, realistic simulation remains a precious tool ahead of real experiments to check without danger that the implementation matches the functional and safety requirements. The simulation tool is especially devoted to the joint design and analysis of control loops and real-time features.
The assessment of off-grid electrification programs in developing countries largely based on mini-grid and solar home system (SHS) has shown that they are faced with low development imparts and sustainability challenges, which has resulted in failure of many projects. This study provides solutions on how to surmount these challenges, leaning on the experience of a hybrid solar-diesel mini-grid at Tsumkwe village in Namibia. It provides analyses of a case study based on empirical evidence from field studies, interviews of representatives of households, public institutions and energy providers. In addition, it investigates the technical challenges and economic impacts of the electrification program. HOMER (TM) and MATLAB (TM) models were used in the analysis and investigations. The findings show that despite the challenges, the system has been sustained because it keyed into an existing structure with growth potentials. The progressive tariff system adopted by the government helped to cushion costs and allow low income households in the energy matrix. Adoption of strict maintenance measures, and implementation of energy efficiency measures prior to the commissioning of the program, resulted in the reduction of costs. The success elements identified in this study could be extrapolated in other sub-Saharan African countries if the challenges are properly addressed. (C) 2017 Elsevier Ltd. All rights reserved.
Recent advances in power generation from renewable resources necessitate conversion of electricity to chemicals and fuels in an efficient manner. Electrocatalytic water splitting is one of the most powerful and widespread technologies. The development of highly efficient, inexpensive, flexible, and versatile water electrolysis devices is desired. This review discusses the significance and impact of the electrolyte on electrocatalytic performance. Depending on the circumstances under which the water splitting reaction is conducted, the required solution conditions, such as the identity and molarity of ions, may significantly differ. Quantitative understanding of such electrolyte properties on electrolysis performance is effective to facilitate the development of efficient electrocatalytic systems. The electrolyte can directly participate in reaction schemes (kinetics), affect electrode stability, and/or indirectly impact the performance by influencing the concentration overpotential (mass transport). This review aims to guide fine-tuning of the electrolyte properties, or electrolyte engineering, for (photo)electrochemical water splitting reactions.
Background: Oxidative stress can induce cell injury in vascular endothelial cells, which is the initial event in the development of atherosclerosis. Although quantitative real-time polymerase chain reaction (qRT-PCR) has been widely used in gene expression studies in oxidative stress injuries, using carefully validated reference genes has not received sufficient attention in related studies. The objective of this study, therefore, was to select a set of stably expressed reference genes for use in qRT-PCR normalization in oxidative stress injuries in human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H2O2). Results: Using geNorm analysis, we found that five stably expressed reference genes were sufficient for normalization in qRT-PCR analysis in HUVECs treated with H2O2. Genes with the most stable expression according to geNorm were U6, TFRC, RPLP0, GAPDH, and ACTB, and according to NormFinder were ALAS1, TFRC, U6, GAPDH, and ACTB. Conclusion: Taken together, our study demonstrated that the expression stability of reference genes may differ according to the statistical program used. U6, TFRC, RPLP0, GAPDH, and ACTB was the optimal set of reference genes for studies on gene expression performed by qRT-PCR assays in HUVECs under oxidative stress study.
A 1 kW-class electrochemical reactor for hydrogen production was developed using bipolar plates. To fabricate thick, large-area electrodes, a particle electrode fabrication method was also introduced. Scanning electron microscopy with energy dispersive X-ray spectroscopy and galvanostatic performance measurements were performed to evaluate the particle electrodes. The results show that the particle electrodes exhibit an excellent charge performance despite the electrode material layer being relatively thick and highly porous. The electrochemical reactor contained 20 single cells stacked together with 30 A h of nickel hydroxide and 15 A h of metal hydride as the positive and negative electrodes, respectively. The electrochemical tests showed that the stack exhibited a high hydrogen production efficiency with a maximum current efficiency of 95.3% for hydrogen production and a hydrogen evolution amount per unit input electrical energy of 259.1 mL/W h at 0.2 C. At high current densities (2.0 C), a rapid temperature increase was also observed during the charging process, which led to a reduction of the hydrogen production efficiency. Therefore, further design modifications are needed to control heat generation during operation of the device. (C) 2016 Published by Elsevier Ltd.
Recent environmental and economic considerations have made the focus of attention new treatment processes of the residual (tail) gas of Claus plants, based on the oxidative decomposition of H2S to Sulphur and Hydrogen, In this work, the thermal, oxidative decomposition of H2S in an homogeneous phase has been studied by developing a comprehensive chemical kinetic model for the oxidation of H2S in a low oxygen atmosphere, by varying the O-2/H2S ratio (0.2-0.35), residence time (150-300 ms), and process temperatures (900-1100 C-omicron). The kinetic model has been developed by combining existing models for the oxidation of H2S, with no tuning of the parameters or kinetic constants and validated in relation to the experimental data. The results show a very good agreement with the experimental values at higher temperatures (1100 C-omicron). At 900 C-omicron, the H2S conversion is well predicted by the model, whereas the H-2 yield and SO2 selectivity are consistently higher than the experimental values. A sensitivity analysis for the complex kinetic system has highlighted the importance of the reaction (O-2 + SO + SO) at lower temperatures. (C) 2016 Elsevier Ltd. All rights reserved.
Flow Induced Motions (FIMs) of rigid circular cylinders, and particularly VIV (Vortex Induced Vibrations) and galloping, are induced by alternating lift. The VIVACE (VIV for Aquatic Clean Energy) Converter uses single or multiple cylinders, in tandem, on elastic end-supports, in synergistic FIM, to convert MHK energy to electricity. Selectively distributed surface roughness is applied to enhance FIM and increase efficiency. In this paper, two cylinders are Used in tandem with center-to-center spacing of 1.57, 2.0 and 2.57 diameters, harnessing damping ratio 0.004<zeta < 0.24, for Reynolds number 30,000 < Re < 120,000. The virtual spring-damping system V-ck in the Marine Renewable Energy Laboratory (MRELab) enables embedded computer-controlled change of viscous-damping and spring-stiffness for fast and mathematically correct oscillator realization, without including the hydrodyllamic force in the closed control loop. Experimental results for oscillatory response, energy harvesting, and efficiency are presented and the envelope of optimal power is derived. All the experiments were conducted in the Low Turbulence Free Surface Water (LTFSW) Channel of the MRELab of the University of Michigan. The main conclusions are: (1) For the tested cylinder spacing, two cylinders harness power is between 2.56 and 13.49 times the power of a single cylinder, the efficiency of two cylinders is between 2.0 and 6.68 of a single cylinder. (2) The MHK power harnessed by the upstream cylinder is increased by up to 100%, affected by the downstream cylinder. (3) The MHK power harnessed by the downstream cylinder and its FIM are affected to a lesser extent by the interaction. (4) VIVACE can harness energy from flows as slow as 0.4 m/s with no upper limit in flow velocity. (5) Close spacing and high spring Stiffness yield highest harnessed power. (6) The optimal harnessed power shifts to softer springs as spacing increases. (C) 2017 Elsevier Ltd. All rights reserved.
Omeprazole is one of the world-wide most frequently prescribed and administered pharmaceuticals in humans for the relief of gastro-intestinal disorders. Despite its high worldwide consumption, omeprazole is rarely detected in urban wastewaters and environmental waters. On the other hand, its human urinary metabolites and transformation products formed through abiotic processes in the environment have been recently documented. Despite these available data, however, there is still a lack of information on the extent of environmental fate and occurrence, on elimination mechanisms and efficiencies in waste water treatment plants. In this study, the relevance of photodegradation processes on the environmental persistence of omeprazole under simulated and solar irradiation was investigated. Photodegradation experiments were performed in distilled water, lake, river and seawater, and revealed that the different matrix in natural waters significantly affect the photolytic behavior of the investigated compound. Overall, the results highlight that photodegradation process by solar irradiation significantly contributes to omeprazole degradation and elimination from the aquatic environment. TPs formed through the process were identified and elucidated by using liquid chromatography high resolution mass spectrometry. In total seven TPs were identified, among of which four were also detected as hydrolysis TPs. The Microtox bioassay showed that solar photolysis is efficient to detoxify omeprazole and its TPs in aqueous solutions. Finally, a systematic investigation was conducted in order to provide information on removal efficiency and occurrence of omeprazole and its metabolites/TPs in 8 WWTPs in North West Greece by performing target and suspect screening analysis. The findings revealed the presence of both parent compound and metabolites/TPs in wastewaters. Given, however, the scarce detection of omeprazole at fairly low concentration levels, from analytical and environmental point of view, further attention should be given to metabolites/fPs instead of the parent compound. (C) 2017 Elsevier B.V. All rights reserved.
An important and plausible impact of a changing global climate is altered power generation from hydroelectric dams. Here we project 21st century global hydropower production by forcing a coupled, global hydrological and dam model with three General Circulation Model (GCM) projections run under two emissions scenarios. Dams are simulated using a detailed model that accounts for plant specifications, storage dynamics, reservoir bathymetry and realistic, optimized operations. We show that the inclusion of these features can have a non-trivial effect on the simulated response of hydropower production to changes in climate. Simulation results highlight substantial uncertainty in the direction of change in globally aggregated hydropower production (similar to-5 to +5% change in mean global production by the 2080s under a high emissions scenario, depending on GCM). Several clearly impacted hotspots are identified, the most prominent of which encompasses the Mediterranean countries in southern Europe, northern Africa and the Middle East. In this region, hydropower production is projected to be reduced by approximately 40% on average by the end of the century under a high emissions scenario. After accounting for each country's dependence on hydropower for meeting its current electricity demands, the Balkans countries emerge as the most vulnerable (similar to 5-20% loss in total national electricity generation depending on country). On the flipside, a handful of countries in Scandinavia and central Asia are projected to reap a significant increase in total electrical production (similar to 5-15%) without investing in new power generation facilities. (C) 2017 Elsevier B.V. All rights reserved.
The hydrothermal electrochemical deposition (HED) synthesis NiSe2 as counter electrode(CE) of dyesensitized solar cells(DSSCs), which shows excellent catalytic activity in reduction of triiodide. Hydrothermal and electro-deposition(ED) have been widely used to synthetize NiSe2, herein, we fistly introduce the HED to produce the NiSe2 material as the CE of DSSCs. In addition, cyclic voltammetry(CV) curves, Tafel plots and electrochemical impedance spectroscopy(EIS) indicated that HED-NiSe2 as CE shows better electrocatalytic activity for reduction of iodine/iodide electrolyte than ED-NiSe2 and Pt. The DSSC fabricated by the HED-NiSe2 CE displays a solar-to-electricity conversion efficiency of 8.24% comparing with 7.68% the convention Pt as reference, and significant higher than that of based on the ED-NiSe2(7.97%). Furthermore, we demonstrate that the HED method is a promising way to design and synthesize advanced CE materials for utilizing solar energy. (C) 2017 Elsevier B. V. All rights reserved.
Hydroidfest 2016 took place on September 23-25 at the UC Davis Bodega Marine Laboratory in Bodega Bay, CA. The meeting brought together cnidarian researchers, with an emphasis on those studying hydrozoans, from North America and other parts of the world. The scientific topics discussed were diverse, including sessions focused on development, regeneration, aging, immunology, symbiosis, and neurobiology. Thanks to the application of modern biological technologies, hydrozoans and other cnidarians are now fertile ground for research in numerous disciplines. Moreover, their amenability to comparative approaches is a powerful asset that was repeatedly showcased during the meeting. Here, we give a brief account of the work that was presented and the opportunities that emerged from the ensuing discussions.
Objectives. To describe (i) the clinical characteristics of workers, exposed to hymenoptera stings, with an ascertained diagnosis of Hymenoptera Venom Allergy (HVA), (ii) the specific role of occupational exposure, (iii) the effect of Venom Immunotherapy (VIT) in reducing the severity of allergic episodes in workers exposed to repeated stings of hymenoptera, and (iv) the management of the occupational consequences caused by allergic reactions due to hymenoptera stings. Methods. Between 2000 and 2013 an observational study, including patients referred to the regional reference hospital of Liguria, Italy, with an ascertained diagnosis of HVA and treated with VIT, was performed. A structured questionnaire was administered to all patients to investigate the occupational features of allergic reactions. These were graded according to standard systems in patients at the first episode, and after re-stings, during VIT. Results. One-hundred and 8four out of the 202 patients referred had a complete data set. In 32 (17.4%) patients, the allergic reaction occurred during work activities performed outdoor. Of these, 31.2% previously stung by hymenoptera at work, and receiving VIT, were re-stung during occupational activity. The grades of reaction developed under VIT treatment resulted clinically less severe than of those occurred at the first sting (p-value = 0.031). Conclusion. Our findings confirmed the clinical relevance of HVA, and described its occupational features in outdoor workers with sensitization, stressing the importance of an early identification and proper management of the professional categories recognized at high risk of hymenoptera stings. The Occupational Physician should be supported by other specialists to recommend appropriate diagnostic procedures and the prescription of VIT, which resulted an effective treatment for the prevention of episodes of severe reactions in workers with a proven HVA.
The separation of aromatic/aliphatic mixtures is significant in chemical industry. Pervaporation has attracted increasing attention due to its low energy consumption and environmentally friendly process. However, the formation of membranes mostly use toxic organic solvents, whereas in this study water was used instead to prepare membrane in separating aromatic/aliphatic mixtures. W3000 were dispersed in water to form micelles, which were then deposited onto the surface of the tubular porous ceramic substrate through the negative pressure-driven assembly method. The emulsion and composite membranes were characterized by TEM, SEM and FTIR. The crosslinking density of W3000 was also tested using NMR XLD analyzing system. The membranes were used for separating aromatic/aliphatic mixtures through pervaporation. The results showed that compared with the membrane prepared by DMF, the pervaporation separation index (PSI) of the composite membrane formed using water as solvent was 3.3-fold increased for separating toluene/n-heptane mixtures. The as-prepared composite membranes showed a better comprehensive pervaporation performance. This facile strategy may have a potential in the application of pervaporation for separating aromatic/aliphatic mixtures in industry. (C) 2017 Elsevier B.V. All rights reserved.
Broadband infrared response has attracted great attention due to its potential applications in silicon based photodetectors. We have studied broadband infrared response of sulfur hyperdoped silicon under femtosecond laser irradiation. The fabricated PN photodiodes exhibit several photoresponse spectral peaks in near and mid-infrared region of electromagnetic spectrum. The onset energies corresponding to the distinct sub-band gap photoresponse features are consistent with the active energy levels of known sulfur within the silicon band-gap. This technique may offer a promising approach to fabricate low-cost broadband silicon based detectors. (C) 2017 Elsevier B. V. All rights reserved.
Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative effective therapeutic strategies for hyperglycemia-associated cancers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
The primary immunodeficiency (PID) diseases comprise a heterogeneous group of inherited disorders of immune function. Technical advancements in whole-genome, whole-exome, and RNA-sequencing have seen the explosion of genetic discoveries in the field of PIDs. The present review aims to focus on a group of immunodeficiency disorders associated with elevated levels of IgM (hyper IgM; HIGM) and provides a clinical differential diagnosis. Most patients present for evaluation of immunodeficiency due to recurrent infections, and laboratory studies show either a clear isolated elevation of serum immunoglobulin M (IgM) with low or absent IgG, IgA, and IgE. Alternatively, IgM levels may be normal or moderately elevated while other serum immunoglobulins are reported below the norms for age but not absent. Mechanistically, these disorders are recognized as defects in immunoglobulin (Ig) class switch recombination (CSR). Importantly, to safeguard genetic stability, CSR utilizes elements of the DNA repair machinery including multi-protein complexes involved in mismatch repair (MMR). Therefore, it is not uncommon for defects in the DNA repair machinery, to present with laboratory findings of HIGM. This review will discuss clinical phenotypes associated with congenital defects associated with HIGM. Clinical manifestations, relevant immunologic testing, inheritance pattern, molecular diagnosis, presumed pathogenesis, and OMIM number, when annotated are compiled. Accepted therapeutic options, when available, are reviewed for each condition discussed. (C) 2016 American Academy of Allergy, Asthma & Immunology.
PurposeTo demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Alterations in cardiac acid-base balance can lead to acute contractile depression and alterations in Ca2+ signaling. The transient reduction in adenosine triphosphate (ATP) consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias. MethodsSpectrally selective radiofrequency (RF) pulses were used to excite the HCO3- and CO2 resonances individually while preserving signal from the injected hyperpolarized [1-C-13]pyruvate. The large flip angle pulses were placed within a three-dimensional (3D) imaging acquisition, which exploited CA-mediated label exchange between HCO3- and CO2. Images at 4.5 x 4.5 x 5 mm(3) resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion. ResultsThe intracellular pH was measured to be 7.150.04 at baseline, and decreased to 6.90 +/- 0.06 following 15 min of continuous -adrenergic stimulation. ConclusionsVolumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1-C-13]pyruvate. The new method is anticipated to enable assessment of stress-inducible ischemia and potential ventricular arrythmogenic substrates within the ischemic heart. Magn Reson Med 77:1810-1817, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Two-person neuroscience, a perspective in understanding human social cognition and interaction, involves designing immersive social interaction experiments as well as simultaneously recording brain activity of two or more subjects, a process termed "hyperscanning." Using newly developed imaging techniques, the interbrain connectivity or hyperlink of various types of social interaction has been revealed. Functional near-infrared spectroscopy (fNIRS)-hyperscanning provides a more naturalistic environment for experimental paradigms of social interaction and has recently drawn much attention. However, most fNIRS-hyperscanning studies have computed hyperlinks using sensor data directly while ignoring the fact that the sensor-level signals contain confounding noises, which may lead to a loss of sensitivity and specificity in hyperlink analysis. In this study, on the basis of independent component analysis (ICA), a source-level analysis framework is proposed to investigate the hyperlinks in a fNIRS two-person neuroscience study. The performance of five widely used ICA algorithms in extracting sources of interaction was compared in simulative datasets, and increased sensitivity and specificity of hyperlink analysis by our proposed method were demonstrated in both simulative and real two-person experiments. (C) 2017 Society of Photo-Optical Instrumentation Engineers (SPIE)
Depression and hypertension frequently present together in clinical practice. Evaluating the interaction between depression and hypertension would help stakeholders better understand the value of depression prevention in primary care. This retrospective study aimed to evaluate the excessive burden of depression on overall health and on health care utilization expenditure among hypertensive patients. A total of 7019 hypertensive patients (ICD-9-CM: 401) were identified from the 2012 Medical Expenditure Panel Survey (MEPS 2012) data, of which 936 patients had depression (ICD-9-CM: 311). Hypertension with depression was associated with worse health status (physical component score, -3.97 [17.9% reduction]; mental component score, -9.14 [9% reduction]), higher utilization of health care services (outpatient visits, 6.4 [63.8% higher]; nights of hospitalization, 0.9 [100% higher]; medication prescription, 22.6 [76.8% higher]), and higher health care expenditures (inpatient, $1953.2 [72% higher]; prescription drugs, $1995.5 [82% higher]).
Objective: To explore the effect of depression on the sleep quality, and the circadian rhythm of ambulatory blood pressure in patients with essential hypertension. Methods: A total of 73 older patients with hypertension were screened for depression and divided into two groups. The Pittsburgh Sleep Quality Index (PSQI) and the circadian rhythm of ambulatory blood pressure were compared between the non-depressed (control) and depressed (case) group. Results: In the case group, 24 h ambulatory SBP and DBP, and nocturnal SBP and DBP were higher than in the control group, and the circadian rhythm of non-dipper was higher (67.22% vs 40.13%, P < 0.01). There was a positive correlation between PSQI and depression (r = 0.432, P < 0.01). Conclusion: There was a significant correlation between sleep quality and depression in older patients with hypertension. Depression increases the circadian rhythm of non-dipper in older patients with hypertension. (C) 2017 Elsevier Ltd. All rights reserved.
Pressure overload has been shown to induce mitogen activated protein kinases (MAPKs) and reactivate the atrial natriuretic factor in the heart. To test the sensitivity of these signals to pressure overload, we assayed the activity of MAPKs extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 in protein lysates from the left ventricle (LV) or white blood cells (WBC) isolated from aortic banded mice with varying levels of pressure overload. In separated mice we measured atrial natriuretic factor mRNA levels by Northern blotting. As expected, a significant induction of atrial natriuretic factor mRNA levels was observed after aortic banding, and it significantly correlated with the trans-stenotic systolic pressure gradient but not with the LV weight: body weight ratio. In contrast, a significant correlation with systolic pressure gradient or LV weight: body weight ratio was observed for all of the MAPK activity detected in LV samples or WBCs. Importantly, LV activation of MAPKs significantly correlated with their activation in WBCs from the same animal. To test whether MAPK activation in WBCs might reflect uncontrolled blood pressure levels in humans, we assayed extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 activation in WBCs isolated from normotensive volunteers, hypertensive patients with controlled blood pressure values, or hypertensive patients with uncontrolled blood pressure values. Interestingly, in hypertensive patients with controlled blood pressure values, LV mass and extracellular signal-regulated kinase phosphorylation were significantly reduced compared with those in hypertensive patients with uncontrolled blood pressure values. These results suggest that MAPKs are sensors of pressure overload and that extracellular signal-regulated kinase activation in WBCs might be used as a novel surrogate biomarker of uncontrolled human hypertension. (Hypertension. 2010;55:137-143.)
Background: Hypertension has been associated to diabetes, and participates in the development of diabetic complications. The spontaneously hypertensive rat (SHR) is the gold standard model for the study of hypertension, and experimental diabetes has been currently investigated in SHR. Wistar-Kyoto rat is usually taken as control for SHR, however, regarding the glycemic homeostasis, WKY may be similar to SHR, when compared to the standard Wistar rat, importantly affecting the interpretation of data. Slc2a4 gene, which encodes the GLUT4 protein, is expressed in insulin-sensitive tissues, such as muscle cells and adipocytes, and alteration in Slc2a4/GLUT4 expression is inversely related to glycemic levels. We investigated the effect of diabetes on the expression of Slc2a4/GLUT4 and glycemic control in Wistar-Kyoto and SHR. Findings: Slc2a4 mRNA (Northern-blotting) and GLUT4 protein (Western-blotting) were investigated in skeletal muscles (soleus and extensor digitorum longus) of Wistar, Wistar-Kyoto and SHR, rendered or not diabetic for 1 month. Non-diabetic SHR shows hyperinsulinemia, and unaltered GLUT4 expression. The hyperglycemia was significantly attenuated in diabetic Wistar-Kyoto and SHR, compared to that observed in diabetic Wistar, although all of them presented the same hypoinsulinemic levels. Besides, diabetes significantly reduced Slc2a4/GLUT4 in Wistar, as expected; however, that was not observed in diabetic Wistar-Kyoto and SHR. Conclusions: Non-diabetic SHR is insulin resistant, despite unaltered GLUT4 expression. Diabetic Wistar-Kyoto and diabetic SHR presented high Slc2a4/GLUT4 expression in skeletal muscle, as compared to diabetic Wistar. This Slc2a4/GLUT4 regulation does not depend on insulin level and possibly protects the WKY and SHR from severe glycemic impairment.
Hypertriglyceridemia (HTG) aggravates the course of acute pancreatitis (AP). Intestinal barrier dysfunction is implicated in the pathogenesis of AP during which dysbiosis of intestinal microbiota contributes to the dysfunction in intestinal barrier. However, few studies focus on the changes in intestine during HTG-related acute necrotizing pancreatitis (ANP). Here, we investigated the changes in intestinal microbiota and Paneth cell antimicrobial peptides (AMPs) in HTG-related ANP (HANP) in rats. Rats fed a high-fat diet to induce HTG and ANP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Rats were sacrificed at 24 and 48 h, respectively. Pancreatic and ileal injuries were evaluated by histological scores. Intestinal barrier function was assessed by plasma diamine oxidase activity and D-lactate level. Systemic and intestinal inflammation was evaluated by tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1 beta and IL-17A expression. 16S rRNA high throughput sequencing was used to investigate changes in intestinal microbiota diversity and structure. AMPs (alpha-defensin5 and lysozyme) expression was measured by real-time polymerase chain reaction (PCR) and immunofluorescence. The results showed that compared with those of normal-lipid ANP (NANP) groups, the HANP groups had more severe histopathological injuries in pancreas and distal ileum, aggravated intestinal barrier dysfunction and increased TNF alpha, IL-1 beta, and IL-17A expression in plasma and distal ileum. Principal component analysis showed structural segregation between the HANP and NANP group. alpha-Diversity estimators in the HANP group revealed decreased microbiota diversity compared with that in NANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. In the HANP group, at phyla level, Candidatus_Saccharibacteria and Tenericutes decreased significantly, whereas Actinobacteria increased. At genus level, Allobaculum, Bifidobacterium, and Parasutterella increased significantly, while Alloprevotella, Anaerotruncus, Candidatus_Saccharimonas, Christensenellaceae_R-7_group, Rikenellaceae_RC9_gut_group, Ruminiclostridium_5, Ruminococcaceae_UCG-005, and Ruminococcaceae_UCG-014 decreased. Compared with those in the NANP rats, mRNA expression of lysozyme and alpha-defensin5 and protein expression of lysozyme decreased significantly in the HANP rats. Moreover, in the NANP rats and the HANP rats, Allobaculum abundance was inversely correlated with lysozyme expression, while Anaerotruncus abundance was positively correlated with it by Spearman test. In conclusion, intestinal microbiota dysbiosis and decreased AMPs of Paneth cells might participate in the pathogenesis of intestinal barrier dysfunction in HANP.
The present study investigated the role of epidermal stem cell-expressed microRNA let-7b in the pathogenesis of hypertrophied anal papillae. Hypertrophied anal papillae were examined for the presence of epidermal stem cells. Epidermal stem cells were identified using flow cytometry and immunofluorescent staining for the cell surface markers, integrin alpha 6 and integrin beta 1 subunits. Expression levels of microRNA let-7b in alpha 6+/beta 1+ and alpha 6-/beta 1-cells were compared using reverse transcription-quantitative polymerase chain reaction and northern blotting. Lentivirus-mediated expression of microRNA let-7b in epidermal stem cells was utilized in order to study the effects of this microRNA on the cell cycle proteins, cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4). MicroRNA let-7b-overexpressing cells were examined using flow cytometry, in order to determine the effects of the microRNA on cell cycle progression. alpha 6+/beta 1+epidermal stem cells were identified in hypertrophic anal papillae. Following isolation and enrichment of the alpha 6+/beta 1+population, these cells were found to have a rapid rate of proliferation in vitro. The expression of cell cycle-related proteins was elevated in this population, compared with that in alpha 6-/beta 1-cells. The expression of microRNA let-7b in alpha 6+/beta 1+epidermal stem cells was significantly lower than that in alpha 6-/beta 1-cells. Two microRNA let-7b target genes, CCND1 and CDK4, were found to be upregulated in alpha 6+/beta 1+cells. When the exogenous precursor, microRNA let-7, was overexpressed in alpha 6+/beta 1+ epidermal stem cells, the cell proliferation rate was significantly lower than that in cells expressing microRNA let-7 containing a mutated seed sequence. The addition of exogenous microRNA let-7 resulted in an increased expression level of mature microRNA let-7b, while the expression of CCND1 and CDK4 was reduced. Epidermal stem cells transfected with microRNA let-7b were arrested in the G2/M phase and the percentage of cells in S-phase was significantly reduced. In conclusion, let-7b expression results in upregulation of the cell cycle-related proteins, CCND1 and CDK4, resulting in the excessive proliferation that leads to the formation of hypertrophic anal papillae.
Objective: The current study examined whether (a) Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms were associated with dysregulation of stress-related mechanisms, and (b) whether ADHD symptoms interact with affective disorders in their association with dysregulated stress-related mechanisms. Methods: Data were obtained from 2307 subjects participating in the Netherlands Study of Depression and Anxiety. Stress-related mechanisms were reflected by the following biomarkers: (1) hypothalamic pituitary -adrenal axis indicators (salivary cortisol awakening curve, evening cortisol, cortisol suppression after a 0.5 mg dexamethasone suppression test (DST)); (2) autonomic nervous system measures (heart rate, pre-ejection period, respiratory sinus arrhythmia); (3) inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha); (4) brain-derived neurotrophic factor. ADHD symptoms were measured using Conners' Adult ADHD Rating Scale and used both dichotomous (High ADHD symptoms (yes/no)) and continuous (Inattentive symptoms, Hyperactive/Impulsive symptoms, and the ADHD index). Results: Regression analyses showed associations between High ADHD symptoms, Inattentive symptoms, the ADHD index and a higher cortisol awakening curve, between Hyperactive/Impulsive symptoms and less cortisol suppression after DST, and between Inattentive symptoms and a longer pre-ejection period. However, the associations with the cortisol awakening curve disappeared after adjustment for depressive and anxiety disorders. No associations were observed between ADHD symptoms and inflammatory markers or BDNF. ADHD symptoms did not interact with affective disorders in dysregulation of stress-related mechanisms. Conclusion: Some associations were observed between ADHD symptoms, the HPA-axis, and the pre-ejection period, but these were mostly driven by depressive and anxiety disorders. This study found no evidence that ADHD symptomatology was associated with dysregulations in inflammatory markers and BDNF. Consequently, ADHD symptoms did not confer an added risk to the disturbances of stress-related mechanisms in an - already at-risk - population with affective disorders. (C) 2017 Elsevier Ltd. All rights reserved.
The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases ('the tetranucleotide hypothesis'); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts.
Drawing together social psychologists' concerns with equality and cognitive psychologists' concerns with scientific inference, 6 studies (N = 841) showed how implicit category norms make the generation and test of hypothesis about race highly asymmetric. Having shown that Whiteness is the default race of celebrity actors (Study 1), Study 2 used a variant of Wason's (1960) rule discovery task to demonstrate greater difficulty in discovering rules that require specifying that race is shared by White celebrity actors than by Black celebrity actors. Clues to the Whiteness of White actors from analogous problems had little effect on hypothesis formation or rule discovery (Studies 3 and 4). Rather, across Studies 2 and 4 feedback about negative cases-non-White celebrities-facilitated the discovery that White actors shared a race, whether participants or experimenters generated the negative cases. These category norms were little affected by making White actors' Whiteness more informative (Study 5). Although participants understood that discovering that White actors are White would be harder than discovering that Black actors are Black, they showed limited insight into the information contained in negative cases (Study 6). Category norms render some identities as implicit defaults, making hypothesis formation and generalization about real social groups asymmetric in ways that have implications for scientific reasoning and social equality.
Microglial cells are phagocytic cells of the central nervous system (CNS) and have been proposed to be a primary component of the innate immune response and maintain efficient CNS homeostasis. Microglial cells are activated during various phases of tissue repair and participate in various pathological conditions in the CNS. Following spinal cord injury (SCI), anoxemia is a key problem that results in tissue destruction. Hypoxia-inducible factor 1-alpha (HIF-1 alpha) may protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. However, numerous studies have revealed that hypoxia upregulates HIF-1 alpha expression leading to the death of microglial cells. The present study investigated the alterations in HIF-1 alpha expression levels and the mechanism of autophagic cell death mediated by HIF-1 alpha in microglial cells induced by hypoxia. Hypoxia was demonstrated to induce HIF-1 alpha expression and autophagic cell death in microglial cells. Enhanced autophagy reduced cell death during the initial stages by restraining the functions of autophagy-associated genes (microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate and Beclin-1) and modulating the expression of inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta). Target value was determined by Cell Counting Kit 8 and cell death by flow cytometry. Transmission electron microscopy, immunohistochemical staining, reverse transcription-quantitative polymerase chain reaction, western blotting, and ELISA were used for further analysis. However, increased expression of HIF-1 alpha induced cell death and autophagic cell death in microglial cells. Furthermore, the effects of the HIF-1 alpha inhibitor 2-methoxyestradiol and HIF-1 alpha small interfering RNA on the death and autophagy of microglial cells in vitro were investigated. These investigations revealed the suppression of autophagy, the decrease of cell viability and the increase of inflammatory cytokines results from HIF-1 alpha inhibition or HIF-1 alpha silencing. In conclusion, the results indicated that appropriate expression of HIF-1 alpha can ameliorate autophagic cell death of microglial cells associated with hypoxia, and may provide a novel therapeutic approach for SCI associated with microglial cell activation.
To perform pathogenic and pathological investigations on explosive epidemics of Hyriopsis cumingii Lea in Hunan Province, China between 2005 and 2011. We isolated pathogenic bacteria SJ-2 from naturally infected Hyriopsis cumingii Lea, and the SJ-2 strain was artificial infected into the normal Hyriopsis cumingii Lea by axe foot injection method. The strain was identified according to conventional bacteriological isolation and identification and molecular biology methods, and pathological changes caused by the bacteria in diseased mussel tissues were observed. According to morphological and culture characteristics, physiological and biochemical tests and 16S rDNA molecular identification, SJ-2 strain shares 99% sequence identity with the type strain of Aeromonas veronii (A. Veronii). Results for antibiotic susceptibility tests showed that among 50 drugs, A. Veronii was highly sensitive to 15 drugs, moderately sensitive to 5 drugs, and showed drug resistance to left drugs. Macroscopical lesions, pathological changes and cytopathology were summarized. The pathogenic bacteria SJ-2 was isolated from Hyriopsis cumingii Lea affected by explosive epidemic disease, and was identified as A. Veronii. SJ-2 strain caused multi-organ lesions and function failure in corresponding organs in the Hyriopsis cumingii Leal, resulting in gradually decreased and disappeared normal physiological metabolism, and eventually death.
C1q is the target recognition sequence of the classical complement pathway and a major link that connects innate and acquired immunity. In this study, a C1qDC homolog, HcC1qDC5, from the triangle-shell pearl mussel (Hyriopsis cumingii) was identified. The complete nucleotide sequence of HcC1qDC5 cDNA consists of a 5'-untranslated terminal region (UTR) of 123 bp, a 3'-UTR of 105 bp with a poly(A) tail, and an open reading frame (ORF) of 1344 bp, which encodes a polypeptide of 447 amino acids. HcC1qDC5 contains a signal peptide and three typical C1q domains. The HcC1qDC5 gene was expressed in all tested tissues, with the highest expression in the. mantle. Staphylococcus aureus or Vibrio parahaemolyticus infection increased the mRNA transcript levels of HcC1qDC5 in the hepatopancreas and mantle. The recombinant HcC1qDC5 protein could bind to Gram-negative and Gram-positive bacteria as well as to different PAMPs (LPS and PGN). RNAi results showed that HcC1qDC5 was involved in V. parahaemolyticus-induced HcTNF and HcWAP expression. The combined results demonstrated that HcC1qDC5 participates in the innate immunity of H. cumingii. (C) 2016 Elsevier Ltd. All rights reserved.
BACKGROUND: In order to study the novel genes related to rat embryonic implantation, a novel implantation-associated gene, Iag-1, was identified and characterized from rat uterus of early pregnancy. Iag-1 was initially derived from suppressive subtracted hybridization of a cDNA library of rat uterus, which was used to analyse differentially expressed genes between the preimplantation and implantation period. METHODS:The full-length cDNA sequence of Iag-1 was cloned from rat uterus on D5.5 of pregnancy by 5'- and 3'-RACE. The expression of Iag-1 in the uterus of early pregnancy, pseudopregnancy, artificial decidualization and activation of delayed implantation was detected by northern blotting, in situ hybridization, western blotting and immunofluorescence. Endometrial stromal cells (ESCs) were isolated from rat uterus. The effect of Iag-1 on ESCs proliferation and apoptosis were determined by MTT assay, TUNEL and Hoechst staining. Apoptosis-related proteins in ESCs were detected by western blotting. RESULTS: Differential patterns of Iag-1 expression were detected in rat embryo and in the uterus during the peri-implantation period. Iag-1 was specifically localized in glandular epithelium and luminal epithelium. In contrast, the expression of Iag-1 was not significantly altered in uterus of pseudopregnancy and artificial decidualization, but was significantly increased in the uterus after activation of delayed implantation. Stable expression of introduced Iag-1 inhibited the proliferation of in vitro-cultured ESCs. Significant apoptosis was also detected in the ESCs overexpressing Iag-1 , along with the enhancement of p53 and Bax protein expression. CONCLUSIONS:Overexpression of Iag-1 can inhibit ESCs proliferation and induce ESCs apoptosis, and p53 and Bax may play an important role in the process of Iag-1-induced apoptosis.
The concepts developed by Ian Hacking during his lectures at the CollSge de France (2000-2006) have provided an important contribution to the debates within the field of philosophy of psychiatry. Professor at the Chair of Philosophy and History of Scientific Concepts after Michel Foucault, Hacking is the author of a reflection on the classification of mental disorders, which arises from the problem of the natural kinds. In order to explain the case studies developed in Hacking's Paris lectures, we first go back to the definition of a series of concepts, then we discuss the status of his scientific metaphors. Finally we analyze the relationship between the notions, respectively, of "transient mental illness" and "culture-bound syndrome". We emphasize that the latter derives from the Canadian transcultural psychiatry.
Introduction: Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy. Method: We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy. Results: In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8 mu g/ml (IQR 5.6-8.1) versus 6.7 mu g/ml (IQR 3.9-8.1), respectively. Patients with an elevated faecal calprotectin >250 mu g/g had lower adalimumab trough levels (median 6.7, IQR 3.9-8) compared to patients with faecal calprotectin <250 mu g/g (median 7.7, IQR 6.1-8.1) though this did not achieve statistical significance (p = .062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2 mu g/ml (IQR 5.7-8.1) compared to those not on concurrent immunomodulator, 6.1 mu g/ml (IQR 2.7-7.7, p = .0297). Conclusion: Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.
This paper presents an edge boosting method for I/O output buffer using signal front detection digital control circuit. The presented architecture detects I/O data or clock signal transitions and activates additional drive strength fingers in the output buffer resulting in output current increase which improves the slew rate, compensating for losses in transmission lines. The presented edge boosting method can be used in the I/O circuits of such standards as DDR(Double Data Rate), USB(Universal Serial Bus), PCI(Peripheral Component Interconnect) etc.
This paper deals with the susceptibility prediction of integrated circuits against the conducted interference coupled on their power supply pins. An integrated operational amplifier OP A694 is studied as a first case. The integrated circuit electromagnetic (ICEM) model is used to describe the inner power distribution network of OP A694 by theoretical study and experimental measurement. A curve fitting method is proposed to obtain the ICEM model parameters from different kinds of measurements without knowing the precise inner physical structure information of OPA694. Then the direct power injection (DPI) experimental test is conducted to measure the susceptibility of OP A694 to conducted sine-wave noise. And from the immunity measurement, a common simulation susceptibility criterion is obtained. Finally the whole simulation model of DPI setup including the ICEM model of OPA694 is established to predict its susceptibility and the model is perfectly verified in a 200MHz frequency range.
Independent Component Analysis (ICA) - one of the basic tools in data analysis - aims to find a coordinate system in which the components of the data are independent. Most of existing methods are based on the minimization of the function of fourth-order moment (kurtosis). Skewness (third-order moment) has received much less attention. In this paper we present a competitive approach to ICA based on the Split Gaussian distribution, which is well adapted to asymmetric data. Consequently, we obtain a method which works better than the classical approaches, especially in the case when the underlying density is not symmetric, which is a typical situation in the color distribution in images. (C) 2017 Elsevier Ltd. All rights reserved.
The structure of oceanic spreading centres and subsurface melt distribution within newly formed crust is largely understood from marine seismic experiments. In Iceland, however, sub-aerial rift elevation allows both accurate surface mapping and the installation of large broadband seismic arrays. We present a study using ambient noise Rayleigh wave tomography to image the volcanic spreading centres across Iceland. Our high resolution model images a continuous band of low seismic velocities, parallelling all three segments of the branched rift in Iceland. The upper 10 km contains strong velocity variations, with shear wave velocities 0.5 km s(-1) faster in the older non-volcanically active regions compared to the active rifts. Slow velocities correlate very closely with geological surface mapping, with contours of the anomalies parallelling the edges of the neo-volcanic zones. The low-velocity band extends to the full 50 km width of the neo-volcanic zones, demonstrating a significant contrast with the narrow (8 km wide) magmatic zone seen at fast spreading ridges, where the rate of melt supply is similarly high. Within the seismically slow rift band, the lowest velocity cores of the anomalies occur above the centre of the mantle plume under the Vatnajtikull icecap, and in the Eastern Volcanic Zone under the central volcano Katla. This suggests localisation of melt accumulation at these specific volcanic centres, demonstrating variability in melt supply into the shallow crust along the rift axis. Shear velocity inversions with depth show that the strongest velocity contrasts are found in the upper 8 km, and show a slight depression in the shear velocity through the mid crust (10-20 km) in the rifts. Our model also shows less intensity to the slow rift anomaly in the Western Volcanic Zone, supporting the notion that rift activity here is decreasing as the ridge jumps to the Eastern Volcanic Zone. (C) 2017 The Author(s). Published by Elsevier B.V.
Collodion baby is a severe form of congenital ichthyosis detected in neonatal period. It often has a characteristic clinical picture. When evolution is not fatal; it often causes dry Ichthyosis. Thanks to molecular biology techniques, prenatal diagnosis can be made since the 10-12 weeks of amenorrhea, allowing genetic counselling. Prognosis depends on several parameters, namely the degree of the initial manifestation, the duration of desquamation, as well as underlying Ichthyosis This rewiew of the literature which aims to clarify the diagnostic aspects and therapeutic treatment as well as the role of the antenatal diagnosis is based on a new observation of a collodion baby born at 34 weeks, of a parturient woman having an index case and of infant deaths occurring in the first day of life.
FRMD7 mutations are associated with X-linked idiopathic congenital nystagmus (ICN); however, the underlying mechanisms whereby mutations of FRMD7 lead to ICN remain unclear. In a previous study, the first FRMD7 splice variant (FRMD7-S) was cloned and identified, and FRMD7-S was hypothesized to play a significant role in neuronal differentiation and development. The present study investigated a novel multiple exon-skipping mRNA splice variant of FRMD7, termed FRMD7_SV2, which was detected in NT2 cells using northern blotting. The mRNA expression levels of FRMD7_SV2 in the developing human fetal brain were examined using reverse transcription polymerase chain reaction (PCR), while the expression levels in NT2 cells treated with retinoid acid (RA) or bone morphogenetic protein-2 were investigated using quantitative PCR. The results revealed that the expression of FRMD7_SV2 was spatially and temporally restricted in human fetal brain development, and was upregulated upon RA-induced neuronal differentiation of the NT2 cells. These results indicated that as a novel splice variant of FRMD7, FRMD7_SV2 may play a role in neuronal development.
Interstitial lung diseases ( ILDs) are a heterogeneous group of lung disorders with distinct clinical, radiological and morphological features. Among ILDs, idiopathic pulmonary fibrosis ( IPF) is associated with the worst prognosis, with a survival worse than many cancers, even after the advent of two anti- fibrotic drugs, shown to halve disease progression. Reaching the correct diagnosis is crucial, as pathogenesis, prognosis and treatment options differ substantially from other interstitial fibrosing processes where immune overactivity plays a role in driving fibrosis. However, a subgroup of patients with fibrotic lung disease mediated by immune dysregulation can experience relentlessly progressive fibrosis despite immunosuppressive treatment, and behave similarly to IPF. It is clear that even in non IPF ILDs, phenotypes of relentlessly progressive disease exist, and molecular pathways may overlap. One of the main challenges for the future is the use of high throughput molecular biology techniques to stratify patients with progressive fibrotic lung disease, in order to identify genetic, epigenetic and protein markers to predict the individual patient's rate of progression and fundamental molecular pathways involved. In this review, we will focus on the challenges in the diagnosis and management of idiopathic pulmonary fibrosis as well as differences and areas of overlap with other fibrotic ILDs, including fibrotic hypersensitivity pneumonitis, connective tissue disease- associated ILD and interstitial pneumonia with autoimmune features.
With the increasing installed capacity of wind power and the interdependencies among multiple energy sectors, optimal operation of integrated energy systems (IES) with combined cooling, heating and power (CCHP) is becoming more important. This paper proposes an optimal dispatch strategy for IES with CCHP and wind power. Natural gas system is modeled and its security constraints are integrated into the optimal dispatch model. The gas shift factor (GSF(gas)) matrix for natural gas system is derived to quantify the impact of gas supply and load at each node on the gas flow through the pipelines so that the pipeline flow equation is linearized. The objective function of the optimization model is to minimize the total operation cost of IES. Then the model is transformed into mixed integer linear programming (MILP) formulation to improve the computation efficiency. Numerical case studies conducted demonstrate the lower operation cost of the proposed model facilitating wind power integration. (C) 2016 Elsevier Ltd. All rights reserved.
Renal damage is the major cause of SLE associated mortality, and IFIT1 expression was elevated in SLE cases in accordance of previous studies. Therefore, we conducted an animal study to identify the role of IFIT1 expression in renal pathological changes. 18 female MRL/lpr mice and same number of female BALB/c mice were enrolled in present study. Quantitative analysis of urine protein, Complement C3 and C4, and anti-ds DNA antibody were conducted. HE and PAS staining and TEM analysis were employed to observe the pathological changes in renal tissue. Significant elevation on urine protein and anti-dsDNA and reduction on Complement C3 and C4 were observed in MRL/lpr mice when comparing the controls in same age. Staining and TEM analysis observed several pathological changes in glomerulus among MRL/lpr mice, including cellular enlargement, basement membrane thickening, and increased cellularcasts. The linear regression analysis found the optical density of IFIT1 was inversely associated with F-actin, Nephrin, and Podocin, but not Synatopodin. In summary, IFIT1 expression is associated with podocytes damage, and capable of suppressing some proteins essential to glomerular filtration.
In high power applications, proper gate control strategy for insulated gate bipolar transistors (IGBTs) can increase their efficient and reliability. As to the feed-back control strategy, the key issues are the control speed and control stability. This paper proposed a new feed-back control method integrated in digital gate driver for high power IGBT. It aims for controlling the current and voltage slope suppressing the voltage overshoot and electromagnetic interference (EMI) in switching transient. The digital gate driver for large power IGBT detects the collector current and voltage in real time. Then the detected analog signal is digitally sampled and sent to the digital core on board. An algorithm similar to bang-bang control is deployed in forward control loop to adjust the gate drive resistance. The control stability and robustness can be guaranteed as a result. The whole detection and control process is accomplished in real time with only hundreds of nanoseconds. Thus, the proposed control method can optimized the IGBT switching transient with high reliability and time effectiveness. Experimental results validate the feasibility of the proposed feed-back digital control method.
Since coal will be widely used in the next decades, mainly in the developing countries such as China and India, carbon capture and storage (CCS) technologies will have a key role in the containment of global warming. This paper presents a techno-economic comparison between the most promising power generation technologies for a CO2-free power generation in a short-term future. In particular, three different power generation technologies have been considered in their conventional (without CCS) and CO2-free configurations: (a) ultra supercritical (USC) pulverized coal combustion, (b) oxy-coal combustion (OCC) and (c) integrated gasification combined cycle (IGCC). Process simulation, based on Aspen Plus and Gate Cycle commercial tools, allows to calculate plant performance, including the energy penalty due to the CCS system (10.9% points for USC and 8.7% points for IGCC). In parallel, a detailed economic assessment shows that, among the commercial-ready technologies, USC could be the most convenient solution for power generation without CCS (presenting a levelized cost of electricity - LCOE - of 38.6 (sic)/MW h, significantly lower than 43.7 (sic)/MW h of IGCC), whereas IGCC becomes competitive for CO2-free systems (with a LCOE of 59.6 (sic)/MW h, to be compared with 63.4 (sic)/MW h of USC). Moreover, oxy-coal combustion, which is currently not mature enough for commercial-scale applications, promises to become strongly competitive for CCS applications due to its relatively low levelized cost of electricity (62.8 (sic)/MW h). This kind of analysis typically presents strong uncertainties, due to the variability of several key parameters (e.g. fuel and CCS prices, determined by the fluctuation of the international markets, or an improvement of the technologies). Therefore, a sensitivity analysis has been done to determine the effects of these potential fluctuation or the improvement on the economic performance of the plant. (C) 2017 Elsevier Ltd. All rights reserved.
Lymphocyte differentiation is set to produce myriad immune effector cells with the ability to respond to multitudinous foreign substances. The uniqueness of this developmental system lies in not only the great diversity of cellular functions that it can generate but also the ability of its differentiation intermediates and mature effector cells to expand upon demand, thereby providing lifelong immunity. Surprisingly, the goals of this developmental system are met by a relatively small group of DNA-binding transcription factors that work in concert to control the timing and magnitude of gene expression and fulfill the demands for cellular specialization, expansion, and maintenance. The cellular and molecular mechanisms through which these lineage-promoting transcription factors operate have been a focus of basic research in immunology. The mechanisms of development discerned in this effort are guiding clinical research on disorders with an immune cell base. Here, I focus on IKAROS, one of the earliest regulators of lymphoid lineage identity and a guardian of lymphocyte homeostasis.
IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-gamma, induces the expression of IL-18BP, IDO and PD-L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-gamma display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-gamma and IL-27. In addition, functional analysis of IL-27-regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels. Importantly, we found that IL-27 induced HLA class I molecule expression in human cancer cells of different histotypes, including tumor cells showing very low expression. IL-27 failed only in a cancer cell line bearing a homozygous deletion in the B2M gene. Altogether, these data point out to a broad set of activities shared by IL-27 and IFN-gamma, which are dependent on the common activation of the STAT1 pathway. These data add further explanation to the anti-tumor activity of IL-27 and also to its dual role in immune regulation.
Accumulated data have shown that alternatively activated macrophage exerts a modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a critical modulator in adaptive and innate immune, has been implicated in autoimmunity and inflammation. Previously, we have reported that IL-33 functions as a protective modulator in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33 primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced colitis. The strong polarized effect of IL-33 was tightly associated with the markedly increased induction of Th2-type cytokines. To confirm the beneficial effects of AAM induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice were transferred to recipient mice with TNBS colitis. The adoptive transfer resulted in prominent inhibition of disease activity and inflammatory cytokines in the TNBS-treated mice. In conclusion, our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis, which is closely related to AAM polarization.
Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia.
The problem of the secure transmission of digital image has paid more and more attention to the network and this paper designs a special image encryption scheme. Image encryption scheme is designed based on the hyper chaos of generalized five-order Henon mapping and five-order cellular neural network (CNN) system. Firstly, the chaotic sequence X, which is regarded as the initial conditions of CNN system, is generated by the five-order generalized Henon mapping. Then another chaotic sequence Y is produced by the CNN system. At last, the cipher image is generated by the transformation of random sequence Y and the original image. Toward the end, the paper makes the simulation experiment and draws a conclusion that the algorithm of image encryption has strong attack resistance, good safety, and suitable to spread in the network through analyzing the statistical characteristics of the image information entropy, correlation and histogram as well as the key space and the sensitivity.
We propose an analog front-end integrated circuit (IC) design for a readout IC (ROIC), which applies a fixed-voltage-bias sensing method with a capacitance transimpedance amplifier (CTIA) to an input stage in order to simplify the circuit structure of the ROIC and the IR sensor characteristic control. For a sample-and-hold stage, in order to display and control a signal detected by the IR sensor using a 2-D focal plane array, a differential delta sampling circuit is proposed, which effectively removes the fixed pattern noise. In addition, a two-stage variable-gain amplifier equipped with a rail-to-rail fully differential operational amplifier is applied to the ROIC to achieve high voltage sensitivity. The output characteristic of the proposed device is 30.84 mV/K and the linearity error rate is less than 0.07%. After checking the performance of the ROIC using an HSPICE simulation, the chip is manufactured and measured using the United Microelectronics Corporation Japan 0.35-mu m standard CMOS process to confirm that the simulation results from the actual design are in close agreement with the measurement results.
Sound and image compete in It Can Pass Through the Wall, as in Fritz Lang's M (1931), to create tension between what is seen and what is heard. This disconnect between image and sound draws attention to the limits of the visual and the possibilities of the audible.
Background and objectives: Literature suggests that imagery rescripting (ImRs) is an effective psychological intervention. Methods: We conducted a meta-analysis of ImRs for psychological complaints that are associated with aversive memories. Relevant publications were collected from the databases Medline, Psychlnfo, and Web of Science. Results: The search identified 19 trials (including seven randomized controlled trials) with 363 adult patients with posttraumatic stress disorder (eight trials), social anxiety disorder (six trials), body dysmorphic disorder (two trials), major depression (one trial), bulimia nervosa (one trial), or obsessive compulsive disorder (one trial). ImRs was administered over a mean of 4.5 sessions (range, 1-16). Effect size estimates suggest that ImRs is largely effective in reducing symptoms from pretreatment to post-treatment and follow-up in the overall sample (Hedges' g = 1.22 and 1.79, respectively). The comparison of ImRs to passive treatment conditions resulted in a large effect size (g = 0.90) at posttreatment. Finally, the effects of ImRs on comorbid depression, aversive imagery, and encapsulated beliefs were also large. Limitations: Most of the analyses involved pre-post comparisons and the findings are limited by the small number of randomized controlled trials. Conclusions: Our findings indicate that ImRs is a promising intervention for psychological complaints related to aversive memories, with large effects obtained in a small number of session. (C) 2016 Elsevier Ltd. All rights reserved.
Imaginative resistance refers to a perceived inability or unwillingness to enter into fictional worlds that portray deviant moralities (Gendler, 2000): we can all easily imagine that dragons exist, but many people feel incapable of imagining fictional worlds in which morality works differently. Although this phenomenon has received much attention from philosophers, no one has attempted to operationalize the construct in a self-report scale. In Study 1, we developed the Imaginative Resistance Scale (IRS), investigated its relationship to theoretically related constructs, and confirmed its structure and reliability (r(alpha) = 0.92) in a large sample. In Study 2, we asked participants to rate scenarios expected to provoke imaginative resistance and predicted these ratings from the IRS and its validity measures. IRS scores accounted for variability in ease of imagining these scenarios over and above gender, political orientation, and three related measures. The results are discussed in terms of theories of imaginative resistance and directions for future research. (C) 2017 Elsevier Ltd. All rights reserved.
Phagocytes display marked heterogeneity in their capacity to induce and control acute inflammation. This has a significant impact on the effectiveness of antimicrobial immune responses at different tissue sites as well as their predisposition for inflammation-associated pathology. Imaging flow cytometry provides novel opportunities for characterization of these phagocyte populations through high spatial resolution, statistical robustness, and a broad range of quantitative morphometric cell analysis tools. This study highlights an integrative approach that brings together new tools in imaging flow cytometry with conventional methodologies for characterization of phagocyte responses during acute inflammation. We focus on a comparative avian in vivo challenge model to showcase the added depth gained through these novel quantitative multiparametric approaches even in the absence of antibody-based cellular markers. Our characterization of acute inflammation in this model shows significant conservation of phagocytic capacity among avian phagocytes compared to other animal models. However, it also highlights evolutionary divergence with regards to phagocyte inflammation control mechanisms based on the internalization of apoptotic cells. (C) 2016 Published by Elsevier Inc.
Regulation of eukaryotic transcription in vivo occurs at distinct stages. Previous research has identified many active or repressive transcription factors (TFs) and core transcription components and studied their functions in vitro and in vivo. Nonetheless, how individual TFs act in concert to regulate mRNA gene expression in a single cell remains poorly understood. Direct observation of TF assembly and disassembly and various biochemical reactions during transcription of a single-copy gene in vivo is the ideal approach to study this problem. Research in this area requires developing novel techniques for single-cell transcription imaging and integrating imaging studies into understanding the molecular biology of transcription. In the past decade, advanced cell imaging has enabled unprecedented capabilities to visualize individual TF molecules, to track single transcription sites, and to detect individual mRNA in fixed and living cells. These studies have raised several novel insights on transcriptional regulation such as the "hit-and-run" model and transcription bursting that could not be obtained by in vitro biochemistry analysis. At this point, the key question is how to achieve deeper understandings or discover novel mechanisms of eukaryotic transcriptional regulation by imaging transcription in single cells. Meanwhile, further technical advancements are likely required for visualizing distinct kinetic steps of transcription on a single-copy gene in vivo. This review article summarizes recent progress in the field and describes the challenges and opportunities ahead. (C) 2016 Elsevier Ltd. All rights reserved.
Imbalance data are defined as a dataset whose proportion of classes is severely skewed. Classification performance of existing models tends to deteriorate due to class distribution imbalance. In addition, over-representation by majority classes prevents a classifier from paying attention to minority classes, which are generally more interesting. An effective ensemble classification method called RHSBoost has been proposed to address the imbalance classification problem. This classification rule uses random undersampling and ROSE sampling under a boosting scheme. According to the experimental results, RHSBoost appears to be an attractive classification model for imbalance data. (C) 2017 Elsevier B.V. All rights reserved.
While much literature has examined immigrants' health in Canada, less attention has focused specifically on the life stress, an important yet understudied post-migration challenge which may lead to poor coping strategies and negative health consequences. For this study, the pooled 2009-2014 Canadian Community Health Survey (CCHS) was analyzed, using multilevel logistic regression to examine the compositional effects (at an individual level) and areal effects (at a CMA/CA level) on reported high life stress. Separate models have been run for immigrants and non-immigrants for comparative purposes. The results reveal different ways in which select individual socioeconomic and lifestyle factors affect life stress. A statistically significant yet small areal effect at the CMA/CA level on life stress was identified for both immigrants and non-immigrants. When comparing immigrants to non-immigrants, factors such as smoking, length of residency in Canada, and mental health status were found to be particularly informative for predicting high life stress among immigrants. A Healthy Immigrant Effect (HIE) is partially evident, as immigrants with a longer stay in Canada are more likely to be highly stressed than recent arrivals. The areal effect on variances in high life stress is minimal, suggesting the importance of focusing on individual-level effects as stress predictors.
It is commonly known that enzymatic transformations are considerably more specific than classical chemical reactions which usually lead to formation of byproducts. That is why the enzymes are a powerful tool in the field of analytical chemistry. The main problems occurring while working with enzymes stem from their relatively high price and sensitivity to non-physiological conditions. The above mentioned disadvantages may be overcome through enzyme immobilization which allows for reusing the biocatalyst as long as it retains its activity. When the immobilization is performed correctly the enzymes are more stable and also more resistant to denaturation. Such an approach in combination with additional benefits of miniaturization, heterogeneous catalysis and flow-mode operation contributes to the various applications of the Immobilized Enzyme Reactors (IMERs) in particular, microfluidic (mu-IMERs). In the present review various types of mu-IMERs were described. Particular attention was paid to techniques of their preparation including immobilization strategies and technical solutions connected with their applications using both capillary and chip format. (C) 2016 Elsevier B.V. All rights reserved.
Background: In October 2010, a pharmacist-driven stewardship program was implemented at the Brigham and Women's Hospital to ensure continued adherence to the prescribing guideline, focusing on indications for intravenous immune globulin (IVIG) use and dosing per ideal body weight. Objective: The primary objective was to describe an IVIG stewardship program at a tertiary academic medical center. Methods: This was a prospective, observational study from January 2013 through December 2014. All patients ordered to receive IVIG during the defined study period were included. The intervention assessed describes a pharmacist-driven IVIG stewardship program for medication approval. The primary end point was guideline compliance based on indication, dose, dosing weight, and frequency. Secondary end points included the number of patients receiving IVIG, indications, orders discontinued as a result of guideline nonadherence, and total amount dispensed. Results: A total of 418 patients were identified during the study time frame. The top indications were: hypogammaglobulinemia in bone marrow transplantation and hematological malignancy (50.7%), acute solid organ rejection (11.8%), and immune thrombocytopenia with bleeding (10.1%). In all, 12 patients (2.9%) received IVIG for an indication nonadherent with the IVIG prescribing guideline; 9 patients (2.2%) and 2 patients (0.5%), respectively, received a different dose or frequency per the prescribed indication; and 12 orders (2.9%) for indications nonadherent to the guideline were discontinued. A total of 26033 g of IVIG were dispensed during the study period. Conclusions: An IVIG stewardship program, including an institution-specific prescribing guideline and a pharmacist-driven stewardship program, may ensure guideline compliance for appropriateness of indication and dose at an academic medical center.
Background. Oxytetracycline (OTC), which is largely employed in zootechnical and veterinary practices to ensure wellness of farmed animals, is partially absorbed within the gastrointestinal tract depositing in several tissues. Therefore, the potential OTC toxicity is relevant when considering the putative risk derived by the entry and accumulation of such drug in human and pet food chain supply. Despite scientific literature highlights several OTC-dependent toxic effects on human and animal health, the molecular mechanisms of such toxicity are still poorly understood. Methods. Here, we evaluated DNA damages and epigenetic alterations by quantitative reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, chromatin immuno-precipitation and Western blot analysis. Results. We observed that human peripheral blood mononuclear cells (PBMCs) expressed DNA damage features (activation of ATM and p53, phosphorylation of H2AX and modifications of histone H3 rnethylation of lysine K4 in the chromatin) after the in vitro exposure to OTC. These changes are linked to a robust inflammatory response indicated by an increased expression of Interferon (IFN)-gamma and type 1 superoxide dismutase (SOD1). Discussion. Our data reveal an unexpected biological in vitro activity of OTC able to modify DNA and chromatin in cultured human PI3MC. In this regard, OTC presence in foods of animal origin could represent a potential risk for both the human and animal health.
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA- 4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer. Current success of cancer immunotherapy is built upon the work of cancer antigens and co-inhibitory signaling molecules identified 20 years ago. Among the large numbers of target antigens, CD19 is the best target for CAR T cell therapy for blood cancer, but CAR-engineered T cell immunotherapy does not yet work in solid cancer. NY-ESO-1 is one of the best targets for TCR-based immunotherapy in solid cancer. Despite the great success of checkpoint blockade therapy, more than 50% of cancer patients fail to respond to blockade therapy. The advent of new technologies such as next-generation sequencing has enhanced our ability to search for new immune targets in onco-immunology and accelerated the development of immunotherapy with potentially broader coverage of cancer patients. In this review, we will discuss the recent progresses of cancer immunotherapy and novel strategies in the identification of new immune targets and mutation-derived antigens (neoantigens) for cancer immunotherapy and immunoprecision medicine.
Both microRNAs and T helper (Th) cells involve in autoimmune diseases and their effects and interactions in immune thrombocytopenia (ITP) remain unclear. In the present study, we investigated the expression profiles of seven immune-related microRNAs (miR-155, 146a, 326, 142-3p, 17-5p, 21 and 181a) and the frequencies of four Th cells (Th1, Th2, Th17 and Treg) in peripheral blood mononuclear cell (PBMCs) of ITP patients and healthy controls. Platelet autoantibodies specific for GPIIb/IIIa or GPIb/IX were measured using MAIPA method. The regulating effect of miR-146a on Th differentiation was evaluated after using agomir. Our results showed that the expression of miR-146a, miR-326 or miR-142-3p in ITP patients was lower than that of controls. The frequencies of Treg cells were decreased, whereas the frequencies of Th17 and Th22 cells were increased significantly in ITP patients compared to those in controls. The expression levels of miR-142-3p and miR-146a were negatively correlated with Th17 cells, respectively. The expression of miR-146a was positively correlated with the frequencies of Treg cells and platelet counts. No significant correlation was found between the miRNAs expression and different autoantibody groups. The up-regulated miR-146a expression with agomir contributed to the differentiation of Th17 and Treg in ITP patients. Moreover, miR-146a was increased in the presence of DEX in PBMCs of ITP patients in vitro. Our study represents the abnormal expression profile of immune-related miRNAs in ITP patients, and miR-146a may be involved in Tregs differentiation and function.
In the broad field of autoimmunity and clinical immunology, experimental evidence over the past few years have demonstrated several connections between the immune system and the nervous system, both central and peripheral, leading to the definition of neuroimmunology and of an immune-brain axis. Indeed, the central nervous system as an immune-privileged site, thanks to the blood-brain barrier, is no longer a dogma as the barrier may be altered during chronic inflammation with disruptive changes of endothelial cells and tight junctions, largely mediated by adenosine receptors and the expression of CD39/CD73. The diseases that encompass the neuroimmunology field vary from primary nervous diseases such as multiple sclerosis to systemic conditions with neuropsychiatric complications, such as systemic lupus erythematosus or vasculitidies. Despite potentially similar clinical manifestations, the pathogenesis of each condition is different, but the interaction between the ultra-specialized structure that is the nervous system and inflammation mediators are crucial. Two examples come from antidsDNA cross-reacting with anti-N-Methyl-o-Aspartate receptor (NMDAR) antibodies in neuropsychiatric lupus or the new family of antibody-associated neuronal autoimmune diseases including classic paraneoplastic syndromes with antibodies directed to intracellular antigens (Hu, Yo, Ri) and autoimmune encephalitis. In the case of multiple sclerosis, the T cell paradigm is now complicated by the growing evidence of a B cell involvement, particularly via aquaporin antibodies, and their influence on Thl and Th17 lineages. Inspired by a productive AARDA-sponsored colloquium among experts we provide a critical review of the literature on the pathogenesis of different immune-mediated diseases with neurologic manifestations and we discuss the basic immunology of the central nervous system and the interaction between immune cells and the peripheral nervous system. (C) 2016 Elsevier Ltd. All rights reserved.
Given immunity's general role in the organism's economy-both in terms of its internal environment as well as mediating its external relations-immune theory has expanded its traditional formulation of preserving individual autonomy to one that includes accounting for nutritional processes and symbiotic relationships that require immune tolerance. When such a full ecological alignment is adopted, the immune system becomes the mediator of both defensive and assimilative environmental intercourse, where a balance of immune rejection and tolerance governs the complex interactions of the organism's ecological relationships. Accordingly, immunology, which historically had affiliated with the biology of individuals, now becomes a science concerned with the biology of communities. With this translocation, the ontological basis of the organism is undergoing a profound change. Indeed, the recent recognition of the ubiquity of symbiosis has challenged the traditional notions of biological individuality and requires a shift in the metaphysics undergirding biology, in which a philosophy of the organism must be characterized by ecological dialectics "all-the-way-down.".
Guillain-Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery. The goal of this research was the identification of serum biomarkers associated with recovery from GBS. To address this objective, a quantitative proteomics approach was used to characterize differences in the serum proteome between a GBS patient and her healthy identical twin in order to lessen variations due to differences in genetic background, and with additional serum samples collected from unrelated GBS (N = 3) and Spinal Cord Injury (SCI) (N = 3) patients with similar medications. Proteomics results were then validated by ELISA using sera from additional GBS patients (N = 5) and healthy individuals (N = 3). All GBS and SCI patients were recovering from the acute phase of the disease. The results showed that Piccolo, a protein that is essential in the maintenance of active zone structure, constitutes a potential serological correlate of recovery from GBS. These results provided the first evidence for the Piccolo's putative role in GBS, suggesting a candidate target for developing a serological marker of disease recovery.
Phytohemagglutinin (PHA)-induced skin swelling response is widely used as a rough surrogate of integrative cell-mediated and innate immunity across multiple vertebrate taxa due to its simplification and feasibility. However, little is known whether there are sex and interspecific differences of immune responsiveness to PHA in ectotherms, especially for anurans. Therefore, we studied sex and species differences of PHA response in three anurans, Asiatic toads (Bufo gargarizans), Dark-spotted frogs (Pelophylax nigromaculatus) and Mongolian toads (Pseudepidalea raddei), captured in northern regions of Anhui Province (China). Footpad thickness was measured prior to (0 h) and after (6, 12, 24, 48 and 72 h) a PHA injection and normalized against saline injection in the opposite footpad. Body mass was recorded at the beginning (0 h) and end of each assay (72 h). Results showed effects of PHA assay, sex and taxa on body mass. Relative maximum swelling response (PHA(max)) ranged from 18.58-29.75%, 9.77 to 20.56% and 21.97 to 31.78% and its occurrence over time was apparent 10.6-19.72 h, 7.74-14.01 h and 17.39-23.94 h postinjection for Asiatic toads, Dark-spotted frogs and Mongolian toads, respectively. Finally, the magnitude or timing of PHAmax in Dark-spotted frogs was significantly thinner and faster than in Mongolian toads, and Asiatic toads had an in-between value, not different from the other two species. The magnitude of PHA(max) was significantly positively correlated with the timing ofPHAmax considering individuals altogether, but not when analyzed within species. Our results indicate that male and female anuran species respond similarly to PHA antigen stimulation, but the magnitude and timing of PHAmax is species-specific. Briefly, we provide new evidence for the suitability of PHA assay in non-model anuran species with different body sizes, and exhort the need to further investigate the nature of PHA assay at the hematological and histological levels in order to extend its application in ecoimmunological studies of amphibians.
Since the mid 1970s, when membrane modules became available, plasma separation techniques have gained in importance especially in the past few years. The advantages of this method are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate and higher efficacy. Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a poor prognosis without treatment. Therapeutic apheresis (TA) in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 40years. The updated information on immunology and molecular biology of different immunologic diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different diseases can be treated by various apheresis methods such as therapeutic plasma exchange (TPE) with substitution solution, or with online plasma or blood purification using adsorption columns, which contain biological or non-biological agents. Here, the authors provide an overview of the most important pathogenic aspects indicating that TA can be a supportive therapy in systemic autoimmune diseases such as renal and neurological disorders. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Committee of the American Society for Apheresis are cited.
During a long time, immunofluorescence has been neglected to benefit of molecular biology especially genetics, transcriptomics, and proteomics analyses. These techniques give good results on cell culture but for organs that are made of numerous cells with several compartments, various states of differentiation as in epidermis, immunohistochemistry is always relevant. Double (triple) staining by immunofluorescence allows positive cells identification in complex cell structure (for example, pericytes and endothelial cells in vessels) and subcellular localizations. In order to, due to improvement of antibodies avoiding especially species cross-reactions, microscopy and specific softwares, quality of staining, and acquired images have been upgraded. Consequently, this technique permits, as molecular biology analyses, quantification of the level of expression as intensity of fluorescence can be measured in each cells and each compartments (nuclear, cytoplasmic). In order to immunofluorescence on cells and tissue needs few materials and gives at the same times qualitative and quantitative results and must be used more widely especially when a mutation was associated to a disease.
Within the past 10 years, several investigators have reported the presence of immunoglobulin G in brain neurons. However, because immunoglobulin molecules were only known to be produced by B-lymphocytes, it was suspected that the neurons were taking immunoglobulin G up from the extracellular fluid. The aim of this study was to determine whether immunoglobulin G was actually being produced by the neurons. By immunohistochemistry and Western blotting analysis, we found that immunoglobulin G was also present in adult mouse brain neurons and isolated neonatal mouse neurons, respectively. More importantly, by in situ hybridization, Northern blotting and single cell reverse transcriptase polymerase chain reaction, the transcripts of rearranged immunoglobulin gamma chain and K chain were also found in adult mouse brain neurons. Further, confocal imaging of primary culture neurons showed that immunoglobulin G immunoreactivity was localized in the neuron cytoplasm, axons and dendrites. Immunoglobulin G extracted from the primary culture neurons could also be detected by Western blotting. Furthermore, the results of sulphur-35 or iodine-125 pulse-labeled immunoprecipitation provided additional confirmation that brain neurons could produce immunoglobulin G. Taken together, the results indicated that immunoglobulin G originated from both early generated and adult mouse neurons. Although the bioactivity of neuron-derived immunoglobulin G was not yet clear, we believed that immunoglobulin G might play an important role in neuronal development. (C) 2007 Elsevier Ltd. All rights reserved.
We found that stem-cell leukemia (SCL), also known as T cell acute-lymphocytic leukemia (Tal-1) gene expression, was upregulated in the maturing rat testis. Strong expression of Tal-1 was detected in the normal maturing rat testis by Northern blotting. Western blotting revealed the protein size to be about 34 kDa. Protein expression was wide-spread in spermatocytes, spermtids and spermatogonia in accordance with the seminiferous epithelium cycle, as determined by an analysis of immunohistochemistry. Gene expression of Tal-1 regulatory gene, NKX3.1, was negatively correlated with Tal-1 expression. Human Tal-1 expression in the maturing testis as well as in bone marrow was observed, which suggests that the gene product is a novel cancer-testis antigen candidate. Taken together, TAL-1 may be involved in cell division, morphological changes, and the development of spermatogenic cells in the normal rat testis.
This report investigated the possible participation of canine distemper virus (CDV) in an eight-year-old, male, Akita dog with neuromuscular disease. Clinically, there was tetraparesis, muscular atrophy, generalized weakness, intolerance to exercise, and diminished or absent spinal reflexes. The dog was serologically negative for Toxoplasma gondii. Necropsy confirmed generalized muscular atrophy. Histopathology revealed white matter demyelinating encephalitis, generalized atrophy and fibrosis of skeletal muscle fibers, myocardial atrophy and fibrosis, loss and demyelination of peripheral nerve fibers, axonal degeneration, endoneural fibrosis, and interstitial pneumonia. Immunohistochemistry identified CDV antigens within the cerebellum, spinal cord, skeletal muscle, lungs, and spleen. RT-PCR and direct sequencing amplified the CDV nucleoprotein gene from the cerebellum and sciatic nerves. Collectively, these findings suggest that this dog demonstrated systemic canine distemper that also affected the muscular system and probably triggered the manifestations of the neuromuscular disease observed in this case. (C) 2016 PVJ. All rights reserved
Background: The identification of immunogenic regions on the surface of antigens, which are able to be recognized by antibodies and to trigger an immune response, is a major challenge for the design of new and effective vaccines. The prediction of such regions through computational immunology techniques is a challenging goal, which will ultimately lead to a drastic limitation of the experimental tests required to validate their efficiency. However, current methods are far from being sufficiently reliable and/or applicable on a large scale. Results: We developed SEPIa, a B-cell epitope predictor from the protein sequence, which is sufficiently fast to be applicable on a large scale. The originality of SEPIa lies in the combination of two classifiers, a naive Bayesian and a random forest classifier, through a voting algorithm that exploits the advantages of both. It is based on 13 sequence-based features, whose values in a 9-residue sequence window are compiled to predict the epitope/non-epitope state of the central residue. The features are related to the type of amino acid, its conservation in homologous proteins, and its tendency of being exposed to the solvent, soluble, flexible, and disordered. The highest signal is obtained from statistical amino acid preferences, but all 13 features contribute non-negligibly in the predictor. SEPIa's average prediction accuracy is limited, with an AUC score (area under the receiver operating characteristic curve) that reaches 0.65 both in 10-fold cross-validation and on an independent test set. It is nevertheless slightly higher than that of other methods evaluated on the same test set. Conclusions: SEPIa was applied to a test protein whose epitopes are known, human beta 2 adrenergic G-protein-coupled receptor, with promising results. Although the actual AUC score is rather low, many of the predicted epitopes cluster together and overlap the experimental epitope region. The reasons underlying the limitations of SEPIa and of all other B-cell epitope predictors are discussed.
Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of specific sugar moieties on the glycan has profound implications on IgG effector functions. Emerging knowledge of how Fc glycans contribute to IgG structure and functions has opened new avenues for the therapeutic exploitation of defined antibody glycoforms in the treatment of cancer and autoimmune diseases. Here, we review recent advances in understanding proinflammatory IgG effector functions and their regulation by Fc glycans.
In this paper we present a simple mathematical model of cancer growth. The model is discrete, it is a linear map (T) on three dimensional Eucledian vector space. But for some values of the parameters there exists a linear vector field on three dimensional Eucledian vector space whose time one map is T. We can analyze what happens to the flow of this vector field on one of the coordinate hyperplanes (see Fig. 5 in Sect. 4). In words this figure depicts, that if you have a bad ratio of growth inhibitor to growth factor cancer grows and if you have a good ratio cancer is eradicated. We can modify the dynamical system to model giving chemo therapy or immune therapy and discuss the consequences. We fit the model predictions to a Gompertz function and this gives a good fit for some values of the parameters (see Figs. 1, 2, 3 and 4). A main topic of the present paper is a mass action kinetic model for cancer growth. This gives a three dimensional ODE model, for which the first orthant is positively invariant. We discretize the linearization of this nonlinear ODE and with appropriate parameter definitions we recover the model T of Sect. 1. For some parameter values the model T induces a two dimensional map of the plane, see Sect. 5 .
Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. (C) 2016 Published by Elsevier Masson SAS.
Peripartum cardiomyopathy is a heart failure syndrome occurring late in pregnancy or during the early post-natal period. The pathophysiology of peripartum cardiomyopathy is not fully understood and various mechanisms have been postulated including an underlying inflammatory process. We here report four cases presenting with acute left ventricular systolic dysfunction. Three out of four of the patients presented with a left ventricular ejection fraction <30% and one with a left ventricular ejection fraction of 35%. All made a full clinical recovery following treatment with high-dose intravenous steroids. This case series adds to the growing body of evidence for the role for immunosuppressants in the management of peripartum cardiomyopathy.
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 <= 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR), which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56d"n NK cells may be important in mediating TFR success. However, a major goal remains in CML to identify the most effective pathways to target to maximize an advantageous immune response and promote TFR success.
The immune system is a critical component in defense against viral, bacterial, parasitic, and fungal diseases. Immunological mechanisms, including immunological mediators, innate immunity, cell-mediated immunity, and humoral-mediated immunity, serve to maintain homeostasis and protect the host from disease. Immunological variation can impact defense mechanisms, however. Two factors in particular that can influence immune function are the single nucleotide polymorphisms (SNPs) and aging. SNPs affecting inflammatory cytokines are an important modifier involved in a number of diseases such as asthma, periodontal disease, atherosclerosis, diabetic retinopathy, psoriasis, and osteoporosis. Age-related alterations to the immune system have also been studied and documented. The genetic makeup of different strains of mice and the age of these different strains cause large differences in susceptibility to infection, with influenza virus infection among the most widely studied. The mechanism of these differences due to either genetics or age is not known but can be investigated in strain-and age-specific infectious disease models.
The immune system of vertebrates confers protective mechanisms to the host through the sensing of stress-induced agents expressed during infection or cell stress. Among them, the first line of host defense composed of the innate immune sensing of these agents by pattern recognition receptors enables downstream adaptive immunity to be primed, mediating the body's appropriate response to clear infection and tissue damage. Mitochondria are bacteria within that allowed the emergence of functional eukaryotic cells by positioning themselves as the cell powerhouse and an initiator of cell death programs. It is striking to consider that such ancestral bacteria, which had to evade host defense at some point to develop evolutionary endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting the immune system against various insults including infection by other pathogens. Mitochondria have indeed become critical regulators of innate immune responses to both pathogens and cell stress. They host numerous modulators, which play a direct role into the assembly of innate sensing machineries that trigger host immune response in both sterile and non-sterile conditions. Several lines of evidence indicate the existence of a complex molecular interplay between mechanisms involved in inflammation and metabolism. Mitochondrial function seems to participate in innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Here, we review the mechanisms by which mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades. (C) 2016 Elsevier Ltd. All rights reserved.
Hundreds of intracellular peptides that are neither antigens nor neuropeptides are present in mammalian cells and tissues. These peptides correspond to fragments of cytosolic, nuclear or mitochondrial proteins. Proteasome inhibition affects the levels of the intracellular peptides in human cell lines. Here, the effect of immuneproteasome expression on the intracellular peptide profile was evaluated, and its functional significance was investigated. The expression of the immuneproteasome in HeLa cells was induced by interferon gamma treatment, and the relative concentrations of the intracellular peptides were compared to those of the control cells using isotope labeling and electron spray mass spectrometry. One of the peptides identified, VGSELIQKY (EL28), corresponds to amino acids 251-259 of the human 19S ATPase regulatory subunit 4. This peptide was increased in the extracts of HeLa cells that had been treated with interferon gamma compared to those of control cells. In vitro, EL28 increased the chymotrypsin, trypsin and caspase-like proteasome activities. In vivo, when covalently linked to a cell-penetrating peptide, EL28 potentiated the ability of interferon gamma to stimulate the expression of the immuneproteasome beta 5i subunit and to increase the proliferation of CD8 + T-cells. The EL28/cell-penetrating peptide construct also improved and positively modulated the secondary IgG anti-bovine serum albumin immune responsiveness elicited in high antibody-responder mice. Together, these results suggest that EL28 is a functional intracellular peptide that can potentiate interferon gamma activity. Biological significance: The functional identification of EL28 advances our understanding regarding the bioactive peptides generated by limited proteolysis within cells. (C) 2016 Elsevier B.V. All rights reserved.
Aims: The aim of this study was to verify the suitable use of candidate 'probiotics' selected by in vitro tests and the importance of in vivo assays to nominate micro-organisms as probiotics and alternative prophylactic treatments for Salmonella Typhimurium infection. Methods and Results: Thirty-three lactic acid bacteria (LAB) isolated from foal's faeces were assessed based on the main desirable functional in vitro criteria. Based on these results, Pediococcus pentosaceus strain 40 was chosen to evaluate its putative probiotic features in a mouse model of Salmonella infection. Daily intragastric doses of Ped. pentosaceus 40 for 10 days before and 10 days after Salmonella challenge (10(6) CFU of Salm. Typhimurium per mouse) led to a significant aggravation in mouse health by increasing weight loss, worsening clinical symptoms and anticipating the time and the number of deaths by Salmonella. Pediococcus pentosaceus modulated cell-mediated immune responses by up-regulation of the gene expression of the proinflammatory cytokines IFN-gamma and TNF-alpha in the small intestine. Conclusion: The usual criteria were used for in vitro screening of a large number of LAB for desirable probiotic functional properties. However, the best candidate probiotic strain identified, Ped. pentosaceus #40, aggravated the experimental disease in mice. Significance and Impact of the Study: These findings emphasize the need for prophylactic or therapeutic effectiveness to be demonstrated in in vivo models to make precise health claims.
Flow cytometry is a method widely used to quantify suspended solids such as cells or bacteria in a size range from 0.5 to several tens of micrometers in diameter. In addition to a characterization of forward and sideward scatter properties, it enables the use of fluorescent labeled markers like antibodies to detect respective structures. Using indirect antibody staining, flow cytometry is employed here to quantify birch pollen allergen (precisely Bet v 1)-loaded particles of 0.5 to 10 mu m in diameter in inhalable particulate matter (PM10, particle size0.5 mu m.
Neutrophil extracellular traps are networks of DNA, histones and neutrophil proteins released in response to infectious and inflammatory stimuli. Although a component of the innate immune response, NETs are implicated in a range of disease processes including autoimmunity and thrombosis. This protocol describes a simple method for canine neutrophil isolation and quantification of NETs using a microplate fluorescence assay. Blood is collected using conventional venipuncture techniques. Neutrophils are isolated using dextran sedimentation and a density gradient using conditions optimized for dog blood. After allowing time for attachment to the wells of a 96 well plate, neutrophils are treated with NET-inducing agonists such as phorbol-12-myristate-13-acetate or platelet activating factor. DNA release is measured by the fluorescence of a cell-impermeable nucleic acid dye. This assay is a simple, inexpensive method for quantifying NET release, but NET formation rather than other causes of cell death must be confirmed with alternative methods.
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types. This system has been used to study immune cells in a few published reports, yet a comprehensive protocol optimized particularly for lymphocytes is lacking. Lymphocytes are fragile cells that survive poorly in ex vivo conditions. Oftentimes lymphocyte subsets are rare, and working with low cell numbers is inevitable. Thus, an experimental strategy that addresses these difficulties is required. Here, we provide a protocol that allows for rapid isolation of viable lymphocytes from lymphoid tissues, and for the analysis of their metabolic states in the extracellular flux analyzer. Furthermore, we provide results of experiments in which the metabolic activities of several lymphocyte subtypes at different cell densities were compared. These observations suggest that our protocol can be used to achieve consistent, well-standardized results even at low cell concentrations, and thus it may have broad applications in future studies focusing on the characterization of metabolic events in immune cells.
Fluorescence-activated cell sorting (FACS) is a technique to purify specific cell populations based on phenotypes detected by flow cytometry. This method enables researchers to better understand the characteristics of a single cell population without the influence of other cells. Compared to other methods of cell enrichment, such as magnetic-activated cell sorting (MCS), FACS is more flexible and accurate for cell separation due to the ability of phenotype detection by flow cytometry. In addition, FACS is usually capable of separating multiple cell populations simultaneously, which improves the efficiency and diversity of experiments. Although FACS has some limitations, it has been broadly used to purify cells for functional studies in both in vitro and in vivo settings. Here we report a protocol using fluorescence-activated cell sorting to isolate a very rare population of immune cells, plasmacytoid dendritic cells (pDC), with high purity from the bone marrow of lupus-prone mice for in vitro functional studies of pDC.
The methods described herein for activation of naive CD4(+) T cells in suspension and their adherence in coverslips for confocal microscopy analysis allow the spatial localization and visualization of gangliosides involved in CD4(+) T cell activation, that complement expression profiling experiments such as flow cytometry, western blotting or real-time PCR. The quantification of ganglioside expression through flow cytometry and their cellular localization through microscopy can be obtained by the use of anti-ganglioside antibodies with high affinity and specificity. Nonetheless, an adequate handling of cells in suspension involves the treatment of culture plates to promote the necessary adherence required for fluorescence or confocal microscopy acquisition. In this work, we describe a protocol for determining GD3 and GD2 ganglioside expression and colocalization with the TCR during naive CD4(+) T cell activation. Also, real-time PCR experiments using < 40,000 cells are described for the determination of the GD3 and GM2/GD2 synthase genes, demonstrating that gene analysis experiments can be performed with a low number of cells and without the need of additional low input RNA kits.
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4+ T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i.e., iPSC-Tregs). The method is based on incorporating the transcription factor FoxP3 and an Ag-specific T cell receptor (TCR) into iPSCs and then differentiating on OP9 stromal cells expressing Notch ligands delta-like (DL) 1 and DL4. Following in vitro differentiation, the iPSC-Tregs express CD4, CD8, CD3, CD25, FoxP3, and Ag-specific TCR and are able to respond to Ag stimulation. This method has been successfully applied to cell-based therapy of autoimmune arthritis in a murine model. Adoptive transfer of these Ag-specific iPSC-Tregs into Ag-induced arthritis (AIA)bearing mice has the ability to reduce joint inflammation and swelling and to prevent bone loss.
Helper T cell development and function must be tightly regulated to induce an appropriate immune response that eliminates specific pathogens yet prevents autoimmunity. Many approaches involving different model organisms have been utilized to understand the mechanisms controlling helper T cell development and function. However, studies using mouse models have proven to be highly informative due to the availability of genetic, cellular, and biochemical systems. One genetic approach in mice used by many labs involves retroviral transduction of primary helper T cells. This is a powerful approach due to its relative ease, making it accessible to almost any laboratory with basic skills in molecular biology and immunology. Therefore, multiple genes in wild type or mutant forms can readily be tested for function in helper T cells to understand their importance and mechanisms of action. We have optimized this approach and describe here the protocols for production of high titer retroviruses, isolation of primary murine helper T cells, and their transduction by retroviruses and differentiation toward the different helper subsets. Finally, the use of this approach is described in uncovering mechanisms utilized by microRNAs (miRNAs) to regulate pathways controlling helper T cell development and function.
The ribosomal spacer PCR (RS-PCR) is a highly resolving and robust genotyping method for S. aureus that allows a high throughput at moderate costs and is, therefore, suitable to be used for routine purposes. For best resolution, data evaluation and data management, a miniaturized electrophoresis system is required. Together with such an electrophoresis system and the in-house developed software (freely available here) assignment of the pattern of bands to a genotype is standardized and straight forward. DNA extraction is simple (boiling prep), setting-up of the reactions is easy and they can be run on any standard PCR machine. PCR cycling is common except prolonged ramping and elongation times. Compared to spa typing and Multi Locus Sequence Typing (MLST), RS-PCR does not require DNA sequencing what simplifies the analysis considerably and allows a high throughput. Furthermore, the resolution for bovine strains of S. aureus is at least as good as spa typing and better than MLST or pulsed-field gel electrophoresis (PFGE). The RS-PCR data base includes presently a total of 141 genotypes and variants. The method is highly associated with the virulence gene pattern, contagiosity and pathogenicity of S. aureus strains involved in bovine mastitis. S. aureus genotype B (GTB) is contagious and causes herds problems causing large costs in the Switzerland and other European countries. All the other genotypes observed in Switzerland infect individual cows and quarters. Genotyping by RS-PCR allows the reliable prediction of the epidemiological and the pathogenic potential of S. aureus involved in bovine intramammary infection (IMI), two key factors for clinical veterinary medicine. Because of these beneficial properties together with moderate costs and a high sample throughput the goal of this publication is to give a detailed, step-by-step protocol for easily establishing and running RS-PCR for genotyping S. aureus in other laboratories.
Dendritic cells (DCs) recognize foreign structures of different pathogens, such as viruses, bacteria, and fungi, via a variety of pattern recognition receptors (PRRs) expressed on their cell surface and thereby activate and regulate immunity. The major function of DCs is the induction of adaptive immunity in the lymph nodes by presenting antigens via MHC I and MHC II molecules to naive T lymphocytes. Therefore, DCs have to migrate from the periphery to the lymph nodes after the recognition of pathogens at the sites of infection. For in vitro experiments or DC vaccination strategies, monocyte-derived DCs are routinely used. These cells show similarities in physiology, morphology, and function to conventional myeloid dendritic cells. They are generated by interleukin 4 (IL-4) and granulocytemacrophage colony-stimulating factor (GM-CSF) stimulation of monocytes isolated from healthy donors. Here, we demonstrate how monocytes are isolated and stimulated from anti-coagulated human blood after peripheral blood mononuclear cell (PBMC) enrichment by density gradient centrifugation. Human monocytes are differentiated into immature DCs and are ready for experimental procedures in a non-clinical setting after 5 days of incubation.
Lymphocyte proliferation in response to antigenic or mitogenic stimulation is a readily quantifiable phenomenon useful for testing immunomodulatory (i.e., immunosuppressive or immunostimulatory) chemical compounds and biologics. One of the earliest steps during mitogenesis is cell enlargement or blastogenic transformation, whereupon the cell volume increases before division. It is usually detectable in the first several hours of T-lymphocyte stimulation. Here, we describe a rapid method to quantify blastogenesis in T lymphocytes isolated from mouse spleens and human peripheral blood mononuclear cells (PBMCs) using an automated cell counter. Various commonly used proliferation assays for the most part are laborious and only reflect the overall population effect rather than individual cellular effects within a population. In contrast, the presented automated cell counter assay provides rapid, direct, and precise measurements of cell diameters that can be used for assessing the effectiveness of various mitogens and immunomodulatory drugs in vitro.
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This process is characterized by the transmigration of activated T cells across brain endothelial cells (ECs), the main constituents of the BBB. However, the consequences on brain EC function upon interaction with such T cells are largely unknown. Here we describe an assay that allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function and barrier integrity during the interaction with T cells over time. The assay makes use of impedance cell spectroscopy, a powerful tool for studying EC monolayer integrity and permeability, by measuring changes in transendothelial electrical resistance (TEER) and cell layer capacitance (Ccl). In direct contact with ECs, stimulated but not naive T cells are capable of inducing EC monolayer dysfunction, as visualized by a decrease in TEER and an increase in Ccl. The assay records changes in EC monolayer integrity in a continuous and automated fashion. It is sensitive enough to distinguish between different strengths of stimuli and levels of T cell activation and it enables the investigation of the consequences of a targeted modulation of T cell-EC interaction using a wide range of substances such as antibodies, pharmacological reagents and cytokines. The technique can also be used as a quality control for EC integrity in in vitro T-cell transmigration assays. These applications make it a versatile tool for studying BBB properties under physiological and pathophysiological conditions.
The hallmark of humoral immunity is to generate functional ASCs, which synthesize and secrete Abs specific to an antigen (Ag), such as a pathogen, and are used for host defense. For the quantitative determination of the functional status of the humoral immune response of an individual, both serum Abs and circulating ASCs are commonly measured as functional readouts. In humans, peripheral blood is the most convenient and readily accessible sample that can be used for the determination of the humoral immune response elicited by host B cells. Distinct B-cell subsets, including ASCs, can be isolated directly from peripheral blood via selection with lineage-specific Ab-conjugated microbeads or via cell sorting with flow cytometry. Moreover, purified naive and memory B cells can be activated and differentiated into ASCs in culture. The functional activities of ASCs to contribute to Ab secretion can be quantified by ELISpot, which is an assay that converges enzyme-linked immunoabsorbance assay (ELISA) and western blotting technologies to enable the enumeration of individual ASCs at the singlecell level. In practice, the ELISpot assay has been increasingly used to evaluate vaccine efficacy because of the ease of handling of a large number of blood samples. The methods of isolating human B cells from peripheral blood, the differentiation of B cells into ASCs in vitro, and the employment of ELISpot for the quantification of total IgM-and IgG-ASCs will be described here.
Peptide-major histocompatibility complex class I (pMHC-I) tetramers have been an invaluable tool to study CD8(+) T-cell responses. Because these reagents directly bind to T-cell receptors on the surface of CD8(+) T-lymphocytes, fluorochrome-labeled pMHC-I tetramers enable the accurate detection of antigen (Ag)-specific CD8(+) T-cells without the need for in vitro re-stimulation. Moreover, when combined with multi-color flow cytometry, pMHC-I tetramer staining can reveal key aspects of Ag-specific CD8(+) T-cells, including differentiation stage, memory phenotype, and activation status. These types of analyses have been especially useful in the field of HIV immunology where CD8(+) T-cells can affect progression to AIDS. Experimental infection of rhesus macaques with simian immunodeficiency virus (SIV) provides an invaluable tool to study cellular immunity against the AIDS virus. As a result, considerable progress has been made in defining and characterizing T-cell responses in this animal model. Here we present an optimized protocol for enumerating SIV-specific CD8(+) T-cells in rhesus macaques by pMHC-I tetramer staining. Our assay permits the simultaneous quantification and memory phenotyping of two pMHC-I tetramer+ CD8(+) T-cell populations per test, which might be useful for tracking SIV-specific CD8(+) T-cell responses generated by vaccination or SIV infection. Considering the relevance of nonhuman primates in biomedical research, this methodology is applicable for studying CD8(+) T-cell responses in multiple disease settings.
Regulatory T cells (Tregs) are an integral part of peripheral tolerance, suppressing immune reactions against self-structures and thus preventing autoimmune diseases. Clinical approaches to adoptively transfer Tregs, or to deplete Tregs in cancer, are underway with promising first outcomes. Because the number of naturally occurring Tregs (nTregs) is very limited, studying certain Treg features using in vitro induced Tregs (iTregs) can be advantageous. To date, the best although not absolutely specific protein marker to delineate Tregs is the transcription factor FOXP3. Despite the importance of Tregs including non-redundant roles of peripherally induced Tregs, the protocols to generate iTregs are currently controversial, particularly for human cells. This protocol therefore describes the in vitro differentiation of human CD4+FOXP3+ iTregs from human naive T cells using a range of Treg-inducing factors (TGF-beta plus IL-2 only, or their combination with retinoic acid, rapamycin or butyrate) in parallel. It also describes the phenotyping of these cells by flow cytometry and qRT-PCR. These protocols result in reproducible expression of FOXP3 and other Treg signature genes and enable the study of general FOXP3-regulatory mechanisms as well as protocol-specific effects to delineate the impact of certain factors. iTregs can be utilized to study various phenotypic aspects as well as molecular mechanisms of Treg induction. Detailed molecular studies are facilitated by relatively large cell numbers that can be obtained. A limitation for the application of iTregs is the relative instability of FOXP3 expression in these cells compared to nTregs. iTregs generated by these protocols can also be used for functional assays such as studying their suppressive function, in which iTregs induced by TGF-beta plus retinoic acid and rapamycin display superior suppressive activity. However, the suppressive capacity of iTregs can differ from nTregs and the use of appropriate controls is crucial.
Bacterial biofilms frequently form on fungal surfaces and can be involved in numerous bacterial-fungal interaction processes, such as metabolic cooperation, competition, or predation. The study of biofilms is important in many biological fields, including environmental science, food production, and medicine. However, few studies have focused on such bacterial biofilms, partially due to the difficulty of investigating them. Most of the methods for qualitative and quantitative biofilm analyses described in the literature are only suitable for biofilms forming on abiotic surfaces or on homogeneous and thin biotic surfaces, such as a monolayer of epithelial cells. While laser scanning confocal microscopy (LSCM) is often used to analyze in situ and in vivo biofilms, this technology becomes very challenging when applied to bacterial biofilms on fungal hyphae, due to the thickness and the three dimensions of the hyphal networks. To overcome this shortcoming, we developed a protocol combining microscopy with a method to limit the accumulation of hyphal layers in fungal colonies. Using this method, we were able to investigate the development of bacterial biofilms on fungal hyphae at multiple scales using both LSCM and scanning electron microscopy (SEM). This report describes the protocol, including microorganism cultures, bacterial biofilm formation conditions, biofilm staining, and LSCM and SEM visualizations.
The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.
A number of methods exist for the transformation of B lymphocytes by the Epstein Barr virus in vitro into immortalized cell lines. We have developed a new method with a powerful and simple strategy for the establishment of B-LCLs, the red blood cell lysis method. This method simplified the PBMC separation procedure with red blood cell removal, and used as little as 0.5 mL of whole blood for establishing EBV-immortalized cell lines, which can proliferate to large cell numbers in a relatively short amount time with a 100% success rate. The method is simple, reliable, time saving, and applicable to treating a large number of the clinical samples.
Reporter mice have been widely used to observe the localization of expression of targeted genes. This protocol focuses on a strategy to establish a new transgenic reporter mouse model. We chose to visualize interleukin (IL) 22 gene expression because this cytokine has important activities in the intestine, where it contributes to repair tissues damaged by inflammation. Reporter systems offer considerable advantages over other methods of identifying products in vivo. In the case of IL-22, other studies had first isolated cells from tissues and then re-stimulated the cells in vitro. IL-22, which is normally secreted, was trapped inside cells using a drug, and intracellular staining was used to visualize it. This method identifies cells capable of producing IL-22, but it does not determine whether they were doing so in vivo. The reporter design includes inserting a gene for a fluorescent protein (tdTomato) into the IL-22 gene in such a way that the fluorescent protein cannot be secreted and therefore remains trapped inside the producing cells in vivo. Fluorescent producers can then be visualized in tissue sections or by ex vivo analysis through flow cytometry. The actual construction process for the reporter included recombineering a bacterial artificial chromosome that contained the IL-22 gene. This engineered chromosome was then introduced into the mouse genome. Homeostatic IL-22 reporter expression was observed in different mouse tissues, including the spleen, thymus, lymph nodes, Peyer's patch, and intestine, by flow cytometry analysis. Colitis was induced by T-cell (CD4(+)CD45RBhigh) transfer, and reporter expression was visualized. Positive T cells were first present in the mesenteric lymph nodes, and then they accumulated inside the lamina propria of the distal small intestine and colon tissues. The strategy using BACs gave good-fidelity reporter expression compared to IL-22 expression, and it is simpler than knock-in procedures.
The stimulation of immune responses is a common tool in invertebrate studies to examine the efficacy and the mechanisms of immunity. This stimulation is based on the injection of non-pathogenic particles into insects, as the particles will be detected by the immune system and will induce the production of immune effectors. We focus here on the stimulation of the melanization response in the mosquito Anopheles gambiae. The melanization response results in the encapsulation of foreign particles and parasites with a dark layer of melanin. To stimulate this response, mosquitoes are inoculated with beads in the thoracic cavity using microcapillary glass tubes. Then, after 24 hr, the mosquitoes are dissected to retrieve the beads. The degree of melanization of the bead is measured using image analysis software. Beads do not have the pathogenic effects of parasites, or their capacity to evade or suppress the immune response. These injections are a way to measure immune efficacy and the impact of immune stimulations on other life history traits, such as fecundity or longevity. It is not exactly the same as directly studying host-parasite interactions, but it is an interesting tool to study immunity and its evolutionary ecology.
It is now well known that T lymphocytes play a critical role in the development of several cardiovascular diseases(1,2,3,4,5). For example, studies from our group have shown that hypertension is associated with an excessive accumulation of T cells in the vessels and kidney during the development of experimental hypertension(6). Once in these tissues, T cells produce several cytokines that affect both vascular and renal function leading to vasoconstriction and sodium and water retention(1,2). To fully understand how T cells cause cardiovascular and renal diseases, it is important to be able to identify and quantify the specific T cell subsets present in these tissues. T cell subsets are defined by a combination of surface markers, the cytokines they secrete, and the transcription factors they express. The complexity of the T cell population makes flow cytometry and intracellular staining an invaluable technique to dissect the phenotypes of the lymphocytes present in tissues. Here, we provide a detailed protocol to identify the surface and intracellular markers (cytokines and transcription factors) in T cells isolated from murine kidney, aorta and aortic draining lymph nodes in a model of angiotensin II induced hypertension. The following steps are described in detail: isolation of the tissues, generation of the single cell suspensions, ex vivo stimulation, fixation, permeabilization and staining. In addition, several fundamental principles of flow cytometric analyses including choosing the proper controls and appropriate gating strategies are discussed.
Monoclonal antibodies are universal binding molecules and are widely used in biomedicine and research. Nevertheless, the generation of these binding molecules is time-consuming and laborious due to the complicated handling and lack of alternatives. The aim of this protocol is to provide one standard method for the generation of monoclonal antibodies using hybridoma technology. This technology combines two steps. Step 1 is an appropriate immunization of the animal and step 2 is the fusion of B lymphocytes with immortal myeloma cells in order to generate hybrids possessing both parental functions, such as the production of antibody molecules and immortality. The generated hybridoma cells were then recloned and diluted to obtain stable monoclonal cell cultures secreting the desired monoclonal antibody in the culture supernatant. The supernatants were tested in enzyme-linked immunosorbent assays (ELISA) for antigen specificity. After the selection of appropriate cell clones, the cells were transferred to mass cultivation in order to produce the desired antibody molecule in large amounts. The purification of the antibodies is routinely performed by affinity chromatography. After purification, the antibody molecule can be characterized and validated for the final test application. The whole process takes 8 to 12 months of development, and there is a high risk that the antibody will not work in the desired test system.
Murine full-thickness skin transplantation is a well-established in vivo model to study alloimmune response and graft rejection. Despite its limited application to humans, skin transplantation in mice has been widely employed for transplantation research. The procedure is easy to learn and perform, and it does not require delicate microsurgical techniques nor extensive training. Moreover, graft rejection in this model occurs in a very reproducible immunological reaction and is easily monitored by direct inspection and palpation. In addition, secondary skin transplantation with donor-matched or third-party skin grafts can be performed on more complex transplant models as an alternative and uncomplicated method to assess donor-specific tolerance. The complications are low and are in general limited to anesthesia overdose or respiratory distress after the procedure. Graft failure, on the other hand, occurs commonly as a result of poor preparation of the graft, incorrect positioning in the graft bed, or inappropriate placement of the bandage. In this article, we present a protocol for full-thickness skin transplantation in mice and describe the important steps necessary for a successful procedure.
Neutrophils (PMN) are best known for their phagocytic functions against invading pathogens and microorganisms. They have the shortest half-life amongst leukocytes and in their non-activated state are constitutively committed to apoptosis. When recruited to inflammatory sites to resolve inflammation, they produce an array of cytotoxic molecules with potent antimicrobial killing. Yet, when these powerful cytotoxic molecules are released in an uncontrolled manner they can damage surrounding tissues. In recent years however, neutrophil versatility is increasingly evidenced, by demonstrating plasticity and immunoregulatory functions. We have recently identified a new neutrophil-derived subpopulation, which develops spontaneously in standard culture conditions without the addition of cytokines/growth factors such as granulocyte colony-stimulating factor (GM-CSF)/interleukin (IL)-4. Their phagocytic abilities of neutrophil remnants largely contribute to increase their size immensely; therefore they were termed giant phagocytes (G phi). Unlike neutrophils, G phi are long lived in culture. They express the cluster of differentiation (CD) neutrophil markers CD66b/CD63/CD15/CD11b/myeloperoxidase (MPO)/neutrophil elastase (NE), and are devoid of the monocytic lineage markers CD14/CD16/CD163 and the dendritic CD1c/CD141 markers. They also take-up latex and zymosan, and respond by oxidative burst to stimulation with opsonized-zymosan and PMA. G phi also express the scavenger receptors CD68/CD36, and unlike neutrophils, internalize oxidized-low density lipoprotein (oxLDL). Moreover, unlike fresh neutrophils, or cultured monocytes, they respond to oxLDL uptake by increased reactive oxygen species (ROS) production. Additionally, these phagocytes contain microtubule-associated protein-1 light chain 3B (LC3B) coated vacuoles, indicating the activation of autophagy. Using specific inhibitors it is evident that both phagocytosis and autophagy are prerequisites for their development and likely NADPH oxidase dependent ROS. We describe here a method for the preparation of this new subpopulation of long-lived, neutrophil-derived phagocytic cells in culture, their identification and their currently known characteristics. This protocol is essential for obtaining and characterizing G phi in order to further investigate their significance and functions.
Although originally developed for predicting transfusion outcomes of serologically incompatible blood, the monocyte monolayer assay (MMA) is a highly versatile in vitro assay that can be modified to examine different aspects of antibody and Fc gamma receptor (Fc gamma R)-mediated phagocytosis in both research and clinical settings. The assay utilizes adherent monocytes from peripheral blood mononuclear cells isolated from mammalian whole blood. MMA has been described for use in both human and murine investigations. These monocytes express Fc gamma Rs (e.g., Fc gamma RI, Fc gamma RIIA, Fc gamma RIIB, and Fc gamma RIIIA) that are involved in immune responses. The MMA exploits the mechanism of Fc gamma R-mediated interactions, phagocytosis in particular, where antibody-sensitized red blood cells (RBCs) adhere to and/or activate Fc gamma Rs and are subsequently phagocytosed by the monocytes. In vivo, primarily tissue macrophages found in the spleen and liver carry out Fc gamma R-mediated phagocytosis of antibody-opsonized RBCs, causing extravascular hemolysis. By evaluating the level of phagocytosis using the MMA, different aspects of the in vivo Fc gamma R-mediated process can be investigated. Some applications of the MMA include predicting the clinical relevance of allo-or autoantibodies in a transfusion setting, assessing candidate drugs that promote or inhibit phagocytosis, and combining the assay with fluorescent microscopy or traditional Western immunoblotting to investigate the downstream signaling effects of Fc gamma R-engaging drugs or antibodies. Some limitations include the laboriousness of this technique, which takes a full day from start to finish, and the requirement of research ethics approval in order to work with mammalian blood. However, with diligence and adequate training, the MMA results can be obtained within a 24-h turnover time.
Cells release small extracellular vesicles (EVs) into the surrounding media. Upon virus infection cells also release virions that have the same size of some of the EVs. Both virions and EVs carry proteins of the cells that generated them and are antigenically heterogeneous. In spite of their diversity, both viruses and EVs were characterized predominantly by bulk analysis. Here, we describe an original nanotechnology-based high throughput method that allows the characterization of antigens on individual small particles using regular flow cytometers. Viruses or extracellular vesicles were immunocaptured with 15 nm magnetic nanoparticles (MNPs) coupled to antibodies recognizing one of the surface antigens. The captured virions or vesicles were incubated with fluorescent antibodies against other surface antigens. The resultant complexes were separated on magnetic columns from unbound antibodies and analyzed with conventional flow cytometers triggered on fluorescence. This method has wide applications and can be used to characterize the antigenic composition of any viral-and non-viral small particles generated by cells in vivo and in vitro. Here, we provide examples of the usage of this method to evaluate the distribution of host cell markers on individual HIV-1 particles, to study the maturation of individual Dengue virions (DENV), and to investigate extracellular vesicles released into the bloodstream.
B cells reactive with a specific antigen usually occur at a frequency of <0.05% of lymphocytes. For decades researchers have sought methods to isolate and enrich these rare cells for studies of their phenotype and biology. Approaches are inevitably based on the principle that B cells recognize native antigen by virtue of cell surface receptors that are representative in specificity of antibodies that will eventually be secreted by their differentiated daughters. Perhaps the most obvious approach to the problem involves use of fluorochrome-conjugated antigens in conjunction with fluorescence-activated cell sorting (FACS). However, the utility of these methods is limited by cell frequency and the achievable rate of analysis and isolation by electronic sorting. A novel method to enrich rare antigen-specific B cells using magnetic nanoparticles that results in high yield enrichment of antigen-reactive B cells from large starting cell populations is described. This method enables improved monitoring of the phenotype and biology of antigen reactive cells before and following in vivo antigen encounter, such as after immunization or during development of autoimmunity.
Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings. Indeed, present therapies that lack this molecular understanding have not been universally effective. Here, we describe methods that we commonly employ in the laboratory to determine how the nature of the interaction between TCRs and pHLA governs T-cell functionality. These methods include the generation of soluble TCRs and pHLA and the use of these reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-cell staining with pHLA multimers. Using these approaches and guided by structural analysis, it is possible to modify the interaction between TCRs and pHLA and to then test how these modifications impact T-cell antigen recognition. These findings have already helped to clarify the mechanism of T-cell recognition of a number of cancer antigens and could direct the development of altered peptides and modified TCRs for new cancer therapies.
The intestine displays an architecture of repetitive crypt structures consisting of different types of epithelial cells, lamina propia containing immune cells, and stroma. All of these heterogeneous cells contribute to intestinal homeostasis and participate in antimicrobial host defense. Therefore, identifying a surrogate model for studying immune response and antimicrobial activity of the intestine in an in vitro setting is extremely challenging. In vitro studies using immortalized intestinal epithelial cell lines or even primary crypt organoid culture do not represent the exact physiology of normal intestine and its microenvironment. Here, we discuss a method of culturing mouse colon tissue in a culture dish and how this ex vivo organ culture system can be implemented in studies related to antimicrobial host defense responses. In representative experiments, we showed that colons in organ culture express antimicrobial peptides in response to exogenous IL-1 beta and IL-18. Further, the antimicrobial effector molecules produced by the colon tissues in the organ culture efficiently kill Escherichia coli in vitro. This approach, therefore, can be utilized to dissect the role of pathogen-and danger-associated molecular patterns and their cellular receptors in regulating intestinal innate immune responses and antimicrobial host defense responses.
Fluorescence correlation spectroscopy (FCS) is a powerful technique for studying the diffusion of molecules within biological membranes with high spatial and temporal resolution. FCS can quantify the molecular concentration and diffusion coefficient of fluorescently labeled molecules in the cell membrane. This technique has the ability to explore the molecular diffusion characteristics of molecules in the plasma membrane of immune cells in steady state (i.e., without processes affecting the result during the actual measurement time). FCS is suitable for studying the diffusion of proteins that are expressed at levels typical for most endogenous proteins. Here, a straightforward and robust method to determine the diffusion rate of cell membrane proteins on primary lymphocytes is demonstrated. An effective way to perform measurements on antibody-stained live cells and commonly occurring observations after acquisition are described. The recent advancements in the development of photostable fluorescent dyes can be utilized by conjugating the antibodies of interest to appropriate dyes that do not bleach extensively during the measurements. Additionally, this allows for the detection of slowly diffusing entities, which is a common feature of proteins expressed in cell membranes. The analysis procedure to extract molecular concentration and diffusion parameters from the generated autocorrelation curves is highlighted. In summary, a basic protocol for FCS measurements is provided; it can be followed by immunologists with an understanding of confocal microscopy but with no other previous experience of techniques for measuring dynamic parameters, such as molecular diffusion rates.
Human noroviruses are a leading cause of epidemic and sporadic gastroenteritis worldwide. Because most infections are either spread directly via the person-to-person route or indirectly through environmental surfaces or food, contaminated fomites and inanimate surfaces are important vehicles for the spread of the virus during norovirus outbreaks. We developed and evaluated a protocol using macrofoam swabs for the detection and typing of human noroviruses from hard surfaces. Compared with fiber-tipped swabs or antistatic wipes, macrofoam swabs allow virus recovery (range 1.2-33.6%) from toilet seat surfaces of up to 700 cm(2). The protocol includes steps for the extraction of the virus from the swabs and further concentration of the viral RNA using spin columns. In total, 127 (58.5%) of 217 swab samples that had been collected from surfaces in cruise ships and long-term care facilities where norovirus gastroenteritis had been reported tested positive for GII norovirus by RT-qPCR. Of these 29 (22.8%) could be successfully genotyped. In conclusion, detection of norovirus on environmental surfaces using the protocol we developed may assist in determining the level of environmental contamination during outbreaks as well as detection of virus when clinical samples are not available; it may also facilitate monitoring of effectiveness of remediation strategies.
Cell-specific restriction of viral replication without concomitant attenuation can benefit vaccine development, gene therapy, oncolytic virotherapy, and understanding the biological properties of viruses. There are several mechanisms for regulating viral tropism, however they tend to be virus class specific and many result in virus attenuation. Additionally, many viruses, including picornaviruses, exhibit size constraints that do not allow for incorporation of large amounts of foreign genetic material required for some targeting methods. MicroRNAs are short, non-coding RNAs that regulate gene expression in eukaryotic cells by binding complementary target sequences in messenger RNAs, preventing their translation or accelerating their degradation. Different cells exhibit distinct microRNA signatures and many microRNAs serve as biomarkers. These differential expression patterns can be exploited for restricting gene expression in cells that express specific microRNAs while maintaining expression in cells that do not. In regards to regulating viral tropism, sequences complementary to specific microRNAs are incorporated into the viral genome, generally in the 3' non-coding regions, targeting them for destruction in the presence of the cognate microRNAs thus preventing viral gene expression and/or replication. MicroRNA-targeting is a technique that theoretically can be applied to all viral vectors without altering the potency of the virus in the absence of the corresponding microRNAs. Here we describe experimental methods associated with generating a microRNA-targeted picornavirus and evaluating the efficacy and specificity of that targeting in vitro. This protocol is designed for a rapidly replicating virus with a lytic replication cycle, however, modification of the time points analyzed and the specific virus titration readouts used will aid in the adaptation of this protocol to many different viruses.
The female reproductive tract (FRT) mucosal immune system serves as the first line of defense. Better knowledge of the genital mucosa is therefore essential for understanding pathogenicity of different pathogens including HIV. Gamma delta (GD) T cells are the prototype of 'unconventional' T cells and represent a relatively small subset of T cells defined by their expression of heterodimeric T-cell receptors (TCRs) composed of gamma and delta chains. This sets them apart from the classical and much better known CD4(+) helper T cells and CD8(+) cytotoxic T cells that are defined by alpha-beta TCRs. GD T cells often show tissue-specific localization and are enriched in epithelium. GD T cells orchestrate immune responses in inflammation, tumor surveillance, infectious disease, and autoimmunity. Here, we present a method to reproducibly isolate and analyze human endocervical intraepithelial GD T lymphocytes. We have used endocervical cytobrush samples from women participating in the Women's Interagency HIV Infection Study (WIHS). Knowledge about GD T cells interactions during conditions in which there is an insult to the vaginal mucosal could be applied to any clinical study in which mucosal vulnerability is addressed, including the development of vaginal microbicides. In addition, knowledge about mucosal GD T cell responses has potential for application of GD T cell-based immune therapy in treating infectious diseases.
The commonality of antibiotic usage in medicine means that understanding the resulting consequences to the host is vital. Antibiotics often decrease host microbiome community diversity and alter the microbial community composition. Many diseases such as antibiotic-associated enterocolitis, inflammatory bowel disease, and metabolic disorders have been linked to a disrupted microbiota. The complex interplay between host, microbiome, and antibiotics needs a tractable model for studying host-microbiome interactions. Our freshwater vertebrate fish serves as a useful model for investigating the universal aspects of mucosal microbiome structure and function as well as analyzing consequential host effects from altering the microbial community. Methods include host challenges such as infection by a known fish pathogen, exposure to fecal or soil microbes, osmotic stress, nitrate toxicity, growth analysis, and measurement of gut motility. These techniques demonstrate a flexible and useful model system for rapid determination of host phenotypes.
High-throughput screening (HTS) is currently the mainstay for the identification of chemical entities capable of modulating biochemical reactions or cellular processes. With the advancement of biotechnologies and the high translational potential of small molecules, a number of innovative approaches in drug discovery have evolved, which explains the resurgent interest in the use of HTS. The oncology field is currently the most active research area for drug screening, with no major breakthrough made for the identification of new immunomodulatory compounds targeting transplantation-related complications or autoimmune ailments. Here, we present a novel in vitro murine fluorescent-based lymphocyte assay easily adapted for the identification of new immunomodulatory compounds. This assay uses T or B cells derived from a transgenic mouse, in which the Nur77 promoter drives GFP expression upon T-or B-cell receptor stimulation. As the GFP intensity reflects the activation/ transcriptional activity of the target cell, our assay defines a novel tool to study the effect of given compound(s) on cellular/biological responses. For instance, a primary screening was performed using 4,398 compounds in the absence of a "target hypothesis", which led to the identification of 160 potential hits displaying immunomodulatory activities. Thus, the use of this assay is suitable for drug discovery programs exploring large chemical libraries prior to further in vitro/in vivo validation studies.
The interferon regulatory factor 5 (IRF5) is crucial for cells to determine if they respond in a pro-inflammatory or anti-inflammatory fashion. IRF5's ability to switch cells from one pathway to another is highly attractive as a therapeutic target. We designed a decoy peptide IRF5D with a molecular modeling software for designing small molecules and peptides. IRF5D inhibited IRF5, reduced alterations in extracellular matrix, and improved endothelial vasodilation in the tight-skin mouse (Tsk/+). The K-d of IRF5D for recombinant IRF5 is 3.72 +/- 0.74 x 10(-6) M as determined by binding experiments using biolayer interferometry experiments. Endothelial cells (EC) proliferation and apoptosis were unchanged using increasing concentrations of IRF5D (0 to 100 mu g/mL, 24 h). Tsk/+ mice were treated with IRF5D (1 mg/kg/d subcutaneously, 21 d). IRF5 and ICAM expressions were decreased after IRF5D treatment. Endothelial function was improved as assessed by vasodilation of facialis arteries from Tsk/+ mice treated with IRF5D compared to Tsk/+ mice without IRF5D treatment. As a transcription factor, IRF5 traffics from the cytosol to the nucleus. Translocation was assessed by immunohistochemistry on cardiac myocytes cultured on the different cardiac extracellular matrices. IRF5D treatment of the Tsk/+ mouse resulted in a reduced number of IRF5 positive nuclei in comparison to the animals without IRF5D treatment (50 mu g/mL, 24 h). These findings demonstrate the important role that IRF5 plays in inflammation and fibrosis in Tsk/+ mice.
The liver plays a decisive role in the regulation of systemic inflammation. In chronic kidney disease in particular, the liver reacts in response to the uremic milieu, oxidative stress, endotoxemia and the decreased clearance of circulating proinflammatory cytokines by producing a large number of acute-phase reactants. Experimental tools to study inflammation and the underlying role of hepatocytes are crucial to understand the regulation and contribution of hepatic cytokines to a systemic acute phase response and a prolonged pro-inflammatory scenario, especially in an intricate setting such as chronic kidney disease. Since studying complex mechanisms of inflammation in vivo remains challenging, resource-intensive and usually requires the usage of transgenic animals, primary isolated hepatocytes provide a robust tool to gain mechanistic insights into the hepatic acute-phase response. Since this in vitro technique features moderate costs, high reproducibility and common technical knowledge, primary isolated hepatocytes can also be easily used as a screening approach. Here, we describe an enzymatic-based method to isolate primary murine hepatocytes, and we describe the assessment of an inflammatory response in these cells using ELISA and quantitative real-time PCR.
NK cell cytotoxicity is a widely used measure to determine the effect of outside intervention on NK cell function. However, the accuracy and reproducibility of this assay can be considered unstable, either because of user's errors or because of the sensitivity of NK cells to experimental manipulation. To eliminate these issues, a workflow that reduces them to a minimum was established and is presented here. To illustrate, we obtained blood samples, at various time points, from runners (n = 4) that were submitted to an intense bout of exercise. First, NK cells are simultaneously identified and isolated through CD56 tagging and magnetic-based sorting, directly from whole blood and from as little as one milliliter. The sorted NK cells are removed of any reagent or capping antibodies. They can be counted in order to establish an accurate NK cell count per milliliter of blood. Secondly, the sorted NK cells (effectors cells or E) can be mixed with 3,3'-Diotadecyloxacarbocyanine Perchlorate (DiO) tagged K562 cells (target cells or T) at an assay-optimal 1: 5 T: E ratio, and analyzed using an imaging flow-cytometer that allows for the visualization of each event and the elimination of any false positive or false negatives (such as doublets or effector cells). This workflow can be completed in about 4 h, and allows for very stable results even when working with human samples. When available, research teams can test several experimental interventions in human subjects, and compare measurements across several time points without compromising the data's integrity.
Lipid analysis performed by high performance thin layer chromatography (HPTLC) is a relatively simple, cost-effective method of analyzing a broad range of lipids. The function of lipids (e. g., in host-pathogen interactions or host entry) has been reported to play a crucial role in cellular processes. Here, we show a method to determine lipid composition, with a focus on the cholesterol level of primary blood-derived neutrophils, by HPTLC in comparison to high performance liquid chromatography (HPLC). The aim was to investigate the role of lipid/cholesterol alterations in the formation of neutrophil extracellular traps (NETs). NET release is known as a host defense mechanism to prevent pathogens from spreading within the host. Therefore, blood-derived human neutrophils were treated with methyl-beta-cyclodextrin (M beta CD) to induce lipid alterations in the cells. Using HPTLC and HPLC, we have shown that M beta CD treatment of the cells leads to lipid alterations associated with a significant reduction in the cholesterol content of the cell. At the same time, M beta CD treatment of the neutrophils led to the formation of NETs, as shown by immunofluorescence microscopy. In summary, here we present a detailed method to study lipid alterations in neutrophils and the formation of NETs.
The identification of an antigenic epitope by the immune system allows for the understanding of the protective mechanism of neutralizing antibodies that may facilitate the development of vaccines and peptide drugs. Peptide scanning is a simple and efficient method that straightforwardly maps the linear epitope recognized by a monoclonal antibody (mAb). Here, the authors present an epitope determination methodology involving serially truncated recombinant proteins, synthetic peptide design, and dot-blot hybridization for the antigenic recognition of nervous necrosis virus coat protein using a neutralizing mAb. This technique relies on the dot-blot hybridization of synthetic peptides and mAbs on a polyvinylidene fluoride (PVDF) membrane. The minimum antigenic region of a viral coat protein recognized by the RG-M56 mAb can be narrowed down by step-by-step trimmed peptide mapping onto a 6-mer peptide epitope. In addition, alanine scanning mutagenesis and residue substitution can be performed to characterize the binding significance of each amino acid residue making up the epitope. The residues flanking the epitope site were found to play critical roles in peptide conformation regulation. The identified epitope peptide may be used to form crystals of epitope peptide-antibody complexes for an x-ray diffraction study and functional competition, or for therapeutics.
One important feature of the major opportunistic human pathogen Staphylococcus aureus is its extraordinary ability to rapidly acquire resistance to antibiotics. Genomic studies reveal that S. aureus carries many virulence and resistance genes located in mobile genetic elements, suggesting that horizontal gene transfer (HGT) plays a critical role in S. aureus evolution. However, a full and detailed description of the methodology used to study HGT in S. aureus is still lacking, especially regarding natural transformation, which has been recently reported in this bacterium. This work describes three protocols that are useful for the in vitro investigation of HGT in S. aureus: conjugation, phage transduction, and natural transformation. To this aim, the cfr gene (chloramphenicol/florfenicol resistance), which confers the Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A (PhLOPSA)-resistance phenotype, was used. Understanding the mechanisms through which S. aureus transfers genetic materials to other strains is essential to comprehending the rapid acquisition of resistance and helps to clarify the modes of dissemination reported in surveillance programs or to further predict the spreading mode in the future.
Inflammation is a local response to infection and tissue damage mediated by activated macrophages, monocytes, and other immune cells that release cytokines and other mediators of inflammation. For a long time, humoral and cellular mechanisms have been studied for their role in regulating the immune response, but recent advances in the field of immunology and neuroscience have also unraveled specific neural mechanisms with interesting therapeutic potential. The so-called cholinergic anti-inflammatory pathway (CAP) has been described to control innate immune responses and inflammation in a very potent manner. In the early 2000s, Tracey and collaborators developed a technique that stimulates the vagus nerve and mimics the effect of the pathway. The methodology is based on the electrical stimulation of the vagus nerve at low voltage and frequency, in order to avoid any side effects of overstimulation, such as deregulation of heart rate variability. Electrical devices for stimulation are now available, making it easy to set up the methodology in the laboratory. The goal of this research was to investigate the potential involvement of prostaglandins in the CAP. Unfortunately, based on earlier attempts, we failed to use the original protocol, as the induced inflammatory response either was too high or was not suitable for enzymatic metabolism properties. The different settings of the original surgery protocol remained mostly unchanged, but the conditions regarding inflammatory induction and the time point before sacrifice were improved to fit our purposes (i. e., to investigate the involvement of the CAP in more limited inflammatory responses). The modified version of the original protocol, presented here, includes a longer time range between vagus nerve stimulation and analysis, which is associated with a lower induction of inflammatory responses. Additionally, while decreasing the level of lipopolysaccharides (LPS) to inject, we also came across new observations regarding mechanistic properties in the spleen.
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immunopathogenesis. However, a pathogenic role for the T helper type 17 (Th17) axis was demonstrated by many studies, while regulatory T cells (T-regs) were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both the T-reg characteristic transcription factor forkhead box protein 3 (FoxP3) and the Th17-defining retinoic acid receptor-related orphan nuclear receptor t (RORt). Studies in a model of acute glomerulonephritis unveiled potent regulatory, but also proinflammatory, functions of RORt(+)FoxP3(+) T-regs. This bi-functional nature prompted us to suggest the name biT(regs)'. Importantly, the pathogenic biT(reg) effects were dependent upon expression of RORt. We thus aimed to evaluate the contribution of RORt(+)FoxP3(+) biT(regs) to pristane-induced SLE and explored the therapeutic potential of interference with RORt activation. Our analyses revealed expansion of IL-17 producing biT(regs) in a distinctive time-course and organ-specific pattern, coincident with the development of autoimmunity and tissue injury. Importantly, specific ablation of RORt activation in endogenous biT(regs) resulted in significant amelioration of pristane-induced pulmonary vasculitis and lupus nephritis. As potential mechanisms underlying the observed protection, we found that secretion of IL-17 by biT(regs) was abrogated completely in FoxP3(Cre)xRORC(fl/fl) mice. Furthermore, T-regs showed a more activated phenotype after cell-specific inactivation of RORt signalling. Finally, and remarkably, biT(regs) were found to potently suppress anti-inflammatory Th2 immunity in a RORt-dependent manner. Our study thus identifies biT(regs) as novel players in SLE and advocates RORt-directed interventions as promising therapeutic strategies.
The MHC class II (MHCII) processing pathway presents peptides derived from exogenous or membrane-bound proteins to CD4+ T cells. Several studies have shown that glycopeptides are necessary to modulate CD4+ T cell recognition, though glycopeptide structures in these cases are generally unknown. Here, we present a total of 93 glycopeptides from three melanoma cell lines and one matched EBV-transformed line with most found only in the melanoma cell lines. The glycosylation we detected was diverse and comprised 17 different glycoforms. We then used molecular modeling to demonstrate that complex glycopeptides are capable of binding the MHC and may interact with complementarity determining regions. Finally, we present the first evidence of disulfide-bonded peptides presented by MI-ICIL This is the first large scale study to sequence glyco- and disulfide bonded MHCII peptides from the surface of cancer cells and could represent a novel avenue of tumor activation and/or immunoevasion.
The evolutionarily conserved protein kinase p38 mediates innate resistance to environmental stress and microbial infection. Four p38 isoforms exist in mammals and may have been co-opted for new roles in adaptive immunity. Murine T cells deficient in p38, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38. Mice with T cells simultaneously lacking p38 and p38 displayed lymphoid atrophy and elevated Foxp3(+) regulatory T cell frequencies. Double deficiency of p38 and p38 in naive CD4(+) T cells resulted in an attenuation of MAPK-activated protein kinase (MK)-dependent mTOR signaling after T cell receptor engagement, and enhanced their differentiation into regulatory T cells under appropriate inducing conditions. Pharmacological inhibition of the p38-MK-mTOR signaling module produced similar effects, revealing potential for therapeutic applications.
Objectives Acute pancreatitis is characterized by a systemic inflammatory response. We hypothesized that the fundamental inflammatory response observed during the initial stages of all acute pancreatitis is not a Th1 but rather a Th17 response. Methods Seven patients with mild AP presenting within three days of symptom onset were recruited. Peripheral blood was drawn for five consecutive days and plasma Th1/Th2/Th17 cytokine levels compared to eleven healthy controls. Plasma cytokine measurements were performed using Th1/ Th2/Th17 Cytokine Bead Array assay and data quantified using FCAP Array software. Results IL-6 levels were significantly elevated in AP patients compared to controls; IL-10 levels were significantly elevated by day 3; IL17A levels increased on day 2 and significantly elevated at day 3 compared to controls declining to non-significant levels by day 4. IFN gamma and TNF alpha levels were low at all time-points. Conclusion IL-17A and IL-10 (an anti-inflammatory cytokine implicated in suppressing Th17 cytokines secreted by macrophages and T cells) were elevated by day 3. In addition IL-6, which helps drive development of Th17 cells, was significantly elevated at all time-points. These preliminary results imply that the underlying AP induced systemic inflammation is polarized to a Th17 rather than a Th1 response.
Introduction Seldom cutaneous leishmaniasis (CL) may present as a lasting and active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T helper (Th1) cells are assumed the most important factor in the outcome of the disease. The present study aims to assess some molecular defects that potentially contribute to Th1 impairment in NHCL. Methods and analysis This prospective observational study will be implemented among five groups. The first and second groups comprise patients afflicted with non-healing and healing forms of CL, respectively. The third group consists of those recovered participants who have scars as a result of CL. Those participants who have never lived or travelled to endemic areas of leishmaniasis will comprise the fourth group. The fifth group comprises participants living in hyperendemic areas for leishmaniasis, although none of them have been afflicted by CL. The aim is to recruit 10 NHCL cases and 30 participants in each of the other groups. A leishmanin skin test (LST) will be performed to assess in vivo immunity against the Leishmania infection. The cytokine profile (interleukin (IL)-12p70, interferon (IFN)-, C-X-C motif chemokine ligand (CXCL)-11 and IL-17a) of the isolated peripheral blood mononuclear cells (PBMCs) will be evaluated through ELISA. Real-time PCR will determine the C-X-C motif chemokine receptor (CXCR)-3 and IL-17a gene expression and expression of IL-12R1 will be assessed by flow cytometry. Furthermore, IL-12B and IL-12RB1 mutation analysis will be performed. Discussion It is anticipated that the outcome of the current study will identify IL-12B and IL-12RB1 mutations, which lead to persistent lesions of CL. Furthermore, our expected results will reveal an association between NHCL and pro-inflammatory cytokines (IL-12p70, IFN- IL-17a and CXCL-11), as well as CXCR-3 expression. Ethics and dissemination This study has been approved by a local ethical committee. The final results will be disseminated through peer-reviewed journals and scientific conferences.
Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy.
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL- 8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8(+) T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-gamma) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-lambda) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8(+) T cells and IFN-gamma have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.
We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below the discrimination threshold negatively impact response, a phenomenon called antagonism. Wecharacterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration. Thus antagonism constitutes a 'phenotypic spandrel': a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of discrimination displaying antagonism, where antagonism strength is linear in distance from the detection threshold. This contrasts with traditional proofreading based models where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simpler models. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FC epsilon RIs, as well as endocrine signalling/disruption.
Vaccination has saved more lives than any other medical procedure. Pathogens have now evolved that have not succumbed to vaccination using the empirical paradigms pioneered by Pasteur and Jenner. Vaccine design strategies that are based on a mechanistic understanding of the pertinent immunology and virology are required to confront and eliminate these scourges. In this perspective, we describe just a few examples of work aimed to achieve this goal by bringing together approaches from statistical physics with biology and clinical research.
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult. We find a rapid increase with age in the number of random insertions and a dramatic increase in diversity. Because the blood accumulates thymic output over time, blood repertoires are mixtures of different statistical recombination processes, and we unravel the mixture statistics to obtain a picture of the time evolution of the early immune system. Sequence repertoire analysis also allows us to detect the statistical impact of selection on the output of the VDJ recombination process. The effects we find are nearly identical between thymus and blood, suggesting that our analysis mainly detects selection for proper folding of the TCR receptor protein. We further find that selection is weaker in laboratory mice than in humans and it does not affect the diversity of the repertoire.
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small molecule drugs. However, only less than 25% of all patients do respond to immunooncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and beta-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations). To improve response rates and to overcome resistance, novel second- and third-generation immuno-oncology drugs are currently evaluated in ongoing phase I/II trials (either alone or in combination) including novel inhibitory compounds (e.g. TIM-3, VISTA, LAG-3, IDO, KIR) and newly developed co-stimulatory antibodies (e.g. CD40, GITR, OX40, CD137, ICOS). It is important to note that co-stimulatory agents strikingly differ in their proposed mechanism of action compared with monoclonal antibodies that accomplish immune activation by blocking negative checkpoint molecules such as CTLA-4 or PD-1/PD-1 or others. Indeed, the prospect of combining agonistic with antagonistic agents is enticing and represents a real immunologic opportunity to 'step on the gas' while 'cutting the brakes', although this strategy as a novel cancer therapy has not been universally endorsed so far. Concerns include the prospect of triggering cytokine-release syndromes, autoimmune reactions and hyper immune stimulation leading to activation-induced cell death or tolerance, however, toxicity has not been a major issue in the clinical trials reported so far. Although initial phase I/II clinical trials of agonistic and novel antagonistic drugs have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy or other immune system targeting drugs; however, numerous questions remain about dose, schedule, route of administration and formulation as well as identifying the appropriate patient populations. In our view, with such a wealth of potential mechanisms of action and with the ability to fine-tune monoclonal antibody structure and function to suit particular requirements, the second and third wave of immuno-oncology drugs are likely to provide rapid advances with new combinations of novel immunotherapy (especially co-stimulatory antibodies). Here, we will review the mechanisms of action and the clinical data of these new antibodies and discuss the major issues facing this rapidly evolving field. (C) 2017 Elsevier Ltd. All rights reserved.
The development of an immuno-PCR assay for quantitation of low amounts of anti-glycan human antibodies is described. The sensitivity of the assay for determination of low-affinity anti-Le(C) IgM has been found to be 4 ng/ml (similar to 100 pg per sample), thus being two orders of magnitude higher compared to the conventional ELISA with the same antigen.
Primary cutaneous gamma delta T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCR gamma showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.
Background: The immunoprecipitation (IP) assay is a valuable molecular biology tool applied across a breadth of fields. The standard assay couples IP to immunoblotting (IP/IB), a procedure severely limited as it is not easily scaled for high-throughput analysis. Results: Here we describe and characterize a new methodology for fast and reliable evaluation of an immunoprecipitation reaction. FLIP (FLuorescence IP) relies on the expression of the target protein as a chromophore-tagged protein and couples IP with the measurement of fluorescent signal coating agarose beads. We show here that FLIP displays similar sensitivity to the standard IP/IB procedure but is amenable to high-throughput analysis. We applied FLIP to the screening of mouse monoclonal antibodies of unknown behavior in IP procedures. The parallel analysis of the considered antibodies using FLIP and IP/western shows good correlation between the two procedures. We also show application of FLIP using unpurified antibodies (hybridoma supernatant) and we developed a publicly available tool for the easy analysis and quantification of FLIP signals. Conclusions: Altogether, our characterizations of this new methodology show that FLIP is an appealing and reliable tool for any application of high-throughput IP.
Throughout their life animals progressively accumulate mostly detrimental changes in cells, tissues and their functions, causing a decrease in individual performance and ultimately an increased risk of death. The latter may be amplified if it also leads to a deterioration of the immune system which forms the most important protection against the permanent threat of pathogens and infectious diseases. Here, we investigated how four baseline innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin and concentrations of nitric oxide) changed with age in free-living great tits (Parus major). We applied both cross-sectional and longitudinal approaches as birds were sampled for up to three years of their lives. Three out of the four selected innate immune parameters were affected by age. However, the shape of the response curves differed strongly among the innate immune parameters. Natural antibody levels increased during early life until mid age to decrease thereafter when birds aged. Complement activity was highest in young birds, while levels slightly decreased with increasing age. Haptoglobin levels on the other hand, showed a linear, but highly variable increase with age, while nitric oxide concentrations were unaffected by age. The observed differences among the four studied innate immune traits not only indicate the importance of considering several immune traits at the same time, but also highlight the complexity of innate immunity. Unraveling the functional significance of the observed changes in innate immunity is thus a challenging next step. (C) 2017 Elsevier Inc. All rights reserved.
Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells. To better understand the influence of the mutational status of p53 on its presentation by the MHC system and on T cell antitumor reactivity, we generated several mutant p53 constructs and expressed them in HLA-A2(+)/p53(-) cells. Upon co-culture with p53-specific T cells, we measured the specific recognition of p53-expressing target cells by means of cytokine secretion, marker upregulation and cytotoxicity, and in parallel determined p53 expression levels by intracellular staining. We also examined the relevance of antigen presentation components on p53 recognition and the impact of mutant p53 expression on cell-cycle dynamics. Our results show that selected p53 mutations altering protein stability can modulate p53 presentation to T cells, leading to a differential immune reactivity inversely correlated with measured p53 protein levels. Thus, p53 may behave differently than other classical tumor antigens and its mutational status should therefore be taken into account when elaborating immunotherapy treatments of cancer patients targeting p53.
The ac impedance spectroscopy measurements are predominantly taken by using impedance analyzers based on analog auto-balancing bridge. However, those bench-top analyzers are generally complicated, bulky and expensive, thus limiting their usage in industrial field applications. This paper presents the development of a compact wideband precision measurement system based on digital auto-balancing bridge. The methods of digital auto-balancing bridge and digital lock-in amplifier are analyzed theoretically. The overall design and several key sections including null detector, direct digital synthesizer-based sampling clock, and digital control unit are introduced in detail. The results show that the system achieves a basic measurement accuracy of 0.05% with a frequency range of 20 Hz-2 MHz. The advantages of versatile measurement capacity, fast measurement speed, small size and low cost make it quite suitable for industrial field applications. It is demonstrated that this system is practical and effective by applying in determining the impedance-temperature characteristic of a motor starter PTC thermistor.
Current sources are critical for the performance of bioimpedance health monitoring device. The challenging features for a high accuracy and wide bandwidth voltage controlled current source are stable and safe current magnitudes. Corresponding to the typical measurement requirements, it should allow typical load impedances in the range from 100 Omega to 10 k Omega and have high output impedance of approximately 10 M Omega at 5 kHz and 1 M Omega at high frequencies up to 1 MHz without harmonics and influence of stray capacitances. Generalized impedance converters and negative impedance converters help to reduce the influence of stray capacitances. In this study, we compare between two types of voltage controlled current sources for grounded loads: Howland and Tietze circuits. Based on this study, we suggest an improved Howland circuit in inverting dual configuration with a negative feedback using the high bandwidth amplifier AD8021. With this configuration, a better accuracy is reached at higher frequencies up to 1 MHz. With the addition of compensation capacitor to the operational amplifier, this circuit configuration is capable to maintain approximately constant current amplitude within an accuracy of less than 0.022% at both low and high frequencies up to 1 MHz. (C) 2015 Elsevier Ltd. All rights reserved.
Purpose:The aim of the present study was to mimic the hierarchical structure of bone tissues by simple sandblasting/acid-etching and anodization to investigate the effects of such surface characteristics on proliferation and differentiation of osteoblasts in high glucose concentrations. By the way, the effects of high glucose levels on osteoblast functions were tested.Methods:MC3T3-E1 cells cultured on sand-blasted and acid-etched (SLA) surface and nano-modified SLA (NMSLA) surface were subjected to normal serum (NS) and diabetic serum (DS), respectively. The surface characteristics were evaluated by scanning electron microscopy. Cell proliferation was assessed using MTT assay. The levels of alkaline phosphatase (ALP) activity and mineralization were measured and compared. Real-time polymerase chain reaction was applied to detect the expression levels of osteogenic genes.Results:NMSLA significantly increased cell proliferation at time points ranging from 3 to 7 days under both serums. Cells cultured on NMSLA surfaces displayed significantly higher ALP activities and mineralization. The expression levels of Runx2 (indicates runt-related protein 2), collagen I (COL1), and osteocalcin (OCN) were notably increased on NMSLA surface compared with SLA surface. Moreover, we found that high glucose increased osteoblast proliferation but decreased differentiation of osteoblast slightly.Conclusion:The hierarchical micro/nano-structured titanium surface has a favorable biocompatibility on simultaneously improving osteoblast proliferation and differentiation in diabetic serum.
OBJECTIVE: The aim of this in vivo study was to evaluate two different types of implant-abutment connections: screwed connection and cemented connection, analyzing peri-implant bacteria microflora as well as other clinical parameters. PATIENTS AND METHODS: Twenty implants were selected, inserted in 20 patients, 10 with a screwed implant-abutment connection (Group 1) and 10 with a cemented implant-abutment connection (Group 2). The peri-implant microflora was collected, after at least 360 days from the prosthetic rehabilitation, using paper points inserted in peri-implant sulcus for 30 s. Polymerase chain reaction (PCR) Real-time analyzed the presence of 9 bacteria periodontal-pathogens and Candida albicans. RESULTS: Our findings showed that bacteria colonized all Groups analyzed, the average bacterial count was 3.7 E + 08 (+/- 1.19) in Group 1, compared to 2.1 E + 08 (+/- 0.16) in Group 2; no statistically significant differences were observed (p >0.0.5). In Group 1, however, bacterial colonization of peri-implant sulci was over the pathogenic threshold for 5 bacteria, indicating a high-risk of peri-implantitis. Also in Group 2, results showed a microflora composed by all bacteria analyzed but, in this case, bacterial colonization of peri-implant sulci was over the pathogenic threshold for only 1 bacterium, indicating a lower risk of peri-implantitis. Moreover, clinical parameters (PPD >3 mm and m SBI >0) confirmed a greater risk of peri-implantitis in Group 1 compared to Group 2 (p < 0.05). CONCLUSIONS: We concluded that, also after only 360 days, implants with screwed connection showed a higher risk of peri-implantitis that implants with cemented connection.
The present study is the first report providing evidence for a physiological role of a truncated form of the mRNA cap-binding protein eIF4E1 (eukaryotic initiation factor 4E1). Our initial observation was that eIF4E, which mediates the mRNA cap function by recruiting the eIF4F complex (composed of eIF4E, 4G and 4A), occurs in two forms in porcine endometrial tissue in a strictly temporally restricted fashion. The ubiquitous prototypical 25 kDa form of eIF4E was found in ovariectomized and cyclic animals. A new stable 23 kDa variant, however, is predominant during early pregnancy at the time of implantation. Northern blotting, cDNA sequence analysis, in vitro protease assays and MS showed that the 23 kDa form does not belong to a new class of eIF4E proteins. It represents a proteolytically processed variant of eIF4E1, lacking not more than 21 amino acids at the N-terminus. Steroid replacements indicated that progesterone in combination with 17 beta-oestradiol induced the formation of the 23 kDa eIF4E. Modified cell-free translation systems mimicking the situation in the endometrium revealed that, besides eIF4E, eIF4G was also truncated, but not eIF4A or PABP [poly(A)binding protein]. The 23 kDa form of eIF4E reduced the repressive function of 4E-BP1 (eIF4E-binding protein 1) and the truncated eIF4G lacked the PABP-binding site. Thus we suggest that the truncated eIF4E provides an alternative regulation mechanism by an altered dynamic of eIF4E/4E-BP1 binding under conditions where 4E-BP1 is hypophosphorylated. Together with the impaired eIF4G-PABP interaction, the modified translational initiation might particularly regulate protein synthesis during conceptus attachment at the time of implantation.
Implicit evaluations reflect people's gut response toward an attitude object and are based on associative processes. They are the starting ground for more reflective processes and subsequent explicit evaluations. The present research examined determinants and consequences of implicit evaluations in a rape case. Situational (i.e. specifics of the rape case) and personal factors (i.e. rape myth acceptance) were demonstrated to influence both explicit and implicit judgments of the rape case. Moreover, sex of participant influenced participants' implicit evaluations but affected explicit judgments only indirectly via the implicit evaluation. People's gut response was shown to affect their explicit judgment of the case, and this effect was particularly pronounced for people with a low need for cognition (i.e. people who do not like to engage in effortful processing). The discussion focuses on the role of implicit cognition and implicit biases in judicial decision-making.
This article reviews the Sex with Children (SWCH) scale and compares its psychometric properties to alternative measures in the field. Examination of the scale indicates that it is one of several instruments which do not proportionally tap into all implicit theory schemas that have been proposed in the literature. This does not help clinicians who aim to target pro-offending schema since the scale appears to neglect certain types of beliefs that are considered to be important in the investigation of child molester cognition. Similar to many other instruments in the field, the SWCH scale is unlikely to identify offenders who outwardly endorse child abuse items, and its discriminant validity may be better viewed as a capacity to differentiate those who disagree less from those who disagree more. The scale possesses excellent reliability properties compared to other instruments. However, recently reported area under the curve calculations indicate that the scale's predictive power for sexual and violent reconviction is no better than chance. It would be useful to develop the SWCH scale so that it does not under-represent important types of pro-offending schema. Copyright (c) 2014 John Wiley & Sons, Ltd.
The transcription factor hepatocyte nuclear factor 1 beta (HNF1 beta) is ubiquitously overexpressed in ovarian clear cell carcinoma (CCC) and is a potential therapeutic target. To explore potential approaches that block HNF1 beta transcription we have identified and characterised extensively the nuclear localisation signal (NLS) for HNF1 beta and its interactions with the nuclear protein import receptor, Importin-alpha. Pull-down assays demonstrated that the DNA binding domain of HNF1 beta interacted with a spectrum of Importin-alpha isoforms and deletion constructs tagged with eGFP confirmed that the HNF1 beta(KKMRRNR235)-K-229 sequence was essential for nuclear localisation. We further characterised the interaction between the NLS and Importin-alpha using complementary biophysical techniques and have determined the 2.4 angstrom resolution crystal structure of the HNF1 beta NLS peptide bound to Importin-alpha. The functional, biochemical, and structural characterisation of the nuclear localisation signal present on HNF1 beta and its interaction with the nuclear import protein Importin-alpha provide the basis for the development of compounds targeting transcription factor HNF1 beta via its nuclear import pathway. (C) 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc.
As maize was domesticated in Mexico around 9,000years ago, local farmers have selected and maintained seed stocks with particular traits and adapted to local conditions. In the present day, many of these landraces are still cultivated; however, increased urbanization and migration from rural areas implies a risk that this invaluable maize germplasm may be lost. In order to implement an efficient mechanism of conservation in situ, the diversity of these landrace populations must be estimated. Development of a method to select the minimum number of samples that would include the maximum number of alleles and identify germplasm harboring rare combinations of particular alleles will also safeguard the efficient ex-situ conservation of this germplasm. To reach this goal, a strategy based on SSR analysis and a novel algorithm to define a minimum collection and rare genotypes using landrace populations from Puebla State, Mexico, was developed as a proof of concept for methodology that could be extended to all maize landrace populations in Mexico and eventually to other native crops. The SSR-based strategy using bulked DNA samples allows rapid processing of large numbers of samples and can be set up in most laboratories equipped for basic molecular biology. Therefore, continuous monitoring of landrace populations locally could easily be carried out. This methodology can now be applied to support incentives for small farmers for the in situ conservation of these traditional cultivars.
Corneal immunoimaging and neuroimaging approaches facilitate in vivo analyses of the cornea, including high-resolution imaging of corneal immune cells and nerves. This approach facilitates the analyses of underlying immune and nerve alterations not detected by clinical slit-lamp examination alone. In this review, we describe recent work performed in our translational ocular immunology center with a focus on "bench-to-bedside" and "bedside-to-bench" research. The ability to visualize dendritiform immune cells (DCs) in patients with laser in vivo confocal microscopy (IVCM), recently discovered in the central murine cornea, has allowed us to demonstrate their utility as a potential surrogate biomarker for inflammatory ocular surface diseases. This biomarker for inflammation allows the measurement of therapeutic efficacy of anti-inflammatory drugs and its utility as an endpoint in clinical trials with high interobserver agreement. IVCM image analyses from our studies has demonstrated a significant increase in DC density and size in ocular disease, a positive correlation between DC density and clinical signs and symptoms of disease and pro-inflammatory tear cytokines, and a strong negative correlation between DC density and subbasal nerve density. In conjunction with preclinical research investigating the inflammatory state in a partial or fully denervated cornea, our results indicated that corneal nerves are directly involved in the regulation of homeostasis and immune privilege in the cornea.
Inbreeding, reproduction between relatives, often impinges on the health and survival of resulting offspring. Such inbreeding depression may manifest itself through immunological costs as inbred individuals suffer increased propensity to disease, infection and parasites compared to outbred conspecifics. Here, we assess how the intestinal parasite loads of wild banded mongooses (Mungos mungo) vary with pedigree inbreeding coefficient (f) and standardized multi-locus heterozygosity. We find a significant association between increased heterozygosity and lower parasite loads; however, this correlation does not stand when considering f. Such findings may be explained by local genetic effects, linkage between genetic markers and genes influencing parasite burdens. Indeed, we find heterozygosity at certain loci to correlate with parasite load. Although these tentative local effects are lost following multiple test correction, they warrant future investigation to determine their strength and impact. We also suggest frequent inbreeding within banded mongooses may mean heterozygosity is a better predictor of inbreeding than pedigree f. This is because inbreeding facilitates linkage disequilibrium, increasing the chances of neutral markers representing genome-wide heterozygosity. Finally, neither f nor heterozygosity had a significant influence on the loads of two specific gastrointestinal parasites. Nevertheless, more heterozygous individuals benefited from reduced overall parasitic infection and genetic diversity appears to explain some variation in parasite burdens in the banded mongoose.
Residential domestic hot water energy consumption represented 16% of the EU household heating demand in 2013. With the improvement of the building insulation envelope, domestic hot water contribution to energy consumption is expected to increase significantly, with values between 20% and 32% in single family buildings, and between 35% to almost 50% in multifamily buildings. This energy, currently lost to the environment, can be recovered by waste water heat recovery systems inside buildings (in building solutions). While most publications in this field focus on shower heat recovery and on waste water as heat source for heat pumps, the detailed impact of waste water heat recovery at a city scale by aggregating building data has not been addressed yet. Furthermore, waste water heat recovery potential and relevance was not yet quantified as a function of the specific inhabitant and household numbers, end-use occurrence, and building type and age. A method to quantify the building-specific energy cost and energy saving potentials, based on pinch analysis, at the urban scale of in-building waste water heat recovery systems is therefore proposed. A complementary method to spatially allocate and characterise grey water streams as to thermal load and temperature levels in function of the building specificities is also developed. These methods are applied in two case studies, first as retrofitting solution in a city in Luxembourg and, second, as optimisation measure for high efficiency residential buildings. Grey water heat recovery would reduce the residential fuel consumption of the city by 63%. An integrated approach combining grey water heat recovery for hot water preheating and a heat pump yields up to 28% and 41% electricity savings for passive single family houses and multifamily buildings, respectively. With the detailed characterisation of various grey water streams as a function of inhabitant number and end -use occurrence, the quantification of the energy savings and costs through heat recovery is improved. The outcomes of urban energy and cost assessments concerning grey water heat recovery are more specific, as the results at building level are aggregated to the considered geographical scope. The proposed method therefore complements current urban energy and cost assessments with the detailed integration of in -building grey water heat recovery systems. (C) 2017 Published by Elsevier Ltd.
The purpose of the study was to investigate types of childhood abuse in a sample of 60 inmates and to explore the relationships between childhood abuse, criminality, and drug addiction. Overall, the sample inmates came from risky families with a high prevalence of crime, drug addiction, and mental health problems. The results showed that a history of child abuse was common, and emotional neglect was more prevalent than physical, emotional, or sexual abuse. The odds for childhood abuse were higher among inmates whose fathers had been addicted to drugs and involved in crime, and whose siblings suffered from mental health problems.
Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r = 0.7033, MCCB social cognition r = 0.7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r = 0.7785, PANSS negative r = 0.7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making. (C) 2016 Elsevier Inc. All rights reserved.
Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to be used for the study of underlying molecular biology of disease, therapeutic drug screening, and transplant-based regenerative medicine. However, methods for the directed differentiation of skeletal muscle for these purposes remain scarce and incomplete. Here, we present a novel, small molecule-based protocol for the generation of multinucleated skeletal myotubes using eight independent iPSC lines. Through combinatorial inhibition of phosphoinositide 3-kinase (PI3K) and glycogen synthase kinase 3 beta (GSK3 beta) with addition of bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2), we report up to 64% conversion of iPSCs into the myogenic program by day 36 as indicated by MYOG(+) cell populations. These cells began to exhibit spontaneous contractions as early as 34 days in vitro in the presence of a serum-free medium formulation. We used this protocol to obtain iPSC-derived muscle cells from frontotemporal dementia (FTD) patients harboring C9orf72 hexanucleotide repeat expansions (rGGGGCC), sporadic FTD, and unaffected controls. iPSCs derived from rGGGGCC carriers contained RNA foci but did not vary in differentiation efficiency when compared to unaffected controls nor display mislocalized TDP-43 after as many as 120 days in vitro. This study presents a rapid, efficient, and transgene-free method for generating multinucleated skeletal myotubes from iPSCs and a resource for further modeling the role of skeletal muscle in amyotrophic lateral sclerosis and other motor neuron diseases.
A new electronic interface for inductive sensors is presented. The proposed circuit is basically a current-feedback operational-amplifier (CFOA)-based sinusoidal oscillator circuit. The circuit uses only one externally connected inductor and exploits to advantage the internal poles of the CFOA. Sinusoidal oscillation at frequency of 122.1 MHz was obtained using the AD844 CFOA and an inductor of inductance = 0.14 mu H with peak-to-peak output voltage = 700 mV.
Industrial waste heat may be one of the answers to future energy demands. Depending on the temperature, industrial waste heat may be used to produce electricity or meet cooling or heating demands at different temperature levels. However, in order to estimate the influence the waste heat may have in future energy systems, the magnitude of the industrial waste heat in the different countries need to be estimated. For Germany, so far, only top-down analyses of the waste heat potential exist, using key figures derived from other studies in other countries. In this paper, the first bottom-up approach for estimating the industrial waste heat potential in Germany is presented. For this approach, an algorithm to evaluate and test the mandatory emission report data from German production companies was developed. In a second step, round about 81,000 data sets have been evaluated to calculate a conservative and lower boundary value for the industrial waste heat. As this conservative, lower boundary based on the collected data from the German industry, the waste heat volume was evaluated as 127 PJ/a or 13 % of the industrial fuel consumption. Results were used to derive key figures with which the missing share of the data was approximated.
Exogenous oxytocin administration is widely reported to improve social cognition in human and nonhuman primate adults. Risk factors of impaired social cognition, however, emerge in infancy. Early interventions-when plasticity is greatest-are critical to reverse negative outcomes. We tested the hypothesis that oxytocin may exert similar positive effects on infant social cognition, as in adults. To test this idea, we assessed the effectiveness of acute, aerosolized oxytocin on two foundational social cognitive skills: working memory (i.e., ability to briefly hold and process information) and social gaze (i.e., tracking the direction of others' gaze) in 1-month-old nursery-reared macaque monkeys (Macaca mulatta). We did not predict sex differences, but we included sex as a factor in our analyses to test whether our effects would be generalizable across both males and females. In a double-blind, placebo-controlled design, we found that females were more socially skilled at baseline compared to males, and that oxytocin improved working memory and gaze following, but only in males. These sex differences, while unexpected, may be due to interactions with gonadal steroids and may be relevant to sexually dimorphic disorders of social cognition, such as male-biased autism spectrum disorder, for which oxytocin has been proposed as a potential treatment. In sum, we report the first evidence that oxytocin may influence primate infant cognitive abilities. Moreover, these behavioral effects appear sexually dimorphic, highlighting the importance of considering sex differences. Oxytocin effects observed in one sex may not be generalizable to the other sex.
Background Child abuse is a health and social problem, and few screening instruments are available for the detection of risk in primary health care. The aim was to develop a screening instrument to be used by professionals in the public health care sector, thus enabling the detection of infants and toddlers at risk of emotional and physical abuse and neglect, and to provide evidence for the feasibility of the instrument in Cyprus, Greece and Spain. Method A total of 50 health professionals from paediatric public health-care centres in the three countries were involved in a three-step process for guiding the development of the screening tool and its application. Results A nine-item screening tool, consisting of items assessing relational emotional abuse, physical abuse and other risk factors, was developed. The screening tool was applied on a total of 219 families with 0 to 3-year-old children attending public health centres in the three countries. Clinicians reported that they agreed on the inclusion of the questions (86.4-100%) and that they found the questions to be useful for the clinical evaluation of the family (63.2-100%). Conclusion The screening tool shows considerable face validity and was reported feasible by an international set of clinicians.
Individual differences in early attention are associated with later social, cognitive, and emotional development, and attentional deficits in the first year are associated with risk for developmental disorders such as Autism Spectrum Disorder (ASD). The First Year Inventory (FYI; Baranek, Watson, Crais, & Reznick, 2003) was developed to identify 12-month-olds at risk for an ASD diagnosis. The current study identifies FYI items that reflect aspects of early attention that might predict future typical and atypical social, cognitive, and emotional development. Using a series of theoretical and statistical methods, we developed 3 attention-based constructs from the FYI: Responding to Social Attention (RSA), Initiating Social Attention (ISA), and Nonsocial Sensory Attention (NSA). A database with completed FYIs was analyzed using these constructs to determine the strength of relations among items. Cronbach's alpha analyses indicated good internal consistency, and item distribution was further supported using a confirmatory factor analysis. Data analyses showed statistically significant relations between the scores on these domains at 12 months and subsequent social responsiveness scores at 3 years. Analyses demonstrating the statistical and predictive validity of these 3 FYI attention constructs support their use for innovative explorations of infant behavioral patterns that can be used to predict typical and atypical individual trajectories in the development of later social, cognitive, and emotional skills.
The objective of this study was to develop a new elaborate method to evaluate infants' liking of foods that could be applied at home and to compare the results of this elaborate method with those of a basic method. Mothers of infants aged 4 to 7 (n = 44) and 12-15 months (n = 46) participated in this study. For the basic method, mothers were asked to assess their infant's global liking at the end of a meal. Then, for the elaborate method, mothers received detailed instructions on how to feed their infant, how infants might express like/dislike and when to stop the meal. During the first nine spoons, they were asked to report the presence/absence of positive and negative behaviours after each spoon, and the infant's initial liking was reported after each triplet of spoons. They also assessed their infant's global liking at the end of the meal. Both methods were applied using three commercial familiar baby foods adapted to each age range. In 4-7-month-olds, the elaborate method showed a significant difference across products for liking, whereas the basic method did not show any difference. In 12-15-month-olds, the elaborate method showed more differences across products for liking than the basic method. In both age groups, negative behaviours, despite being less frequently reported, provided better liking discrimination than positive behaviours. In conclusion, the elaborate method produced better product liking discrimination than the basic method by focusing maternal attention on infants' eating behaviours since the first spoons. (C) 2017 Elsevier Ltd. All rights reserved.
Infant-directed speech (IDS) is the particular voice register observed in the majority of parents in interaction with their infants and differs from natural speech used in conversations with adults by showing exaggerated prosodic features. These prosodic features are supposed to have effects on regulating infant arousal and attention, fostering infant pre-linguistic and linguistic competences and enhancing the expression of positive affect. The present set of meta-analyses was conducted to test these associations and the role of moderators during the first two years of infant life. The results confirmed an overall association between IDS prosody and infant outcomes with prosodic values typical of IDS associated with better outcomes. This association was confirmed for attentional, pre-linguistic and linguistic outcomes with a greater effect on pre-linguistic than linguistic outcomes. An insufficient number of studies was found to test the association with infant emotion expression. Many limitations in the existing body of literature were found, such as a lack of empirical papers exploring IDS prosody in relation to infant outcomes using natural observations. The results and limitations were discussed in light of the necessity to examine the interplay between the quality of IDS prosody and other aspects of parental communicative and care giving competences. To do so, the contribution of scholars from different fields is needed with the aim to fully understand the multidimensional determinants and influential mechanisms of IDS. (C) 2017 Elsevier Inc. All rights reserved.
Overall analysis and understanding of mechanisms are of great importance for treatment of infantile pneumonia due to its high morbidity and mortality worldwide. In this study, we preliminarily explored the function and mechanism of focal adhesion kinase (FAK) in regulation of inflammatory response induced by lipopolysaccharides in A549 cells. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis were used to explore the correlation of FAK expression with cell apoptosis, viability, and the inflammatory cytokine activity in A549 cells. The results showed that knockdown of FAK enhanced cell viability, suppressed apoptosis, and decreased inflammatory cytokine activity. In addition, downregulation of FAK could activate the Wnt and nuclear factor kappa B signaling pathways. These findings suggest that FAK might be involved in progression of infantile pneumonia and could be a new therapeutic target for this disease.
Legislation in the United States, such as the Child Abuse Prevention and Treatment Act and the Individuals With Disabilities Education Improvement Act, mandates service system collaboration to meet the complex needs of young children with disabilities who have experienced abuse. This literature review examines extant literature related to young children with disabilities who have experienced abuse. Gaps in the literature are identified and future directions are discussed.
Context: The human papillomaviruses (HPVs) are a major global health burden, playing a part in diseases ranging from genital warts to malignancies such as penile cancer in men and cervical cancer in women. Objective: To explore the molecular biology and epidemiology of HPV infection; the diseases linked to it; and current prevention strategies, including the potential role of vaccination. Evidence acquisition: The relevant papers, reviews, and guidelines pertaining to the topics were collected for the purpose of this review from PubMed and online guidelines resources including the European Association of Urology and the Centers for Disease Control and Prevention. Evidence synthesis: The current knowledge on genital HPV in men is explained and summarised. Conclusions: There is an urgent need for more data on the incidence and persistence of HPV at the different anatomic sites, the incidence of external genital lesions, and the types of HPV in these lesions. This will allow a more comprehensive understanding of the natural history of HPV infection and its progression to both benign and malignant disease in men and will help formulate the development and implementation of vaccination programs. Patient summary: This review explores the molecular biology and epidemiology of human papillomavirus (HPV) infection; the diseases linked to it; and current prevention strategies, including the potential role of vaccination. There is an urgent need for more data on the incidence and persistence of HPV at the different anatomic sites, the incidence of external genital lesions, and the types of HPV in these lesions. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Unravelling the molecular mechanisms of disease manifestations is important to understand pathologies and symptom development in plant science. Bacteria have evolved different strategies to manipulate their host metabolism for their own benefit. This bacterial manipulation is often coupled with severe symptom development or the death of the affected plants. Determining the specific bacterial molecules responsible for the host manipulation has become an important field in microbiological research. After the identification of these bacterial molecules, called "effectors," it is important to elucidate their function. A straightforward approach to determine the function of an effector is to identify its proteinaceous binding partner in its natural host via a yeast two-hybrid (Y2H) screen. Normally the host harbors numerous potential binding partners that cannot be predicted sufficiently by any in silico algorithm. It is thus the best choice to perform a screen with the hypothetical effector against a whole library of expressed host proteins. It is especially challenging if the causative agent is uncultivable like phytoplasma. This protocol provides step-by-step instructions for DNA purification from a phytoplasma-infected woody host plant, the amplification of the potential effector, and the subsequent identification of the plant's molecular interaction partner with a Y2H screen. Even though Y2H screens are commonly used, there is a trend to outsource this technique to biotech companies that offer the Y2H service at a cost. This protocol provides instructions on how to perform a Y2H in any decently equipped molecular biology laboratory using standard lab techniques.
The demand for expertise in pathology for the diagnosis of infectious diseases (ID) is continually growing, due to an increase in ID in immunocompromised patients and in the (re)-emergence of common and uncommon diseases, including tropical infections and infections with newly identified microbes. The microbiology laboratory plays a crucial role in diagnosing infections, identifying the responsible infectious agents and establishing sensitivity of pathogens to drug therapy. Pathology, however, is the only way to correlate the presence of an infectious agent with the reaction it evokes at cell and tissue level. For pathologists working in the field of ID pathology, it is essential to dispose of competence in cell and tissue pathology as well as in microbiology. Expertise in ID includes understanding of taxonomy and classification of pathogens as well as morphological criteria supporting their identification. Moreover, ID pathologists must master the methods used to detect pathogens in fixed cell and tissue samples, notably immunohistochemistry, in situ hybridization and the polymerase chain reaction. Paradoxically, the increasing frequency of lesions caused by pathogens and diagnosed in a pathology laboratory appears to be paralleled by a gradual loss of expertise of pathologists in the field of infectious and tropical diseases. We contend that this may be due at least in part to the continuously increasing number of samples of tumor tissue pathologists deal with and the rapidly expanding number of tissue based biomarkers with predictive value for new anti-cancer therapies. In this review, we highlight current and future issues pertaining to ID pathology, in order to increase awareness of its importance for surgical and molecular pathology. The intention is to contribute to the development of best practice in ID pathology.
Background: Infertility is one of the major social issues. Due to the asymptomatic cervical infection associated with Staphylococcus aureus (S. aureus), the majority of patients remain undiagnosed. The present study intended to assess the frequency of S. aureus isolated from infertile women's endocervix in northwest Iran. Materials and Methods: In a descriptive cross sectional study, specimens were randomly collected during vagina examination using a sterile speculum and swabbing. After performance of antibiotic susceptibility testing, polymerase chain reaction (PCR) was used to identify methicillin-resistance S. aureus (MRSA) and toxic shock syndrome toxin-1 (TSST-1). Results: About 26 (26%) and 9 (9%) women's urogenital tracts were colonized by S. aureus and Candida spp., respectively, of which three (11.5%) patients were infected with fungi and S. aureus, simultaneously. Antibiotic susceptibility results showed high activity of vancomycin and co-trimoxazole on isolates. Regarding PCR results, mecA sequences were detected in 7 (26.9%) strains, whilst the tst gene encoding TSST-1 was not detected in any of clinical strains. Conclusion: The prevalence of S. aureus was very high in infertile women. Therefore, it demands all patients undergoing infertility treatment to be investigated thoroughly for this type of infection.
This paper addresses a significant paradox in biomaterials science; biocompatibility phenomena have been experienced and described for over 50 years but without an agreed understanding of the framework of mechanisms that control the events that occur when a biomaterial is exposed to the tissues of the human body. The need for such an understanding has become more urgent as biomaterials are now used in wide-ranging applications such as tissue engineering, drug and gene delivery, and imaging contrast agents. A detailed analysis of these phenomena, especially in terms of clinical outcomes rather than in vitro experiments, determines that two overarching mechanisms, mechanotransduction and sterile inflammation associated with damage associated molecular patterns, are responsible for the vast majority of phenomena. In contrast, interfacial interactions, for so long being assumed to play pivotal roles in biocompatibility, especially relating to protein adsorption, are actually relatively unimportant unless, through conformational changes, they are able to participate in 3D ECM development. Critical to this new view of biocompatibility is the fact that the combination of mechanotransduction and sterile inflammation, especially focusing on inflammasome activation and the immunology of the balance between inflammation and fibrosis, allows biomaterials science to encompass mechanisms of innate and adaptive immunity without recourse to the traditional implications of pathogen induced responses of the immune system. In this way, a system of biocompatibility pathways can be generated; these are able to explain a wide range of clinical biocompatibility challenges, including nanoparticle translocation and internalization, intraocular lens opacification, leukocyte dominated responses to metallic wear debris in joint replacement, stem cell differentiation of nanostructured hydrogels, tissue responses to incontinence meshes, and restenosis of intravascular stents. Perhaps even more importantly, the identification of these molecular pathways of biocompatibility offers prospects of the control of the host response by targeting specific points in these pathways, for example the inhibition of epithelial to mesenchymal transformation that can result in excessive fibrosis, and the inhibition of activation of the NLRP3 inflammasome following exposure to biomaterial-induced stresses; this should lead to a more effective translation of biocompatibility understanding into better clinical outcomes.
Inflammation in the retinal pigment epithelium is an important contributor to the pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated from the root of Scutellaria baicalensis and has multiple pharmacological effects, including anti-inflammatory effects. The present study sought to determine if the pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE-19 cells were pre-conditioned with different concentrations of wogonin (0-50 mu M) prior to induction of inflammation with LPS (2 mu g/ml). Transepithelial electrical resistance analysis demonstrated that 24 h treatment with 10 and 50 mu M wogonin ameliorated LPS-induced changes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence analyses revealed that wogonin restrained LPS-induced tight junction proteins, claudin-1 and ZO-1. LPS-induced upregulation of inflammatory mediators in ARPE-19 cells, including IL-1 beta, IL,-6, IL,-8, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and TNF-alpha was reduced after pre-treatment with wogonin. In addition, RT-qPCR and western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS-stimulated ARPE-19 cells. This is a novel mechanism indicating that pre-treatment with wogonin could attenuate the TLR4/NF-kappa B-mediated inflammatory response in LPS-stimulated ARPE-19 cells, and thus could be a potential therapy for the treatment of AMD.
ObjectiveEstablish whether inflammatory biomarkersserum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-)are related to key symptoms of depression, including anxiety and fatigue, in a cross-sectional, out-patient setting to identify biomarkers that reflect psychiatric symptomatology in a naturalistic, real-life population. MethodsWe measured SAA, CRP, IL-6, and TNF- in plasma samples from 89 adult psychiatric out-patients by multiplex, high-sensitivity electrochemiluminescent assays. Psychiatric symptoms were evaluated using the Hamilton Depression Rating Scale (HAMD-17), the Patient Health Questionnaire (PHQ-9), and the Center for Epidemiological Studies Depression Scale (CES-D). ResultsPlasma SAA was most robustly associated with depressive symptoms across diagnostic boundaries in this cohort of out-patients. Elevated SAA was significantly associated with higher total scores on the HAMD-17 scale and correlated with multiple scale items that rated symptoms of fatigue and depressed mood, but not with anxiety-related items. ConclusionsSAA might constitute a cross-diagnostic marker indicative of depressed mood and fatigue in a naturalistic patient setting. Because SAA activates Toll-like receptors 2 and 4, present on macrophages and glial cells, its association with depression severity could also implicate this inflammatory mediator in the pathogenesis of mood disorders.
Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23 days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS >= 12) and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228 controls were analyzed with an inflammation protein panel using multiplex proximity extension assay technology, comprising of 92 inflammation-associated markers. A summary inflammation variable was also calculated. Logistic regression, LASSO and Elastic net analyses were implemented. Forty markers were lower in late pregnancy among women with depressive symptoms postpartum. The difference remained statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and IL-10, after Bonferroni correction. The summary inflammation variable was ranked as the second best variable, following personal history of depression, in predicting depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1 were validated in relation to methylation status of loci in the respective genes in a different population, using openly available data. This explorative approach revealed differences in late pregnancy levels of inflammation markers between women presenting with depressive symptoms postpartum and controls, previously not described in the literature. Despite the fact that the results do not support the use of a single inflammation marker in late pregnancy for assessing risk of postpartum depression, the use of STAM-BP or the novel notion of a summary inflammation variable developed in this work might be used in combination with other biological markers in the future. (C) 2017 The Authors. Published by Elsevier Ltd.
Purpose To evaluate the prevalence of large drusen in a uveitis clinic population. Design Retrospective, cohort study. Methods Patients with primary, non-infectious uveitis 55years or older who were seen at the National Eye Institute of the National Institutes of Health from 2004 through August 2013 were reviewed using electronic medical records and photographic databases. Patients were classified as having age-related macular degeneration (AMD) if either eye had large drusen, geographic atrophy or neovascular AMD according to definitions used by the Eye Diseases Prevalence Research Group (EDPRG). The expected number of cases and standardised mortality ratio (SMR) for large drusen were estimated based on EDPRG estimates. Results We identified 177 patients aged 55years as having primary non-infectious uveitis; 170 (96.0%) had gradable fundus photos. Average age was 65.07.5years (range 55-87), and 87 were non-Hispanic white, 66 non-Hispanic black, 6 Hispanic white and 11 of other race/ethnicity. Large drusen were identified in four patients (2.4%; 95% CI 0.6 to 6.0). No patients were identified to have late AMD. In the uveitis cohort, the SMR for cases of large drusen, which was adjusted for age, was calculated to be 0.32 (95% CI 0.12 to 0.70) for the whole cohort, 0.28 (95% CI 0.09 to 0.79) for non-Hispanic whites and 0.46 (95% CI 0.14 to 1.29) for non-Hispanic blacks. Conclusions Large drusen prevalence among patients with uveitis 55years of age appears less than the prevalence in the general US population after accounting for differences in age distribution, especially for non-Hispanic whites. Although the racial and gender distribution in this study population is not directly representative of the general US population, results of this study suggest possible sparing of patients with uveitis from AMD. A larger systematic study with greater power would be needed to confirm these findings.
Purpose Kyrieleis retinal periarteritis reflects the severe intraocular inflammation experienced by the eye. Its aetiology has not been well established, since only nine cases have been reported and there is no pathological study available in the literature. We determine the pathogenesis of Kyrieleis periarteritis based on interpretation of multimodal imaging findings. Methods Charts of patients with Kyrieleis arteritis seen between 2006 and 2014 were retrieved from eight uveitis referral centres throughout the world. Follow-up ranged from 5 to 12months. Results Twenty-five eyes with Kyrieleis arteritis from 25 patients were included in the study. Nineteen patients (72%) were male and six (28%) were female. Twenty-three patients were diagnosed with toxoplasmosis retinochoroiditis and two patients had cytomegalovirus retinitis. Fluorescein angiography, fundus autofluorescence and indocyanine green angiography were performed on 25/25 (100%) eyes. In eight eyes (32%), baseline spectral domain optical coherence tomography (SD-OCT) scans were performed along the segmental Kyrieleis arteritis. Fluorescein angiography showed early hypofluorescence and intermediate hyperfluorescence associated with the areas of focal arteritis, whereas indocyanine green angiography of these accumulations showed early hypofluorescence and late hyperfluorescence. Fundus autofluorescence revealed an increased autofluorescence of the vessels corresponding to the Kyrieleis plaques, while SD-OCT scans along the segmental Kyrieleis arteritis showed hyperreflectivity of the vessel wall. Conclusions These imaging modalities provide in vivo, quasi-histologic images demonstrating that Kyrieleis plaques are characterised by an inflammatory involvement within the vessels' endothelium.
Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes. During mammalian pregnancy, maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. This review focuses on the specific immune parameters that become altered during human pregnancy, the identity and function of some immune modulators that have been best characterized to date, as well as a comprehensive evaluation of the pregnancy-associated mechanisms that downregulate proinflammatory immunity to a level sufficient to prevent the triggering of premature common pathway of labor and damage to developing organs.
Objective: To examine differences in inflammation markers in sexually active versus abstinent women and observe changes in inflammation markers across the menstrual cycle. Cycle-related immune fluctuations may have evolved to reduce interference with conception. If so, reproductively active (i.e., sexually active) women should show the most variability in cytokine expression. Design: Participants provided serum samples at menses and ovulation (from which cytokines were assayed) and saliva samples at menses and during follicular, ovulation, and luteal phases (from which C-reactive protein [CRP] was assayed). Participants self reported intercourse frequency during the study. Setting: Academic research laboratory. Patient(s): Thirty-two healthy, naturally cycling premenopausal women (sexually active, n = 15; abstinent, n = 17). Intervention(s): Observational study. Main Outcome Measure(s): Levels of proinflammatory cytokines (interleukin-6 [IL-6], interferon gamma [IFN-7], tumor necrosis factor-alpha [INF-alpha]), an anti-inflammatory cytokine (interleukin-4 [IL-41), and a marker of total inflammation (CRP). Result(s): Sexually active women had higher levels of all of the immune markers measured, including both pro- and antiinflammatory cytokines, than abstinent women. Relative to sexually active women, abstinent women had less change across the menstrual cycle in levels of CRP. Among sexually active women, higher intercourse frequency predicted greater midcycle decreases in CRP, IL-6, and IFN-7 and midcycle increases in IL-4. Conclusion(s): Sexual activity may stimulate a complex interaction between pro- and anti-inflammatory cytokines that subsequently drives midcycle declines in inflammation. (C)2016 by American Society for Reproductive Medicine.
Transfusion of blood cell components is frequent in the therapeutic arsenal; it is globally safe or even very safe. At present, residual clinical manifestations are principally inflammatory in nature. If some rare clinical hazards manifest as acute inflammation symptoms of various origin, most of them linked with conflicting and undesirable biological material accompanying the therapeutic component (infectious pathogen, pathogenic antibody, unwanted antigen, or allergen), the general feature is subtler and less visible, and essentially consists of alloimmunization or febrile non-hemolytic transfusion reaction. The present essay aims to present updates in hematology and immunology that help understand how, when, and why subclinical inflammation underlies alloimmunization and circumstances characteristic of red blood cells and - even more frequently - platelets that contribute inflammatory mediators. Modern transfusion medicine makes sustained efforts to limit such inflammatory hazards; efforts can be successful only if one has a clear view of each element's role.
Inflammation is an elaborate reflex response of the body to the action of harmful agents. This reaction manifests itself in the form of functional and structural changes of vascular tissues. The inflammatory response is the result of the human evolutionary process. It has three main stages, which are closely related to each other and evolve simultaneously: tissue dystrophy (alteration); impairment of blood circulation (transudation of fluid and migration of leukocytes) and multiplication of cellular elements (proliferation). These phenomena express both a disturbance of biological activity in body tissues and the defense mechanisms to restore the damaged areas. There are two interrelated processes which are often inseparable from each other in the inflammatory response. First, there is the pathological process itself, the tissue damage in form of dystrophy, necrobiosis or necrosis. Second, there is the physiological mechanism of defense, the process of recovery or the physiological response against the disease", manifested as exudation, phagocytosis and proliferation. Simultaneity of both processes is characteristic to inflammatory processes.
BackgroundPatterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain. ObjectivesWe sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under the curve (AUC) in children and adult Hutterite colony members with laboratory-confirmed influenza. MethodsA cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during three influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load was determined for influenza A-positive samples. ResultsFor seasonal H1N1, younger age was associated with a larger AUC, female sex was associated with decreased peak viral load and reduced viral shedding duration, while the presence of comorbidity was associated with increased peak viral load. For H3N2, younger age was associated with increased peak viral load and increased AUC. For pandemic H1N1, younger age was associated with increased peak viral load and increased viral AUC, female sex was associated with reduced peak viral load, while inapparent infection was associated with reduced peak viral load, reduced viral shedding duration, and reduced viral AUC. ConclusionsPatterns of molecular viral shedding vary by age, sex, comorbidity, and the presence of symptoms. Predictor variables vary by influenza A subtype.
H9N2 Influenza subtype has emerged in Tunisia causing epidemics in poultry and resulting in major economic losses. New mutations in their hemagglutinin and neuraminidase proteins were acquired, suggesting their potential to directly infect humans. Effective surveillance tools should be implemented to help prevent potential spillover of the virus across species. We have developed a highly sensitive real time immuno-polymerase chain reaction (RT-I-PCR) method for detecting H9N2 virus. The assay applies aptamers as ligands to capture and detect the virus. First, a panel of specific ssDNA aptamers was selected via a one step high stringency protocol. Next, the panel of selected aptamers was characterized for their affinities and their specificity to H9N2 virus. The aptamer showing the highest binding affinity to the virus was used as ligand to develop a highly sensitive sandwich Aptamer I-PCR. A 3-log increase in analytical sensitivity was achieved as compared to a routinely used ELISA antigen test, highlighting the potential of this approach to detect very low levels of virus particles. The test was validated using clinical samples and constitutes a rapid and a label-free platform, opening a new venue for the development of aptamer based viability sensing for a variety of microorganisms of economic importance in Tunisia and surrounding regions. (C) 2017 Elsevier B.V. All rights reserved.
Caregivers of children living with HIV/AIDS (CLWHA) face unique challenges due to disease-related stigma and discrimination, isolation from society, financial constraints, grief and mortality of loved one. A descriptive cross-sectional study was conducted at Udupi ART centre to assess the caregiver burden, psychological distress and their associated factors among the caregivers of CLWHA in Udupi District. The convenience sampling technique was used to collect the data from 171 caregivers and analysed with the help of SPSS version 15.0. Majority of caregivers were female (64.9%) with mean age of 38.1 +/- 9.6 years. About 64.3% caregivers were HIV-positive and 63.2% were biological parents of CLWHA. Mild-to-severe caregiver burden on Zarit Burden Inventory (ZBI) was reported among 84.8% of caregivers, and mild-to-severe psychological distress on General Health Questionnaire (GHQ-12) was reported among 49.7% caregivers. Relationship with child was found to be a significant predictor of caregiver burden as compared to other relatives/foster (P<0.001). Relationship with child (P 0.004), Alcohol use (P 0.008) and Schooling of children (P 0.049) were reported as significant predictors of psychological distress. Study concludes that caregiver burden and psychological distress were high among caregivers of CLWHA. Psychological problems of caregivers need to be addressed and integrated along with the clinical care of HIV-infected children at ART centres.
Anxiety and depression, which are highly prevalent in adolescence, are both characterized by a negative attentional bias. As Attentional Bias Modification (ABM) can reduce such a bias, and might also affect emotional reactivity, it could be a promising early intervention. However, a growing number of studies also report comparable improvements in both active and placebo groups. The current study investigated the effects of eight online sessions of visual search (VS) ABM compared to both a VS placebo-training and a no-training control group in adolescents with heightened symptoms of anxiety and/or depression (n = 108). Attention bias, interpretation bias, and stress-reactivity were assessed pre- and post-training. Primary outcomes of anxiety and depressive symptoms, and secondary measures of emotional resilience were assessed pre- and post-training and at three and six months follow-up. Results revealed that VS training reduced attentional bias compared to both control groups, with stronger effects for participants who completed more training sessions. Irrespective of training condition, an overall reduction in symptoms of anxiety and depression and an increase in emotional resilience were observed up to six months later. The training was evaluated relatively negatively. Results suggest that online ABM as employed in the current study has no added value as an early intervention in adolescents with heightened symptoms. (C) 2017 The Authors. Published by Elsevier Ltd.
In order to realize the human body temperature fast and non-contact measurement, an infrared thermometer is designed. The infrared human body temperature sensor is mainly used to convert the human body's infrared into voltage signal, an operational amplifier to amplify the signal, filter circuit to filter the signal, the analog signal into digital signal by the A/D conversion circuit, data processing by the MCU, LCD display and voice reporting body temperature and time, so the human body non-contact measurement is realized. The experimental results show that: the device can realize the temperature and time of acquisition, the measurement error is not more than 0.5 degrees C, voice broadcast and liquid crystal display the temperature and time, overrun alarm and other functions.
Infrastructure services are essential to human development. Yet, the drivers of service access at a global scale remain largely unexplored. This paper presents trends and global patterns in access to water, sanitation, electricity, and telephony services. Using a panel data set from 1990 to 2010, we empirically explore plausible determinants of access rates to key infrastructure services. Although per-capita GDP is correlated with access rates, access still varies significantly at comparable income levels. Much of this variation is explained by differences in population density. Access levels are higher for urban areas and highest for water, followed by sanitation, electricity, and telephony. (c) 2017 Elsevier Ltd. All rights reserved.
Production of human papillomavirus type 16 major capsid protein L1 in undifferentiated cells is negatively regulated by several yet unidentified cis-acting inhibitory RNA elements, among which a major element is located within the first 514 nucleotides of the L1-mRNA. By Northern blotting we examined effect of the major element on the steady-state level of mRNA transiently transcribed in 293T cells from the firefly luciferase (Fluc) gene combined with the L1 DNA fragment encoding the major element. As reported previously, the element down-regulated steady-state level of the mRNA. The most efficient down-regulation was achieved by insertion of the element near the 5' end of mRNA, resulting in an undetectable level of the mRNA. The longer the distance from the 5' end of the mRNA to the element, the weaker the down-regulation. The half-life of the mRNA having the element was similar to that of normal Fluc-mRNA. When the element near the 5' end was removed by splicing, the steady-state level of the resultant mRNA was raised to a readily detectable level. The steady-state level of RNA synthesized by RNA polymerase-I was not influenced by the presence of the element. Taken together, it is suggested that DNA region encoding the major inhibitory element does not disturb transcription and that the pre-mRNA is degraded by an RNA element-mediated mechanism after the splicing step in the course of mRNA maturation.
Scholars have hypothesized that victimization elicits distinctive effects on women's pathways to prison and subsequent prison maladjustment, but few researchers have investigated gender differences in this relationship. Using nationally representative samples of men and women housed in state prisons, we examine gender differences in the effects of experiencing different types of nonstranger victimization prior to prison on inmate maladjustment. Results indicate that pre-prison nonstranger victimization affects men's and women's maladjustment similarly, with some gender differencesspecifically, the effect of being physically assaulted by a nonstranger as an adult on violent misconduct was stronger among men, as was the effect of child abuse on men's depressive symptoms. Our findings suggest the effects of experiencing nonstranger victimization prior to incarceration on prison maladjustment may be gender-neutral more so than gender-specific. Based on our findings, nonstranger victimization should be deemed important in theories of men's maladjustment as well as in theories of women's maladjustment.
The aim of this study was to examine the gender differences in various types of childhood abuse and family history of crime, substance abuse, and mental health problems. Our study was conducted among 110 Israeli female and male inmates (50 female and 60 male inmates). The findings indicated a higher rate of multiple types of childhood abuse among the female inmates compared with the male inmates. The findings also revealed that female inmates reported more prevalence of parents' substance abuse, crime, and family's mental health problems than the male inmates did. Moreover, the female inmates reported higher rates of emotional, physical, and sexual abuse associated with family history variables compared with the male inmates. Furthermore, the findings indicated that female inmates whose siblings were involved in substance abuse and crime reported higher rates of sexual and emotional abuse compared with the male inmates. We discussed the implications of these findings.
Background: Growing evidence emphasizes the relevance of sphingolipids for metabolism and immunity of antigen-presenting cells (APC). APCs are key players in balancing tolerogenic and encephalitogenic responses in immunology. In contrast to the well-known prominent effects of sphingosine-1-phosphate (S1P) on lymphocyte trafficking, modulatory effects on APCs have not been fully characterized. Methods: Frequencies and activation profiles of dendritic cell (DC) subtypes, monocytes, and T cell subsets in 35 multiple sclerosis (MS) patients were evaluated prior and after undergoing fingolimod treatment for up to 24 months. Impact of fingolimod and S1P on maturation and activation profile, pro-inflammatory cytokine release, and phagocytotic capacity was assessed in vitro and ex vivo. Modulation of DC-dependent programming of naive CD4+ T cells, as well as CD4+ and CD8+ T cell proliferation, was also investigated in vitro and ex vivo. Results: Fingolimod increased peripheral slanDC count-CD1+ DC, and monocyte frequencies remained stable. While CD4+ T cell count decreased, ratio of Treg/Th17 significantly increased in fingolimod-treated patients over time. CD83, CD150, and HLADR were all inhibited, but CD86 was upregulated in DCs after incubation in the presence of fingolimod. Fingolimod but not S1P was associated with reduced release of pro-inflammatory cytokines from DCs and monocytes in vitro and ex vivo. Fingolimod also inhibited phagocytic capacity of slanDCs and monocytes. After fingolimod, slanDCs demonstrated reduced potential to induce interferon-gamma-expressing Th1 or IL-17-expressing Th17 cells and DC-dependent T cell proliferation in vitro and in fingolimod-treated patients. Conclusions: We present the first evidence that S1P-directed therapies can act additionally as immunomodulators that decrease the pro-inflammatory capabilities of APCs, which is a crucial element in DC-dependent T cell activation and programming.
Phagocytosis and autophagy in macrophages have been shown to be essential to both innate and adaptive immunity. Lysosomes are the main catabolic subcellular organelles responsible for degradation and recycling of both extracellular and intracellular material, which are the final steps in phagocytosis and autophagy. However, the molecular mechanisms underlying lysosomal functions after infection remain obscure. In this study, we conducted a quantitative proteomics analysis of the changes in constitution and glycosylation of proteins in lysosomes derived from murine RAW 264.7 macrophage cells treated with different types of pathogens comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses (herpes simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus, VSV). In total, 3,704 lysosome-related proteins and 300 potential glycosylation sites on 193 proteins were identified. Comparative analysis showed that the aforementioned pathogens induced distinct alterations in the proteome of the lysosome, which is closely associated with the immune functions of macrophages, such as toll-like receptor activation, inflammation and antigen-presentation. The most significant changes in proteins and fluctuations in glycosylation were also determined. Furthermore, Western blot analysis showed that the changes in expression of these proteins were undetectable at the whole cell level. Thus, our study provides unique insights into the function of lysosomes in macrophage activation and immune responses.
Purpose of review The purpose of this review is to summarize recent advances in our understanding of the complex immunology of intestinal transplantation and allograft rejection. Recent findings Recent findings highlight the importance of the intestinal microbiome for intestinal homeostasis and the role of newly discovered innate lymphoid cells in intestinal transplantation. In addition, the role of host antimicrobial Th17 responses in the pathogenesis of inflammatory bowel diseases and intestinal allograft rejection has been further elucidated. Summary Research on the complex immune system of the intestine has continued to reveal more intricacies and connections with each study performed, making treatment of intestinal transplant patients more multifaceted. The interaction, communication, and relationships between areas such as the microbiome, innate lymphoid cells, and Th17 cells reveal possible targets for therapy and further areas requiring ongoing research.
Gap junctions are clusters of intercellular channels that are associated with embryonic development and neural signaling. Innexins, invertebrate gap junction proteins, have been identified in Drosophila and Caenorhabditis. Here, we report the isolation and characterization of two novel members of the insect innexin family, Bm inx2 and Bm inx4, from embryos of the silkworm, Bombyx mori, during the germ-band formation stage. Bm inx2 is a single copy gene with one exon, while Bm inx4 is a single copy gene with four exons and three introns. The predicted proteins show structural similarities with other innexin family members, including four transmembrane (TM) domains, two extracellular loops (ELs), one cytoplasmic loop (CL), and typical conserved amino acids. Bm inx2 is phylogenetically orthologous to the other insect inx2 genes, but Bm inx4 is not orthologous to any known innexin including Dm inx4. Interestingly, Northern blotting and in situ hybridization showed that Bm inx2 was variously expressed across all developmental stages and in various tissues, with high expression seen in the nervous system at the time of embryogenesis. In contrast, Bm inx4 was transiently expressed at the germ-band formation stage of embryogenesis, and was specifically expressed in the ovary and testis during the larval and pupal stages. The isolation and characterization of these novel genes should form the basis for further study of the functional events that occur during development and neuronal communication in B. mori. (c) 2007 Published by Elsevier Ltd.
Recent work has demonstrated the importance of post-transcriptional gene regulation in toxic responses. In the present study, we used two rat models to investigate mRNA translation in the liver following xenobiotic-induced toxicity. By combining polysome profiling with genomic methodologies, we were able to assess global changes in hepatic mRNA translation. Dio3 (iodothyronine deiodinase type III) was identified as a gene that exhibited specific translational repression and had a functional role in a number of relevant canonical pathways. Western blot analysis indicated that this repression led to reduced D3 (the protein expressed by Dio3) levels, enhanced over time and with increased dose. Using Northern blotting techniques and qRT-PCR (quantitative reverse transcription-PCR), we confirmed further that there was no reduction in Dio3 mRNA, suggesting that translational repression of Dio3 is an important determinant of the reduced D3 protein expression following liver damage. Finally, we show that drug-induced hepatotoxicity appears to cause localized disruptions in thyroid hormone levels in the liver and plasma. We suggest that this leads to reduced translation of Dio3 mRNA, which results in decreased D3 production. It may therefore be possible that this is an important mechanism by which the liver can, upon early signs of damage, act rapidly to maintain its own energy equilibrium, thereby avoiding global disruption of the hypothalamic-pituitary-thyroid axis.
Cadmium-free quantum dots (QDs) have attracted great attention in biological and biomedical applications due to their less content of toxic metals, but their potential toxicity investigations on molecular biology level are rarely involved. Since few studies have addressed whether InP/ZnS QDs could bind and alter the structure and function of human serum albumin (HSA), in vitro interaction between InP/ZnS QDs and HSA was systematically characterized by multispectroscopic approaches. InP/ZnS QDs could quench the intrinsic fluorescence of HSA via static mode. The binding site of InP/ZnS QDs was mainly located at subdomain IIA of HSA. Some thermodynamic parameters suggested that InP/ZnS QDs interacted with HSA mainly through electrostatic interactions. As further revealed by three dimensional spectrometry, FT-IR spectrometry and circular dichroism technique, InP/ZnS QDs caused more global and local conformational change of HSA than CdSe/ZnS QDs, which illustrated the stronger binding interaction and higher potential toxicity of InP/ZnS QDs on biological function of HSA. Our results offer insights into the in vitro binding mechanism of InP/ZnS QDs with HSA and provide important information for possible toxicity risk of these cadmium-free QDs to human health. (C) 2016 Elsevier B.V. All rights reserved.
Inpp5f-v3 is a transcriptional variant of Inpp5f (inositol polyphosphate-5-phosphatase F) and locates in distal mouse chromosome 7. It is a paternally expressed imprinted gene in mouse. In this study, we examined the spatiotemporal patterns of Inpp5f-v3 gene during the mouse development. The northern blotting analysis revealed that only one transcript approx 2.7 kb of Inpp5f-v3 was detected in brain. The signals were only observed in brain by the whole-mount in situ hybridization at embryonic day 11.5 (E11.5). The results of quantitative real-time PCR (QRT-PCR) showed that the expression of Inpp5f-v3 increased gradually from the E11.5 to E17.5 and reached the highest at E17.5, then decreased at E18.5 during the brain development. Inpp5f-v3 gene was strongly expressed in the cerebral cortex, olfactory bulb, external germinal layer of cerebellum and ventricular zone (Vz) during the embryonic development (E15.5-E19.5), whereas the expression increased in the olfactory bulb and the cerebellum after birth by using in situ hybridization. The results also demonstrated that the expression of Inpp5f-v3 gene mainly located in olfactory bulb and hippocampus at postnatal day 7 (P7) and adulthood. These results suggest that Inpp5f-v3 is specifically expressed in mouse brain, and may function in the development of mouse brain.
Although some novel antimicrobial peptides (AMP) have been successfully isolated from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these peptides are still elusive. The homolog of NF-kappa B transcription factor Relish, designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids. Similar to Drosophila Relish and the mammalian p100, it is a compound protein containing a conserved Rel homology domain, an IPT (Ig-like, plexins, transcription factors) domain and an I kappa B-like domain (four ankyrin repeats), the nuclear localization signal RKRRR is also detected at the residues 449-453, suggesting that it has homology to Relish and it is a member of the Rel family of transcription activator proteins. Reverse transcription quantitative polymerase chain reaction analysis reveals that BdRelish mRNAs are detected in different quantities from various tissues and the highest transcription level of BdRelish is determined in fat body. The injection challenge of Escherichia coli and Staphylococcus aureas significantly upregulated the expression of BdRelish. The injection of BdRelish dsRNA markedly reduced the expression of BdRelish and decreased the transcription magnitude of antimicrobial peptides. Individuals injected BdRelish dsRNA died at a significantly faster rate compared with the control groups. Therefore, BdRelish is vital for the transcription of AMPs to attack the invading bacteria.
The kissing bug Rhodnius prolixus is both an important vector of Chagas' disease and an interesting model for investigation into the field of physiology, including lipid metabolism. The publication of this insect genome will bring a huge amount of new molecular biology data to be used in future experiments. Although this work represents a promising scenario, a preliminary analysis of the sequence data is necessary to identify and annotate the genes involved in lipid metabolism. Here, we used bioinformatics tools and gene expression analysis to explore genes from different genes families and pathways, including genes for fat breakdown, as lipases and phospholipases, and enzymes from beta-oxidation, fatty acid metabolism, and acyl-CoA and glycerolipid synthesis. The R. prolixus genome encodes 31 putative lipase genes, including 21 neutral lipases and 5 acid lipases. The expression profiles of some of these genes were analyzed. We were able to identify nine phospholipase A2 genes. A variety of gene families that participate in fatty acid synthesis and modification were studied, including fatty acid synthase, elongase, desaturase and reductase. Concerning the synthesis of glycerolipids, we found a second isoform of glycerol -3-phosphate acyltransferase that was ubiquitously expressed throughout the organs. Finally, all genes involved in fatty acid beta-oxidation were identified, but not a long-chain acyl-CoA dehydrogenase. These results provide fundamental data to be used in future research on insect lipid metabolism and its possible relevance to Chagas' disease transmission. (C) 2016 Elsevier B.V. All rights reserved.
Mythimna separata walker (Lepidoptera: Noctuidae) is a polyphagous pest of nearly 100 families of more than 300 kinds of food and industrial crops. So far, both nucleotide and protein sequence information has been rarely available in database for M. separata, strictly limiting molecular biology research in this insect species. In this study, we carried out a transcriptome sequencing for M. separata. The sequencing and subsequent bioinformatics analysis yielded 69,238 unigenes, among which 45,227 unigenes were annotated to corresponding functions by blasting with high homologous genes in database, giving annotation rate of 65.32%. Several lepidopteran insects gave best matches with the transcriptome data. To gain insight into the mechanism of insecticide resistance in M. separata, 15 families of genes encoding insecticide resistance-related proteins were investigated. Substantial numbers of unigenes in these families were identified in the transcriptome data, and 17 out of 21 selected unigenes were successfully amplified. Expressions of most of these genes were detected at larval stages and in gut tissue, as was consistent with their putative involvement in insecticide resistance. Our study provides most comprehensive transcriptome data for M. separata to date, and also provides reference sequence information for other Noctuidae family insects.
We examined the extent to which emerging adults engage in different behaviors on Instagram, a popular social networking site, to gain attention and validation from others via "likes." We also examined individual differences in the frequency of like-seeking behavior and motives for Instagram use as mediators of these relationships. Participants (N = 198 and 265 (replication study)) were recruited via an online crowdsourcing portal to complete a survey. Results demonstrated that, as predicted, participants engaged in an assortment of different like-seeking behaviors. Further, a two-factor solution emerged, with like-seeking behavior separated by whether they were normative (i.e., common or accepted, e.g., using filters or hashtags) or deceptive (e.g., buying likes or changing one's appearance in photos using software). Deceptive like-seeking was predicted by stronger narcissism and a weaker sense of peer belonging, whereas normative like-seeking was predicted by stronger narcissism and a stronger sense of peer belonging. Further, consistent with hypotheses, significant mediators of the relation between narcissism and deceptive like-seeking included motives to use Instagram to increase popularity and showcase creativity. Results help to identify young people who are more susceptible to engaging in deceptive, potentially harmful acts to gain attention and validation on Instagram. (C) 2017 Elsevier Ltd. All rights reserved.
In an effort to enhance instruction and reach more students, educators design engaging online learning experiences, often in the form of online videos. While many instructional videos feature a picture-inpicture view of instructor, it is not clear how instructor presence influences learners' visual attention and what it contributes to learning and affect. Given this knowledge gap, this study explored the impact of instructor presence on learning, visual attention, and perceived learning in mathematics instructional videos of varying content difficulty. Thirty-six participants each viewed two 10-min-long mathematics videos (easy and difficult topics), with instructor either present or absent. Findings suggest that instructor attracted considerable visual attention, particularly when learners viewed the video on an easy topic. Although no significant difference in learning transfer was found for either topic, participants' recall of information from the video was better for easy topic when instructor was present. Finally, instructor presence positively influenced participants' perceived learning and satisfaction for both topics and led to a lower level of self-reported mental effort for difficult topic. (C) 2017 Elsevier Ltd. All rights reserved.
An area-efficient self-trimming technique for precision chopper-stabilized instrumentation amplifier (IA) is presented. The amplifier uses a reconfigurable differential pair for the input stage and it is automatically configured to reduce the mismatch of the differential pair, suppressing the chopper ripple. To confirm the effectiveness of the proposed scheme, an IA with the complete calibration logic is fabricated in a standard 180-nm CMOS and achieves active area, less than offset voltage, input-referred noise, and current consumption. The noise efficiency factor of the amplifier is 7.2.
The article considers design features of the main modifications of analog interface for sensor systems, implemented on the base of differential difference op amps (DDA). Unlike classical structures of instrumentation amplifiers (IA) with junction coupling of stages, the suggested circuit solutions give small suppression of offset voltage (<= 30 mu V) and provide common-mode rejection more than -97dB in conditions of radiation and low temperature effects. Feeding of inherent compensation circuits of parasitic impedances of IA circuit according to the algorithm extends its bandwidth by a factor of 3-5. The article suggests new modifications of two-stage DDAs with higher voltage gain.
Previous studies in our laboratory have shown that one of the earliest events during hepatocarcinogenesis in the albumin SV40 T antigen (Alb SV40 T Ag) transgenic rat is the duplication of chromosome 1q3.7-4.3, a region which contains the imprinted and coordinately regulated genes lgf2 and H19. We have also shown that this duplication is associated with the biallelic expression of the normally monoallelically-expressed H19. These results, however, are seemingly at odds with studies in the mouse that have shown a conservation of fetal regulatory patterns of these two genes in hepatic neoplasms. We therefore aimed in this study to determine the allelic origin of lgf2 expression in hepatocellular carcinomas of the Ab SV40 T Ag transgenic rat. Sprague-Dawley Alb SV40 T Ag transgenic rats and Brown Norway rats were reciprocally mated and the expression of lgf2 in hepatocellular carcinomas of the resulting F, transgene-positive female rats was analyzed by Northern blotting and RT-PCR. We determined that lgf2 was expressed exclusively from the paternal allele, which prompted the study (by the same methods) of the allelic origin of H19 in the same hepatocellular carcinomas in order to determine if the two genes remained coordinately regulated. our results demonstrate fetal-like re-expression of lgf2 and deregulation of H19 in singular hepatocellular carcinomas of the rat. These results imply that another regulatory mechanism other than the generally accepted ICR/CTCF mechanism may play a role in the control of lgf2 and H19 expression. (C) 2007 Wiley-Liss, Inc.
Liu S, Liu R, Chiang Y, Song L, Li X, Jin T, Wang Q. Insulin detemir enhances proglucagon gene expression in the intestinal L cells via stimulating beta-catenin and CREB activities. Am J Physiol Endocrinol Metab 303: E740-E751, 2012. First published July 17, 2012; doi:10.1152/ajpendo.00328.2011.-Insulin therapy using insulin detemir (d-INS) has demonstrated weight-sparing effects compared with other insulin formulations. Mechanisms underlying these effects, however, remain largely unknown. Here we postulate that the intestinal tissues' selective preference allows d-INS to exert enhanced action on proglucagon (Gcg) expression and the production of glucagon-like peptide (GLP)-1, an incretin hormone possessing both glycemia-lowering and weight loss effects. To test this hypothesis, we used obese type 2 diabetic db/db mice and conducted a 14-day intervention with daily injection of a therapeutic dose of d-INS or human insulin (h-INS) in these mice. The body weight of the mice after 14-day daily injection of d-INS (5 IU/kg) was decreased significantly compared with those injected with the same dose of h-INS or saline. The weight-sparing effect of d-INS was associated with significantly elevated circulating levels of total GLP-1 and reduced food intake. Histochemistry analysis demonstrated that d-INS induced rapid phosphorylation of protein kinase B (Akt) in the gut L cells of normal mice. Western blotting showed that d-INS stimulated Akt activation in a more rapid and enhanced fashion in the mouse distal ileum compared with those by h-INS. In vitro investigation in primary fetal rat intestinal cell (FRIC) cultures showed that d-INS increased Gcg mRNA expression as determined by Northern blotting and real-time RT-PCR. Consistent with these in vivo investigations, d-INS significantly increased GLP-1 secretion in FRIC cultures. Consistently, d-INS was also shown to induce rapid phosphorylation of Akt in the clonal gut cell line GLUTag. Furthermore, d-INS increased beta-catenin phosphorylation, its nuclear translocation, and enhanced cAMP response element-binding protein (CREB) phosphorylation in a phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-sensitive manner. We suggest that the weight-sparing benefit of d-INS in mice is related to its intestinal tissues preference that leads to profound stimulation of Gcg expression and enhanced GLP-1 secretion in intestinal L cells, potentially involving the activation of insulin/beta-catenin/CREB signaling pathways.
This study examines the expression of the insulin-like growth factor type 1 receptor (TGF-1R) in colorectal neoplasia. Previous studies have shown that the IGF-1R is expressed at high levels in normal embryonic stem cells and in many cancer phenotypes. However, lower IGF-1R levels are expressed in some advanced cancer phenotypes. The timing of and the reasons for these changes in expression during the evolution of a cancer are not understood. Here, we examine IGF-1R expression in the evolution of colorectal cancer by means of Northern blotting and immunohistochemistry validated by tissue and reagent controls and Western blotting. We show for the first time that (1) in normal colorectal crypts, epithelial stem cells in the basal crypt region express high IGF-1R levels, which decrease to low levels when these cells migrate to and differentiate in the mid and upper crypt regions; (2) in tumor initiation in aberrant crypt foci, all of the transformed cells express high levels of the IGF-1R at stem cell levels throughout the crypt axis; (3) in tumor progression in adenomatous and cancerous crypts, tumor cells of an epithelial type morphology express high levels of the IGF-1R; (4) in advanced cancers, low levels of the IGF-1R are expressed in invasive foci where cancer cells dedifferentiate to a mesenchymal-type morphology and show a loss of cell adhesion. Interestingly, these cells can form an alternating pattern with mesenchymal type cells that show cell adhesion and high levels of IGF-1R expression. In summary, this study shows that high-level IGF-1R expression in colorectal neoplasia is initiated by an abnormality of stem cell programed differentiation in the aberrant crypt focus. However, low-level IGF-1R expression is found in some invasive cancers where it is consequent to cancer cell dedifferentiation to a mesenchymal type morphology with loss of cell adhesion. Crown Copyright (c) 2007 Published by Elsevier Inc. All rights reserved.
Insulin receptor substrates (IRSs) are well known to play crucial roles in mediating intracellular signals of insulin-like growth factors (IGFs)/insulin. Previously, we showed that IRS-1 forms high molecular mass complexes containing RNAs. To identify RNAs in IRS-1 complexes, we performed ultraviolet (UV) cross-linking and immunoprecipitation analysis using HEK293 cells expressing FLAG IRS-1 and FLAG IRS-2. We detected the radioactive signals in the immunoprecipitates of FLAG IRS-1 proportional to the UV irradiation, but not in the immunoprecipitates of FLAG IRS-2, suggesting the direct contact of RNAs with IRS-1. RNAs cross-linked to IRS-1 were then amplified by RT-PCR, followed by sequence analysis. We isolated sequence tags attributed to 25 messenger RNAs and 8 non-coding RNAs, including small nucleolar RNAs (snoRNAs). We focused on the interaction of IRS-1 with U96A snoRNA (U96A) and its host Rack1 (receptor for activated C kinase 1) pre-mRNA. We confirmed the interaction of IRS-1 with U96A, and with RACK1 pre-mRNA by immunoprecipitation with IRS-1 followed by Northern blotting or RT-PCR analyses. Mature U96A in IRS-1 / mouse embryonic fibroblasts was quantitatively less than WT. We also found that a part of nuclear IRS-1 is localized in the Cajal body, a nuclear subcompartment where snoRNA mature. The unanticipated function of IRS-1 in snoRNA biogenesis highlights the potential of RNA-associated IRS-1 complex to open a new line of investigation to dissect the novel mechanisms regulating IGFs/insulin-mediated biological events.
This paper presents a nonlinear control technique based on feedback Relay systems for photovoltaics applications in converters and inverters. Describes the design of the control law from the state equations of Buck converter, the analysis of limit cycles, stability of the systems to obtain digital control law for further simulation and implementation in programmable logic devices (PLD). We performed the programming of the control technique in hardware description language (VHDL), later we implement in a CPLD and development the prototype of a Buck converter. Finally simulations and tests to the prototype were realized, obtaining optimal results of performance.
We investigate analog single event transient (ASET) generation in an LM124 operational amplifier using focused pulsed x-rays and 800 nm femtosecond laser pulses. We report improvements that have been made to the pulsed x-ray experimental apparatus which include normal incidence geometry and a high speed x-ray chopper that allows us to reduce the pulse repetition frequency of the synchrotron derived x-ray pulse train. The addition of the chopper allows us to measure ASETs that have long relaxation times. We show that ASETs can be generated through metallization on the LM124, and that for equivalent pulse energy incident on the part, the x-ray response from areas covered by metal (and inaccessible to the laser) are different than the x-ray response from areas with no metallization, i.e. "metal-free". We use the laser pulses to generate ASETs at the same metal-free locations of x-ray induced ASETs. The shapes of the ASETs generated by the two methods are compared. We use the differences seen from the two generation methods to estimate the charge generation/collection produced by the pulsed x-rays and then estimate what LET this would correspond to for heavy ions. This work shows that pulsed x-rays can be used to characterize analog devices for single event effects.
The increasing share of variable renewable energy sources and the improving requirements on system security and reliability are calling for important changes in our energy systems. The synergies between energy supply networks are of great importance to satisfy the development of the integrated energy system (IES). Hence this paper presents the study of the coordinated scheduling strategy (CSS), in which, the models of the electricity network and gas network are developed in detail, and the operation constraints of the networks are fully considered. The purpose of the CSS is to optimize the conflicting benefits of the electricity network arid gas network for daily operation of the IES, while satisfying the operation constraints. In the CSS, a multi-objective optimization algorithm is applied to obtain a Pareto-optimal solution set, and a multiple attribute decision analysis (MADA) using interval evidential reasoning (IER) is developed to determine a final optimal daily operation solution for the IES. Simulation studies are conducted on an IES consisting of a modified IEEE 30-bus electricity network and a 15-node gas network to verify the effectiveness of the CSS, and to evaluate the interdependency between the electricity network and gas network. (C) 2016 Published by Elsevier Ltd.
An integrated photo-bioelectrochemical (IPB) system is innovative through integrating microbial fuel cells (MFCs) with algal bioreactors for simultaneous organics degradation, nutrient removal, and bio-energy production. A mathematical model has been developed for simulating and understanding the performance of the IPB system. The model inputs include influent COD (chemical oxygen demand), NH-N, total phosphorus, external resistance and flow rate, while the outputs include the biomass growth, COD degradation, nutrient removal, and electricity generation. The determination of unknown model parameters was assisted with sensitivity analysis. Satisfactory model fitting and validation was achieved, with low root-mean-square error of 5.6% and 0.2%, respectively, for biomass concentration and current generation under varied COD input. The simulated results suggested that the organic input and flow rate had more significant impacts on the growth of algal biomass than other input factors, while COD, flow rate and external resistance were of importance for current generation. The optimal condition for improving this particular IPB system was predicted to have a COD concentration above 150 mg L-1 and the flow rate at 0.1 mL min(-1). This IPB model is the first attempt of the kind for the optimization of an integrated bioprocess of electrochemical reactions and algal growth. (C) 2017 Elsevier Ltd. All rights reserved.
Solar energy for building applications may significantly reduce the conventional energy consumption and the related carbon dioxide emissions. The comprehensive utilization of integrated solar thermal and photovoltaic systems is undoubtedly a subject of interest. In the present paper, an optimization model was proposed for integrated solar energy systems, aiming to figure out the optimal utilization and economical efficiency of solar energy resources for buildings in cold plateau areas. A case study in Lhasa city was further carried out in order to evaluate the energy and economic performance of the developed model. The results indicated that solar photovoltaic systems are preferred than solar thermal systems for typical office buildings in cold plateau areas with rich solar energy resources. In addition, a sensitivity analysis was performed to investigate the influences of financial subsidies and commercial electricity prices on the system economical performance. Furthermore, life cycle assessment was conducted to compare and analyze the performances of an optimization system and a conventional system. (C) 2016 Elsevier Ltd. All rights reserved.
Engaging undergraduates in research is essential for teaching them to think like scientists, and it has become a desired component of classroom and laboratory instruction. Research projects that span an entire semester expose students to a variety of concepts and techniques and allow students to use experiments to learn scientific principles, understand why specific techniques are applicable, critically analyze varied data, and examine how experimentation leads to acquiring knowledge. To provide an experience with these features, a semester long research project was integrated into a combined lecture and laboratory course, Molecular Biology. The project utilized the zebrafish model to examine gene expression during embryonic development and required students to develop and test hypotheses about the timing of expression of previously uncharacterized genes. The main goals for the project were to provide opportunities for students to develop critical thinking skills required for conducting research and to support the content goals of the course. To determine whether these goals were met, student performance on the steps of the project and related pre-test and post-test questions was examined. (C) 2016 by The International Union of Biochemistry and Molecular Biology
Integrative medicine (IM) has received increasing attention since the 1990s, but few studies have explored the key factors of the IM model in health care. This study aimed to describe the IM model in leading centers operating in the USA and Germany. A 28-item structured survey and semi-structured interviews were conducted in six centers providing integrative medicine in the USA and Germany, and were analyzed using a convergent mixed-method approach. The elements in common across all six centers were the following: (1) involvement of general physicians (GP) in delivering complementary and alternative medicine (CAM) services; (2) requirement for GP or medical referral or recommendation to CAM services; (3) involvement of an integrative physician (IP) as a "gatekeeper"; (4) focus on research, education, and clinical practice; and (5) ongoing academic activities. The key elements differentiating the two countries were the following: (1) level of requirements for GP referral to CAM services; (2) differences in IM service delivery, including treatment modalities used; (3) accessibility of CAM services to patients; (4) interaction between team members and patients; (5) perception of CAM/IM; and (6) perception of patient-centered care. Themes underpinning these elements are the following: cultural aspects in conceptualizing IM health care; communication within IM programs; and resource availability for delivering IM services, which impacts patient engagement and team collaboration in the IM framework. Delivering IM health care requires a model of care that encourages interaction between all stakeholders. Developing a comprehensive conceptual framework to support IM practice is required to facilitate efficient and safe patient care.
When lepidopteran larvae are infected by a large quantity of pathogens or parasitized by nonadaptive parasitoids hemocytes in the hemocoel will encapsulate these foreign invaders Cellular encapsulation requires hemocytes particularly plasmatocytes to change their states from nonadhesive spherical cells into adhesive spreading cells However It is unclear how the changes of plasmatocytes are regulated Here we report that the integrin beta 1 subunit from hemocytes of Ostrinia furnacalis (Ofint beta 1) plays an important role in regulating the spreading of plasmatocytes The full length cDNA sequence (4477 bp) of Ofint beta 1 was cloned from hemocytes Phylogenetic analysis showed that Ofint beta 1 belonged to the integrin beta PS family of Drosophila melanogaster with highest sequence identity (78 7%) to the beta-integrin of Pseudoplusia includens Structural analysis of the deduced amino acid sequence indicated that Ofint beta 1 had similar functional domains to known beta-integrins in other lepidopteran insects RT-PCR Northern blotting Western blotting and immunohistochemical analyses showed that OfINT beta 1 was expressed mainly in hemocytes especially in plasmatocytes and weakly in fat body Malpighian tubes and epidermis After hemocytes had spread onto slides fewer antibodies to OfINT beta 1 bound to the surface of plasmatocytes Furthermore anti-OfINT beta 1 serum clearly inhibited the spreading of plasmatocytes Together these results indicate that OfINT beta 1 may play an important role in regulating the spreading of plasmatocytes (C) 2010 Elsevier Ltd All rights reserved
We outline an evolutionary-embodied-epistemological (EEE) account of intellectual arrogance (IA), proposing that people psychologically experience their important beliefs as valued possessions - mental materialism - that they must fight to keep - ideological territoriality - thereby disposing them toward IA. Nonetheless, IA should still vary, being higher among people taking a hostile and domineering epistemic stance (rejecting reality, resisting evidence) than among those taking an open and deferential one (embracing reality, respecting evidence). Such variations can be predicted from people's standing on the communion-agency circumplex at multiple levels of analysis (i.e. from their social inclusion and status; dispositional warmth and competence; and behavioral amiability and assertiveness). Using pre-validated indices of mental materialism and ideological territoriality, and an argument evaluation task permitting the quantification of rational objectivity and egotistical bias, we obtained consistent correlational evidence that, as hypothesized, IA is the highest when agency is high and communion low, validating the EEE account.
Several studies have demonstrated that mothers with intellectual disability (ID) have a higher prevalence of mental health illness, lower socio-economic status, and a higher risk of alcohol and drug use compared to mothers without ID. The children of mothers with ID are over-represented in child protection and legal proceedings but are generally a less studied group than the mothers. The aim of this study was to investigate if children born to mothers with ID had an increased risk of being diagnosed with mental illness, injuries, and violence compared with children of mothers without ID. The study comprised a population based cohort of children born in Sweden between 1999 and 2005. Data were collected from the Medical Birth Register and linked with two other national registers; ICD-10 codes were used for medical diagnoses, including ID. The children were followed from birth to seven years of age. In total, 478,577 children were included, of whom 2749 were born to mothers with ID. Children of mothers with ID were at a greater risk of having mental health problems (adjusted odds ratio (OR)= 2.02; 95% confidence interval (CI) = 1.74-2.35) and ID (OR = 4.14; CI = 2.95-5.82) in early childhood. They had an increased risk for injuries due to falls (OR = 1.15; CI 1.04-1.27). The largest risk related to trauma was violence and child abuse (OR =3.11; CI = 1.89-5.12). In conclusion, children of mothers with ID had an increased risk for injuries, violence, and child abuse. We therefore suggest that parents with ID should receive evidence based support so that their children receive the best care and protection. (C) 2017 The Author(s). Published by Elsevier Ltd.
The paper proposes to evaluate achievement of main results in operation of intellectual mechatronic systems with digital control by the obtained information effect. In this respect, common information requirements with intellectual components are considered as a basic information factor which influences on the process of mechatronic system designing. Therefore, some parameters have been accentuated and they can help to provide rather complete description of the processes used for obtaining and using systematic information within the volume of the intellectual mechatronic system. Conformity degree of control vector parameters synthesized by the system and identification results of its current states have been selected as an information criterion of the control efficiency. A set of expected probability values for location of each parameter of an control object and a mechatronic system within the required tolerances has been used for formation of possible states. The paper shows that when a complex information description of the system is used then it is expedient to use an expert assessment of selection probability for allowable control vectors which ensure a system transfer to favorable states. This approach has made it possible to pinpoint main information and technical specifications of the intellectual mechatronic system: structural construction (informational and technical compatibility and information matching of its components); control object (uncertainty of its state and information vector, information capacity of the mechatronic system); control actions (their hierarchy and entropic balance of control process, managerial resource of mechatronic system); functioning result (informational effect and control efficiency criterion, probabilistic selection of system states). In accordance with the fulfilled analysis it is possible to note the most effective directions for practical use of the proposed informational approach for creation of the intellectual mechatronic system: comparison of alternative design solutions based on the analysis of calculation assessments on unconditional entropy of the control object and the system; simulation with the aim to accept a final systematic option while constructing digital controlling block of the created system; complex application of experts' knowledge, most comprehensive introduction of knowledge to the process of mechatronic system designing.
Interconnected electricity networks, or Supergrids, are considered as a possible solution to tackle challenges associated with near and far-future supply of electricity. These include, but are not limited to, reducing Green House Gas emissions and reliance on non-renewable fossil fuels. Supergrids can help to tackle these challenges, for example, by providing a reliable interconnection platform for wider application (and development) of renewable technologies. However, there is a range of risks and uncertainties associated with selecting appropriate interconnections. Heretofore these have been a hindrance to developing interconnections and therefore a Risk-Based Framework (RBF) which addresses these risks and uncertainties could encourage the wider uptake of Supergrids. This paper presents for the first time such a robust framework. The RBF comprises of four stages; (1) initial screening for selecting candidate countries, (2) risk identification, (3) risk semi-quantification and (4) risk quantification. In stage 4 the uncertainties associated with the identified risks are quantified using a cost-risk model under uncertainty based on a whole life appraisal approach. The usefulness of the approach, demonstrated using the UK as a case study, showed that greatest cost risks are associated with (a) regulatory framework, and (b) changes in energy policy. The most desirable interconnection option for the UK was identified as France. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a low power, compact, and low-complexity pulse-width modulation-based interface circuit for capacitive MEMS sensors. The circuit is designed using a ring oscillator, an RC controlled pulse generator with high-pass filter, and a self-tuning inverter comparator to produce pulse width, which is proportional to differential capacitance and independent of parasitic capacitance. The high-pass filter is utilized to reduce the bandwidth of noise sources. The circuit provides control over sensitivity, dynamic range, and nominal point for the capacitance measurement by selecting controlling parameters, such as resistance of the RC pulse generator, biasing voltage of the self-tuning inverter comparator, and a reference capacitor using digital control signals. The circuit provides high linearity with higher sensitivity and lower power consumption. The sensitivity of the circuit is 0.56 to 3.62 mu s/pF depending on the controlling parameters. The maximum dynamic sensing range is 22 to 270 pF depending on the controlling parameters. The interface circuit is designed and fabricated using the United Microelectronics Corporation (UMC) 0.18-mu m CMOS technology. It occupies an active area of 0.17 mm(2) and consumes 98 mu W. A capacitive MEMS-based pressure sensor is also connected with the interface circuit to measure pressure throughout the digestive tract. The sensitivity for pressure from 101 to 200 kPa is 60 ns/kPa and from 50 to 101 kPa is 23 ns/kPa.
This paper presents a closed-loop interface for micro-machined accelerometer sensor based on a force-feedback sigma-delta loop. A high-order closed-loop accelerometer interface circuit is investigated, and a time-shared multiplexing electrostatic feedback technique is used to eliminate feedthrough between feedback signals and pick-up charge signals. A low noise capacitance detection circuit is proposed with correlated-double-sampling technique to eliminate the 1/f noise and offset of operational amplifier. The interface is fabricated in a standard 0.5 mu m CMOS process and the active circuit area is about 13 mm(2). The chip consumes 20 mW from a 5 V supply with a sampling clock of 250 kHz. The average noise floor of the digital accelerometer is about -115 dBV/Hz(1/2) over a 1.5 kHz bandwidth. Corresponding to a sensitivity of 302 mV/g, the measured resolution of the accelerometer system is about 6 mu g/Hz(1/2). The nonlinearity is 0.085 %. The figure of merit shows that the proposed sigma-delta interface achieves a good performance.
Prunus necrotic ringspot virus (PNRSV) is a common pollen-borne virus that can infect many Prunus species. While some strains cause serious adverse effects (e.g., rugose mosaic virus), many strains are relatively symptomless in sweet cherry (Prunus avium). However, even symptomless strains can cause adverse reactions in some cherry rootstocks, such as Gisela T (Gi) 7 (P. cerasus x P. canescens). Using interfering RNAs (RNAi) to induce gene silencing, the rootstocks Gi6 (PNRSV-tolerant) and Gi7 (PNRSV-sensitive) were transformed with the RNAi vector pART27-PNRSV containing an inverted repeat (IR) region of PNRSV, using Agrobacterium tumefaciens strain EHA105. This yielded 19 independent transgenic events for Gi6 and three for Gi7. Regenerated plants exhibited a normal phenotype. The presence of the PNRSV-fragment was confirmed by Southern blot. Northern blotting revealed the presence of small interfering RNAs (siRNA) in five of ten transgenic events tested. The transgenic lines were then inoculated with a combination of PNRSV and Prune Dwarf Virus (PDV). After one year, the transgenic Gi7 showed no infection symptoms and was negative for PNRSV in ELISA assays. Non-transgenic Gi7 plants developed serious virus infection symptoms and died. Even though Gi6 is tolerant of PNRSV, inoculation still caused infection, making it a symptomless carrier. In contrast, the inoculated transgenic Gi6 remained negative for PNRSV in ELISA assays. These results indicate RNAi-mediated gene silencing is effective in inducing virus resistance for cherry rootstocks, which may be useful for conferring virus resistance to commercial scions while producing non-genetically modified fruits.
Aim: A number of adipocytokines have been suggested to be involved in the disruption of glucose metabolism, and also in the development of various diabetic complications. We attempted to identify and analyze additional adipocytokines, to better understanding the roles of adipocytes and adipocytokines. Methods: An oligo-capping signal sequence trap, developed in our laboratory for screening the cDNAs of secretory proteins, was used to sreen cDNAs expressed in mouse white adipose tissue. Profiles of the genes identified in mice and cultured cells were further investigated by northern blotting and luciferase assay. Results: A cDNA fragment of interferon-stimulated gene 12b (ISG12b) was obtained in the search. A northern blot analysis revealed ISG12b to be highly expressed in white adipose tissue. Interferon a (IFN alpha) was shown to induce ISG12b expression in the adipose tissue of BL6 mice in vivo, and also in a 3T3-L1 preadipocyte cell line in vitro. The level of ISG12b was higher in mature adipocytes than in preadipocytes. A promoter analysis demonstrated that the 369bp upstream from the transcription initiation site of ISG12b mRNA contain strong promoter activity, and the interferon-stimulated response elements (ISREs) were not present within the 5593bp upstream region. Conclusion: ISG12b is an additional candidate for a adipocytokine induced to express in adipose tissue by interferon.
The concept of intergenerational transmission of intimate partner violence (IPV) has been an important topic of research. Experts have contended that this brutal path in which violence is transmitted to subsequent generations may be avoidable. This study examined whether public perceptions of the legal regulation of IPV and the certainty of sanction deter the prevalence of IPV. Data from 3,800 households were obtained from a nationwide survey conducted in South Korea. Due to a skewed distribution of the prevalence of IPV, this study applied a zero-inflated Poisson (ZIP) model, which has been shown to address issues of skewed count variables. In addition, use of a ZIP model allowed us to examine factors associated with the occurrence and frequency of IPV. Results showed that child abuse experience and perceptions of the law were associated with the occurrence of IPV. Individuals who experienced child abuse were more likely to perpetrate IPV, whereas those aware of the law were less likely to perpetrate IPV. Witnessing IPV between parents was associated with an increased frequency of IPV. Results suggest that by increasing awareness of laws against domestic violence, IPV may be reduced or prevented.
We examined the intergenerational transmission of parent-child relationship qualities in a population-based Finnish sample of 1418 participants (G2) and their mothers (G1). At baseline, G1 (Mage=38) reported qualities of the parent-child relationship in terms of emotional warmth and acceptance towards G2 (age range 3-18). After 28years, G2 (Mage=39) rated the qualities of the parent-child relationship regarding their own children using the same questionnaire. Emotional warmth and acceptance were transmitted across generations even after controlling for demographic and family characteristics in both generations. The transmission was stronger for emotional warmth than acceptance. For emotional warmth, intergenerational transmission was stronger for men than women. The findings provide evidence for the long-term transmission of parenting quality across generations.
An accurate inter-laboratory comparison (ILC) concerning the electrical quantities in low frequency between the laboratory for the calibration of multifunction electrical instruments of the National Institute of Metrology Research (INRIM) and a secondary high level electrical calibration laboratory was performed with satisfactory results. The instrument involved in the ILC was a top class multifunction electrical calibrator, chosen for its wide measurement fields and its excellent definability requiring therefore very small uncertainties to calibrate it. This ILC was the first high accuracy comparison exercise at INRIM involving a grid of about one hundred and thirty measurement points. The ILC allowed to check adequately the measurement capabilities, techniques and uncertainties of this secondary laboratory. Attention was paid to evaluate the correlated terms between the two laboratories measurements. The calibrator showed high stability and resulted more appropriate than fixed standards or than a 8.5 digits multimeter to the aim of the ILC. (C) 2017 Elsevier Ltd. All rights reserved.
This paper proposes a new phase current reconstruction technique for interleaved three-phase bidirectional dc-dc converters using a single current sensor. In the proposed current reconstruction algorithm, a single current sensor is employed at the dc-link, and the dc-link current information is sampled at either the peak or valley point of the pulse-width modulation (PWM) carriers regularly. From the obtained current information, all phase currents are reconstructed in a single PWM cycle. After that, the digital current controller is applied to achieve current balancing in each phase. Compare to the previous multiple current sensor method, the proposed strategy reduces the number of the current sensors in the interleaved three-phase bidirectional converter as well as reducing potential current sensing error caused by non-ideal characteristics of the multiple current sensors. The effectiveness of the proposed method is verified from the experiments based on a 3kW three-phase bidirectional converter prototype for the automotive battery charging application.
The interleaved multilevel DC-DC converters have advantages of low voltage stress of the switches and diodes and reduction of filter size. Particularly series input parallel output (ISOP) configuration is well suited for high output voltage and large output current application but input series output series (ISOS) configuration enable the utilization of low voltage rating switches in high voltage input and high voltage output applications that require galvanic isolation. The series connection of the isolated DC-DC converters at the input side also can be used for higher voltage application. While multilevel topology offers many new features, it also necessitates a balance control of the input capacitors. The paper describes the operating principles of the balancing circuit, analyzes the fundamental relationships, introduces principles of the operation of the circuit. The paper shows experimental results based on a few practical application examples. The paper discusses design of the transformer with balancing winding for ISOP, ISOS and parallel connection of the DC-DC converters to provide independent voltage balancing of input capacitors.
Interleukin-1 (IL-1beta) beta and major histocompatibility complex (MHC) play an important role during pregnancy. Expression of non-classical class MHC II RT1-DM antigen and classical class MHC I RT1-A antigen induced by IL-1beta was examined by Northern blotting, Western blotting and immunohistochemistry. IL-1beta treatment significantly increased the expression of RT1-A and RT1-DM in early and mid pregnancy. In late pregnancy, expression of RT1-DM significantly increased in uteri and decreased in placenta. Immunohistochemical studies indicated that, in early pregnancy, RT1-DM protein mainly localized to luminal and glandular uterine epithelium, and RT1-A was present in deciduas basalis, outer layer of luminal epithelium and glandular epithelium. During mid and late pregnancy, RT1-DM was present in maternal blood vessels and syncytio-trophoblast of labyrinthine zone, and RT1-A was present in maternal blood vessels and trophoblastic epithelium of the labyrinthine layers. These findings show that exogenous IL-1beta affects expression of RT1-DM and RT1-A and does not affect the localization of corresponding molecules during pregnancy.
AIM: To identify the effects of interleukin (IL) -13 on retinal pigment epithelial (RPE) cells and the IL -13 level in aqueous humor of age-related macular degeneration (AMD) patients. METHODS: IL -13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19 cells were treated with 10 ng/mL IL -13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of alpha-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expression of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta)and vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL -13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33 +/- 17.64 vs 27.12 +/- 5.65 pg/mL; P<0.01). In vitro, IL -13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. a-SMA mRNA in ARPE-19 cell were increased (1.017 +/- 0.112 vs 1.476 +/- 0.168; P<0.001) and ZO-1 decreased (1.051 +/- 0.136 vs 0.702 +/- 0.069; P<0.001) after treated with 10 ng/mL IL -13 for 48h. The protein expression of a-SMA and ZO-1 also showed the same tendency (a-SMA: P=0.038; ZO-1: P=0.008). IL -13 significantly reduced the level of TNF-a (44.7 +/- 01.67 vs 31.79 +/- 3.53 pg/mL; P=0.005) at 48h, but the level of TGF-I32 was significantly increased from 34.44 +/- 2.92 to 57.61 +/- 6.31 pg/mL at 24h (P=0.004) and from 61.26 +/- 1.11 to 86.91 +/- 3.59 pg/mL at 48h (P<0.001). While expressions of VEGF didn't change after IL -13 treatment. CONCLUSION: IL -13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.
Objective Limited data exist on child abuse-related immune variation during pregnancy, despite implications for maternal and infant health and extensive data showing that abuse history and depression are related to increased inflammation in other populations. This study examined associations among child abuse, depression, circulating levels of inflammatory markers, and perinatal health in pregnant adolescents, a group at high risk for childhood abuse and poor birth outcomes. Methods Pregnant teenagers (n = 133; 14-19 years; 89.5% Latina) reported on abuse and depression and had two blood draws (24-27 and 34-37 gestational weeks, second and third trimesters, respectively) for interleukin-6 (IL-6) and C-reactive protein; birth outcomes were collected. Results Abuse and depression interacted to predict higher IL-6 at second trimester (B = 0.006, p = .011) such that severely abused adolescents with high depression had higher IL-6 relative to severely abused adolescents with low depression; depression did not differentiate IL-6 levels for those with low abuse severity. Abuse and IL-6 also interacted to predict gestational age at birth (B = 0.004, p = .040) such that those with low abuse and high IL-6 and those with high abuse and low IL-6 had infants with earlier gestational age at birth. Cortisol at the second trimester mediated the association between IL-6 and gestational age at birth (indirect effect estimate=-0.143, p < .039). Conclusions Depression severity distinguished IL-6 levels among more severely abused pregnant Latina adolescents, but it was unrelated to IL-6 among less severely abused adolescents. Cortisol explained the relationship between IL-6 and earlier gestational age at birth. Multiple adversities and inflammation may influence birth outcomes and potentially affect intergenerational health.
A novel independent Th-cell subset, characterized by high expression of interleukin (IL)-9, has been recognized as the "Th9" subset. Although Th9 cells are important in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We therefore first determined whether Th9 cells were presentin a mouse model of AR. We then investigated the their involvement in the distribution of CD4+ T-cell subsets and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9 Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR in BALB/c mice. We measured nasal rubbing motion, sneezing and eosinophils, as well as the Th1 (Th1 cell percentage, Ifn-gamma. mRNA/protein, T-bet mRNA), Th2 (Th2 cell percentage, Il-4 mRNA/protein, Gata3 mRNA), Th9 (Th9 cell percentages Il-9 mRNA/protein, PU. 1 and Irf4 mRNA), Th17 (Th17 cell percentage, Il-17 mRNA/protein, Ror.t mRNA), and Treg (Treg cell percentage, Foxp3 mRNA) responses in the nasal mucosa. Treatment with anti-IL-9 Abs markedly reduced nasal rubbing, sneezing, eosinophil infiltration, and Th2, Th9, and Th17 responses, and increased the Treg response. Our findings emphasize the importance of IL-9/Th9 in the pathogenesis of AR, and suggest that anti-IL-9 Ab treatment may be an effective therapeutic strategy for AR.
Wind power generation of electricity has gained popular support because of its low environmental impact and its low costs relative to other renewable energy sources. However, concerns have been raised in the power sector that wind power generation will come at the price of increased damage to other power generators. Wind power generation is naturally volatile which requires other power sources to start up and shut down in accordance with weather conditions, which for instance coal or gas generators are in general not built to do. The previous literature has used simulations to show that the damage done and the associated costs can be substantial. We use a dataset containing all reported failures in the Nordic electricity market Nord Pool and data for Danish wind power generation. The analysis shows that for both Denmark and the rest of Nord Pool the short-term costs associated with the volatility of wind power generation are non-significant. (C) 2016 Elsevier Ltd. All rights reserved.
This paper refers to recovering waste heat from the hot gases exhausted by internal combustion engines (ICEs) driving electric generators (EGs) at full and partial load. The topic is of particular interest for developing countries where electric grids are underdeveloped or missing and electricity is generated locally by using classical fuels. The heat recovery system is based on an Organic Rankine Cycle (ORC). A novel method is proposed for the optimum design of ORC-based systems operating in combination with ICE at partial EG loads. First, ORC-based systems coupled with ICEs operating at full EG load is treated. Specific results for the operation at full EG load are as follows: (i) the optimum superheating increment ranges between 30 and 40 degrees C, depending on the type of the working fluids; (ii) a pinch point temperature difference exits between the flue gas temperature and the working fluid at the evaporator inlet; (iii) the total area of the evaporator is very close to the total area of the condenser, a fact which facilitates manufacturing; (iv) the surface area of the preheater zone is about 75% of the total surface area, while those of the boiler zone and superheater zone is about 13.5% and 11.5%, respectively. Second, the case of the ORC-based systems coupled with ICEs operating at partial EG load is considered. Specific results for this case are as follows: (v) the net power may be maximized by optimizing the working fluid mass flow rate; (vi) when the ICE is coupled with an ORC-based system, the overall thermal efficiency of the combined system, eta(ICE-ORC), is higher than the thermal efficiency of the ICE operating alone. As an example, for the case treated here, 'eta(ICE-ORC) is higher than Hits. by 6.00%, 5.85% and 5.91%, for EG loads of 100%, 75% and 50%, respectively. (C) 2017 Elsevier Ltd.
Background: The world's top three cereals, based on their monetary value, are rice, wheat, and corn. In cereal crops, DNA extraction is difficult owing to rigid non-cellulose components in the cell wall of leaves and high starch and protein content in grains. The advanced techniques in molecular biology require pure and quick extraction of DNA. The majority of existing DNA extraction methods rely on long incubation and multiple precipitations or commercially available kits to produce contaminant-free high molecular weight DNA. Results: In this study, we compared three different methods used for the isolation of high-quality genomic DNA from the grains of cereal crop, Zea mays, with minor modifications. The DNA from the grains of two maize hybrids, M10 and M321, was extracted using extraction methods DNeasy Qiagen Plant Mini Kit, CTAB-method (with/ without 1% PVP) and modified Mericon extraction. Genes coding for 45S ribosomal RNA are organized in tandem arrays of up to several thousand copies and contain codes for 18S, 5.8S and 26S rRNA units separated by internal transcribed spacers ITS1 and ITS2. While the rRNA units are evolutionary conserved, ITS regions show high level of interspecific divergence and have been used frequently in genetic diversity and phylogenetic studies. In this study, the genomic DNA was then amplified with PCR using primers specific for ITS gene. PCR products were then visualized on agarose gel. Conclusion: The modified Mericon extraction method was found to be the most efficient DNA extraction method, capable to provide high DNA yields with better quality, affordable cost and less time.
Background Working with victims and perpetrators of child sexual abuse has been shown to cause secondary traumatic stress (STS) in child protection professionals. Aims To examine the role of gender and personality on the development of secondary trauma responses. Methods A study of Internet child abuse investigators (ICAIs) from two UK police forces. Participants completed a personality test together with tests for anxiety, depression, burnout, STS and post-traumatic stress disorder to assess secondary trauma. The data were normally distributed and the results were analysed using an independent t-test, Pearson correlation and linear regression. Results Among 126 study subjects (50 females and 75 males), there was a higher incidence of STS in investigators who were female, introverted and neurotic. However, there were lower levels of STS in the participants in this study than those found in other studies. Conclusions Psychological screening and surveillance of ICAI teams can help to identify risk factors for the development of STS and identify where additional support may be required.
Control over digital transactions has steadily risen in recent years, to an extent that puts into question the Internet's traditional openness. To investigate the origins and effects of such change, the paper formally models the historical evolution of digital control. In the model, the economy-wide features of the digital space emerge as a result of the endogenous adaptation (co-evolution) of users' preferences (culture) and platform designs (technology). The model shows that: a) in the digital economy there exist two stable cultural-technological equilibria: one with intrinsically motivated users and low control; and the other with purely extrinsically motivated users and high control; b) before the opening of the Internet to commerce, the emergence of a low-control-intrinsic-motivation equilibrium was favored by the specific set of norms and values that formed the early culture of the networked environment; and c) the opening of the Internet to commerce can indeed cause a transition to a high-control-extrinsic-motivation equilibrium, even if the latter is Pareto inferior. Although it is too early to say whether such a transition is actually taking place, these results call for a great deal of attention in evaluating policy proposals on Internet regulation.
Interpersonal space is a nonverbal indicator of affiliation and closeness. In this study we investigated the effects of oxytocin (OT), a neuropeptide known for its social role in humans, on interpersonal space. In a double blind placebo controlled study we measured the effect of intranasal OT on the personal distance preferences of different familiar (friend) and unfamiliar (stranger) protagonists. Behavioral results showed that participants preferred to be closer to,a friend than to a stranger. Intranasal OT was associated with an overall distancing effect, but this effect was significant for the stranger and not for the friend. The imaging results showed interactions between treatment (OT, placebo) and protagonist (friend, stranger) in regions that mediate social behavior including the dorsomedial prefrontal cortex (dmPFC), a region associated with the mentalizing system. Specifically, OT increased activity in the dmPFC when a friend approached the participants but not when a stranger approached. The results indicate that the effect of OT on interpersonal space greatly depends on the participant's relationship with the protagonist. This supports the social salience theory, according to which OT increases the salience of social cues depending on the context. (C) 2016 Elsevier Ltd. All rights reserved.
The problem of inter-regional interchange scheduling in the presence of stochastic generation and load is considered. An interchange scheduling technique based on a two-stage stochastic minimization of expected operating cost is proposed. Because directly solving the stochastic optimization is intractable, an equivalent problem that maximizes the expected social welfare is formulated. The proposed technique leverages the operator's capability of forecasting locational marginal prices and obtains the optimal interchange schedule without iterations among operators. Several extensions of the proposed technique are also discussed.
This paper illustrates the development, up to prototype stage, of an electromechanical actuation system for a medium-voltage vacuum contactor. Such development is carried out using a multi-domain simulation-based mechatronic approach, i.e. developing coordinated sub-models for the mechanism linking the actuator to the movable parts of the interrupter, the rotational electromagnetic actuator, and the power and control electronic circuit supplying the actuator and governing the system via a digital control unit. After a preliminary analysis, the modeling, design and check of the parts via coordinated simulations is presented. A prototype of the system, manufactured to validate the design procedure is finally presented.
Intervertebral disc degeneration (IDD) is considered to be the main cause of many spinal disorders; however, its underlying pathophysiology is not clearly understood. Recent studies indicate that excessive mechanical loading may serve a major role in the initiation of IDD. The aim of the present study was to explore the effect of noninvasive cumulative axial loading on the intervertebral discs of the lumbar spine using a novel rabbit model. Rabbits in the experimental group were placed into individual tubes specifically designed to force maintenance of an upright posture and were loaded with a heavy collar to increase the intradiscal pressure of their lumbar spine. Radiograph imaging and magnetic resonance imaging (MRI) was performed every 4 weeks to provide evidence of disc degeneration. At the end of the experiment, the animals were sacrificed and disc specimens were harvested for quantitative polymerase chain reaction and histological analysis. MRI results revealed significant and progressive reductions in the signal intensities of lumbar discs in the experimental group compared with the control group throughout the 14-week study period. The expression level of type I collagen was significantly increased and the expression levels of type II collagen and aggrecan were significantly decreased in the experimental group compared with the control group (P<0.05). Histological examination revealed marked structural changes in the experimental group, including fibrocartilage-like tissue ingrowth and accelerated fibrotic changes of the nucleus pulposus. The results of the present study indicate that noninvasive cumulative axial load is able to induce accelerated degenerative changes in rabbit lumbar discs, which may provide useful information for the establishment of a novel animal model of IDD for the research of IDD in humans.
Background and aims Little is known about the intestinal epithelial expression and secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and monocytes. We aimed to study CXCL10 gene expression and regulation by the pro-inflammatory cytokines interleukin (IL)-1 beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in intestinal epithelial cell lines. Materials and methods CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29 and DLD1 human colon epithelial cells, treated with IL-1 beta, TNF-alpha, IFN-gamma alone or in combination with each other by real-time polymerase chain reaction (PCR), Northern blotting and enzyme-linked immunoabsorbent assay (ELISA). Transient transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10-kappa B2 mutant promoter and gelshifts and supershifts for nuclear factor (NF)-kappa B were also performed. Results Real-time PCRs and ELISA experiments revealed that IL-1 beta was the strongest and earliest inducer of CXCL10 messenger ribonucleic acid (mRNA) expression and protein secretion in Caco-2 cell line, whereas INF-gamma had a delayed kinetics. There was a strong synergistic effect of either TNF-alpha or IL-1 beta with IFN-gamma both on CXCL10 mRNA expression and protein secretion in all three cell lines. Real-time PCR and ELISA experiments using a specific NF-kappa B inhibitor and transfection experiments with a NF-kappa B-binding defective CXCL10 promoter construct revealed that the induction of CXCL10 by IL-1 beta and its synergism with IFN-gamma is NF-kappa B dependent. Conclusion These data demonstrate that in colonic epithelial cells, depending on the cellular context and utilizing the NF-kappa B pathway, IL-1 beta alone and/or in synergism with IFN-gamma may play a major role in the induction of CXCL10.
Mast cells are innate immune cells that respond rapidly to infection in barrier tissues such as the skin and intestinal mucosa. Expulsion of parasitic worms in the gut involves a robust type 2 host response, and an acute mastocytosis is often generated at the site of infection. However, the role of mast cells in resistance to worm infections appears to be parasite specific. Mast cells are also involved in tissue repair, but the long-term contribution of mast cell activation after worm expulsion has not been definitively studied. In this issue of European Journal of Immunology, Sorobetea et al. [ Eur. J. Immunol. 2017. 47: 257-268] demonstrate that activated mast cells persist in the large intestinal lamina propria and intraepithelial compartment long after worm expulsion, resulting in continued local and systemic presence of the mast cell protease mast cell protease 1 (MCPt-1) and enhanced intestinal permeability. In this commentary, we discuss these findings in the wider context of mast cell function in health and disease.
In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor ( Notch), and targets ( Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, upregulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a c-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development.
The postnatal development of intestine is associated with a decline in brush border lactase activity in rodents. This is similar to adulthood hypolactasia, a phenomenon prevalent in humans worldwide. In the present study, the effect of luminal proteases from adult rat intestine was studied in vitro on intestinal lactase activity in saline control, thyroxine, insulin and cortisone treated rat pups. Lactase levels were determined by enzyme analysis and Western blotting. mRNA levels encoding lactase were determined by Northern blotting. Administration of thyroxine for 4 days reduced (P < 0.05) lactase activity, but insulin treatment had no effect in 8-day-old rat intestine. However, cortisone administration augmented (P < 0.01) lactase activity, under these conditions. Western blot analysis showed decreased lactase signal corresponding to 220-kDa protein band in thyroxine treated animals. However, the intensity of lactase signal was high in cortisone treated animals compared to controls. mRNA levels encoding lactase showed a 6.8-kb mRNA transcript in saline and hormone treated rats. mRNA levels encoding lactase were increased in cortisone treated animals but were reduced in thyroxine injected pups compared to controls. Microvillus membranes from saline (P < 0.01) and thyroxine (P < 0.05) or insulin (P < 0.01) treated rats upon incubation with luminal wash from adult rat intestine showed a significant decline in lactase activity. These findings suggest that thyroxine, insulin or cortisone induced changes in lactase expression in suckling rat intestine make it susceptible to luminal proteases, which may in part be responsible for observed maturational decline in lactase activity in adult rat intestine.
This study examined the associations between intimate partner violence (IPV) during pregnancy, mother-to-infant bonding failure, and postnatal depressive symptoms at 1 month postnatal. This study also examined if these relationships would be mediated by antenatal depressive symptoms. This study was a prospective cohort study that investigated effects between the third trimester of pregnancy and 1 month after childbirth. The Japanese version of the Index of Spouse Abuse (ISA), the Japanese version of the Mother-Infant Bonding Scale (MIBS), and the Japanese version of the Hospital Anxiety and Depression Scale (HADS) were used to measure IPV during pregnancy, bonding failure with infants, and depressive symptoms during pregnancy and the postnatal period respectively. Structural equation modeling (SEM) was used to find the associations between those four variables. The final path model of the SEM showed good fit with the data. IPV during pregnancy was associated with mother-to-infant bonding failure at 1 month postnatal, whereas IPV during pregnancy was not significantly associated with postnatal depressive symptoms at 1 month postnatal. In addition, this study demonstrated that the associations between IPV during pregnancy, mother-to-infant bonding failure, and postnatal depressive symptoms at 1 month postnatal were mediated by antenatal depressive symptoms. The results of this study indicated the need for interventions for IPV and psychological health care for abused pregnant women to prevent antenatal depressive symptoms in prenatal health settings. Those interventions by perinatal health professionals would help to prevent bonding failure with infants and postnatal depressive symptoms after childbirth.
Intimate partner violence (IPV) has potentially severe and long-lasting mental health consequences for survivors, including elevated symptoms and diagnoses of posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder (GAD). The current study examined the relationship between three self-report measures of psychological distress and ratings obtained from the corresponding clinician-administered measures in women seeking assessment for mental health problems following IPV (N = 185). PTSD symptoms were assessed using the self-report Impact of Event Scale-Revised (IES-R) and the interview-based Clinician-Administered PTSD Scale (CAPS). Depression symptoms were assessed using the self-report Beck Depression Inventory-II (BDI-II) and the depressive disorders sections from the clinician-administered Anxiety Disorders Interview Schedule-IV (ADIS-IV). Anxiety symptoms were assessed using the self-report Beck Anxiety Inventory (BAI) and the clinician-administered GAD section from the ADIS-IV. Results indicated that psychological distress was prevalent in the sample, with 27% receiving a PTSD diagnosis, 40% diagnosed with a depressive disorder, and 55% meeting criteria for GAD. Although each self-report measure was significantly and positively correlated with its corresponding clinician-administered measure, rates of diagnostic concordance were mixed. The BDI-II showed a high degree of agreement with the ADIS-IV depression section, but the IES-R and the CAPS were discordant at classifying PTSD. The BAI had acceptable sensitivity but poor specificity in relation to the ADIS-IV GAD section. These findings suggest that multiple assessment modalities should be considered when rating symptoms and estimating the prevalence of diagnoses among survivors of IPV.
Intimate partner violence (IPV) and teen dating violence (TDV) are widespread, preventable public health problems in the United States. Children exposed to IPV between their caregivers and adolescent victims of TDV suffer not only immediate risks to their physical safety, but also long-term health sequelae. The emergency department presents a unique opportunity for physicians to screen for various forms of family violence and intervene on behalf of the victims. Screening for IPV and TDV is widely recommended by national health organizations including the American College of Emergency Physicians. Effective screening protocols require a multidisciplinary approach informed by knowledge of local community resources.
Intracerebral hemorrhage (ICH) is a lifethreat-ening type of stroke. Previous studies have reported that bone marrow mesenchymal stem cells (BMSCs) may exert beneficial effects on the treatment of ICH. However, it remains unknown whether the neuroprotection exerted by BMSCs on ICH is due to the differentiation of BMSCs, or the trophic factors secreted into their conditioned medium (CM). In addition, growth-associated protein-43 (GAP-43) is a protein associated with neurite extension, which may be considered a prospective therapeutic target in the treatment of ICH. The present study investigated whether administration of BMSC-CM could be considered as an alternative to the established treatment of direct BMSC transplantation; in addition, the underlying mechanisms were evaluated. Neurological function tests, brain water content, reverse transcription -quantitative polymerase chain reaction and western blotting were used in present study. The current study indicated that the neuroprotective effects of BMSC implantation and BMSC-CM treatment are similar, and that both decrease the severity of post-ICH cerebral edema, as well as improving neurological functions. At the molecular level, treatment with BMSC-CM resulted in a marked elevation in the expression of GAP-43 and interleukin (IL) -10, in addition to a significant reduction in the expression levels of IL-1a, tumor necrosis factor-a and IL-6. Following application of a phosphorylated-extracellular signal-regulated kinase (ERK1/2) inhibitor, PD98059, in a BMSC-CM rat model, the mRNA and protein expression levels of GAP-43 were significantly attenuated. Therefore, the findings of the present study demonstrated that treatment with BMSC-CM may be an alternative to direct BMSC transplantation in a rat model of ICH. The mechanism underlying BMSC-CM-mediated neuroprotection may be associated with anti-inflammatory effects, as well as activation of GAP-43 transcription and expression through ERK-1/2 phosphorylation. Therefore, the ERK-1/2-GAP-43 signaling pathway may be considered a potential novel application target of BMSC-CM for the treatment of neurological diseases.
OBJECTIVE Benign external hydrocephalus (BEH) is an enlargement of the subarachnoid spaces (SASs) that can be seen in young children. It is controversial whether children with BEH are predisposed to developing subdural hemorrhage (SDH) with or without trauma. This issue is clinically relevant as a finding of unexplained SDH raises concerns about child abuse and often prompts child protection and law enforcement investigations. METHODS This retrospective study included children (1-24 months of age) who underwent head CT scanning after an accidental fall of less than 6 feet. Head CT scans were reviewed, cranial findings were documented, and the SAS was measured and qualitatively evaluated. Enlarged SAS was defined as an extraaxial space (EAS) greater than 4 mm on CT scans. Clinical measurements of head circumference (HC) were noted, and the head circumference percentile was calculated. The relationship between enlarged SAS and HC percentile, and enlarged SAS and intracranial hemorrhage (ICH), were investigated using bivariate analysis. RESULTS Of the 110 children included in this sample, 23 had EASs greater than 4 mm. The mean patient age was 6.8 months (median 6.0 months). Thirty-four patients (30.9%) had ICHs, including subarachnoid/subpial (6.2%), subdural (6.2%), epidural (5.0%), and unspecified extraaxial hemorrhage (16.5%). Enlarged SAS was positively associated with subarachnoid/subpial hemorrhage; there was no association between enlarged SASs and either SDH or epidural hemorrhage. A larger SAS was positively associated with larger HC percentile; however, HC percentile was not independently associated with ICH. CONCLUSIONS Enlarged SAS was not associated with SDH, but was associated with other ICHs. The authors' findings do not support the theory that BEH predisposes children to SDH with minor accidental trauma.
Objective: The objective was to describe the endometrial milieu of stable transplant patients and healthy women before and after levonorgestrel intrauterine system (LNG-IUS) insertion. Study design: Women between 18 and 45 years of age desiring LNG-IUS insertion were enrolled with a 2:1 ratio of healthy to stable solid organ transplant patients. The first visit entailed a blood draw, uterine lavage and endometrial biopsy followed by LNG-IUS insertion. Follow-up visit involved a repeat serum draw, uterine lavage and endometrial biopsy. Cytokine levels were measured in the uterine lavage and serum by quantifying inflammatory biomarkers. Immunohistochemistry staining was performed on the endometrial tissue to measure macrophage levels. Statistical analysis included a nonparametric analysis that compared medians of the marker levels before and after intrauterine device (IUD) insertion within the group and between the two groups. Results: Sixteen participants completed the study: 5 solid organ transplant patients and 11 healthy patients. For the serum, there were no marked changes in the cytokines or soluble receptor levels in either group after IUD insertion. However, in the uterine lavage, there was an increase in cytokine levels post-IUD insertion for both healthy and transplant women. For the endometrial tissue, there was evidence of macrophage activity in both groups after device insertion. Conclusions: This pilot study investigated the uterine environment of the transplant patient population. Findings have pointed to the strong local inflammatory response following LNG-IUS insertion for the transplant recipients. In addition, these preliminary findings will help power a larger study that can investigate the safety and effectiveness of the IUD in this patient population. (C) 2016 The Authors. Published by Elsevier Inc.
The development of multi-photon intravital microscopy, in particular two-photon microscopy (2PM), has been a breakthrough technique for deep-tissue imaging of dynamic cell behavior inside live organisms and has substantially advanced the field of immunology. However, intravital time-lapse imaging over prolonged time periods is complicated by slow tissue drifts caused by vital activity, leading to shifting fields of views and making the acquired image sequence partially or completely unanalyzable. To solve this issue, we have established a system that performs continuous drift offset correction in real time using fine pattern matching during 2PM acquisition. We incorporated an extensive use of graphical processing unit (CPU) for high-speed computing required for real time correction during data acquisition. This allowed us to perform prolonged acquisitions and increase the proportion of analyzable datasets to nearly 100% in lymphoid and non -lymphoid tissues. Considering the straightforward implementation of our newly developed system, we anticipate that it will be applicable for other users interested in improving the quality of live imaging data acquisition. (C) 2016 Elsevier B.V. All rights reserved.
The present work was aimed at developing vector construct(s) suitable for restoring fertility in transgenic male sterile tobacco plants expressing male-sterility-inducing ORFH522 in tapetal cell layer (Nizampatnam et al. Planta 229:987-1001, 2009). PTGS vectors that could produce either intron spliced hairpin RNA against the orfH522 or induce silencing of orfH522 by heterologous 3'UTR region were developed using the selected 316 bp (orf316) fragment of orfH522. The constructs were independently mobilized into Agrobacterium and used for transforming tobacco. The T(1) generation plants carrying the restorer gene cassettes in homozygous condition were identified and crossed with the male sterile transgenic tobacco plants to obtain the hybrid seeds. PCR analysis of hybrid plants indicated segregation for the sterility inducing cassette while all the plants carried the restorer cassette. Hybrid plants produced fertile pollen grains and formed normal capsules upon selfing. Further molecular analyses of these hybrid plants with RT-PCR, Northern blotting and siRNA detection, revealed that intron interrupted hairpin RNA (ihp-RNA) mediated gene silencing was more effective compared to silencing by heterologous 3'UTR (SHUTR) as indicated by the complete degradation of orfH522 transcripts and formation of higher levels of orf316 specific siRNA molecules in plants carrying ihp-RNA restorer construct. Segregation analyses of F(2) (selfed hybrid) plants confirmed the co-segregation of gene cassettes and the traits in Mendelian di-hybrid ratio (9:3:3:1). Taken together, the results established that intron hairpin and transitive RNAi mediated silencing of orfH522 transcripts restored fertility in transgenic male sterile tobacco plants expressing orfH522 and ihp-RNA was more efficient in silencing orfH522 transcripts.
Since the European Union enforced the ban on antibiotic growth promoters in 2006, the research has been focused on natural feed additives which would have a proven positive impact on both production and animal health. Inulin is both the most commonly used and the most effective probiotic additive. The mechanism of inulin interactions with the avian body is complex, multidirectional and not fully understood. Despite a number of unresolved issues, many authors have demonstrated the positive impact of inulin on the host organism. Dietary supplementation of poultry feeding with inulin contributes to the modulation of intestinal microbiota through favouring a quick proliferation of beneficial Bifidobacterium and Lactobacillus strains and inhibiting the growth of pathogenic microbes. There are indications that inulin-provoked changes in the host gut microbiota in poultry may alter the structure and histomorphology of the intestinal mucosa and improve its absorption capacity in poultry. It has also been demonstrated that inulin may affect the immune system and the systemic metabolism of minerals and lipids. The reports on inulin effects on the body and performance of poultry are often contradictory, as the effectiveness of this prebiotic is strongly dependent on the type and dose used, and the duration of its administration.
Aims and Objectives:Recent studies show that lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC) share similar genetic molecular biology. There are increasing concerns regarding the biological significance of LCIS. The aim of this study is to investigate whether the presence of coexisting LCIS in ILC affects tumor biology and behavior and to correlate it with other clinicopathologic parameters.Materials and Methods:In this study, 254 cases of ILC were included. Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor (PR), E-cadherin, human epidermal growth factor receptor (HER2), and MIB-1 of 254 ILC cases were retrieved. The patient with ILC and coexisting LCIS were compared with pure ILC cases with respect to different clinicopathologic parameters.Results:Of the 254 cases, 107 cases were pure ILC and 147 cases were ILC with coexisting LCIS. Seventy-six (76/184, 41.32%) cases showed axillary lymph node metastases. Lymph node metastasis was absent in 108 cases, micrometastasis was present in 5 cases, and stage N1, N2, N3 in 51, 5, and 15 cases, respectively. Nodal involvement, locoregional and distant recurrence of ILC with LCIS were less frequent compared with ILC without LCIS with P-value of 0.034 and 0.007, respectively. The presence of coexisting LCIS in ILC predicted higher disease-free survival (DFS) compared with pure ILC (P=0.034, log-rank test). When divided into different strata, ER-positive ILC cases with associated LCIS cases showed better DFS than ER-positive pure ILC cases (P=0.021, log-rank test). Similarly, ILC cases with LCIS in patient less than 50 years showed better DFS than the patient less than 50 years with pure ILC (P=0.045, log-rank test).Conclusions:In conclusion, ILC coexisting with lobular carcinoma in situ (ILC+LCIS) is characterized by less nodal involvement, lower locoregional, and distant recurrence and better DFS than pure ILC. When divided into different strata, ER-positive and less than 50-year groups with ILC+LCIS show even significant better DFS than pure ILC. These findings suggest that there is biological significance of coexisting LCIS in ILC and that this may have more effect on tumor aggressiveness in certain strata of ILC.
In this paper a twofold inverse problem for orthogonal matrix functions in the Wiener class is considered. The scalar-valued version of this problem was solved by Ellis and Gohberg in 1992. Under reasonable conditions, the problem is reduced to an invertibility condition on an operator that is defined using the Hankel and Toeplitz operators associated to the Wiener class functions that comprise the data set of the inverse problem. It is also shown that in this case the solution is unique. Special attention is given to the case that the Hankel operator of the solution is a strict contraction and the case where the functions are matrix polynomials. (C) 2017 Elsevier Inc. All rights reserved.
An indirect hysteresis voltage digital control is proposed for single-phase half-bridge inverters. Because of the slow response to the switching modulation, it is difficult to control the voltage by hysteresis method directly. In this study, the output voltage is controlled indirectly by using the adaptive band hysteresis current control, which is fast response, robustness, and independent on the system parameters. The reference current is computed based on the desired reference output voltage, and the hysteresis band is controlled to maintain the switching frequency at a constant value. Simulation results show good performances of the proposed control method in both cases: ac and dc reference output voltage.
The model of a voltage source inverter depends on its output filter. The parameters of this filter can differ significantly from their nominal values due to power losses in the core of the output coil and changes in its inductance. Only Multi-Input-Single-Output control systems can effectively reduce inverter output voltage distortions for a standard nonlinear rectifier RC load. However, their design requires knowledge of the actual values of the inverter parameters. The novelty of the paper is that it connects the designs of two MISO control systems with a method of the automated measurements of the voltage source inverter parameters. The breadboard verification is also included.
Voltage inverters are the most common kind of actuator to interface with variable frequency electrical systems. They are usually driven by a modulation block that provides the gating signals for the switches. Direct digital control avoids the modulation block, being the gating signals directly produced by the controller. In such configuration, the control of the electrical system is a discrete time and quantized-actuation problem. This paper analyzes the harmonic content in sinusoidal steady state resulting from such configuration. The analysis illustrates the higher harmonic content, providing lower bounds for such content in the case of low ratios of commutation to fundamental frequencies. Also, the dependence of harmonic content with duty cycle and with commutation losses is exposed. The findings apply to different kind of control structures, regardless of its design or tuning parameters. Some of them are experimentally compared. A two-level three-phase inverter is used in the analysis for its relevance and simplicity although the procedure can be applied to any number of phases or levels. (C) 2016 International Association for Mathematics and Computers in Simulation (IMACS). Published by Elsevier B.V. All rights reserved.
This study deals with the design of a load sensorless multi-loop control system for the stand-alone inverter. In the proposed strategy, only the inverter current is measured, which is practically required for both control and protection purposes, then the load voltage and current are both estimated using the linear Kalman filter algorithm, and the gradient descent adaptive control method, respectively. The estimated quantities are used as feedback signals of an inner-outer double-loop controller, which uses a proportional-resonant outer-controller to regulate the output voltage with minimum steady-state error and a simple proportional inner-controller to provide active damping and improve the transient performance. The controller parameters are designed in the frequency domain based on the required bandwidth and stability margin. Furthermore, the controllability and observability, as well as the stability of overall digital control system, including the dynamics of estimators, are analytically investigated. Simulation and experimental results, with a 600 VA prototype, confirm the theoretical achievements and illustrate the excellent performance of the proposed estimation and control scheme.
Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4-5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. (C) 2016 Elsevier Inc. All rights reserved.
Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liquids (Is). Although they possess core characteristics that are similar to those of Its (e.g., low volatility, non-flammability, low melting points, low vapor pressure, dipolar nature, chemical and thermal stability, high solubility, and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chemical, electrochemical, and biological sectors. To date, the applications of DESs have shown great promise, especially in the medical and biotechnological fields. In spite of these various achievements, the safety concern for these mixtures must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biological industry, first, they must be established as safe mixtures. Hence, the biotechnological applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES-based research. First, it describes the properties of these mixtures with ample focus on their toxicity profiles. Second, it provides an overview of the breakthroughs that have occurred and the foreseeable prospects of the use of DESs in various biotechnological and biological applications. (C) 2016 Elsevier Inc. All rights reserved.
Flowers are the main sexual reproductive organs in plants. The shapes, colours and scents of corolla of plant flowers are involved in attracting insect pollinators and increasing reproductive success. The process of corolla senescence was investigated in Ipomoea purpurea (Convolvulaceae) in this study. In the research methods of plant anatomy, cytology, cell chemistry and molecular biology were used. The results showed that at the flowering stage cells already began to show distortion, chromatin condensation, mitochondrial membrane degradation and tonoplast dissolution and rupture. At this stage genomic DNA underwent massive but gradual random degradation. However, judging from the shape and structure, aging characteristics did not appear until the early flower senescence stage. The senescence process was slow, and it was completed at the late stage of flower senescence with a withering corolla. We may safely arrive at the conclusion that corolla senescence of I.purpurea was mediated by programmed cell death (PCD) that occurred at the flowering stage. The corolla senescence exhibited an obvious temporal rhythm, which demonstrated a high degree of coordination with pollination and fertilization.
Intimate partner violence (IPV) in sub-Saharan Africa affects 36% of the population. Several African countries rank among the highest globally. In this article, we present evidence on the prevalence, determinants, and impact of IPV across several sub-Saharan African countries interpreted against the backdrop of social ecological theory. We also describe prevention or intervention programs tested in different regions of Africa, selecting only those programs which were published in a journal outlet and which met a high criteria of implementation and methodology (n = 7). Based on our review of the empirical literature, some risk factors for violence documented in Western societies are the same in Africa, including poverty, drinking, a past history of child abuse or posttraumatic stress disorder, and highly traditional gender role beliefs. Low education is also associated with IPV for both women and men. In Africa, partner abuse intersects with the HIV pandemic, making violence prevention especially urgent. African programs to prevent IPV are often incorporated with HIV prevention; community building and community engagement are emphasized more in Africa than in North America or Europe, which invoke more individually focused approaches. Some programs we review lowered HIV exposure in women; others contributed to reduced violence perpetration among men. The programs show sufficient promise to recommend replication and dissemination in sub-Saharan Africa.
Iris yellow spot virus (IYSV), an emerging disease of onion crops, was identified by transmission electron microscopy, enzyme linked immunosorbent assay, and reverse transcription polymerase chain reaction in Costa Rica. Onion plants had straw- colored, elongated lesions and tip dieback. Costa Rican IYSV nucleocapsid partial sequences (15 isolates) grouped with isolates from North and Central America and from New Zealand.
This essay will examine the expos of the realities regarding poverty, immorality and sexual crime in the Irish Free State by the radical journal Honesty (1925-1931). Honesty was edited by the socialist republican James W. Upton, a man with a longstanding commitment to the rights of women and the poor. Upton was by instinct anti-establishment in an era when the country's religio-political leadership was insecure and keen to manage the Free State's news agenda. Something they attempted in the service of projecting what was viewed as an ideologically acceptable image of life in the Free Sate, to both domestic and foreign audiences. Upton viewed this policy as a manifestation of the social and political cant favoured by the Free State's leadership, which was aided and abetted by, and gave succour to, the hypocrisy of wider bourgeois Free State society. A coalition of forces, Upton reasoned, that damaged the interests of the most vulnerable sections of Irish society, in particular, the nation's women and children living on or below the breadline. However, notwithstanding it radicalism and reputation in the Free State, Honesty has been largely lost to the history of Irish journalism.
Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (+/- 1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood.
Objective: To evaluate the transepithelial transport of sodium, glucose, potassium, and water and the mRNA level of the sodium-glucose cotransporter (SGLT1) and the facilitated sugar transporter (GLUT2) in the small intestine of iron-deficient rats. Methods: After 6 wk of receiving diets with low or normal iron content, rats (Wistar-EPM) were subjected to two experiments: 1) evaluation of the transepithelial transport of sodium, glucose, potassium, and water by an "in vivo" experimental model of intestinal perfusion and 2) determination of relative SGLT1 and GLUT2 mRNA levels in the proximal, intermediate, and distal portions of the small intestine by the northern blotting technique. Results: Hemoglobin and hepatic iron levels were statistically lower in the anemic rats. The mean transepithelial transports of sodium (-33.0 mu Eq . min(-1) . cm(-1)), glucose (426.0 mu M . min(-1) . cm(-1)), and water (0.4 mu L . min(-1) . cm(-1)) in the small intestine of the anemic rats were significantly lower than in the control group (349.1 mu Eq . min(-1) cm(-1), 842.6 mu M . min(-1) . cm(-1), and 4.3 mu l . min(-1) cm(-1), respectively, P < 0.05). The transepithelial transport of potassium was similar for both groups. The relative SGLT1 mRNA levels of the anemic rats in the intermediate (1.796 +/- 0.659 AU) and distal (1.901 +/- 0.766 AU) segments were significantly higher than the values for the control rats (intermediate 1.262 +/- 0.450 AU, distal 1.244 +/- 0.407 AU). No significant difference was observed for the relative SLGT1 mRNA levels in the proximal segment or for the GLUT2 mRNA levels in all segments. Conclusion: Iron deficiency decreases the absorption of glucose, sodium, and water and increases SGLT1 mRNA in the intermediate and distal segments of the small intestine of rats. (C) 2011 Elsevier Inc. All rights reserved.
Electrocoagulation with an iron-air fuel cell is an innovative arsenate removal system that can operate without an external electricity supply. Thus, this technology is advantageous for treating wastewater in remote regions where it is difficult to supply electricity. In this study, the possibility of real applications of this system for arsenate treatment with electricity production was verified through electrolyte effect investigations using a small-scale fuel cell and performance testing of a liter-scale fuel cell stack. The electrolyte species studied were NaCl, Na2SO4, and NaHCO3. NaCl was overall the most effective electrolyte for arsenate treatment, although Na2SO4 produced the greatest electrical current and power density. In addition, although the current density and power density were proportional to the concentrations of NaCl and Na2SO4, the use of concentrations above 20 mM of NaCl and Na2SO4 inhibited arsenate treatment due to competition effects between anions and arsenate in adsorption onto the iron hydroxide. The dominant iron hydroxide produced at the iron anode was found to be lepidocrocite by means of Raman spectroscopy. A liter-scale four-stack iron-air fuel cell with 10 mM NaCl electrolyte was found to be able to treat about 300 L of 1 ppm arsenate solution to below 10 ppb during 1 day, based on its 60-min treatment capacity, as well as produce the maximum power density of 250 mW/m(2). (C) 2017 Elsevier Ltd. All rights reserved.
Irrigation water has been recognized as an important microbial risk factor for fruits and vegetables in many production areas, but there is still a lack of information about how the microbiological quality of different irrigation water sources and climatic conditions influence the safety of vegetables produced in Brazil. This study evaluated the distribution of generic E. coli and the prevalence of E. coil O157:H7 in two different water sources (ponds and streams bordering farmlands and urban areas) used for irrigation and on commercially produced lettuces in Southern Brazil. We also evaluated the effect of agricultural factors and meteorological conditions in the potential contamination of water and produce samples. A longitudinal study was conducted on four farms during a year (July 2014 to August 2015). The results showed generic E. coli prevalence of 84.8% and 38.3% in irrigation water samples and on lettuces, respectively, indicating irrigation water as an important source of contamination of lettuces. No significant differences were detected in the counts of E. coli between the two different surface water sources. The climatic conditions, particularly rainfall and environmental temperature, have influenced the high concentration of E. coil. The highest loads of E. coil in irrigation water and on lettuces were found during the warmest time of the year. E. coli O157:H7 was detected by qualitative polymerase chain reaction (qPCR) in 13 water samples but only 4 were confirmed by isolation in culture media. (C) 2017 Elsevier Ltd. All rights reserved.
BackgroundIrritability, a frequent complaint in children with psychiatric disorders, reflects increased predisposition to anger. Preliminary work in pediatric clinical samples links irritability to attention bias to threat, and the current study examines this association in a large population-based sample. MethodsWe studied 1,872 children (ages 6-14) using the Development and Well-Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL), and dot-probe tasks. Irritability was defined using CBCL items that assessed temper tantrums and hot temper. The dot-probe task assessed attention biases for threat-related (angry face) stimuli. Multiple regression analysis was used to assess specificity of associations to irritability when adjusting for demographic variables and co-occurring psychiatric traits. Propensity score matching analysis was used to increase causal inference when matching for demographic variables and co-occurring psychiatric traits. ResultsIrritability was associated with increased attention bias toward threat-related cues. Multiple regression analysis suggests associations between irritability and threat bias are independent from demographic variables, anxiety, and externalizing traits (attention-deficit/hyperactivity, conduct, and headstrong/hurtful), but not from broad internalizing symptoms. Propensity score matching analysis indicated that this association was found for irritable versus nonirritable groups matched on demographic and co-occurring traits including internalizing symptoms. ConclusionsIrritability in children is associated with biased attention toward threatening information. This finding, if replicated, warrants further investigation to examine the extent to which it contributes to chronic irritability and to explore possible treatment implications.
Objective: The genetic surroundings of blaCTX-M-15 in Escherichia coli recovered from faeces of travellers returning to the UK from overseas were compared with those among established UK strains to provide further insights into the spread of bla(CTX-M-15) in the UK. Methods: From August 2006 to January 2008, 1031 faecal specimens were collected at the North West London NHS Trust from general practice patients with a clinical history of diarrhoea following recent international travel. Cefuroxime-resistant E. coli were isolated on cystine-lactose-electrolyte deficient agar and those that produced extended-spectrum beta-lactamases (ESBLs) were identified by double disc synergy test (DDST). The molecular environments surrounding bla(CTX-M-15) were investigated by PCR, DNA sequencing, gene cloning and northern blotting. Results: 182/1031 (18%) E. coli isolated from returning travellers gave a positive DDST, and were confirmed by PCR to produce CTX-M ESBLs; 174 (96%) had blaCTX-M-15, including 21 belonging to clone ST131. Among these 174 isolates, the environment upstream of blaCTX-M-15 consisted of either: (i) an intact ISEcp1 (n=108); (ii) various lengths of truncated ISEcp1 (n=58); or (iii) a 24 bp remnant of ISEcp1 (n=8). Two different promoters were found to transcribe bla(CTX-M-15), resulting in different levels of cephalosporin resistance. Conclusion: E. coli with CTX-M-15 ESBL from returning travellers harboured previously seen UK bla(CTX-M-15) genetic environments (intact or 24 bp remnant of ISEcp1) as well as bla(CTX-M-15) genetic environments previously unseen in the UK (various lengths of truncated ISEcp1), which suggest overseas acquisition and highlight the difficulty of control in a time of population mobility and travel.
Islamic State of Iraq and Syria (ISIS) has recently carried out atrocities both in the Middle East and localized terror attacks in several western countries killing hundreds and wounding thousands. Many executions and attacks were broadcast within clever media campaigns containing warnings of future attacks. We examined anxiety of a future ISIS threat along with its association to self-reported sleep difficulties in a sample of adult Israelis (N = 1007). We demonstrated this association in different models beyond the effects of additional potential variables which have been noted to affect sleep, such as reported health, exposure to terror, exposure to ISIS media, psychological variables such as general anxiety, depression and post-traumatic stress disorder symptoms. In all cases, a strong positive relationship between ISIS anxiety and sleep symptoms was obtained. Issues concerning the relationship between anxiety of a future threat and sleep symptoms, as well as the notion of sleep difficulties being a marker for such anxiety, are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
The genes encoding monomer- and dimer-type isocitrate dehydrogenase (IDH) isozymes from a psychrotrophic bacterium, Pseudomonas psychrophila, were cloned and sequenced. Open reading frames of the genes were 2,226 and 1,257 bp in length and corresponded to polypeptides composed of 741 and 418 amino acids, respectively. The deduced amino acid sequences showed high sequence identity with those of psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea, (about 70% identity) and the respective types of the putative IDH genes from other bacteria of genus Pseudomonas (more than 80% identity). The two genes were located in opposite direction from each other with a spacer of 463 bases in the order of dimeric and monomeric IDH genes on the chromosomal DNA, but analyses of northern blotting and 5'-terminal regions of the mRNAs revealed that they are transcribed independently. The expression of monomer- and dimer-type IDH genes in C. maris are known to be cold- and acetate-inducible, respectively, while only slight inductions by low temperature and/or acetate were observed in the expression of the P. psychrophila monomer- and dimer-type IDH genes. Both of these IDH isozymes overproduced in Escherichia coli showed mesophilic properties, in contrast with monomer- and dimer-type IDHs of C. maris as cold adapted and mesophilic enzymes, respectively. The substitution of Glu55 residue in the P. psychrophila monomeric IDH for Lys, which is the corresponding residue conserved between the cold-adapted monomeric IDHs from C. maris and C. psychrerythraea, by site-directed mutagenesis resulted in the decreased thermostability and the lowered optimum temperature of activity, suggesting that this residue is involved in the mesophilic properties of the P. psychrophila monomeric IDH.
Which issues do political parties emphasize in campaigns? Selecting the issues to emphasize in campaigns is treated with the same importance as policy positioning. Nevertheless, little attention has been paid to understanding parties' strategies of issue competition in presidential elections under multiparty systems. By analyzing statements of presidential candidates in the 2002, 2007, and 2012 Korean presidential debates, we find that presidential candidates use their issue emphasis strategies differently in presidential elections according to party size and ideological relationships with other parties. Specifically, a small party's candidates have been more likely than mainstream parties' candidates to pursue their issue ownership advantage. In addition, a mainstream party's candidates have emphasized the issues of a small party more than those of his own party when the two parties have had a similar ideological foundation, whereas, when there were no such ideological similarities, a mainstream party's candidate has only focused on issues of the mainstream party. Our results imply that the political communication used by political parties and candidates is conditioned not only by political contexts such as electoral systems or party systems but also by the size and ideology of parties.
Background: Itraconazole has been proved therapeutically effective against a variety of human cancers. This study assessed the effect of itraconazole on the Hedgehog (Hh) pathway and proliferation of human gastric cancer cells. Methods: CCK-8 assay and colony formation assay were used to assess the effects of itraconazole on proliferation of gastric cancer cells. The expression of Hh signaling components in gastric cancer cells treated with itraconazole was evaluated by reverse-transcription polymerase chain reaction, immunoblotting and dual luciferase assay. Tumor xenograft models were used to assess the inhibitory effect of itraconazole on the proliferation of gastric cancer cells in vivo. Results: Itraconazole could remarkably inhibit the proliferation of gastric cancer cells. When in combination with 5-FU, itraconazole significantly reduced the proliferation rate of cancer cells. Furthermore, itraconazole could regulate the G1-S transition and induce apoptosis of gastric cancer cells. Hh signaling was abnormally activated in human gastric cancer samples. In vitro, studies showed that the expression of glioma-associated zinc finger transcription factor 1 (Gli1) was decreased at both transcriptional and translational levels after treatment with itraconazole. Dual luciferase assay also indicated that itraconazole could inhibit the transcription of Gli1. In vivo studies demonstrated that monotherapy with itraconazole by oral administration could inhibit the growth of xenografts, and that itraconazole could significantly enhance the antitumor efficacy of the chemotherapeutic agent 5-FU. Conclusions: Hh signaling is activated in gastric tumor and itraconazole can inhibit the growth of gastric cancer cells by inhibiting Gli1 expression.
Imprinted genes control fetal and placental growth in mice and in rare human syndromes, but the role of these genes in sporadic intrauterine growth restriction (IUGR) is less well-studied. We measured the ratio of mRNA from a maternally expressed imprinted gene, PHLDA2, to that from a paternally expressed imprinted gene, MEST, by Northern blotting in 38 IUGR-associated placentae and 75 non-IUGR placentae and found an increase in the PHLDA2/MEST mRNA ratio in IUGR (p = 0.0001). Altered expression of PHLDA2 and MEST was not accompanied by changes in DNA methylation within their imprinting centers, and immunohistochemistry showed PHLDA2 protein appropriately restricted to villous and intermediate cytotrophoblast in the IUGR placentae. We next did a genome-wide survey of mRNA expression in 14 IUGR placentae with maternal vascular under-perfusion compared to 15 non-IUGR placentae using Affymetrix U133A microarrays. In this series six imprinted genes were differentially expressed by ANOVA with a Benjamini-Hochberg false discovery rate of 0.05, with increased expression of PHLDA2 and decreased expression of MEST, MEG3, GATM, GNAS and PLAGL1 in IUGR placentae. At lower significance, we found IGF2 mRNA decreased and CDKN1C mRNA increased in the IUGR cases. We confirmed the significant reduction in MEG3 non-translated RNA in IUGR placentae by Northern blotting. In addition to imprinted genes, the microarray data highlighted non-imprinted genes acting in endocrine signaling (LEP, CRH, HPGD, INHBA), tissue growth (IGF1), immune modulation (INDO, PSG-family genes), oxidative metabolism (GLRX), vascular function (AGTR1, DSCR1) and metabolite transport (SLC-family solute carriers) as differentially expressed in IUGR vs. non-IUGR placentae.
A total of 7778 host-seeking adult Dermacentor reticulatus (Ixodida: Ixodidae) ticks were examined for the prevalence of Francisella tularensis holarctica (Thiotrichales: Francisellaceae) in a natural focus of tularaemia in the floodplain forest-meadow ecosystem along the lower reaches of the Dyje (Thaya) river in South Moravia (Czech Republic) between 1995 and 2013. Ticks were pooled (10 specimens per pool) and their homogenates inoculated subcutaneously in 4-week-old specific pathogen-free mice. Dead mice were sectioned, their spleens cultivated on thioglycollate-glucose-blood agar and impression smears from the spleen, liver and heart blood were Giemsa-stained. Sixty-four pools were positive for F.tularensis: the overall minimum infection rate (MIR) was 0.82%. Overall MIRs for the 4714 female and 3064 male D.reticulatus examined were 0.89 and 0.72%, respectively; MIRs fluctuated across years between 0.0 and 2.43%. The estimated bacterial load in infected ticks varied from 0.84 to 5.34 log(10) infectious F.tularensis cells per tick (i.e. from about seven to 220000 cells). Ticks with low loads were more prevalent; more than 1000 infectious cells were detected in 24 ticks (0.3% of all ticks and 37.5% of infected ticks). Monitoring of D.reticulatus for the presence and cell numbers of F.tularensis may be a valuable tool in the surveillance of tularaemia.
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which transduces cytokine and growth factor signalling. Analysis of TYK2 loss-of-function revealed its important role in immunity to infection, (auto-) immunity and (auto-) inflammation. TYK2-deficient patients unravelled high similarity between mice and men with respect to cellular signalling functions and basic immunology. Genome-wide association studies link TYK2 to several autoimmune and inflammatory diseases as well as carcinogenesis. Due to its cytokine signalling functions TYK2 was found to be essential in tumour surveillance. Lately TYK2 activating mutants and fusion proteins were detected in patients diagnosed with leukaemic diseases suggesting that TYK2 is a potent oncogene. Here we review the cell intrinsic and extrinsic functions of TYK2 in the characteristics preventing and enabling carcinogenesis. In addition we describe an unexpected function of kinase-inactive TYK2 in tumour rejection. (C) 2015 The Authors. Published by Elsevier Ltd.
Certain special biological characteristics of Japanese quails (Coturnix coturnix japonica) could enable quicker and less expensive laboratory experiments than similar studies using mice or chickens. Moreover, due to some physiological similarities with humans, quails have been recognized as an ideal laboratory model for experiments in some fields such as immunology, endocrinology, and reproductive biology. The aim of this study was to acquire normal ultrasonographic images of reproductive organs of female Japanese quails in order to facilitate laboratory experiments on reproductive biology and to determine a non-invasive in-life alternative to carcass analysis. Thirty female Japanese quails of different ages were used for ultrasound scanning of ovaries, follicles, ova, oviducts and eggs. In addition, five quails were euthanized for experiments using a direct standoff imaging technique. It was possible to identify different sizes of follicles ranging from small white follicles (0.14cm) to large yellow follicles (2.57cm), post-ovulatory follicles (POFs), ova at various stages of development, oviducts, and also eggs within the oviducts. These findings demonstrate that ultrasound scanning of female Japanese quail reproductive organs might be a beneficial diagnostic tool for applications such as studying reproductive physiology, anticipating the beginning or the end of the breeding season, detecting any pathological disorders easily, and identifying non-productive females which could lead to more cost-efficient laboratory procedures.
JC polyomavirus-associated nephropathy (JC-PVAN) is a rare but challenging cause of renal dysfunction. We report JC-PVAN in a renal allograft recipient and highlight the obstacles in definitive diagnosis of this disease entity. A deceased-donor renal transplant recipient was diagnosed with JC polyomavirus nephritis 4 years after transplantation. Immunosuppressive agents were subsequently reduced, resulting in an initial stabilization of renal function. We present this interesting case and discuss the challenges with diagnosing and treating this rare entity.
Jet electrochemical machining is a promising shaping method that has the potential to replace traditional sinking ECM in the industry owing to its flexibility and stability. However, its machining quality is impaired by the occurrence of a unique phenomenon (i.e., the anode cannot be uniformly dissolved with high nozzle travel rate). This paper aims to analyze this unique phenomenon from the viewpoint of anodic behavior and to select the optimum travel rate parameter window. The anodic behavior of TB6 titanium alloy in sodium chloride solution was investigated by linear sweep voltammetry, cyclic voltammetry, electrochemical impedance spectroscopy and chronoamperometry. A time-dependent mechanism of pitting/large localized corrosion/polishing for the anodic interface structure was developed. The full electricity quantity of the equivalent oxide layer capacitor, Q, was proposed as a criterion for the initiation of uniform dissolution state. Subsequently, a novel model that incorporates the parameter Q was developed to account for the effect of anodic behavior. This model is able to predict the machined profile as well as the localized corrosion range. Finally, the effect of nozzle travel rate on jet ECM performance was investigated, and a nozzle travel rate of 10 to 25 mu m s(-1) was selected as the optimum parameter window in the present work. (C) 2017 Elsevier Ltd. All rights reserved.
Although the role of social cognition in leadership perception has been emphasized frequently in recent years, research using this approach in an organizational context is rare. This study investigated subordinates' perceptions of their managers as leaders (that is, to what extent they perceive their manager as a leader) as a potential mediating factor explaining the relationship between managers' self-monitoring and their subordinates' attitudes toward their organizations. The study was carried out with middle-level managers (N=64) and their subordinates (N=210) from various business organizations in Turkey. Results indicate that subordinates' leadership perceptions of their managers mediate the relationship between managers' self-monitoring and their subordinates' affective and normative organizational commitment. These results provide insight into some of the antecedents and outcomes of leadership perception.
The current study measured adults' P350 and N170 ERPs while they interacted with a character in a virtual reality paradigm. Some participants believed the character was controlled by a human (avatar condition, n=19); others believed it was controlled by a computer program (agent condition, n=19). In each trial, participants initiated joint attention in order to direct the character's gaze toward a target. In 50% of trials, the character gazed toward the target (congruent responses), and in 50% of trials the character gazed to a different location (incongruent response). In the avatar condition, the character's incongruent gaze responses generated significantly larger P350 peaks at centro-parietal sites than congruent gaze responses. In the agent condition, the P350 effect was strikingly absent. Left occipitotemporal N170 responses were significantly smaller in the agent condition compared to the avatar condition for both congruent and incongruent gaze shifts. These data suggest that beliefs about human agency may recruit mechanisms that discriminate the social outcome of a gaze shift after approximately 350ms, and that these mechanisms may modulate the early perceptual processing of gaze. These findings also suggest that the ecologically valid measurement of social cognition may depend upon paradigms that simulate genuine social interactions.
This paper presents an optimal bid submission in a day-ahead electricity market for the problem of joint operation of wind with photovoltaic power systems having an energy storage device. Uncertainty not only due to the electricity market price, but also due to wind and photovoltaic powers is one of the main characteristics of this submission. The problem is formulated as a two-stage stochastic programming problem. The optimal bids and the energy flow in the batteries are the first-stage variables and the energy deviation is the second stage variable of the problem. Energy storage is a way to harness renewable energy conversion, allowing the store and discharge of energy at conveniently market prices. A case study with data from the Iberian day-ahead electricity market is presented and a comparison between joint and disjoint operations is discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Tunneling field-effect transistors (TFETs) are gaining attention because of their good scalability and low leakage current. However, they suffer from low on-state current and severe ambipolar conductivity. To address these issues, in this paper, we have proposed a novel junctionless nanowire TFET with induced source side tunneling realized by a hetero-gate-dielectric (HGD JN-TFET). This approach induces a local dip in the conduction band edge at the tunneling junction leading to an abrupt transition between the on and off-states as well as subthreshold swing (SS) as low as 45 mV/dec at low drain voltages. The proposed structure provides I-on of 8.7 x 10(-6) A/mu m and I-off of 1.1 x 10(-11) A/mu m. Also, we have shown that the length of high-k gate insulator as well as its dielectric constant can significantly affect the performance and power efficiency of this device.
In the realm of state trial courts, child abuse and neglect (dependency) proceedings are unique. Dependency proceedings place courts in the position, not of determining an ultimate result, but of overseeing the ongoing actions of a state agency. The court proceedings can continue on up to twenty-one years without a culminating trial. We must revise our rules of appellate procedure to protect review of dependency decisions so that children and families have the access to justice they deserve.
With the increasing incidence and prevalence of antibiotic contamination in animal-derived food and drug resistance around the world, early and specific detection of antibiotic residues has garnered significant attention. Herein, for the first time, we devise a facile, label free and portable aptasensor for quantitative determination of Kanamycin (KANA) by electrochemical impedance spectroscopy (EIS), which accompanying the assembly of in-vitro selected single strand DNA (ssDNA) anti-KANA-aptamer functionalized screen printed carbon electrodes (SPCEs) used as transducer. The target detection is based on specific recognition by KANA-aptamer covalently immobilized on SPCEs surface. The surface morphology and electrochemical properties of aptasensor were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and EIS. Under optimized experimental conditions, the devised aptasensor exhibited a dynamic range 1.2-600 ngmL(-1) with linearity 1.2-75 ngmL(-1) and limit of detection (LOD) 0.11 ng mL(-1) (S/N =3) of KANA. The developed aptasensor are endowed with a good selectivity and specificity to KANA without interference from competitive analogues (streptomycin and gentamicin). For practical application, the aptasensor performance was verified in spiked milk samples and the acceptable recovery percentage of 96.88-100.5% (%RSD = 4.56, n=3) was obtained in milk samples. (C) 2017 Elsevier B.V. All rights reserved.
Seed germination and early seedling establishment are critical stages during a plants life cycle. These stages are precisely regulated by multiple internal factors, including phytohormones and environmental cues such as light. As a family of small molecules discovered in wildfire smoke, karrikins (KARs) play a key role in various biological processes, including seed dormancy release, germination regulation, and seedling establishment. KARs show a high similarity with strigolactone (SL) in both chemical structure and signaling transduction pathways. Current evidence shows that KARs may regulate seed germination by mediating the biosynthesis and/or signaling transduction of abscisic acid (ABA), gibberellin (GA) and auxin [indoleacetic acid (IAA)]. Interestingly, KARs regulate seed germination differently in different species. Furthermore, the promotion effect on seedling establishment implies that KARs have a great potential application in alleviating shade avoidance response, which attracts more and more attention in plant molecular biology. In these processes, KARs may have complicated interactions with phytohormones, especially with IAA. In this updated review, we summarize the current understanding of the relationship between KARs and SL in the chemical structure, signaling pathway and the regulation of plant growth and development. Further, the crosstalk between KARs and phytohormones in regulating seed germination and seedling development and that between KARs and IAA during shade responses are discussed. Finally, future challenges and research directions for the KAR research field are suggested.
Ganoderma lingzhi is a kind of precious medicinal mushroom. MicroRNAs (miRNAs) play an important role in the regulation of a broad range of biological processes. In this study, we first report on the miRNAs of the G. lingzhi sporocarp. In total, 132 known miRNAs and 34 putative candidate (PC) miRNAs were identified for the first time in G. lingzhi sporocarp. Through target gene prediction, 111 of 132 known miRNAs had targeted genes, 58 of them had more than one, and most predicted targeted genes might be regulated by more than one miRNA; functional enrichment by KEGG analysis demonstrated that target genes related to cancer and signal transduction occupied the largest proportion. A total of seven miRNAs (four known miRNAs and three PC miRNAs) that had high abundance were selected for expression confirmation by quantitative real-time PCR (qRT-PCR) and northern blotting. This is the first comprehensive study of the miRNA composition in G. lingzhi, which resulted in the addition of a significant number of novel miRNA sequences to miRBase and laid the foundation for further understanding of the function of miRNAs in the regulation of G. lingzhi. (c) 2016 Published by Elsevier B.V. on behalf of The Mycological Society of Japan.
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage. Expression of CD5, which correlates with TCR signal strength, was reduced on DP and mature CD4 and CD8 cells, as a result of thymocyte-intrinsic Kif7-deficiency, and Kif7-deficient T-cells from radiation chimeras activated less efficiently when stimulated with anti-CD3 and anti-CD28 in vitro. Kif7-deficient thymocytes showed higher expression of the Hedgehog target gene Ptch1 than WT, but were less sensitive to treatment with recombinant Shh, and Kif7-deficient T-cell development was refractory to neutralisation of endogenous Hh proteins, indicating that Kif7-deficient thymocytes were unable to interpret changes in the Hedgehog signal. In addition, Kif7-deficiency reduced cell-surface MHCII expression on thymic epithelial cells.
Natural killer (NK) cell activity is regulated by activating and inhibitory signals transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR gene repertoire among individuals may affect disease outcome. Sepsis development and severity may be influenced by genetic factors affecting the immune response. Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I ligands in critical patients, aiming to identify patterns that could be associated with sepsis. Male and female patients (ages ranging between 14 and 94 years-old) were included. DNA samples from 211 patients with sepsis and 60 controls (critical care patients with no sepsis) collected between 2004 and 2010 were included and genotyped for KIR genes using the polymerase chain reaction method with sequence-specific oligonucleotide (PCR-SSO), and for HLA genes using the polymerase chain reaction method with sequence-specific primers (PCR-SSP). The frequencies of activating KIR2DS1 and KIR3DS1 in sepsis patients when compared to controls were 41.23% versus 55.00% and 36.49% versus 51.67% (p = 0.077 and 0.037 respectively before Bonferroni correction). These results indicate that activating KIR genes 2DS1 and 3DS1 may more prevalent in critical patients without sepsis than in patients with sepsis, suggesting a potential protective role of activating KIR genes in sepsis. (C) 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Kin17 DNA and RNA binding protein (Kin17) is a highly conserved protein that participates in DNA replication, DNA repair and cell cycle progression. Recently, the tumor-promoting function of Kin17 has been demonstrated and increasingly studied. In the present study, the role of Kin17 in the invasion and metastasis of non-small cells lung cancer (NSCLC) was investigated. Elevated Kin17 mRNA and protein expression was identified in a total of 97 NSCLC and benign lung lesion tissue specimens. Kin17 overexpression was significantly correlated with high tumor grade and lymph node metastasis, indicating poor patient prognosis. Scratch and Transwell assays demonstrated that the knockdown of KIN17 inhibited the ability of NSCLC cells to migrate and invade. Furthermore, reverse transcription-quantitative polymerase chain reaction and western blot analyses confirmed that knockdown of KIN17 decreased the expression of matrix metalloproteinase 7, epidermal growth factor receptor and v-myc avian myelocytomatosis viral oncogene homolog. The results of the present study indicate that Kin17 is markedly overexpressed in NSCLC tissues compared with benign lung lesion and peritumoral tissue. The upregulation of KIN17 may serve an important role in the metastasis of NSCLC cells. These results indicate that Kin17 is a novel diagnostic and prognostic biomarker of NSCLC, in addition to being a potential therapeutic target for the treatment of patients with NSCLC.
Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: "KIR3DL1; HLA-BW4-Thr80" and "KIR3DL1 -HLA-BW4-A1." None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.
Background:The klf10 gene could indirectly modify gamma-globin chain production and hence the level of fetal hemoglobin (HbF) ameliorating the phenotype of beta-hemoglobinopathies and the response to hydroxycarbamide (hydroxyurea [HU]) therapy. In this study, we aimed to evaluate the frequency of different genotypes for the klf10 gene in beta-thalassemia major (B-TM), beta-thalassemia intermedia (B-TI), and sickle cell disease (SCD) patients by polymerase chain reaction and to assess its relation to disease phenotypes and HU response. Methods:This cross-sectional study included 75 patients: 50 B-TM, 12 SCD, and 13 B-TI patients (on stable HU dose). The relation of the klf10 gene polymorphism (TIEG, TIEG1, EGR alpha) (rs3191333: c*0.141C >T) to phenotype was studied through baseline mean corpuscular volume, HbF, and transfusion history, whereas evaluation of response to HU therapy was carried out clinically and laboratory. Results:The frequency of the mutant klf10 genotype (TT) and that of the mutant allele (T) was significantly higher among B-TM patients compared with those with B-TI and SCD patients. Only homozygous SCD patients for the wild-type allele within the klf10 gene had a significantly lower transfusion frequency. The percentage of HU responders and nonresponders between different klf10 polymorphic genotypes among B-TI or SCD patients was comparable. Conclusions:Although the klf10 gene does not play a standalone role as an HbF modifier, our data support its importance in ameliorating phenotype among beta-hemoglobinopathies.
Sustainability science is a solution-oriented discipline. Yet, there are few theory-rich discussions about how this orientation structures the efforts of sustainability science. We argue that Niklas Luhmann's social system theory, which explains how societies communicate problems, conceptualize solutions, and identify pathways towards implementation of solutions, is valuable in explaining the general structure of sustainability science. From Luhmann, we focus on two key concepts. First, his notion of resonance offers us a way to account for how sustainability science has attended and responded to environmental risks. As a product of resonance, we reveal solution-oriented research as the strategic coordination of capacities, resources, and information. Second, Luhmann's interests in self-organizing processes explain how sustainability science can simultaneously advance multiple innovations. The value logic that supports this multiplicity of self-organizing activities as a recognition that human and natural systems are complex coupled and mutually influencing. To give form to this theoretical framework, we offer case evidence of renewable energy policy formation in Texas. Although the state's wealth is rooted in a fossil-fuel heritage, Texas generates more electricity from wind than any US state. It is politically antagonistic towards climate-change policy, yet the state's reception of wind energy technology illustrates how social and environmental systems can be strategically aligned to generate solutions that address diverse needs simultaneously. This case demonstrates that isolating climate change-as politicians do as a separate and discrete problem-is incapable of achieving sustainable solutions, and resonance offers researchers a framework for conceptualizing, designing,
Epistemic contextualism is one of the most hotly debated topics in contemporary epistemology. Contextualists claim that know' is a context-sensitive verb associated with different evidential standards in different contexts. Contextualists motivate their view based on a set of behavioural claims. In this paper, I show that several of these behavioural claims are false. I also show that contextualist test cases suffer from a critical confound, which derives from people's tendency to defer to speakers' statements about their own mental states. My evidence consists in results from several behavioural experiments. I conclude that contextualism is an idle hypothesis and I propose some general methodological lessons.
Lung cancer remains the leading cause of cancer-related deaths in both men and women. However, the discovery of several oncogenic driver mutations and the development of immune checkpoint inhibitors resulted in improved clinical outcomes for most patients. Although activating KRAS mutations are the most common recurring molecular events in lung adenocarcinoma, little progress has been made during the past decades with no new agents being approved for this indication. The elucidation of the underlying biology of this diverse patient subgroup offers great potential and renewed hope regarding the rational development, rigorous evaluation and subsequent approval of novel targeted agents and combinations which will effectively suppress compensatory escape routes and the emergence of resistance, issues that have plagued previous attempts. Here, we review in a structured manner all aspects of KRAS positive non small cell lung cancer, including the molecular biology, clinicopathologic characteristics, the prognostic and predictive value of KRAS mutations, as well as previous and contemporary approaches towards the treatment of this elusive target. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
In recent years, molecular biology has proven to be a great asset in our understanding of mechanisms in genodermatoses. However, bench to bedside translation research lags far behind. Advances in lab-on-a chip technologies enabled programmable, reconfigurable, and scalable manipulation of a variety of laboratory procedures. Sample preparation, microfluidic reactions, and continuous monitoring systems can be integrated on a small chip. These advantages have attracted attention in various fields of clinical application including diagnosis of inherited skin diseases. This review lists an overview of the underlying genes and mutations and describes prospective application of lab-on-a-chip technologies as solutions to challenges for point-of-care genodematoses diagnosis. (C) 2016 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in shorter time and with lower reagent consumption than a standard laboratory. Their miniaturization interferes with the multiple functions that the biochemical procedures require. In order to address this issue, our paper presents, for the first time, the integration on a single glass substrate of different thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal treatments and on-chip detection of biomolecules. The proposed System on-Glass hosts thin metal films acting as heating sources; hydrogenated amorphous silicon diodes acting both as temperature sensors to monitor the temperature distribution and photosensors for the on-chip detection and a ground plane ensuring that the heater operation does not affect the photodiode currents. The sequence of the technological steps, the deposition temperatures of the thin films and the parameters of the photolithographic processes have been optimized in order to overcome all the issues of the technological integration. The device has been designed, fabricated and tested for the implementation of DNA amplification through the Polymerase Chain Reaction (PCR) with thermal cycling among three different temperatures on a single site. The glass has been connected to an electronic system that drives the heaters and controls the temperature and light sensors. It has been optically and thermally coupled with another glass hosting a microfluidic network made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR process chamber. The successful DNA amplification has been verified off chip by using a standard fluorometer. (C) 2016 Elsevier B.V. All rights reserved.
Purpose: Labor is thought to positively influence immune system development in the offspring, but studies investigating the impact of different modes of delivery on maternal immune system cells are scarce. Therefore, the aim of this study was to investigate the effect of labor on maternal peripheral blood T-cell subsets and on the recently described regulatory T and B cells. Methods: Cross-sectional study comparing the absolute counts and percentages of peripheral blood T-cell subsets (maturation and activation profiles) and regulatory T and B cells between healthy pregnant women who delivered their newborns via elective cesarean (no labor; n = 14) and those who had a spontaneous vaginal delivery (after labor; n = 18). The cells were characterized using flow cytometry. Results: We found that compared to the women who had elective cesareans, those who had spontaneous vaginal deliveries had significantly (P < .05) lower absolute counts of B cells (median [cells/L]: 146 [interquartile range, IQR = 49] vs 192 [IQR = 65]) and natural killer-like T (NKT-like) cells (median [cells/L]: 154 [IQR = 125] vs 224 [IQR = 117]) in the peripheral blood. No further significant differences, particularly in regulatory T and B cells, were identified between the study groups. Conclusion: Labor does not seem to have a major impact on maternal peripheral blood T-cell subsets or regulatory T and B cells.
Medical biochemistry is the usual name for clinical biochemistry or clinical chemistry in Serbia, and medical biochemist is the official name for the clinical chemist (or clinical biochemist). This is the largest sub-discipline of the laboratory medicine in Serbia. It includes all aspects of clinical chemistry, and also laboratory hematology with coagulation, immunology, etc. Medical biochemistry laboratories in Serbia and medical biochemists as a profession are part of Health Care System and their activities are regulated through: the Health Care Law and rules issued by the Chamber of Medical Biochemists of Serbia. The first continuous and organized education for Medical Biochemists (Clinical Chemists) in Serbia dates from 1945, when the Department of Medical Biochemistry was established at the Pharmaceutical Faculty in Belgrade. In 1987 at the same Faculty a five years undergraduate study program was established, educating Medical Biochemists under a special program. Since the academic year 2006/2007 the new five year undergraduate (according to Bologna Declaration) and four-year postgraduate program according to EC4 European Syllabus for Postgraduate Training in Clinical Chemistry and Laboratory Medicine has been established. The Ministry of Education and Ministry of Public Health accredited these programs. There are four requirements for practicing medical biochemistry in the Health Care System: University Diploma of the Faculty of Pharmacy (Study of Medical Biochemistry), successful completion of the professional exam at the Ministry of Health after completion of one additional year of obligatory practical training in the medical biochemistry laboratories, membership in the Serbian Chamber of Medical Biochemists and licence for skilled work issued by the Serbian Chamber of Medical Biochemists. In order to present laboratory medical biochemistry practice in Serbia this paper will be focused on the following: Serbian national legislation, healthcare services organization, sub-disciplines of laboratory medicine and medical biochemistry as the most significant, education in medical biochemistry, conditions for professional practice in medical biochemistry, continuous quality improvement, and accreditation. Serbian healthcare is based on fundamental principles of universal health coverage and solidarity between all citizens.
Background: In clinical practice, laboratory results are often important for making diagnostic, therapeutic, and prognostic decisions. Interpreting individual results relies on accurate reference intervals and decision limits. Despite the considerable amount of resources in clinical medicine spent on elderly patients, accurate reference intervals for the elderly are rarely available. The SENIORLAB study set out to determine reference intervals in the elderly by investigating a large variety of laboratory parameters in clinical chemistry, hematology, and immunology. Methods/design: The SENIORLAB study is an observational, prospective cohort study. Subjectively healthy residents of Switzerland aged 60 years and older were included for baseline examination (n=1467), where anthropometric measurements were taken, medical history was reviewed, and a fasting blood sample was drawn under optimal preanalytical conditions. More than 110 laboratory parameters were measured, and a biobank was set up. The study participants are followed up every 3 to 5 years for quality of life, morbidity, and mortality. The primary aim is to evaluate different laboratory parameters at age-related reference intervals. The secondary aims of this study include the following: identify associations between different parameters, identify diagnostic characteristics to diagnose different circumstances, identify the prevalence of occult disease in subjectively healthy individuals, and identify the prognostic factors for the investigated outcomes, including mortality. Discussion: To obtain better grounds to justify clinical decisions, specific reference intervals for laboratory parameters of the elderly are needed. Reference intervals are obtained from healthy individuals. A major obstacle when obtaining reference intervals in the elderly is the definition of health in seniors because individuals without any medical condition and any medication are rare in older adulthood. Reference intervals obtained from such individuals cannot be considered representative for seniors in a status of age-specific normal health. In addition to the established methods for determining reference intervals, this longitudinal study utilizes a unique approach, in that survival and long-term well-being are taken as indicators of health in seniors. This approach is expected to provide robust and representative reference intervals that are obtained from an adequate reference population and not a collective of highly selected individuals.
The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course-based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students ' high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast. Initially, student pairs use both qualitative and quantitative assays to assess the ability of their p53 mutant to activate expression of reporter genes, and they localize their mutation within the p53 structure. Through facilitated discussion, students suggest possible molecular explanations for the transactivation defects displayed by their p53 mutants and propose experiments to test these hypotheses that they execute during the second part of the course. They use a western blot to determine whether mutant p53 levels are reduced, a DNA-binding assay to test whether recognition of any of three p53 target sequences is compromised, and fluorescence microscopy to assay nuclear localization. Students studying the same p53 mutant periodically convene to discuss and interpret their combined data. The course culminates in a poster session during which students present their findings to peers, instructors, and the greater biosciences community. Based on our experience, we provide recommendations for the development of similar large introductory lab courses. (C) 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 45(2): 161-178, 2017.
Regional labour force participation across the European Union: a time-space recursive modelling approach with endogenous regressors. Spatial Economic Analysis. Although there is an abundant regional labour market literature taking a spatial perspective, only a few studies have explored extending the analysis of labour force participation with spatial effects. This paper revisits this important issue, proposing a time-space recursive modelling approach that builds on and appraises Fogli and Veldkamp's methodology from 2011 and finding for the United States that participation rates vary with past values in nearby regions. Major shortcomings in their study are corrected for, including stationarity and the control for endogenous regressors other than the time and space-time-lagged dependent variable using system generalized method of moments (GMM). The paper also highlights interaction effects among explanatory variables for the first time in this context. Using a panel of 108 regions across the European Union over 1986-2010, the results for total, male and female participation rates throw a new light on the socio-economic relevance of different determinants. Importantly, characteristics in neighbouring regions play a significant role, and neglecting endogeneity is found to have serious consequences, underlining increased attention on the specification and estimation of spatial econometric models with endogenous regressors.
The taxonomic differentiation among lactic acid bacteria (LAB) using only phenotypic methods is inadequate. In the past, several phenotypic techniques have been applied in identification of different species of LAB from Nigerian indigenous fermented foods. In this study, two less-expensive and rapid molecular techniques were employed in the identification and differentiation of LAB species isolated from some Nigerian fermented foods: gari (cassava mash), fufu (cassava dough) and ogi (maize gruel) to avoid the common errors that are synonymous with the use of conventional methods. The size of the amplified products for the LAB species using universal primers fD1 and rD1 was about 1500 bp. The differentiation of the three predominant LAB, Lactobacillus plantarum, Pediococcus pentosaceus and Weissella confusa to species level was performed by intergenic transcribed spacer (ITS-PCR) and amplified ribosomal DNA restriction analysis (ARDRA) using three restriction endonucleases: HinfI, HaeIII and RsaI. In summary, the study demonstrated that the ARDRA and ITS-PCR analysis are simple, fast and efficient methods that can be used for the routine identification and rapid differentiation of LAB species which are often regularly used as probiotics, starter culture and biopreservative in fermented foods consumed since they are generally regarded as safe (GRAS). (C) 2016 Elsevier Ltd. All rights reserved.
The aim of this study was to compare the concentration of salivary immunoglobulin A (IgA) and the selected interleukins (IL)-1 beta, IL-6, IL-8 and IL-10 in young individuals with presence and non-presence of Lactobacillus reuteri in saliva after a three-week intervention with probiotic lozenges. The study group consisted of 47 healthy individuals aged 18-32 years with no clinical signs of oral inflammation. In a randomised, double-blind, placebo-controlled, cross-over trial participants ingested two lozenges per day containing two strains of the probiotic bacterium L. reuteri or placebo lozenges. The intervention and wash-out periods were three weeks. Stimulated and unstimulated whole saliva was collected at baseline and immediately after termination of the intervention periods. The samples were analysed for total protein, salivary IgA and selected cytokines. In this extended analysis, data were collected by analysing baseline and follow-up saliva samples related to ingestion of the probiotic lozenges for the presence of L. reuteri through DNA-extraction, PCR-amplification and gel-electrophoresis. At baseline, 27% of the individuals displayed presence of L. reuteri and 42% were positive immediately after the three-week probiotic intervention. Individuals with presence of L. reuteri in saliva had significantly higher (P<0.05) concentrations of salivary IgA and %IgA/protein at the termination of the probiotic intake compared with non-presence. No differences in the cytokine levels were observed. In conclusion, detectable levels of L. reuteri in saliva coincided with higher concentrations of salivary IgA and %IgA/protein in stimulated whole saliva after the three-week daily intake of probiotic lozenges. Our findings suggest that monitoring the presence of probiotic candidates in the oral environment is important to interpret and understand their possible immune-modulating role in maintaining oral health.
Tuberculosis (TB) remains among the most deadly diseases in the world. The only available vaccine against tuberculosis is the bacille Calmette-Guerin (BCG) vaccine, which does not ensure full protection in adults. There is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. We are exploring the use of lactic acid bacteria (LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the successful expression and surface display of a Mycobacterium tuberculosis fusion antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus plantarum. The AgE6 fusion antigen was targeted to the bacterial surface using two different anchors, a lipoprotein anchor directing the protein to the cell membrane and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of the two anchors induced antigen-specific proliferative responses in lymphocytes purified from TB-positive donors. Similarly, both strains induced immune responses in mice after nasal or oral immunization. The impact of the anchoring strategies was reflected in dissimilarities in the immune responses generated by the two L. plantarum strains in vivo. The present study comprises an initial step toward the development of L. plantarum as a vector for M. tuberculosis antigen delivery. IMPORTANCE This work presents the development of Lactobacillus plantarum as a candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top infectious diseases worldwide, and the only available vaccine, bacille Calmette-Guerin (BCG), fails to protect adults and adolescents. Direct antigen delivery to mucosal sites is a promising strategy in tuberculosis vaccine development, and lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles for mucosal immunization. We have engineered L. plantarum strains to produce a Mycobacterium tuberculosis fusion antigen and to anchor this antigen to the bacterial cell wall or to the cell membrane. The recombinant strains elicited proliferative antigenspecific T-cell responses in white blood cells from tuberculosis-positive humans and induced specific immune responses after nasal and oral administrations in mice.
PCR detection and quantification of vaginal lactobacilli remains problematic because of the high level of genetic heterogeneity and taxonomic complexity within the genus Lactobacillus. The aim of the present study was to identify conserved sequences among the genomes of major species of vaginal lactobacilli that could be used for the development of a PCR-based method for quantitative determination of vaginal microbiota-specific lactobacilli. Comparative analysis of the genomes of several species of vaginal lactobacilli allowed us to identify conserved regions in the rplK gene, which encodes ribosomal protein L11, and to design group-specific PCR primers and a probe for selected species from the L acidophilus complex, including major vaginal lactobacilli Lactobacillus crispatus, L gasseri, L iners and L jensenii as well as other species that are less common in vaginal microbiota. The applicability of the new assay in routine diagnostic testing was evaluated using a set of clinical samples. The assay was able to detect and quantify vagina-associated lactobacilli within a wide range of initial DNA template concentrations, indicating promising potential for clinical applications. (C) 2016 Elsevier Ltd. All rights reserved.
In the study of engineering, experimentation plays a great role in understanding the concepts. Teaching in engineering is always challenging as theoretical study should be augmented with experiments so that students get a feel of the real life applications of the concepts they study. Automation and control laboratory is an area where students can not verify the ladder diagrams; they develop for various applications, unless they have a Programmable Logic Controller, PLC in the lab. But the new concept of virtual lab has enabled us to teach the concepts of ladder diagrams and development of control systems using PLC very easily. Students could develop ladder diagrams and design digital control systems using the simulation environment given in the virtual lab platform and implement the logics developed by them. Study carried out at institute and the exit surveys shows that the students are more convinced about the results, as they could test them on a platform.
This article shows how Lamarckism was essential in the birth of the French school of molecular biology. We argue that the concept of inheritance of acquired characters positively shaped debates surrounding bacteriophagy and lysogeny in the Pasteurian tradition during the interwar period. During this period the typical Lamarckian account of heredity treated it as the continuation of protoplasmic physiology in daughter cells. F,lix d'H,relle applied this conception to argue that there was only one species of bacteriophage and Jules Bordet applied it to develop an account of bacteriophagy as a transmissible form of autolysis and to analyze the new phenomenon of lysogeny. In a long-standing controversy with Bordet, EugSne Wollman deployed a more morphological understanding of the inheritance of acquired characters, yielding a particulate, but still Lamarckian, account of lysogeny. We then turn to Andr, Lwoff who, with several colleagues, completed Wollman's research program from 1949 to 1953. We examine how he gradually set aside the Lamarckian background, finally removing inheritance of acquired characters from the resulting account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex dual role of Lamarckism as it moved from an assumed explanatory framework to a challenge that the nascent molecular biology had to overcome.
Correct identification of medicinal plant ingredients is essential for their safe use and for the regulation of herbal drug supply chain. Loop-mediated isothermal amplification (LAMP) is a recently developed approach to identify herbal medicine species. This novel molecular biology technique enables timely and accurate testing, especially in settings where infrastructures to support polymerase chain reaction facilities are lacking. Studies that used this method have altered our view on the extent and complexity of herbal medicine identification. In this review, we give an introduction into LAMP analysis, covers the basic principles and important aspects in the development of LAMP analysis method. Then we presented a critical review of the application of LAMP-based methods in detecting and identifying raw medicinal plant materials and their processed products. We also provide a practical standard operating procedure (SOP) for the utilization of the LAMP protocol in herbal authentication, and consider the prospects of LAMP technology in the future developments of herbal medicine identification and the challenges associated with its application.
Pratylenchus zeae parasitizes various crops and damages the host roots, resulting in decreased yield and quality of the host plants. Alignments of mitochondrial DNA (mtDNA) Cytochrome Oxidase I (COI (TM)) sequences revealed the genetic variation among Pratylenchus species. The results indicated 0.2-2.4% intraspecific variations for mtDNA COI sequences among eight P. zeae populations, and 25.4-35.1% interspecific variations between P. zeae and other Pratylenchus species. Based on the mtDNA COI (TM) region, a loop-mediated isothermal amplification (LAMP) assay was developed for the rapid and specific detection of P. zeae. The optimal conditions for the LAMP assay were 64 A degrees C for 40 min. The LAMP products were confirmed using conventional polymerase chain reaction (PCR), analysis with the restriction enzyme Bam HI and visual inspection by adding SYBR Green I to the products. The LAMP assay could detect P. zeae populations from different hosts and different geographical origins specifically. The LAMP assay was also sensitive, detecting 0.1 individual P. zeae, which was 10 times more sensitive than conventional PCR. This is the first report of the detection of Pratylenchus spp. using LAMP. In addition, the results also suggested that use of the COI gene might allow for good resolution at the Pratylenchus species level.
There are two adult life history types among lamprey species, nonparasitic and parasitic, with the former commencing the final interval of sexual maturation immediately after metamorphosis. There are no extensive studies that directly compare hormone profiles during the life cycles of nonparasitic and parastic lamprey species, yet such data may explain differences in development, reproductive maturation, and feeding status. The present study uses immunohistochemistry to show the life cycle profiles for gonadotropin-releasing hormones (GnRH-I and -III) in the brain of the nonparasitic species, the American brook lamprey, Lampetra appendix, for comparison with the extensive, published, immunohistochemical data on these hormones in the parasitic species, the sea lamprey, Petromyzon marinas. The complete cDNAs for the two lamprey prohormones, proopiocortin (POC), and proopiomelanotropin (POM), were cloned for L. appendix and both nuclectide and deduced amino acid sequences were compared with those previously published for P. marinas. The POC and POM cDNAs for both species were used in expression studies, with Northern blotting, throughout their life cycles. Although GnRH-I and -III immunohistochemistry revealed a similar distribution of immunoreactive cells and fibers in the two species during the life cycles, a qualitative evaluation of staining intensity in L. appendix, implied early activity in the brains of metamorphosis of this species, particularly in GnRH-I. GnRH-III seems to be important in larval life and early metamorphosis in both species. A novel feature of this immunohistochemical study is the monthly observations of the distribution and relative intensity of the two GnRHs during the critical period of final sexual maturation that lead to spawning and then the spent animal. L. appendix POC and POM nucleotide sequences had 92.9 and 94.6% identity, respectively, with P. marinus POC and POM and there was an earlier increase in their expression during metamorphosis and postmetamorphic life. Since there was some correlation between the timing of metamorphic development, gonad maturation, and brain irGnRH intensity with POC and POM expression in L. appendix, it was concluded that these prohormones yield posttranslational products that likely play a substantial role in development and maturation events that lead to the nonparasitic adult life history of this species. (c) 2005 Elsevier Inc. All rights reserved.
A simple experimental setup for measuring Planck's constant, using Landauer quantization of the conductance between touching gold wires, is described. It consists of two gold wires with thickness of 500 mu m and 1.5 cm length, and an operational amplifier. The setup costs less than $30 and can be realized in every teaching laboratory in two weeks. The use of an oscilloscope is required.
Over the years, the restorative benefits of the natural environment have been taken seriously. These restorative effects continue to be verified in research from both the psychological and physiological perspectives. The latest functional magnetic resonance imaging (fMRI) technology provides an opportunity to further explore the psychophysiological aspects of these benefits from the natural environment. This study aimed to compare the restorative value of four types of landscape environments (urban, mountain, forest, and water) through questionnaires and by investigating the relationship between the different environments and brain region activity by means of fMRI. Based on a one-way analysis of variance, a significant difference was found between the restorative value of the urban and natural environments the most value being in the water and mountain environments and least in the urban environment. In support of this psychological result, the brain was found to respond similarly, showing increased activity in the visual and attentional focus areas when an urban environment is viewed as opposed to a natural environment. These findings reveal a new approach to test the restorative value of an environment and support the restorative effect of the natural environment. (C) 2017 The Authors. Published by Elsevier B.V.
The Tropical Montane Cloud Forest (TMCF) is a hydrologically unique and highly vulnerable ecosystem to changes in land-use and climate. Assessing the impacts of these changes needs to consider soil-water dynamics. In particular, the organic layer and its functioning requires attention because its difference in water retention characteristics and root density compared to the underlying mineral soils. A higher root density and a higher water storage capacity of the organic layer compared to the mineral soils suggests that most nutrient and water uptake occurs in this layer. However, hydraulic properties of mineral soils and their impact on hydrology of TMCFs have been poorly studied. Here we provide organic layer water retention curves for TMCF soils that were measured in the laboratory. With these data we assessed the potential land-use and climate change impacts on TMCF soil moisture dynamics. From the land-use change perspective, we estimated the water storage capacity loss by slash-and-burn deforestation practices. These estimates show that the storage loss ranges from 35 to 59 mm when TMCFs are converted to pastures. This is several times higher than the estimated TMCF canopy storage capacity (2 to 5 mm). Therefore, the higher peak flow observations in deforested catchments might not only be explained by a decreasing canopy water storage but also likely due to a decreasing soil water storage. From the climate change perspective, we evaluated the effect of contrasting dry season conditions on soil moisture and transpiration using a 1-D water-flow model, and assessed the sensitivity of these hydrological variables to uncertainties in saturated hydraulic conductivity. Although transpiration was not limited by soil moisture during the mild dry season, it was affected during the severe dry season and continued to decline under expected climate change with the prolongation of dry spells. Our results show that the organic layer is a key element in TMCF's hydrological functioning and call for an increased focus on the role of organic soils when evaluating effects of land-use change. (C) 2017 Elsevier B.V. All rights reserved.
A closed loop frequency tracking electronics circuit has been proposed for the measurement of pressure and temperature using a newly developed Langasite (LGS) piezo crystals. The ambient force and heat applied on the LGS crystal produces the shift in its resonant frequency. The proposed closed loop electronics tracks the shift in resonant frequency and measures the pressure and temperature by relating to the difference in frequency shift. The steady state oscillation condition of the resonator circuit is analytically derived and experimentally verified. The experimental setup consists of an operational amplifier based resonator circuit connected to the langasite piezo crystal placed between a double side diametric forces loading device with temperature controller bath. The diametric force applied on the LGS crystal produces the frequency shift in its fundamental mechanical vibration mode (Cmode). Similarly, the change in temperature produces the frequency shift in its second mechanical vibrational mode (Bmode). The frequency shifts are measured using two separate closed loop resonator electronics for two different measurand. Whenever the force on the LGS crystal is changed by the external unknown pressure, an additional intrinsic material property change is added to the piezo and changes the fundamental oscillating resonant frequency. The closed loop resonant circuit tracks the change in resonance frequency and vibrates the LGS with the new resonance frequency depends on the external pressure strength. Similar procedure is followed for temperature induce frequency tracking measurement also. The proposed frequency tracking electronics concept is simple and it is found that it has high sensitivity and linearity.
When two targets are presented within approximately 500 ms of each other in the context of rapid serial visual presentation (RSVP), participants' ability to report the second target is reduced compared to when the targets are presented further apart in time. This phenomenon is known as the attentional blink (AB). The AB is increased in magnitude when the first target is emotionally arousing. Emotionally arousing stimuli can also capture attention and create an AB-like effect even when these stimuli are presented as to-be-ignored distractor items in a single-target RSVP task. This phenomenon is known as emotion-induced blindness (EIB). The phenomenological similarity in the behavioral results associated with the AB with an emotional T1 and EIB suggest that these effects may result from similar underlying mechanisms - a hypothesis that we tested using event-related electrical brain potentials (ERPs). Behavioral results replicated those reported previously, demonstrating an enhanced AB following an emotionally arousing target and a clear EIB effect. In both paradigms highly arousing taboo/sexual words resulted in an increased early posterior negativity (EPN) component that has been suggested to represent early semantic activation and selection for further processing in working memory. In both paradigms taboo/sexual words also produced an increased late positive potential (LPP) component that has been suggested to represent consolidation of a stimulus in working memory. Therefore, ERP results provide evidence that the EIB and emotion-enhanced AB effects share a common underlying mechanism.
It is shown that negative capacitance (NC) circuits can be systematically used to improve the gain-bandwidth product of the operational amplifiers (opamps). The NC circuit moves the nondominant pole of the opamp to higher frequency by decreasing the parasitic capacitance of the critical node. The impedance at the input of the NC circuits is neither purely capacitive nor negative at all frequencies. A design guide is presented by deriving the circuit model for a conventional NC circuit and investigating the extent of the improvement that can be achieved in a circuit by the use of the NC circuit. The model is then used to present the design guide for widebanding the multistage opamps with large capacitive loads. Based on the proposed method, a three-stage opamp with a 15-nF capacitive load was designed and fabricated in a 0.18-mu m CMOS process. The measurements confirm that the opamp satisfies the design target of 1.5-MHz bandwidth at the power consumption of 75 mu W.
The EU Large Combustion Plant Directive (LCPD) is a major but largely unstudied environmental regulation. Most of the 1585 large combustion plants in this analysis are electricity supply plants or combined heat and power plants. We find that, controlling for country characteristics and plant size, plants in the electricity supply, combined heat and power, district heating, and paper industries have a higher probability of being opted-out of the emission limit values (ELVs), which necessitates eventual plant closure. Controlling for plant size and industry, increasing the amount of solid fuel or natural gas utilized at a plant is associated with a decreased likelihood of being opted-out of the ELVs. (C) 2017 Elsevier Ltd. All rights reserved.
We present a scalable computing framework for the solution stochastic multiobjective optimization problems. The proposed framework uses a nested conditional value-at-risk (hCVaR) metric to find compromise solutions among conflicting random objectives. We prove that the associated nCVaR minimization problem can be cast as a standard stochastic programming problem with expected value (linking) constraints. We also show that these problems can be implemented in a modular and compact manner using PLASM (a Julia-based structured modeling framework) and can be solved efficiently using PIPS-NLP (a parallel nonlinear solver). We apply the framework to a CHP design study in which we seek to find compromise solutions that trade-off cost, water, and emissions in the face of uncertainty in electricity and water demands. (C) 2017 Elsevier Ltd. All rights reserved.
Large-array resistive sensors have found a variety of applications from industrial instrumentation to medical wearable applications. In such large-array sensors, several non-idealities limit the accuracy of the readout circuit. In this paper, after analyzing the crosstalk error caused by the input offset voltage and input bias current of the operational amplifier, a novel double-sampling technique is proposed to considerably reduce the error. Spice simulation results of a 20 x 20 array confirm that for a 1-M Omega resistance, the proposed technique can decrease the maximum measureable relative error from 20% to 0.089%. Furthermore, the measurement results of a 20 x 20 array confirm that for a resistance value of 19 M Omega being measured, the proposed technique can reduce the error from 84% to 0.69%.
Background. It has become evident that increased nitric oxide (NO) generation may be associated with production of reactive oxygen species, such as peroxynitrite (ONOO-). Peroxynitrite has been postulated to be responsible for several of the cytotoxic effects previously ascribed to NO. Since cellular arginine uptake has been shown to modulate nitric oxide synthase activity, we were intrigued to study the effect of ONOO- on arginine traffic in renal mesangial cells. Methods. Arginine uptake, CAT-1 and CAT-2 mRNA expression by northern blotting analysis, and CAT-1 protein content using western blotting were determined in mesangial cells pre-treated with peroxynitrite (0.1 and 0.5 mM) for 2 h. Results. Peroxynitrite induced a significant increase in arginine uptake and CAT-2 mRNA expression compared with untreated cells. In contrast, CAT-1 mRNA expression and protein abundance were diminished. Conclusions. In rat mesangial cells, peroxynitrite augments arginine uptake via augmentation of CAT-2 while decreasing CAT-1 expression.
The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-gamma, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. On the other hand, when evaluating the impact of the co-infection on the parasitic burden, co-infected mice presented a marked decrease in the total number of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infettion. Taken together, our major findings suggest that Ascaris and VACV co-infection may potentiate the virus-associated pathology by the down modulation of the VACV-specific immune response. Moreover, this study provides new evidence of how helminth parasites may influence the course of a coincident viral infection. (C) 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
The laryngeal carcinoma related gene 1 (LCRG1) has been implicated as a tumor suppressor in laryngeal cancer. However, the microRNAs (small non-coding RNAs of approximately 22 nucleotides in length) that regulate LCRG1 expression remain elusive. In this study, quantitative PCR analysis first showed that the average level of miR-21-5p was elevated in primary laryngeal carcinoma tissues compared to paired adjacent non-tumor tissues. Thus, we explored the potential regulation of miR-21-5p on LCRG1. PITA algorithm predicted that two sites within LCRG1 mRNA 3'UTR, which reside at +743 position and +938 position, respectively, might be targeted by miR-21-5p. Dual luciferase reporter assay confirmed that miR-21-5p mimic specifically decreased luciferase activity of the reporter harboring 3'UTR+743 target site. With respect to the 3'UTR+938 site, the influence of miR-21-5p on luciferase activity was not sequence specific. Further, we observed that miR-21-5p mimic transfection decreased the LCRG1 protein in human laryngeal carcinoma Hep2 cells as indicated by Western blotting analysis, and promoted cell growth, migration and invasion as evidenced by MTT assay and transwell migration assay and matrigel invasion assay. Of note, the effects of miR-21-5p inhibitor treatment are opposite to those of the miR-21-5p mimic. Taken together, this study identifies that the tumor suppressor LCRG1 is targeted by the oncogenic miR-21-5p. This finding may help us to better understand the dysregulation of cancer-associated genes associated with microRNAs and eventually improve the diagnosis and target therapy for laryngeal carcinoma.
Objective. To determine the presence of human papillomavirus (HPV) in head and neck squamous cell carcinoma, specifically in the larynx without the bias of other sublocations, and to describe the different serotypes of HPV and their impact on overall and disease-free survival after 10-year follow-up. Study Design. Retrospective case series with chart review of ear, nose, and throat oncologic database. Setting. Academic tertiary care hospital. Subjects. A total of 123 samples of larynx squamous cell carcinoma were included, only from the glottis and treated only with surgery between 1977 and 2005. Methods. DNA extraction was carried out by polymerase chain reaction, and subsequent visualization was performed in low-density arrays. Results were compared with histologic, clinicopathologic, and survival parameters, with a 10-year follow-up. Results. HPV DNA was detected in 22.76% (n = 28) of the samples. Eleven genotypes were detected, 2 of which had never been described in the larynx (HPV43 and HPV62). No increasing trend of HPV was observed over time. HPV presence did not correlate with better survival during the follow-up. Smoking was proven as an independent factor in relation to the presence of HPV. Conclusion. HPV may represent a notable factor in the development of a subset of laryngeal squamous cell carcinoma without significant influence on overall and disease-free survival. More studies, including oncogene transcription proteins, would be necessary to draw more relevant conclusions about the relevance of HPV infection in the larynx.
Laser ablation in liquid (LAL) has received considerable attention over the last decade, and is gradually becoming an irreplaceable technique to synthesize nanocrystals and fabricate functional nanostructures because it can offer effective solutions to some challenges in the field of nanotechnology. The goal of this review is to offer a comprehensive summary of recent developments of LAL in nanocrystal synthesis and nanostructure fabrication. First, we will introduce the fundamental processes of microsecond, nanosecond, and femtosecond LAL, and how the active species act differently in plasma, cavitation bubbles, and droplets in the different LAL processes. Second, a variety of LAL-based techniques for nanomaterials synthesis and processing are presented, such as electric-, magnetic-, and temperature-field LAL, as well as electrochemically assisted LAL, pulsed laser deposition in liquid, and laser writing of nanopatterns in liquid. Third, new progress in LALgenerated nanomaterials is described. Fourth, we emphasize five applications of LALgenerated nanomaterials that have emerged recently in the fields of optics, magnetism, environment, energy, and biomedicine. Finally, we consider the core advantages of LAL, the limitations of LAL and corresponding solutions, and the future directions in this promising research area. (C) 2017 The Author(s).
Laser-based additive manufacturing has attracted much attention as a promising 3D printing method for metallic components in recent years. However, surface roughness of additive manufactured components has been considered as a challenge to achieve high performance. In this work, we demonstrate the capability of fiber laser in polishing rough surface of additive manufactured Ti-based alloys as Ti-6A1-4V and TC11. Both as-received surface and laser-polished surfaces as well as cross-section subsurfaces were analyzed carefully by White-Light Interference, Confocal Microscope, Focus Ion Beam, Scanning Electron Microscopy, Energy Dispersive Spectrometer, and X-ray Diffraction. Results revealed that as-received Ti-based alloys with surface roughness more than 5 ism could be reduce to less than 1 pm through laser polishing process. Moreover, microstructure, microhardness and wear resistance of laser-polished zone was investigated in order to examine the thermal effect of laser polishing processing on the substrate of additive manufactured Ti alloys. This proof-of-concept process has the potential to effectively improve the surface roughness of additive manufactured metallic alloy by local polishing method without damage to the substrate.
Late-life depression (LLD) is a common emotional and mental disability in the elderly population characterized by the presence of depressed mood, the loss of interest or pleasure in daily activities, and other depression symptoms. It has a serious effect on the quality of life of elderly individuals and increases their risk of developing physical and mental diseases. It is an important area of research, given the growing elderly population. Brain functional connectivity modifications represent one of the neurobiological biomarker for LLD even if to date remains poorly understood. In our study, we enrolled 10 elderly patients with depressive symptoms compared to 11 age-matched healthy controls. All participants were evaluated by means of neuropsychological tests and underwent the same functional magnetic resonance imaging (fMRI) protocol to evaluate modifications of brain resting state functional connectivity. Between-group differences were observed for the Geriatric Depression Scale and Hamilton Depression Rating Scale, with higher scores for patients with LLD. Voxel-wise, 1-way analysis of variance revealed between-group differences in left frontoparietal network (lFPN) and sensory motor network (SMN): Increased intrinsic connectivity in the LLD group was observed in the left dorsolateral prefrontal cortex and in the left superior parietal lobule of the lFPN and increased intrinsic connectivity in the LLD group was observed in the bilateral primary somatosensory cortex of the SMN. Our findings support the use of resting state fMRI as a potential biomarker for LLD; even if to confirm the relationship between brain changes and the pathophysiology of LLD, longitudinal neuroimaging studies are required.
A novel three-dimensional DNA-AuNPs network structure amplification strategy was employed to design a lateral flow biosensor by introducing streptavidin coated gold nanoparticles (Au-SA) in this paper. They act as amplification probes which aggregate numerous gold nanoparticles (AuNPs) on test line by forming a threedimensional DNA-AuNPs network structure in the presence of target. Sensitive detection of nucleic acid with point-of-care analysis is significant for infectious agent, early diagnosis and treatment of genetic diseases. The use of these particles in rapid ultrasensitive point of care (POC) lateral flow assays lead to a linear range from 0.1 pM to 250 nM with a limit of detection of 0.01 pM without polymerase chain reaction (PCR). The proposed method could increase the sensitivity by 4 orders of magnitudes than traditional sandwich assays labeled with AuNPs. Furthermore, the assay owns good reproducibility and stability, which will prove practical diagnostic applications.
IntroductionThe etiological diagnosis of pleural effusion is a difficult task because the diagnostic tools can only establish a definitive etiological diagnosis in at most 76% of cases. ObjectivesTo verify the diagnostic accuracy of the latex agglutination test (LAT) for the etiological diagnosis of pleural effusions caused by Streptococcus pneumoniae and Haemophilus influenzae type b. MethodsAfter thoracocentesis, paired fresh samples of pleural fluid from 418 children and adolescents were included in this investigation. They were tested blindly and simultaneously through counterimmunoelectrophoresis (CIE) and LAT for both bacteria. Sensitivity, specificity, predictive values and likelihood ratios (LR) were calculated taking CIE as a reference standard. ResultsThe sensitivity and specificity of LAT was 100% (95% confidence interval, 94.4%-100%) and 83.3% (95% confidence interval, 79.0%-87.0%), respectively, whereas the positive (calculated from Bayes' theorem) and negative predictive values were, respectively, lower than 1% and 100% (95% confidence interval, 98.8%-100%). Positive and negative LR were 6.0 (95% confidence interval, 4.7-7.6) and zero, respectively. ConclusionsOur results suggest that LAT is a useful tool for the etiological diagnosis of pleural effusion. It is a reliable, rapid, simple to perform and shows an excellent yield in our studied population, helping to prescribe appropriate antibiotics for this clinical condition.
This paper examined the prevalence of depressive symptomotology among women of Mexican ancestry (N = 205), over the age of 18, of diverse incomes and nativity. We examined differences in rates of diagnosis by Spanish/English preference and the sensitivity and specificity of three common measures: the Patient Health Questionnaire (PHQ9), the Kessler Psychological Distress Scale (K-10), and depression questions from the Composite International Diagnostic Interview, Short Form (MDD CIDI-SF); PHQ9 was used as the "gold standard" measure. Results indicated 18-32 % of participants met criteria for depression with higher rates found among Spanish preference participants. The K-10 had significantly higher sensitivity (0.81) but lower specificity (0.79) than the MDD CIDI-SF items (0.57 and 0.89, respectively). This study suggests that the K-10 and MDD CIDI-SF measures are complementary to each other for screening of depressive symptomatology. Implications for cultural and linguistic assessment of depression are further discussed.
Objective: The purpose of this study was to present a case report and review the relevant literature on laxative-induced dermatitis being mistaken for scald injury and child abuse. Case: A 33-month-old girl presented with partial thickness burn to the buttocks and perineum, which were suspected to be caused by child abuse. On further investigation, the parents had been administering large doses of laxatives to the child for chronic constipation. Discussion: Child abuse by burning has characteristic physical examination findings, which differ from the pattern of laxative-induced dermatitis that has been reported in the literature. Diapers appear to be a risk factor for laxative-induced dermatitis. Surprisingly, the dose of laxative does not correlate with the severity of the burn injury. All physicians must be aware of the possibility of laxative-induced dermatitis mimicking scald burn injury to the buttocks. Parents should be educated about the risk of administering over-the-counter laxatives to children.
With the increasing applications of ionic liquids (ILs), the toxicity of ILs has drawn increasing attention in recent years, especially the influences of different anions and alkyl-chain lengths on the acute toxicity to aquatic organisms. We performed a study on the acute toxicity of 1-alkyl-3-methylimidazolium nitrate ([C(n)mim]NO3] (n = 2, 4, 6, 8, 10, 12)), 1-hexyl-3-methylimidazolium ILs ([C(6)mim]R (R = Cl-, Br-, BF4-, PF6-)) to zebrafish (Danio rerio). We also evaluated the sensibility of the investigated animals and the stability of ILs in water via high performance liquid chromatography (HPLC, Agilent 1260, Agilent Technologies Inc., USA) to prove the reliability of the present study. The results illustrated that the test zebrafish (Danio rerio) were sensitive to the reference toxicant and that the investigated ILs in water were stable. The 50% lethal concentration (LC50) was used to represent the acute toxicity to zebrafish (Dario rerio). The present study showed that the highest toxic IL is [C(12)mim]NO3 and the lowest toxic IL is [C(2)mim]NO(3)on Danio rerio. The LC(50)s for ILs with different anions had similar values. Accordingly, we believe that ILs with different alkyl-chain lengths cause greater effects than other anions on acute toxicity to aquatic organisms. Furthermore, the present study can also provide scientific methods for future studies to select and assess ILs.
The growing demand for electric vehicles entails an increased consumption of critical energetic and non-energetic abiotic resources, necessary for an optimal performance of the vehicle. The depletion of these resources and the future availability to meet their demand appears to be a potential limitation for the expansion of the electrified vehicle industry. The goal of this study is to perform a detailed life cycle analysis, including manufacturing, use and disposal, of key components of EV powertrains, identifying materials and processes responsible for abiotic depletion impact. This study also investigates the sensitivity of the results to the choice of Life Cycle Assessment (LCA) impact methods. For this, a LCA is performed on an integrated electric drive, by considering seven impact methods. Results show that energetic resources consumption generate the largest impact, followed by metals and lastly by mineral resources. The consumption of electricity in each life cycle is a crucial factor in the generation of total impact. There are agreements among methods on the materials and processes contributing the most to depletion, given the differences in approach used by each impact method. (C) 2016 Elsevier B.V. All rights reserved.
Purpose Application of zero valent iron nanoparticles is an innovative technology for ground water treatment and soil remediation. There are several methods to synthesise nano scale zero valent iron (nZVI), namely through bottom-up methods which consists on chemical reactions using strong reducing agents. In this work, the environmental impacts and costs were determined for two methods, namely the traditional one that uses sodium borohydride and the green method that uses extracts obtained from natural products. Methods The consideration of environment and economic aspects in the earlier stages of the synthesis processes and in the development of new materials is of great importance since it can help to decide if alternative methods are promising and should be further developed aiming more sustainable processes. In this work, life cycle assessment (LCA) was used as an ecodesign strategy evaluating environmental performance of the two synthesis methods, identifying critical stages of the synthesis processes of nZVI. An economic evaluation and a sensitivity analysis considering a different scenario for electricity production were also performed. Results and discussion The results obtained in this study showed that the green synthesis method presents lower environmental impacts than the traditional one, roughly 50% lower in the first scenario. In the second scenario, environmental impact of green synthesis corresponds to 38% of the environmental impact of traditional synthesis. In the green method, the critical stage is the extraction process which is closely related to the electricity production. In the traditional method, the reactant use is the critical stage that is related to the production of sodium borohydride. The economic evaluation indicated that the traditional synthesis method is much more expensive than the green synthesis (roughly eight times higher). Conclusions From the results obtained, it is possible to conclude that the green synthesis method presents lower environmental impacts in both scenarios and lower costs than the traditional synthesis.
Lead (Pb) in public drinking water supplies has garnered much attention since the outset of the Flint water crisis. Pb is a known hazard in multiple environmental matrices, exposure from which results in long-term deleterious health effects in humans. This discussion paper aims to provide a succinct account of environmental Pb exposures with a focus on water Pb levels (WLLs) in the United States. It is understood that there is a strong correlation between WLLs and blood Pb levels (BLLs), and the associated health effects. However, within the Flint water crisis, more than water chemistry and Pb exposure occurred. A cascade of regulatory and bureaucratic failures culminated in the Flint water crisis. This paper will discuss pertinent regulations and responses including their limitations after an overview of the public health effects from Pb exposure as well as discussion on our limitations on monitoring and mitigating Pb in tap water. As the Flint water crisis also included increased Legionnares' disease, caused by Legionella pneumophila, this paper will discuss factors influencing L. pneumophila growth. This will highlight the systemic nature of changes to water chemistry and public health impacts. As we critically analyze these important aspects of water research, we offer discussions to stimulate future water quality research from a new and systemic perspective to inform and guide public health decision-making. (C) 2017 Elsevier B.V. All rights reserved.
Eliminating the leakage current is one of the most important issues for transformerless three-phase photovoltaic (PV) systems. In this paper, the leakage current elimination of a three-phase four-leg PV inverter is investigated. With the common-mode loop model established, the generation mechanism of the leakage current is clearly identified. Different typical carrier-based modulation methods and their corresponding common-mode voltages are discussed. A new modulation strategy with Boolean logic function is proposed to achieve the constant common-mode voltage for the leakage current reduction. Finally, the different modulation methods are implemented and tested on the TMS320F28335 DSP +XC3S400 FPGA digital control platform. The experimental results verify the effectiveness of the proposed solution.
The human left inferior parietal lobule (LIPL) plays a pivotal role in many cognitive functions and is an important node in the default mode network (DMN). Although many previous studies have proposed different parcellation schemes for the LIPL, the detailed functional organization of the LIPL and the exact correspondence between the DMN and LIPL subregions remain unclear. Mounting evidence indicates that spontaneous fluctuations in the brain are strongly associated with cognitive performance at the behavioral level. However, whether a consistent functional topographic organization of the LIPL during rest and under task can be revealed remains unknown. Here, they used resting- state functional connectivity (RSFC) and task- related coactivation patterns separately to parcellate the LIPL and identified seven subregions. Four subregions were located in the supramarginal gyrus (SMG) and three subregions were located in the angular gyrus (AG). The subregion- specific networks and functional characterization revealed that the four anterior subregions were found to be primarily involved in sensorimotor processing, movement imagination and inhibitory control, audition perception and speech processing, and social cognition, whereas the three posterior subregions were mainly involved in episodic memory, semantic processing, and spatial cognition. The results revealed a detailed functional organization of the LIPL and suggested that the LIPL is a functionally heterogeneous area. In addition, the present study demonstrated that the functional architecture of the LIPL during rest corresponds with that found in task processing. (C) 2017Wiley Periodicals, Inc.
Forensic clinical anatomy is a new practical application of the discipline of Clinical Anatomy for ascertaining and evaluating medicolegal questions. In particular, individual anatomy (normal anatomy, anatomical variations, age-, disease-, or surgery-related modifications) can acquire significant relevance in various fields of legal medicine such as child abuse, sudden death, medical responsibility and/or liability, personal injury and damage. Anatomical data of forensic interest frequently arise from the correct application of methods of ascertainment; anatomical methods may then be required for further comprehensive analysis. The rigorous interpretation of anatomical data, derived from the ascertainment phase and analyzed on the basis of pertinent literature, can be pivotal for the correct application of evaluation criteria in various forensic contexts. Clin. Anat. 30:2-5, 2017. (c) 2016 Wiley Periodicals, Inc.
The Rhizobia are collectively comprised of gram negative soil bacteria that have the ability to form symbiotic nitrogen-fixing root and/or stem nodules in association with leguminous plants. The taxonomy of these bacteria is continually in a state of flux, in large part due to rapid development of refined molecular biology techniques. The isolation and characterization of new, and often different, legumes-nodulating bacteria on a variety of plant hosts has resulted in the naming of many new rhizobial species. Here we update the taxonomy of the legume-nodulating bacteria and describe newly identified rhizobia capable of nodulating edible legumes and legume trees. In 1990, there was only one bacterial species that was known to nodulate common bean worldwide (Rhizobium leguminosarum sv. phaseoli), one species that nodulated faba bean (Rhizobium leguminosarum sv. viciae), and two species that nodulated soybean (Bradyrhizobium japonicum and Rhizobium fredii). Today, nearly 14, 11, 6, 5, 5, 4, 3 and 2 species have been defined that are capable of nodulating common bean, soybean, cowpea, chickpea, peanut, lentils, faba bean and pea, respectively. The recent use of whole genome based taxonomy (genomotaxonomy) will surely change how we define this important group of bacteria. The identification of several rhizobial species that are able to nodulate and fix nitrogen with edible legumes may enhance the production of these crops and can compensate for worldwide deficiencies in human nutritional needs in the future.
Background: Leishmania use exosomes to communicate with their mammalian hosts and these secreted vesicles appear to contribute to pathogenesis by delivering protein virulence factors to macrophages. In other eukaryotes, exosomes were found to carry RNA cargo, such as mRNAs and small non-coding RNAs, capable of altering recipient cell phenotype. Whether leishmania exosomes also contain RNAs which they are able to deliver to bystander cells is not known. Here, we show that leishmania exosomes indeed contain RNAs and compare and contrast the RNA content of exosomes released by Leishmania donovani and Leishmania braziliensis. Results: We purified RNA from exosomes collected from axenic amastigote culture supernatant and found that when compared with total leishmania RNA, exosomes mainly contained short RNA sequences. Exosomes with intact membranes were capable of protecting their RNA cargo from degradation by RNase. Moreover, exosome RNA cargo was delivered to host cell cytoplasm in vitro. Sequencing of exosomal RNA indicated that the majority of cargo sequences were derived from non-coding RNA species such as rRNA and tRNA. In depth analysis revealed the presence of tRNA-derived small RNAs, a novel RNA type with suspected regulatory functions. Northern blotting confirmed the specific and selective enrichment of tRNA-derived small RNAs in exosomes. We also identified a number of novel transcripts, which appeared to be specifically enriched in exosomes compared to total cell RNA. In addition, we observed the presence of sequences mapping to siRNA-coding regions in L. braziliensis, but not in L. donovani exosomes. Conclusions: These results show that leishmania exosomes are selectively and specifically enriched in small RNAs derived almost exclusively from non-coding RNAs. These exosomes are competent to deliver their cargo of novel, potential small regulatory RNAs to macrophages where they may influence parasite-host cell interactions. The remarkably high degree of congruence in exosomal RNA content between L. donovani and L. braziliensis, argues for the presence of a conserved mechanism for exosomal RNA packaging in leishmania. These findings open up a new avenue of research on non-canonical, small RNA pathways in this trypanosomatid, which may elucidate pathogenesis and identify novel therapeutic approaches.
Leishmaniasis is an arthropod-borne disease that affects approximately 2 million people worldwide annually. The aims of this study were to detect the presence of Leishmania (Kinetoplastida: Trypanosomatidae) DNA and the feeding preferences of probable vector species in an endemic focus of Leishmania infantum in Turkey. Entomological sampling was performed in August and October 2015 in Aydn province, where cases of human and canine leishmaniasis have been reported previously. A total of 1059 sandfly specimens comprising nine species belonging to two genera, Phlebotomus and Sergentomyia (both: Diptera: Psychodidae), and five subgenera of the Phlebotomus genus (Phlebotomus, Paraphlebotomus, Larroussius, Adlerius and Transphlebotomus) were collected in five villages. Among all Phlebotomus specimens, Phlebotomus neglectus (39%) was noted as the most abundant species, followed by Phlebotomus tobbi (18%). LeishmaniaDNA was detected in pools from P.neglectus, P.tobbi and Sergentomyia dentata by kDNA polymerase chain reaction (PCR). LeishmaniaDNA from Phlebotomus specimens was identified as L.infantum, but LeishmaniaDNA from Sergentomyia spp. could not be identified to species level by ITS-1 real-time PCR. The detection of LeishmaniaDNA in wild-caught P.neglectus and the high percentage (24.2%) of human DNA in engorged specimens suggests that P.neglectus is probably an important vector species for L.infantum in Aydn province.
Transmission of canine leishmaniosis (CanL) is described in three consecutive generations of female Boxers living in a non-endemic environment in the Czech Republic. Infection of the first generation female likely occurred during a breeding visit to Italy and the dog died with typical clinical signs of the disease but without definitive laboratory diagnosis. The second and third generation offsprings never left the Czech Republic, suffered from clinical CanL confirmed by polymerase chain reaction and serology, and were apparently infected by transplacental transmission. Persistence of CanL in the Czech Republic over 7 years with a suspected origin in an endemic region and progression of infection through subsequent generations in a non-endemic country exemplifies that this disease may establish itself also in areas where no obvious vectors are present. (C) 2017 Published by Elsevier B.V.
Lemur tyrosine kinase-3 (LMTK3) is a member of the serine/threonine tyrosine kinase family, which is thought to be involved in tumor progression and prognosis. The purpose of the present study was to determine the diagnostic significance and therapeutic targets in thyroid cancer. ELISA assay was used to detect the protein expression of serum LMTK3. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were employed to measure the expression of LMTK3. Flow cytometry was used to determine the cell cycle. Transwell assay was used to measure the invasion and migration of SW579 cells and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect cell apoptosis. The LMTK3 level was positively associated with disease stage and pathological type, whereas there was no correlation between LMTK3 level and gender, age, tumor size or lymph node metastasis. The serum LMTK3 level was significantly increased in 102 thyroid carcinoma patients compared with 52 benign thyroid tumor patients and 50 healthy volunteers (P= 0.001). The protein and mRNA expression of LMTK3 was markedly higher in thyroid cancer patients compared with patients with benign thyroid tumors. Notably, LMTK3 knockdown retarded proliferation, invasion and migration in SW579 cells. In addition, downregulation of LMTK3 promoted apoptosis in SW579 cells. These findings indicated that LMTK3 knockdown retards the growth of thyroid cancer cells partly through inhibiting proliferation, invasion, migration and inducing apoptosis in SW579 cells. It may serve as a useful diagnostic biomarker and a novel therapeutic target for patients with thyroid cancer.
Objectives: To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia. Methods: We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism. Results: More patients in the good response group (27%) had LEPR Q223R than in the bad response group (16%, P =.046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPR Q223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline (P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 +/- 0.92, P =.036) and total cholesterol levels (change: -1.77 +/- 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant. Conclusion: LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.
Leptospirosis is a systemic infection that causes, among others, acute kidney injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and reproductive loss. In an effort to reduce uterine inflammatory responses induced by Leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and astragalin in a mouse model. Our results showed that treatment with emodin, thymol, and astragalin alleviated uterine inflammation induced by leptospira infection via suppression of pro-inflammatory cytokine expression and prevented tissue damage. Furthermore, we used primary endometrium epithelial cells to show that treatment with these chemicals inhibited the expression of proinflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Western blot results showed that these chemicals suppressed the phosphorylation of p38, p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. These results indicate that treatment with emodin, thymol, and astragalin suppressed inflammatory response by regulating NF-kappa B and mitogen-activated protein kinase signaling pathways in leptospira-infected uterine and endometrium epithelial cells of mice.
With the increasing use of real-time PCR techniques, Leptospira isolation has mostly been abandoned for the diagnosis of human leptospirosis. However, there is a great value of collecting Leptospira isolates to better understand the epidemiology of this complex zoonosis and to provide the researchers with different isolates. In this study, we have successfully isolated different Leptospira strains from BacT/Alert aerobic blood culture bottles and suggest that this privileged biological material offers an opportunity to isolate leptospires. (C) 2017 Elsevier Inc. All rights reserved.
Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder of purine metabolism caused by a mutation in Xq26.2-q26.3 (OMIM 308000.0004). The presence of the diagnostic triad, i.e. signs of self-injurious behavior (SIB) and results of pedigree analysis and novel molecular biology & genetic testing, confirms the diagnosis of LNS. With a level of hypoxanthine guanine phosphoribosyl-transferase 1 (HPRT1) enzyme activity < 2%, patients develop neurological, neurocognitive, and neuromotor symptoms along with SIB. Described here is a case of 4-year-old boy who was diagnosed with LNS. The boy displayed SIB, i.e. biting of the lips and fingers, and he had cerebral venous sinus thrombosis caused by LNS.
In human leukaemia, resistance to chemotherapy leads to treatment ineffectiveness or failure. Previous studies have indicated that cancers with increased levels of aerobic glycolysis are insensitive to numerous forms of chemotherapy and respond poorly to radiotherapy. Whether glycolysis serves a key role in drug resistance of leukaemia cells remains unclear. The present study systematically investigated aerobic glycolytic alterations and regulation in K562/adriamycin (ADM) multidrug-resistant (MDR) and ADM-sensitive K562 leukaemia cells in normoxia, and the association between drug resistance and improper glycometabolism. The cell proliferating activity was assessed with an MTT colorimetric assay, glycolysis, including glucose consumption, lactate export and key-enzyme activity was determined by corresponding commercial testing kits. The expression levels of hexokinase-II (HK-II), lactate dehydrogenase A (LDHA), glucose transporter-4 (GLUT-4), AKT, p-AKT473/308, mammalian target of rapamycin (mTOR), p-mTOR, c-Myc and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were analyzed by western blot or reverse transcription-quantitative polymerase chain reaction (RT-qPCR). K562/ADM cells exhibited increased glucose consumption and lactate accumulation, increased lactate dehydrogenase, hexokinase and pyruvate kinase activities, and reduced phosphofructokinase activity. In addition, K562/ADM cells expressed significantly more HK-II and GLUT-4. Notably, inhibition of glycolysis effectively killed sensitive and resistant leukaemia cells and potently restored the sensitivity of MDR cells to the anticancer agent ADM. The AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (mTOR) signalling pathway, a crucial regulator of glycometabolic homeostasis, mediated over-activation and upregulation of c-Myc expression levels in K562/ADM cells, which directly stimulated glucose consumption and enhanced glycolysis. In conclusion, the present study demonstrated that MDR leukaemia cells exhibit increased aerobic glycolytic activity and that this may be responsible for resistance to chemotherapeutics in leukaemia MDR cells via activation of the AKT-mTOR-c-Myc signalling pathway. Therefore, inhibition of aerobic glycolysis may be a potential therapeutic strategy to efficiently treat multidrug resistance in relapsed or refractory leukaemia and cancers.
To observe the biological characteristic and the prognoses in patients with acute erythroleukemia (AEL). The results of 167 patients with newly diagnosed AEL, from January 2004 and June 2014 in the department of Hematology, Shandong Province Chinese Medicine Hospital, were reviewed by morphology, immunology, cytogenetics, molecular biology. Flow cytometry analysis indicated that CD13 (96.1 %), CD33 (95.1 %), CD117 (87.4 %) and CD34 (79.4 %) were highly expressed in AEL. 56 of 148 (37.8 %) AEL patients had a variety of cytogenetic abnormalities, 27 of 148 (18.2 %) patients were complex karyotype (abnormal involving 3 or more chromosomes), the abnormalities of chromosomes 3, 5, 7 and 8 were more frequently involved and the most common one was +8, accounting for 35.7 % of all abnormal karyotype, followed by 5q- (17.9 %). Mutation analysis showed CEBPA mutation ratio of AEL patients was 44.0 % (11/25), that of NPM1as 15.4 % (4/26). Initial induced remission rate of AEL was 56.6 % (30/53), compared by 33.3 % (4/12) of MDSM6. Survival analysis was shown that the overall survival in female was better than that in male (P = 0.047). The overall survival time of transplantation group was significantly longer than chemotherapy group (P = 0.000). The OS of 13-39 years old group was the best, 40-49 years old group took second place, >50 years old group appeared to be the worst. Patients with AML-M-6 had dysplasia in varying degrees in granulocyte, erythrocyte and megakaryocyte series. Periodic acid-Shiff reaction staining in polychromatic erythroblast and ortho-chromatic erythroblast had a specificity in the diagnosis of AEL. AEL had its own unique biological features, and allogeneic hematopoietic stem cell transplantation could significantly improve its poor prognosis.
This paper sets forth a novel approach to calculate the levelized cost of electricity (LCOE) using a probabilistic model that accounts for endogenous input parameters. The approach is applied to the example of a nuclear and gas power project. Monte Carlo simulation results show that a correlation between input parameters has a significant effect on the model outcome. By controlling for endogeneity, a statistically significant difference in the mean LCOE estimate and a change in the order of input leverages is observed. Moreover, the paper discusses the role of discounting options and external costs in detail. In contrast to the gas power project, the economic viability of the nuclear project is considerably weaker. (C) 2017 Elsevier Ltd. All rights reserved.
Analysis of microarray data obtained by comparing gene expression between 2-week-old infant and 7-week-old mature SD rat testes revealed novel targets involved in tumor suppression. Reverse-transcription polymerase chain reaction and Northern blotting indicated that Tusc3 gene expression was upregulated in the normal maturing testis and prostate and other organs such as the cerebrum and ovary. Tumor suppressor candidate 3 protein expression was detected in these same organs at a size of about 40 kDa, in accord with the predicted molecular size. In situ hybridization and immunohistochemistry showed that mRNA and protein localization were prevalent in the testis spermatocytes and interstitial cells such as the Leydig cells, as well as prostate epithelial cells. These data suggest that TUSC3 is deeply involved in spermatogenesis in the testis, inducing sperm differentiation and maturation, and plays a role in normal prostate development and tumor suppression.
Individuals are not merely passive vessels of whatever beliefs and opinions they have been exposed to; rather, they are attracted to belief systems that resonate with their own psychological needs and interests, including epistemic, existential, and relational needs to attain certainty, security, and social belongingness. Jost, Glaser, Kruglanski, and Sulloway (2003) demonstrated that needs to manage uncertainty and threat were associated with core values of political conservatism, namely respect for tradition and acceptance of inequality. Since 2003 there have been far more studies on the psychology of left-right ideology than in the preceding half century, and their empirical yield helps to address lingering questions and criticisms. We have identified 181 studies of epistemic motivation (involving 130,000 individual participants) and nearly 100 studies of existential motivation (involving 360,000 participants). These databases, which are much larger and more heterogeneous than those used in previous meta-analyses, confirm that significant ideological asymmetries exist with respect to dogmatism, cognitive/perceptual rigidity, personal needs for order/structure/closure, integrative complexity, tolerance of ambiguity/uncertainty, need for cognition, cognitive reflection, self-deception, and subjective perceptions of threat. Exposure to objectively threatening circumstances-such as terrorist attacks, governmental warnings, and shifts in racial demography-contribute to modest "conservative shifts" in public opinion. There are also ideological asymmetries in relational motivation, including the desire to share reality, perceptions of within-group consensus, collective self-efficacy, homogeneity of social networks, and the tendency to trust the government more when one's own political party is in power. Although some object to the very notion that there are meaningful psychological differences between leftists and rightists, the identification of "elective affinities" between cognitive-motivational processes and contents of specific belief systems is essential to the study of political psychology. Political psychologists may contribute to the development of a good society not by downplaying ideological differences or advocating "Swiss-style neutrality" when it comes to human values, but by investigating such phenomena critically, even-or perhaps especially-when there is pressure in society to view them uncritically.
To decrease the use of fossil fuels and face the energetic demand, the integration of renewable energy is a necessary step. Part of this renewable energy can be supplied by the production of electricity from photovoltaic panels and windfarms. The massive use of these intermittent energies will lead to overproduction periods, and there is consequently a need to convert this surplus of electricity into a storable form of energy. Power-to-gas (PtG) technology consists in using electricity to convert water into hydrogen by electrolysis, and then to synthetize methane from carbon dioxide and hydrogen. Techno-economic and Life Cycle Assessment of methane production via the combination of anaerobic digestion and PtG technology have been applied to sewage sludge valorization. Process studies and equipment design have been addressed considering already available technologies. Sensitivity analyses have been done on biogas upgrading technologies, electricity prices, annual operation time and composition of the electricity mix with also a comparison between PtG and direct injection. It appears that the more the electricity is expensive, the longer the operation time of the methanation process must be to be competitive with injection of methane from biogas. Reduction of electricity consumption of the electrolysis step decreases production costs. Even if the current context does not feature adapted conditions to ensure an economically viable chain, the evolution of the energetic context in the next few years as well as the expected technological improvements will contribute to overall cost reduction. From an environmental point of view, continuous PtG generates more greenhouse gases than direct injection, but intermittent operation with use of renewable electricity can significantly reduce GHG emissions. From an endpoint impacts perspective, impact from continuous PtG are higher than biogas upgrading, but much lower than fossil energy. Future development of low electricity consumption of the electrolysis process, and integration of renewable credits from CO2 valorization can increase the competitiveness of this technology. (C) 2016 Published by Elsevier Ltd.
Electrical arcs emit extremely high intensity light across a wide spectrum that can damage eye delicate structures, such as the cornea or the retina. Developing industry safety standards to mitigate light hazards is a critical component of arc flash safety. Accurate measurement of light intensity is the first step in understanding the level of eye protection needed. Traditionally, light measurement devices are an assembly of light detecting resistors made from cadmium sulfide (CdS) or silicon (Si) cells. However, their response times are inadequate for capturing the peak light intensity or the dynamic changes during the initial arc flash. In addition, the brightness of an arc flash is greater than the measurable light levels from traditional light measurement devices. Furthermore the light sensitivity of traditional sensors does not match the Commission Internationale de l'Eclairage (CIE) luminosity function V(lambda) curve, which defines the human eye's sensitivity to bright light as a function of wavelength under typical ambient light conditions. This paper discusses a novel light measurement technique to overcome the limitations of traditional approaches. This design is capable of measuring the light intensity of the arc flash as perceived by human eyes. These results can be used to evaluate the potential of an arc flash to harm the eyes.
The use of laser microbeams and optical tweezers in a wide field of biological applications from genomic to immunology is discussed. Microperforation is used to introduce a welldefined amount of molecules into cells for genetic engineering and optical imaging. The microwelding of two cells induced by a laser microbeam combines their genetic outfit. Microdissection allows specific regions of genomes to be isolated from a whole set of chromosomes. Handling the cells with optical tweezers supports investigation on the attack of immune systems against diseased or cancerous cells. With the help of laser microbeams, heart infarction can be simulated, and optical tweezers support studies on the heartbeat. Finally, laser microbeams are used to induce DNA damage in living cells for studies on cancer and ageing.
Conversion of lignocellulosic biomass to electricity using fuel cell technologies is a promising but challenging research topic for sustainable electricity production. This is because that lignocellulosic biomass generally cannot be directly used as a fuel for electricity generation in a conventional fuel cell with high efficiency. Typical fuel cells that can convert lignocellulosic biomass to electricity under mild conditions (< 100 degrees C) include microbial fuel cells (MFC) and novel direct biomass fuel cells (DBFC) such as that mediated by polyoxo-metalates (POMs) developed recently. However, the efficiency and power output for these low-temperature fuel cells still need to be improved for practical applications. In this review, we focus on the research advances of electricity generation in fuel cells that can be operated at low temperatures. More specifically, we discussed the progress, challenge and perspectives of biomass-fueled MFCs. Recent interesting researches on DBFC were also highlighted in terms of the efficiency, principles, and technological obstacles. As concluded in this work, lignocellulosic biomass is a promising feedstock for fuel cells because it is renewable, carbon neutral, and sustainable. However, the power density of lignocelluose-fueled MFC are usually far below that required for commercial applications. Improving fermentable sugar release from lignocellulosic biomass and increasing the cell output power are the main research points. DBFC can obtain a high theoretical exergy recovery; however, it is still in its early stage of development with low efficiency. More research should be focused on the electrode development, cell design, parameter optimization, process integration, as well as understanding fundamental process mechanisms.
Expression profiling of miRNAs has the ability to reveal the essence of somatic embryogenesis (SE). qRT-PCR is one of the most commonly used techniques for dynamic miRNA detection but requires optimal reference genes for data reliability. This is the first report on reference gene validation for miRNA expression normalization in Lilium (Lilium pumilum DC. Fisch. and Lilium davidii var. unicolor). In this study, seventeen miRNAs together with two snRNAs (U4, U6), one rRNA (5S rRNA) and three protein-coding genes (FP, ACT, GAPDH) were selected as reference candidates, and their expression stability was validated by qRT-PCR among eleven developing SE cultures in two lilies. Four normalization algorithms, including geNorm, BestKeeper, NormFinder and RefFinder, were also used to evaluate the stability of the reference candidates. For Lilium pumilum DC. Fisch., lpu-miR159a was the optimal reference gene during SE, followed by lpu-miR408b, while U6 was the least stable reference candidate. For Lilium davidii var. unicolor, FP presented greater stability than did half of the miRNA candidates, but the best reference gene was lda-miR162, followed by lda-miR159a. Further analysis of the expression level of miR156 and miR529 was used to evaluate the validity of the reference genes in both lilies. In general, miRNAs are superior to common protein-coding genes and snRNAs/rRNAs as reference genes for miRNA expression normalization during Lilium SE, and the most suitable reference miRNA is different between two species in the same Lilium genus. This is a pioneer study using suitable miRNAs as reference genes in Lilium and constitutes a small but essential step for the further exploration of miRNA function in Lilium, thus offering valuable references for other plants.
Many of the great morphologists of the nineteenth century marvelled at similarities between the limbs of diverse species, and Charles Darwin noted these homologies as significant supporting evidence for descent with modification from a common ancestor. Sir Richard Owen also took great care to highlight each of the elements of the forelimb and hindlimb in a multitude of species with focused attention on the homology between the hoof of the horse and the middle digit of man. The ensuing decades brought about a convergence of palaeontology, experimental embryology and molecular biology to lend further support to the homologies of tetrapod limbs and their developmental origins. However, for all that we now understand about the conserved mechanisms of limb development and the development of gross morphological disturbances, little of what is presented in the experimental or medical literature reflects the remarkable diversity resulting from the 450 million year experiment of natural selection. An understanding of conserved and divergent limb morphologies in this new age of genomics and genome engineering promises to reveal more of the developmental potential residing in all limbs and to unravel the mechanisms of evolutionary variation in limb size and shape. In this review, we present the current state of our rapidly advancing understanding of the evolutionary origin of hands and feet and highlight what is known about the mechanisms that shape diverse limbs. This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.
Limonium bicolor, a typical recretohalophyte, has a specialized salt-secreting structure in the epidermis called the salt gland and plays a significant role in improving saline land. Understanding the molecular mechanisms of salt secretion and salt gland development requires an efficient L. bicolor transformation system, which is described in this report. Leaf explants were incubated with Agrobacterium tumefaciens strain EHA105 harboring the plasmid pTCK303 containing the beta-glucuronidase gene (GUS) as the transgene reporter and the hygromycin B resistance gene as a selectable marker. Up to 96.9% of leaves were induced to regenerate shoots on an Murashige and Skoog (MS) medium supplemented with 4.4 mu M 6-benzyladenine and 1.1 mu M alpha-naphthaleneacetic acid; roots were induced on the MS medium containing 2.5 mu M indole-3-butyric acid. This tissue culture system was suitable for Agrobacterium-mediated transformation of L. bicolor. Pre-cultivated explants (2 d old) were incubated with Agrobacterium (0.6-0.7 at OD600) in a shaking culture for 20 min; the explants and bacterium were co-cultivated for 4 d in the dark before the explants were transferred to a selection medium containing 8 mg/L hygromycin B and 600 mg/L piperacillin sodium (added to prevent continued Agrobacterium growth). Histochemical assays and PCR to detect the GUS gene showed that transformation frequency was 4.43%. Quantitative PCR and Northern blotting further verified the integration and presence of the GUS gene in L. bicolor. This is the first report of an Agrobacterium-based transformation system for L. bicolor. The system will facilitate a research on the identity and function of genes involved in salt gland development and salt secretion.
Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating the biological functions and underlying molecular mechanisms of glioma. Here, we investigated the expression level and biological function of linc-OIP5 in glioma. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine the expression of linc-OIP5 in glioma tissues and in adjacent normal tissues. Level of linc-OIP5 was up-regulated in glioma tissues and significantly correlated with the advanced tumor stage (III/IV). Subsequently, the efficacy of knockdown of linc-OIP5 by linc-OIP5-small interfering RNA (siRNA) was evaluated in vitro, and we found that knockdown of linc-OIP5 can inhibit glioma cells proliferation, migration in vitro and tumor formation in vivo. Further mechanistic studies revealed the effect of linc-OIP5 knockdown on glioma cell phenotype at least partially through down-regulation of YAP and inhibition of Notch signaling pathway activity. Thus, our study provides evidence that linc-OIP5 is a potential therapeutic target and novel molecular biomarker for glioma. (C) 2017 Published by Elsevier B.V.
A quickest change detection (QCD) algorithm is proposed to address the problem of detecting and identifying line outages in a power system. The statistics of electricity demand are assumed to be known and propagated through a linearized model of the equations describing the power flow balance at each node of the network. The proposed algorithm incorporates the transient dynamics of the power system following a line outage and is applied to the measurements of voltage phase angles, which are collected using phasor measurement units. This adaptive algorithm is developed by treating the QCD problem as a dynamic composite hypothesis testing problem. It is shown to have superior performance compared with other line outage detection algorithms previously proposed in the literature. Case studies demonstrating this gain in performance are illustrated through the IEEE 118-bus test system.
The control system described in this work implements automatically a digital controller that achieves the highest possible cross-over frequency for the specified phase margin by applying a design method based on the measured frequency response of the DC/DC converter, identified by the system itself. The algorithms for the design, identification process and control of the converter are implemented on a SoC (System on Chip). The proposed algorithm to calculate the controller is described and the identification process and the designed compensator are validated through measurements on an actual converter.
A digital dual-mode linear quadratic regulator (LQR) with feedforward optimal controller is presented, which allows voltage control of a boost converter for wide-load-range condition, whether in continuous conduction mode (CCM) or in discontinuous conduction mode (DCM). Based on the conventional LQR method, the proposed controller is designed and makes the following two improvements. First, in order to eliminate the phase error caused by right-half-phase zero emerged in non-minimum phase boost converter, a feedforward controller is implemented by zero phase error tracking control technique because the inverse of non-minimum phase system is unstable. Second, since the models of DC-DC converter in CCM or DCM are different, the proposed control strategy allows boost converter to autonomously operate in CCM or DCM controller by utilising a mode detector. The proposed mode detector greatly enhances the control performance in both operating modes. Finally, the proposed controller has been implemented for voltage control of a boost converter. The simulation and experimental results show the proposed controller offers better performance in both transient response and frequency response than the conventional LQR controller.
Aim: Endothelial lipase (EL) is a member of the lipoprotein lipase family that regulates HDL metabolism. EL is known to act as a bridging molecule for monocytes or lipoproteins in vascular endothelial cells. We investigated the role and regulatory mechanisms of EL expression in macrophages. Methods: Macrophages originating from wild-type (EL+/+) and EL-deficient (EL-/-) mice were stimulated with lipopolysaccharide (LPS). The expression of EL mRNA was evaluated by northern blotting. DiI-LDL was used to measure the uptake of native low-density lipoprotein (nLDL). Results: LPS increased EL mRNA levels by increasing intracellular oxidative stress in the macrophages. LPS did not affect EL expression in macrophages derived from Toll-like receptor 4 (TLR4) gene mutant mice, C3H/HeJ. The uptake of nLDL after LPS-treatment was significantly lower in macrophages from EL-/- mice than those from EL+/+ mice. Simvastatin suppressed the LPS-induced upregulation of EL expression and uptake of nLDL. Conclusions: EL expression is upregulated by LPS via TLR4 and promotes the uptake of nLDL by macrophages. Simvastatin inhibits the LPS-induced up-regulation and uptake in macrophages. Thus, our findings provide a novel role for EL in lipoprotein metabolism and would expand the range of anti-atherogenic effects of statins.
Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed that S1P release from erythrocytes is mediated by an ATP-dependent transporter. In this study, we attempted to establish a rapid and reliable method for measuring the S1P transport activity in erythrocytes by using a fluorescent S1P analog, 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled S1P. NBD-S1P was released from erythrocytes in a time-dependent manner. The NBD-S1P release was reduced after exposure to glyburide, which is an inhibitor of the S1P transporter in erythrocytes. Moreover, the release of NBD-S1P and S1P from erythrocytes was competitively inhibited by intracellular S1P and NBD-S1P, respectively. These results showed that the erythrocyte S1P transporter exports NBD-S1P. We optimized the sample-preparation conditions and lipid extraction to increase the sensitivity of the assay. Furthermore, we successfully measured NBD-S1P release without lipid extraction by decreasing the concentration of BSA in the assay buffer to 0.1%. This method will be useful for the high-throughput screening of S1P transporter inhibitors using conventional fluorometers.
Lipid biosynthesis and its regulation have been studied mostly in the nonoleaginous yeast Saccharomyces cerevisiae that serves as a model for eukaryotic cells. On the other hand, the yeast Yarrowia lipolytica has been put forward as a model for oleaginous microorganisms because its genetics is known and tools for its genetic manipulation are becoming increasingly available. A comparison of the lipid biosynthetic pathways that function in these two microorganisms shows many similarities in key biosynthetic and regulatory steps. An example is the enzyme phosphatidic acid phosphatase that controls the synthesis of triacylglycerol (TAG) in both yeasts. Controlling the TAG synthesis is crucial for metabolic engineering efforts that aim to increase the production of microbial lipids (i.e. single cell oils) because TAG comprises the final product of these processes. At the same time the comparison reveals fundamental differences (e.g. in the generation of acetyl-CoA for lipid biosynthesis) stemming from the oleaginous nature of Y. lipolytica. These differences warranty more studies in Y. lipolytica where the biochemistry and molecular biology of oleaginicity can be further explored.
Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol's action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to the nucleosome. Our findings support that cholesterol assists 10 and 30 nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.
In crustaceans, the fascinating processes of maturation, reproductive molting and carapace coloration are regulated by hydrophobic molecules. Interestingly, most of the molecules are ligands of lipocalin. To understand the role of lipocalin in the aforementioned processes at molecular level, we isolated a cDNA that belongs to the lipocalin family, from a central nervous system cDNA library of Macrobrachium rosenbergii. We monitored the spatial and temporal distributions of the mRNA by using Northern Blotting analysis. Our results demonstrated that this gene expresses abundantly in the subepidermal adipose tissue, while faintly in the hepatopancreas and central nervous system. However, no signal was detected in other tissues including muscle, gill and ovary. Its expression levels in subepidermal adipose tissue during various stages of maturation as well as through the whole molting cycle showed that prawn lipocalin is involved in sexual maturation, as the maximal level was observed just after molt. (C) 2007 Published by Elsevier Inc.
Important insights into the role of interfacial composition and structure in controlling the digestion of oil-water emulsions have been gained in the last decade. The driving interest relies on: i) the necessity of controlling the digestion of lipids to decrease or delay fat intake to address the obesity crisis existing worldwide and ii) assuring the bioaccessibility of bioactive emulsified lipids or hydrophobic bioactive compounds. This article mainly reviews the relationship between the composition and structure of protein and polysaccharides stabilized emulsions and their susceptibility to in vitro lipolysis. The analysis concentrates on emulsions where (1) proteins or (2) polysaccharides are used as single emulsifiers, (3) emulsions stabilized by protein-polysaccharide conjugates, (4) protein-polysaccharide multilayer emulsions where the primary emulsion is formed by a protein, (5) protein-polysaccharide emulsions where proteins are the main emulsifiers and the polysaccharides perform as stabilizers. The mechanisms involved in the control of the rate and extent of lipolysis are discussed with special attention given to the interactions between emulsions components and bile salts as a critical point for controlling lipids digestion. (C) 2016 Elsevier Ltd. All rights reserved.
Previous studies have reported that lipoxin A(4) (LXA(4)) may exert a renoprotective effect on ischemia/reperfusion injury in various animal models. The underlying mechanism of LXA(4)-induced renoprotection during ischemia/reperfusion injury remains to be elucidated. The present study investigated LXA4-induced protection on renal tubular cells subjected to hypoxia/reoxygenation (H/R) injury, and determined the effects of peroxisome proliferator-activated receptor-gamma (PPAR gamma) and heme oxygenase-1 (HO-1) on LXA(4) treatment. HK-2 human tubular epithelial cells exposed to H/R injury were pretreated with LXA4, signal molecule inhibitors or the HO-1 inhibitor zinc protoporphyrin-IX, or were transfected with PPAR. small interfering RNA (siRNA) or nuclear factor E2-related factor 2 (Nrf2) siRNA. The protein and mRNA expression levels of PPAR. and HO-1 were analyzed using western blotting and reverse transcription-quantitative polymerase chain reaction. Binding activity of Nrf2 to the HO-1 E1 enhancer was determined using chromatin immunoprecipitation. Nrf2 binding to the HO-1 antioxidant responsive element (ARE) was assessed using electrophoretic mobility shift assay. Preincubation of cells with LXA(4) exposed to H/R injury led to a decreased production of inducible nitrogen oxide synthase, malondialdehyde,gamma-glutamyl transpeptidase, leucine aminopeptidase and N-acetyl-gamma-glucosaminidase. In addition, LXA(4) pretreatment increased cell viability, protein and mRNA expression levels of PPAR. and HO-1 and PPAR. and HO-1 promoter activity. SB20358 is a p38 mitogen-activated protein kinase (p38 MAPK) pathway inhibitor, which reduced LXA(4)-induced PPAR. expression levels. LXA4 treatment upregulated p38 MAPK activation, Nrf2 nuclear translocation and increased binding activity of Nrf2 to HO-1 ARE and E1 enhancer in cells exposed to H/r injury. Transfection of thecells with PPAR gamma siRNA reduced the LXA(4)-induced Nrf2 translocation. Transfection of the cells with PPAR. siRNA or Nrf2 siRNA also reduced the LXA(4)-induced increase in HO-1 expression. In conclusion, LXA(4)-induced protection of renal tubular cells against H/R injury was associated with the induction of PPAR. and HO-1, via activation of the p38 MAPK pathway, as well as Nrf2 nuclear translocation and binding to HO-1 ARE and E1 enhancer. Therefore, LXA(4)-induced renoprotection is associated with activation of the p38 MAPK/PPAR gamma/Nrf2-ARE/HO-1 pathway.
Objectives: Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20). Materials and methods: Forty-nine patients with NSCLC harboring EGFR-activating mutations were enrolled, and circulating free DNAs (cfDNAs) were extracted from the plasma of 21 and 28 patients before treatment and after progression following EGFR-TKI treatment, respectively. Results: Using reference genomic DNA containing each mutation, the detection limit of each assay was determined to be 0.1%. The sensitivity and specificity of detecting exon 19 deletions and L858R mutations, calculated by comparing the mutation status in the corresponding tumors, were 70.6% and 93.3%, and 66.7% and 100%, respectively, showing similar results compared with previous studies. T790M was detected in 43% of 28 cfDNAs after progression with EGFR-TKI treatment, but in no cfDNAs before the start of the treatment. Conclusion: This chip-based dPCR assay can facilitate detection of EGFR mutations in cfDNA as a minimally invasive method in clinical settings. (C) 2017 Elsevier B.V. All rights reserved.
Background. The use of plasma as a "liquid biopsy" has gained increasing attention. The purpose of the present study was to evaluate the diagnostic and prognostic utility of the perioperative detection and quantitation of mRNAs encoding human telomerase reverse transcriptase (hTERT) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in plasma from patients with cancer of the larynx or hypopharynx. Methods. We recruited 47 patients with laryngeal cancer and 2 patients with hypopharyngeal cancer, plus 27 healthy subjects. A blood sample was taken from each patient before and after surgical resection of the tumor. We quantified hTERT mRNA and GAPDH mRNA in plasma by real-time polymerase chain reaction (PCR). Results. Detection of hTERT mRNA before surgery had diagnostic value (sensitivity, 22%; specificity, 100%). Detection was more frequent in patients with supraglottic tumors than glottic tumors (p = .02) and was related to subsequent recurrence (p = .02). Preoperative levels of hTERT mRNA in plasma were higher in patients with subsequent recurrence (p = .046) and/or metastases (p = .047). The disease-free survival (DFS) and overall survival (OS) of patients with plasma samples positive for hTERT mRNA was poorer than that of patients with negative samples. Mean levels of plasma GAPDH mRNA in untreated patients were higher than in healthy subjects (p < .001). Conclusion. Detection and quantitation of hTERT and GAPDH mRNA in patients' plasma might be clinically significant in cases of laryngeal and hypopharyngeal cancer. (C) 2017 Wiley Periodicals, Inc.
This paper proposes a positive temperature coefficient (PTC) self-heating method, in which EVs can be operated independently of external power source at low temperature, with a lithium-ion battery (LIB) pack discharging electricity to provide PTC material with power. Three comparative heating experiments have been carried out respectively. With charge/discharge tests implemented, results demonstrate the superiority of the self-heating method, proving that the discharge capability, especially the discharge capacity of the self-heated pack is better than that of the external power heated pack. In order to evaluate the heating effect of this method, further studies are conducted on temperature distribution uniformity in the heated pack. Firstly, a geometric model is established, and heat-generation rate of PTC materials and LIB are calculated. Then, thermal characteristics of the self-heating experiment processes are numerically simulated, validating the accuracy of our modeling and confirming that temperature distributions inside the pack after heating are kept in good uniformity. Therefore, the PTC self-heating method is verified to have a significant effect on the improvement of performance of LIB at low temperature.
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines for mass vaccination of farmed fish species. Furthermore, using various examples from the human and veterinary vaccine development, we propose additional approaches to fish vaccine design also considering recent advances in fish mucosal immunology and novel molecular tools. Finally, we discuss the pros and cons of using the zebrafish as a pre-screening animal model to potentially speed up vaccine design and testing for aquaculture fish species. (C) 2016 The Authors. Published by Elsevier Ltd.
BACKGROUND & AIMS: Choline kinase a ( CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma ( HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor-adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens ( HCC and non-tumor-adjacent tissues) were also analyzed. CHKA gene copy number was quantified and findings were validated by quantitative reverse transcription polymerase chain reaction analysis. CHKA messenger RNA and protein levels were determined by polymerase chain reaction, immunohistochemical, and immunoblot analyses. CHKA was examined in 2 hepatocyte cell lines and 7 HCC-derived cell lines, and knocked down with small interfering RNAs in 3 HCC cell lines. Cells were analyzed in proliferation, wound healing, migration, and invasion assays. Cells were injected into tail veins of mice and tumor growth and metastasis were quantified. Immunoprecipitation and immunofluorescence assays were conducted to determine interactions between CHKA and the epidermal growth factor receptor ( EGFR) and the mechanistic target of rapamycin complex 2. RESULTS: Levels of CHKA messenger RNA were frequently increased in HCC tissues compared with nontumor tissues; increased expression was associated with amplification at the CHKA loci. Tumors that expressed high levels of CHKA had more aggressive phenotypes, and patients with these tumors had shorter survival times after surgery compared to patients whose tumors expressed low levels of CHKA. HCC cell lines that stably overexpressed CHKA had higher levels of migration and invasion than control HCC cells, and formed larger xenograft tumors with more metastases in mice compared to HCC cells that did not overexpress CHKA. CHKA was required for physical interaction between EGFR and mechanistic target of rapamycin complex 2. This complex was required for HCC cells to form metastatic xenograft tumors in mice and to become resistant to EGFR inhibitors. CONCLUSIONS: We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness and reduced survival times of patients. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2.
Multiple long non-coding RNAs (lncRNAs) have been demonstrated to be involved in liver disease. Increased cyclooxygenase-2 (COX-2) levels have also been reported to be involved in the progression of liver cirrhosis. In the present study, the correlations between lncRNA-COX-2 RNA expression levels, COX-2 mRNA expression levels and liver fibrosis were examined. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) in mice for 2months (CCl4-2M) or 3months (CCl4-3M). Liver histopathological evaluation was conducted using hematoxylin and eosin and Masson trichrome staining. Hepatic expression of COX-2 and lncRNA-COX-2 was evaluated by reverse transcriptionquan-titative polymerase chain reaction and immunohistochemical staining. Compared with the control group, fibrotic areas were increased four and nine times in the CCl4-2M group and the CCl4-3M group, respectively. LncRNA-COX-2 and COX-2 upregulation were observed in the cirrhotic liver. COX-2 mRNA expression levels and lncRNA-COX-2 RNA expression levels were significantly positively correlated with the fibrotic area. In addition, COX-2 mRNA expression was significantly positively correlated with lncRNA-COX-2 expression. These results suggest that expression of COX-2 and lncRNA-COX-2 increased with the progression of liver fibrosis. LncRNA-COX-2 may potentially be considered as a novel therapeutic target for liver fibrosis.
Background & Aims: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance. Methods: C57BL/6 (H-2b) mice were treated with adeno-associated viral (AAV) vector targeting the expression of the MHC class I molecule H-2K(d) to hepatocytes, before transplantation with fully allogeneic pancreatic islet from BALB/c mice (H-2d). Results: AAV H-2K(d) treated mice were tolerant to the alloantigen, as demonstrated by its long-term expression by the hepatocytes, even after a highly immunogenic challenge with an adenoviral vector. After chemical induction of diabetes, the AAV treated mice had significantly delayed rejection of fully allogeneic pancreatic islet grafts, with more than 40% of recipients tolerant (>100 days). AAV-mediated expression of H-2Kd in the liver induced the local expansion of CD8(+) T lymphocytes with allospecific suppressive properties. The adoptive transfer of these liver-generated CD8(+) Tregs into naive diabetic mice promoted the long-term survival of allogeneic pancreatic islet grafts. Conclusion: AAV-mediated long-term expression of a single MHC class I molecule in the liver induces the generation of a subset of allo-specific CD8(+) Treg cells, which promote tolerance toward fully allogeneic graft. Liver gene transfer represents a promising strategy for in vivo induction of donor-specific tolerance. Lay summary: The liver has a special immune system, biased toward tolerance. In this study, we investigated the possibility of harnessing this property of the liver to induce tolerance to an allogeneic transplantation. We demonstrate for the first time that the in vivo gene transfer of an allogeneic antigen with an adeno-associated viral vector to mouse hepatocytes induces the expansion of a population of CD8(+) regulatory T lymphocytes. These Tregs are then instrumental in preventing the rejection of allogeneic pancreatic islets transplanted in these animals. Allogeneic transplantation is the main treatment for the end-stage diseases of a number of organs. Life-long immunosuppressive treatments are still required to limit graft rejection, and these treatments exhibit serious side effects. Our present findings open a new avenue for promoting allo-specific tolerance via in vivo induction of CD8(+) Treg expansion. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
Recent years have seen a growing interest in PBC within the scientific community, healthcare providers and industries, coupled with great advances in the understanding of the molecular and genetic basis and the natural history of the disease. Several disease-modifying agents targeting the immune-mediated response and bile-acid therapies are at different stages of development, some with promising results. A new drug, obeticholic acid, has been recently registered in the US and Europe as a second-line treatment in refractory PBC. International cohort studies have highlighted a disease heterogeneity, and so the need to provide patients with a more personalised management based on their risk of disease progression. Major challenges remain the development of surrogate endpoints in clinical trials acceptable to regulatory authorities, in a disease with a relatively low rate of events; and the development of clinical tools for patient's risk stratification and selection of those with greatest potential benefit from second-line therapies.
The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses. In this review, we characterize cells of the TME with pro-and anti-tumor function in primary and metastatic liver tumors. Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic approaches targeting the TME could unleash tumor-specific immune responses to improve survival of liver cancer patients. Published by Elsevier Inc.
Background: Previous studies have indicated that Tec tyrosine kinase is differentially expressed in the regenerating liver. The purpose of the present study was to further investigate the potential involvement of Tec tyrosine kinase in hepatocyte proliferation and liver regeneration. Methods: Tec kinase gene expression after partial (two-thirds) hepatectomy was examined by representational difference analysis. Tissue distribution and potential involvement of Tec kinase in liver regeneration and hepatocyte proliferation were then determined by northern blotting, reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Full-length rat Tec cDNA was cloned. Results: Using this cDNA as the probe, northern blotting showed that Tec was specifically expressed in liver and kidney, the highest expression of Tec being detected in embryonic day 15-19 fetal livers. In contrast, the expression level of Tec in adult and neonatal rat livers was significantly decreased. Similar results were obtained from western blotting analyzes. It was thus hypothesized that Tec might be involved in hepatocyte proliferation. To test this hypothesis, Tec expression was examined in regenerating rat livers. An increase in Tec expression and activation of Tec kinase were observed within 1 h after partial hepatectomy. Moreover, it has been shown that hepatocyte growth factor (HGF) dramatically induces Tec expression in primary rat hepatocytes. Additionally, it was observed that Tec gene expression in serum-starved liver tumor cell line HepG2 was substantially decreased. Stimulation with 10% fetal bovine serum and insulin but not epidermal growth factor resulted in dramatic elevation of Tec expression in these cells. Conclusion: Tec is an inducible early response gene that might enhance hepatocyte proliferation and liver regeneration.
The aim of this single-center cross-sectional study was to detect the prevalence of selected periodontal pathogenic bacteria and active matrix metalloproteinase-8 (aMMP-8) level in patients before (preLTx) and after liver transplantation (postLTx). Periodontal pocket depth (PPD) and clinical attachment loss (CAL) were assessed. Subgingival biofilm samples were analyzed using polymerase chain reaction (PCR) to detect 11 common periodontal pathogens. Gingival crevicular fluid (GCF) samples were analyzed with enzyme-linked immunosorbent assay (ELISA) to determine aMMP-8 level and assigned to a scoring system: score 0: 0-8 ng/ml, score 1: 8-20 ng/ml, and score 2: >20 ng/ml. The following were used for the statistical analysis: t test, Mann-Whitney U test, Fishers test (alpha = 5 %). In total, 110 patients (preLTx: n = 35, postLTx: n = 75) could be included in the study. Periodontal findings were not significantly different between groups. In microbiological analysis, a significantly higher prevalence of Campylobacter rectus in preLTx group was detected (p = 0.03). Significantly more patients with score 0 in postLTx group (p = 0.024) and significantly more patients with score 1 in preLTx group were found (p = 0.004). Furthermore, aMMP-8 concentrations for patients with moderate periodontitis were significantly lower in postLTx group compared to preLTx group (p = 0.045). Additionally, in postLTx group, aMMP-8 concentration was significantly higher in patients with severe periodontitis compared to those with no/mild periodontitis (p = 0.016). LTx appears to affect aMMP-8 level, but not bacterial findings in patients after LTx. Determination of aMMP-8 level in patients after LTx with immunosuppressive medication might lead to wrong interpretation of the results.
In this paper, an adaptive synchronous rectifier (SR) driving scheme for the LLC resonant converters using the ripple counter concept is proposed, along with two methods of implementation. With the proposed scheme, the SR drain to source voltage is sensed to detect the body diode conduction, based on which the SR on-time can be well tuned to eliminate the body diode conduction. One proposed implementation tunes the SR on-time every switching cycle based on the ripple detection; another proposed implementation tunes the SR on-time every nth switching cycle (n = 1, 2, 3...) based on the ripple counter, which is suitable for the high frequency LLC converters. The proposed SR driving scheme has the simple implementation, requires only low-cost digital controllers and occupies very few controller resources. More importantly, since the digital controllers have already been widely adopted in the control of the LLC converters, the proposed adaptive SR driving method can be embedded into these digital controllers with little extra cost. Furthermore, how to integrate the proposed SR driving method with closed-loop control is explained in details. Experimental results are demonstrated on a 130kHz LLC converter with 100MHz microcontroller (MCU) and a 500kHz LLC converter with a 60MHz MCU and a ripple counter.
in this paper, the dynamics of the half-bridge LLC resonant converter are investigated based on the small signal model and a piecewise PI regulation is studied and derived by simulation. Small-signal dynamics of the circuit under consideration contain many factors that may affect regulation accuracy and performance of digitally controlled regulators. The load factor is specifically addressed here. The objective of this paper is to introduce a digital piecewise PI compensation to achieve time-optimal response to an external disturbance such as a step load transient.
Long non-coding RNAs (lncRNAs), which represent a new frontier in molecular biology, play important roles in regulating gene expression at epigenetic, transcriptional and post-transcriptional levels. More and more lncRNAs have been found to play important roles in normal cell physiological activities, and participate in the development of varieties of tumors and other diseases. Previously, we have only been able to determine the function of lncRNAs through multiple mechanisms, including genetic imprinting, chromatin remodeling, splicing regulation, mRNA decay, and translational regulation. Application of technological advances to research into the function of lncRNAs is extremely important. The major tools for exploring lncRNAs include microarrays, RNA sequencing (RNA-seq), Northern blotting, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), RNA interference (RNAi), RNA-binding protein immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP), crosslinking-immunopurification (CLIP), and bioinformatic prediction. In this review, we highlight the functions of lncRNAs, and advanced methods to research lncRNA-protein interactions.
Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer. This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC). The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR). We found that 16 out of 67 CC had MSI-L CC and 7 with MSI-H. In comparison with that in five non-tumor colonic samples, microarray indicated that 1492 lncRNAs and 1639 mRNAs were upregulated while 1804 lncRNAs and 1073 mRNAs downregulated in four pMMR early-stage CC. Bioinformatic analyses revealed that the differentially expressed mRNAs were involved in the process of cell division, angiogenesis, apoptotic, differentiation, the PI3K-Akt/p53/TNF pathways and others. The co-expression lncRNA and mRNA networks indicated five hot spots with significantly high co-expression degrees. Further quantitative RT-PCR revealed that 4 out of 6 lncRNAs were significantly upregulated while the other 2 lncRNAs were downregulated in the CC. Stratification analysis demonstrated that 5 out of 6 lncRNAs were significantly associated with TNM stage and/or distant metastasis in this population. Differentially expressed lncRNAs were significantly associated with clinical features of patients with pMMR CC and may participate in the tumorigenesis of pMMR CC.
Loki Patera is one of the most dramatically time-variable volcanic features on Io, exhibiting episodic brightening events every 1-3 years that may produce over 15% of lo's global heat flow. We observed three such brightening events with adaptive optics imaging at the Keck and Gemini N telescopes over the course of 70 nights of observation in 2013-2016. The high cadence and multi-wavelength nature of the observations provides constraints on models for activity at Loki Patera. The Matson et al. (2006) model for Loki Patera as an overturning basaltic magma sea is adapted to fit the observations of all three events. In particular, we adjust the details of the overturn progression, and modify the lava thermal properties to include dependencies on temperature and porosity, to improve the fit to the data. The preferred models find overturn front propagation velocities of 1.2-1.7 km/day, corresponding to resurfacing rates of 1500-2200 m(2)/s. The time intervals of 440-540 days between successive events are roughly consistent with the 540-day period calculated by Rathbun et al. (2002) for events prior to 2001. The best coverage was obtained for the 2016 brightening; model fits to this event require a lava bulk thermal conductivity of 0.55-0.75 W/m/K, with the best fit obtained for a value of similar to 0.7 W/m/K and an average porosity that decreases during cooling. For all three events, the overturn front appears to propagate around the patera in the clockwise direction, opposite to what has been inferred for past brightening events. There is evidence that the overturn may be more complex than a single propagating wave, perhaps involving multiple simultaneous resurfacing waves as well as portions of the patera that are active even after the nominal bright phase has ended. The measured intensities are anomalously low when Loki Patera is viewed at high emission angles, suggestive of topographic shadowing due to a raised area or the edge of the depression in which the magma sea resides. (C) 2017 Elsevier Inc. All rights reserved.
There is an unmet need for herbal medicine identification using a fast, sensitive, and easy-to-use method that does not require complex infrastructure and well-trained technicians. For instance, the detection of adulterants in Lobelia chinensis herbal product has been challenging, since current detection technologies are not effective due to their own limits. High Resolution Melting (HRM) has emerged as a powerful new technology for clinical diagnosis, research in the food industry and in plant molecular biology, and this method has already highlighted the complexity of species identification. In this study, we developed a method of species specific detection of L. chinensis using HRM analysis combined with internal transcribed spacer 2. We then applied this method to commercial products purporting to contain L. chinensis. Our results demonstrated that HRM can differentiate L. chinensis from six common adulterants. HRM was proven to be a fast and accurate technique for testing the authenticity of L. chinensis in herbal products. Based on these results, a HRM approach for herbal authentication is provided .
In the last decade, China has implemented more public-private partnership (PPP) projects in the water sector compared to other sectors. However, efficient management of risks in these projects remains problematic. While there have been many studies that have examined risks associated with PPPs in China, the experience of local governments with risks has received little or no attention in the literature. Moreover, the stages at which the risks are significant and how these risks are interrelated have not been researched. This paper examines risks as experienced from the local government's perspective and how they manifest across five PPP stages: (1) feasibility, (2) procurement, (3) construction, (4) operation, and (5) transfer. The interrelationship between the risks across the PPP stages is also examined. Data was collected via questionnaire surveys and interviews, and it was analyzed using quantitative and qualitative analysis. The findings reveal critical risk for local governments and how their impacts vary across project stages. Some of the risks influence other risks both within and across the five PPP stages. The findings provide significant insight into the dynamic nature risks in PPP water projects, which has important implications for practitioners when developing risk mitigation strategies. (C) 2017 American Society of Civil Engineers.
The skin can serve as an interstitial Na+ reservoir. Local tissue Na+ accumulation increases with age, inflammation and infection. This increased local Na+ availability favors pro-inflammatory immune cell function and dampens their anti-inflammatory capacity. In this review, we summarize available data on how NaCl affects various immune cells. We particularly focus on how salt promotes pro-inflammatory macrophage and T cell function and simultaneously curtails their regulatory and anti-inflammatory potential. Overall, these findings demonstrate that local Na+ availability is a promising novel regulator of immunity. Hence, the modulation of tissue Na+ levels bears broad therapeutic potential: increasing local Na+ availability may help in treating infections, while lowering tissue Na+ levels may be used to treat, for example, autoimmune and cardiovascular diseases.
In order to obtain very precise measurements of the position of agents located at a considerable distance using a sensor system based on position sensitive detectors (PSD), it is necessary to analyze and mitigate the factors that generate substantial errors in the system's response. These sources of error can be divided into electronic and geometric factors. The former stem from the nature and construction of the PSD as well as the performance, tolerances and electronic response of the system, while the latter are related to the sensor's optical system. Here, we focus solely on the electrical effects, since the study, analysis and correction of these are a prerequisite for subsequently addressing geometric errors. A simple calibration method is proposed, which considers PSD response, component tolerances, temperature variations, signal frequency used, signal to noise ratio (SNR), suboptimal operational amplifier parameters, and analog to digital converter (ADC) quantitation SNRQ, etc. Following an analysis of these effects and calibration of the sensor, it was possible to correct the errors, thus rendering the effects negligible, as reported in the results section.
The reliance on sales taxation has increased in both states and counties. This study aggregated county-level data and empirically explored the associations between state-local sales taxes and economic activity by industry types in county governments for the period of 1990-2013. The results revealed negative associations of sales tax rates with economic activity, especially in the manufacturing industry. Further, the findings provided the spatial dependence of economic activity across counties as a form of possible spillover. This study suggests that policymakers should pay attention to how the manufacturing and retail industries respond to any changes in sales tax rates for business activity.
The prosperity of location-based services (LBSs) makes more and more people pay close attention to personal privacy. In order to preserve users privacy, several schemes utilized a trusted third party (TTP) to obfuscate users, but these schemes were suspected as the TTP may become the single point of failure or service performance bottleneck. To alleviate the suspicion, schemes with collaborative users to achieve k-anonymity were proposed. In these schemes, users equipped with short-range communication devices could communicate with adjacent users to establish an anonymous group. With this group, the user can obfuscate and hide herself behind at least k - 1 other users. However, these schemes are usually more effcient in snapshot services than continuous ones. To cope with the inadequacy, with the help of caching in mobile devices, we propose a query information blocks random exchange and results caching scheme (short for CaQBE). In this scheme, a particular user is hidden behind collaborative users in snapshot service, and then the caches further preserve the privacy in continuous service. In case of the active adversary launching the query correlation attack and the passive adversary launching the impersonation attack, a random collaborative user selection and a random block exchange algorithm are also utilized. Then based on the feature of entropy, a metric to measure the privacy of the user against attacks from the active and passive adversaries is proposed. Finally, security analysis and experimental comparison with other similar schemes further verify the optimal of our scheme in effectiveness of preservation and effciency of performance.
This study examined the incidence of PTSD and psychiatric co-morbidity among women who experienced stillbirth and investigated the relationship between locus of control, trauma characteristics of stillbirth, posttraumatic cognitions, PTSD and co-morbid psychiatric symptoms following stillbirth. Fifty women recorded information on stillbirth experiences, and completed the Posttraumatic Stress Diagnostic Scale, General Health Questionnaire-28, Edinburgh Post-natal Depression Scale, Rotter's Locus of Control Scale and the Posttraumatic Cognitions Inventory. 60, 28 and 12 % met the diagnostic criteria for probable full-PTSD, partial and no-PTSD respectively. Sixty-two percent and 54 % scored at or above the cutoff of the General Health Questionnaire-28 and postnatal depression respectively. Women who experienced stillbirth reported significantly more psychiatric co-morbid and post-natal depressive symptoms than the comparison group. Both groups were similar in locus of control. Women who experienced stillbirth reported negative cognitions about the self the most. After adjusting for postnatal depression, trauma characteristics were significantly correlated with Posttraumatic cognitions which, in turn, were significantly correlated with PTSD and psychiatric co-morbidity. Locus of control was not significantly correlated with psychological outcomes. Mediational analyses showed that negative cognitions about self mediated the relationship between trauma characteristics and psychiatric co-morbidity only. Women reported a high incidence of probable PTSD and co-morbid psychiatric symptoms following stillbirth. Stillbirth trauma characteristics influenced how they negatively perceived themselves. This then specifically influenced general psychological problems rather than PTSD symptoms.
In this paper, we propose a multi-cue object representation for image classification using the standard bag-of-words model. Ever since the success of the bag-of-words model for image classification, several modifications of it have been proposed in the literature. These variants target to improve key aspects, such as efficient and compact dictionary learning, advanced image encoding techniques, pooling methods, and efficient kernels for the final classification step. In particular, "soft-encoding" methods such as sparse coding, locality constrained linear coding, Fisher vector encoding, have received great attention in the literature, to improve upon the "hard-assignment" obtained by vector quantization. Nevertheless, these methods come at a higher computational cost while little attention has been paid to the extracted local features. In contrast, we propose a novel multi-cue object representation for image classification using the simple vector quantization, and show highly competitive classification performance compared to state-of-the-art methods on popular datasets like Caltech-101 and MICC Flickr-101. Apart from the object representation, we also propose a novel keypoint detection scheme that helps to achieve a classification rate comparable to the popular dense keypoint sampling strategy, at a much lower computational cost. (C) 2017 Elsevier Ltd. All rights reserved.
This article explores the ways in which London lives were written together during the Romantic period, considering representations across different genres and media including: poetry by William Wordsworth, Richard Horwood's house-by-house Plan of the city (1792-9), Fores's New Guide for Foreigners ([?1789]), the 1788 volume of Harris's List of Covent Garden Ladies, Richard Phillips' Modern London (1804) and Pierce Egan's Life in London (1820-1). It pays particular attention to recovering evidence of marginalised individuals, whose lives were never written at book or article length, but of whom traces survive in glimpses and in aggregated forms such as plate series and directories. It also discusses the life writing of communities through the representation of common knowledge and the use of statistics, contrasting the confident assertions of knowledge made in guides, mapping and topography with the more conflicted and fragmented modes common in poetry and novels. Through examining these issues, it contends that there are considerable benefits in thinking of life writing as being intrinsic to a far wider range of discourses than the standard biographical and autobiographical modes, arguing that a broader conception is invaluable for recovering occluded existences, modelling collective experience and understanding the hierarchies implicit in the ways in which lives are culturally inscribed.
Social attachment is a biological and affective need. When this need is not met, people experience loneliness. Loneliness is associated with impaired social cognition, and is a risk factor for broad based morbidity across the adult lifespan even after controlling for multiple factors. However, little is known about loneliness in schizophrenia. Eighty-seven non-depressed individuals with schizophrenia or schizoaffective disorder (including 51 inpatients) and 58 control subjects completed the revised UCLA Loneliness scale. Social cognition was assessed with a self-report questionnaire and a performance-based task. Social trait perception was assessed with a facial task. Comorbid medical diagnoses were available for all inpatients. Patients reported greater loneliness levels than controls, while in- and out-patients did not significantly differ. In patients, loneliness was associated with self-report measures of social cognition. Patients' loneliness scores predicted a diagnosis of drug abuse/dependence, number of drugs used, hypertension and abnormal hemoglobin A1c levels. Patients experienced higher levels of loneliness than controls, independently of their objective social isolation. Loneliness did not rely on the same psychological processes in patients than in controls. Loneliness in schizophrenia is a symptom that deserves more scrutiny, particularly as it relates to the high prevalence of metabolic syndrome in this population.
Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non-tumor tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT-qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit-8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC-7901 and MGC-803) compared with normal tissues and a normal human gastric epithelial cell line (GES-1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC-7901 and MGC-803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer.
This paper introduces a high power density step-up converter for LED applications, based on a hybrid serial-output (HSO) architecture [1], which is suitable for on-chip implementation. In this system, the output voltage is formed by stacking the output of a switched-capacitor (SC) converter on top of a boost converter output. The high power density SC converter processes around a half of the power of the system and is left unregulated. The boost converter processes the remainder of the power and regulates the output voltage. In comparison with conventional boost-based solutions, the introduced boost-SC HSO drastically reduces the passive component volume and decreases peak voltage stress of switches. Experimental results obtained with a 3.7 V to 13 V, 2.6 W, 1080 kHz prototype show that the introduced SC-boost HSO converter has about three times smaller reactive component area than a conventional boost having the same power processing efficiency.
Xyloglucan endotransglycosylase (XET) catalyses the transglycosylation of xyloglucan, the major hemicellulose polymer, which has been thought to mediate the cross-linkining of cellulose microfibrils in cellular walls and proposed to be involved in the control of cell wall relaxation. To understand the relationship between longan fruit growth and XET gene expression patterns, three XET genes from fruit were identified and then their expression profiles in pericarp and aril tissues of fruit at different development stages were investigated. Three full-length cDNAs of 1077, 1093 and I IS I bp encoding XETs, named DIXET1, DIXET2 and DIXET3, respectively, were isolated from expanding fruit using RT-PCR and RACE-PCR (rapid amplification of cDNA ends) methods. Northern blotting analysis showed that three DIXET mRNAs exhibited different patterns during fruit growth and development. Accumulation of MET] kept changeable during the fruit growth and development, DI-XET2 mRNA accumulations in the pericarp, and in the aril increased gradually following fruit growth during the whole fruit developmental stage. In addition, DIXET3 did not accumulate in the pericarp during the whole fruit development stage, but it could be detected in the aril of fruit during the rapid aril growth stage (63-74 DAA). These results indicated that DIXET2 was associated with growth of pericarp and aril in longan fruit, while DIXET1 was related to pericarp growth and DIXET3 was primarily responsible for aril growth. To further characterize the expressions of three XETs regulated by plant growth substances, alpha-naphthalene acetic acid (NAA) and thidiazuron (TDZ) were used to treat longan fruit at 21 DAA and 56 DAA when pericarp, and aril grew rapidly respectively, it was found that treatment at 21 DAA, only TDZ increased the accumulation of DIXET2 mRNA at 12 h after treatment. However, both NAA and TDZ increased the accumulation of DIXET3 after 36 h treatment, although DIXET-3 did not accumulate in the whole fruit. While, treatment at 56 DAA, both NAA and TDZ increased the accumulations of DIXETs in aril except DIXET3 in aril by NAA treatment. In addition. the expression patterns of the three XETs showed different tissue specificity. These results suggested that XET genes played a different role in longan fruit growth and showed different response to plant growth substances which existed difference at different growth stage. (C) 2007 Published by Elsevier Ireland Ltd.
Soya bean (Glycine max (L.) Merr.) is sought after for both its oil and protein components. Genetic approaches to add value to either component are ongoing efforts in soya bean breeding and molecular biology programmes. The former is the primary vegetable oil consumed in the world. Hence, its primary usage is in direct human consumption. As a means to increase its utility in feed applications, thereby expanding the market of soya bean coproducts, we investigated the simultaneous displacement of marine ingredients in aquafeeds with soya bean-based protein and a high Omega-3 fatty acid soya bean oil, enriched with alpha-linolenic and stearidonic acids, in both steelhead trout (Oncorhynchus mykiss) and Kampachi (Seriola rivoliana). Communicated herein are aquafeed formulations with major reduction in marine ingredients that translates to more total Omega-3 fatty acids in harvested flesh. Building off of these findings, subsequent efforts were directed towards a genetic strategy that would translate to a prototype design of an optimal identity-preserved soya bean-based feedstock for aquaculture, whereby a multigene stack approach for the targeted synthesis of two value-added output traits, eicosapentaenoic acid and the ketocarotenoid, astaxanthin, were introduced into the crop. To this end, the systematic introduction of seven transgenic cassettes into soya bean, and the molecular and phenotypic evaluation of the derived novel events are described.
Oxidative stress is suggested to be central to the ageing process, with endogenous antioxidant defence and repair mechanisms in place to minimize damage. Theoretically, supplementation with exogenous antioxidants might support the endogenous antioxidant system, thereby reducing oxidative damage, ageing-related functional decline and prolonging life- and health-span. Yet supplementation trials with antioxidants in animal models have had minimal success. Human epidemiological data are similarly unimpressive, leading some to question whether vitamin C, for example, might have pro-oxidant properties in vivo. We supplemented cold exposed (7 12 degrees C) female C57BL/6 mice over their lifespan with vitamin C (ascorbyl-2-polyphosphate), widely advocated and self administered to reduce oxidative stress, retard ageing and increase healthy lifespan. No effect on mean or maximum lifespan following vitamin C treatment or any significant impact on body mass, or on parameters of energy metabolism was observed. Moreover, no differences in hepatocyte and lymphocyte DNA oxidative damage or hepatic lipid peroxidation was seen between supplemented and control mice. Using a DNA macroarray specific for oxidative stress-related genes, we found that after 18 months of supplementation, mice exhibited a significantly reduced expression of several genes in the liver linked to free-radical scavenging, including Mn-superoxide dismutase. We confirmed these effects by Northern blotting and found additional down-regulation of glutathione peroxidase (not present on macroarray) in the vitamin C treated group. We suggest that high dietary doses of vitamin C are ineffective at prolonging lifespan in mice because any positive benefits derived as an antioxidant are offset by compensatory reductions in endogenous protection mechanisms, leading to no net reduction in accumulated oxidative damage. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
One of the important topics in morphometry that received high attention recently is the longitudinal analysis of shape variation. According to Kendall's definition of shape, the shape of object appertains on non-Euclidean space, making the longitudinal study of configuration somehow difficult. However, to simplify this task, triangulation of the objects and then constructing a non-parametric regression-type model on the unit sphere is pursued in this paper. The prediction of the configurations in some time instances is done using both properties of triangulation and the size of great baselines. Moreover, minimizing a Euclidean risk function is proposed to select feasible weights in constructing smoother functions in a non-parametric smoothing manner. These will provide some proper shape growth models to analysis objects varying in time. The proposed models are applied to analysis of two real-life datasets.
Background: Little is known about the course of depression in midlife women. This study aims to identify factors that distinguish risk factors for persistent or recurrent depression from those of a milder course across 13-years of follow-up. Methods: 297 Black and White premenopausal women aged 42-52 were enrolled at the Study of Women's Health Across the Nation Pittsburgh site. Psychiatric interviews obtained information on lifetime psychiatric diagnoses at baseline and occurrences of depression annually. We identified four depression patterns: 91(31%) had Persistent/recurrent major depressive disorder (MDD), 27(9%) Single Episode MDD, 35 (12%) Minor Depression (minD) only, 144(48%) No Depression. We compared baseline risk factors for the Persistent/recurrent MDD group with each of the other three. Results: A lifetime history of major or minor depression (p-values =.001-.08) and 2+ very upsetting life events in the previous year (p-values=.003-.04) were more likely to be reported by women in the Persistent/recurrent group than in the other three. The Persistent/recurrent group was more likely to report a family history of depression (p=.03) than the MinD group, and to report current sleep problems (p=.002) at baseline than the Single Episode MDD group. Limitations: Small numbers of women with minD or a Single Episode MDD. Childhood maltreatment and family depression history were retrospectively reported. Conclusions: A Persistent/recurrent depression course is common during midlife. In addition to personal and family histories of depression, providers of midlife health care should recognize that current sleep problems and recent very upsetting events are strong risk factors for a pernicious depression course. (C) 2016 Elsevier B.V. All rights reserved.
The quality of the caregiver-child relationship is key to the well-being of children but assumptions based on research in western countries about the benefits of different types of substitute care may be questionable when applied elsewhere. This study assessed the quality of caregiver-child relationships and their association with child abuse in foster and residential care in Nigeria. The findings are relevant to European and North American countries as 4% of those looked after and 6% of care entrants in England are of African heritage and it is too easy to draw wrong conclusions about the care they might have received in their own countries. The study scrutinised 314 children aged 7-17 years from foster (157) and residential care settings (157) and assessed the caregiver-child relationship using the Positive Relationship Scale. The child abuse measure covered physical, sexual and emotional components and aggregated these into a single score. The subsequent analysis explored differences in child abuse between foster and residential care and the significance of other factors influencing levels of child abuse. It was found that the children in residential care had more positive relationships with caregivers than did those in foster care, even though abuse occurred in both settings. There were no gender differences in experiences of child abuse in either setting but children under the age of 12 were significantly more likely to have been abused while in care than those over this age. For children in residential care, age was the most significant factor associated with abuse. As these findings provide a perspective on children in substitute care in a West African city, they may be useful to social workers elsewhere who are responsible for children of African heritage, as they suggest that abuse often occurs in foster homes and that child-carer relationships in residential establishments can be good.
Membrane type1 matrix metalloproteinase (MT1-MMP) is implicated in pericellular proteolysis, and, together with tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), in the activation of pro-matrix metalloproteinase-2 on the cell surface. It is expressed on the cell surface either activated or as a proenzyme. A soluble form of MT1-MMP (sMT1-MMP) has been previously identified in periprosthetic tissues and fluid of patients with loose arthroplasty endoprostheses. The aim of this study was to examine periprosthetic tissues and fluids from patients with loose arthroplasty endoprostheses, as well as tissues and fluids from patients with other disorders, for the presence of sMT1-MMP, and to investigate its activation state and possible role. With antibody against MT1-MMP, a protein with molecular mass of similar to 57kDa was detected by western blotting in all samples tested, representing a soluble form of MT1-MMP, which cannot be ascribed to alternative splicing, as northern blotting showed only one transcript. With various biochemical methods, it was shown that this species occurs in a latent form bearing the N-terminal prodomain, and, additionally, it is bound to TIMP-2, which appeared to be bound via its C-terminal domain to a site different from the active site. Cell ELISA and immunohistochemical analysis revealed that, besides fibroblasts, all other cells, such as inflammatory, epithelial, endothelial, giant and cancer cells, express MT1-MMP on their plasma membrane as a proenzyme. Taking into account the proteolytic abilities of MT1-MMP, the latent sMT1-MMP-TIMP-2 complex could be considered as a new interstitial collagenase. However, the exact role, the production mechanism and the cell origin of this complex remain to be elucidated.
A digital low dropout regulator (D-LDO) manages to operate at low voltage and scale with process. But, the tradeoff between current efficiency and transient response speed limits its applications. In this work, a coarse-fine-tuning technique with burst-mode operation is employed to advance this trade-off. Once the output voltage under/overshoot is detected, the power MOS array changes with x16 unit size at 500 MHz sampling frequency for a fixed time, comparing with xi size and 50 MHz in steady state. The limit cycle oscillation (LCO) in steady state is reduced by a feed-forward compensation zero with negligible power and area overheads. The proposed D-LDO is simulated in a 65 nm CMOS process, achieving a 60 mV voltage undershoot and 0.36 ps FOM of speed with a 60 mu A quiescent current, and mode-1 LCO in steady state.
In this paper, a low voltage low dropout (LDO) regulator is designed and simulated in 0.13 mu m CMOS technology, which converts an input voltage of 1.2V into a stable regulated output voltage of 1.1 V using Ng-Spice circuit simulator. The two stage operational amplifier (Op-Amp) is used as an error amplifier (EA). Here, the Artificial Bee Colony (ABC) evolutionary algorithm based optimizer is demonstrated for solving the problem of the device sizing and other parameters of Op-Amp and optimization. This approach for designing two stage Op-Amp circuit does not require any analytical calculations and handles non-linear effects of sub-micron devices very effectively. The designed LDO is tested for a change in load current for 0-100 mA and it is found that the power supply rejection ratio (PSRR) is found to be 78.5 dB at 1 KHz and 28.7 dB at 10 MHz. The settling time of less than 1 mu sec observed during testing of line and load regulations.
As a driven accelerator, the CYCIAE-100 cyclotron is designed by China Institute of Atomic Energy for the Beijing Radio Ion-beam Facility project. The cyclotron RF system is designed to use two RF power sources of 100 kW to drive two half-wavelength cavities respectively. Two Dee accelerating electrodes are kept separately from each other inside the cyclotron, while their accelerating voltages are maintained in phase by the efforts of LLRF control. An analog-digital hybrid LLRF system has been developed to achieve cavity tuning control, dee voltage amplitude and phase stabilization etc. The analog subsystems designs are focused on RF signal up/down conversion, tuning control, and dee voltage regulation. The digital system provides an RF signal source, aligns the cavity phases and maintains a Finite State Machine. The digital parts combine with the analog functions to provide the LLRF control. A brief system hardware introduction will be given in this paper, followed by the review of several major characteristics of the digital control in the 100 MeV cyclotron LLRF system. The commissioning is also introduced, and most of the optimization during the process was done by changing the digital parts. (C) 2016 Elsevier B.V. All rights reserved.
The study was carried out in 48 poultry flocks to elucidate the roles of various complicating pathogens involved along with Newcastle disease (ND)/ low pathogenic avian influenza (LPAI) outbreaks. Necropsy was conducted and samples were collected for the isolation of Newcastle disease virus (NDV), Influenza A virus, infectious bronchitis virus (IBV), pathogenic bacteria; molecular detection of infectious laryngotracheitis virus (ILTV), fowl adeno virus (FAV), chicken anaemia virus (CAV), Mycoplasma synoviae (MS) and Mycoplasma gallisepticum (MG). The isolation results confirmed that 18/48 flocks (37%) were positive for the presence of hemagglutinating agents. Out of 18 hemagglutination (HA) positive flocks, 11 flocks (61%) were positive for both avian influenza virus (AIV) and NDV; 4 flocks (22%) were positive for NDV; and 3 flocks (17%) were positive for AIV. Sequence analysis of hemagglutinin and neuraminidase genes of AIV revealed that all were belonging to LPAI-H9N2 subtype. Sequence analysis of F gene of NDV revealed that they belong to virulent type. The PCR results confirmed the presence of three to seven etiological agents (CAV, FAV, ILTV, MG, MS and avian pathogenic E. coli along with LPAI/NDV from all the 18 HA-positive flocks. The detection rate of triple, quadruple, quintuple, sextuple and sevenfold infections was 17% (3 flocks), 28% (5 flocks), 11%, (2 flocks) 28% (5 flocks) and 17% (3 flocks), respectively. In conclusion, the disease complex involved more than one pathogen, primarily resulting from the interplay between LPAI-H9N2 and NDV; subsequently this could be exacerbated by co-infection with other agents which may cause exacerbated outbreaks that may otherwise go undetected in field.
This paper proposes a low power and low output ripple regulator for radio frequency identification tags. The inner blocks of regulator is supplied from elementary stages output of rectifier. The proposed operational amplifier works on AB class and its bias is in adaptive biasing form. The bandgap reference and sampling voltage resistors used in this paper are completely designed with transistors which culminate in low power dissipation. The regulator output voltage is 1.07 V, while the output ripple is +/- 1.1 mV. The value of line regulation, power supply rejection ratio, and regulator efficiency are 5.5 mV/V, 45.2 dB, and 71.3%, respectively. A 111 mu W power consumption has been calculated with 20 K omega load. The simulation is done with the help of Cadence software in 0.18 mu m CMOS technology, while its operational frequency is 960 MHz. The layout of the proposed regulator is 0.00125 mm(2).
We are developing a fully depleted silicon-on-insulator (FD-SOI) CMOS readout integrated circuit (ROIC) operated at temperatures below 4 K. Its application is planned for the readout circuit of high-impedance far-infrared detectors for astronomical observations. We designed a trans-impedance amplifier (TIA) using a CMOS operational amplifier (OPAMP) with FD-SOI technique. The TIA is optimized to readout signals from a germanium blocked impurity band (Ge BIB) detector which is highly sensitive to wavelengths of up to 200 m. For the first time, we demonstrated the FD-SOI CMOS OPAMP combined with the Ge BIB detector at 4.5 K. The result promises to solve issues faced by conventional cryogenic ROICs.
Temperature is the bottleneck for the anaerobic treatment of domestic wastewater in temperate climates. Most previous attempts to achieve anaerobic treatment at low temperatures have attempted to acclimatize mesophilic sludge and have failed at temperatures below 10-13 degrees C. We describe an alternative approach using communities from environments that have been exposed to low temperatures over evolutionary time-scales as seed for such reactors. Batch reactors were inoculated with a mixture of soils and sediments from the high Arctic and an Alpine lake to treat UV-sterilized raw domestic wastewater at 4, 8 and 15 degrees C. To evaluate the intrinsic treatment capacity of the bacteria the specific rates of methanogenesis and hydrolysis were evaluated. Specific methanogenic activity at 4, 8 and 15 degrees C was 63, 7.6 and 10.3 fmol CH4 cell(-1) day(-1) respectively. Specific putative hydrolysis rates were 76.2, 186.6 and 251.9 fgrams COD cell(-1) day(-1). Hydrolysis was twice as temperature sensitive as methanogenesis (Q(10): 4.62 and 1.57 respectively). The specific rates are over ten times higher than we have previously observed in microcosms fed with settled wastewater at the same temperatures. The results imply that inoculating reactors with cold-adapted communities is a promising way to develop biomass capable of treating anaerobic wastewater treatment at low temperatures whilst achieving an effluent that conforms to the EC Directive COD standards. Large-scale reactors are feasible if satisfactory cell concentrations can be achieved. (C) 2017 Published by Elsevier Ltd.
In plants, low temperatures can activate the CBF cold response pathway playing a prominent role in cold acclimation by triggering a set of cold-related gene expressions. CBF homologous gene, designated as LpCBF3, from a cold-tolerant perennial ryegrass (Lolium perenne L.) accession was identified. It carries the sequences for nuclear localization signal (NLS), AP2 DNA-binding domains and an acidic activation present in most of the plant CBF proteins. Southern analysis indicated the presence of three homologs of LpCBF3 gene in perennial ryegrass genome, and only one amino acid variation in LpCBF3 protein between cold-tolerant and -sensitive perennial ryegrass accessions. In their putative promoter regions, some differential regions were found. Northern blotting and RT-PCR analysis found that LpCBF3 reached the highest expression after 1.5 h of cold treatment (4C). The COR homologous gene, a downstream gene of CBF, can be expressed in the plant stem of cold-tolerant perennial ryegrass accessions without cold treatment. Without cold treatment, the COR gene cannot be activated in cold-sensitive perennial ryegrass accessions. Cold treatment can prompt expression levels of COR homologous genes in both perennial ryegrass accessions. In transgenic Arabidopsis, the overexpression of LpCBF3 with the 35S promoter resulted in dwarf-like plants, later flowering and greater freezing tolerance.
Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22-1.30) and 1.17 (95% CI: 1.14-1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.
Objective: This case-control study explored correlations between LP-PLA2 gene polymorphisms (A379V, V279F, and R92H) and susceptibility and severity of acute pancreatitis (AP) in a Chinese population. Materials and Methods: From October 2013 to October 2015, 94 AP patients were chosen as the case group. According to the Acute Physiology and Chronic Health Evaluation (APACHE) II score standard, AP patients were divided into a mild AP (MAP) group (n = 46) and severe AP (SAP) group (n = 48). The 48 SAP patients were further divided into an SAP with multiple organ dysfunction syndrome (MODS) group (n = 42) and SAP without MODS group (n = 6). Meanwhile, 96 healthy subjects who received physical examinations at the study hospitals were selected as the control group. Serum lipoprotein-associated phospholipase A2 (LP-PLA2) levels were detected by an enzyme-linked immunosorbent assay (ELISA). The A379V (s1051931), V279F (rs16874954), and R92H (rs13989) polymorphisms of the LP-PLA2 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significant differences in the frequencies of the LP-PLA2 gene polymorphisms between the AP group and the control group. The distribution of V279F-AA+AC genotype and R92H-AA+AG genotype in the AP group was higher than that in the control group, whereas the SAP group and SAP with MODS group distributions were higher than those in the MAP group and SAP without MODS group (both p < 0.05). G-C-A, G-A-G, and G-C-G haploids formed by A379V, V279F, and R92H may be associated with AP susceptibility. LP-PLA2 gene polymorphisms could affect serum LP-PLA2 level, whereas the V279F-A allele gene, the R92H-A allele gene, serum LP-PLA2 level, and serum amylase may be independent risk factors for AP (all p < 0.05). Conclusion: These results demonstrated that the LP-PLA2 gene polymorphisms, V279F and R92H, may be associated with susceptibility to and severity of AP.
Histone methylation is a complicate and dynamic epigenetic modification that regulates gene transcription, chromosomal structure and cell differentiation. Here, we discovered the interaction between the H3K4 demethylase, lysine specific demethylase 1 (LSD1, an important component of CoREST repressor complex) and the H3K27 methyltransferase, enhancer of zeste homolog 2 (EZH2, an essential component of PRC2). Immuno-precipitation and GST-pull down assay were performed to observe the interaction between the proteins. The MCF-7 cells were cultured and transfected with the siRNA. The mRNA and proteins were examined by using the real-time polymerase chain reaction (RT-PCR) and western blot assay, respectively. HPLC and LC-MS/MS analysis were performed to purify the proteins. RTPCR- based quantitative ChIP analysis were performed. LSD1 interacts with histone modification protein EZH2 in MCF-7 cells. LSD1 and EZH2 target a few common genes. LSD1 knockdown and EZH2 knockdown affect protein expression. LSD1 knockdown and EZH2 knockdown affect the proteins involving in IFN signaling pathway. LSD1 and EZH2 modify histone methylation at IRF9 gene locus. We systematically analyzed the proteins that are affected by either LSD1 or EZH2 knockdown with proteomic approaches and identified that the interferon pathway and some other pathways are commonly affected. The interaction between LSD1 and EZH2 stabilizes the binding of LSD1 to the promoter region of IRF9, which is a key transcription factor of the interferon pathway. In conclusion, our study revealed that the coordination between histone demethylases and methyl-transferases might serve as a double lock system to suppress the expression of interferon stimulated genes. (C) 2017 Published by Elsevier Masson SAS.
Pricing and hedging exotic options using local stochastic volatility models drew a serious attention within the last decade, and nowadays became almost a standard approach to this problem. In this paper we show how this framework could be extended by adding to the model stochastic interest rates and correlated jumps in all three components. We also propose a new fully implicit modification of the popular Hundsdorfer and Verwer and Modified Craig-Sneyd finite-difference schemes which provides second-order approximation in space and time, is unconditionally stable and preserves positivity of the solution, while still has a linear complexity in the number of grid nodes.
The blow fly, Lucilia cuprina (Wiedemann, 1830) is a parasitic insect of major global economic importance. Maggots of this fly parasitize the skin of animal hosts, feed on excretions and tissues, and cause severe disease (flystrike or myiasis). Although there has been considerable research on L. cuprina over the years, little is understood about the molecular biology, biochemistry and genetics of this parasitic fly, as well as its relationship with its hosts and the disease that it causes. This Situation might change with the recent report of the draft genome and transcriptome of this blow fly, which has given new and global insights into its biology, interactions with the host animal and aspects of insecticide resistance at the molecular level. This genomic resource will likely enable many fundamental and applied research areas in the future. The present article gives a background on L. cuprina and myiasis, a brief account of past and current treatment, prevention and control approaches, and provides a perspective on the impact that the L cuprina genome should have on future research of this and related parasitic flies, and the design of new and improved interventions for myiasis. (C) 2016 Elsevier Inc. All rights reserved.
Objective: The objective of this study was to construct a recombinant vector expressing siRNA targetedly inhibiting aquaporin 3 (AQP3), and to evaluate the effects of AQP3 inhibition on the proliferation and invasion of XWLC-05 human lung cancer cells. Methods: We obtained human AQP3 sequence from the Genbank and established the recombinant vector expressing siRNA targeting AQP3. After the transfection of the recombinant vectors, the expression of AQP3 was determined by RT-PCR and western blot. The MTS assay, flow cytometry and Transwell assay were conducted to detect the proliferation, cell cycle process, apoptosis and invasion of XVVLC-05 cells. Then the activity of metal matrix proteinase (MMP) 2 was determined by gelatin zymography. Tumor formation in vivo experiments were also conducted in nude mice. Results: RNA interference (RNAi) of AQP3 substantially suppressed the XWLC-05 cell proliferation and invasion, blocked the cell cycle progressing and promoted cell apoptosis. In addition, the activity of MMP2 was remarkably attenuated in RNAi group. AQP3 RNAi did not affect the tumor formation rate in nude mice but reduced the tumor growth. Conclusion: The inhibition of AQP3 retarded the growth and invasiveness of XWLC-05 lung cancer cells and decreased the activity of MMP2. (C) 2017 Elsevier Inc. All rights reserved.
Background: The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. Methods: Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies. In addition scratch assay with time lapse microscopy and in vivo xenograft tumor and mouse metastasis assays were performed. Results: ITSN-1s, a prevalent protein of lung tissue, is significantly downregulated in human LC cells and LC tissue. Restoring ITSN-1s protein level decreases LC cell proliferation and clonogenic potential. In vivo studies indicate that immunodeficient mice injected with A549 + ITSN-1s cells develop less and smaller metastatic tumors compared to mice injected with A549 cells. Our studies also show that restoring ITSN-1s protein level increases the interaction between Cbl E3 ubiquitin ligase and Eps8 resulting in enhanced ubiquitination of the Eps8 oncoprotein. Subsequently, downstream unproductive assembly of the Eps8-mSos1 complex leads to impaired activation of the small GTPase Rac1. Impaired Rac1 activation mediated by ITSN-1s reorganizes the cytoskeleton (increased thick actin bundles and focal adhesion (FA) complexes as well as collapse of the vimentin filament network) in favor of decreased LC cell migration and metastasis. Conclusion: ITSN-1s induced Eps8 ubiquitination and impaired Eps8-mSos1 complex formation, leading to impaired activation of Rac1, is a novel signaling mechanism crucial for abolishing the progression and metastatic potential of LC cells.
During the peripartum period, the lung must respond to dramatic changes in circulating hormones, nutritional factors, and physiologic signals during its transition to becoming the organ of gas exchange. Protein synthesis consumes a significant proportion of metabolic resources and is inhibited by many environmental stresses. We hypothesized that translational control mechanisms play a role in the perinatal lung. Immunoblots of late-gestation (Fetal Day [FD] 17-22) rat lung extracts revealed gradual decreases in phosphorylated forms of the mammalian target of rapamycin effectors, eukaryotic initiation factor (eIF) 4E-binding protein, p70 56 kinase, and ribosomal protein 56, followed by sharp increases on Postnatal Day 1 (P1). Immunohistochemistry showed phospho-56 staining was most prominent in epithelial cells of the large and small airways. m(7)GTP-sepharose pulldown experiments showed a decrease in association of translation initiation factor, eIF4E, with its inhibitor, eIF4E-binding protein, and a concomitant increase in eIF4E association with eIF4G immediately after birth, and polysome profiles confirmed a decrease in abundance of large polysomes between FD19 and FD22, which was reversed on P1. Microarray analysis of polysomal versus total RNA from FD19, FD22, and P1 lungs was used to identify specific genes, the association of which with large polysomes changed either pre- or postnatally. RT-PCR and Northern blotting were used to confirm translational changes in selected candidate genes, including a prenatal increase in IL-18 and a postnatal decrease in regulatory subunit 2 of protein phosphatase 1. Translational regulation of IL-18 and protein phosphatase 1 regulatory (inhibitor) subunit 2 is gene-specific, as these changes contrast with the corresponding global changes in polysome abundance.
The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects. (C) 2017 Elsevier GmbH. All rights reserved.
Objective. LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. Methods. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. Results. A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN. Conclusion. Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment.
Systemic lupus erythematosus (SLE) is an autoimmune disorder with complex genetic underpinnings. This review attempts to assemble the myriad of genomic findings to build a clearer picture of the pathobiology of SLE to serve as a guide for therapeutics. Over 100 genes are now known for SLE, and several more penetrant ones have led to the emergence of more defined lupus phenotypes. Also discussed here are the targeted therapies that have come up on the horizon and the specific biologic mechanisms of more traditional therapies which have only recently been explored. The diagnostic toolbox has been enhanced by the addition of new antibodies, gene expression signatures, and mutation panels. This provides an opportunity to piece together the lupus puzzle and even revisit the clinical classification of SLE.
In this paper, the stability issue of Lur'e systems governed by a control law stabilising their forward Euler approximate model is investigated. More specifically, the considered control law is obtained by exploiting the advantages of a new Lur'e type Lyapunov function with disconnected level sets. This Lyapunov function is adapted to discrete-time Lur'e systems and to the structure of the forward Euler approximate model. The main result consists of linear matrix inequality conditions allowing to guarantee that the continuous-time Lur'e system associated with the proposed digital control law is globally asymptotically stable. The relevance of this approach is illustrated using a numerical example.
We detected luteinizing hormone receptor (LHR) mRNA in the immature rat uterus by northern blotting and downregulation of this receptor mRNA after pregnant mare serum gonadotropin (PMSG)-human chorionic gonadotropin (hCG) treatment. After administration of hCG, the mRNA levels in the rat uterus declined to an extremely low level from Days 1 to 3 and then rebounded and reached higher than pretreatment values at Day 4. At Day 5 the levels were 3-fold higher than the control levels. The cultured uterus displayed an hCG concentration-dependent increase in cAMP production in the medium. Immunohistochemical experiments showed that these receptor proteins were expressed in the epithelial cells of the endometrium. These results suggest that functional LHRs are present in the immature rat uterus and are downregulated by signals resulting from hCG treatment. These data may support the idea that LH acts on the uterus to inhibit contraction at ovulation. Although the precise role of the LHR in the uterus remains unknown, this study may provide a model with which to investigate the regulation of LHR.
Background: Profilin is a small actin-binding protein that contributes to the allergenic potency of many fruits and vegetables, including tomato. Two highly similar genes encoding tomato profilin have been isolated and designated as allergen Lyc a 1.01 and Lye a 1.02. Objective: The aim of the study was to generate profilin-reduced hypoallergenic tomato fruits by silencing of both genes in transgenic tomato plants by means of RNA interference (RNAi). Methods: The efficiency of gene silencing was documented by means of Northern blotting, immunoblotting, and skin prick testing. Results: Quantification of the remaining protein revealed that profilin accumulation in transgenic fruits was decreased 10-fold compared with that seen in untransformed controls. This decrease was sufficient to cause a reduced allergenic reactivity in patients with tomato allergy, as determined with skin prick tests. Because most patients with tomato allergy are not monosensitized to profilin, the IgE reactivity to the profilin-silenced tomato fruits in vivo varied widely between individuals tested. Conclusion: We could demonstrate the efficient silencing of both profilin genes in transgenic tomato plants using RNAi This resulted in Lyc a 1-diminished tomato fruits, providing proof of concept and demonstrating that RNAi can be used to design allergen-reduced food. However, simultaneous silencing of multiple allergens will be required to design hypoallergenic tomatoes. Clinical implications: Our findings demonstrate the feasibility of creating low-allergenic food by using RNAL This concept constitutes a novel approach to allergen avoidance.
Isolation of RNA from recalcitrant tree tissues has been problematic due to large amounts of secondary metabolites and interfering compounds in their cells. We have developed an efficient RNA extraction method, which yielded high-quality RNA preparations from tissues of the lychee tree. The method reported here utilized EDTA, LSS, and CTAB to successfully inhibit RNase activities. It was found that a high ionic strength brought about by 2 M NaCl was necessary. In addition, secondary metabolites and other interfering compounds were effectively removed using sodium borate and PVPP under a deoxidized condition. The quality of purified RNA was tested by both RACE and Northern blotting analysis, ensuring that the RNA could be used for subsequent gene expression analysis. This method has been successfully applied to purify RNA from 15 other plant species. In conclusion, the protocol reported here is expected to have excellent applications for RNA isolation from recalcitrant plant tissues.
BACKGROUND/OBJECTIVES: Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS: Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and 30 pM lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B (NF-kappa B), inhibitor kappa B (I kappa B), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor a (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) were determined via enzyme-linked immunosorbent assays. RESULTS: In cells treated with lycopene and LPS, the mRNA expression of TNF-alpha, IL-1 beta, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of PGE2 and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of NF-kappa B and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS: Lycopene restrains NF-kappa B and JNK activation, which causes inflammation, and suppresses the expression of TNF-alpha, IL-1 beta, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.
The tobacco beta-1,3-glucanase gene (GLU), alfalfa defensin gene alfAFP, and their bivalent gene GLU-AFP were introduced into tomato cv. Micro-Tom via Agrobacterium-mediated method. Transformants were obtained and confirmed by GUS histochemical staining, PCR, and Southern blotting. Northern blotting analysis with GLU and APF probes revealed a variation in the expression among these transformants at transcription level. One to three copies of the transgene were, respectively, integrated into the tomato nuclear genome. Performance test of resistance to Ralstonia solanacearum with T-1 generation transgenic tomato lines showed that the transgenic lines exhibited higher resistance to the infected pathogens than nontransgenic plants, and the resistance levels were related to expression levels of the transgene, showing a dose effect. The transgenic tomato harboring GLU - AFP cassette showed the highest disease resistance, which suggested that the alfAFP and glucanase genes have synergistical effects on the resistance to R. solanacearum. Some independent lines with high disease resistance, low variability, and stable expression of transgenes could be selected for further studies and molecular breeding.
The immune function of the chicken spleen depends on its different compartments of red and white pulps, but little is known about the mechanism underlying lymphocyte homing towards the different compartments. In the present study, the role of lymphocyte homing in the chicken spleen was investigated during lipopolysaccharide (LPS) stimulation. Morphological analysis demonstrated the cuboidal endothelial cells of the splenic sheathed capillary facilitated the passage of lymphocyte homing to the chicken spleen. The tissue-specific adhesion molecules-vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MADCAM-1) expressed on the sheathed capillary, which suggested the high endothelial venule (HEV)-like vessels of the chicken spleen. Electron microscope analysis showed LPS activated the endothelium of the sheathed capillary and recruited lymphocytes to the chicken spleen. Transferring of 5, 6-carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled lymphocytes depicted the rout of lymphocyte homing to the compartments of the chicken spleen was from the white pulp to the red pulp. Furthermore, the mRNA and protein levels of adhesion molecular integrin beta 1 and VCAM-1 increased after LPS stimulation. The mechanism underlying the integrin beta 1 and VCAM-1 during LPS stimulation might be associated with the integrin linked kinase (ILK)-dependent regulation of protein kinase B (PKB/AKT). This study firstly shows lymphocyte homing in the chicken spleen after LPS-induced inflammation. These results contribute to our knowledge of comparative immunology and provide a better means for investigating the pharmacological strategies concerning the possible role of lymphocyte homing in inflammation and immunological reactions in infectious disease.
This review provides a synopsis for genetic counselors of the major concepts of lymphoma predisposition: genomic instability, immune deficiency, inappropriate lymphoproliferation, and chronic antigen stimulation. We discuss syndromes typifying each of these mechanisms. Importantly, our review of the genetic counseling literature reveals sparse discussion of genetically-based immune-mediated lymphoma predisposition, which we address in depth here. We aim to increase awareness among genetic counselors and colleagues in oncology about familial susceptibility and facilitate critical thinking about lymphoma risk assessment. Clinical application of this knowledge is aided by recommendations for collection of personal and family history to guide risk assessment and testing. Lastly, we include a special discussion of genetic counseling issues including perceptions of the context, nature, and magnitude of lymphoma risk, as well as coping with awareness of susceptibility to lymphoma.
The anomalous distribution of adhesive proteins throughout on the cell surface of the Mycobacterium tuberculosis H(37)Rv and their contribution in cell surface adhesion and host-pathogen interaction remain elusive. The completion of M. tuberculosis H(37)Rv genome sequence analysis gives some interesting information about polymorphic GC-rich repetitive sequence (PGRS) subfamily of M. tuberculosis that encodes fibronectin binding proteins (FnBP), which have been extensively studied, but the function in the pathogenesis of most of these proteins remains unknown and unclear. This review addresses the M. tuberculosis entry mechanism in the host cell. In particular, an effort has been made to focus on several aspects, (a) association of FnBP encodes by PE PGRS protein family of M. tuberculosis during host-pathogen interactions. (b) Effect of calcium ions in and outside of the host cell is overriding to maintenance of calcium trafficking in phagocytosis. Furthermore, FnBP may be a potential source of antigenic variation that participating in evoking immune response. M. tuberculosis entry mechanism does not have a major influence alone, involvement of calcium ions, perhaps shed light on host-pathogen interaction relationship, and could open up new avenues for development of novel drug by targeting M. tuberculosis FnBP and blockade of selective adhesions could be useful for therapeutics. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 820-826, 2016
Introduction:Mycobacterium abscessus is an emerging mycobacteria that is responsible for lung diseases and healthcare-associated extrapulmonary infections. Recent findings support its taxonomic status as a single species comprising 3 subspecies designated abscessus, bolletii and massiliense. We performed a review of English-language publications investigating all three of these subspecies.Areas covered: Worldwide, human infections are often attributable to environmental contamination, although the isolation of M. abscessus in this reservoir is very rare. Basic research has demonstrated an association between virulence and cell wall components and cording, and genome analysis has identified gene transfer from other bacteria. The bacteriological diagnosis of M. abscessus is based on innovative tools combining molecular biology and mass spectrometry. Genotypic and phenotypic susceptibility testing are required to predict the success of macrolide (clarithromycin or azithromycin)-based therapeutic regimens. Genotyping methods are helpful to assess relapse and cross-transmission and to search for a common source. Treatment is not standardised, and outcomes are often unsatisfactory.Expert commentary:M. abscessus is still an open field in terms of clinical and bacteriological research. Further knowledge of its ecology and transmission routes, as well as host-pathogen interactions, is required. Because the number of human cases is increasing, it is also necessary to identify more active treatments and perform clinical trials to assess standard effective regimens.
Mac-2 binding protein (Mac-2BP) is a secreted tumor antigen that is elevated in many cancers and implicated in tumor metastasis, as well as cell adhesion and immune functions. We focused on the human telomerase reverse transcriptase (hTERT) induced Mac-2BP expression and the relationship between Mac-2BP expression and the progression of gastric cancer. A cDNA expression array analysis was performed on the telomerase-negative cell line, SW13, which was engineered to overexpress hTERT when compared with the parental SW13 cell. hTERT-induced Mac-2BP expression was confirmed via RT-PCR and Northern blotting. ELISA and flow cytometric analyses revealed that Mac-2BP protein was increased by 2- to 4-fold in hTERT-overexpressing cells compared with the mock control. Mac-2BP expression was significantly reduced when the overexpressed hTERT was neutralized by the introduction of hTERT-specific siRNA. These results suggest that Mac-2BP expression is modulated by hTERT. Mac-2BP levels in both gastric cancer cells and tumor tissues were determined via Northern blot analysis and immunohistochemistry. Mac-2BP protein was highly expressed in most gastric cancer cell lines, and gastric tumor tissues were stained more densely than normal tissues. The intracellular and secreted Mac-2BP levels were also evaluated ilia ELISA, indicating that Mac-2BP was expressed and secreted more abundantly in gastric cancer patients than in healthy donors. The elevated serum Mac-2BP level in gastric tumor patients was also significantly associated with distant metastasis (p = 0.05) and higher tumor stage (p = 0.04). Our findings suggest that Mac-2BP is induced by hTERT. and that it may prove to be a useful prognostic marker for the detection of malignant progression of metastatic stomach cancers. (c) 2006 Wiley-Liss, Inc.
Several simian adenoviruses (AdVs) have been detected and isolated in various species of non-human primates with the goals of monitoring the health of wildlife and investigating their potential for zoonotic disease transmission. Here, we provide evidence of AdV infection in wild Assamese macaques (Macaca assamensis assamensis) at Phu Khieo Wildlife Sanctuary, Thailand, based on polymerase chain reaction of non-invasively collected fecal samples. Eight out of 110 fecal samples (7.3%), or five out of 87 monkeys (5.7%), showed evidence of AdV infection. All infected individuals were infants or juveniles. Phylogenetic analysis based on the sequence of hexon and polymerase genes revealed two different AdV genotypes. One genotype clustered in the human AdV-G group, while another showed 100% identity with previously reported AdVs of captive Chinese rhesus macaques (Macaca mulatta), which may be tentatively classified as a new species of AdV in non-human primates while awaiting further supporting evidence.
Affective coldness is one of the main features of Machiavellianism. Recent studies have revealed that Machiavellians are emotionally detached and that this "affective blunting" is associated with intense feelings, emotional instability, negative emotions, and difficulty in enduring distress. We used brain-imaging techniques to investigate emotion regulation in Machiavellianism at a neuropsychological level. We used situations in which participants were required to demonstrate emotional flexibility to explore the controversy surrounding the fact that Machiavellianism is associated with both cold-mindedness and emotional instability. Participants performed a reappraisal task in which emotionally evocative pictures (from the International Affective Picture System) were presented in different contexts (negative, positive, and neutral). They were asked to interpret a scenario according to its title and to reinterpret it according to another context created by a new title (e.g., negatively labeled pictures shifted to positively labeled ones). During task performance, Machiavellians showed increased activation of brain regions associated with emotion generation-for example, the amygdala and insula. This indicates that Machiavellian individuals are able to be involved emotionally in social situations. Increased activation in the temporal and parahippocampal regions during reappraisal suggests that Machiavellians use semantic-perceptual processes to construct alternative interpretations of the same situation and have enhanced memory for emotional stimuli. Furthermore, they seem to possess an intense awareness that leads them to shift attention from external to internal information to detect environmental changes. These cognitive processes may enable them to adjust their behavior quickly. This study supports the flexibility hypothesis of Machiavellianism and suggests that Machiavellians' approach to emotion regulation is linked to their rational mode of thinking.
Nanoscale resistive memory devices are expected to fuel dense integration of electronic synapses for large-scale neuromorphic systems. To realize such a brain-inspired computing chip, a compact CMOS spiking neuron that performs in situ learning and computing while driving a large number of resistive synapses is desired. This brief presents a novel leaky integrate-and-fire neuron design that implements the dual-mode operation of current integration and synaptic drive, with a single operational amplifier (opamp) and enables in situ learning with crossbar resistive synapses. The proposed design was implemented in a 0.18-mu m CMOS technology. Measurements show neuron's ability to drive a thousand resistive synapses and demonstrate in situ associative learning. The neuron circuit occupies a small area of 0.01mm(2) and has an energy efficiency value of 9.3 pJ/spike/synapse.
Background: The correct protein coding region identification is an important and latent problem in the molecular biology field. This problem becomes a challenge due to the lack of deep knowledge about the biological systems and unfamiliarity of conservative characteristics in the messenger RNA ( mRNA). Therefore, it is fundamental to research for computational methods aiming to help the patterns discovery for identification of the Translation Initiation Sites (TIS). In the field of Bioinformatics, machine learning methods have been widely applied based on the inductive inference, as Inductive Support Vector Machine (ISVM). On the other hand, not so much attention has been given to transductive inference-based machine learning methods such as Transductive Support Vector Machine (TSVM). The transductive inference performs well for problems in which the amount of unlabeled sequences is considerably greater than the labeled ones. Similarly, the problem of predicting the TIS may take advantage of transductive methods due to the fact that the amount of new sequences grows rapidly with the progress of Genome Project that allows the study of new organisms. Consequently, this work aims to investigate the transductive learning towards TIS identification and compare the results with those obtained in inductive method. Results: The transductive inference presents better results both in F-measure and in sensitivity in comparison with the inductive method for predicting the TIS. Additionally, it presents the least failure rate for identifying the TIS, presenting a smaller number of False Negatives (FN) than the ISVM. The ISVM and TSVM methods were validated with the molecules from the most representative organisms contained in the RefSeq database: Rattus norvegicus, Mus musculus, Homo sapiens, Drosophila melanogaster and Arabidopsis thaliana. The transductive method presented F-measure and sensitivity higher than 90% and also higher than the results obtained with ISVM. The ISVM and TSVM approaches were implemented in the TransduTIS tool, TransduTIS-I and TransduTIS-T respectively, available in a web interface. These approaches were compared with the TISHunter, TIS Miner, NetStart tools, presenting satisfactory results. Conclusions: In relation to precision, the results are similar for the ISVM and TSVM classifiers. However, the results show that the application of TSVM approach ensured an improvement, specially for F-measure and sensitivity. Moreover, it was possible to identify a potential for the application of TSVM, which is for organisms in the initial study phase with few identified sequences in the databases.
A symbolic macromodel for slew and settling characterization of fully differential switched-capacitor (SC) integrators is proposed in this work. This model is intended for fast behavioral simulation of data converters in the time-domain. The main advantages of the proposed model are: 1) it can be created automatically without the need of running a transient simulation; 2) it is fully composed of circuit elements that can be simulated by SPICE or MATLAB; 3) it is created in symbolic form so that adjustment of the transistor-level circuit is directly reflected in the macromodel without the need of remodeling. The proposed modeling methodology is validated by applying to SC integrators implemented by two different operational amplifiers. The step response waveforms of the integrator model have good agreement to the transistor-level simulation results with a speedup of about 20x.
This paper describes a macromodel of operational amplifiers for compressor circuit design. The macromodel allows to simulate the operational amplifier with singlepower supply as well as double-power supply. The output waveforms using the macromodel are compared with those using the pre-set model only with double-power supply. The output voltages using the present macromodel are amplified in the region less than 200 mV input voltages and are compressed in the region larger than 200mV. On the other hand, the output voltages using the pre-set model are constantly amplified in the whole region. It has been found that the macromodel that can take into account the behavior of a single power supply is suitable in simulating of compressor circuits.
Long-range electrostatic forces play an important role in molecular biology, particularly in macromolecular interactions. However, calculating the electrostatic forces for irregularly shaped molecules immersed in water is a difficult task. Here, we report a new tool, DelPhiForce, which is a tool in the DelPhi package that calculates and visualizes the electrostatic forces in biomolecular systems. In parallel, the DelPhi algorithm for modeling electrostatic potential at user-defined positions has been enhanced to include triquadratic and tricubic interpolation methods. The tricubic interpolation method has been tested against analytical solutions and it has been demonstrated that the corresponding errors are negligibly small at resolution 4 grids/angstrom. The DelPhiForce is further applied in the study of forces acting between partners of three protein-protein complexes. It has been demonstrated that electrostatic forces play a dual role by steering binding partners (so that the partners recognize their native interfaces) and exerting an electrostatic torque (if the mutual orientations of the partners are not native-like). The output of DelPhiForce is in a format that VMD can read and visualize, and provides additional options for analysis of protein-protein binding. DelPhiForce is available for download from the DelPhi webpage at http://compbio.clemson.edu/downloadDir/delphiforce.tar.gz (C) 2017 Wiley Periodicals, Inc.
Mucosal immunity at the intestinal level is constantly challenged by the presence of external food and microbial antigens and must be kept under strict control to avoid the rise of aberrant inflammation. Among cells of the innate immunity, macrophages expressing the chemokine receptor CX3CR1 are strategically located near the gut epithelial barrier. These cells contribute to the maintenance of homeostasis by producing the anti-inflammatory cytokine IL-10; however, their role in the control of full blown inflammation and tissue injury is controversial. In this study we investigated mice proficient or deficient for the expression of the CX3CR1 receptor in a model of dextran sulphate sodium (DSS) induced acute colitis. We found that KO mice (CX3CR1(GFP/GFP)) had a more severe disease compared to WT mice (CX3CR1(GFP/+)), both in terms of histological examination of colonic tissues and leukocyte infiltration, with an expansion of macrophages and CD4-Th17 lymphocytes. The expression of several inflammatory mediators (IL-1 beta, IL-6, IFN gamma, iNOS) was also significantly upregulated in KO mice, despite higher IL-10 production. Overall, our study demonstrates that macrophages expressing a functional CX3CR1 receptor have an important and non-redundant role in controlling the abnormal intestinal inflammation that may lead to tissue damage. (C) 2016 Elsevier GmbH. All rights reserved.
The works of Richard Wagner have been celebrated for their impact on progressive elements in European culture, as a bridge from romanticism to modernism. In France the influence of Wagner on symbolist writers and artists, and musicians sympathetic to them, has emerged as particularly significant. But there was also a conservative response to Wagner that has received much less attention in the scholarly literature. This filiation is exemplified in the figure of Alberic Magnard and his opera Berenice (1911), which he claimed was influenced by a "classical" Wagner. This article considers the classicism of Berenice and its composer from several perspectives: portrayals of temperament that demonstrate consonance with classical precepts, political readings that emphasize classical values, the legacy of the French theater of the seventeenth century, and strategies of tonal organization and motivic development related to the German symphony extending back to Beethoven.
Magnesium silicide (Mg2Si) is the one of the most attractive and promising green thermo-electric material to convert the heat into electricity in the mid temperature range (RT to 600 degrees C). However, synthesizing of Mg2Si compound through liquid and solid state processing carries several challenges such as processing time, inhomogenous stoichiometry and phase purity. The alternative method is demonstrated by rapid in-situ synthesis of pure nano-crystalline Mg2Si doped with Bi (0-0.025 at.%) by spark plasma sintering (SPS). XRD and electron microscopy studies confirm the formation of Mg2Si compound and EDS confirm chemical and doping homogeneity. The superior power factor of 11 mu W/cm-k(2) is achieved at 550 degrees C. (C) 2017 Elsevier B.V. All rights reserved.
Post-stroke depression (PSD) is a common psychiatric complication of stroke that is associated with a poor outcome in stroke patients. Our aim was to assess the association between the serum magnesium levels and the presence of PSD in Chinese patients. Two hundred nine stroke patients were included in the study. Depressive symptoms were measured by the 17-Hamilton Rating Scale for Depression at 3 months after stroke. Based on the depressive symptoms, diagnoses of depression were made in line with the DSM-IV criteria for PSD. Serum magnesium levels were evaluated using the dimethyl aniline blue colorimetric method at admission. Multivariate analyses were conducted using logistic regression models. Further, 120 normal subjects were recruited, and their serum magnesium levels were also measured as control. At 3 months, fifty-nine patients (28.2%) were diagnosed as PSD. The serum magnesium levels were significantly lower in both PSD patients and non-PSD patients than in normal subjects (p < 0.001). Indeed, patients with PSD showed lower serum magnesium levels (p < 0.001) than did non-PSD patients at admission. In the multivariate analyses, after adjusting for potential variables, we found that an increased risk of PSD was associated with serum magnesium levels <= 0.84mmol/L (OR 2.614, 95% CI 1.178-5.798, p=0.018). Low serum magnesium levels at admission were found to be associated with the presence of PSD at 3 months after stroke.
The combination of nanoparticles with the polymerase chain reaction (PCR) can have benefits such as easier sample handling or higher sensitivity, but also drawbacks such as loss of colloidal stability or inhibition of the PCR. The present work systematically investigates the interaction of magnetic iron oxide nanoparticles (MIONs) with the PCR in terms of colloidal stability and potential PCR inhibition due to interaction between the PCR components and the nanoparticle surface. Several types of MIONs with and without surface functionalisation by sodium citrate, dextran and 3-aminopropyl-triethoxysilane (APTES) were prepared and characterised by Transmission Electron Microscopy (TEM), dynamic light scattering (DLS) and Fourier Transform Infrared (FT-IR) spectroscopy. Colloidal stability in the presence of the PCR components was investigated both at room temperature and under PCR thermo-cycling. Dextran-stabilized MIONs show the best colloidal stability in the PCR mix at both room and elevated temperatures. Citrate and APTES-stabilised as well as uncoated MIONs show a comparable PCR inhibition near the concentration 0.1 mg ml(-1) while the inhibition of dextran stabilized MIONs became apparent near 0.5 mg ml(-1). It was demonstrated that the PCR could be effectively carried out even in the presence of elevated concentration of MIONs up to 2 mg ml(-1) by choosing the right coating approach and supplementing the reaction mix by critical components, Taq DNA polymerase and Mg2+ ions. (C) 2017 Elsevier B.V. All rights reserved.
Early integration of sustainability decisions and mineralogical attributes into the design of minerals processing units offers potential for reducing environmental impacts at mining and processing sites. The objective of this study is to demonstrate how the integration of sustainability indicators and mineralogical attributes could be achieved in developing an integrated modelling framework of a magnetic separator. A magnetic separator unit model based on existing literature was developed to include process stream mineralogical data and to output sustainability indicators. The overall sustainability of processing three ore types (low, medium and high grade iron ore) was evaluated using the developed model. Novel measures for evaluating magnetic separation (Grade Recovery Deviation Index (GRDI)) and energy efficiency (Rotational Energy Transfer Efficiency (RETE)) that incorporate the use of ore characteristics were developed in this study. These measures were used to calculate the separation and energy efficiency sustainability indicator ratings. In total eleven magnetic separator sustainability indicators were identified. Each indicator was assigned a weighting value out of 10 based on its importance. Of the 11 sustainability indicators identified; safety, reliability, Carbon dioxide (CO2) emissions, water use, noise and job creation ratings did not vary with changing mineralogical attributes of the feed ore. GRDI, RETE, electricity cost, particle emissions and waste generation ratings were observed to be dependent on the ore characteristics and therefore their values varied with different feed ore grades. The Analytic Hierarchy Process (AHP) and Weighted Sum Method (WSM) methods were applied to the sustainability indicator ratings and weightings to evaluate an overall sustainability cardinal score of processing a particular ore feed. Results of this study demonstrate the dependence of overall process sustainability indicators on feed ore mineralogical attributes. The results also provide an indication of the effect of ore variability (typical within a single deposit) on sustainability indicators. (C) 2016 Elsevier Ltd. All rights reserved.
Magnetic force spectroscopy is a rapidly developing single molecule technique that has found numerous applications at the interface of physics and biology. Since the invention of the first magnetic tweezers, a number of modifications to the approach have helped to relieve the limitations of the original design while amplifying its strengths. Inventive molecular biology solutions further advanced the technique by expanding its possible applications. In its present form, the method can be applied to both single molecules and live cells without resorting to intense irradiation, can be easily multiplexed, accommodates multiple DNAs, displays impressive resolution, and allows a remarkable ease in the stretching and twisting of macromolecules. In this review, we describe the architecture of magnetic tweezers, key requirements for experimental design and analysis of data, and outline several applications of the method that illustrate its versatility.
We present a magnetically actuated microfluidic transistor (valve), an on-chip micro-valve that uses magnetorheological fluids micropatterned onto an elastomeric membrane to develop an ultra-compact solution for digital control of microfluidic circuits. We simulated the micro-valves theoretically and also characterized micro-fabricated devices experimentally. We simulated the effects of channel and valve geometry on the deformability of the valve. We experimentally characterized the effects of channel and valve geometry on the ability to reversibly close channels fully. We characterized the microfabricated valves in the flow rate range of 0.02-1 mu l/min. Among the various kinds of valves examined, for lower flow rates, circular valves with a 700 mu m diameter in 300 mu m width channel, and in higher flow rates, rectangular valves 700 mu m wide in the same channel show the best ability in terms of valve closure and response time. The fabrication and the integration of the proposed valve are compatible with a range of polymer microfabrication technologies having the advantage of simple fabrication, small size, and no external power requirement. These valve structures can be promising solutions for pumping and active flow control for portable analytical instrumentation, point-of-care diagnostic devices, and even wearable microfluidic devices. [2015-0296]
Sugarcane grassy shoot (SCGS) disease is associated with the presence of 16SrXI group phytoplasmas that are transmitted by leafhoppers; limited studies have been performed in India toward its natural transmission. To determine the insect vectors that transmit the disease in nature, leafhopper species from SCGS-infected fields at Shahjahanpur, Central Uttar Pradesh, India, were collected and analyzed for phytoplasma presence using nested polymerase chain reaction with phytoplasma-specific primers. An similar to 1.2-kb amplified DNA fragment was detected in nested PCR from the three major leafhopper species, viz. Maiestas portica (Melichar), Exitianus indicus (Ross) and Cofana unimaculata (Signoret), and the symptomatic sugarcane leaves of variety CoS 07250. BLASTn analysis of similar to 1.2-kb 16S rDNA partial sequences obtained from symptomatic sugarcane plants and these leafhoppers revealed 99-100 % sequence identities among themselves and 99 % identity with other reported strains of 'Candidatus Phytoplasma oryzae' (16SrXI group). Phylogenetic analysis of 16S rRNA sequences of SCGS, M. portica, C. unimaculata and E. indicus phytoplasma strains also indicated the closest phylogenetic relationship with those of 'Ca. P. oryzae' group. Transmission tests and population sampling study further confirmed that M. portica and C. unimaculata were vectors of the SCGS phytoplasma from diseased to healthy sugarcane plants. The identification of new vectors of SCGS phytoplasma suggested that these leafhopper species may be responsible for secondary spread of SCGS phytoplasma.
To date, transcriptome profile analysis of maize seedlings in response to cold stress have been well documented; however, changes in protein species abundance of maize seedlings in response to cold stress are still unknown. Herein, leaves from the maize inbred line W9816 (a cold-resistance genotype) were harvested at three-leaf stage, and were used to identify the differential abundance protein species (DAPS) between chilling stress (4 degrees C) and control conditions (25 degrees C). iTRAQ-based quantitative proteomic were used in this study. As a result, 173 DAPS were identified after chilling stress. Bioinformatic analysis showed that 159 DAPS were annotated in 38 Gene Ontology functional groups, 108 DAPS were classified into 20 clusters of orthologous groups of protein categories, 99 DAPS were enrichment in KEGG pathways. Antioxidants assays validated that the iTRAQ results were reliable. Based on functional analysis, we concluded that the adaptive response of maize seedlings to chilling stress might be related to alleviation of photodamage caused by the over-energized state of thylakoid membrane, more energy produced through glycolysis, increased abundance of stress-responsive protein species, and improvement in the overall ability to scavenge ROS. Posttranscriptional regulation and posttranslational modifications also play important roles for maize to adapt to chilling stress. Biological significance: The major challenge for maize breeders is the complexity of the response to chilling stress. Although extensive researches have been focus on maize chilling stress using segregating populations, epigenetics, transcriptomics, molecular biology, however, the molecular mechanism of chilling stress in maize remains to be further elucidated. In the present paper, a differential proteomic analysis was performed and the results revealed the adaptive response of maize seedlings to chilling stress might be related to alleviation of photodamage caused by the over-energized state of thylakoid membrane, more energy produced through glycolysis, increased abundance of stress-responsive protein species, improvement in the overall ability to scavenge ROS, including detoxifying enzymes and antioxidants. Posttranscriptional regulation and posttranslational modifications also play important roles for maize to adapt to chilling stress. This approach identified new protein species involved in posttranslational modifications, signal transduction, lipid metabolism, inorganic ion transport and metabolism and other biological processes that were not previously known to be associated with chilling stress response. (C) 2016 Elsevier B.V. All rights reserved.
Background: Neuroimaging, immunologic, and pharmacologic studies have emphasized the role of 5-HT2A and 5-HT3A serotonin receptors in the pathophysiology of major depression.Aim: The aim of this study was to measure the relative expression of 5-HT2A and 5-HT3A receptor mRNA in peripheral blood mononuclear cells (PBMCs) of patients with major depressive disorder (MDD).Method: 5-HT2A and 5-HT3A receptor mRNA expressions were examined in PBMCs of 25 medication-naive-patients with MDD, 25 medication-free MDD patients, and 25 healthy controls. 5-HT2A and 5-HT3A receptor mRNA expressions were measured using real-time quantitative PCR. This study evaluated patients' clinical symptoms using the Hamilton Depression Rating Scale-17 items (HDRS) and the Beck Depression Inventory (BDI).Results: Relative 5-HTR2A mRNA expression was significantly higher in PBMCs of all MDD patients when compared with healthy controls (Z = -3.875, p0.05). MDD patients showed significant correlations between 5-HTR2A mRNA expression and HDRS scores (rs=0.902, p<0.001) and BDI scores (rs=0.878, p<0.001).Conclusion: This study showed that depressed patients, irrespective of treatment, have higher 5-HTR2A mRNA levels in PBMCs than healthy subjects. It also provided evidence that 5-HTR2A mRNA levels in PBMCs of MDD patients could be associated with the severity of depression and the duration of the illness.
Background: Patients with major depressive disorder (MDD) present heterogeneous clinical symptoms, and childhood abuse is associated with deepening of psychopathology. The aim of this study was to identify structural brain abnormalities in MDD and to assess further differences in gray matter density (GMD) associated with childhood abuse in MDD. Methods: Differences in regional GMD between 34 MDD patients and 26 healthy controls were assessed using magnetic resonance imaging and optimized voxel-based morphometry. Within the MDD group, further comparisons were performed focusing on the experience of maltreatment during childhood (23 MDD with child abuse vs 11 MDD without child abuse). Results: Compared with healthy controls, the MDD patient group showed decreased GMD in the bilateral orbitofrontal cortices, right superior frontal gyrus, right posterior cingulate gyrus, bilateral middle occipital gyri, and left cuneus. In addition, the patient group showed increased GMD in bilateral postcentral gyri, parieto-occipital cortices, putamina, thalami, and hippocampi, and left cerebellar declive and tuber of vermis. Within the MDD patient group, the subgroup with abuse showed a tendency of decreased GMD in right orbitofrontal cortex, but showed increased GMD in the left postcentral gyrus compared to the subgroup without abuse. Conclusions: Our findings suggest a complicated dysfunction of networks between cortical-subcortical circuits in MDD. In addition, increased GMD in postcentral gyrus and a possible reduction of GMD in the orbitofrontal cortex of MDD patients with abuse subgroup may be associated with abnormalities of body perception and emotional dysregulation.
Major histocompatibility (MH) class II receptors are expressed on the surface of specialized antigen-presenting cells in vertebrate immune systems. Their function is to present peptides derived from exogenous pathogens to CD4+ T cells. Variation in the level of expression of these genes has been linked to pathogenesis in various diseases. Very little has been published on the function of MH class II receptors in teleost fish to date. In this study, we have produced polyclonal antibodies recognizing MH class II alpha and beta proteins of rainbow trout and employed them to characterize the expression pattern of these genes. Deglycosylation using N-glycosidase F and endoglycosidase H showed that MH class II alpha is glycosylated in rainbow trout. MH class II beta was also found to be glycosylated as reported previously. Results from Northern blotting revealed that the expression of these genes was not affected by exposure of rainbow trout to temperature of 5 degrees C. However, at 2 degrees C, downregulation of MH class II alpha and beta genes was evident at both the mRNA and protein levels as assessed by Northern and Western blotting, respectively. Because MH class II antigens play an important role in generating an immune response to bacterial and fungal pathogens, downregulation of these genes at low temperature could account for the susceptibility of fish to low temperature-related diseases such as bacterial cold-water disease and winter saprolegniosis.
Objective: To access a new step using PCR to amplify the targeted mtDNA sequence for detecting specifically Plasmodium vivax and its co-infections, false positive and false negative results with Plasmodium falciparum. Methods: In this study we have standardized a new technical approach in which the target mitochondrial DNA sequence (mtDNA) was amplified by using a PCR technique as a tool to detect Plasmodium spp. Species specific primers were designed to hybridize with cytochrome c oxidase gene of P. vivax (cox I) and P. falciparum (cox III). Two hundred blood samples were collected on the basis of clinical symptoms which were initially examined through microscopic analysis after preparing Giemsa stained thick and thin blood smears. Afterwards genomic DNA was extracted from all samples and was then subjected to PCR amplification by using species specific primers and amplified segments were sequenced for confirmation of results. Results: One-hundred and thirty-two blood samples were detected as positive for malaria by PCR, out of which 64 were found to be positive by PCR and 53 by both microscopy and PCR for P. vivax infection. Nine samples were found to be false negative, one P. vivax mono infection was declared as co infection by PCR and 3 samples identified as having P. falciparum gametes were confirmed as P. vivax by PCR amplification. Sensitivity and specificity were found to be 85% and 92% respectively. Conclusion: Results obtained through PCR method were comparatively better and reliable than microscopy.
Background: Malaria is a major world health issue and its continued burden is due in part to difficulties in the diagnosis of the illness. The World Health Organization recommends confirmatory testing using microscopy based techniques or rapid diagnostic tests (RDT) for all cases of suspected malaria. In regions where Plasmodium species are indigenous there are multiple etiologies of fever leading to misdiagnoses especially in populations where HIV is prevalent and children. To determine the frequency of malaria infection in febrile patients over an 8 month period at the Regional Hospital in Bamenda Cameroon we evaluated the clinical efficacy of the Flourescence and Staining Technology (FAST) Malaria stain and ParaLens Advance(TM) microscopy system (FM) and compared it with conventional bright field microscopy and Giemsa stain (GS). Methods: Peripheral blood samples from 522 patients with a clinical diagnosis of "suspected malaria" were evaluated using GS and FM methods. A nested PCR assay was the gold standard to compare the two methods. PCR positivity sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) were determined. Results: Four hundred ninety nine samples were included in the final analysis. Of these 30 were positive via PCR (6.01%) with a mean PPV of 19.62% and 27.99% for GS and FM respectively. The mean NPV was 95.01% and 95. 28% for GS and FM respectively. Sensitivity was 26.67% in both groups and specificity was 92.78% and 96.21% for GS and FM respectively. An increased level of diagnostic discrepancy was observed between technicians based upon skill level using GS which was not seen with FM. Conclusions: The frequency of malarial infections confirmed via PCR among patients presenting with fever and other symptoms of malaria was dramatically lower than that anticipated based upon physicians' clinical suspicions. A correlation between technician skill and accuracy of malaria diagnosis using GS was observed that was less pronounced using FM. Additionally FM increased the specificity and improved the PPV suggesting this relatively low cost approach could be useful in resource limited environments. Anecdotally physicians were reluctant to not treat all patients symptomatically before results were known and in spite of a negative microscopic diagnosis highlighting the need for further physician education to avoid this practice of overtreatment. A larger study in an area with a known high prevalence is being planned to compare the two microscopy methods against available RDTs.
Four species of malaria parasite, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi infect humans living in the Khanh Phu commune, Khanh Hoa Province, Vietnam. The latter species also infects wild macaque monkeys in this region. In order to understand the transmission dynamics of the three species, we attempted to detect gametocytes of the three species in the blood of infected individuals, and sporozoites in the salivary glands of mosquitoes from the same region. For the detection of gametocyte-specific mRNA, we targeted region 3 of pfg377, pvs25, pmg and pks25 as indicators of the presence of P. falciparum, P. vivax, P. malariae and P. knowlesi gametocytes, respectively. Gametocyte-specific mRNA was present in 37, 61, 0 and 47% of people infected with P. falciparum (n = 95), P. vivax (n = 69), P. malariae (n = 6) or P. knowlesi (n = 32), respectively. Wefound that 70% of mosquitoes that had P. knowlesi in their salivary glands also carried human malaria parasites, suggesting that mosquitoes are infected with P. knowlesi from human infections.
Malaria is the most devastating parasitic disease of humans, caused by the unicellular protozoa of the Plasmodium genus, such as Plasmodium falciparum (Pf) and is responsible for up to a million deaths each year. Pf life cycle is complex, with transmission of the parasite between humans via mosquitos involving a remarkable series of morphological transformations. In the bloodstream, the parasites undergo asexual multiplications inside the red blood cell (RBC), where they mature through the ring (R), trophozoite (T) and schizont (S) stages, and sexual development, resulting in gametocytes (G). All symptoms of malaria pathology are caused by the asexual blood stage parasites. Flow cytometry methods were previously used to detect malaria infected (i) RBCs, in live or fixed cells, using DNA (Hoechst) and RNA (Thiazole Orange) stains. Here, by using imaging flow cytometry, we developed improved methods of identifying and quantifying each of the four parasite blood stages (R, T, S and G). This technique allows multi-channel, high resolution imaging of individual parasites, as well as detailed morphological quantification of Pf-iRBCs cultures. Moreover, by measuring iRBC morphological properties, we can eliminate corrupted and extra cellular (dying) parasites from the analysis, providing accurate quantification and robust measurement of the parasitemia profile. This new method is a valuable tool in malaria molecular biology research and drug screen assays. (C) 2016 Elsevier Inc. All rights reserved.
Background: Sensitive methods for detecting asymptomatic malaria infections are essential for identifying potential transmission reservoirs and obtaining an accurate assessment of malaria epidemiology in low-endemicity areas aiming to eliminate malaria. PCR techniques to detect parasite nucleic acids (DNA or RNA) are among the most commonly used molecular methods. However, most of these methods are of low throughput and cannot be used for large-scale molecular epidemiological studies. A recently developed capture and ligation probe-PCR (CLIP-PCR) is claimed to have the sensitivity of molecular techniques and the high throughput capacity needed for screening purposes. This study aimed to compare several molecular methods for detecting asymptomatic and submicroscopic Plasmodium infections in healthy residents of a malaria-hypoendemic region in Southeast Asia, where malaria elimination is in sight. Method: This study compared three molecular detection methods side-by-side, namely nested PCR targeting the rRNA genes, nested RT-PCR to detect parasite rRNA, and CLIP-PCR to detect parasite rRNA in 1005 healthy individuals in northeastern Myanmar. For nested PCR and RT-PCR, parasite DNA and total RNA were extracted from similar to 100 mu L of blood, whereas RNA used for CLIP-PCR was from a 3 mm disk of dried blood filter paper. The sensitivity and specificity of these methods were compared with those of conventional light microscopy. In addition, RT-PCR and quantitative RT-PCR (qRT-PCR) targeting the Pvs25 gene in Plasmodium vivax were used to assess gametocyte prevalence in the samples. Results: Light microscopy detected Plasmodium infections in only 1.19% of the residents harbouring the parasites. CLIP-PCR had slightly better performance and detected Plasmodium infections in 1.89% of the population. Further improvement was achieved by nested PCR to detect parasite DNA, which detected P.vivax and Plasmodium falciparum infections in 2.39% of the residents. The nested RT-PCR targeting rRNA, however, detected as many as 187 (18.61%) individuals having Plasmodium infections with P. vivax being the predominant species (176 P. vivax, 5 P. falciparum and 6 P. falciparum/P.vivax mixed infections). Of the 210 Plasmodium-positive samples detected by all molecular methods, 115 were Pvs25-positive by qRT-PCR, indicating that a large proportion of asymptomatic individuals were gametocyte carriers. Conclusion: Nested RT-PCR based on the detection of asexual-stage parasite rRNA was the most sensitive, with a more than sixfold higher sensitivity than the other two molecular methods of parasite detection. CLIP-PCR has an increased throughput, but its sensitivity in this study was much lower than those of other molecular methods, which may be partially due to the smaller amount of RNA input used.
Background: There are no data on the burden of malaria in pregnancy (MiP) in Laos, where malaria still remains prevalent in the south. Methods: Two cross-sectional surveys were conducted in 2014 to assess the prevalence of MiP in Vapi District, Salavan Province, southern Laos: the first consisted of screening 204 pregnant women during pregnancies [mean (95 % CI) gestational age: 23 (22-25) weeks] living in 30 randomly selected villages in Vapi District; the second was conducted among 331 pregnant women, who delivered during the study period in Vapi and Toumlane District Hospitals and in Salavan Provincial Hospital. Peripheral and placental malaria was detected using rapid diagnostic tests (RDT), thick blood smears (TBS) and real-time quantitative polymerase chain reactions (RT-qPCR). Factors associated with low birth weight (LBW) and maternal anaemia were assessed. Results: In the villages, 12/204 women (5.9 %; 95 % CI 3.1-10.0) were infected with malaria as determined by RT-qPCR: 11 were Plasmodium vivax infections and 1 was mixed Plasmodium vivax/Plasmodium falciparum infection, among which 9 were sub-microscopic (as not detected by TBS). History of malaria during current pregnancy tended to be associated with a higher risk of MiP (aIRR 3.05; 95 % CI 0.94-9.88). At delivery, two Plasmodium falciparum submicroscopic infections (one peripheral and one placental) were detected (4.5 %; 0.6-15.5) in Vapi District. In both surveys, all infected women stated they had slept under a bed net the night before the survey, and 86 % went to the forest for food-finding 1 week before the survey in median. The majority of infections (94 %) were asymptomatic and half of them were associated with anaemia. Overall, 24 % of women had LBW newborns. Factors associated with a higher risk of LBW were tobacco use (aIRR 2.43; 95 % CI 1.64-3.60) and pre-term delivery (aIRR 3.17; 95 % CI 2.19-4.57). Factors associated with a higher risk of maternal anaemia were no iron supplementation during pregnancy, Lao Theung ethnicity and place of living. Conclusions: The prevalence of MiP in this population was noticeable. Most infections were asymptomatic and submicroscopic vivax malaria, which raises the question of reliability of recommended national strategies for the screening and prevention of MiP in Laos.
Background. The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/mu L, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts.
Introduction: An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack.Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models.Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.
Background: Emergence of insecticide resistance in malaria vectors is a real threat to future goals of elimination and control of malaria. Therefore, the objective of this study was to assess research trend on insecticide resistance of Anopheles mosquito. In specific, number of publications, countries, institutions, and authors' research profile, citation analysis, international collaborations, and impact of journals publishing documents on insecticide resistance will be presented. It was conducted via Scopus search engine which was used to retrieve relevant data. Keywords used were based on literature available on this topic. The duration of study was set from 1996-2015. Results: A total of 616 documents, mainly as original research articles (n = 569; 92.37%) were retrieved. The average number of citations per article was 26.36. Poisson log-linear regression analysis indicated that there was a 6.00% increase in the number of publications for each extra article on pyrethroid resistance. A total of 82 different countries and 1922 authors participated in publishing retrieved articles. The United Kingdom (UK) ranked first in number of publications followed by the United States of America (USA) and France. The top ten productive countries included seven African countries. The UK had collaborations mostly with Benin (relative link strength = 46). A total of 1817 institution/ organizations participated in the publication of retrieved articles. The most active institution/ organization was Liverpool School of Tropical Medicine. Retrieved articles were published in 134 different scientific peer reviewed journals. The journal that published most on this topic was Malaria Journal (n = 101; 16.4%). Four of the top active authors were from South Africa and two were from the UK. Three of the top ten cited articles were published in Insect Molecular Biology journal. Six articles were about pyrethroid resistance and at least two were about DDT resistance. Conclusion: Publications on insecticide resistance in malaria vector has gained momentum in the past decade. International collaborations enhanced the knowledge about the situation of vector resistance in countries with endemic malaria. Molecular biology of insecticide resistance is the key issue in understanding and overcoming this emerging problems.
The genus Malassezia comprises commensal yeasts on human skin. These yeasts are involved in superficial infections but are also isolated in deeper infections, such as fungemia, particularly in certain at-risk patients, such as neonates or patients with parenteral nutrition catheters. Very little is known about Malassezia epidemiology and virulence. This is due mainly to the difficulty of distinguishing species. Currently, species identification is based on morphological and biochemical characteristics. Only molecular biology techniques identify species with certainty, but they are time-consuming and expensive. The aim of this study was to develop and evaluate a matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) database for identifying Malassezia species by mass spectrometry. Eighty-five Malassezia isolates from patients in three French university hospitals were investigated. Each strain was identified by internal transcribed spacer sequencing. Forty-five strains of the six species Malassezia furfur, M. sympodialis, M. slooffiae, M. globosa, M. restricta, and M. pachydermatis allowed the creation of a MALDI-TOF database. Forty other strains were used to test this database. All strains were identified by our Malassezia database with log scores of >2.0, according to the manufacturer's criteria. Repeatability and reproducibility tests showed a coefficient of variation of the log score values of < 10%. In conclusion, our new Malassezia database allows easy, fast, and reliable identification of Malassezia species. Implementation of this database will contribute to a better, more rapid identification of Malassezia species and will be helpful in gaining a better understanding of their epidemiology.
A transgenic male sterile line of upland cotton was generated by the ectopic expression of the monooxygenase (MNX) gene from Arabidopsis thaliana via Agrobacterium-mediated transformation. The bacterium harbored a plasmid pBinplus carrying a 1.25-kb MNX coding sequence together with a GUS reporter gene; the former was driven by the MS2 promoter of a male sterility gene in Arabidopsis, and the latter was under the control of CaMV 35S promoter. Twenty-seven putative transgenic plants (T(0)) were obtained, all of which showed GUS activity and positive signals of NPTII and MNX genes by PCR analysis, and also showed male sterility to some extent. It was further confirmed by Southern blotting that one copy of the NPTII and MNX gene was integrated in the genome of the plants which expressed male sterility to a higher degree. Northern blotting assay also demonstrated that the transgenes stably transcribed in the genome of the transgenic plants in F(4) generation. The male sterile plants usually display lower plant height, shortened internodes, shrunken anthers without pollen grains or with some abortive pollen grains, and unusual leaves with deeper multi-lobes. Microscope observations on the meiosis processes of pollen mother cells (PMCs) showed that the abortion of pollen grains mainly resulted from abnormalities of meiosis such as direct degeneration of PMCs, degenerations of dyad and tetrads, amitosis, lagging chromosomes, and the multi-polar segregations of chromosomes and so on. This study indicates a method of developing novel cotton male sterile materials for potential application in agriculture and for engineering of male sterility in other important crops.
Background: Maleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human. The aim of this study is to experimentally explore the effects of maleic acid on human neuronal cells. Methods: A microarray-based transcriptome profiling was performed to offer a better understanding of the effects of maleic acid on human health. Gene expression profiles of human neuroblastoma SH-SY5Y cells exposed to three concentrations of maleic acid (10, 50, and 100 mu M) for 24 h were analyzed. Genes which were differentially expressed in dose-dependent manners were identified and further analyzed with an enrichment analysis. The expression profile of selected genes related to the inferred functional changes was validated using quantitative polymerase chain reaction (qPCR). Specific fluorescence probes were applied to observe the inferred functional changes in maleic acid-treated neuronal cells. Results: A total of 316 differentially expressed genes (141 upregulated and 175 downregulated) were identified in response to the treatment of maleic acid. The enrichment analysis showed that DNA binding and metal ion binding were the significant molecular functions (MFs) of the neuronal cells affected by maleic acid. Maleic acid exposure decreased the expression of genes associated with calcium and thiol levels of the cells in a dose-dependent manner. The levels of intracellular calcium and thiol levels were also affected by maleic acid dose-dependent. Discussion: The exposure to maleic acid is found to decrease the cellular calcium and thiol levels in human neuronal cells at both transcriptional and functional levels. This study reported the first transcriptomic profiling of human neuronal cells treated with maleic acid. It is also the first experimental validation of chemical effects predicted by in silico toxicogenomics approaches. The proposed approach may be useful in understanding the potential effects of other poorly characterized chemicals on human health.
The prevalence of child abuse is higher in families with psychosocial vulnerabilities or when one or both parents experienced abuse or neglect during childhood. While the most widespread intervention approaches in Canada (e.g. material support or parenting skills programs) show mixed results in providing changes in mistreatment cycles, we examine clinical practice focused on generational repetition of trauma. In order to explore this topic, this paper has 4 objectives and will be supported by a narrative review of the literature: (1) to document the causalities of child maltreatment; (2) to identify the clinical challenges of struggling parents; (3) to develop a critical analysis of the intervention programs commonly spread in Canada; (4) to take into account multifaceted vulnerabilities of these families through innovative practice perspectives. (C) 2015 Societe francaise de psychologie. Published by Elsevier Masson SAS. All rights reserved.
alpha-Farnesene is a volatile sesquiterpene in the natural coating of apple fruit. Oxidation products of this sesquiterpene are thought to induce superficial scald in apple. A cDNA encoding a-farnesene synthase converting farnesyl diphosphate to a-farnesene was obtained by using RT-PCR from peel of apple fruit (Accession No. AY563622). Comparison of the sequence of the cDNA with AFS-1 gene registered in the GenBank (AY182241) showed that these sequences shared high similarity in nucleotide sequence and homology in deduced amino acid sequence. Southern blotting suggested that there was only one copy in the genome of apple. Northern blotting showed that the AFS gene played a key role in a-farnesene synthesis during the 10 days after apples were removed from cold storage and warmed to room temperature. Expression of the AFS gene was influenced by treatment with DPA and 1-MCP.
Assembly of eukaryotic ribosomes is an elaborate biosynthetic process that begins in the nucleolus and requires hundreds of cellular factors. Analysis of rRNA processing has been instrumental for studying the mechanisms of ribosome biogenesis and effects of stress conditions on the molecular milieu of the nucleolus. Here, we describe the quantitative analysis of the steady-state levels of rRNA precursors, applicable to studies in mammalian cells and other organisms. We include protocols for gel electrophoresis and northern blotting of rRNA precursors using procedures optimized for the large size of these RNAs. We also describe the ratio analysis of multiple precursors, a technique that facilitates the accurate assessment of changes in the effi ciency of individual pre-rRNA processing steps.
The effects of changes in mandated child maltreatment reporting laws have not been systematically evaluated. To better understand the effects of these changes, the objectives of the present study are: (1) to assess the relationships between report rates and state universal and clergy reporting laws in 2010; (2) to compare the changes in total, confirmed, and maltreatment type report rates and with changes in reporting laws from 2000 to 2010, and (3) to examine whether there is any relationship with report rates and the nature of the mandated reporting law change. We used county-level data from the U.S. National Child Abuse and Neglect Data System for the years 2000 and 2010 to evaluate changes in reporting rates for total reports, confirmed reports, and confirmed maltreatment types while controlling for concurrent changes in child and community variables. We found that trends in 2010 for increased total and confirmed reports were similar to 2000 for counties with universal and/or clergy reporting requirements, which significantly contributed to report rates even after controlling for child and community factors. Universal reporting was associated with higher report rates for physical and sexual abuse, and clergy reporting requirements were associated with more sexual abuse, medical neglect and psychological maltreatment confirmed reports. However, while counties in states that changed their clergy reporting laws had higher increases in total reports, they had fewer confirmed physical and sexual abuse, neglect, and psychological maltreatment reports. More pronounced changes were noted in a state that made more pronounced changes in its clergy reporting laws. Policymakers should consider whether changing requirements for mandated reporting meaningfully improves child maltreatment identification. (C) 2016 Elsevier Ltd. All rights reserved.
When living organisms independently invade a new environment, the evolution of similar phenotypic traits is often observed. An interesting but contentious issue is whether the underlying molecular biology also converges in the new habitat. Independent invasions of tropical intertidal zones by woody plants, collectively referred to as mangrove trees, represent some dramatic examples. The high salinity, hypoxia, and other stressors in the new habitatmight have affected both genomic features and protein structures. Here, we developed a new method for detecting convergence at conservative Sites (CCS) and applied it to the genomic sequences of mangroves. In simulations, the CCS method drastically reduces random convergence at rapidly evolving sites as well as falsely inferred convergence caused by the misinferences of the ancestral character. In mangrove genomes, we estimated similar to 400 genes that have experienced convergence over the background level of convergence in the nonmangrove relatives. The convergent genes are enriched in pathways related to stress response and embryo development, which could be important for mangroves' adaptation to the new habitat.
The ferric uptake regulator (Fur) is an iron-dependent transcriptional regulator that regulates genes related to iron acquisition, oxidative stress response, and various other functions. Transcription of fur is typically self-regulating and sensitive to iron and oxidative stress. Following the identification of a fur gene in the genome of the bovine pathogen Mannheimia haemolytica, an attempt was made to characterize the transcriptional control of M. haemolytica fur. Northern blotting, RT-PCR, and primer extension were done to determine that M. haemolytica fur is transcribed using three distinct promoters, two of which are located within the upstream fldA gene. The third promoter is located upstream of a conserved hypothetical protein and drives transcription of a tricistronic message. Quantitative real time PCR experiments indicated that unlike current models of Fur regulation, M. haemolytica fur transcription is unchanged by iron depletion at logarithmic phase and repressed by iron depletion at stationary phase. (c) 2007 Elsevier B.V. All rights reserved.
The glycolipid biosurfactants mannosylerythritol lipids (MELs) attract great attention for their biodegradability, super emulsifying properties and versatile bioactivities. In this study, the MEL deriving from Ceriporia lacerate CHZJU was identified as MEL-A, and its critical micelle concentration and emulsifying activities were assessed. To examine the production of MELs from Ceriporia lacerate, a Plackett-Burman design and response surface methodology were used to optimize the culture nutrients. The optimal medium contains 1 g/L yeast extract, 1.5 g/L (NH4)(2)SO4, 0.5 g/L KH2PO4, 0.04 g/L CaCl2, 119.6 mL/L soybean oil and 0.297 g/L MnSO4. Subsequent verification revealed that the yield of MELs was 129.64 +/- 5.67 g/L. Furthermore, an unstructured kinetic model was developed for mycelial growth, MEL production and substrate utilization. This work provides insight into Ceriporia lacerate CHZJU, a predominant fungus producing MEL-A. Optimization using response surface methodology enhanced the mannosylerythritol lipid recovery. Importantly, we developed fermentation kinetic modelling for mannosylerythritol lipid production. (C) 2017 Elsevier Ltd. All rights reserved.
Nowadays, with the introduction and application of new information technologies in manufacturing, various advanced manufacturing modes and national strategies have been put forward and paid more and more attention, such as Industry 4.0, Industrial Internet, Cyber-Physical System or Cyber Manufacturing, Made in China 2025, Internet Plus Manufacturing, Cloud Manufacturing, etc. For these modes and strategies, how to realize the effective and intelligent supply-demand matching (SDM) of various manufacturing resources and capabilities (MR&C) in the form of service is one of the common issues and aims. In order to provide a uniformed research platform for related researchers both in academic and industry, the concept of manufacturing service SDM simulator (SDMSim) is proposed in this paper. A hypernetwork based architecture for the simulator is designed, as well as its seven key functions and subsystems, including manufacturing service management, manufacturing task management, manufacturing service SDM hypernetwork, manufacturing service SDM problem formulation and configuration, matching and scheduling algorithms/strategies selection and design, statistical analysis, and visualization. It illustrates that SDMSim has the potential to serve the users of manufacturing service provider, manufacturing service consumer, manufacturing service operator in the field of SoM, as well as the related researchers. (C) 2016 Elsevier Ltd. All rights reserved.
In this paper considerations related to possibly best selection of current mirror architecture for current biasing of operational amplifier in pixel matrices are presented. Monte Carlo simulations focusing on global parameter variation are conducted, presented and discussed.
This paper addresses the problem of robust H-infinity filtering design for uncertain Markov jump systems (MJSs) with mode-dependent quantized output and partly unknown transition probabilities. The data transmission and exchange are completed over a digital communication channel such that the system outputs need to be quantized before transmission. Attention is mainly concentrated on tackling the parameter uncertainty, unknown transition probabilities and output quantization. The parameter uncertainty considered in this paper is assumed to be norm-bounded, and the exact information of transition probabilities matrix is partly unavailable. The quantization error of the output is transformed into a bounded nonlinearity via a model transformation. A mode-dependent filter is designed to ensure that the filtering error system is stochastically stable and has an Ho, noise attenuation performance index. Finally, simulation results are provided to illustrate the validity of the proposed results. (C) 2017 Elsevier B.V. All rights reserved.
An audience can have a profound effect on the dynamics of communicative interactions. As a result, non-human primates often adjust their social decision-making strategies depending on the audience composition at a given time. Here we sought to test how the unique vocal behaviour of multiple audience members affected decisions to communicate. To address this issue, we developed a novel experimental paradigm in which common marmosets directly interacted with multiple 'virtual monkeys' (VMs), each of whom represented an individual marmoset with distinct vocal behaviour. This active social signalling paradigm provided subjects an opportunity to interact with and learn about the behaviour of each VM in the network and apply this knowledge in subsequent communicative decisions. We found that subjects' propensity to interact with particular VMs was determined by the behaviour of each VM in the audience and suggests that marmoset social decision-making strategies are highly adaptive to nuances of the immediate communication network.
The circum-Hellas area of Mars borders Hellas Planitia, a giant impact similar to 4.0-4.2 Ga old making the deepest and broadest depression on Mars, and is characterized by a complex pattern of fracture sets, lobate scarps, grabens, and volcanic plains. The numerous lobate scarps in the circum-Hellas region mainly formed in the Late Noachian and, except Amenthes Rupes, have been scarcely studied. In this work, we study the mechanical behavior and thermal structure of the crust in the circum-Hellas region at the time of lobate scarp formation, through the modeling of the depth of faulting beneath several prominent lobate scarps. We obtain faulting depths between similar to 13 and 38 km, depending on the lobate scarp and accounting for uncertainty. These results indicate low surface and mantle heat flows in Noachian to Early Hesperian times, in agreement with heat flow estimates derived from lithospheric strength for several regions of similar age on Mars. Also, faulting depth and associate heat flows are not dependent of the local crustal thickness, which supports a stratified crust in the circum-Hellas region, with heat-producing elements concentrated in an upper layer that is thinner than the whole crust. (C) 2017 Elsevier Inc. All rights reserved.
Marsupials are born immunologically premature, relying on cells and molecules in maternal milk for immune protection. Both immunoglobulin and complement proteins have been identified in marsupial milk, but the expression of specific complement proteins remains largely unexplored. We report partial cDNA sequences for two complement-activating proteins, C3, C1r, CFP and MASP2, in liver tissues from red-tailed phascogale (Phascogale calura). Conservation of functionally relevant motifs were identified in the translated cDNA sequences from phascogale C3, CFP and MASP2 and their eutherian homologues. Gene expression of representative molecules from each of the major complement pathways was also investigated in whole body tissues from 1 to 18 day old animals and liver tissues from 31-day to 14 month old animals. Average complement expression in whole bodies and liver tissues of C1r, CFP, MASP2 and C3 increased significantly in juveniles compared to pouch young, presumably due to the maturation of the young's own complement system. Comparing expression in liver tissues only, we found that the average CFP expression were higher in pouch young compared to juveniles, while results were still statistically similar to the average expression of all tissues for C1r, MASP2 and C3. The average complement expression then significantly decreased as the animals aged into adulthood. (C) 2016 Elsevier Ltd. All rights reserved.
The present study analyzed the capacity for mentalization of patients with bipolar disorder (BD) and their first-degree relatives (FDR) and examined the implications of clinical variables and cognitive deficits. The study recruited 31 patients with type I BD, 18 FDR, and 31 paired healthy controls. Their capacity for mentalization was explored by means of first-and secondorder false-belief tasks, the hinting task, and the Movie for the Assessment of Social Cognition (MASC). Patients and FDR were found to have a theory of mind (ToM) deficit when they were evaluated with the MASC, which was also related to a worse neurocognitive performance and to being a patient or FDR. The evidence of ToM deficits in FDRs supports the hypothesis that these deficits could be an independent trait marker for cognitive deficit. Further research is needed on FDR of patients with BD, using sensitive ToM assessment instruments such as the MASC.
Understanding the molecular basis of schizophrenia is essential for disease management, and several molecular biology tools have been employed for this purpose. Mass spectrometry, which is used mostly in proteomic and metabolomic studies, is one such tool. Here, we present the first psychiatric study to use mass spectrometry imaging (MSI) with desorption electrospray ionization (DESI). Preparation of samples for use with DESI-MSI is remarkably simple and quick and preserves the spatial distribution of analytes. By using this tool, we found differences in the phospholipid content in schizophrenia postmortem brains. These results validate both the role of phospholipids in schizophrenia and the value of this MS tool in furthering the understanding of the molecular aspects of the disease. (C) 2015 Elsevier B.V. All rights reserved.
The performance of a commercial, real-time PCR. assay was compared with traditional bacterial culture for the identification of Streptococcus uberis and Staphylococcus aureus in bovine milk collected at different stages of lactation. Initial validation tests using fresh and frozen quarter milk samples identified factors that affected the success of the PCR. Therefore, the standard protocol was adjusted for samples collected at the first milking postpartum (colostrum) and from clinical mastitis cases. The adjustment involved PCR testing both undiluted and diluted (1 in 10 with sterile water) DNA extracts. The performance comparison between culture and the PCB assay used milk samples collected aseptically from individual quarters of mixed-age spring-calving dairy cows, during early, mid, and late lactation. Bacterial culture results were used to select a subset of samples for PC.R. testing (n = 315) that represented quarters with a current or prior Strep. uberis or Staph,. aureus infection. Compared with culture, PCR had a sensitivity of 86.8% and specificity of 87.7% for detecting Strep. uberis (kappa = 0.74) and 96.4% and 99.7%, respectively, for detecting Staph. aureus (kappa = 0.96). The dilution of DNA extracts for colostrum and clinical samples increased the relative sensitivity from 79.2% to 86.8% for Strep. uberis detection and from 92.9% to 96.4% for Staph. aureus, presumably through diluting unidentified PCR, inhibitors. The sensitivity for detecting Strep. uberis using PCR, relative to culture, was similar throughout lactation (85-89%), whereas relative specificity was lowest immediately postcalving (64%) but improved in mid and late lactation (98%). Specificity estimates for samples collected in early lactation can be optimized by reducing the cutoff cycle threshold (Ct) value from the recommended value of 37 to 34. Although using this value improved specificity (77%), it reduced test sensitivity (77%). The PCR. assay lacked agreement with culture in early lactation, specifically for diagnosing Strep. uberis. Thus, PCB. should not be used as the only tool for diagnosing mastitis in early lactation.
Objectives To assess the effectiveness of a 6-week, cognitive behavioral therapy (CBT) group-based enhancement to home visiting to address stress and prevent depression as compared with home visiting as usual in low income mothers of young children. Methods We conducted a randomized controlled trial with 95 low-income mothers of young children to assess the effectiveness of a 6-week, cognitive behavioral group-based enhancement to Healthy Families America and Parents as Teachers home visiting (HV/CBT = 49) to address stress and prevent depression as compared with home visiting as usual (HV = 46). Booster sessions for the HV/CBT group were offered at 3 and 6 months. Participants completed measures of coping, stress and depression at three points: baseline prior to randomization, post-intervention, and 6 months post-intervention. Parent child interaction was also measured at 6 months. Results Intent-to-treat analyses found improved coping and reduced stress and depression post-intervention. While impacts on these outcomes were attenuated at 6 months, positive impacts were observed for selected aspects of mothers' interactions with their children. Maternal characteristics at baseline were associated with participation in the intervention and with post-intervention and 6-month outcomes. Mothers with lower levels of stress and those with fewer children were more likely to attend intervention sessions. Mothers with lower levels of stress had more favorable post intervention outcomes. Conclusions CBT group-based enhancement to home visiting improved maternal coping, reduced stress and depression immediately post intervention but not at 6 months, suggesting more work is needed to sustain positive gains in low-income mothers of young children.
The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.
A 27-to-3-phase thyristor matrix converter using a model predictive control (MPC) is considered. Compared to the standard method the MPC considers the coupled overall system. Due to this, all 273 19683 switching states are to be considered. The result of the MPC strategy is, compared to classical control, a drastic reduction of the commutation frequency and respectively the converter losses. However, besides the advantages there are still some problems with the use of MPC for thyristor matrix converter. Therefor this contribution presents extensions of the standard direct model predictive control strategy to overcome these problems. The result is a predictive control structure with a fallback level for problematic working areas. By this, a low total harmonic distortion (THD) as well as a high efficiency can be achieved.
In preeclampsia and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, impaired trophoblast invasion and excessive fibrin deposition in the placental intervillous space is associated with fetal compromise. However, little information is available whether modulation of placental protease expression-potentially causing impaired trophoblast invasion-is associated with the HELLP syndrome. Total RNA and protein were extracted from placental tissue from 11 females with HELLP syndrome and 8 controls matched for gestational age. mRNA expression of matrix metalloprotease (MMP)-2 and -9, tissue inhibitors of metalloprotease (TIMP)-1, -2, and -3, and urokinase-type plasminogen activator receptor (uPAR) was determined by Northern blotting. Protein expression of MMP-2 and -9, and TIMP-1 and -2 was detected by Western blotting and that of uPA, uPAR, and plasminogen activator inhibitor (PAI)-1 by ELISA. In patients with HELLP syndrome, mRNA expression of MMP-2 and TIMP-2 was decreased, whereas TIMP-1 and -3 levels were unchanged. MMP-9 and uPAR mRNA was undetectable in both groups. Protein expression of all investigated proteolytic factors remained unchanged. Our findings at the mRNA level suggest a decrease in matrix remodeling in placentae from patients with HELLP syndrome compared with control pregnancies, although this is not supported at the protein level.
Mature landfill leachate is difficult to be treated due to its complex composition, high concentration of ammonia, and low carbon/nitrogen ratio (C/N). Simultaneous partial nitrification, Anammox and denitrification (SNAD) with intermittent aeration was developed to achieve nitrogen removal from mature landfill leachate. An ammonia conversion efficiency of 99.3 +/- 0.3% and total nitrogen (TN) removal efficiency of 99 +/- 0.1% were obtained under the influent NH4+ -N, SCOD and TN of 1950 +/- 250 mg/L 1900 +/- 200 mg/L and 2300 +/- 75 mg/L, respectively. Full utilization of carbon source and high efficient Anammox were two significant factors in SNAD process. Based on the nitrogen balance, the nitrogen removal contribution was 77.1% for Anammox, and 15.6% for dehitrification. Three dimensional excitation-emission matrix (EEM) fluorescence spectroscopy was used to detect dissolved organic matter (DOM) in a typical operation cycle for the first time, demonstrating that DOM increased during the anoxic phase and facilitated the reduction of excess NO3--N by denitrification. Quantitative polymerase chain reaction (QPCR) analysis revealed dominant bacterial groups, aerobic ammonia-oxidizing bacteria (AOB) and anaerobic ammonia oxidizing bacteria (AnAOB), which accounted for 12.99% and 8.32% of total bacteria respectively. As a whole, in the SNAD process, nitrogen and COD are removed from the wastewater simultaneously. (C) 2016 Elsevier B.V. All rights reserved.
Mayas, having experienced genocide, exile, and severe poverty, are at high risk for the consequences of cumulative trauma that continually resurfaces through current fear of an uncertain future. Little is known about the mental health and alcohol use status of this population. This correlational study explored t/he relationship of cumulative trauma as it relates to social determinants of health (years in the United States, education, health insurance status, marital status, and employment), psychological health (depression symptoms), and health behaviors (alcohol use) of 102 Guatemalan Mayas living in Southeast Florida. The results of this study indicated that, as specific social determinants of health and cumulative trauma increased, depression symptoms (particularly among women) and the risk for harmful alcohol use (particularly among men) increased. Identifying risk factors at an early stage before serious disease or problems are manifest provides room for early screening leading to early identification, early treatment, and better outcomes.
This review explores the past two decades of research on ancient Maya skeletons. The focus is on how this work has contributed to our understanding of health, diet, social change, inequality, migration and mobility, war, violence, and ritual practice, with special attention given to recent methodological developments and debates in the bioarchaeology of the Maya. This review essay highlights the most recent findings in the bioarchaeology of the Maya and how those results were achieved. The essay concludes with suggestions for future research and highlights areas of potential collaboration that have been underutilized to address broader anthropological questions.
The emergence of the mobilized colistin resistance gene, representing a novel mechanism for bacterial drug resistance, challenges the last resort against the severe infections by Gram-negative bacteria with multi-drug resistances. Very recently, we showed the diversity in the mcr-1-carrying plasmid reservoirs from the gut microbiota. Here, we reported that a similar but more complex scenario is present in the healthy swine populations, Southern China, 2016. Amongst the 1026 pieces of Escherichia coli isolates from 3 different pig farms, 302 E. coli isolates were determined to be positive for the mcr-1 gene (30%, 302/ 1026). Multi-locus sequence typing assigned no less than 11 kinds of sequence types including one novel Sequence Type to these mcr1- positive strains. PCR analyses combined with the direct DNA sequencing revealed unexpected complexity of the mcr-1-harbouring plasmids whose backbones are at least grouped into 6 types four of which are new. Transcriptional analyses showed that the mcr-1 promoter of different origins exhibits similar activity. It seems likely that complex dissemination of the diversified mcr-1-bearing plasmids occurs amongst the various ST E. coli inhabiting the healthy swine populations, in Southern China.
BACKGROUND: The mda-7/IL-24 receptor belongs to the type 11 cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy. METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were amplified by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed. RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1; BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor. CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.
Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK cell functions to promote tumor immune escape and progression, and therefore are considered key targets in cancer immunotherapy. Recent studies determined a key role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known that ceramide plays a key role in regulation of mammalian cell apoptosis. In this study, we aimed to determine the efficacy and underlying molecular mechanism of ceramide in suppression of MDSCs. Treatment of tumor-bearing mice with LCL521, a lysosomotropic inhibitor of acid ceramidase, significantly decreased MDSC accumulation in vivo. Using a MDSC-like myeloid cell model, we determined that LCL521 targets lysosomes and increases total cellular C16 ceramide level. Although MDSC-like cells have functional apoptosis pathways, LCL521-induced MDSC death occurs in an apoptosis-and necroptosis-independent mechanism. LCL521 treatment resulted in an increase in the number of autophagic vesicles, heterolysosomes and swollen ERs. Finally, concomitant inhibition of cathepsin B and cathepsin D was required to significantly decrease LCL521-induced cell death. Our observations indicate that LCL521 targets lysosomes to activate cathepsin B and cathepsin D, resulting in interrupted autophagy and ER stress that culminates in MDSC death. Therefore, a ceramidase inhibitor is potentially an effective adjunct therapeutic agent for suppression of MDSCs to enhance the efficacy of CTL-based cancer immunotherapy.
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers. We show that MEAF6-1 splicing is stimulated by neuronal RNA splicing factor SRRM4. Rather than inducing neuroendocrine trans-differentiation of cells in prostate adenocarcinoma, MEAF6-1 upregulation stimulates cell proliferation, anchorage-independent cell growth, invasion and xenograft tumor growth. Gene microarray identifies that these MEAF6-1 actions are in part mediated by the ID1 and ID3 genes. These findings suggest that the MEAF6-1 variant does not induce neuroendocrine differentiation of prostate cancer cells, but rather facilitates t-NEPC progression by increasing the proliferation rate of cells that have acquired neuroendocrine phenotypes.
Recently there has been renewed interest in large-scale games in several research disciplines, with diverse application domains as in the smart grid, cloud computing, financial markets, biochemical reaction networks, transportation science, and molecular biology. Prior works have provided rich mathematical foundations and equilibrium concepts but relatively little in terms of robustness in the presence of uncertainties. In this paper, we study mean field games with uncertainty in both states and payoffs. We consider a population of players with individual states driven by a standard Brownian motion and a disturbance term. The contribution is threefold: First, we establish a mean field system for such robust games. Second, we apply the methodology to production of an exhaustible resource. Third, we show that the dimension of the mean field system can be significantly reduced by considering a functional of the first moment of the mean field process.
Measurement of bone strain is the key factor in the bone biology studies to understand the changes in the structure of bone mass. This will be helpful in the improvement of treatment process for the patients suffered due to bone diseases. The system for the design of bone strain requires the components which include sensors, amplifiers, analog to digital converters (ADC), filter and the processing unit. Whenever the bone is loaded, it creates a small adjustment in the bone mass. The measurement of bone strain system requires more accuracy because of this very minimum variation in the structure of bone mass. Strain gauge sensors are used to sense the change in interconnected plates of bone mass (strain). The strain is a minimum value and in the range of micros, it desires to be processed to get the original value of strain. The processing of the signal is easier if it is a digital signal when compared to analog signal. Hence the voltage signal from the sensor measuring the strain is transmitted. Then the transmitted signal is amplified through operational amplifier and the analog signal is converted to digital using the comparator circuit. These operational amplifier and comparator circuit are designed using Complementary Metal Oxide Semiconductor (CMOS) technology to reduce the power consumption and simulated with the help of Mentor graphics. The system takes long time to measure the strain so that the system power consumption should be low. Thus the analysis of strain is useful in the treatment of orthopedic diseases.
Age, race, and sex are linked to social cognitive performance among healthy individuals, but whether similar effects are evident in schizophrenia is unknown. Data from 170 individuals with schizophrenia or schizoaffective disorder and 98 healthy controls were used to examine relations between these demographic factors and performance across multiple domains and measures of social cognition. Sex was not related to performance on any domain, but older age was related to poorer emotion recognition from dynamic stimuli in both patients and controls. In patients, older age was also associated with better abilities to decipher hints. Both Caucasian patients and controls performed better than African American individuals on emotion recognition and mental state attribution tasks that use only Caucasian individuals as visual stimuli. Findings suggest rather limited influences of demographic factors but do demonstrate normative age and race effects among patients. Findings also highlight important methodological considerations for measurement of social cognition.
Meat adulteration has posed considerable risks to public health. In this study, we developed a novel realtime quantitative PCR method for the detection of some mammalian and poultry species that are used as meat products or meat adulterants. The method was based on the detection of the single-copy nuclear gene myostatin. The specificity, heterogeneity, and copy number of myostatin were evaluated. Additionally, we determined the sensitivity and precision of the method. The results revealed that myostatin had high specificity and low heterogeneity among different mammalian and poultry species. The limit of detection was 5 pg of animal genomic DNA or 0.001% meat ingredient, and the limit of quantification was 10 pg of animal genomic DNA or 0.01% meat ingredient. The quantification results of 12 blind samples showed that the biases between the measured and true values were <25%. Therefore, the developed quantitative real-time PCR method for mammalian and poultry species is suitable for identification and quantification of different meat ingredients as a reference gene. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Traumatic brain injury (TBI) triggers both immediate (primary) and long-term (secondary) tissue damages. Secondary damages can last from hours to days or even a lifetime. Secondary damages implicate several mechanisms, including influence of inflammatory mediators, mainly cytokines, on excitability of ion channels. However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and excitability in distal intact neurons. Methods: Mixed cultures of mouse cortical astrocytes and neurons were subjected to mechanical injury (trauma) to mimic TBI in vitro. Expression of various cytokines in these cultures were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. A trauma-conditioned medium with or without brain-derived neurotrophic factor (BDNF) was added to mouse primary cortical neurons for 6 and 24 h to mimic combined effects of multiple inflammatory cytokines on VGSCs. Spike behaviors of distal intact neurons were examined by whole-cell patch-clamp recordings. Results: Mechanical injury in mixed cortical neuron-astrocyte cultures significantly increased expression levels of multiple cytokines, including interleukin (IL)-1 beta, IL-6, tumor necrosis factor-a, monocyte chemoattractant protein-1, chemokine (C-C motif) ligand-5, IL-10, and transforming growth factor-beta 1, at 6 and 24 h after injury. Incubation in trauma-conditioned medium increased functional VGSCs in neuronal membranes and Na+ currents. Enhanced VGSCs were almost completely abolished by BDNF, and reinforcement of Na+ currents was also reduced in a dose-dependent manner. BDNF (30 ng/mL) also significantly reversed reduced neuronal cell viability, which was induced by medium conditioned at 6 h. At 6 and 24 h, trauma-conditioned medium significantly increased spike frequency but not spike threshold. Conclusions: In TBI, the combined effect of inflammatory cytokines is directly involved in VGSC, Na+ current, and excitability dysfunction in distal intact neurons. BDNF may partly exert neuroprotective effects by maintaining balance of VGSC function in distal intact neurons.
Background: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABA(A)Rs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABA(A)Rs, there is a group of GABA(A)Rs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. Methods: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABA(A)R agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. Results: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. Conclusions: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well.
One of the promising ways for solving the water scarcity's problem in the world is distillation of the ocean's salt water by thermal methods. This method can be competitive with other methods, if required thermal energy is supplied by recovering the heat wastes of other energy systems such as gas turbine (GT) power plant. In this paper, a combined cycle of solid oxide fuel cell (SOFC) and GT can be used as thermal resource of multiple effect desalination system. Combination of these three system leads to reduce in total energy consumption, reduce in exhaust pollutants and reduce in operation and maintenance cost as well as increasing total efficiency in comparison with conventional individual systems. Exergoeconomic analysis of this hybrid system was performed to find out technical and economical optimal working point The system costs and revenues estimated, and the effect of two important design parameters (i.e., operational temperature and current density of SOFC) on exergy efficiency and levelized cost of electricity (LCOE) were investigated. Implementing GA optimization on the system and calculating the optimal values of the design parameter leads to rise of the exergy efficiency from 57% up to 63.5% and levelized cost of electricity was decreased to 0.0643 $/kwh. (C) 2017 Elsevier B.V. All rights reserved.
Background Mediator complex 19 (Med19) is a pivotal subunit of the Mediator complex, and its aberrant expression is involved in tumourigenesis. We aimed to explore the mechanism by which Med19 promotes the proliferation of breast cancer. Methods Lentivirus-mediated inhibition of Med19, ectopic expression of Med19 and ectopic expression of core-binding factor subunit alpha 2 to translocation 3 (CBFA2T3) were applied in human breast cancer cell lines. Human breast cancer cell proliferation was determined using CCK8 and colony formation assays after lentivirus infection. The expression of Med19, CBFA2T3 and HEB was measured by real-time reverse transcription polymerase chain reaction and Western blotting. The correlation between Med19 and CBFA2T3 expression in tissue from 25 cases of human breast cancer was analysed. Results In this study, we demonstrate that cell proliferation and colony formation capacity were significantly inhibited after Med19 inhibition in vitro. The expression of CBFA2T3 was distinctly up-regulated in MDA-MB-231 and MCF-7 human breast cancer cells when Med19 was knocked down; however, the expression of HEB, which is targeted by CBFA2T3, was down-regulated. Meanwhile, ectopic expression of Med19 in BT-549 and Hs578T human breast cancer cells inhibited CBFA2T3 expression but enhanced HEB expression. The proliferation capacity of human breast cancer cells was increased when Med19 was overexpressed, but the effect of Med19 up-regulation could be reversed by CBFA2T3 overexpression. Furthermore, a negative correlation between Med19 and CBFA2T3 expression was demonstrated by Western blotting in human breast cancer tissue. Conclusions These results suggest that Med19 promotes breast cancer cell proliferation and that this effect is associated with CBFA2T3 and HEB. These results provide new insights into the potential role of Med19 in the regulation of breast carcinogenesis, and Med19 may be a useful therapeutic target in breast cancer therapy.
Vertical integration has been extensively implemented across medical school curricula but has not been widely attempted in the field of biochemistry. We describe a novel curricular innovation in which a near-peer learning model was used to implement vertical integration in our medical school biochemistry course. Senior medical students developed and facilitated a case-based small group session for first year biochemistry students. Students were surveyed before and after the session on their attitudes about biochemistry, as well as the effectiveness of the session. Prior to the session, the students believed biochemistry was more important to understanding the basic science of medicine than it was to understanding clinical medicine or becoming a good physician. The session improved students' attitudes about the importance of biochemistry in clinical medicine, and after the session they now believe that understanding biochemistry is equally important to the basic sciences as clinical medicine. Students would like more sessions and believe the senior student facilitators were knowledgeable and effective teachers. The facilitators believe they improved their teaching skills. This novel combination of near-peer learning and vertical integration in biochemistry provided great benefit to both first year and senior medical students, and can serve as a model for other institutions. (C) 2016 by The International Union of Biochemistry and Molecular Biology
Children with medical complexity and victims of medical child abuse may have similar clinical presentations. Atypical or unexplained signs and symptoms due to rare diseases may lead providers to suspect medical child abuse when not present. Conversely, medical child abuse may be the cause of or coexist with medical complexity. Careful consideration of whether or not medical child abuse is present is essential when assessing a child with medical complexity since either diagnosis has significant consequences for children and families.
The purpose of this study was to investigate the influence of spirituality, religiosity, personal beliefs, and previous contact with health issues on the level of empathy in medical students. Jefferson Scale of Empathy-Student Version, WHOQOL-Spirituality, Religiousness and Personal Beliefs, and Duke University Religion Index were applied to 285 Brazilian medical students. The findings suggest that meaning of life and previous mental health treatment but not Religiosity were positively related to empathy. We suggest that more attention should be given for prevention and treatment of mental health issues, and further studies are needed to understand and replicate these findings.
Patients with advanced cancer frequently experience anxiety, depression and poor quality of life (QOL), as well as physical symptoms such as fatigue and weakness. Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear. We performed a study comparing medical Qigong (QG) and standard endurance and strength training (SET) in patients with advanced stage non-small cell lung (NSCLC) and gastrointestinal (GI) cancers. A randomized, cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy. Patients received supervised QG or SET twice-weekly for 6 weeks. Psychological functioning, QOL, symptoms and physical functioning were assessed before and after each intervention period. Nineteen patients completed both interventions. Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL. However, SET treatment was better at improving perceived strength (P = 0.05) and walking distance (P = 0.02). The order in which interventions were performed had a significant impact on the improvement in certain symptoms (sleep quality, breathlessness, P < 0.05), QOL (P = 0.01) and walking distance (P = 0.008). In all cases, the beneficial effects of the exercise interventions were markedly reduced during the second interval. QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients. However, SET leads to greater improvements in exercise capacity and helps reduce some symptoms. The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study.
TNF alpha-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated macrophages, modulates inflammation; however, its mechanism of action and role in the activation of macrophages are not fully understood. Herewe observed markedly augmented LPS-induced inflammatory lung injury and mortality in TSG6(-/-) mice compared with WT (TSG6(+/+)) mice. Treatment of mice with intratracheal instillation of TSG6 prevented LPS-induced lung injury and neutrophil sequestration, and increased survival in mice. We found that TSG6 inhibited the association of TLR4 with MyD88, thereby suppressing NF-kappa B activation. TSG6 also prevented the expression of proinflammatory proteins (iNOS, IL-6, TNF alpha, IL-1 beta, and CXCL1) while increasing the expression of anti-inflammatory proteins (CD206, Chi3l3, IL-4, and IL-10) in macrophages. This shift was associated with suppressed activation of proinflammatory transcription factors STAT1 and STAT3. In addition, we observed that LPS itself up-regulated the expression of TSG6 in TSG6(+/+) mice, suggesting an autocrine role for TSG6 in transitioning macrophages. Thus, TSG6 functions by converting macrophages from a proinflammatory to an anti-inflammatory phenotype secondary to suppression of TLR4/NF-kappa B signaling and STAT1 and STAT3 activation.
Ischemia-reperfusion injury (IRI) occurs when there is transient hypoxia due to the obstruction of blood flow (ischemia) followed by a subsequent re-oxygenation of the tissues (reperfusion). In the skin, ischemia-reperfusion (IR) is the main contributing factor to the pathophysiology of pressure ulcers. While the cascade of events leading up to the inflammatory response has been well studied, the spatial and temporal responses of the different subsets of immune cells to an IR injury are not well understood. Existing models of IR using the clamping technique on the skin flank are highly invasive and unsuitable for studying immune responses to injury, while similar non-invasive magnet clamping studies in the skin flank are less-than-ideal for intravital imaging studies. In this protocol, we describe a robust model of non-invasive IR developed on mouse ear skin, where we aim to visualize in real-time the cellular response of immune cells after reperfusion via multiphoton intravital imaging (MP-IVM).
This paper identifies several directions to improve the performances of the operating mechanism for medium voltage circuit breakers in order to get variable moving characteristics of the moving contact adjusted to the value of the switching current. Different drive solutions currently used in the operation of vacuum circuit breakers and SF6 were analyzed comparatively, as well as the performances they have to meet depending on the application. The solution proposes the use of a system with a microprocessor able to independently control the operation of moving contacts by stepper motors and the acquisition of the circuit breaker functional parameters.
Background Papillary (PTC) and medullary (MTC) thyroid carcinomas represent two distinct entities, but quite frequently, they may occur simultaneously. Aim To provide genetic analysis of PTC and MTC occurring in the same patient (PTC/MTC) to elucidate their origin. Methods Sequencing analysis of RAS, BRAF and RET oncogenes hot spots mutations in tumoral and normal tissues of 24 PTC/MTC patients. Results Two of 24 patients (8.3 %) were affected by familial MTC (FMTC) harboring RET germline mutations in all tissues. Eight of 22 (36.4 %) sporadic cases did not show any somatic mutation in the three tissue components. Considering the MTC component, 10/22 (45.4 %) patients did not show any somatic mutation, 7 of 22 (31.8 %) harbored the M918T RET somatic mutation and 4/22 (18.2 %) presented mutations in the H-RAS gene. In an additional case (1/22, 4.6 %), H-RAS and RET mutations were simultaneously present. Considering the PTC component, 1 of 24 (4.2 %) patients harbored the V600E BRAF mutation, 1 of 24 (4.2 %) the T58A H-RAS mutation and 1 of 24 (4.2 %) the M1T K-RAS mutation, while the remaining PTC cases did not show any somatic mutation. In one case, the MTC harbored a RET mutation and the PTC a BRAF mutation. None of the mutations found were present in both tumors. Conclusion To our knowledge, this is the first study analyzing a possible involvement of RET, BRAF and RAS oncogene mutations in PTC/MTC. These data clearly suggest that the classical activating mutations of the oncogenes commonly involved in the pathogenesis of PTC and MTC may not be responsible for their simultaneous occurrence.
Resistance to anticancer medications often leads to poor outcomes. The present study explored an effective approach for enhancing chemotherapy targeted against human cancer cells. Real-time quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed overexpression of members of aldo-keto reductase (AKR) 1C family, AKR1C1, AKR1C2, AKR1C3, and AKR1C4, in cisplatin, cis-diamminedichloroplatinum (II) (CDDP)resistant human cancer cell lines, HeLa (cervical cancer cells) and Sa3 (oral squamous cell carcinoma cells). The genes were downregulated using small-interfering RNA (siRNA) transfection, and the sensitivity to CDDP or 5-fluorouracil (5-FU) was investigated. When the genes were knocked down, sensitivity to CDDP and 5-FU was restored. Furthermore, we found that administration of mefenamic acid, a widely used non-steroidal anti-inflammatory drug (NSAID) and a known inhibitor of AKR1Cs, enhanced sensitivity to CDDP and 5-FU. The present study suggests that AKR1C family is closely associated with drug resistance to CDDP and 5-FU, and mefenamic acid enhances their sensitivity through its inhibitory activity in drug-resistant human cancer cells. Thus, the use of mefenamic acid to control biological function of AKR1C may lead to effective clinical outcomes by overcoming anticancer drug resistance.
BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has recently been reported to cause a folate-responsive syndrome displaying a phenotype that includes megaloblastic anemia and severe combined immunodeficiency. OBJECTIVE: To describe our investigative approach to the molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1 deficiency. METHODS: The methods used were exome sequencing and analysis of variants in genes involved in the folate metabolic pathway in a family with 2 affected siblings. Routine laboratory and research data were analyzed to gain an in-depth understanding of innate, humoral, and cell-mediated immune function before and after folinic acid supplementation. RESULTS: Interrogation of exome data for concordant variants between the siblings in the genes involved in folate metabolic pathway identified a heterozygous mutation in exon 3 of the MTHFD1 gene that was shared with their mother. In view of highly suggestive phenotype, we extended our bioinformatics interrogation for structural variants in the MTHFD1 gene by manual evaluation of the exome data for sequence depth coverage of all the exons. A deletion involving exon 13 that was shared with their father was identified. Routine laboratory data showed lymphopenia involving all subsets and poor response to vaccines. In vitro analysis of dendritic cell and lymphocyte function was comparable to that in healthy volunteers. Treatment with folinic acid led to immune reconstitution, enabling discontinuation of all prophylactic therapies. CONCLUSIONS: Exome sequencing demonstrated MTHFD1 deficiency as a novel cause of a combined immunodeficiency. Folinic acid was established as precision therapy to reverse the clinical and laboratory phenotype of this primary immunodeficiency. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Gametogenesis is a complex process wherein germ cells develop from primordial diploid cells into haploid gametes. To understand the mechanisms controlling gametogenesis, we identified a novel germ-cell-specific gene, Gcse. Gcse produces two major transcripts that are 1589bp (Gcse-l) and 906bp (Gcse-s) in length. Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) analyses of multiple tissues reveal that Gcse-l is expressed in both adult testes and ovaries, but Gcse-s is expressed only in adult testes. During female gonad development, Gcse-l is expressed from embryonic day 13.5 to adulthood, specifically in oocytes, and maintained in ovulated and fertilized eggs. However, Gcse-s signals were detected only in ovulated oocytes and fertilized eggs but not in adult ovary. During male gonad development, strong Gcse-l signals were detected in late pachytene spermatocytes and round spermatids. However, Gcse-s transcripts exist only in round spermatids. Furthermore, the expression of GCSE-L proteins and their subcellular localizations within cells are stage specific. GCSE-L is detected in the nucleus of late pachytene spermatocytes. During meiosis, GCSE-L is translocated to acrosome regions in spermatids and maintained in the acrosome of spermatozoa. GCSE-L colocalizes with acrosin and lectin peanut agglutinin in the Golgi apparatus. However, GCSE-S proteins are expressed only in the nucleus of spermatids. From these results, we suggest that GCSE proteins play roles in meiosis and may be involved in acrosome biogenesis during spermiogenesis.
Family study can provide estimates of overall genetic influences on a particular trait because family relationships provide accurate measures of average genetic sharing. However, evidence of genetic contributions to skin phenotypes is limited, which may preclude genetic studies to identify genetic variants or to understand underlying molecular biology of skin traits. This study aimed to estimate genetic and environmental contributions to selected dermatologic phenotypes, that is, to melanin index, sebum secretion, and skin humidity level in a Korean twin-family cohort. We investigated more than 2,000 individuals from 486 families, including 388 monozygotic twin pairs and 82 dizygotic twin pairs. Variance component method was used to estimate genetic influences in terms of heritability. Heritability of skin melanin index, sebum secretion, and skin humidity (arm and cheek) were estimated to be 0.44 [ 95% CI 0.38-0.49], 0.21 [ 95% CI 0.16-0.26], 0.13 [ 95% CI 0.07-0.18], and 0.11 [ 95% CI 0.06-0.16] respectively, after adjusting for confounding factors. Our findings suggest that genetics play a major role on skin melanin index, but only mild roles on sebum secretion and humidity. Sebum secretion and skin humidity are controlled predominantly by environmental factors notably on shared environments among family members. We expect that our findings add insight to determinants of common dermatologic traits, and serve as a reference for biologic studies.
Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non-lesional skin of patients and from the non-sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real-time polymerase chain reaction. Both factors were significantly lower in lesional than non-lesional skin and controls, while they were significantly higher in non-lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non-lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non-lesional levels of POMC, as well as between the lesional and non-lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.
Cancer/testis (CT) antigens are promising targets for immunotherapy due to their restricted expression in the germ cells of the testis in healthy tissue and high immunogenicity. The aim of the present study was to determine whether transmembrane protein 31 (TMEM31) is a CT antigen and to investigate the pattern of TMEM31 expression during the progression of melanoma. The pattern of expression of human TMEM31 mRNA in multiple human tissues was determined through reverse transcription-polymerase chain reaction analysis. TMEM31 protein expression was analyzed in the human testis, in addition to 128 primary melanoma and 64 metastatic melanoma samples through immunohistochemistry analysis. TMEM31 was identified to be predominantly expressed in the testis and weakly expressed in the placenta. In addition, TMEM31 protein expression was detected in 120/190 (63.16%) melanoma samples (primary and metastatic). The intensity of TMEM31 staining in metastatic and primary melanomas was determined through semiquantitative integrated optical density (IOD) analysis, and identified to be significantly increased in metastatic melanoma compared with primary melanoma (0.24 +/- 0.03 vs. 0.09 +/- 0.01 IOD/area; P<0.001). The expression of TMEM31 protein was significantly increased in metastatic compared with primary melanoma samples (76.56 vs. 56.35%; P=0.017). The results of the present study suggest that TMEM31 is a novel CT antigen that serves an essential role in melanoma metastasis, in addition to being a potential immunotherapeutic target for the treatment of patients with melanoma.
Cucurbit viruses have been associated with important economic losses in Xinjiang of China. Therefore, a comprehensive survey and sample collection was performed during the 2013 and 2014 growing seasons from the major melon-growing locations in Xinjiang which is the largest area for melon production in China. Samples were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) to detect Watermelon mosaic virus (WMV), Zucchini yellow mosaic virus (ZYMV), Cucumber mosaic virus (CMV), Papaya ringspot virus (PRSV), Squash mosaic virus (SqMV), Tomato ringspot virus (ToRSV), Moroccan watermelon mosaic virus (MWMV), Tomato spotted wilt virus (TSWV), Watermelon silver mottle virus (WSMoV), Cucumber green mottle mosaic virus (CGMMV), and Zucchini yellow fleck virus (ZYFV). We collected 492 melon samples with virus-like symptoms. Out of these, 94.5 % of the samples were infected by at least one of these viruses. WMV was the most prevalent virus detected. WMV, CMV, and ZYMV were detected in 77.0 %, 60.0 %, and 41.1 % of infected samples, respectively, and the infection rate of these three viruses changed significantly among melon cultivars. Other viruses analysed were not detected in any sample tested. The number of multiple infections was high (average 57.2 %), with the most common double infection WMV + CMV (17.8 %), closely followed by WMV + ZYMV (14.4 %). Statistical analysis of the potential association among viruses showed that there was a strong association between several viruses for multiple infections. An analysis of WMV genetic diversity suggested that all isolates obtained in this study clustered into group A and that purifying selection was restricting variability in the population.
This paper proposes a splittable amplifier technique that can be either decomposed into two identical halves or merged for enhancing the utilization of the amplifier power and alleviating the memory effect, when applying operational amplifier (opamp) sharing. In a two-phase clock system, the amplifier can be split into two identical small amplifiers in one phase simultaneously for use in two circuits. Next, the two small amplifiers can be merged into one amplifier in the other phase for usage in another circuit. Compared with the conventional opamp sharing, a more power-efficient amplifier arrangement is achieved in the split mode. In this paper, three individual sample and-hold (S/H) circuits with the proposed technique are designed to demonstrate the efficiency of memory effect cancellation. The simulations show that in contrast to the output spectrum of two S/H circuits with conventional opamp sharing, the spurious tones due to the memory effect can be suppressed by at least 14.66 dB in the split mode and at least 7.32 dB in the combination mode with a 0.6-VP-P input signal when using the proposed technique.
In this paper a new circuit for practical emulation of a floating memristor is presented. The circuit is simple, flexible and built around the current-feedback operational-amplifier and avoids the use of analog-to-digital and digital-to-analog converters and the analog multiplier. The circuit is simpler than the very few available similar circuits. The application of the proposed floating memristor emulator in designing an FM-to-AM converter confirms the functionality of the proposed circuit. Experimental results are included.
Memristor is a nano device that exhibits unique IV pinched hysteresis loop with switching mechanism and has ability to remember its last state. These interesting memristor characteristics encourage researchers to understand the new device and develop its potential applications. The problem is memristor has not yet available in current market due to the cost and technical difficulties in fabrication nanoscale device. Thus, the only way is develop model for memristor. In this paper, few SPICE memristor models are selected and their I-V behaviors are compared to a physical memristor to verify model similarity with actual device. Next a new approach of CMOS memristor application is proposed. An interfacing circuit between SPICE memristor model and CMOS circuit is presented. The interfacing circuit is composed by write circuit (to program memristor resistance) and read circuit (to read memristor current) using operational amplifier and current mirror. This interfacing circuit is very important to incorporate memristor into CMOS for CMOS-memristor application studies.
In this paper, a new floating analog memristance simulator circuit based on second generation current conveyors and passive elements is proposed. Theoretical derivations are presented which decribe the circuit characteristics. The hardware of proposed simulator circuit is built using commercially available components. Theoretical derivations are validated with PSPICE simulation and experimental results. Performance of circuit was tested with simple example circuits. All results show that proposed simulator circuit provides frequency dependent pinched hysteresis loop and nonvolatility features. Exciting frequency, minimum and maximum memristance values and memristance range can be adjustable with simple passive element values. Simulator circuit has a frequency range of 1Hz to 40 kHz.
Memristor has been claimed as the passive fourth fundamental circuit element in 1971. About four decades later, a physical realization which presents memristor behavior has resulted in significant interest on memristor and it is continuing to increase at a growing rate. Memristor can provide new possibilities in analog circuit design thanks to its properties which cannot be mimicked by older passive circuit elements. Since no practically available memristor exist on the market yet, obtaining of a practical implementation which behaves like a memristor is important from the point of view real-world circuit design. In this paper, an ultra low-voltage ultra low-power DTMOS-based memristor design is presented. Ultra low-voltage, ultra low-power operational amplifier and ultra low-voltage, ultra low-power multiplier are also designed to use in the implementation. Memristor design is composed of these two type active blocks using CMOS 0.18 A mu m process technology with symmetric +/- 0.25 V supply voltages. Our memristor is used in a second order Sallen-Key band-pass filter topology. Designed memristor-based Sallen-Key band-pass filter is then used for real electroencephalogram data processing. The simulation results show that the design of adjustable memristor memristance/memductance provides tunable filter parameters and without any significant distortion with appropriate parameter set even at ultra-low power levels and at very-low frequencies.
This paper presents a new memristor emulator circuit. The circuit is built around the current-feedback operational-amplifier and exploits the nonlinear transfer characteristic of the operational transconductance amplifier to provide continuous change in the memresistance. This is in contrast with many of the available memristor emulators which can provide only binary memresistance levels. Moreover, the emulator enjoys a low impedance input and is suitable for current driving rather than voltage driving. The functionality of the proposed memristor emulator is confirmed by implementing a well-known reactance-less multivibrator circuit. Experimentally obtained results are included. (C) 2014 Elsevier GmbH. All rights reserved.
In the submandibular gland (SMG) of mice, a duct portion called the granular convoluted 14 tubule (GCT) is developed preferentially in males with puberty. This sexual dimorphism is androgen-dependent, but the underlying molecular mechanisms are unclear. We have demonstrated that the expression of a transcription factor JunD is regulated in association with the androgen-induced differentiation of GCT cells from striated duct (SD) cells. Menin, a nuclear protein encoded by the MEN1 tumor-suppressor gene, is known to bind JunD, thereby inhibiting its activity. In the present study, we examined the expression of menin in the mouse SMG by use of Northern blotting, Western blotting, and immunohistochemistry. Immunoreactivity for menin was higher in the female than male gland, and localized to the nuclei of intercalated duct cells and a subpopulation of SD cells. In contrast, GCT cells in males appeared negative for menin. The levels of menin in the SMG were increased with castration in males and decreased by repeated administration of testosterone to females or to castrated males. After a single administration of testosterone to females, many SD cells newly gained nuclear menin, which was lost as the cells converted to GCT cells by 48 hrs. These patterns of the expression and localization of menin were quite similar to those of JunD. Furthermore, the coimmunoprecipitation analysis of the SMG homogenates indicated that menin binds JunD in vivo. The present study suggests that the JunD-menin complex plays significant roles in the androgen-dependent differentiation of the duct system in the mouse SMG.
Background. Serogroup B meningococcal disease caused 7 US university outbreaks during 2013-2016. Neisseria meningitidis can be transmitted via asymptomatic nasopharyngeal carriage. MenB-FHbp (factor H binding protein), a serogroup B meningococcal (MenB) vaccine, was used to control a college outbreak. We investigated MenB-FHbp impact on meningococcal carriage. Methods. Four cross-sectional surveys were conducted in conjunction with MenB-FHbp vaccination campaigns. Questionnaires and oropharyngeal swabs were collected from students. Specimens were evaluated using culture, slide agglutination, real-time polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted prevalence ratios (aPRs) were calculated using generalized estimating equations. Results. During each survey, 20%-24% of participants carried any meningococcal bacteria and 4% carried serogroup B by rt-PCR. The outbreak strain (ST-9069) was not detected during the initial survey; 1 student carried ST-9069 in the second and third surveys. No carriage reduction was observed over time or with more MenB-FHbp doses. In total, 615 students participated in multiple surveys: 71% remained noncarriers, 8% cleared carriage, 15% remained carriers, and 7% acquired carriage. Ten students acquired serogroup B carriage: 3 after 1 MenB-FHbp dose, 4 after 2 doses, and 3 after 3 doses. Smoking (aPR, 1.3; 95% confidence interval [CI], 1.1-1.5) and male sex (aPR, 1.3; 95% CI, 1.1-1.5) were associated with increased meningococcal carriage. Conclusions. Carriage prevalence on campus remained stable, suggesting MenB-FHbp does not rapidly reduce meningococcal carriage or prevent serogroup B carriage acquisition. This reinforces the need for high vaccination coverage to protect vaccinated individuals and chemoprophylaxis for close contacts during outbreaks.
This study examined the effects of exposure to specific message features on the usage of mental health video games applications. Based on linguistic agency and disease causality, participants with mild depression read messages assigning agency to depression or to humans and depicting depression as external or internal before accessing a video game designed for handling depression symptoms. Assigning internal causality language led to greater game usability and higher intentions of using the games. Game performance and time spent playing the games, was higher for external causality language. Overall, findings from this study demonstrate the effectiveness of specific message prompt features to promote video game experience for mental health apps. (C) 2017 Elsevier Ltd. All rights reserved.
This article explores the impact of losing a child, especially losing all children (including losing the only child), on the mental health, happiness and loneliness of parents. The Chinese government has implemented strict restrictions on the number of births for each family since the 1970s, resulting in the creation of millions of only-child families. Using the 2011 baseline data from the China Health and Retirement Longitudinal Study, we find that the bereavement of a child is associated with lower levels of mental health and happiness and higher levels of loneliness for the parents, even after we adjust for demographic and socioeconomic characteristics. The effects are significantly stronger for losing all the children. Results have strong implications for the population-control, elderly-care and mental-care policies especially in China and developing countries, where the social security system is not yet sound.
People living with HIV/AIDS (PHA) often concurrently cope with mental health disorders that may greatly influence HIV and other health-related outcomes. The objective of this study was to examine the prevalence and correlates of self-reported mental health disorder diagnosis among a cohort of harder-to-reach HIV-positive individuals in British Columbia, Canada. Between 2007 and 2010, 1000 PHA who had initiated ART were enrolled in the Longitudinal Investigation into Supportive and Ancillary health services (LISA) study. Socio-demographic, behavioral, health-care utilization and psychosocial information was collected through interviewer-led questionnaires and linked to longitudinal clinical variables through the provincial Drug Treatment Program at the BC Centre for Excellence in HIV/AIDS. We identified the prevalence of all-type and specific mental health disorders among this population. Of the 916 participants included in this analysis, 494 (54%) reported ever having a mental health disorder diagnosis. Mood (85%) and anxiety (65%) disorders were the two most frequently reported mental health conditions. Self-reported all-type mental health disorder was independently associated with decreased overall functioning (adjusted odds ratio [AOR]=0.90, 95% confidence interval [CI]=0.83-0.98) and life satisfaction (AOR=0.81, 95% CI=0.74-0.89), and having higher stigma score (AOR=1.11, 95%CI=1.02-1.21). Participants reporting any mental health disorder were more likely to report a history of sexual assault (AOR=2.45, 95% CI=1.75-3.43) and to have used case management services (AOR=1.63, 95%CI=1.17-2.27). Our findings uncovered a high burden of mental health disorders among harder-to-reach PHA and suggest that PHA with at least one mental health disorder diagnosis are disproportionately impacted by sexual violence and stigma.
Understanding complex problems such as climate change is difficult for most nonaEuroscientists, with serious implications for decision making and policy support. Scientists generate complex computational models of climate systems to describe and understand those systems and to predict the future states of the systems. Non-scientists generate mental models of climate systems, perhaps with the same aims and perhaps with other aims too. Often, the predictions of computational models and of mental models do not correspond with important implications for human decision making, policy support, and behaviour change. Recent research has suggested non-scientists' poor appreciation of the simple foundations of system dynamics is at the root of the lack of correspondence between computational and mental models. We report here a study that uses a simple computational model to 'run' mental models to assess whether a system will evolve according to our aspirations when considering policy choices. We provide novel evidence of a dual-process model: how we believe the system works today is a function of ideology and worldviews; how we believe the system will look in the future is related to other, more general, expectations about the future. The mismatch between these different aspects of cognition may prevent establishing a coherent link between a mental model's assumptions and consequences, between the present and the future, thus potentially limiting decision making, policy support, and other behaviour changes.
The dorsomedial prefrontal cortex (dmPFC) is part of the mentalizing network, a set of brain regions consistently engaged in inferring mental states. However, its precise function in this network remains unclear. It has recently been proposed that the dmPFC is involved in high-level abstract (i.e., categorical) identification or construction of both social and non-social stimuli, referred to as "high construal." This was based on the observation of greater activation in the dmPFC shared by a high construal social condition (trait inference based on visually presented behavior) and a high construal non-social condition (categorization of visually presented objects) vs. matched low construal conditions (visual description of the same pictures). However, dmPFC activation has been related to task contexts requiring responses based on self-guided generation of mental content or decisions as compared to responses more directly determined by the experimental context (e.g., free vs. rule-governed choice). The previously reported dmPFC activity may reflect differences in task constraint (i.e., the extent to which the task context guided the process) confounded with the construal manipulation. Therefore, in the present study, we manipulated construal level and constraint independently, while participants underwent functional magnetic resonance imaging (fMRI). As before, participants visually described (low level construal) or categorized (high level construal) pictures of objects. Orthogonal to this, the description or categorization task had to be performed on either one object (low constraint) or on two objects simultaneously (high constraint), limiting the number of possible responses. Statistical analysis revealed common greater activation in both high construal conditions (high and low constraint) than in their low construal counterparts, replicating the influence of construal level on dmPFC activation (greater involvement in high than low construal), but no influence of constraint. In line with previous proposals and earlier work, we suggest that the dmPFC is involved in high-construal abstraction across different domains.
Parental mentalizing - the parent's ability to envision the child'smental states (such as desires, thoughts, or wishes) - has been argued to underlie a parent's ability to respond sensitively to their child's emotional needs, and thereby promote advantageous cognitive and socio-emotional development. Mentalizing is typically operationalized in terms of how parents talk to or about their infants. This work extends research on mentalizing by operationalizing parental mentalizing exclusively in terms of nonverbal, bodily based, interactive behavior, namely parental embodied mentalizing(PEM). The purpose of the current researchwas twofold: (1) to establish the reliability and validity of the PEM coding system; and (2) to evaluate whether such measurement predicts infant and child cognitive and socio-emotional functioning. Assessing 200 mother-infant dyads at 6 months using the coding of PEM proved both reliable and valid, including predicting child attachment security at 15 and 36 months, and language abilities, academic skills, behavior problems, and social competence at 54 months, in many cases even after taking into consideration traditional measures of parenting, namely maternal sensitivity. Conceptual, empirical, and clinical implications are discussed.
Mercury (Hg) is an environmental toxicant being present in the environment as elemental Hg (Hg), inorganic and organic Hg compounds. The nervous system is supposed to be the key target for Hg toxicity. Research indicates that selenium (Se) may be used as a protective agent against Hg neurotoxicity. Therefore, the aim of this review is to examine new implications of the molecular biology of Hg neurotoxicity, and specifically to focus on the influence of Se compounds and interfering thiols on Hg neurotoxicity at the molecular level. Mercury and Se form stable coordination compounds, and Hg species are characterized by higher affinity to selenol groups as compared to thiol groups. Therefore, Se-containing molecules are targets for Hg binding that may at least partially mediate the biological outcome of Hg-Se interaction. Molecular interaction between these elements also involves mutual interaction between Hg and various selenoproteins. Experimental data demonstrate that Se treatment modifies brain Hg retention, modulates neurotoxicity and oxidative stress in the nervous tissue of animals. Human data also indicate that molecular interaction between Hg and Se may have a significant influence on neurodevelopment, brain functioning, and neurodegeneration. It is hypothesized that the effectiveness of Se protection against Hg neurotoxicity may be determined by the dose of elements as well as their particular chemical forms. Further studies are required to estimate the intimate mechanisms of Hg and Se interaction in vivo. (C) 2016 Elsevier B.V. All rights reserved.
Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFa and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPAR gamma. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPAR gamma and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity.
Since discovery of Middle East respiratory syndrome coronavirus (MERS-CoV), a novel betacoronavirus first isolated and characterized in 2012, MERS-CoV real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays represent one of the most rapidly expanding commercial tests. However, in the absence of extensive evaluations of these assays on positive clinical material of different sources, evaluating their diagnostic effectiveness remains challenging. We describe the diagnostic performance evaluation of 3 common commercial MERS-CoV rRT-PCR assays on a large panel (n = 234) of upper respiratory tract specimens collected during an outbreak episode in Saudi Arabia. Assays were compared to the RealStar (R) MERS-CoV RT-PCR (Alton Diagnostics, Hamburg, Germany) assay as the gold standard. Results showed i) the TIB MolBiol (R) LightMix UpE and Orfl a assays (TIB MolBiol, Berlin, Germany) to be the most sensitive, followed by ii) the Anyplex (TM) Seegene MERS-CoV assay (Seegene, Seoul, Korea), and finally iii) the PrimerDesign (TM) Genesig (R) HCoV_2012 assay (PrimerDesign, England, United Kingdom). We also evaluate a modified protocol for the PrimerDesign (TM) Genesig (R) HCoV_2012 assay. (C) 2017 Elsevier Inc. All rights reserved.
Objective:Although increasing evidence has shown that long noncoding RNAs (lncRNAs) play an important regulatory role in pluripotency and differentiation of mesenchymal stem cells, little is known about the role of lncRNA in maxillary sinus membrane stem cells (MSMSCs). The goal of this study was to investigate the expression profile and function of lncRNAs on osteogenic differentiation of MSMSCs.Materials and Methods:By using lncRNA microarray, we identify a novel osteogenesis differentiation-related lncRNA of MSMSCs (lncRNA-MODR). The functional role of lncRNA-MODR in regulating osteogenesis was evaluated by quantitative real-time polymerase chain reaction, western blot, and alizarin red staining. Bioinformatic analyses of the predicted target genes (gene ontology, pathway, and network analysis) were applied for further study of lncRNA-MODR.Results:We show that lncRNA-MODR is gradually upregulated during osteogenic differentiation. lncRNA-MODR overexpression upregulated, whereas lncRNA-MODR silencing decreased the expression of the osteogenic key marker, runt-related transcription factor 2 (RUNX2). In-depth analyses showed that lncRNA-MODR acts as a molecular sponge for microRNA-454 (miR-454) and that prevents RUNX2 from mi-454-mediated suppression.Conclusion:The lncRNAs act as a competing endogenous RNA to sequester microRNA-454 (miR-454), leading to heightened RUNX2 expression and thus promotes osteogenesis of MSMSCs.
Mesenteric lymph is vital for immune cell trafficking and intestinal fluid and chyle transport, which aid homeostatic maintenance. There have been few reports investigating the profiles and circulatory dynamics of mesenteric lymph microRNAs (miRNAs). The present study aimed to provide a comprehensive analysis of miRNAs in normal rodent mesenteric lymph. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-based array analysis was performed to examine the expression levels of 375 miRNAs in normal rat mesenteric lymph. Using differential centrifugation, the presence of miR-150, a representative lymph miRNA, in exosomes was assessed. Rat small intestine epithelial cell line IEC-6-derived exosomes were prepared from culture supernatants of cells transfected with cel-miR-238-3p, and were used to trace the administered exosomes in vivo and to investigate the invivo delivery of lymph miRNAs via mesenteric lymphatics into the systemic circulation following injection of celmiR-238-3p-exo-somes. RT-qPCR-based array analysis detected 287 miRNAs in lymph, and 21 miRNAs that were significantly differentially expressed between lymph and plasma. Lymph fractionation analysis demonstrated that some cell-free lymph miR-150 was distributed in the exosome-containing microsomal fraction. Furthermore, in vivo analysis of lymph miRNA delivery revealed that exosomal cel-miR-238-3p was markedly distributed in the lung compared with in the liver, kidney and spleen, thus indicating that the lung is the major organ responsible for clearance of exosomal lymph miRNAs. These findings provide novel insights into the modulation of gene expression by mesenteric lymph miRNAs in the lung.
Meshless methods for convection-dominated flow problems have the potential to reduce the computational effort required for a given order of solution accuracy compared to mesh-based methods. The state of the art in this field is more advanced for elliptic partial differential equations than for time-dependent convection diffusion problems. In this paper, we introduce a new meshless method that it based on combining the modified method of characteristics with the radial basis functions during the solution reconstruction. The method belongs to a class of fractional time-stepping schemes in which a predictor stage is used for the discretization of convection terms and a corrector stage is used for the treatment of diffusion terms. Special attention is given to the application of this method to solve convection-dominated flow problems in two-dimensional domains. Numerical results are shown for several test examples including the incompressible Navier Stokes equations and the computed results support our expectations for a stable and highly accurate meshless method. (C) 2016 International Association for Mathematics and Computers in Simulation (IMACS). Published by Elsevier B.V. All rights reserved.
Background. Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities that may affect the progression of various cancers. Malignant ascites contains high levels of LPA as well as vascular endothelial growth factor (VEGF). Although LPA receptors are widely expressed in normal as well as cancer cells, little is known about the effect of LPA on host cells. Therefore, we evaluated the effect of LPA specifically on peritoneal mesothelial cells (PMC), and assessed another aspect of LPA in tumor biology mediated through the host cells. Materials and methods. The effect of LPA on the production of VEGF was evaluated by ELISA and northern blotting. Next, we quantified human- and mouse-VEGF separately in ascitic fluid of nude mice inoculated intraperitoneally with a human gastric cancer, MKN45, and thus evaluated the ratio of host-derived VEGF in malignant ascites. Results. Addition of 10 to 80 mu m LPA enhanced VEGF production by PMC through gene activation. The effect was strongly inhibited by pre-treatment with PTX or Ki16425, indicating that the effect was mainly dependent on the LPA1 signal. Of the VEGF in ascitic fluid at 3 weeks after tumor inoculation, 12.8% was derived from mouse cells. At 6 weeks, however, the ratio of host-derived VEGF was reduced to 5.0%, suggesting that the ratio of host-derived VEGF may be higher in the earlier phase. Conclusion. Because tumor growth is often associated with an increase of LPA concentration in ascites, stimulation of VEGF production in PMC might have an important role in the growth of cancer cells disseminated in the peritoneal cavity. (c) 2006 Elsevier Inc. All rights reserved.
Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura with a poor prognosis. The most active first-line regimens are platinum compounds and pemetrexed. There is no standard second-line treatment in MPM. Advances in the understanding of tumor molecular biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. Unfortunately none of the explored targeted treatments can currently be recommended as routine treatment in MPM. We reviewed the biological pathways involved in MPM, the clinical trials about targeted therapy, and possible related mechanisms of resistance. We suggest that specific genetic markers are needed as targets of selective therapy. By this way the selection of patients based on the molecular profile may facilitate a therapeutic strategy that allows the use of the most appropriate drug for each patient. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Background: The complexity of RNA regulation is one of the current frontiers in animal and plant molecular biology research. RNA-binding proteins (RBPs) are characteristically involved in post-transcriptional gene regulation through interaction with RNA. Recently, the mRNA-bound proteome of mammalian cell lines has been successfully cataloged using a new method called interactome capture. This method relies on UV crosslinking of proteins to RNA, purifying the mRNA using complementary oligo-dT beads and identifying the crosslinked proteins using mass spectrometry. We describe here an optimized system of mRNA interactome capture for Arabidopsis thaliana leaf mesophyll protoplasts, a cell type often used in functional cellular assays. Results: We established the conditions for optimal protein yield, namely the amount of starting tissue, the duration of UV irradiation and the effect of UV intensity. We demonstrated high efficiency mRNA-protein pull-down by oligo-d(T)(25) bead capture. Proteins annotated to have RNA-binding capacity were overrepresented in the obtained medium scale mRNA-bound proteome, indicating the specificity of the method and providing in vivo UV crosslinking experimental evidence for several candidate RBPs from leaf mesophyll protoplasts. Conclusions: The described method, applied to plant cells, allows identifying proteins as having the capacity to bind mRNA directly. The method can now be scaled and applied to other plant cell types and species to contribute to the comprehensive description of the RBP proteome of plants.
During the last decade games have arguably become the largest form of leisure information systems (IS). However, today games are also increasingly being employed for a variety of instrumental purposes. Although games have garnered a substantial amount of research attention during the last decade, research literature is scattered and there is still a lack of a clear and reliable understanding of why games are being used, and how they are placed in the established utilitarian-hedonic continuum of information systems. To address this gap, we conducted a meta-analysis of the quantitative body of literature that has examined the reasons for using games (48 studies). Additionally, we compared the findings across games that are intended for either leisure or instrumental use. Even though games are generally regarded as a pinnacle form of hedonically-oriented ISs, our results show that enjoyment and usefulness are equally important determinants for using them (though their definitive role varies between game types). Therefore, it can be posited that games are multi-purpose ISs which nevertheless rely on hedonic factors, even in the pursuit of instrumental outcomes. The present study contributes to and advances our theoretical and empirical understanding of multi-purpose ISs and the ways in which they are used. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Metabolic syndrome (MetS) significantly correlates with exercise. MetS also has an independent and inverse correlation to quality of life (QoL). However, few studies have examined the association between exercise and QoL in people with MetS. The aim of this study was to ascertain the relationship between exercise and QoL in a MetS population. Methods: This was a cross-sectional study using public data from the Sixth Korean National Health and Nutrition Examination Survey in 2014 (n = 7550). MetS was defined on the basis of the revised National Cholesterol Education Program criteria. Demographic factors, three types of exercise (resistance, flexibility, walking), five subsets of EuroQoL (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and QoL scores (EQ-VAS), were investigated. Independent associations of each exercise on five subsets of QoL were determined using odds ratios (OR) adjusted for four demographic factors (age group, sex, weight change, and area of residence) using multivariate logistic regression analysis. Results: Prevalence of MetS was 26.4% and the ratio of subjects performing resistance, flexibility, or walking exercise was 17.7%, 45.8%, and 71.5% among this population, respectively. EQ-VAS of exercisers was significantly higher than that of non-exercisers in resistance, flexibility, and walking exercise. Although resistance and flexibility exercise did not correlate with any subsets of QoL, mobility and self-care were significantly associated with walking exercise (OR = 0.635, 95% CI = 0.439-0.919 and OR = 0.577, 95% CI = 0.348-0.958, respectively). Conclusions: All exercisers showed higher QoL scores than non-exercisers. Among QoL subsets, mobility and self-care were independently associated with walking exercise in the MetS population. Regular walking exercise was important to higher QoL in those with MetS. This is the first clinical report to indicate that QoL could be independently influenced by walking exercise.
Objectives: To describe longitudinal relationships of metabolic syndrome (MetS) to cognitive decline and functional disability in a sample of older non-institutionalized men. Methods: data from 1991 to 2000 of the Italian cohorts of the Finland, Italy, the Netherlands, Elderly (FINE) study, were used. Global cognitive function and functional disability, defined as limitations in mobility, basic (ADLs) and instrumental activities of daily living (IADLs) were screened in 1991 and 2000. MetS was defined according to the NCEP ATP-III criteria. Results: The study sample consisted of 195 men, baseline age 76.1 +/- 3.1 years. Baseline MetS was prospectively associated with greater 10-year cognitive and functional decline in ADLs and IADLs. After multiple adjustment including age, education, marital status, ApoE epsilon 4 allele, cerebrovascular disease and initial cognitive and depressive status, MetS predicted cognitive decline (B = - 1.684, 95% CI = - 2.202 to - 1.167, p < 0.001) and risk of IADLs (OR = 1.09, 95% CI = 1.01-1.20, p = 0.048) and ADLs disability (OR = 1.35, 95% CI = 1.12-1.62, p < 0.001). Interestingly, such associations were not attributable to individual altered components of MetS nor to their sum. Incident disability in ADLs and IADLs were not explained by parallel decline in cognitive function. Conclusions: MetS as an entity was associated with accelerated cognitive and functional decline in a population-based sample of very old men. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Purpose Triglycerides are considered an emerging risk factor for cardiovascular mortality. Recent evidence relating depression and metabolic syndrome (MetS) implicated triglyceride levels. We thus investigated interrelations of self-reported depression severity (Zung) and MetS-related biological measures with CVD risk estimates in MetS patients. Methods N = 101 patients fulfilling International Diabetes Federation criteria for MetS from a nationwide sampled treatment cohort for MetS with familial T2DM risk or manifest T2DM in a Ukrainian governmental health care system were participants. Both laboratory and non-laboratory measures were included. Recent European cardiological SCORE system CVD risk estimates were used as outcome variables. Results Following correlation matrix, we entered all variables into principal component analysis (PCA; 76.7% explained variance), followed by hierarchical regression and structural equation modeling (SEM). The PCA suggested a one-factor solution, where the latent variable showed highest loadings of SCORE risk estimates, triglycerides, depression severity, and pulse pressure. A comprehensive SEM was adjusted with 92.7% explained variance: overall CVD risk related to depression, pulse pressure, triglycerides, and fasting glucose. Conclusion The findings in this MetS sample suggest that triglycerides and depression severity are the key variables among MetS biomarkers in cross-sectionally associating with the fatal and total SCORE risk estimates in MetS.
Cellular metabolism has emerged as an important regulator of adaptive immunity. While the metabolic requirements of conventional T cells are increasingly understood, the role of cellular metabolism in Foxp3(+) regulatory T (Treg) cells is less clear. Although it is well accepted that repression of Akt/mTOR, HIF-1 alpha and aerobic glycolysis are important for the efficient generation of Treg cells in vitro, clear evidence how these pathways impact on Treg-cell development in vivo is limited. Furthermore, newer studies have shown that the same pathways that appear to suppress Treg-cell development are active in and required for functionally mature Treg cells. Thus, it becomes increasingly evident that development and function of regulatory T cells require different wiring of metabolic pathways. Finally, it is likely that critical differences remain to be uncovered between the metabolism of resting or 'naive' Treg cells and those fully differentiated and actively engaged in suppression. In this comment, we briefly discuss our current understanding of Treg-cell metabolism and the need to address this area with new approaches based on in vivo models.
The northern fowl mite, Ornithonyssus sylviarum, is the most damaging ectoparasite on egg-laying hens in the United States. One potential strategy for management is breeding for mite resistance. Genes of white leghorn chickens linked to the major histocompatibility complex (MHC) were previously identified as conferring more (B21 haplotype) or less (B15 haplotype) mite resistance. However, immune responses can be energetically costly to the host and affect the economic damage incurred from mite infestations. We tested energy costs (resting metabolic rate) of mite infestations on egg-laying birds of both MHC B-haplotypes. Resting metabolic rates were documented before (pre-) mite infestation, during (mid-) infestation, and after peak (late) mite infestation. Mite scores, economic parameters (egg production, feed consumption), and physiological aspects such as skin inflammation and skin temperature were recorded weekly. Across experiments and different infestation time points, resting metabolic rates generally were not affected by mite infestation or haplotype, although there were instances of lower metabolic rates in infested versus control hens. Skin temperatures were recorded both at the site of mite feeding damage (vent) and under the wing (no mites), which possibly would reflect a systemic fever response. Ambient temperatures modified skin surface temperature, which generally was not affected by mites or haplotype. Feed conversion efficiency was significantly worse (4.9 to 17.0% depending on trial) in birds infested with mites. Overall egg production and average egg weight were not affected significantly, although there was a trend toward reduced egg production (2 to 8%) by infested hens. The MHC haplotype significantly affected vent skin inflammation. Birds with the mite-resistant B21 haplotype showed earlier onset of inflammation, but a reduced overall area of inflammation compared to mite-susceptible B15 birds. No significant differences in resting energy expenditure related to mite infestation or immune responses were detected. Potential breeding for resistance to mite infestation using these two haplotypes appears to be neutral in terms of impact on hen energy costs or production efficiency, and may be an attractive option for future mite control.
Through a series of long-term column experiments, the fate of three common pharmaceuticals (carbamazepine (CBZ), diclofenac, and indomethacin) and their major phase I metabolites in soil aquifer treatment (SAT) were monitored. CBZ concentration increased by a factor of two (from 37 to ca. 70 ng/L) regardless of the treatment conditions, and its metabolites, 10,11-dihydro-10hydroxycarbamazepine (approximately 500 ng/L after SAT) and CBZ-10,11-epoxide (12-42 ng/L after SAT) were not effectively removed after SAT. Our results indicated that some metabolites of pharmaceuticals are present at much higher concentration than the original forms in the SAT effluent, and that some metabolites are more persistent during SAT with a relatively short retention time (i.e., 30 days). The study indicated that more attention should be paid to the formation and fate of metabolites in the water quality management of SAT effluent.
By proposing a three-hierarchy meta-frontier data envelopment analysis (DEA), this paper first decomposes CO2-emissions efficiency and the potential for emissions reduction into the following three components: structural, technical, and management. Based on these components, we then conduct an empirical analysis of China's total-factor CO2-emissions efficiency, its potential for CO2-emissions reduction, and its corresponding implementation path. The results show that CO2-emissions efficiency in Mainland China is relatively low because of structural inefficiency, technical inefficiency, and management inefficiency. The Chinese government is expected to realize a large quantity of CO2-emissions reduction potential (nearly 40% of the current total CO2-emissions) through adjusting the industrial structure, narrowing the technology gap among regions, promoting the reform of marketization, and strengthening environmental regulation. The causes of CO2-emissions inefficiency and the distribution of potential reductions in emissions show a distinct spatial difference characteristic. Therefore, this paper also formulates emissions-reduction strategies for China's 30 provinces according to their specific situations, noting the direction of the industrial structure adjustment and the path to improving CO2-emissions efficiency.
In recent years, there have been particular emphases worldwide on the development and optimization of bioprocesses for the utilization of biomass. An essential component of the biomass processing conduit has been the need for robust biocatalysts as high-performance tools for both the depolymerization of lignocellulosic biomass and synthesis of new high-value bio-based chemical entities. Through functional screening of the metagenome of the hindgut bacterial symbionts of a termite, Trinervitermes trinervoides, we discovered open reading frames for 25 cellulases and hemicellulases. These were classified into 14 different glycoside hydrolase (GH) families: eight GH family 5; four GH9, two GH13, and one each in GH2, GH10, GH11, GH26, GH29, GH43, GH44, GH45, GH67, and GH94 families. Of these, eight were overexpressed and partially characterized to be shown to be endocellulases (GH5C, GH5E, GH5F, and GH5G), an exocellulase (GH5D), endoxylanases (GH5H and GH11), and an alpha-fucosidase (GH29). The GH11 (Xyl1) was of particular interest as it was discovered to be a multimodular beta-1,4-xylanase, consisting of a catalytic domain and two carbohydrate-binding modules (CBMs). The CBM functions to selectively bind insoluble xylan and increases the rate of hydrolysis. The primary structure of GH11 showed a classical catalytic dyad of glutamic acid residues that generally forms part of the active site in GH11 enzyme family. This endoxylanase was optimal at pH 6 and 50 degrees C, and generated xylobiose and xylotriose from various xylan sources, including beechwood, birchwood, and wheat arabinoxylan. The catalytic ability of GH11 against natural substrate (e.g., wheat arabinoxylan) renders GH11 as a potential useful biocatalyst in the effective dismantling of complex plant biomass architecture. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
We address the important step of determining an effective subset of heuristics in selection hyper heuristics. Little attention has been devoted to this in the literature, and the decision is left at the discretion of the investigator. The performance of a hyper-heuristic depends on the quality and size of the heuristic pool. Using more than one heuristic is generally advantageous, however, an unnecessary large pool can decrease the performance of adaptive approaches. Our goal is to bring methodological rigour to this step. The proposed methodology uses non-parametric statistics and fitness landscape measurements from an available set of heuristics and benchmark instances, in order to produce a compact subset of effective heuristics for the underlying problem. We also propose a new iterated local search hyper-heuristic using multi-armed bandits coupled with a change detection mechanism. The methodology is tested on two real-world optimization problems: course timetabling and vehicle routing. The proposed hyper-heuristic with a compact heuristic pool, outperforms state-of-the-art hyper-heuristics and competes with problem specific methods in course timetabling, even producing new best-known solutions in 5 out of the 24 studied instances. (C) 2017 Elsevier B.V. All rights reserved.
Industrial emissions must be dramatically reduced to avoid the potentially dangerous effects of climate change. In order to contribute to the necessary cuts, this article focuses on the energy and material efficiency of sheet metal forming. The processes considered include traditional methods, such as drawing and stretch forming, and newer technologies developed in recent decades such as hydroforming (fluid cell forming), superplastic forming, and incremental sheet forming. In this analysis, we conduct case studies on forming processes at leading US car and aerospace manufacturers. The case studies include electrical power measurements on the forming machines and also consider the impacts of making the dies, sheet metal, and lubricant. Cradle-to-gate energy demands and environmental impacts are modeled in SimaPro using data based on ecoinvent 3.1 database values. The results show that idling consumes significant electricity; however, other than for incremental forming, the impacts of press electricity are small compared to the impacts of making the sheet metal. The case studies inform generalized models for each process that allow per part impacts to be estimated based only on final part material, size (surface area, thickness, and depth), and the number of parts produced over the die-set lifespan. The models are used to investigate the potential to reduce cradle-to-gate energy requirements by using incremental forming instead of drawing to form parts. It is found that there are significant potential savings for small production runs, consistent with part development/prototyping. However, these savings vary depending on the part size and the relative buy-to-fly ratio (material yield) of the two processes. The results of this study highlight that for small production numbers over the die lifespan the impacts of die-making are important. However, as production numbers increase above one hundred parts per die set, the impacts of making the sheet metal become dominant. It is therefore concluded that researchers interested in reducing the environmental impacts of sheet metal forming concentrate on innovations that would reduce sheet metal blanking and post-forming trimming losses. (C) 2017 Elsevier B.V. All rights reserved.
The new Reference Resistance Design (RRD) method, recently developed by Rotter [1], for the manual dimensioning of metal shell structures effectively permits an analyst working with only a calculator or spreadsheet to take full advantage of the realism and accuracy of an advanced nonlinear finite element (FE) calculation. The method achieves this by reformulating the outcomes of a vast programme of parametric FE calculations in terms of six algebraic parameters and two resistances, each representing a physical aspect of the shell's behaviour. The formidable challenge now is to establish these parameters and resistances for the most important shell geometries and load cases. The systems that have received by far the most research attention for RRD are that of a cylindrical shell under uniform axial compression and uniform bending. Their partial algebraic characterisations required thousands of finite element calculations to be performed across a four-dimensional parameter hyperspace (i.e. length, radius to thickness ratio, imperfection amplitude, linear strain hardening modulus). Handling so many nonlinear finite element models is time-consuming and the quantities of data generated can be overwhelming. This paper illustrates a computational strategy to deal with both issues that may help researchers establish sets of RRD parameters for other important shell systems with greater confidence and accuracy. The methodology involves full automation of model generation, submission, termination and processing with object-oriented scripting, illustrated using code and pseudocode fragments. (C) 2017 The Authors. Published by Elsevier Ltd.
Ideas are commonly described using metaphors; a bright idea appears like a "light bulb'' or the "seed'' of an idea takes root. However, little is known about how these metaphors may shape beliefs about ideas or the role of effort versus genius in their creation, an important omission given the known motivational consequences of such beliefs. We explore whether the light bulb metaphor, although widespread and intuitively appealing, may foster the belief that innovative ideas are exceptional occurrences that appear suddenly and effortlessly-inferences that may be particularly compatible with gendered stereotypes of genius as male. Across three experiments, we find evidence that these metaphors influence judgments of idea quality and perceptions of an inventor's genius. Moreover, these effects varied by the inventor's gender and reflected prevailing gender stereotypes: Whereas the seed (vs. light bulb) metaphor increased the perceived genius of female inventors, the opposite pattern emerged for male inventors.
Background: The optimisation of trypanosomosis control programs warrants a good knowledge of the main vector of animal and human trypanosomes in sub-Saharan Africa, the tsetse fly. An important aspect of the tsetse fly population is its trypanosome infection prevalence, as it determines the intensity of the transmission of the parasite by the vector. We therefore conducted a systematic review of published studies documenting trypanosome infection prevalence from field surveys or from laboratory experiments under controlled conditions. Publications were screened in the Web of Science, PubMed and Google Scholar databases. Using the four-stage (identification, screening, eligibility and inclusion) process in the PRISMA statement the initial screened total of 605 studies were reduced to 72 studies. The microscopic examination of dissected flies (dissection method) remains the most used method to detect trypanosomes and thus constituted the main focus of this analysis. Meta-regression was performed to identify factors responsible for high trypanosome prevalence in the vectors and a random effects meta-analysis was used to report the sensitivity of molecular and serological tests using the dissection method as gold standard. Results: The overall pooled prevalence was 10.3% (95% confidence interval [CI] = 8.1%, 12.4%) and 31.0% (95% CI = 20. 0%, 42.0%) for the field survey and laboratory experiment data respectively. The country and the year of publication were found to be significantly factors associated with the prevalence of trypanosome infection in tsetse flies. The alternative diagnostic tools applied to dissection positive samples were characterised by low sensitivity, and no information on the specificity was available at all. Conclusion: Both temporal and spatial variation in trypanosome infection prevalence of field collected tsetse flies exists, but further investigation on real risk factors is needed how this variation can be explained. Improving the sensitivity and determining the specificity of these alternative diagnostic tools should be a priority and will allow to estimate the prevalence of trypanosome infection in tsetse flies in high-throughput.
Background: The formation of distant metastases constitutes a complex process with a variety of different genes and pathways involved. To improve patient survival, it is necessary to understand the underlying mechanisms of metastasis to allow for targeted intervention. Methods: This review provides an overview of the general concepts of metastasis, focusing on the most important genes and pathways involved and on interventional strategies. Results: Cancer cells undergo different steps to form metastasis: most prominently, local invasion, intravasation, survival in the circulation, arrest at a distant organ site and extravasation, micrometastasis formation, and metastatic colonization. In order to pass these steps, different molecular pathways are of major importance: EGF/RAS/RAF/MEK/ERK, PI3K/Akt/mTOR, HGF/Met, Wnt/beta-catenin, and VEGF signaling. The HGF/Met regulator MACC1 and the Wnt signaling target S100A4 have been shown to play a major role in the metastatic process. Each gene and pathway provides an opportunity for therapeutic intervention. Conclusion: Since metastasis represents a highly limiting factor in cancer therapy causing 90% of cancer deaths, it is imperative to reveal the underlying mechanisms. This is fundamental for uncovering prognostic markers and new targeted therapy options. (C) 2017 S. Karger GmbH, Freiburg
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC-27 and MKN-45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma-associated oncogene (Gli)-1, Gli-2 and Gli-3 were examined using western blot and reverse transcriptionquan-titative polymerase chain reaction analyses. RNA interference was used to detect whether the effects of metformin treatment on the Shh signaling pathway were dependent on AMP-activated protein kinase (AMPK). The results revealed that the protein and mRNA levels of Shh and Gli-1 were decreased by metformin treatment in the two cell lines in a dose-and time-dependent manner. Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli-2 and Gli-3. The small interfering RNA-induced depletion of AMPK reversed the suppressive effect of metformin on recombinant human Shh-induced expression of Gli-1 in HGC-27 gastric cancer cells. Therefore, metformin inhibited the Shh signaling pathway in the gastric cancer cell lines and the inhibitory effect of metformin on the Shh pathway was AMPK-dependent.
Methamphetamine (MA) produces long-lasting deficits in dopaminergic neurons in the long-term use via several neurotoxic mechanisms. The effects of MA on mitochondrial biogenesis is less studied currently. So, we evaluated the effects of repeated escalating MA regimen on transcriptional factors involved in mitochondrial biogenesis and glial-derived neurotrophic factor (GDNF) expression in substantia nigra (SN) and striatum of rat. In male Wistar rats, increasing doses of MA (1-14mg/kg) were administrated twice a day for 14 days. At the 1st, 14th, 28th, and 60th days after MA discontinuation, we measured the PGC1, TFAM and NRF1 mRNA levels, indicator of mitochondrial biogenesis, and GDNF expression in SN and striatum. Furthermore, we evaluated the glial fibrillary acidic protein (GFAP) and Iba1 mRNA levels, and the levels of tyrosine hydroxylase (TH) and -synuclein (-syn) using immunohistochemistry and real-time polymerase chain reaction (PCR). We detected increments in PGC1 and TFAM mRNA levels in SN, but not striatum, and elevations in GDNF levels in SN immediately after MA discontinuation. We also observed increases in GFAP and Iba1 mRNA levels in SN on day 1 and increases in Iba1 mRNA on days 1 and 14 in striatum. Data analysis revealed that the number of TH+ cells in the SN did not reduce in any time points, though TH mRNA levels was increased on day 1 after MA discontinuation in SN. These data show that repeated escalating MA induces several compensatory mechanisms, such as mitochondrial biogenesis and elevation in GDNF in SN. These mechanisms can reverse MA-induced neuroinflammation and prevent TH-immunoreactivity reduction in nigrostriatal pathway. J. Cell. Biochem. 118: 1369-1378, 2017. (C) 2016 Wiley Periodicals, Inc.
Using 17 chemical elements as a proxy for stellar DNA, we present a full phylogenetic study of stars in the solar neighbourhood. This entails applying a clustering technique that is widely used in molecular biology to construct an evolutionary tree from which three branches emerge. These are interpreted as stellar populations that separate in age and kinematics and can be thus attributed to the thin disc, the thick disc and an intermediate population of probable distinct origin. We further find six lone stars of intermediate age that could not be assigned to any population with enough statistical significance. Combining the ages of the stars with their position on the tree, we are able to quantify the mean rate of chemical enrichment of each of the populations, and thus show in a purely empirical way that the star formation rate in the thick disc is much higher than that in the thin disc. We are also able to estimate the relative contribution of dynamical processes such as radial migration and disc heating to the distribution of chemical elements in the solar neighbourhood. Our method offers an alternative approach to chemical tagging methods with the advantage of visualizing the behaviour of chemical elements in evolutionary trees. This offers a new way to search for ' common ancestors' that can reveal the origin of solar neighbourhood stars.
Adipose and endothelial dysfunction is associated with cardiovascular disease. Perivascular adipose tissue (PVAT) directly surrounds vessels and influences vessel function via a paracrine effect, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) modulates the metabolic pathway, thus, the present study hypothesized that activation of AMPK in PVAT may regulate endothelial function in pathological settings. The present study investigated the effect of methotrexate (MTX) on adipocytokine expression in PVAT with an emphasis on the regulation of endothelial function. The effects of MTX and the mechanisms involved were investigated using a relaxation assay and western blot analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels. ELISA assay was used to quantify the level of TNF-alpha and IL-6. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipocytokine expression in PVAT. MTX treatment inhibited nuclear factor-kappa B p65 phosphorylation and downregulated expression of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, whereas adiponectin expression increased. MTX increased AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK via small interfering RNA diminished its modulatory effect, indicating that MTX inhibits inflammation in an AMPK-dependent manner. The present study prepared conditioned medium from PA-stimulated PVAT to induce endothelial dysfunction and observed that pre-treatment of PVAT with MTX effectively restored the loss of acetylcholine-induced vasodilation and increased endothelial nitric oxide synthase phosphorylation in the rat aorta. The results of the present study demonstrated that MTX ameliorated inflammation-associated adipocytokine dysregulation and thus prevented endothelial dysfunction. These data provide further pharmacological evidence regarding the beneficial effects of MTX in cardiovascular diseases.
Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.
The purpose of this review is to introduce Metschnikowia to the yeast researcher community and to convince readers that the genus is a worthwhile object of study in developmental biology, genetics, ecology and biotechnology. Metschnikowia sits at the foundation of modern immunology, having been instrumental in the discovery of animal phagocytosis. Some 81 species form a monophyletic group within the Metschnikowiaceae, which also include the smaller genus Clavispora and a few clades of Candida species. The family stands out by the habit of forming, by meiosis, only two ascospores, which in Metschnikowia are needle shaped. In some cases, the spores can reach enormous proportions, exceeding 200 mu m in length; in others, ascus formation is preceded by the development of chlamydospores. The adaptive value of such features remains to be elucidated. Extensive genetic studies are lacking, but attempts to apply methods developed for model species have been successful. Some species are found at the plant-insect interface whereas others are pathogens of aquatic animals and have served as model organisms in the exploration of host-parasite theory. Some species are globally distributed and others exhibit extreme endemism. Many species are remarkably easy to recover by sampling their known habitats. M. pulcherrima and close relatives may play an important role in wine quality and produce pulcherrimin, an iron-dipeptide complex that can interfere with the growth of other microorganisms. Some symbiotic species incapable of growth in culture media have been assigned to the genus, but their kinship with the group remains to be demonstrated. Copyright (c) 2016 John Wiley & Sons, Ltd.
Mexico has entered in an important dynamic of structural changes in the energy area, proof of this, it is the Energy Reform 2013 and the Energy Transition Law published the last December 24th, 2015, thus it is important to carry out studies of the impacts of future politics in the consumption of the population, so this study estimate an energy demand system using microdata collected from 97,817 households in a National Households Income and Expenditure Survey (ENIGH acronyms in Spanish, Encuesta Nacional de Ingresos y Gastos de los Hogares) in the 20-years period from 1994 to 2014. The magnitudes of all the fuels are smaller than one indicating that electricity, LPG, gasoline and public transport are normal goods, while LPG is the most inelastic energy source. The geographic factor shows that households in the north of Mexico tend to consume more gasoline, whereas in the south of the country, the lowest share of LPG expenditure is reported. The rigorous evaluation of energy demanded in households will help policy makers to put forward more efficient reforms.
Neoantigen is a patient-specific tumor antigen resulted from mutations during oncogenesis. Emerging data suggested that immune responsiveness against neoantigens correlated with the success of clinical tumor immunotherapies. Nowadays, the majority of studies on neoantigens have focused on MHC class I restricted antigens recognized by CD8+ T cells. With improved understanding of the underlying principles of tumor biology and immunology, increasing emphasis has been put on CD4+ T cells and MHC class II restricted antigens. MHC class II restricted neoantigen has the potential to be a promising target of tumor immunotherapy, although the limited comprehension and technical difficulties need to be overcome before being applied into clinical practice. This review discussed the immunologic mechanism, screening technique, clinical application, limitations and prospectives of MHC class II restricted neoantigens in tumor immunotherapy. CD (C) 2017 Elsevier B.V. All rights reserved.
In euryhaline teleosts, osmoregulation is a fundamental and dynamic process that is essential for the maintenance of ion and water balance, especially when fish migrate between fresh water (FW) and sea water (SW) environments. The European eel has proved to be an excellent model species to study the molecular and physiological adaptations associated with this osmoregulatory plasticity. The life cycle of the European eel includes two migratory periods, the second being the migration of FW eels back to the Sargasso Sea for reproduction. Various anatomical and physiological changes allow the successful transition to SW. The aim of this study was to use a microarray approach to screen the osmoregulatory tissues of the eel for changes in gene expression following acclimation to SW. Tissues were sampled from fish at selected intervals over a 5-mo period following FW/SW transfer, and RNA was isolated. Suppressive subtractive hybridization was used for enrichment of differentially expressed genes. Microarrays comprising 6,144 cDNAs from brain, gill, intestine, and kidney libraries were hybridized with appropriate targets and analyzed; 229 differentially expressed clones with unique sequences were identified. These clones represented the sequences for 95 known genes, with the remaining sequences (59%) being unknown. The results of the microarray analysis were validated by quantification of 28 differentially expressed genes by Northern blotting. A number of the differentially expressed genes were already known to be involved in osmoregulation, but the functional roles of many others, not normally associated with ion or water transport, remain to be characterized.
Gene expression profiling of suprachiasmatic nucleus, ventrolateral preoptic area and the lateral hypothalamus was used to identify genes regulated diurnally in the hypothalamus of Mus musculus. The putative transcription regulator, cysteine and histidine-rich domain-containing, zinc binding protein 1, which had not been previously described in brain, was found to cycle diurnally in hypothalamus and forebrain with peak levels of mRNA expression during the dark phase. mRNA for the brain-type fatty acid binding protein 7 was found to change rhythmically in hypothalamic and extra-hypothalamic brain regions reaching peak levels early in the light phase suggesting that lipid metabolism is under circadian regulation in astrocytes. Rhythmically expressed genes in suprachiasmatic nucleus identified here were compared with previous reports in a meta-analysis. Genes held in common included fabp7, and the period gene, Per2. Also identified were genes implicated in guanosine-mediated signaling pathways that included dexamethasone-induced ras-related protein one (dexras1), regulator of G-protein signaling (rgs) 16, and ras-like family member 11b. Northern blotting confirmed diurnal changes in mRNA expression in the hypothalamus for these genes. Ras-like family member 11b was examined in more detail using in situ hybridization and antiphase diurnal changes in expression in suprachiasmatic nucleus and arcuate nucleus were identified implicating the gene in circadian-related, guanosine-mediated signaling. The transcription transactivator protein, CBP/p300-lnteracting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain, which had not been previously identified in brain, was enriched in suprachiasmatic nucleus and discrete regions of the hypothalamus and forebrain. The potential regulatory role of CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain in the transcription of genes like TGF-alpha implicates the protein in diurnal activity rhythms. These results demonstrate the ability of gene expression profiling to identify potential candidates important in circadian or homeostatic processes. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.
In the present study, microbial cellulose (MC) as a carbohydrate polymer was made conductive by oxidative polymerization with aniline. Sulfate-reducing bacteria (SRB) were immobilized on the surface of the conductive biopolymer, and this was used as a biocathode in a bioreduction process to reduce Cr (VI) as a model of heavy metals. The results of Fourier transform infrared analysis confirmed that the polyaniline was distributed on the cellulose surface. The maximum tensile stress of the conductive biopolymer was obtained 23 MPa using calculating Young's modulus. A current density of 60 mA/m(2) was determined as optimal, and an increase in pH from 5 to 7 significantly reduced the required time for reduction of Cr (VI). The system reached >99% removal of Cr (VI) within 1.5 h at pH 7. Kinetic experiment studies showed a high constant rate (mean K-obs 0.78, R-2 0.95). The results showed that the conductive MC can be used as an appropriate bioelectrode to reduce Cr (VI) in bioelectrochemical processes. It is expected that experimental results could be used as a reference for the utilization of MC in bioelectrochemical systems. (C) 2017 Published by Elsevier Ltd.
Metagenomics is a robust, interdisciplinary approach for studying microbial community composition, function, and dynamics. It typically involves a core of molecular biology, microbiology, ecology, statistics, and computational biology. Exciting outcomes anticipated from these studies include unraveling of complex interactions that characterize the ecological milieu of microbial communities. Diverse habitats from which metagenomes have been reported include human guts, caterpillar guts, thermal vents in oceans, ore deposits, polar caps, and even soils that adhere to plant roots. Knowledge generated from metagenomic projects has tremendous potential to benefit human health, agriculture, and ecosystem functions. This article provides a brief history of technical advances in metagenomics, including DNA sequencing methods, and some case studies. A specific example is provided of microbial metagenomes found at the roots of native grass species (family Poaceae) that can grow on degraded lands undergoing revegetation.
Microbial electrochemical systems (MESs) are an attracting technology for the disposal of wastewater treatment and simultaneous energy production. In MESs, at the anode microorganisms through the catalytic activity generates electrons that can be converted into electricity or other valuable chemical compounds. Microorganisms those having ability to donate and accept electrons to and from anode and cathode electrodes, respectively are recognized as 'exoelectrogens'. In the MESs, it renders an important function for its performance. In the present mini-review, we have discussed the role of microbiome including pure culture, enriched culture and mixed culture in different BESs application. The effects of operational and biological factors on microbiome development have been discussed. Further discussion about the molecular techniques for the evaluation of microbial community analysis is addressed. In addition different electrochemical techniques for extracellular electron transfer (EET) mechanism of electroactive biofilms have been discussed. This review highlights the importance of microbiome in the development of MESs, effective operational factors for exo-electrogens activities as well their key challenges and future technological aspects are also briefly discussed. (C) 2017 Elsevier Ltd. All rights reserved.
A low-cost mini tubular microbial fuel cell (MFC) was developed for treating groundwater that contained benzene in monitoring wells. Experimental results indicate that increasing the length and density, and reducing the size of the char particles in the anode effectively reduced the internal resistance. Additionally, a thinner polyvinyl alcohol (PVA) hydrogel separator and PVA with a higher molecular weight improved electricity generation. The optimal parameters for the MFC were an anode density of 1.22 g cm(-3), a coke of 150 mu m: an anode length of 6 cm, a PVA of 105,600 g mol(-1), and a separator thickness of 1 cm. Results of continuous-flow experiments reveal that the increasing the sets of MFCs and connecting them in parallel markedly improved the degradation of benzene. More than 95% of benzene was removed and electricity of 38 mW m(-2) was generated. The MFC ran continuously up to 120 days without maintenance. (C) 2017 Elsevier Ltd. All rights reserved.
Anolyte acidification is a drawback restricting the electricity generation performance of the buffer-free microbial fuel cells (MFC). In this paper, a small amount of alkali-treated anion exchange resin (AER) was placed in front of the anode in the KCl mediated single-chamber MFC to slowly release hydroxyl ions (OH-) and neutralize the H+ ions that are generated by the anodic reaction in two running cycles. This short-term alkaline intervention to the KCl anolyte has promoted the proliferation of electroactive Geobacter sp. and enhanced the self-buffering capacity of the KCl-AER-MFC. The pH of the KCl anolyte in the KCl-AER-MFC increased and became more Stable in each running cycle compared with that of the KCl-MFC after the short-term alkaline intervention. The maximum power density (P-max) of the KCl-AER-MFC increased from 307.5 mW.m(-2) to 542.8 mW.m(-2), slightly lower than that of the PBS-MFC (640.7 mW.m(-2)). The coulombic efficiency (CE) of the KCl-AER-MFC increased from 54.1% to 61.2% which is already very close to that of the PBS-MFC (61.9%). The results in this paper indicate that short-term alkaline intervention to the anolyte is an effective strategy to further promote the performance of buffer-free MFCs. (C) 2017 Elsevier B.V. All rights reserved.
Biocathode microbial fuel cells (MFCs) have been shown to be useful in reductively changing Cr(VI) into Cr(III)-related precipitates on the surface of electrochemically active bacteria (EAB), but the occurrence of intracellular Cr(VI) reduction in the EAB are still unclear. Based on the four EAB isolated from Cr(VI)-reduced biocathode MFCs and tentatively assigned to Stenotrophomonas sp. YS1, Stenotrophomonas maltophilia YS2, Serratia marcescens YS3 and Achromobacterxylosoxidans YS8, a naphthalimide-rhodamine based Cr(III) fluorescent probe was used for the first time to sense the intracellular Cr(III) ions, inevitably and transiently formed from Cr(VI) reduction in these EAB. More Cr(VI) was reduced in the MFC biocathodes, resulting in intracellular accumulation of total chromium of 45.1 +/- 1.3-60.5 +/- 1.4% with a composite of Cr(III) ions (23.7 +/- 2.6-27.3 +/- 1.1%) and other forms of chromium-complex (18.7 +/- 2.5-32.2 +/- 0.8%), In the open circuit controls, intracellular total chromium only ranged 10.2 +/- 1.5-11.7 +/- 0.8% (Cr(III) ions: 8.2 +/- 0.6-9.5 +/- 0.9%; other forms: 0.2 +/- 0.6-0.3 +/- 0.9%). This study illustrates that cathode directed more intracellular Cr(VI) reduction in the EAB and gives an alternative approach for developing imaging and functionally sensing Cr(III) ions in the MFC biocathodes. (C) 2016 Elsevier B.V. All rights reserved.
A novel microbial fuel cell (MFC) was developed to enhance simultaneous nitrification and denitrification (SND) by employing electrons from the anode. The cathode chamber of the reactor consisted of a membrane aerated biofilm reactor (MABR) which was made of an electroconductivity aerated membrane. The maximum power density of 4.20 +/- 0.12 W m(-3) was obtained at a current density of 4.10 +/- 0.11 A m(-2) (external resistance = 10 Omega). Compared with an open-circuit system, the removal rates of NI4+-N and TN were improved by 9.48 +/- 0.33% and 19.80 +/- 0.84%, respectively, which could be ascribed to the electrochemical denitrification. The anode (chemical oxygen demand, COD) and cathode (NO3-) chambers reached the maximum coulombic efficiencies (CEs) of 40.67 +/- 1.05% and 42.84 +/- 1.14%, respectively. It suggested that the electroconductivity MABR has some advantages in controlling aeration intensity, thus improving SND and CEs. Overall, EAM-MFC could successfully generate electricity from wastewater whilst showing high capacity for removing nitrogen at a low COD/N ratio of 2.8 +/- 0.07 g COD g(-1) N. (C) 2016 Elsevier B.V. All rights reserved.
Microbial fuel cells (MFC) have recently received increasing attention due to their promising potential in sustainable wastewater treatment and contaminant removal. In general, contaminants can be removed either as an electron donor viamicrobial catalyzed oxidization at the anode or removed at the cathode as electron acceptors through reduction. Some contaminants can also function as electron mediators at the anode or cathode. While previous studies have done a thorough assessment of electron donors, cathodic electron acceptors and mediators have not been as well described. Oxygen is widely used as an electron acceptor due to its high oxidation potential and ready availability. Recent studies, however, have begun to assess the use of different electron acceptors because of the (1) diversity of redox potential, (2) needs of alternative and more efficient cathode reaction, and (3) expanding of MFC based technologies in different areas. The aim of this review was to evaluate the performance and applicability of various electron acceptors and mediators used in MFCs. This review also evaluated the corresponding performance, advantages and disadvantages, and future potential applications of select electron acceptors (e.g., nitrate, iron, copper, perchlorate) and mediators.
A bio-electrochemical strategy was developed for constructing a simple and sensitive levofloxacin (LEV) sensor based on a single chamber microbial fuel cell (SC-MFC) using FePO4 nanoparticles (NPs) as the cathode catalyst instead of traditional Pt/C. In this assembled sensor device, FePO4 NPs dramatically promoted the electrooxidation of oxygen on the cathode, which helps to accelerate the voltage output from SC-MFC and can provide a powerful guarantee for LEV detection. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) were used to fully characterize the FePO4 NPs. Under the optimized COD condition (3 mM), the LEV with a concentration range of 0.1-1000 pg/L could be detected successfully, and exhibited the excellent linear interval in the concentration range of 0.1-100 pg/L. During this range of concentrations of LEV, a temporary effect on the anode of exoelectrogenic bacterial in less than 10 min could occur, and then came back to the normal. It exhibited a long-term stability, maintaining the stable electricity production for 14 months of continuous running. Besides, the detection mechanism was investigated by quantum chemical calculation using density functional theory (DFT).
Using chemical vapor deposition methods to prepare carbon nanotubes growing in situ on a carbon felt, graphene and polyaniline were applied to the carbon felt for modifying carbon nanotubes. Microbial fuel cell was constructed with graphene/polyaniline-modified carbon nanotubes as anode, graphite as cathode, and glucose solution as substrate. The effects of electrodes, substrate concentration, and temperature on the properties of microbial fuel cell have been studied. At 38 A degrees C using glucose solution of 1450 mg L-1 and external resistance of 2500 Omega, the optimum output voltage of 687 mV and removal rate of 83% for chemical oxygen demand were obtained in the microbial fuel cell. The prepared nanomaterials are stable and reusable.
With the increasing concern about the serious global energy crisis and high energy consumption during high content solid wastes (HCSWs) treatment, microbial fuel cell (MFC) has been recognized as a promising resource utilization approach for HCSW stabilization with simultaneous electrical energy recovery. In contrast to the conventional HCSW stabilization processes, MFC has its unique advantages such as direct bio-energy conversion in a single step and mild reaction conditions (viz., ambient temperature, normal pressure, and neutral pH). This review mainly introduces some important aspects of electricity generation from HCSW and its stabilization in MFC, focusing on: (1) MFCs with different fundamentals and configurations designed and constructed to produce electricity from HCSW; (2) performance of wastes degradation and electricity generation; (3) prospect and deficiency posed by MFCs with HCSW as substrates. To date, the major drawback of MFCs fueled by HCSW is the lower power output than those using simple substrates. HCSW hydrolysis and decomposition would be a major tool to improve the performance of MFCs. The optimization of parameters is needed to push the progress of MFCs with HCSW as fuel. (C) Higher Education Press and Springer-Verlag Berlin Heidelberg 2017
Excess consumption of energy by humans is compounded by environmental pollution, the greenhouse effect and climate change impacts. Current developments in the use of algae for bioenergy production offer several advantages. Algal biomass is hence considered a new bio-material which holds the promise to fulfil the rising demand for energy. Microalgae are used in effluents treatment, bioenergy production, high value added products synthesis and CO2 capture. This review summarizes the potential applications of algae in bioelectrochemically mediated oxidation reactions in fully biotic microbial fuel cells for power generation and removal of unwanted nutrients. In addition, this review highlights the recent developments directed towards developing different types of microalgae MFCs. The different process factors affecting the performance of microalgae MFC system and some technological bottlenecks are also addressed. (C) 2017 Elsevier Ltd. All rights reserved.
Microbial fuel cells (MFCs) can treat organic compounds from domestic wastewater without aeration, but an additional procedure is required to remove nitrogen. This study developed a flat-panel air-cathode MFC (FA-MFC) that was comprised of five MFC units connected in series and operated to remove organic and nitrogen compounds from domestic wastewater with a short hydraulic retention time (HRT) of 2.5 h. During eight months of operation, the removal efficiencies of chemical oxygen demand (COD) and total nitrogen (TN) increased, reaching 85% and 94%, respectively, and the effluent COD and TN concentrations were 20.7 +/- 2.5 mg/L and 1.7 +/- 0.1 mg/L, respectively. The greatest removals of COD and TN were in the first and second unit (0.62 kg-N/m(3)/d of TN removal rate). The FA-MFC system allowed simultaneous removals of COD and TN from domestic wastewater, although it led to minimal power output (6.3 W/m(3) in the first unit). Because any abiotic ammonia loss was not found under the supplied potential of similar to 1.1 V at a short HRT of 30 min, the biological nitrogen removal was thought as a dominant mechanism for TN removal in the FA-MFCs. Microbial community analysis revealed that, near the cathode, Nitrosomonas-like strains contributed to nitrification and Nitratireductor-like strains led to denitrification. Acidovorax-like strains, known for their metabolic diversity, were ubiquitous and appeared to contribute to organics and nitrogen removal in anode and cathode biofilms. This study provides proof of concept that the FA-MFC system has a promise for energy sustainable wastewater treatment. (C) 2017 Elsevier B.V. All rights reserved.
In the present study, two novel dominant genera i.e., Advenella kashmirensis and Desulfovibrio aminophilus in consortium, as confirmed by IlluminaMiSeq has been used in the anode side of a microbial fuel cell reactor to find out the influence of cathode environment on cell performance. A model terminal electron acceptor (TEA), KMnO4 at different pHs has been used in the cathode side. An oxidation peak obtained at -0.478 vs Ag/AgCI (-0.281 V vs SHE) corresponding to S-0/H2S (-0.280V vs SHE) in cyclic voltammogram confirms the complete mineralization of sulphate to biogenic elemental sulphur in accordance with the microbial community. Higher cathodic pH 10 has a detrimental effect on the cell performance as the power density is reduced to half to that for aqKMnO(4) (pH = 6.86) catholyte. Solution resistance is found to be low for aqKMnO(4)(60 ohm) and high i.e. 124.5 ohm for aqKMnO(4) with pH = 10, which corroborates to highest power density obtained for aqKMnO(4). Buffering of the catholyte provided stability to the system with lowest internal resistance of 40 ohm and comparable performance. The highest current density (25 A/m(3)) and power density (7.8 W/m(3)) is obtained with aqueous KMnO4 at pH 6.86. The developed consortium can be successfully utilized in microbial fuel cells for simultaneous electricity generation and wastewater treatment. (C) 2017 Elsevier B.V. All rights reserved.
In order to optimize energy production in MFCs, a better understanding of anodic communities is essential. Our objective was to determine the taxonomic structure of the bacterial communities present at the surface of the anode during the formation and development of electro-active biofihns in MFCs inoculated with fresh primary clarifier overflow. Quantitative microbial community dynamics were evaluated as a function of time and electrical performance using 16S rRNA gene-based phylogenetic microarrays and flow cytometry. Results show that the bacterial community stabilized partially but not completely when voltage output was stable. Geobacter appeared to be the predominant genus, whose growth was associated with voltage, while some other genus still developed or declined after the voltage stabilization. Flow cytometry revealed that some genus showing a decreasing proportional fluorescence intensity over time were still actively respiring bacteria, and thus, active albeit minor members of the biofilm. Finally, this study shows that anodic biofilm selection and maturation is still occurring after more than 20 days of operation and over ten days after voltage is stabilized.
Twelve single chambered, air-cathode Tubular Microbial Fuel Cells (TMFCs) have been filled up with fruit and vegetable residues. The anodes were realized by means of a carbon fiber brush, while the cathodes were realized through a graphite-based porous ceramic disk with Nafion membranes (117 Dupont). The performances in terms of polarization curves and power production were assessed according to different operating conditions: percentage of solid substrate water dilution, adoption of freshwater and a 35 mg/L NaCI water solution and, finally, the effect of an initial potentiostatic growth. All TMFCs operated at low pH (pH = 3.0 +/- 0.5), as no pH amendment was carried out. Despite the harsh environmental conditions, our TMFCs showed a Power Density (PD) ranging from 20 to 55 mW/m(2) kg(waste) and a maximum CD of 20 mA/m(2) kg(waste), referred to the cathodic surface. COD removal after a 28-day period was about 45%. The remarkably low pH values as well as the fouling of Nafion membrane very likely limited TMFC performances. However, a scale-up estimation of our reactors provides interesting values in terms of power production, compared to actual anaerobic digestion plants. These results encourage further studies to characterize the graphite-based porous ceramic cathodes and to optimize the global TMFC performances, as they may provide a valid and sustainable alternative to anaerobic digestion technologies. (C) 2016 Elsevier Ltd. All rights reserved.
Microbial fuel cells (MFCs) are novel bio-electrochemical device for spontaneous or single step conversion of biomass into electricity, based on the use of metabolic activity of bacteria. The design and use of MFCs has attracted considerable interests because of the potential new opportunities they offer for sustainable production of energy from biodegradable and reused waste materials. However, the associated slow microbial kinetics and costly construction materials has limited a much wider commercial use of the technology. In the past ten years, there has been significant new developments in MFCs which has resulted in several-fold increase in achievable power density. Yet, there is still considerable possibility for further improvement in performance and development of new cost effective materials. This paper comprehensively reviews recent advances in the construction and utilization of novel anodes for MFCs. In particular, it highlights some of the critical roles and functions of anodes in MFCs, strategies available for improving surface areas of anodes, dominant performance of stainless-steel based anode materials, and the emerging benefits of inclusion of nanomaterials. The review also demonstrates that some of the materials are very promising for large scale MFC applications and are likely to replace conventional anodes for the development of next generation MFC systems. The hurdles to the development of commercial MFC technology are also discussed. Furthermore, the future directions in the design and selection of materials for construction and utilization of MFC anodes are highlighted.
Among many energy harvesting techniques with great potential, microbial fuel cell (MFC) technology is arguably the most underdeveloped. Even so, excitement is building, as microorganisms can harvest electrical power from any biodegradable organic source (e.g. wastewater) that is readily available in resource-limited settings. Nevertheless, the requirement for endless introduction of organic matter imposes a limiting factor to this technology, demanding an active feeding system and additional power. Here, we demonstrated self-sustaining bioelectricity generation from a microliter-scale microbial fuel cell (MFC) by using the syntrophic interaction between heterotrophic exoelectrogenic bacteria and phototrophs. The MFC continuously generated light-responsive electricity from the heterotrophic bacterial metabolic respiration with the organic substrates produced by photosynthetic bacteria. Without additional organic fuel, the mixed culture in a 90-mu L-chamber MFC generated self-sustained current for more than 13 days, while the heterotrophic culture produced current that decreased dramatically within a few hours. The current from the mixed culture was about 70 times greater than that of the device with only photosynthetic bacteria. The miniaturization provided a short start-up time, a well-controlled environment, and small internal resistance. Those advantages will become the general design platform for micropower generation. (C) 2017 Elsevier B.V. All rights reserved.
This study investigated the effect of carbon fibers as brush anode materials on the performance of microbial fuel cells (MFCs). Two types of carbon fibers with different electrical resistivity and functionality polyacrylonitrile (PAN) (rho: 28.0 mu Omega m) and pitch (rho: 2.05 mu Omega m) were investigated. X-ray photoelectron spectroscopy analysis showed that the PAN- and pitch-based carbon fibers presented almost the same surface elements and functional groups, and there was no significant difference in microbial growth on the brush anodes. Current interrupt and steady discharging methods demonstrated the pitch-based carbon brush anodes had lower ohmic resistance and generated higher power density. After nitric acid treatment, the power density generated by the PAN- and pitch-based anodes increased by 29.3% and 26.7%, achieving 816 and 895 mW m(-2), respectively. Using pitch-based carbon fiber brush as anode attained better performance than the widely used PAN-based carbon brush. The acid treated pitch-based carbon fibers provide a promising alternative to highly efficient anode materials for the extensive application of MFCs. (C) 2017 Elsevier B.V. All rights reserved.
A new facultative anaerobic exoelectrogenic strain LZ-1, belonging to Citrobacter freundii, has been isolated. This strain can produce current densities of 843.9 and 865.6 mu A cm(-2) using citrate or acetate as carbon source in a three-electrode configuration. The electricity generation performance was also analyzed in a dual-chamber MFC system, reaching a maximum power density of 1233 mW m(-2). In addition to acetate and citrate, other carbon sources such as pyruvate, formate, acetate, citrate and fumarate could also be utilized to produce current by strain LZ-1. Data supports the presence of electroacfive c-type cytochromes in C. freundii sp. when grown on ITO electrodes, by linking spectroscopy and electrochemistry in situ. Since facultative strains possess many desirable properties compared to anaerobic strains, strain LZ-1 represents a promising exoelectrogenic species in engineering of biological catalysts for microbial electrochemistry.
Produced water (PW) is the largest waste stream in the oil production process: it contains light polar and aliphatic hydrocarbons, production process compounds, dissolved gases, anions and cations. Disposal of PW is subjected to strict legislations. Oil producing countries are focused on finding effective and economic methods for its treatment. Some physical and chenlical methods have been used for treatment of PW and biological treatments have been proven to efficiently remove dissolved hydrocarbon compounds. Coupling of anaerobic biological treatment with electrochemical technology in microbial fuel cells (MFCs) can in principle lead to the production of clean water and electric energy. The suitability of MFCs for improving the treatment of PW was investigated in the present Work. For the first time, the simple design of single chamber MFCs fed with real PW (PW-MFCs) was studied, in different configurations: (i) with and without membrane; (ii) with and without Pt cathodic catalyst. The results demonstrate the effectiveness of the membraneless configuration without chemical catalyst at the cathode. Even though the electrical output of PW-MFCs was very low (3 mW m(-2)), it is currently the best reported performance. Furthermore, almost complete hydrocarbon degradation was achieved for each fed-cycle (96.6 +/- 1.94%). The Coulombic efficiency was limited by the difficulty to obtain strict anaerobic condition at the anode, since the biocathode of PW-MFCs remained more permeable to oxygen than in acetate-fed MFCs. The DNA sequencing of operating anodic biofilm detected electroactive Desulfobulbaceae mixed to aerobic biodegraders (Burkholderiales) likely through cycling sulfur compounds, which enriched from the PW initial pool in the hypersaline environment. Above all, the results pointed to the practical possibility of using a MFC to enhance and monitor the PW biodegradation process. In fact, the MFC electrical output indicated the occurrence of anaerobic degradation, while the electrochemical parameters of cathode (Tafel slope) resulted correlated to aerobic degradation, suggesting the possibility to design an on-line sensor of the biotechnological industrial treatments of PW. (C) 2016 Elsevier Ltd. All rights reserved.
Knowledge surrounding the trillions of microbes that inhabit the human gut has bloomed exponentially in recent years, and the emerging concept of a gut-brain axis represents a major shift in how we think about neurological health. A recent workshop at the University of British Columbia, Canada brought together multi-disciplinary leaders in the field of microbiomics and brain health and aimed to serve as a springboard for future combined endeavors in these areas. This article provides the motivation for, and overview of, the workshop, and the next steps in establishing a cross-disciplinary initiative on Brain Health and the Microbiome.
Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro-and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction: Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. Development: We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Conclusions: Multiple evidence points to the rote of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us. (C) 2015 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.
Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-theshelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.
Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken -actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system. Three different methods [fluorescence microscopy, flow cytometry and quantitative polymerase chain reaction (QPCR)] were employed to search for TG cells and gene products in blood and other tissues of non-TG rabbits. Venus positive peripheral blood mononuclear cells (PBMCs) were not detected in the blood of non-TG littermates or non-TG does by flow cytometry. Tissue samples (liver, kidney, skeletal and heart muscle) also proved to be Venus negative examined with fluorescence microscopy, while histology sections and PBMCs of TG rabbits showed robust Venus protein expression. In case of genomic DNA (gDNA) sourced from tissue samples of non-TG rabbits, CAGGS promoter-specific fragments could not be amplified by QPCR. Our data showed the lack of detectable cell transfer between TG and non-TG rabbits during gestation.
An ultimate goal for those engaged in research to develop implantable medical devices is to develop mechatronic implantable artificial organs such as artificial pancreas. Such devices would comprise at least a sensor module, an actuator module, and a controller module. For the development of optimal mechatronic implantable artificial organs, these modules should be self-powered and autonomously operated. In this study, we aimed to develop a microcontroller using the BioCapacitor principle. A direct electron transfer type glucose dehydrogenase was immobilized onto mesoporous carbon, and then deposited on the surface of a miniaturized Au electrode (7 mm(2)) to prepare a miniaturized enzyme anode. The enzyme fuel cell was connected with a 100 mu F capacitor and a power boost converter as a charge pump. The voltage of the enzyme fuel cell was increased in a stepwise manner by the charge pump from 330 mV to 3.1 V, and the generated electricity was charged into a 100 mu F capacitor. The charge pump circuit was connected to an ultra-low-power microcontroller. Thus prepared BioCapacitor based circuit was able to operate an ultra-low-power microcontroller continuously, by running a program for 17 h that turned on an LED every 60 s. Our success in operating a microcontroller using glucose as the sole energy source indicated the probability of realizing implantable self-powered autonomously operated artificial organs, such as artificial pancreas.
Cell capturing and separation is frequently involved in researches in immunology, diagnostics and pathology. In recent years, different new methods for cell capturing and separation based on microfluidic platform have been developed. With microfluidic chip, rapid and low cost detection can be implemented with small sample and reagent volumes. In this review, two methods of microfluidic cell separation, immune-capture and label-free separation, are introduced. Immuno-capture, a more traditional method, can separate cells with high specificity and provide highly purified target cells. Newly developed label-free method performs separation by utilizing the physical and biological features of target cells, and can keep cell's integrity and activity. Although there are a couple of issues to be resolved before microfluidic cell separation gets widespread commercial use, such as multi-system integration and industrial-scale manufacture, it has already attracted extraordinary research attention and has been in the path on rapid development. It is believed that cell capturing and separation methods based on microfluidic chip have broad application prospect in life science and biomedical field.
We created a novel laminar-flow based microbial fuel cell (MFC) array to be an integrable and scalable power sourcefor portable lab-on-a-chip (LOC) devices. The microfluidic MFC enabled the laminar flow of anolyte and catholyte streams in a microchannel without any physical membranes while the device harvested electricity by utilizing ion transfers through the laminar interface which acts as a virtual membrane. The array prototype incorporated four series-connected fuel cells and was operated with two common inlets for the continuous introduction of the anolyte and catholyte. In the anodic flow region, microorganisms oxidized organic media and completed respiration by transferring the electrons to the anodes. The protons generated by the anodic reactions passed through the liquid-liquid interfaces and traveled to the cathodic streams. The electrons then moved across the external resistors to the cathodes where they combined with the protons and reduced oxidant (i.e. catholyte). The array generated a maximum power output of 60.5,W/cm(2) using a 100 kg(2) load, which outperformed a single laminar flow MFC unit by a factor of approximately 4. The series or parallel application of this array structure, using microfluidic MFCs integrated into a single LOC device, can offer the potential for on-chip power generation. (C) 2016 Elsevier B.V. All rights reserved.
The integration of nucleic acids detection assays in microfluidic devices represents a highly promising approach for the development of convenient, cheap and efficient diagnostic tools for clinical, food safety and environmental monitoring applications. Such tools are expected to operate at the point-of-care and in resource-limited settings. The amplification of the target nucleic acid sequence represents a key step for the development of sensitive detection protocols. The integration in microfluidic devices of the most popular technology for nucleic acids amplifications, polymerase chain reaction (PCR), is significantly limited by the thermal cycling needed to obtain the target sequence amplification. This review provides an overview of recent advances in integration of isothermal amplification methods in microfluidic devices. Isothermal methods, that operate at constant temperature, have emerged as promising alternative to PCR and greatly simplify the implementation of amplification methods in point-of-care diagnostic devices and devices to be used in resource-limited settings. Possibilities offered by isothermal methods for digital droplet amplification are discussed.
This article presents a microfluidic approach for the integration of the process of aptamer selection via systematic evolution of ligands by exponential enrichment (SELEX). The approach employs bead-based biochemical reactions in which affinity-selected target-binding oligonucleotides are electrokinetically transferred for amplification, while the amplification product is transferred back for affinity selection via pressure-driven fluid flow. The hybrid approach simplifies the device design and operation procedures by reduced pressure-driven flow control requirements and avoids the potentially deleterious exposure of targets to electric fields prior to and during affinity selection. In addition, bead-based reactions are used to achieve the on-chip coupling of affinity selection and amplification of target-binding oligonucleotides, thereby realizing on-chip loop closure and integration of the entire SELEX process without requiring offline procedures. The microfluidic approach is thus capable of closed-loop, multiround aptamer enrichment as demonstrated by selection of DNA aptamers against the protein immunoglobulin E with high affinity (K-D = 12 nM) in a rapid manner (4 rounds in approximately 10 h).
Microglia exist under physiological conditions in a resting state but become activated after neuronal injury. Recent studies have highlighted the reciprocal role of neurons in controlling both the number and activity of microglia. In this study, microglia derived from newborn rat cortices were cultured and activated by interferon-gamma(IFN gamma) treatment, then exposed to recombinant Sema3A or conditioned medium derived from stressed embryonic cortical neurons. We found that activation of microglia by IFN gamma induced differential upregulation of the semaphorin receptors Plexin-A1 and Neuropilin-1. This result was confirmed by Northern blotting, reverse transcription-PCR, and Western blotting. Furthermore, recombinant Sema3A induced apoptosis of microglia when added to the in vitro culture, and a similar result was obtained on activated microglia when Sema3A was produced by stressed neurons. Using an in vivo model of microglia activation by striatal injection of lipopolysaccharide demonstrated a corresponding upregulation of Plexin-A1 and Neuropilin-1 in activated microglia and enhanced production of Sema3A by stressed adult neurons. These results suggest a novel semaphorin-mediated mechanism of neuroprotection whereby stressed neurons can protect themselves from further damage by activated microglia.
Hybrid microgrids are expected to play an important role in the expansion of access to electricity in developing countries. While most of these systems are operated with dispatch strategies which do not make use of predictions about the load or about the availability of renewable energy resources, forecast-based strategies have recently gained attention as an alternative to bring down operation costs. In this work, we develop a framework to assess this potential under a range of assumptions about the quality of load and photovoltaic generation forecasts. The application of the methodology to a village of 600 households reveals cost savings ranging between 2% and 7% depending on the forecast quality and the composition of the microgrid. We also show that sizing microgrid components under the assumption of a predictive operation strategy results in a design with a higher share of intermittent generation. (C) 2017 Elsevier Ltd. All rights reserved.
Microinsurance has recently received much attention as a promising tool to protect poor individuals from important shocks. Yet, voluntary demand from people has been low, shedding doubt on the viability of microinsurance as a useful risk management tool. To better understand this puzzle, this paper reviews both the theoretical and empirical literature on the demand for insurance. While people's lack of understanding of insurance does seem to limit the demand for it, several more fundamental factors, such as price, quality, limited trust in the insurer, and liquidity constraints also seem to have an important role in explaining the puzzle. (C) 2017 Elsevier Ltd. All rights reserved.
Microneedles (MNs) are micron-scale polymeric or metallic structures that offer distinct advantages for vaccines by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. These advantages, along with recent studies showing therapeutic benefits achieved using traditional intradermal injections in human cancer patients, suggest MN delivery might enhance cancer vaccines and immunotherapies. We recently developed a new class of polyelectrolyte multilayers based on the self assembly of model peptide antigens and molecular toll-like receptor agonists (TLRa) into ultrathin, conformal coatings. Here, we reasoned that these immune polyelectrolyte multilayers (iPEMs) might be a useful platform for assembling cancer vaccine components on MN arrays for intradermal delivery from these substrates. Using conserved human melanoma antigens and a potent TLRa vaccine adjuvant, CpG, we show that iPEMs can be assembled on MNs in an automated fashion. These films, prepared with up to 128 layers, are approximately 200 nm thick but provide cancer vaccine cargo loading >225 mu g/cm(2). In cell culture, iPEM cargo released from MNs is internalized by primary dendritic cells, promotes activation of these cells, and expands T cells during coculture. In mice, application of iPEM-coated MNs results in the codelivery of tumor antigen and CpG through the skin, expanding tumor-specific T cells during initial MN applications and resulting in larger memory recall responses during a subsequent booster MN application. This study support MNs coated with PEMs built from tumor vaccine components as a well-defined, modular system for generating tumor-specific immune responses, enabling new approaches that can be explored in combination with checkpoint blockade or other combination cancer therapies.
Cadmium (Cd) accumulation in rice and its subsequent transfer to food chain is a major environmental issue worldwide. Understanding of Cd transport processes and its management aiming to reduce Cd uptake and accumulation in rice may help to improve rice growth and grain quality. Moreover, a thorough understanding of the factors influencing Cd accumulation will be helpful to derive efficient strategies to minimize Cd in rice. In this article, we reviewed Cd transport mechanisms in rice, the factors affecting Cd uptake (including physicochemical characters of soil and ecophysiological features of rice) and discussed efficient measures to immobilize Cd in soil and reduce Cd uptake by rice (including agronomic practices, bioremediation and molecular biology techniques). These findings will contribute to ensuring food safety, and reducing Cd risk on human beings. (C) 2017 Elsevier Ltd. All rights reserved.
In the study of host pathogen interactions, vaccines and drug delivery, particulate delivery system are widely used to mimic pathogen size, pattern recognition receptor agonist presentation, and target cells or organs. However, some of the polymeric systems used in particulate delivery have inherent inflammatory properties that are variable and nonspecific. These properties enhance their adjuvant activity, but confound the analysis of signaling mechanisms. Here, we present a method for particle coating with minimal background immune activation via passivation of the surface with silica-silane. We show herein that a silica-silane shell passivates polymer particles rendering them inert to activation of innate immune cells. The method is broadly applicable and can be used to coat polymeric particles of many different compositions. This method of silica-silane coating also allows conjugation of amine-bearing agonists and provides for controlled variation of agonist loading. Finally, we demonstrate our particles maintain and enhance qualities of known pathogens, making this a potentially general method for improving immune agonist activity.
Very little is known regarding regulation of microRNA (miRNA) biogenesis in normal tissues, tumors, and cell lines. Here, we profiled the expression of 225 precursor and mature miRNAs using real-time PCR and compared the expression levels to determine the processing patterns. RNA from 22 different human tissues, 37 human cancer cell lines, and 16 pancreas and liver tissues/tumors was profiled. The relationship between precursor and mature miRNA expression fell into the following four categories: (1) a direct correlation exists between the precursor and mature miRNA expression in all cells/tissues studied; (2) direct correlation of the precursor and mature miRNA exists, yet the expression is restricted to specific cell lines or tissues; (3) there is detectable expression of mature miRNA in certain cells and tissues while the precursor is expressed in all or most cells/tissues; or (4) both precursor and mature miRNA are not expressed. Pearson correlation between the precursor and mature miRNA expression was closer to one for the tissues but was closer to zero for the cell lines, suggesting that processing of precursor miRNAs is reduced in cancer cell lines. By using Northern blotting, we show that many of these miRNAs (e. g., miR-31, miR-105 and miR-128a) are processed to the precursor, but in situ hybridization analysis demonstrates that these miRNA precursors are retained in the nucleus. We provide a database of the levels of precursor and mature miRNA in a variety of cell types. Our data demonstrate that a large number of miRNAs are transcribed but are not processed to the mature miRNA.
MicroRNAs (miRNAs) are a class of small non-coding RNAs (18-24 nucleotides (nt)) that regulate gene expression. MiRNAs exist widely in animals, plants and humans, and play fundamental roles in many biological processes, such as growth, development, differentiation and reproduction, etc. MiRNA is believed to be involved in the regulation of nearly 30% of all human genes and its expression level is closely related to some major diseases of mankind. Thus, quantitive detection and expression analysis of miRNA are significant to the understanding of functional mechanism of miRNAs, the diagnosis and treatment of diseases, and the development of the correlated gene drugs, etc. MiRNA detection is mostly based on the hybridization and amplification techniques of nucleic acids, which includs northern blotting technique, microarray, in situ hybridization, real-time reverse transcription PCR, isothermal rolling circle amplification and conjugated polymer-based miRNA detection. With the discovery of miRNA in different species and the thoroughly functional research of miRNA, the detection methods have been improved continuously and the new techniques, involving amplification, labeled probe and detection, have been developed successively. This paper summarizes the progress of miRNA detection, reviews the advantages and the disadvantages of all kinds of methods and prospects the miRNA detection trends.
MicroRNAs are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidences indicate that miRNAs have different expression profiles and play crucial roles in numerous cellular processes. Delivery and expression of transgenes for cancer therapy must be specific for tumors to avoid killing of healthy tissues. Many investigators have shown that transgene expression can be suppressed in normal cells using vectors that are responsive to microRNA regulation. To overcome this problem, miR-145 that exhibits downregulation in many types of cancer cells was chosen for posttranscriptional regulatory systems mediated by microRNAs. In this study, a psiCHECK-145T vector carrying four tandem copies of target sequences of miR-145 into 3'-UTR of the Renilla luciferase gene was constructed. Renilla luciferase activity from the psiCHECK-145T vector was 57% lower in MCF10A cells with high miR-145 expression as compared to a control condition. Additionally, overexpression of miR-145 in MCF-7 cells with low expression level of miR-145 showed more than 76% reduction in the Renilla luciferase activity from the psiCHECK-145T vector. Inclusion of miR-145 target sequences into the 3'-UTR of the Renilla luciferase gene is a feasible strategy for restricting transgene expression in a breast cancer cell line while sparing a breast normal cell line. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Background: Ovarian cancer is the leading lethal, gynecological malignancy in the United States. No doubt, the continued morbidity and mortality of ovarian cancer reflects a poor understanding of invasive mechanisms. Recent studies reveal that ovarian cancers express aberrant microRNAs (miRNAs or miRs), some of which have oncogenic or tumor suppressor properties. Several studies suggested that miR-205 is involved in tumorigenesis. Presently, we investigate the molecular mechanisms and target of miR-205 in ovarian cancer. Methods: Quantitative real-time polymerase chain reaction and western blot were performed to assess miR-205 and transcription factor 21 (TCF21) expression in ovarian cancer and normal ovary samples. The effect of miR-205 on TCF21 was determined by luciferase reporter assay and western blot. The effect of miR-205 and TCF21 on cell invasion was quantitated using transwell invasion assay. Result: miR-205 expression was increased in ovarian cancer and it promoted the invasive behavior of ovarian cancer cell lines (OVCAR-5, OVCAR-8 and SKOV-3). miR-205 directly targeted TCF21, which was significantly decreased in ovarian cancer tissue. miR-205 inhibited TCF21 expression and as a consequence blunted the inhibitory effect of TCF21 on cell invasion. Matrix Metalloproteinases (MMPs) play an important role in cancer invasion and metastasis. TCF21 inhibited MMP-2 and MMP-10 and decreased ovarian cancer cell invasion. Co-transfection of TCF21 expression plasmid with miR-205 mimic diminished the inhibitory effect of TCF21 on MMP-2 and MMP-10 in ovarian cancer cells. Conclusion: miR-205 appears to have an important role in the spread of ovarian cancer by targeting TCF21. These findings offer a new mechanism of ovarian cancer tumorigenesis, which could be useful for the development of new therapeutic approaches to ovarian cancer treatment.
Carcinogenesis is driven by an accumulation of mutations and genetic lesions, which leads to activation of oncogenes and inactivation of tumor suppressor genes. However, the molecular mechanisms by which the expression of these genes was regulated in pancreatic cancer remains unclear. In this study, we investigated the regulatory effects of microRNA and methylation on the expression of k-ras, TP53 and PTEN genes in pancreatic cancer cells. The protein and miRNA levels were measured by Western blotting and Northern blotting, respectively. Xenograft pancreatic tumor models were established by inoculating BxPC-1, Capan-2, and Panc-1 tumor cells into athymic nu/nu mice. A disparate level of KRAS, p53, PTEN, Dnmts, and Dicer 1 proteins as well as let-7i, miR-22, miR-143, and miR-29b miRNA was observed in BxPC-1, Capan-2, and Panc-1 cells. Knockdown of Dicer 1 expression in BxPC-3 and Panc-1 cells resulted in significant increases in KRAS, p53, PTEN, and Dnmts protein levels and significant decreases in miR-22, miR-143, let-7i, and miR-29b expression. Knockdown of Dicer 1 expression in Capan-2 cells significantly increased p53 and PTEN expression, while significantly decreased miR-22 and miR-143 expression, but had no effects on PTEN. Dnmts, let-7i, and miR-29b expression. Knockdown of Dicer 1 expression significantly inhibited xenograft BxPC-3 tumor growth, but promoted xenograft Panc-1 tumor growth. In contrast, knockdown of Dicer 1 expression had no effect on xenograft Capan-2 tumor growth. Our study suggested that different pancreatic cancer cell lines exhibited obvious discrepancies in gene expression profiles, implying that different molecular mechanisms are involved in the carcinogenesis of pancreatic cancer subclasses. Our study highlighted the importance of personalized therapy. (C) 2012 Elsevier Inc. All rights reserved.
The aim of the present study was to investigate regulatory relationships among hypoxia-inducible factor-1 (HIF-1), microRNA and erythroid transcription factors. K562 cells were transfected with HIF-1 knockout or with overexpression lentivirus of plasmid (MOI 10). The cells were divided into 3 groups: the negative control, overexpressing and interference groups. The cells were cultured under normoxia and hypoxia. Expression of miR-17*, miR-363 and miR-574-5p in the three groups was determined by quantitative PCR. Expression levels of erythroid transcription factor mRNAs such as GATA-1/GATA-2 and nuclear factor-erythroid 2 (NF-E2) were measured using RT-qPCR while the protein expression was studied using western blot analysis. Under normoxia or hypoxia, the levels of miR-17*, miR-363 and miR-574-5p in the overexpression group were higher than those in the other groups. Differences were statistically significant (P<0.05). Under hypoxia, the level of miR-363 in the interference group was less than that in the negative control group and difference was statistically significant (P<0.05). The level of GATA-1 mRNA in the overexpression group was higher than that in the negative control group, however, in the interference group the level was lower than that in the overexpression group under both normoxic and hypoxic conditions. The level of GATA-2 mRNA in the interference group was higher than that in other two groups under normoxic or hypoxic conditions. The NF-E2 mRNA was reversely related to GATA-2. The levels of HIF-1, GATA-1 and NF-E2 mRNAs in the negative control under hypoxia were higher than those of normoxia. The level of HIF-1 mRNA in the overexpression group in hypoxia was lower than that in normoxia, while the GATA-1 and GATA-2 mRNA showed a reverse association. The levels of HIF-1 and GATA-2 mRNA in the interference group under hypoxia were higher compared to those of normoxia. Differences were statistically significant (P<0.05). Western blot results suggested that GATA-1, GATA-2 and NF-E2 protein expression correlated with changes in their respective mRNA transcription levels. The results therefore suggested that GATA-l and miR-363 were involved in the regulation of hematopoiesis via the HIF-1 pathway in K562 cells under hypoxic condition. The hsa-miR-17* and hsa-miR-574-5p were not entirely dependent on HIF-1, suggesting possible complex regulatory mechanisms involved in hypoxia.
MicroRNAs (miRNAs) represent a family of small noncoding RNAs with important regulatory roles in diverse biological processes ranging from cell differentiation to organism development. In chickens, the full set of miRNAs and the expression patterns of miRNAs during development are still poorly understood when compared to the other vertebrates. In this study, we identified 29 novel miRNAs and 140 potential miRNA loci in the chicken genome by combining the experimental and computational analyses. Detailed expression patterns of 49 miRNAs were first characterized by Northern blotting and indicated the cooperativity of the miRNA expression with their function in embryogenesis and organogenesis. Twenty-seven miRNA clusters were systematically evaluated in the chicken genome and diverse expression patterns for closely linked miRNAs were observed. Our results significantly expand the set of known miRNAs in the chicken and provide the basis for understanding the structural and functional evolution of miRNA genes in vertebrates. (C) 2008 Elsevier B.V. All rights reserved.
microRNAs (miRNAs) are small non-coding RNAs that execute regulation of gene expression at the post-transcriptional level. Information on turmeric miRNAs is very rare. In the present study, we have identified 27 conserved and 40 non-conserved miRNA families by high-throughput Illumina sequencing and downstream in silico analysis. We could also identify 97 novel candidate miRNAs specific to turmeric. Selected miRNAs were validated by stem-loop RT-PCR and northern blotting. The targets were predicted for identified miRNAs and were found to be involved in plant growth and development, stress response and metabolism. Expression pattern of selected conserved miRNAs in response to drought stress was analyzed by stem-loop qRT-PCR. This is the first report on miRNA content of turmeric transcriptome, which might serve as a foundation for more future work on miRNA based gene regulation in this medicinally important spice crop.
Background: MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Sequential cleavage of miRNA precursors results in a similar to 22 nucleotide duplex of which one strand, the mature miRNA, is typically loaded into the RNA-induced silencing complex (RISC) while the passenger strand is degraded. Very little is known about how genetic variation might affect miRNA biogenesis and function. Results: We re-sequenced the MIR1-1, MIR1-2, MIR133A1, MIR133A2, and MIR133B genes, that encode the cardiac-enriched miRNAs, miR-1 and miR-133, in 120 individuals with familial atrial fibrillation and identified 10 variants, including a novel 79T >C MIR133A2 substitution. This variant lies within the duplex at the 3' end of the mature strand, miR-133a-3p, and is predicted to prevent base-pairing and weaken thermostability at this site, favoring incorporation of the passenger strand, miR-133a-5p, into RISC. Genomic DNA fragments containing miR-133a-2 precursor sequences with 79T and 79C alleles were transfected into HeLa cells. On Northern blotting the 79T allele showed strong expression of miR-133a-3p with weak expression of miR-133a-5p. In contrast, the 79C allele had no effect on miR-133a-3p but there was a significant increase (mean 3.6-fold) in miR-133a-5p levels. Deep sequencing of small RNA libraries prepared from normal human and murine atria confirmed that nearly all the mature miR-133a was comprised of miR-133a-3p and that levels of miR-133a-5p were very low. A number of isomiRs with variations at 5' and 3' ends were identified for both miR-133a-3p and miR-133a-5p, with 2 predominant miR-133a-3p isomiRs and one predominant miR-133a-5p isomiR. Bioinformatics analyses indicate that the major miR-133a-3p and 5p isomiRs have numerous predicted target mRNAs, only a few of which are in common. Conclusions: Multiple miR-133a isomiRs with potential different mRNA target profiles are present in the atrium in humans and mice. We identified a human 79T >C MIR133A2 variant that alters miRNA processing and results in accumulation of the miR-133a-5p strand that is usually degraded.
Aim: To explore the microRNA (miRNA) expression in renal clear cell carcinoma (RCCC). Methods: We compared the miRNA expression profiles in 11 pairs of RCCC and adjacent nontumorous tissue (NT) from 11 RCCC patients, using a mammalian miRNA microarray containing whole human mature and precursor miRNA sequences. To verify microarray results, Northern blotting was carried out on 5 randomly selected miRNAs. Results: Totally 81 miRNAs were identified valid expression in RCCC samples, 48 of which specifically detected in RCCC samples, 17 of which detected downregulated in RCCC compared to NT sample, 2 upregulated and 14 without significant difference. MiRNAs in RCCC tissues exhibit an overall higher expression level than NT tissue. The chip results were confirmed by northern blot analysis. Conclusion: Our study may help to clarify the molecular mechanisms involved in the pathogenesis of RCCC, and miRNAs potentially serve as a novel diagnostic biomarker of RCCC. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
MicroRNAs (miRNAs) are a class of small noncoding RNAs similar to 22 nt in length that regulate gene expression and play fundamental roles in multiple biological processes, including cell differentiation, proliferation and apoptosis as well as disease processes. The study of miRNA has thus become a rapidly emerging field in life science. The detection of miRNA expression is a very important first step in miRNA exploration. Several methodologies, including cloning, northern blotting, real-time RT-PCR, microRNA arrays and ISH (in situ hybridization), have been developed and applied successfully in miRNA profiling. This review discusses the main existing microRNA detection technologies, while emphasizing microRNA arrays.
MicroRNAs (miRNAs) are small non-coding RNAs involved in fine-tuning of gene regulation. Antisense oligonucleotides (ONs) are promising tools as anti-miRNA (anti-miR) agents toward therapeutic applications and to uncover miRNA function. Such anti-miR ONs include 2'-O-methyl (OMe), cationic peptide nucleic acids like K-PNA-K3, and locked nucleic acid (LNA)-based anti-miRs such as LNA/DNA or LNA/OMe. Northern blotting is a widely used and robust technique to detect miRNAs. However, miRNA quantification in the presence of anti-miR ONs has proved to be challenging, due to detection artifacts, which has led to poor understanding of miRNA fate upon anti-miR binding. Here we show that anti-miR ON bound to miR-122 can prevent the miRNA from being properly precipitated into the purified RNA fraction using the standard RNA extraction protocol (TRI-Reagent), yielding an RNA extract that does not reflect the real cellular levels of the miRNA. An increase in the numbers of equivalents of isopropanol during the precipitation step leads to full recovery of the targeted miRNA back into the purified RNA extract. Following our improved protocol, we demonstrate by Northern blotting, in conjunction with a PNA decoy strategy and use of high denaturing PAGE, that high-affinity anti-miRs (K-PNA-K3, LNA/DNA, and LNA/OMe) sequester miR-122 without causing miRNA degradation, while miR-122 targeting with a lower-affinity anti-miR (OMe) seems to promote degradation of the miRNA. The technical issues explored in this work will have relevance for other hybridization-based techniques for miRNA quantification in the presence of anti-miR ONs.
MicroRNAs (miRNAs) comprise a group of small noncoding RNA molecules thought to have contributed to the evolution of vertebrate brain homogeneity and diversity. The miRNA miR-124 is well conserved between invertebrates and vertebrates and is expressed abundantly in the central nervous system (CNS). We identified miR-124 in the medaka, Oryzias latipes, and investigated its role in neural development. The five candidate genes for medaka precursor miR-124 are unlinked on four different chromosomes and differ in nucleotide length. Their sequences suggest that they can generate functional miRNAs through conventional miRNA biogenesis by folding into stem-loop structures. Whole-mount in situ hybridization and northern blotting revealed that mature miR-124 is specifically expressed in the CNS and the eyes starting at two days post-fertilization. We also examined the sequences and expression of medaka Polypyrimidine tract binding protein 1 (Ptbp1), a possible direct target of miR-124. The 3'UTR of medaka Ptbp1 contains predicted binding motifs (target sites) for miR-124. A GFP reporter assay for the target sites or the entire 3'UTR showed that exogenous miR-124 silences PTBP1 expression in vivo. Our study suggests that medaka miR-124 is involved in post-transcriptional regulation of target genes in neural development and that medaka miR-124 homologs may have spatiotemporal roles different from those in other vertebrates.
MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. Using deep sequencing and Northern blotting, we characterized miRNA expression in wild type and miR-155-deficient dendritic cells (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence of miR-155 on the expression levels of other miRNAs. For example, miR-455 is negatively regulated in miR-155-deficient cells possibly due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our comprehensive data sets, we propose a model of hierarchical miRNA expression dominated by miR-155 in DCs and macrophages. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. Recent evidence indicates that miRNAs can function both as tumor suppressors and as oncogenes. It has been demonstrated that in glioblastoma multiforme miR-21 and 221 are upregulated whereas miR-128 and 181 are downregulated. Expression of miR-21, 221, 128a, 128b, 128c, 181a, 181b, 181c was studied using real-time quantitative reverse transcriptase polymerase chain reaction and northern blotting for human astrocytic tumors with different grade of malignancy. miR-21 and 221 were overexpressed in glioma samples, whereas miRNA 181b was downregulated compared with normal brain tissue. miRNA-21 was hyperexpressed in all tumor samples whereas higher levels of miRNA-221 were found in high-grade gliomas. This study is the first analysis of miRNAs in astrocytic tumor at different stages of malignancy. The different expression pattern observed in tumors at different stages of malignancy is probably dependent on the cell-specific repertoire of target genes of tumors sharing different molecular pathways activity and suggests miRNAs may have also a place in diagnosis and staging of brain tumors.
microRNAs (miRs) have been investigated as a novel class of regulators of cellular processes, including proliferation, apoptosis and metabolism. In particular, miR-30b has been demonstrated to be deregulated in certain types of cancer, including lung, colorectal and gastric cancer. Previous studies of miR-30b in renal clear cell carcinoma demonstrated that the expression level of miR-30b was associated with distant metastasis. However, the function of miR-30b in renal cell carcinoma (RCC) remained to be elucidated. In the present study, the expression of miR-30b in 31 paired RCC tissues from four cell lines (786-O, 769-P, ACHN and 293T) was detected by reverse transcription-quantitative polymerase chain reaction. In addition, the effect of miR-30b on cell proliferation in RCC cells was also determined using MTT and Cell Counting Kit-8 assay analyses. Furthermore, the function of miR-30b in cell migration and invasion was determined by wound scratch and Transwell assays. Flow cytometry was also performed to quantify the effect of miR-30b on cell apoptosis. The results of the current study indicated that miR-30b was upregulated in RCC tissues from affected cell lines when compared with adjacent normal tissues and a normal kidney cell line, which is different to the downregulation of miR-30b as observed in other types of cancer. miR-30b is associated with RCC cell proliferation, invasion, migration and apoptosis, which indicated that miR-30b acts as an oncogene in RCC. To the best of our knowledge, the present study is the first to demonstrate the upregulation of miR-30b in RCC tissues and describe miR-30b as an oncogene in RCC in the regulation of cell proliferation, migration, invasion and apoptosis. Further studies will define the target gene of miR-30b in RCC and investigate the potential role of miR-30b as a biomarker for RCC.
Aberrant expression of microRNAs (miRNAs) and processing defects in their biogenesis pathway are a widespread phenomenon in tumors, conveying great importance to the analysis of miRNA expression, regulation, and biogenesis to gain knowledge about their role in cancer. Besides Drosha and Dicer, Argonaute proteins are key players in miRNA processing. In addition to their role as components of the RNA-induced silencing complex (RISC) executing target silencing, Argonautes mediate posttranscriptional regulation of miRNA maturation by creating an additional intermediate processing step, the Ago2-cleaved precursor miRNA (ac-pre-miRNA), and enhancing the production or stability of mature miRNAs. Here, we describe the detection of miRNA levels by Northern blotting and the identification of the 3' end of miRNAs by precursor cloning to accentuate two of the many roles of Argonaute proteins. In addition, we describe a method to optimize RNAi experiments by increasing the efficacy and specificity of target silencing via Ago2 cotransfection.
Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state.
MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in post-transcriptional regulation. Their target genes are involved in a variety of biological processes such as development, metabolism, and stress response. Panicum miliaceum L. (Panicum) is an important grain crop, but, until now, no miRNAs have been identified in this plant. Using a homology search based on expressed sequence tag (EST) analysis and miRNA precursor secondary structure, a total of 43 new miRNAs were identified. The miRNAs were found to be unevenly distributed among 11 miRNA families. Target analysis using the plant small RNA target analysis server psRNATarget showed that the newly identified miRNAs can potentially regulate 68 target genes. Ten of the 11 miRNA families were annotated as involved in RNA regulation, suggesting they may play an essential role in post-transcriptional regulation in Panicum. Selected miRNAs representing eight of the families were verified by northern blotting, indicating that the prediction method that we used to identify the miRNAs was effective.
The ability to identify and stratify patients that will respond to specific therapies has been transformational in a number of disease areas, particularly oncology. It is anticipated that this will also be the case for cell-based therapies, particularly in complex and heterogeneous diseases such as rheumatoid arthritis (RA). Recently, clinical results with expanded allogenic adipose-derived mesenchymal stem cells (eASCs) have indicated clinical efficacy in highly refractory RA patients. In this study, we set out to determine if circulating microRNAs (miRNAs) could be identified as potential biomarkers associated with response to eASCs in these RA patients. The miRNA expression profiles of pre-treatment plasma samples from responder and nonresponder patients were determined using microarrays. Ten miRNAs were identified that were differentially expressed in the responder group as compared to the nonresponder group. To confirm the differential expression of these 10 miRNA biomarkers, they were further assayed by quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR). From this analysis, three miRNAs, miR-26b-5p, miR-487b-3p and miR-495-3p, were confirmed as being statistically significantly upregulated in the responder group as compared with the nonresponder group. Receiver operating characteristic analysis confirmed their diagnostic potential. These miRNAs could represent novel candidate stratification biomarkers associated with RA patient response to eASCs and are worthy of further clinical validation.
There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.
The review presents the opening story, biogenesis and functions of basic groups of human's small noncoding RNA: microRNA and short interfering RNA. These RNA molecules inhibit gene expression during translation by RNA interference. It was found that microRNA and short interfering RNA circulate in bioliquids and can serve as biomarkers of different human diseases because of its conservative sequences, tissue specificity and resistance to environment factors. The paper considers techniques to study noncoding RNA (cloning, bioinformatics analysis and hybridization methods: northern-blotting, RT-PCR, in situ hybridization, microarray analysis, reporter analysis). Possible noncoding RNA-targeted therapy can suggest delivery microRNA, anti-microRNA, antagomirs, microRNA-sponges to target tissue by virus molecules, liposomes or nanoparticles.
Insulin-like growth factor-binding protein-3 acts as a tumor suppressor that inhibits the PI3K/AKT signaling pathway due to blocking insulin growth factor-1 binding to its receptor. We hypothesized that insulin-like growth factor-binding protein-3 might be targeted by microRNA-125b and promote tumor invasion and poor outcome in non-small-cell lung cancer via activation of the PI3K/AKT signaling pathway. Real-time polymerase chain reaction and immunohistochemistry were performed to determine the level of microRNA-125b, insulin-like growth factor-binding protein-3 messenger RNA, and phosphorylated-AKT expression in 105 tumors from non-small-cell lung cancer patients. Low insulin-like growth factor-binding protein-3 messenger RNA levels and positive phosphorylated-AKT expression were more commonly found in patients with high microRNA-125b tumors than low microRNA-125b tumors. A poorer overall survival and relapse-free survival were observed in patients with high microRNA-125b tumors than low-microRNA-125b tumors in p53-mutated patients, but not in p53-wild-type patients. Mechanistically, microRNA-125b promotes invasion ability in p53-mutated cells via the PI3K/AKT activation by targeting of insulin-like growth factor-binding protein-3, but this effect was not observed in p53-wild-type cells. An increase in phosphorylated-AKT expression due to targeting of insulin-like growth factor-binding protein-3 by microRNA-125b was responsible for cell invasion in p53-mutated cells. In conclusion, the microRNA-125b level promotes invasive ability in p53-mutated cells via PI3K/AKT activation by targeting of insulinlike growth factor-binding protein-3, thereby resulting in p53-mutated non-small-cell lung cancer patients with poor outcomes.
Colorectal carcinoma (CRC) is a malignant solid tumor arising from the large intestine and is associated with an increasing incidence and poor prognosis. Further understanding of the molecular mechanisms underlying CRC may contribute to the development of novel effective therapeutic strategies. MicroRNAs (miRs), including miR-155, have been reported to be associated with the etiology and biology of CRC; however, the molecular mechanisms by which miR-155 affect CRC remain to be fully elucidated. The present study used a multidisciplinary approach, involving reverse transcription-quantitative polymerase chain reaction, northern blotting, MTT assay, cell cycle progression analysis, immunoblotting, and animal experiments, to determine the possible targets of miR-155 in CRC cells. miR-155 was found to be overexpressed in CRC tissue samples, compared with paired normal colon tissue samples. In addition, the inhibition of miR-155 induced a deceleration in CRC cell proliferation and inactivation of the Wnt/-catenin signaling pathway. miR-155 suppression also reduced the growth of CRC xenografts in an animal model. HMG-box transcription factor 1 (HBP1) was identified as a novel target of miR-155, which mediated its effect on CRC via the Wnt/-catenin pathway. Furthermore, patients with CRC exhibiting higher serum levels of miR-155 exhibited reduced survival rates. In conclusion, the present study demonstrated that miR-155 may contribute to the progression and growth of CRC by enhancing the Wnt/-catenin pathway in an HBP1-associated mechanism. Therefore, miR-155 may be considered a promising therapeutic target for the treatment of CRC.
In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit-8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24. The expressions of miR-294 in bladder cancer cells including J82, HT1376, T24, and SW780 were significantly increased compared to those in human bladder epithelium cells (both HCV29 and SV-HUC-1). The proliferation rate, surviving fraction, migration, and invasion of T24 cells in miR-294 mimetic transfected group were significantly increased, while they were significantly decreased by miR-294 inhibitor transfection. Moreover, miR-294 suppression could increase the apoptotic rate of T24 cells. In addition, drug resistance of T24 cells to cisplatin was increased in miR-294 mimetic-treated group, while it was decreased by miR-294 inhibitor compared to empty control. Overexpression of miR-294 could upregulate NRAS expression in T24 cells and activate PI3K/AKT and JAK/STAT pathways. We found that miR-294 expression was positively related with proliferation and motility of T24 cells. Moreover, miR-294 suppression could promote the sensitivity of T24 cells to cisplatin. We also found miR-294 could upregulate NRAS and activate the PI3K/AKT and JAK/STAT pathways in T24 cells.
MicroRNA-34 (miR-34), in particular miR-34a, has a negative regulatory effect on osteosarcoma cell proliferation, migration and invasion. Notably, it is also a post-transcriptional regulatory factor of (sex determining region Y)-box 2 (Sox-2), which is required for osteosarcoma cell self-renewal and tumorigenesis. As a direct regulator of Sox-2, miR-34a has been hypothesized to be greatly associated with the regulation of malignancies in osteosarcoma. To investigate the role of miR-34a in the malignancies of osteosarcoma, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression level of miR-34a in osteospheres. The results revealed that the miR-34a, b and c were suppressed in osteosarcoma stem-like cells (OSCs) and osteospheres. The introduction of miR-34a mimics and short hairpin (sh) RNA targeting Sox-2 mRNA (shSox-2) in human OSCs markedly reduced their transformation properties in vitro and their capacity to form tumors in soft agar. Furthermore, the epigenetic expression of miR-34a and shSox-2 inhibited the expression of the stem cell marker, stem cell antigen-1 and led to the failure of osteosphere formation, respectively. The data of the present study indicated that the inhibitory role of miR-34a on tumor growth and metastasis of osteosarcoma may function by reducing the maintenance of osteosphere self-renewal capacity, elimination of tumorigenic ability and invasion of osteosarcoma in vitro. These findings may provide the basis for a novel therapeutic target of osteosarcomas based on inducing the expression of miR-34a.
Currently, 5.4 million Americans suffer from AD, and these numbers are expected to increase up to 16 million by 2050. Despite tremendous research efforts, we still do not have drugs or agents that can delay, or prevent AD and its progression, and we still do not have early detectable biomarkers for AD. Multiple cellular changes have been implicated in AD, including synaptic damage, mitochondrial damage, production and accumulation of A beta and phosphorylated tau, inflammatory response, deficits in neurotransmitters, deregulation of the cell cycle, and hormonal imbalance. Research into AD has revealed that miRNAs are involved in each of these cellular changes and interfere with gene regulation and translation. Recent discoveries in molecular biology have also revealed that microRNAs play a major role in post-translational regulation of gene expression. The purpose of this article is to review research that has assessed neuroprotective and neurodegenerative characteristics of microRNAs in brain samples from AD transgenic mouse models and patients with AD. (C) 2016 Elsevier Inc. All rights reserved.
MicroRNAs (miRNAs) are a family of non-protein-coding, endogenous, small RNAs. They are a group of gene regulators that function mainly by binding the 3' untranslated regions of specific target messenger RNA (mRNA) leading to gene inactivation by repression of mRNA transcription or induction of mRNA. Mature miRNAs are short molecules approximately 22 nucleotides in length. They regulate a wide range of biological functions from cell proliferation and death to cancer progression. Cellular miRNA expression levels can be used as biomarkers for the onset of disease states and in gene therapy for genetic disorders. Methods for detection of miRNA mainly include northern blotting, microarray, polymerase chain reaction (PCR). This review focuses on the use of electrochemical biosensors for the detection of microRNA. (c) 2013 Elsevier B.V. All rights reserved.
Nervous necrosis virus (NNV), one of the most prevalent fish pathogens, has caused fatal disease of viral nervous necrosis (VNN) in many marine and freshwater fishes, and resulted in heavy economic losses in aquaculture industry worldwide. However, the morecular mechanisms underlying the pathogenicity of NNV remain elusive. In this study, the expression profiles of microRNA (miRNA) were investigated in grouper fin (GF-1) cells infected with red-spotted grouper nervous necrosis virus (RGNNV) via deep sequencing technique. The results showed that a total of 220 miRNAs were identified by aligning the small RNA sequences with the miRNA database of zebrafish, and 18 novel miRNAs were predicted using miRDeep2 software. Compared with the non-infected groups, 51 and 16 differentially expressed miRNAs (DE-miRNAs) were identified in the samples infected with RGNNV at 3 and 24 h, respectively. Six DEmiRNAs were randomly selected to validate their expressions using quantitative reverse transcription polymerase chain reaction (qRT-PCR), the results showed that their expression profiles were consistent with those obtained by deep sequencing. The target genes of the DE-miRNAs covered a wide range of functions, such as regulation of transcription, oxidation-reduction process, proteolysis, regulation of apoptotic process, and immune response. In addition, the effects of four DE-miRNAs including miR-1, miR-30b, miR-150, and miR-184 on RGNNV replication were evaluated, and the results showed that over-expression of each of the four miRNAs promoted the replication of RGNNV. These data provide insight into the molecular mechanism of RGNNV infection, and will benefit for the development of effective strategies to control RGNNV infection. (C) 2017 Elsevier Ltd. All rights reserved.
Since the discovery of the first mammalian microRNA (miRNA) more than two decades ago, a plethora of miRNAs has been identified in humans, now amounting to more than 2500. Essential for post-transcriptional regulation of gene networks integral for developmental pathways and immune response, it is not surprising that dysregulation of miRNAs is often associated with the aetiology of complex diseases including cancer, diabetes and autoimmune disorders. Despite massive expansion of small RNA studies and extensive investigation in diverse disease contexts, the role of miRNAs in type 1 diabetes has only recently been explored. Key studies using human islets have recently implicated virus-induced miRNA dysregulation as a pivotal mechanism of beta cell destruction, while the interplay between miRNAs, the immune system and beta cell survival has been illustrated in studies using animal and cellular models of disease. The role of specific miRNAs as major players in immune system homeostasis highlights their exciting potential as therapeutics and prognostic biomarkers of type 1 diabetes.
Microscopic colitis (MC) refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD), which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords "microscopic colitis", "collagenous colitis", "lymphocytic colitis", and "review" for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.
As one of the most successfully commercialized distributed energy resources, the long-term effects of microturbines (MTs) on the distribution network has not been fully investigated due to the complex thermo-fluid-mechanical energy conversion processes. This is further complicated by the fact that the parameter and internal data of MTs are not always available to the electric utility, due to different ownerships and confidentiality concerns. To address this issue, a general modeling approach for MTs is proposed in this paper, which allows for the long-term simulation of the distribution network with multiple MTs. First, the feasibility of deriving a simplified MT model for long-term dynamic analysis of the distribution network is discussed, based on the physical underStanding of dynamic processes that occurred within MTs. Then a three-stage identification method is developed in order to obtain a piecewise MT model and predict electro-mechanical system behaviors with saturation. Next, assisted with the electric power flow calculation tool, a fast simulation methodology is proposed to evaluate the long-term impact of multiple MTs on the distribution network. Finally, the model is verified by using Capstone 00 micro turbine experiments, and further applied to the dynamic simulation of a modified IEEE 37-node test feeder with promising results. (C) 2016 Elsevier Ltd. All rights reserved.
The life cycle assessment of several zinc oxide (ZnO) nanostructures, fabricated by a facile microwave technique, is presented. Key synthesis parameters such as annealing temperature, varied from 90 degrees C to 220 degrees C, and microwave power, varied from 110 W to 710 W, are assessed. The effect of these parameters on both the structural characteristics and the environmental sustainability of the nanostructures is examined. The nanostructures were characterized by means of X-ray diffraction (XRD), focused ion beam scanning electron microscopy (FIB-SEM), ultraviolet-visible spectroscopy (UV-Vis), Photoluminescence (PL) and Brunauer-Emmett-Teller (BET) analysis. Crystalline site was found to be 22.40 nm at 110 W microwave power, 24.83 nm at 310 W, and 24.01 nm at 710 W. Microwave power and synthesis temperature were both directly proportional to the surface area At 110 W the surface area was 10.44 m(2)/g, at 310 W 12.88 m(2)/g, and at 710 W 14.60 m(2)/g; while it was found to be 11.64 m(2)/g at 150 degrees C and 18.09 m(2)/g at 220 degrees C. Based on these, a life cycle analysis (LCA) of the produced ZnO nanoparticles was carried out, using the ZnO surface area (1 m(2)/g) as the functional unit It was found that the main environmental weaknesses identified during the production process were; (a) the use of ethanol for purifying the produced nanomaterials and (b) the electricity consumption for the ZnO calcination, provided by South Africa's fossil-fuel dependent electricity source. When the effect of the key synthesis parameters on environmental sustainability was examined it was found that an increase of either microwave power (from 110 to 710 W) or synthesis temperatures (from 90 to 220 degrees C), results in higher sustainability, with the environmental footprint reduced by 27% and 41%, respectively. Through a sensitivity analysis, it was observed that an electricity mix based on renewable energy could improve the environmental sustainability of the nanoparticles by 25%. (C) 2017 Elsevier B.V. All rights reserved.
Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the alpha(1A) subunit of voltage-gated Ca(V)2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.
The present study examines 579 Indian publications on "Migraine" research as covered in Scopus database during 2006-15, experiencing an annual growth rate of 17.37%, citation impact per paper of 8.32, international collaborative publication share of 9.80% and global publication share of 2.56%. The global publications share on "Migraine" came from several countries, of which the top 10 most productive countries accounted for 75.30% share of global publications output during 2006-15. A large number of Indian organizations and authors participated in Indian research on "Migraine" research during 2006-15, of which the top 15 organizations and 15 authors contributed 31.26% and 25.22% publications share and 70.50% and 23.50% citation share respectively of the Indian output and citations. Medicine, among subjects, contributed the largest publications (63.90%), followed by pharmacology, toxicology & pharmaceutics (34.72%), neurosciences (14.16%), biochemistry, genetics & molecular biology (13.64%) and chemistry (3.97%) during 2006-15. Indian publications on migraine research appeared in several journals, of which the top 15 journals contributed 32.64% share of the India's output. The top 14 highly cited papers registered 53 to 1087 citations, and together contributed 2094 citations, leading to the average citation per paper of 149.57. Concludes that there is an urgent need to frame a national policy in this area, undertake more R&D and recognize migraine research as a public health problem and allocate more healthcare funds in this area.
Purpose: To assess the influence of 14-3-3-beta in modulating the migration and invasion of human glioma cells. Methods: To profile the genes associated with malignant glioma cell motility, differential display-polymerase chain reaction was performed and the findings were validated by Northern blotting in the U343MG-A, U87MG, and U87MG-10' human glioma cell lines. Antisense 14-3-3-beta cDNA plasmid was transfected into U87MG ('U87-YA-3'). To follow motility changes after transfection, simple scratch test and matrigel assay were performed. Morphological and cytoskeletal changes were documented by light and confocal microscopy. In addition, doubling times of the transfectant and endogenous 14-3-3-beta levels were determined in various glioma cell lines with different motilities. Results: 14-3-3-beta was highly expressed in U87MG cells. U87-YA-3 cells became small and flat, and actin was depolarized. Furthermore, U87-YA-3 cell motility was inhibited markedly versus parental U87MG cells. The doubling times of transfected and parent cells were 32 and 37 hours, respectively. Endogenous 14-3-3-beta expression in the human glioma cell lines was proportional to their migratory and invasive abilities. Conclusion: 14-3-3-beta modulates the migration and invasion in U87MG cells, which may be useful in developing therapeutic approaches for the treatment of glioma.
Background: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies. Methods: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively. Results: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET). Conclusions: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer.
Migration, acculturation, and psychiatric disorders may cause stress and adaptation processes differently in men and women, but empirical research is scarce. In a retrospective study n = 62 Turkish migrants and n = 62 native German inpatients with depressive or anxiety disorders, matched for age, gender, and diagnoses, were compared using a 10-item instrument for the assessment of migration- and acculturation related stressors (MIGSTR10). Gender differences in the prevalence of stressors and in the total sum of stressors were calculated and compared between migrants and indigenous patients. Results showed a higher global stress level in migrants and in women than in men with migration background. Regarding single stressors, the perceived loss of status was significantly more prevalent and more pronounced in men than in women (P < 0.05) whereas guilt feelings were more severe in women with Turkish migration background compared to men (P < 0.05). Gender differences of perceived stress should be taken into account in migration and acculturation research.
Amino-functionalized metal-organic frameworks have attracted much attention because of their potential applications in many fields such as catalysis, adsorption and separation of CO2, further modification. In this work, we report that amino-functionalized MIL-101(Cr) with a large BET surface area of 3262 m(2)/g has been successfully synthesized by the reduction of MIL-101(Cr)-NO2 prepared under solvent-free conditions. Additionally, it has been demonstrated that the obtained material with high surface area exhibited superior catalytic activity in Henry reaction. (C) 2017 Elsevier B.V. All rights reserved.
Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) A beta 42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of A beta 42, tau and p-tau181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181 and increased tau/A beta 42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Ab and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD. (C) 2017 Elsevier Inc. All rights reserved.
Background Respiratory illnesses are a leading cause of morbidity and medical discharge in the military. This study aimed to investigate the effects of baseline aerobic fitness on haematological, salivary and mood variables, and simultaneously, in a novel approach, to identify factors precipitating illness and attrition rate in recruits during military training. Methods Thirty-five healthy male recruits from an Army Training Regiment undertaking 12 weeks of training were prospectively investigated. Their 2.4 km run time (RT) was used as a surrogate of baseline aerobic fitness. Saliva and venous blood samples were analysed for secretory IgA, full blood counts and cell cytokine production (interleukin (IL) 6 and IL-8), respectively. Each recruit completed questionnaires on mood profile, and gastrointestinal and upper respiratory tract symptoms (URTS). Results Significant salivary and haematological perturbations were observed and coincided with increased duration of URTS/week and mood disturbance over this military training period. From Start to End: leucocyte count decreased by 28% (p<0.001); neutrophil percentage (%) decreased by 13% (p<0.01); lymphocyte % increased by 17% (p<0.05); the neutrophil:lymphocyte ratio decreased by 22% (p<0.01); eosinophil% increased by 71% (p<0.01). From Start to Mid to End: monocyte% increased by 68% at Mid (p<0.01) but only by 30% at End (p<0.01); IL-6 increased by 39% at Mid (p<0.01) and a further 61% by End. The 2.4km RT was significantly associated with URTS duration (p<0.01). In addition, a 1-min increase in 2.4km RT increased a recruit's risk 9.8-fold of developing URTS lasting, on average, 3.36 days/week. In recruits ranked with high-URTS duration their RT was 48 s slower (p<0.01) than those with low-URTS, and their attrition rate reached 45%. Conclusions The least fit recruits may have found training more physically demanding as reflected in the higher URTS duration, which may have led to a high attrition rate from the Army. It is worth considering that baseline aerobic fitness might be an important factor in illness development and attrition rate in recruits during this type of military training.
Traceability of foods has become very important problem respect to food quality and typicalness of foods. Cheeses' milk origin cannot be identified by the consumer and they are sold at different prices under various product names. Recently, this has caused the problem of 'adulteration'. The aim of this study is to determine the amount and origin of milk used in cheese production by using real-time PCR which has been used for identification of animal species in dairy products. In this study, 90 different cheeses offered for sale in Turkey of 30 brands from various sources such as cow, sheep and goat have been studied. At the end of the study, only 36.67% of samples were determined to be produced from 100% cow milk. In the remaining 1333%, a mixture of goat and sheep milk have been found. Only one sample of sheep cheese was produced from 100% sheep milk. In goat cheese samples, 16.67% of cheese was produced from 100% sheep milk and the origin of only 10% was identified as 100% cow milk. No linear relationship could be determined between chemical composition, fatty acids ratios and amount and origin of cheeses (P < 0.05). (C) 2016 Elsevier Ltd. All rights reserved.
A two-stage large-capacitive-load amplifier with multiple cross-coupled small-gain stages is proposed in this paper. The cross-coupled structure of the small-gain stages augments the large-signal responses, providing significant improvement in the effective output-stage transconductance and, hence, the gain-bandwidth product (GBW). Implemented in a standard 0.13-mu m CMOS technology and powered by a 0.7 V supply with a current consumption of 20 mu A, the proposed amplifier achieves the GBW of 1.17 MHz and the phase margin of 74.8 degrees while driving a capacitive load of 9.5 nF. The average slew rate is 0.3679 V/mu s. The on-chip compensation capacitor is only 1.62 pF. The active chip area is 0.0056 mm(2).
Mimosine, which is a natural plant amino acid present in the Leucaena genus, is able to induce hypoxia-inducible factors (HIFs). Previous evidence has indicated that HIF regulates angiogenesis-osteogenesis coupling in bone metabolism, and it has previously been reported that mimosine inhibits prostaglandin (PG)F-2 alpha-induced osteoprotegerin (OPG) synthesis without affecting interleukin-6 (IL-6) production in osteoblast-like MC3T3-E1 cells. In addition, PGE(1) has been demonstrated to induce OPG synthesis via activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in these cells, and PGE(1) stimulates IL-6 production via the activation of protein kinase A. In the present study, the effects of mimosine on the PGE(1)-stimulated synthesis of OPG and IL-6 were investigated in osteoblast-like MC3T3-E1 cells. The concentrations of OPG and IL-6 were measured using relevant ELISA kits. OPG mRNA was measured by semi-quantitative reverse transcription polymerase chain reaction. The phosphorylation of p38 MAP kinase and SAPK/JNK was analyzed by western blotting. Mimosine significantly reduced PGE(1)-induced release of OPG and OPG mRNA expression levels without affecting the release of IL-6. In addition, deferoxamine, which is also a normoxic HIF inducer, significantly inhibited PGE(1)-induced OPG release and OPG mRNA expression levels; however, it had little effect on IL-6 release. Furthermore, mimosine and deferoxamine failed to affect PGE(1)-stimulated phosphorylation of p38 MAP kinase or SAPK/JNK. These results strongly suggest that normoxic HIF inducers attenuate PGE(1)-stimulated OPG synthesis without affecting IL-6 production in osteoblasts.
Over the last several decades, there has been a wealth of illuminating work on processes implicated in social cognition. Much less has been done in articulating how we learn the contours of particular concepts deployed in social cognition, like the concept MENTALISTIC AGENT. Recent developments in learning theory afford new tools for approaching these questions. In this article, I describe some rudimentary ways in which learning theoretic considerations can illuminate philosophically important aspects of the MENTALISTIC AGENT concept. I maintain that MENTALISTIC AGENT is an essentialized concept (cf. Gelman, in The essential child, 2003; Keil, in Concepts, kinds, and cognitive development, 1992) and that learning-theoretic considerations help explain why the concept is not tied to particular traits.
Background: Smokers increasingly seek alternative interventions to assist in cessation or reduction efforts. Mindfulness meditation, which facilitates detached observation and paying attention to the present moment with openness, curiosity, and acceptance, has recently been studied as a smoking cessation intervention. Aims: This review synthesizes randomized controlled trials (RCTs) of mindfulness meditation (MM) interventions for smoking cessation. Methods: Five electronic databases were searched from inception to October 2016 to identify English-language RCTs evaluating the efficacy and safety of MM interventions for smoking cessation, reduction, or a decrease in nicotine cravings. Two independent reviewers screened literature using predetermined eligibility criteria, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-KnappSidik-jonlonan method for random-effects models. The quality of evidence was assessed Using the GRADE approach. Findings: Ten RCTs of MM interventions for tobacco use met inclusion criteria. Intervention duration, intensity, and comparison conditions varied considerably. Studies used diverse comparators such as the American Lung Association's Freedom from Smoking (FFS) program, quitline counseling, interactive learning, or treatment as usual (TAU). Only one RCT was rated as good quality and reported power calculations indicating sufficient statistical power. Publication bias was detected. Overall, mindfulness meditation did not have significant effects on abstinence or cigarettes per day, relative to comparator groups. The small number of studies and heterogeneity in interventions, comparators, and outcomes precluded detecting systematic differences between adjunctive and monotherapy interventions. No serious adverse events were reported. Conclusions: MM did not differ significantly from comparator interventions in their effects on tobacco use. Low-quality evidence, variability in study design among the small number of existing studies, and publication bias suggest that additional, high-quality adequately powered RCTs should be conducted. (C) 2017 Elsevier Ltd. All rights reserved.
Mindfulness has been studied extensively in both basic and clinical settings; however, discussions still persist. The current research approached this issue by creating a new measure of trait mindfulness. The construct defined within is end-state mindfulness and is a tendency to see things as they are moment by moment without any judgment. The newly created scale was validated in three studies. End-state mindfulness was negatively correlated with rumination, suppression, neuroticism, and better-than-average effect, but was not correlated with both positive and negative trait-affectivity; it also moderated negative emotional reactions in the context of mortality salience. End-state mindfulness was differentiated from the past measure of mindfulness in many aspects. (C) 2016 Elsevier Ltd. All rights reserved.
This study investigated the association of mindfulness and racial socialization messages on approach-oriented coping strategies among African Americans. Three hundred African American college students completed measures of mindfulness, racial socialization, and coping strategy preference. The results revealed that a higher degree of mindfulness and culturally based racial socialization messages are positively associated with both planning and active coping strategies. The study also found that mindful observation was positively related to all of the minority and culturally based racial socialization messages. This research has discovered that racial socialization messages are related to mindfulness, suggesting that these two metacognitive self-regulatory strategies promote adaptive coping strategy selection and potentially buffer the negative consequences of stressors for African Americans. Stress-reduction programs that promote cultural pride and reinforcement as well as mindfulness techniques may be ideal for African Americans grappling with race-related stressors.
The mindful reappraisal hypothesis of the Mindfulness-to-Meaning Theory (Garland et al. in Psychol Inquiry 26(4):293-314, 2015a; Psychol Inquiry 26(4):377-387, 2015b) proposes that mindfulness generates eudaimonic well-being by promoting positive reappraisal, the positive psychological process through which stressful events are re-construed as benign, meaningful, or growth-promoting. To test this hypothesis, we examined prospective relations between state mindfulness and positive reappraisal in a community sample participating in a mindfulness-based intervention (MBI). At seven weekly time points throughout the MBI, participants (N = 234) engaged in a 10-min mindfulness meditation exercise at home and completed a measure of the degree of state mindfulness experienced during the meditation, as well as a measure of their use of positive reappraisal over the previous week. Support for the mindful reappraisal hypothesis of the Mindfulness-to-Meaning Theory was found: in latent growth curve and multivariate autoregressive latent trajectory models, increases in the trajectory of state mindfulness experienced during meditation were significantly and robustly associated with more frequent use of positive reappraisal over the course of participation in the 8 week-long MBI. Thus, mindfulness and reappraisal may reciprocally enhance one another as interdependent components of a positive feedback loop whose structure might be best described as an upward spiral.
Despite growing evidence in support of mindfulness as an underlying mechanism of mindfulness-based interventions (MBIs), it has been suggested that nonspecific therapeutic factors, such as the experience of social support, may contribute to the positive effects of MBIs. In the present study, we examined whether change in mindfulness and/or social support mediated the effect of Mindfulness-Based Cancer Recovery (MBCR) compared to another active intervention (i.e. Supportive Expressive Group Therapy (SET)), on change in mood disturbance, stress symptoms and quality of life. A secondary analysis was conducted of a multi-site randomized clinical trial investigating the impacts of MBCR and SET on distressed breast cancer survivors (MINDSET). We applied the causal steps approach with bootstrapping to test mediation, using pre- and post-intervention questionnaire data of the participants who were randomised to MBCR (n = 69) or SET (n = 70). MBCR participants improved significantly more on mood disturbance, stress symptoms and social support, but not on quality of life or mindfulness, compared to SET participants. Increased social support partially mediated the impact of MBCR versus SET on mood disturbance and stress symptoms. Because no group differences on mindfulness and quality of life were observed, no mediation analyses were performed on these variables. Findings showed that increased social support was related to more improvement in mood and stress after MBCR compared to support groups, whereas changes in mindfulness were not. This suggests a more important role for social support in enhancing outcomes in MBCR than previously thought.
Mindreading refers to the ability to attribute mental states, including thoughts, intentions and emotions, to oneself and others, and is essential for navigating the social world. Empirical mindreading research has predominantly featured children, groups with autism spectrum disorder and clinical samples, and many standard tasks suffer ceiling effects with neurologically typical (NT) adults. We first outline a case for studying mindreading in NT adults and proceed to review tests of emotion perception, cognitive and affective mentalizing, and multidimensional tasks combining these facets. We focus on selected examples of core experimental paradigms including emotion recognition tests, social vignettes, narrative fiction (prose and film) and participative interaction (in real and virtual worlds), highlighting challenges for studies with NT adult cohorts. We conclude that naturalistic, multidimensional approaches may be productively applied alongside traditional tasks to facilitate a more nuanced picture of mindreading in adulthood, and to ensure construct validity whilst remaining sensitive to variation at the upper echelons of the ability.
This paper investigates the distribution of intergranular forces within uncemented mine backfills using the discrete element method (DEM) and compares it with the existing analytical method. The virtual backfilling is modeled via the DEM to simulate the underground mining stopes backfilling with uncemented granular materials. Normal and shear forces of all particle contacts within the model backfill are tracked and analyzed with particular attention to the effect of sidewall friction. The DEM evaluates normal force chains and reveals a concentration of high forces within the model backfill. The DEM shows profiles of forces that are distinctly different from those obtained from analytical solutions. Quantitative analyses of the spatial distribution of forces, number of contact points, and changes in the orientation of forces are presented. The DEM demonstrates its capacity as a good tool for looking closely into the backfill on a particle scale. It highlights potential force distribution and concentration within a backfill and shows the limitations of analytical solutions, which helps engineers in the mining industry to better understand the possible mechanisms within backfill. (C) 2016 American Society of Civil Engineers.
Rural electrification rates in India lag behind government goals, in part due to the inability of distribution companies (discoms) to fund central grid expansion. In the absence of central grid electrification, mini-grids offer significant potential for an immediate pathway toward rural electrification and the attendant gains in economic growth and productivity. Yet private investment in mini-grids has been virtually absent in India. Using a comprehensive life-cycle cost analysis, we find that mini-grids based on solar PV power and storage are more economical than incumbent energy services available to households without central grid connection. Under current law, a prospective entrepreneur in India does not require a license or certification in order to build a mini-grid and subsequently provide electricity services in the area covered by said installation. Conversely, there is no legal or regulatory framework that specifies what is to happen if the central grid were to be extended to an area that is already covered by a mini-grid. We report detailed survey evidence from interviews with entrepreneurs, analysts and policymakers whose assessments converge on the same point: mini-grid investments would be jeopardized in the event of central grid extension, precisely because discoms would, by regulatory order, provide electricity services at highly subsidized rates, well below their full economic cost. Our fieldwork suggests that the threat of central grid extension is a gateway barrier preventing mini-grid development in India. The issues associated with the gateway barrier have common elements with the so-called holdup problem as identified in the economics of organizations. There have been two recent federal policy guidelines and one actual state-level policy addressing the regulatory status of mini-grids. We examine the effectiveness of these policies/proposals in terms of an entrepreneur's willingness to develop mini-grids in the future. (C) 2016 Elsevier Ltd. All rights reserved.
Research has consistently demonstrated that children living in low-income families, particularly those in poverty, are at a greater risk of child maltreatment: however, causal evidence for this relationship is sparse. We use child maltreatment reports from the National Child Abuse and Neglect Data System: Child File from 2004 to 2013 to investigate the relationship between changes in a state's minimum wage and changes in child maltreatment rates. We find that increases in the minimum wage lead to a decline in overall child maltreatment reports, particularly neglect reports. Specifically, a $1 increase in the minimum wage implies a statistically significant 9.6% decline in neglect reports. This decline is concentrated among young children (ages 0-5) and school-aged children (ages 6-12); the effect diminishes among adolescents and is not significant. We do not find that the effect of increases in the minimum wage varies based on the child's race. These findings are robust to a number of specifications. Our results suggest that policies that increase incomes of the working poor can improve children's welfare, especially younger children, quite substantially. (C) 2016 Elsevier Ltd. All rights reserved.
Purpose It is common to evaluate children who have sustained minor head trauma with computed tomography (CT) of the head. Scalp swelling, in particular, has been associated with intracranial injury. A subset of patients, however, present in delayed fashion, often days after the head trauma, as soft tissue edema progresses and their caregiver notices scalp swelling. We explore the value of further workup in this setting. Methods We conducted a retrospective review of a prospectively collected cohort of children <= 24 months of age presenting to the Texas Children's Hospital with scalp swelling more than 24 h following a head trauma. Cases were collected over a 2-year study period from June 1, 2014 to May 31, 2016. Results Seventy-six patients comprising 78 patient encounters were included in our study. The mean age at presentation was 8.8 months (range 3 days-24 months). All patients had noncontrast CT of the head as part of their evaluation by emergency medicine, as well as screening for nonaccidental trauma (NAT) by the Child Protection Team. The most common finding on CT head was a linear/nondisplaced skull fracture (SF) with associated extra-axial hemorrhage (epidural or subdural hematoma), which was found in 31/78 patient encounters (40%). Of all 78 patient encounters, 43 patients (55%) were discharged from the emergency room (ER), 17 patients (22%) were admitted for neurologic monitoring, and 18 patients (23%) were admitted solely to allow further NAT evaluation. Of those patients admitted, none experienced a neurologic decline and all had nonfocal neurologic exams on discharge. No patient returned to the ER in delayed fashion for a neurologic decline. Of all the patient encounters, no patient required surgery. Conclusions Pediatric patients <= 24 months of age presenting to the ER in delayed fashion with scalp swelling after minor head trauma-who were otherwise nonfocal on examination-did not require surgical intervention and did not experience any neurologic decline. Further radiographic investigation did not alter neurosurgical management in these patients; however, it should be noted that workup for child abuse and social care may have been influenced by CT findings, suggesting the need for the future development of a clinical decision-making tool to help safely avoid CT imaging in this setting.
Myocardial ischemic preconditioning up-regulated protein 1 (Mipu1) was cloned in our laboratory. Male Wistar rats were subjected to left anterior coronary artery ligation and sham-operation and sacrificed at 1 h, 3 h, 6 h, 12 h, 24 h, 3 d or 5 d after ligation. Expression of Mipu1 mRNA and protein were assessed by Northern blotting, real-time quantitative RT-PCR, In Situ hybridization and Western blotting. Expression of Mipu1 was up-regulated at 3 h and lasted to 12 h with a peak at 6 h. Mipu1 mRNA and protein signals express in the endothelium and myocardium in normal and infarcted heart, mainly in infarcted zone. Fluorescent immunocytochemistry showed that Mipu1 protein was localized to the nuclei of H9c2 myogenic cells and was upregulated after the cells being exposed to H2O2. These observations indicates that Mipu1 may play a role in maintaining vascular homeostasis and protecting the myogenic cells from being injured by ischemia-reperfusion or oxidation stress.
Background & Aims: miR-122 is the most abundant microRNA in the liver and regulates metabolic pathways including cholesterol biosynthesis, fatty acid synthesis, and oxidation. However, little is known about mechanisms that regulate the expression of miR-122 in the liver. The aim of this study was to identify key transcriptional regulators for miR-122 expression through intensively studying its primary transcript and promoter region. Methods: Bioinformatics analysis, Northern blotting, RT-PCR, and 5'/3' RACE were performed to analyze miR-122 primary transcript structure, its promoter region, and potential transacting factor binding sites. Reporter gene assays integrated with truncation and site-mutation in miR-122 promoter were performed to determine the trans-activation effect of HNF4 alpha to miR-122-promoter in vitro. ChIP and EMSA assays were performed to determine HNF4 alpha binding to miR-122 promoter. Finally, forced expression and RNAi were performed to verify the regulatory roles of HNF4 to miR-122 expression in vitro and in vivo. Results: Here, we show that miR-122 is processed from a long spliced primary transcript directed by a distal upstream promoter region conserved across species. We dissected this promoter region and identified putative binding sites for liver-enriched transcriptional factors that contribute to the regulation of miR-122 expression, including a putative binding site for hepatocyte nuclear factor 4 alpha (HNF4 alpha). We demonstrate that HNF4 alpha binds to the miR-122 promoter region through the conserved DR-I element. We observed the DR-1-element-dependent activation effect of HNF4 alpha on the conserved miR-122 promoter and the activation could be further enhanced by the addition of PGC1 alpha. Using overexpression and knockdown strategies, we show that HNF4 alpha positively regulates miR-122 expression in both Huh7 cells and the mouse liver. Conclusions: Our results suggest that HNF4 alpha is a key regulator of miR-122 expression in the liver. 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Background: MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth. Although many microRNAs were found to express in central nervous system (CNS), the role of the regulatory networks in which they are involved and their function in the pathological process of nerve cells are only just emerging. In the present study, the possible mechanisms by which one neuronal miRNAs, miR-125b, affected the growth of nervous cells were investigated using in vitro cell line model. Methods: The expression pattern of miR-125b in ATRA-treated human glioma cell lines was detected by Northern blotting and in situ localization. The effect of miR-125b on the proliferation and apoptosis of human glioma cells was analyzed by MTS assay, TUNEL and Flow cytometry analysis. In addition, the identification of target gene of miR-125b was studied by dual-luciferase activity assay and Immunoblot Analysis. Results: We found differential expression of miR-125b in 1.0 mu M all-trans-retinoic acid (ATRA)-treated human glioma cell lines. Up-regulation of miR-125b partially restored cell viability and inhibited cell apoptosis in U343 cells treated by ATRA. Down-regulation of miR125b decreased human glioma cells proliferation and enhanced the sensitivity of human glioma cells to ATRA-induced apoptosis. In addition, we found an inverse relationship between the expression of miR125b and the cell apoptosis-related protein Bcl-2 modifying factor (Bmf), and miR-125b can interact with 3'-untranslated region (UTR) of Bmf. Conclusion: These findings indicate that overexpression of miR125b promotes human glioma cell proliferation and inhibits ATRA-induced cell apoptosis and low expression of miR-125b sensitizes cells to ATRA-induced apoptosis. BMF may play an important role in the process of miR-125b influencing cell apoptosis. Copyright (C) 2009 S. Karger AG, Basel
miRNAs are non-coding RNA molecules typically 18-22 nucleotides long that can suppress the expression of their target genes. Several laboratories have attempted to identify miRNAs from the pig that are involved in Salmonella infection. These bioinformatics strategies using the newly available genomic sequence are generally successful. Here, we report an in silico identification of miRNAs in pig focusing on the Salmonella infection pathway, and further investigated the differential expression of those miRNAs by quantitative real-time PCR during pre- and post-natal stage of Salmonella inoculation from the peripheral blood of commercially breed pigs. We identified 29 miRNAs that have predicted targets in the Salmonella infection pathway and nine of them were not yet described in pig. In addition, the expression of nine selected miRNAs was validated in the peripheral blood by northern blotting. Through expression analyses, differences were found between pre- and post-natal stages of Salmonella inoculation for miR-221, miR-125b and miR-27b - all of them were suppressed 2 days after Salmonella inoculation. The predicted targets of those three miRNAs were validated by luciferase reporter assays. We show that FOS is a direct target of miR-221, miR-125b can suppress MAPK14, and miR-27b can target IFNG. These findings will be helpful in understanding the function and processing of these miRNAs in Salmonella infection. The miRNA differentially expressed in the peripheral blood of commercial breed pigs suggest that it can be used as genetic markers for salmonella infection resistance in pigs.
Malignant astrocytomas are the most common primary brain tumors. The critical characterizes of astrocyomas are their aggressive and infiltrative in the brain, which leads to uncontrollable by conventional forms of therapy. MicroRNAs are small RNAs that had been found to regulate their targets by specific binding to the 3'-untranslated region (3'UTR) of mRNA. Recent advances in understanding the molecular biology of these tumors have revealed that microRNA (miRNA) disruption may play important roles in the pathogenesis of astrocytomas. And some of the miRNA alterations were found in the serum of astrocytoma patients. In this study, we studied the expression profile of miR-128, in the different stages of astrocytoma tissues and two human astrocytoma cell lines, A172 and T98G cells. We found that the levels of miR-128 are decreased in the A172 and T98G cells when compared to normal human astrocyte (NHA). Furthermore, the levels of miR-128 decreased gradually to the pathological stages of astrocytomas. We also identified that TROVE2 is a novel target of miR-128 by the luciferase reporter system. Furthermore, the expression levels of TROVE2 are dramatically increased with the pathological stages increasing. Finally, the levels of TROVE2 are negatively correlated with miR-128 in astrocytoma tissues. Our data provided novel evidence for the miR-128 and TROVE2 in the development of human astrocytomas.
Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection.
Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing. Similarly, relatively little is known about the relationship of miR-140-5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in glioma progression. In this study, we found that miR-140-5p expression was significantly decreased in glioma tissues and in the glioma cell-lines U87 and U251 as compared with non-cancerous brain tissues by quantitative real-time polymerase chain reaction. In addition, miR-140-5p inhibited glioma cell proliferation and invasion and promoted glioma cell apoptosis both in vivo and in vitro. Interestingly, while the expression levels of miR-140-5p were higher in glioma cells, the messenger RNA or protein expression levels of vascular endothelial growth factor A and matrix metalloproteinase-2 were lower in glioma cells as determined by quantitative real-time polymerase chain reaction, western blot assay, and immunohistochemistry. By contrast, downregulation in the expression levels of miR-140-5p augmented the messenger RNA and protein expression levels of both vascular endothelial growth factor A and matrix metalloproteinase-2. These findings suggested that miR-140-5p inhibited glioma proliferation and invasion by regulating the vascular endothelial growth factor A/matrix metalloproteinase-2 signaling pathway both in vitro and in vivo.
Background: The Toll-like receptor 2 (TLR2)-driven tissue response may promote neoangiogenesis and tumour growth by mechanisms that are poorly understood. Methods: We investigated the expression levels of TLR2 and associated-miRNAs in colorectal carcinoma (CRC) tissues and cell lines using real-time PCR, northern blotting and western blotting. Survival curver was generated by Log-Rank test and the role of TLR2 signalling in tumour invasion and migration was determined by transwell analysis kits. Results: We observed that the tissues from CRC patients express relatively high levels of TLR2. Targeting TLR2 markedly reduces the invasion and migration of CRC cells. We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2. Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo. Conclusion: miR-143 blocks the TLR2 signalling pathway in human CRC cells. This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.
AIM To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer. METHODS The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells. RESULTS The expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3'-untranslated region (3'-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3'-UTR, and disruption of miR-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3'-UTR activity and disruption of miR-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemoresistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44. CONCLUSION miR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.
To secure the functionality of activated macrophages in the innate immune response, efficient life span control is required. Recognition of bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce the expression of cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis is scarce. To identify miRNAs differentially expressed in response to LPS, cDNA libraries from untreated and LPS-activated murine macrophages were analyzed by deep sequencing and regulated miRNA expression was verified by Northern blotting and qPCR. Employing TargetScan(TM) we identified CASPASE-3 (CASP-3) mRNA that encodes a key player in apoptosis as potential target of LPS-induced miR-155. LPS-dependent primary macrophage activation revealed TLR4-mediated enhancement of miR-155 expression and CASP-3 mRNA reduction. Endogenous CASP-3 and cleaved CASP-3 protein declined in LPS-activated macrophages. Accumulation of miR-155 and CASP-3 mRNA in miRNA-induced silencing complexes (miRISC) was demonstrated by ARGONAUTE 2 (AGO2) immunoprecipitation. Importantly, specific antagomir transfection effectively reduced mature miR-155 and resulted in significantly elevated CASP-3 mRNA levels in activated macrophages. In vitro translation assays demonstrated that the target site in the CASP-3 mRNA 3'UTR mediates miR-155-dependent Luciferase reporter mRNA destabilization. Strikingly, Annexin V staining of macrophages transfected with antagomir-155 and stimulated with LPS prior to staurosporine (SSP) treatment implied that LPS-induced miR-155 prevents apoptosis through CASP-3 mRNA down-regulation. In conclusion, we report that miR-155-mediated CASP-3 mRNA destabilization in LPS-activated RAW 264.7 macrophages suppresses apoptosis, as a prerequisite to maintain their crucial function in inflammation.
The aim of the present study was to evaluate the functions of miR-200c in the regulation of tumor growth and metastasis in renal cancer cells, and to investigate the underlying mechanisms. In this study, miR-200c was up- and downregulated in two renal cancer cell lines, namely ACHN and A498, and the proliferation, colony formation, migration and invasion of the cells were measured. The expression levels of various mRNAs and proteins were then analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. It was found that miR-200c suppressed proliferation, migration and invasion of the renal cancer cells and, conversely, the inhibition of endogenous miR-200c resulted in increased cell proliferation and metastasis. Furthermore, a luciferase reporter assay revealed that miR-200c directly targeted the 3 untranslated regions of the oncogenes B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) and E2F transcription factor 3 (E2F3) mRNAs, reduced the expression of Bmi-1 and E2F3 and regulated the expression of downstream genes, including E-cadherin, N-cadherin, vimentin, p14 and p16. These results indicate a tumor suppressor role for miR-200c in renal cancer cells via the direct targeting of Bmi-1 and E2F3.
MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498 associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in ESCC when compared with the nonneoplastic esophageal tissues (P < .05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared with the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reductions of cell proliferation, barrier penetration, and colony formation when compared with control and wild-type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC and in vitro analysis have confirmed the tumor suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC. (C) 2017 Elsevier Inc. All rights reserved.
Background: MicroRNAs are endogenously expressed, small non-coding RNAs that modulate gene expression by targeting specific mRNAs, resulting in translational repression or mRNA degradation. Although miR-584-5p has been reported to play a vital role in various malignancies, its role and the molecular mechanisms underlying the effects of miR-584-5p in gastric cancer (GC) remain to be clarified. In this study, we investigated the role of miR-584-5p in GC. Methods: The expression of miR-584-5p and its specific target gene were determined in human GC specimens and cell lines by microRNA real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR) and Western blot. The effects of miR-584-5p depletion or ectopic expression on GC proliferation were evaluated in vitro using CCK-8 proliferation assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assays and cell-cycle assays and the in vivo effects were investigated using a mouse tumorigenicity model. Cell apoptosis was evaluated by in vitro flow cytometric analysis, cell viability assays and in vivo TUNEL assays. Luciferase reporter assays were employed to identify interactions between miR-584-5p and its specific target gene. Results: A series of in vitro and in vivo gain-and loss-of-function assays revealed that miR-584-5p inhibited GC cell proliferation, while apoptosis was induced. Luciferase reporter assays and Western blot analysis revealed WWP1 to be a direct target of miR-584-5p. The effects of miR-584-5p-mimic were rescued by WWP1 overexpression. In contrast, the effects of the miR-584-5p-inhibitor were impaired by WWP1-shRNA. Furthermore, miR-584-5p expression levels correlated negatively with WWP1 protein expression in GC tissues and GC cell lines. A series of investigations indicated that miR-584-5p promoted senescence and activated the TGF beta signaling pathway by downregulation of WWP1. Conclusion: Taken together, these results suggest that downregulation of miR-584-5p contributes to tumor progression by downregulation of WWP1, thus, highlighting the potential of miR-584-5p as a therapeutic target for human GC.
Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for similar to 80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.
MicroRNAs (miRNAs) are short, similar to 22 nucleotide length RNAs that perform gene regulation. Recently, miRNA has been shown to be linked with the onset of cancer and other diseases based on miRNA expression levels. It is important, therefore, to understand miRNA function as it pertains to disease onset; however, in order to fully understand miRNA's role in a disease, it is necessary to detect the expression levels of these small molecules. The most widely used miRNA detection method is Northern blotting, which is considered as the standard of miRNA detection methods. This method, however, is time-consuming and has low sensitivity. This has led to an increase in the amount of detection methods available. These detection methods are either solid phase, occurring on a solid support, or solution phase, occurring in solution. While the solid-phase methods are adaptable to high-throughput screening and possess higher sensitivity than Northern blotting, they lack the ability for in vivo use and are often time-consuming. The solution-phase methods are advantageous in that they can be performed in vivo, are very sensitive, and are rapid; however, they cannot be applied in high-throughput settings. Although there are multiple detection methods available, including microarray technology, luminescence-based assays, electrochemical assays, etc., there is still much work to be done regarding miRNA detection. The current gaps of miRNA detection include the ability to perform multiplex, sensitive detection of miRNA with single-nucleotide specificity along with the standardization of these new methods. Current miRNA detection methods, gaps in these methods, miRNA therapeutic options, and the future outlook of miRNA detection are presented here.
Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21 and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126 and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-beta(2) expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell dedifferentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e and miR-200a expression were associated with shorter overall and disease-free survival in patients with esophageal adenocarcinoma; however, miR-16-2, miR-30e and miR-200a expression were not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.
The discovery and characterization of microRNAs (miRNAs) and other families of short RNAs has led to a rapid expansion of research directed at elucidating their expression patterns and regulatory functions. Here, we describe a convenient, sensitive, and straightforward method to detect and quantitate specific miRNA levels in unfractionated total RNA samples. The method, based on splinted ligation, does not require specialized equipment or any amplification step, and is significantly faster and more sensitive than Northern blotting. We demonstrate that the method can be used to detect various classes of small regulatory RNAs from different organisms.
microRNAs (miRNAs) are tiny ribo-regulatory molecules involved in various essential pathways for persistence of cellular life, such as development, environmental adaptation, and stress response. In recent years, miRNAs have become a major focus in molecular biology because of their functional and diagnostic importance. This interest in miRNA research has resulted in the development of many specific software and pipelines for the identification of miRNAs and their specific targets, which is the key for the elucidation of miRNA-modulated gene expression. While the well-recognized importance of miRNAs in clinical research pushed the emergence of many useful computational identification approaches in animals, available software and pipelines are fewer for plants. Additionally, existing approaches suffers from mis-identification and annotation of plant miRNAs since the miRNA mining process for plants is highly prone to false-positives, particularly in cereals which have a highly repetitive genome. Our group developed a homology-based in silico miRNA identification approach for plants, which utilizes two Perl scripts "SUmirFind" and "SUmirFold" and since then, this method helped identify many miRNAs particularly from crop species such as Triticum or Aegliops. Herein, we describe a comprehensive updated guideline by the implementation of two new scripts, "SUmirPredictor" and "SUmirLocator," and refinements to our previous method in order to identify genuine miRNAs with increased sensitivity in consideration of miRNA identification problems in plants. Recent updates enable our method to provide more reliable and precise results in an automated fashion in addition to solutions for elimination of most false-positive predictions, miRNA naming and miRNA mis-annotation. It also provides a comprehensive view to genome/transcriptome-wide location of miRNA precursors as well as their association with transposable elements. The "SUmirPredictor" and "SUmirLocator" scripts are freely available together with a reference high-confidence plant miRNA list.
The microRNAs (miRNAs) are an extensive class of small noncodin g RNAs (18-25 nucleotides) with important roles in the regulation of gene expression. Although a large number of miRNAs have been identified in a variety of eukaryotic systems, the function of the vast majority of these molecules remains unknown. To study the functions of miRNAs, it is crucial to determine their spatial and temporal expression patterns. Although there are some existing methods that can analyze the expression of miRNAs, it is not an easy task for routine gene-expression studies. In this study, we have established a simple method to detect the expression of mature miRNAs. Total RNA was polyadenylated by poly(A) polymerase, and then cDNA was synthesized by a specific reverse transcriptase (RT) primer and reverse transcriptase using the poly(A)-tailed total RNA as templates. The expression of several mature miRNAs was assayed by this method. The expression profile of two miRNAs, determined by the polymerase chain reaction (PCR) assay, was identical to that determined by Northern blotting. All these data show that the poly(A)-tailed RT-PCR is a convenient method to detect the expression of miRNAs.
MicroRNAs (miRNAs) are important modulators of gene expression in eukaryotic cells. However RNAs of the same size in bacteria have not been specifically discussed previously. Here, we provide a library of miRNA-size RNAs (msRNAs), which were registered by deep sequencing in Streptococcus mutans. Bioinformatic analysis of the whole set revealed more than 900 individual msRNA species. The cellular content of selected msRNAs was verified by quantitative RT-PCR and Northern blotting. The high abundance and discrete size of the subset of registered msRNAs suggest their functional significance, although the precise biological role of the RNA species revealed in S. mutans which is one of the principle causative agents of dental caries, has to be elucidated.
Development of a rapid and accurate quantification method for the detection of microRNAs (miRNAs) has been desired, in particular, when they are differently expressed in normal and pathological conditions. However, various methods for the quantification of small non-coding RNAs as well as miRNAs have been described. These methods mainly include hybridization-based approaches such as primer extension, northern blotting, microarray profiling, and reverse transcription (RT) PCR. Here, we developed a simple and rapid method based on stem-loop primer-based real-time PCR assay for sensitive and accurate detection of mature miRNAs. Initially, a miRNA-specific stem-loop RT primer is used for RT, which is followed by TaqMan real-time PCR assay using specific forward primer in combination with universal reverse primer and TaqMan probe. The assay has shown high sensitivity (a parts per thousand currency sign50 copies/reaction) for miRNA detection in two breast cancer cell lines, MCF-7 and MDA-MB-231. This assay might be implicated as a rapid and cost effective method for the detection of small non-coding RNAs.
Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor- (TGF-)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF--stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF- by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), -smooth muscle actin, and fibroblast-specific protein1 in TGF--treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF- through activation of SphK1. Furthermore, it was observed that TGF--stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR(2) also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF--stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR(2) siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF--induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis.
All interpersonal interactions are underpinned by action: perceiving and understanding the actions of others, and responding by planning and performing self-made actions. Perception of action, both self-made and observed, informs ongoing motor responses by iterative feedback within a perception-action loop. This fundamental phenomenon occurs within single-cells of the macaque brain which demonstrate sensory and motor response properties. These 'mirror' neurons have led to a swathe of research leading to the broadly accepted idea of a human mirror system. The current review examines the putative human mirror system literature to highlight several inconsistencies in comparison to the seminal macaque data, and ongoing controversies within human focused research (including mirror neuron origin and function). In particular, we will address the often-neglected other side to the 'mirror': complementary and opposing actions. We propose that engagement of the mirror system in meeting changing task-demands is dynamically modulated via frontal control networks. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The amygdala is known as a key brain region involved in the explicit and implicit processing of emotional faces, and plays a crucial role in salience detection. Not until recently was the mismatch negativity (MMN), a component of the event-related potentials to an odd stimulus in a sequence of stimuli, utilized as an index of preattentive salience detection of emotional voice processing. However, their relationship remains to be delineated. This study combined the fMRI scanning and event-related potential recording by examining amygdala reactivity in response to explicit and implicit (backward masked) perception of fearful and angry faces, along with recording MMN in response to the fearfully and angrily spoken syllables dada in healthy subjects who varied in trait anxiety (STAI-T). Results indicated that the amplitudes of fearful MMN were positively correlated with left amygdala reactivity to explicit perception of fear, but negatively correlated with right amygdala reactivity to implicit perception of fear. The fearful MMN predicted STAI-T along with left amygdala reactivity to explicit fear, whereas the association between fearful MMN and STAI-T was mediated by right amygdala reactivity to implicit fear. These findings suggest that amygdala reactivity in response to explicit and implicit threatening faces exhibits opposite associations with emotional MMN. In terms of emotional processing, MMN not only reflects preattentive saliency detection but also stands at the crossroads of explicit and implicit perception. Hum Brain Mapp 38:140-150, 2017. (c) 2016 Wiley Periodicals, Inc.
Significance: In the last years, metabolic reprogramming, fluctuations in bioenergetic fuels, and modulation of oxidative stress became new key hallmarks of tumor development. In cancer, elevated glucose uptake and high glycolytic rate, as a source of adenosine triphosphate, constitute a growth advantage for tumors. This represents the universally known Warburg effect, which gave rise to one major clinical application for detecting cancer cells using glucose analogs: the positron emission tomography scan imaging. Recent Advances: Glucose utilization and carbon sources in tumors are much more heterogeneous than initially thought. Indeed, new studies emerged and revealed a dual capacity of tumor cells for glycolytic and oxidative phosphorylation (OXPHOS) metabolism. OXPHOS metabolism, which relies predominantly on mitochondrial respiration, exhibits fine-tuned regulation of respiratory chain complexes and enhanced antioxidant response or detoxification capacity. Critical Issues: OXPHOS-dependent cancer cells use alternative oxidizable substrates, such as glutamine and fatty acids. The diversity of carbon substrates fueling neoplastic cells is indicative of metabolic heterogeneity, even within tumors sharing the same clinical diagnosis. Metabolic switch supports cancer cell stemness and their bioenergy-consuming functions, such as proliferation, survival, migration, and invasion. Moreover, reactive oxygen species-induced mitochondrial metabolism and nutrient availability are important for interaction with tumor microenvironment components. Carcinoma-associated fibroblasts and immune cells participate in the metabolic interplay with neoplastic cells. They collectively adapt in a dynamic manner to the metabolic needs of cancer cells, thus participating in tumorigenesis and resistance to treatments. Future Directions: Characterizing the reciprocal metabolic interplay between stromal, immune, and neoplastic cells will provide a better understanding of treatment resistance.
Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel mitopathogenic mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to - and likely will continue to enhance the progress of modem medicine. (C) 2016 The Authors. Published by Elsevier B.V.
Twin-arginine translocation (Tat) pathways have been well-characterized in bacteria and chloroplasts. Genes encoding a TatC protein are found in almost all plant mitochondrial genomes but to date these have not been extensively investigated. For the first time it could be demonstrated that this mitochondrial-encoded TatC is a functional gene that is translated into a protein in the model plant Arabidopsis thaliana. A TatB-like subunit localized to the inner membrane was also identified that is nuclear-encoded and is essential for plant growth and development, indicating that plants potentially require a Tat pathway for mitochondrial biogenesis.
Manganese superoxide dismutase (MnSOD) plays an important role in crustacean immune defense reaction by eliminating oxidative stress. Knowledge on MnSOD at molecular level allows us to understand its regulatory mechanism in crustacean immune system. A novel mitochondrial manganese superoxide dismutase (mMnSOD) was cloned from hepatopancreas of Chinese shrimp Fenneropenaeus chinensis by 3' and 5' rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA consists of 1185 bp with a 660 bp open reading frame, encoding 220 amino acids. The deduced amino acid sequence contains a putative signal peptide of 20 amino acids. Sequence comparison showed that the mMnSOD of F. chinensis shares 88% and 82% identity with that of giant freshwater prawn Macrobrachium rosenbergii and blue crab Callinectes sapidus, respectively. mMnSOD transcripts were detected in hepatopancreas, hemocytes, lymphoid organ, intestine, ovary, muscle and gill by Northern blotting. RT-PCR analysis indicated that mMnSOD showed different expression profiles in shrimp hemocytes and hepatopancreas after artificial infection with while spot syndrome virus (WSSV). In addition, a fusion protein containing mMnSOD was produced in vitro. LC-ESI-MS analysis showed that two peptide fragments (-GDVNTVISLAPALK- and -NVRPDYVNAIWK-) of the recombinant protein were identical to the corresponding sequence of M. rosenbergii mMnSOD, and the enzyme activity of the refolded recombinant protein was also measured. (c) 2006 Elsevier Ltd. All rights reserved.
The left ventricular hypertrophy (LVH) is one of the most important organ damage targets in hypertension. Despite the involvement of multiple factors, the genetic factors have been shown to have an important function in the pathogenesis of LVH. The aim of our study was to evaluate the role of mitochondria in LVH for Chinese hypertensives. A systematic and extended mutational screening for the mitochondrial genome has been initiated in a large cohort of Chinese population by the Geriatric Cardiology Clinic at the Chinese PLA General Hospital, Beijing, China. Specific mutations within the mitochondria were further evaluated. Changes of total RNAs (tRNAs) were measured by northern blotting using nonradioactive digoxigenin (DIG)-labeled oligodeoxynucleotides specific for each RNA. Rates of oxygen consumption in intact cells were determined with av YSI 5300 oxygraph. Sequence analysis of mitochondrial DNA in one Chinese pedigree identified a novel A-G transition at position 4401 (A4401G) at the junction of tRNA(Met) and tRNA(Gln). The noncoding region mutation appeared to affect the processing of precursors in these mitochondrial tRNAs. The reduction in the rate of respiration and marked decreases in the steady-state levels of tRNA(Met) and tRNA(Gln) were detected in the cells carrying this mutation. The novel mutation was absent in 270 Chinese control patients. In conclusion, the noncoding mitochondrial sequence alteration (A4401G) alters mitochondrial function, implicating this mutation in the pathogenesis of LVH in Chinese hypertensives.
Alteration of mitogen activated protein (MAP) kinase signaling in transgenic mice can ameliorate post-myocardial infarction (MI) remodeling. However, pre-existing changes in transgenic hearts and clinically unrealistic transgene expression likely affect the response to injury; it is unknown whether clinically relevant induction of transgene expression in an otherwise normal heart can yield similar benefits. Constitutively active MEK1 (aMEK1) or LacZ adeno-associated virus 9 (AAV9) vectors were injected into the left ventricular (LV) chambers of mice either just before or after coronary ligation. Hearts were evaluated via Western blot, quantitative polymerase chain reaction, histology, and echocardiography. AAV9-mediated aMEK1 delivery altered ERK1/2 expression/activation as in transgenic mice. Transgene expression was not immediately detectable but plateaued at 17 days, and therefore did not likely impact acute ischemia as it would in transgenics. With AAV9aMEK1 injection just prior to MI, robust expression in the infarct border zone during post-MI remodeling increased border zone wall thickness and reduced infarct size versus controls at 4 weeks, but did not induce global hypertrophy. Significant improvements in local and global LV function were observed, as were trends toward a preservation of LV volume. Delivery after ligation significantly lowered transgene expression in the infarct border zone and did not yield structural or functional benefits. The primary benefits observed in transgenic mice, ameliorated remodeling, and reduced chronic infarct size, were achievable via clinically relevant gene transfer of aMEK1, supporting ongoing translational efforts. Important differences, however, were observed, and consideration must be given to the timing and distribution of transgene delivery and expression. J. Cell. Biochem. 118: 775-784, 2017. (C) 2016 Wiley Periodicals, Inc.
In 1972, Sharp et al. described a new autoimmune rheumatic disease that they called MCTD, characterized by overlapping features of SSc, SLE, PM/DM, high levels of anti-U1snRNP and low steroid requirements with good prognosis. MCTD was proposed as a distinct disease. However, soon after the original description, questions about the existence of such a syndrome as well as disputes over the features initially described began to surface. The conundrum of whether MCTD is a distinct disease entity remains controversial. We undertook a literature review, focusing on the articles reporting new data about MCTD published in the last decade, to determine whether any new observations help to answer the conundrum of MCTD. After reviewing recent data, we question whether the term MCTD is appropriately retained, preferring to use the term undifferentiated autoimmune rheumatic disease.
Despite continued interest in the use of mixed OR/MS methods, limited attention has been paid in the literature to generic lessons that could be gained from mixing methods in practice. Many organisational problems demand the use of a mixed method approach and thus recognising and sharing lessons could prove beneficial to both practitioners and researchers. This paper reports on an in-depth evaluation of a case study involving risk identification and quantification of the Northern Isles New Energy Solutions (NINES) project which sought to trial and plan a new energy system. The intervention involved a mixed method approach and client feedback on the efficacy of the approach was sought. The evaluation reported in this paper is carried out using a set of themes taken from the literature and seeks to highlight transferable lessons. The set of lessons that emerge are presented along with their implications for both general OR modelling practice and the specific situation of mixing OR/MS methods. The paper concludes by discussing the implications of the work and directions for future work which will be of interest to both practitioners and researchers interested in mixed method OR/MS work. (C) 2016 Elsevier Ltd. All rights reserved.
This paper presents a design for a mixed-signal pulse width modulator (MSPWM) integrated circuit that targets the digital control of high-frequency switched-mode DC DC power supplies (SMPS). Previous designs consider digital pulse width modulators (DPWM) implementations that encounter important design issues, such as power consumption, non-linearity, layout dependency, trimming capability and temperature dependency. This work presents effective solutions, suitable for large-scale production of ICs, since it combines high-precision, high-linearity and temperature-independent standard analog circuits, which are commonly offered by the semiconductor industry, with the simplicity and reuse of digital PID compensation as input. The 8-bit prototype designed for a 0.18-mu m CMOS process operates at switching frequency of 2 MHz, draws only 96.25 mu A from a 1.8 V supply and takes 0.029 mm(2), including the non-overlapping control logic of SMPS power devices. (C) 2016 Elsevier B.V. All rights reserved.
Geotrichum candidum is a ubiquitous yeast and an essential component in the production of many soft cheeses. We developed a multilocus sequence typing (MLST) scheme with five retained loci (NUP116, URA1, URA3, SAPT4 and PLB3) which were sufficiently divergent to distinguish 40 sequence types (STs) among the 67G. candidum strains tested. Phylogenetic analyses defined five main clades; one clade was restricted to environmental isolates, three other clades included distinct environmental isolates and dairy strains, while the fifth clade comprised 34 strains (13 STs), among which all but two were isolated from milk, cheese or the dairy environment. These findings suggest an adaptation to the dairy ecosystems by a group of specialized European G. candidum strains. In addition, we developed a polymerase chain reaction inter-long terminal repeat scheme, a fast and reproducible random amplification of polymorphic DNA-like method for G. candidum, to type the closely related dairy strains, which could not be distinguished by MLST. Overall, our findings distinguished two types of dairy strains, one forming a homogeneous group with little genetic diversity, and the other more closely related to environmental isolates. Neither regional nor cheese specificity was observed in the dairy G. candidum strains analysed. This present study sheds light on the genetic diversity of both dairy and environmental strains of G. candidum and thus extends previous characterizations that have focused on the cheese isolates of this species. Copyright (c) 2016 John Wiley & Sons, Ltd.
Humans have a biological predisposition to form attachment to social partners. This attachment, however, is not restricted to humans: non-human and inanimate targets are often involved. People are increasingly engaged with their mobiles but whether their behaviour toward these devices can be regarded as an attachment behaviour has not yet been experimentally tested. Here we hypothesized the existence of mobile attachment. We expected people to seek the proximity of the mobile and give stress response upon separation from it, which manifests both at behavioural and physiological level. We also predicted that separation from the mobile should induce specific separation related emotions, which leads to increased attention to separation-related stimuli. We applied a version of the Strange Situation Test using a mobile phone, with behavioural, physiological, cognitive and self report measures, and the emotional Stroop test. Additionally, we constructed a questionnaire to self assess mobile attachment. Separation from the mobile induced behavioural and physiological stress, proximity seeking behaviour, and an attentional bias to separation-related stimuli for participants with higher mobile attachment. These effects were only observable when no other mobile was present. According to the questionnaire, secure base and safe haven are also relevant aspects of attachment to a mobile. These results support that humans form attachment toward their mobile which is similar to social attachment. This could emerge by cultural recycling of the attachment system's evolutionary structures. (C) 2017 Elsevier Ltd. All rights reserved.
The aim of this paper, is to propose a solution for the model adequacy verification in indirect adaptive control beside the classical known validation tests. The dynamic system that was selected to verify the proposed solution, is represented by a flexible transmission described by a complex four order model. Using the selected model adequacy index, it is studied the influence of the SPAB signal and perturbation amplitude on the model adequacy and control solution, for two different tracking performances selections. The proposed solution, comes to overcome the model validation problems encountered in real-time applications, with the main advantage of improving the model identification and control solutions.
Performance of any digital control scheme applied to inverters, or any other power electronic structures, can significantly suffer due to time delays. These time delays can be linear and nonlinear. An example of a linear delay is the delay due to sampling, control calculation and application of the new voltage state, which results in a constant delay present in each control cycle. An example of a non-linear delay is the inverter dead-time, which is different depending on the selected switching state and the direction of the load current. Both types of delays are well-known and are addressedin literature. At the same time, the known solutions result in significantly more complicated hardware and/or software implementations. Introduction of MPC to power electronics gives a new and unique opportunity to compensate for both types of the delays in a clear and effective way. This can be done by including the delays, both linear and non-linear, in the model predictions. As an illustration, this paper presents an MPC-based design of closed-loop current control with linear delay compensation for voltage source inverters. The paper also proposes a variable rate MPC-based voltage modulator which combines harmonic suppression with inverter dead-time compensation. The main points of the paper are illustrated by extensive simulation and experimenal results.
This paper is concerned with the problem of model reduction for neutral-type control system. For a given stable neutral-type control system, our attention is focused on the construction of a reduced-order model, which not only approximates the original system well in a robust performance but is also translated into a linear lower-dimensional system. Sufficient condition is proposed for the asymptotic stability with an error performance for the error system. Then, the model reduction problem is solved by using the projection approach, which casts the model reduction subject to linear matrix inequality constraints by employing the cone complementary linearization algorithm. Moreover, by further extending the results, model reduction with special structures is obtained, i.e., no neutral-type model. A numerical simulation example is provided to demonstrate the effectiveness and applicability of the proposed controller design approach.
Rice stripe tenuivirus (RSV) is a filamentous, negative-strand RNA virus causing severe diseases on rice in Asian countries. The viral particle is composed predominantly of a nucleocapsid protein (NP) and genomic RNA. However, the molecular details of how the RSV NP interacts with genomic RNA during particle assembly remain largely unknown. Here, we modeled the NP-RNA complex and show that polar amino acids within a predicted groove of NP are critical for RNA binding and protecting the RNA from RNase digestion. RSV NP formed pentamers, hexamers, heptamers, and octamers. By modeling the higher-order structures, we found that oligomer formation was driven by the N-terminal amino arm of the NP. Deletion of this arm abolished oligomerization; the N-terminally truncated NP was less able to interact with RNA and protect RNA than was the wild type. These findings afford valuable new insights into molecular mechanism of RSV NPs interacting with genomic RNA.
It is challenging yet desirable to quantitatively control the expression of a target gene in practice. We design a device-Proportional Biological Operational Mu-circuit (P-BOM) incorporating AND/OR gate and operational amplifier into one circuit and explore its behaviors through simulation. The results imply that will be possible to regulate input-output proportionally by manipulating the RBS of hrpR, hrpS, tetR and output gene and used in the sensing of environmental weak signals such as dioxins.
Gene promoters have variable repartition of AGCT nucleotides according to some probabilistic behaviours essentially depending on their position in a string. The paper aims to provide a model for this configuration. With this model we derive non-uniform confidence bounds for those probability distributions in the strings. A uniform bound deriving from previous works in Wu and Zhao [Inference of trends in time series. J R Stat Soc B. 2007; 69: 391-410] is more demanding for the model. A data-based study allows to clarify our suggestions and open the way for applications in molecular biology.
Petrochemical plants require the addition and removal of energy to and from the process and the movement of material to, from, and within the process piping and vessels. These fundamental mass and energy transfer requirements are typically achieved through the use of process utilities, which include electricity, steam, fuel gas, cooling water and compressed air. Utilities are responsible for a significant portion of the operating cost of a plant. Therefore, reduction in the consumption of utilities is a common process optimisation area. The situation is different when it comes to the generation and transportation of these utilities, which are often overlooked with regard to optimisation. In this paper, the potential benefits of utility optimisation are illustrated with particular focus on the generation and transportation areas. The main objectives are reductions in electrical energy consumption and cost and are illustrated for a dual circuit cooling water system. This system is non-linear and also hybrid in the sense that it contains both continuous and discrete input variables, which significantly complicates the design and implementation of control and optimisation solutions. This paper illustrates how the cost and energy consumption of a hybrid system can be reduced through the implementation of hybrid non-linear model predictive control (HNMPC) and economic HNMPC (EHNMPC). The results are compared to that of a base case and an Advanced Regulatory Control (ARC) case, showing that significant additional benefit may be achieved through the implementation of these advanced control and optimisation techniques. The paper further illustrates that additional capital is not necessarily required for the implementation of these techniques. (C) 2017 Elsevier Ltd. All rights reserved.
Prior studies have identified key factors that influence recycling intention. However, these studies rarely pay attention to the interaction of attitude and subjective norm that influences recycling intention. This study applied a conceptual model by extending the Theory of Planned Behavior (TPB) for addressing the gap. The study collected 246 responses through a street survey in Hong Kong. Findings revealed that two interaction terms (i.e., experiential attitude and subjective norm; instrumental attitude and subjective norm) influenced recycling intention. It implies that subjective norm plays a crucial role in motivating recycling behaviors. Moreover, subjective norm could increase the likelihood of recycling for people exhibiting positive experiential attitude, and motivate people who possess limited knowledge on recycling benefits of practicing recycling behaviors. Policy implications were drawn from the findings. Limitations of the study and future research direction were also discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Terms to be familiar with before you start to solve the test: chromatin, nucleases, sucrose density gradient centrifugation, melting point, gel electrophoresis, ethidium bromide, autoradiography, Southern blotting, Northern blotting, Sanger sequencing, restriction endonucleases, exonucleases, linker DNA, chloroform extraction, nucleosomes, nucleosomal histones, histone H1, nonhistone proteins, laminin, lamin, solenoid, DNA methylation, CpG islands, histone acetylation, centromere, histone octamers, "beads-on-a-string'', euchromatin, heterochromatin.
The aim of this study was to detect the IS900 region of Mycobacterium aoium subsp. paratuberculosis (MAP) in bovine milk samples using real-time polymerase chain reaction (qPCR) and conventional PCR, and to study the agreement between these tests. A total of 121 bovine milk samples were collected from herds considered positive for MAP, from the State of Pernambuco, Brazil. MAP DNA was detected in 20 samples (16.5%) using conventional PCR and in 34 samples (28.1%) using qPCR. MAP DNA was detected in all of the 6 animal farms studied. Moderate agreement was found between qPCR and conventional PCR results, where the sensitivity and specificity of conventional PCR in relation to qPCR were 50% and 96.6%, respectively. Thus, the IS900 region of MAP was found in bovine milk samples from the State of Pernambuco. To the best of our knowledge, this is the first report of MAP DNA found in bovine milk in Northeast Brazil. We also demonstrated the qPCR technique is more sensitive than conventional PCR with respect to detection of MAP in milk samples. (C) 2016 Published by Elsevier Editora Ltda.
The present study focuses on Cryptosporidium infections of foals in Brazil. A total of 92 animals of different breeds from 11 farms in the vicinity of Aracatuba in the state of Sao Paulo, were examined. According to PCR targeting the 18S rRNA gene, Cryptosporidium sp. DNA was detected in 21.7% (20/92) of foals. Good quality 18S rRNA, actin, HSP70 and gp60 genes nPCR amplicons were obtained from five fecal samples. PCR amplification and sequencing of a fragment of the GP60 sporozoite surface glycoprotein gene revealed C parvum genotypes IIaAl8G3R1, lIaAl5G2R1. Interestingly, we also detected in two foals a GP60 genotype related to the human parasite C. hominis. (C) 2016 Elsevier B.V. All rights reserved.
Methylation of cytosine bases (5-methylcytosine, 5mC) occurring in vertebrate genomes is usually associated with transcriptional silencing. 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are the recently discovered modified cytosine bases produced by enzymatic oxidation of 5mC, whose biological functions remain relatively obscure. A number of approaches ranging from biochemical to antibody based techniques have been employed to study the genomic distribution and global content of these modifications in various biological systems. Although some of these approaches can be useful for quantitative assessment of these modified forms of 5mC, most of these methods do not provide any spatial information regarding the distribution of these DNA modifications in different cell types, required for correct understanding of their functional roles. Here we present a highly sensitive method for immunochemical detection of the modified forms of cytosine. This method permits co-detection of these epigenetic marks with protein lineage markers and can be employed to study their nuclear localization, thus, contributing to deciphering their potential biological roles in different experimental contexts.
The canonical set of amino acids leads to an exceptionally wide range of protein functionality. Nevertheless, the set of residues still imposes limitations on potential protein applications. The incorporation of noncanonical amino acids can enlarge this scope. There are two complementary approaches for the incorporation of noncanonical amino acids. For site-specific incorporation, in addition to the endogenous canonical translational machineries, an orthogonal aminoacyl-tRNA-synthetase-tRNA pair must be provided that does not interact with the canonical ones. Consequently, a codon that is not assigned to a canonical amino acid, usually a stop codon, is also required. This genetic code expansion enables the incorporation of a noncanonical amino acid at a single, given site within the protein. The here presented work describes residue-specific incorporation where the genetic code is reassigned within the endogenous translational system. The translation machinery accepts the noncanonical amino acid as a surrogate to incorporate it at canonically prescribed locations, i.e., all occurrences of a canonical amino acid in the protein are replaced by the noncanonical one. The incorporation of noncanonical amino acids can change the protein structure, causing considerably modified physical and chemical properties. Noncanonical amino acid analogs often act as cell growth inhibitors for expression hosts since they modify endogenous proteins, limiting in vivo protein production. In vivo incorporation of toxic noncanonical amino acids into proteins remains particularly challenging. Here, a cell-free approach for a complete replacement of L-arginine by the noncanonical amino acid L-canavanine is presented. It circumvents the inherent difficulties of in vivo expression. Additionally, a protocol to prepare target proteins for mass spectral analysis is included. It is shown that L-lysine can be replaced by L-hydroxy-lysine, albeit with lower efficiency. In principle, any noncanonical amino acid analog can be incorporated using the presented method as long as the endogenous in vitro translation system recognizes it.
The recent development of a high-throughput single-cell assay technique enables the screening of novel enzymes based on functional activities from a large-scale metagenomic library(1). We previously proposed a genetic enzyme screening system (GESS) that uses dimethylphenol regulator activated by phenol or p-nitrophenol. Since a vast amount of natural enzymatic reactions produce these phenolic compounds from phenol deriving substrates, this single genetic screening system can be theoretically applied to screen over 200 different enzymes in the BRENDA database. Despite the general applicability of GESS, applying the screening process requires a specific procedure to reach the maximum flow cytometry signals. Here, we detail the developed screening process, which includes metagenome preprocessing with GESS and the operation of a flow cytometry sorter. Three different phenolic substrates (p-nitrophenyl acetate, p-nitrophenyl-beta-D-cellobioside, and phenyl phosphate) with GESS were used to screen and to identify three different enzymes (lipase, cellulase, and alkaline phosphatase), respectively. The selected metagenomic enzyme activities were confirmed only with the flow cytometry but DNA sequencing and diverse in vitro analysis can be used for further gene identification.
FINA, filtration isolation of nucleic acids, is a novel extraction method which utilizes vertical filtration via a separation membrane and absorbent pad to extract cellular DNA from whole blood in less than 2 min. The blood specimen is treated with detergent, mixed briefly and applied by pipet to the separation membrane. The lysate wicks into the blotting pad due to capillary action, capturing the genomic DNA on the surface of the separation membrane. The extracted DNA is retained on the membrane during a simple wash step wherein PCR inhibitors are wicked into the absorbent blotting pad. The membrane containing the entrapped DNA is then added to the PCR reaction without further purification. This simple method does not require laboratory equipment and can be easily implemented with inexpensive laboratory supplies. Here we describe a protocol for highly sensitive detection and quantitation of HIV-1 proviral DNA from 100 mu l whole blood as a model for early infant diagnosis of HIV that could readily be adapted to other genetic targets.
Imaging of Frster resonance energy transfer (FRET) is a powerful tool for examining cell biology in real-time. Studies utilizing FRET commonly employ two-dimensional (2D) culture, which does not mimic the three-dimensional (3D) cellular microenvironment. A method to perform quenched emission FRET imaging using conventional widefield epifluorescence microscopy of cells within a 3D hydrogel environment is presented. Here an analysis method for ratiometric FRET probes that yields linear ratios over the probe activation range is described. Measurement of intracellular cyclic adenosine monophosphate (cAMP) levels is demonstrated in chondrocytes under forskolin stimulation using a probe for EPAC1 activation (ICUE1) and the ability to detect differences in cAMP signaling dependent on hydrogel material type, herein a photocrosslinking hydrogel (PC-gel, polyethylene glycol dimethacrylate) and a thermoresponsive hydrogel (TR-gel). Compared with 2D FRET methods, this method requires little additional work. Laboratories already utilizing FRET imaging in 2D can easily adopt this method to perform cellular studies in a 3D microenvironment. It can further be applied to high throughput drug screening in engineered 3D microtissues. Additionally, it is compatible with other forms of FRET imaging, such as anisotropy measurement and fluorescence lifetime imaging (FLIM), and with advanced microscopy platforms using confocal, pulsed, or modulated illumination.
RNA sequencing (RNAseq) is a versatile method that can be utilized to detect and characterize gene expression, mutations, gene fusions, and noncoding RNAs. Standard RNAseq requires 30 - 100 million sequencing reads and can include multiple RNA products such as mRNA and noncoding RNAs. We demonstrate how targeted RNAseq (capture) permits a focused study on selected RNA products using a desktop sequencer. RNAseq capture can characterize unannotated, low, or transiently expressed transcripts that may otherwise be missed using traditional RNAseq methods. Here we describe the extraction of RNA from cell lines, ribosomal RNA depletion, cDNA synthesis, preparation of barcoded libraries, hybridization and capture of targeted transcripts and multiplex sequencing on a desktop sequencer. We also outline the computational analysis pipeline, which includes quality control assessment, alignment, fusion detection, gene expression quantification and identification of single nucleotide variants. This assay allows for targeted transcript sequencing to characterize gene expression, gene fusions, and mutations.
Telomere is a ribonucleoprotein structure that protects chromosomal ends from aberrant fusion and degradation. Telomere length is maintained by telomerase or an alternative pathway, known as alternative lengthening of telomeres (ALT)(1). Recently, C. elegans has emerged as a multicellular model organism for the study of telomere and ALT(2). Visualization of repetitive sequences in the genome is critical in understanding the biology of telomeres. While telomere length can be measured by telomere restriction fragment assay or quantitative PCR, these methods only provide the averaged telomere length. On the contrary, fluorescence in situ hybridization (FISH) can provide the information of the individual telomeres in cells. Here, we provide protocols and representative results of the method to determine telomere length of C. elegans by fluorescent in situ hybridization. This method provides a simple, but powerful, in situ procedure that does not cause noticeable damage to morphology. By using fluorescently labeled peptide nucleic acid (PNA) and digoxigenin-dUTP-labeled probe, we were able to visualize two different repetitive sequences: telomere repeats and template of ALT (TALT) in C. elegans embryos and gonads.
Cellular processes such as mitosis and cell differentiation are governed by changes in cell shape that largely rely on proper remodeling of the cell cytoskeletal structures. This involves the assembly-disassembly of higher-order macromolecular structures at a given time and location, a process that is particularly sensitive to perturbations caused by overexpression of proteins. Methods that can preserve protein homeostasis and maintain near-to-normal cellular morphology are highly desirable to determine the functional contribution of a protein of interest in a wide range of cellular processes. Transient depletion-rescue experiments based on RNA interference are powerful approaches to analyzeprotein functions and structural requirements. However, reintroduction of the target protein with minimum deviation from its physiological level is a real challenge. Here we describe a method termed adenofection that was developed to study the role of molecular chaperones and partners in the normal operation of dividing cells and the relationship with actin remodeling. HeLa cells were depleted of BAG3 with siRNA duplexes targeting the 3'UTR region. GFP-tagged BAG3 proteins were reintroduced simultaneously into >75% of the cells using recombinant adenoviruses coupled to transfection reagents. Adenofection enabled to express BAG3-GFP proteins at near physiological levels in HeLa cells depleted of BAG3, in the absence of a stress response. No effect was observed on the levels of endogenous Heat Shock Protein chaperones, the main stressinducible regulators of protein homeostasis. Furthermore, by adding baculoviruses driving the expression of fluorescent markers at the time of cell transduction-transfection, we could dissect mitotic cell dynamics by time-lapse microscopic analyses with minimum perturbation of normal mitotic progression. Adenofection is applicable also to hard-to-infect mouse cells, and suitable for functional analyses of myoblast differentiation into myotubes. Thus adenofection provides a versatile method to perform structure-function analyses of proteins involved in sensitive biological processes that rely on higher-order cytoskeletal dynamics.
Forster resonance energy transfer (FRET)-based studies have become increasingly common in the investigation of GPCR signaling. Our research group developed an intra-molecular FRET sensor to detect the interaction between Ga subunits and GPCRs in live cells following agonist stimulation. Here, we detail the protocol for detecting changes in FRET between the beta 2-adrenergic receptor and the Gas C-terminus peptide upon treatment with 100 mu M isoproterenol hydrochloride as previously characterized1. Our FRET sensor is a single polypeptide consisting serially of a full-length GPCR, a FRET acceptor fluorophore (mCitrine), an ER/K SPASM (systematic protein affinity strength modulation) linker, a FRET donor fluorophore (mCerulean), and a Ga C-terminal peptide. This protocol will detail cell preparation, transfection conditions, equipment setup, assay execution, and data analysis. This experimental design detects small changes in FRET indicative of proteinprotein interactions, and can also be used to compare the strength of interaction across ligands and GPCR-G protein pairings. To enhance the signal-to-noise in our measurements, this protocol requires heightened precision in all steps, and is presented here to enable reproducible execution.
Green fluorescent protein (GFP) and its variants are widely used tools for studying protein localization and dynamics of events such as cytoskeletal remodeling and vesicular trafficking in living cells. Quantitative methodologies using chimeric GFP fusions have been developed for many applications; however, GFP is somewhat resistant to proteolysis, thus its fluorescence persists in the lysosome/vacuole, which can impede quantification of cargo trafficking in the endocytic pathway. An alternative method for quantifying endocytosis and post-endocytic trafficking events makes use of superecliptic pHluorin, a pH-sensitive variant of GFP that is quenched in acidic environments. Chimeric fusion of pHluorin to the cytoplasmic tail of transmembrane cargo proteins results in a dampening of fluorescence upon incorporation of the cargo into multivesicular bodies (MVBs) and delivery to the lysosome/vacuole lumen. Thus, quenching of vacuolar fluorescence facilitates quantification of endocytosis and early events in the endocytic pathway. This paper describes methods using pHluorin-tagged cargos for quantification of endocytosis via fluorescence microscopy, as well as population-based assays using flow cytometry.
Caspases are the key mediators of apoptotic cell death via their proteolytic activity. When caspases are activated in cells to levels detectable by available technologies, apoptosis is generally assumed to occur shortly thereafter. Caspases can cleave many functional and structural components to cause rapid and complete cell destruction within a few minutes. However, accumulating evidence indicates that in normal healthy cells the same caspases have other functions, presumably at lower enzymatic levels. Studies of non-apoptotic caspase activity have been hampered by difficulties with detecting low levels of caspase activity and with tracking ultimate cell fate in vivo. Here, we illustrate the use of an ultrasensitive caspase reporter, CaspaseTracker, which permanently labels cells that have experienced caspase activity in whole animals. This in vivo dual color CaspaseTracker biosensor for Drosophila melanogaster transiently expresses red fluorescent protein (RFP) to indicate recent or on-going caspase activity, and permanently expresses green fluorescent protein (GFP) in cells that have experienced caspase activity at any time in the past yet did not die. Importantly, this caspase-dependent in vivo biosensor readily reveals the presence of non-apoptotic caspase activity in the tissues of organ systems throughout the adult fly. This is demonstrated using whole mount dissections of individual flies to detect biosensor activity in healthy cells throughout the brain, gut, malpighian tubules, cardia, ovary ducts and other tissues. CaspaseTracker detects non-apoptotic caspase activity in long-lived cells, as biosensor activity is detected in adult neurons and in other tissues at least 10 days after caspase activation. This biosensor serves as an important tool to uncover the roles and molecular mechanisms of non-apoptotic caspase activity in live animals.
Structural interactions between the endoplasmic reticular (ER) and mitochondrial membranes, in domains known as mitochondria-associated membranes (MAM), are crucial hubs for cellular signaling and cell fate. Particularly, these inter-organelle contact sites allow the transfer of calcium from the ER to mitochondria through the voltage-dependent anion channel (VDAC)/glucose-regulated protein 75 (GRP75)/inositol 1,4,5triphosphate receptor (IP3R) calcium channeling complex. While this subcellular compartment is under intense investigation in both physiological and pathological conditions, no simple and sensitive method exists to quantify the endogenous amount of ER-mitochondria contact in cells. Similarly, MAMs are highly dynamic structures, and there is no suitable approach to follow modifications of ER-mitochondria interactions without protein overexpression. Here, we report an optimized protocol based on the use of an in situ proximity ligation assay to visualize and quantify endogenous ER-mitochondria interactions in fixed cells by using the close proximity between proteins of the outer mitochondrial membrane (VDAC1) and of the ER membrane (IP3R1) at the MAM interface. Similar in situ proximity ligation experiments can also be performed with the GRP75/IP3R1 and cyclophilin D/IP3R1 pairs of antibodies. This assay provides several advantages over other imaging procedures, as it is highly specific, sensitive, and suitable to multiple-condition testing. Therefore, the use of this in situ proximity ligation assay should be helpful to better understand the physiological regulations of ER-mitochondria interactions, as well as their role in pathological contexts.
With this method, consecutive cryosections are collected to enable both microscopy applications for tissue histology and enrichment of RNA for gene expression using adjacent regions from a single mouse skeletal muscle. Typically, it is challenging to achieve adequate homogenization of small skeletal muscle samples because buffer volumes may be too low for efficient grinding applications, yet without sufficient mechanical disruption, the dense tissue architecture of muscle limits penetration of buffer reagents, ultimately causing low RNA yield. By following the protocol reported here, 30 mu m sections are collected and pooled allowing cryosectioning and subsequent needle homogenization to mechanically disrupt the muscle, increasing the surface area exposed for buffer penetration. The primary limitations of the technique are that it requires a cryostat, and it is relatively low throughput. However, high-quality RNA can be obtained from small samples of pooled muscle cryosections, making this method accessible for many different skeletal muscles and other tissues. Furthermore, this technique enables matched analyses (e.g., tissue histopathology and gene expression) from adjacent regions of a single skeletal muscle so that measurements can be directly compared across applications to reduce experimental uncertainty and to reduce replicative animal experiments necessary to source a small tissue for multiple applications.
Optogenetic tools allow isolated, functional investigations of almost any signaling molecule within complex signaling pathways. A major obstacle is the controlled delivery of light to the cell sample and hence the most popular tools for optogenetic studies are microscopy-based cell analyses and in vitro experiments. The flow cytometer has major advantages over a microscope, including the ability to rapidly measure thousands of cells at single cell resolution. However, it is not yet widely used in optogenetics. Here, we present a device that combines the power of optogenetics and flow cytometry: the LED Thermo Flow. This device illuminates cells at specific wavelengths, light intensities and temperatures during flow cytometric measurements. It can be built at low cost and be used with most common flow cytometers. To demonstrate its utility, we characterized the photoswitching kinetics of Dronpa proteins in vivo and in real time. This protocol can be adapted to almost all optically controlled substances and substantially expands the set of possible experiments. More importantly, it will greatly simplify the discovery and development of new optogenetic tools.
Multi-protein complexes, rather than single proteins acting in isolation, often govern molecular pathways regulating cellular homeostasis. Based on this principle, the purification of critical proteins required for the functioning of these pathways along with their native interacting partners has not only allowed the mapping of the protein constituents of these pathways, but has also provided a deeper understanding of how these proteins coordinate to regulate these pathways. Within this context, understanding a protein's spatiotemporal localization and its protein-protein interaction network can aid in defining its role within a pathway, as well as how its misregulation may lead to disease pathogenesis. To address this need, several approaches for protein purification such as tandem affinity purification (TAP) and localization and affinity purification (LAP) have been designed and used successfully. Nevertheless, in order to apply these approaches to pathway-scale proteomic analyses, these strategies must be supplemented with modern technological developments in cloning and mammalian stable cell line generation. Here, we describe a method for generating LAP-tagged human inducible stable cell lines for investigating protein subcellular localization and protein-protein interaction networks. This approach has been successfully applied to the dissection of multiple cellular pathways including cell division and is compatible with high-throughput proteomic analyses.
The Xenopus oocyte as a heterologous expression system for proteins, was first described by Gurdon et al.(1) and has been widely used since its discovery (References 2 - 3, and references therein). A characteristic that makes the oocyte attractive for foreign channel expression is the poor abundance of endogenous ion channels(4). This expression system has proven useful for the characterization of many proteins, among them ligand-gated ion channels. The expression of GABA(A) receptors in Xenopus oocytes and their functional characterization is described here, including the isolation of oocytes, microinjections with cRNA, the removal of follicular cell layers, and fast solution changes in electrophysiological experiments. The procedures were optimized in this laboratory(5),(6) and deviate from the ones routinely used(7-9). Traditionally, denuded oocytes are prepared with a prolonged collagenase treatment of ovary lobes at RT, and these denuded oocytes are microinjected with mRNA. Using the optimized methods, diverse membrane proteins have been expressed and studied with this system, such as recombinant GABAA receptors(10-12), human recombinant chloride channels(13), Trypanosome potassium channels(14), and a myo-inositol transporter(15),(16). The methods detailed here may be applied to the expression of any protein of choice in Xenopus oocytes, and the rapid solution change can be used to study other ligand-gated ion channels.
Nitric Oxide (NO center dot) is a small radical, which mediates multiple important cellular functions in mammals, bacteria and plants. Despite the existence of a large number of methods for detecting NO center dot in vivo and in vitro, the real-time monitoring of NO center dot at the single-cell level is very challenging. The physiological or pathological effects of NO center dot are determined by the actual concentration and dwell time of this radical. Accordingly, methods that allow the single-cell detection of NO center dot are highly desirable. Recently, we expanded the pallet of NO center dot indicators by introducing single fluorescent protein-based genetically encoded nitric oxide (NO center dot) probes (geNOps) that directly respond to cellular NO center dot fluctuations and, hence, addresses this need. Here we demonstrate the usage of geNOps to assess intracellular NO center dot signals in response to two different chemical NO center dot liberating molecules. Our results also confirm that freshly prepared 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC-7) has a much higher potential to evoke change in intracellular NO center dot levels as compared with the inorganic NO center dot donor sodium nitroprusside (SNP). Furthermore, dual-color live-cell imaging using the green geNOps (G-geNOp) and the chemical Ca2+ indicator fura-2 was performed to visualize the tight regulation of Ca2+ -dependent NO center dot formation in single endothelial cells. These representative experiments demonstrate that geNOps are suitable tools to investigate the real-time generation and degradation of single-cell NO center dot signals in diverse experimental setups.
Live-cell imaging is used to simultaneously capture time-lapse images of angiotensin type 1a receptors (AT1aR) and intracellular compartments in transfected human embryonic kidney-293 (HEK) cells following stimulation with angiotensin II ( Ang II). HEK cells are transiently transfected with plasmid DNA containing AT(1a)R tagged with enhanced green fluorescent protein (EGFP). Lysosomes are identified with a red fluorescent dye. Live-cell images are captured on a laser scanning confocal microscope after Ang II stimulation and analyzed by software in three dimensions (3D, voxels) over time. Live-cell imaging enables investigations into receptor trafficking and avoids confounds associated with fixation, and in particular, the loss or artefactual displacement of EGFP-tagged membrane receptors. Thus, as individual cells are tracked through time, the subcellular localization of receptors can be imaged and measured. Images must be acquired sufficiently rapidly to capture rapid vesicle movement. Yet, at faster imaging speeds, the number of photons collected is reduced. Compromises must also be made in the selection of imaging parameters like voxel size in order to gain imaging speed. Significant applications of live-cell imaging are to study protein trafficking, migration, proliferation, cell cycle, apoptosis, autophagy and protein-protein interaction and dynamics, to name but a few.
The last decades have witnessed the explosion of scientific interest around gene expression control mechanisms at the RNA level. This branch of molecular biology has been greatly fueled by the discovery of noncoding RNAs as major players in post-transcriptional regulation. Such a revolutionary perspective has been accompanied and triggered by the development of powerful technologies for profiling short RNAs expression, both at the high-throughput level (genome-wide identification) or as single-candidate analysis (steady state accumulation of specific species). Although several state-of-art strategies are currently available for dosing or visualizing such fleeing molecules, Northern Blot assay remains the eligible approach in molecular biology for immediate and accurate evaluation of RNA expression. It represents a first step toward the application of more sophisticated, costly technologies and, in many cases, remains a preferential method to easily gain insights into RNA biology. Here we overview an efficient protocol (Enhanced Northern Blot) for detecting weakly expressed microRNAs (or other small regulatory RNA species) from Drosophila melanogaster whole embryos, manually dissected larval/adult tissues or in vitro cultured cells. A very limited amount of RNA is required and the use of material from flow cytometry-isolated cells can be also envisaged.
The use of the ligninolytic fungi Trametes versicolor for the degradation of micropollutants has been widely studied. However, few studies have addressed the treatment of real wastewater containing pharmaceutically active compounds (PhAC) under non-sterile conditions. The main drawback of performing such treatments is the difficulty for the inoculated fungus to successfully compete with the other microorganisms growing in the bioreactor. Id the present study, several fungal treatments were performed under non-sterile conditions in continuous operational mode with two types of real wastewater effluent, namely, a reverse osmosis concentrate (ROC) from a wastewater treatment plant and a veterinary hospital wastewater (VHW). In all cases, the setup consisted of two parallel reactors: one inoculated with T. versicolor and one non-inoculated, which was used as the control. The main objective of this work was to correlate the operational conditions and traditional monitoring parameters, such as laccase activity, with PhAC removal and the composition of the microbial communities developed inside the bioreactors. For that purpose a variety of biochemical and molecular biology analyses were performed: phospholipid fatty acids analysis (PLFA), quantitative PCR (qPCR) and denaturing gradient gel electrophoresis (DGGE) followed by sequencing. The results show that many indigenous fungi (and not only bacteria, which were the focus of the majority of previously published research) can successfully compete with the inoculated fungi (i.e., Trichoderma asperellum overtook T. versicolor in the ROC treatment). We also showed that the wastewater origin and the operational conditions had a stronger impact on the diversity of microbial communities developed in the bioreactors than the inoculation or not with T. versicolor. (C) 2016 Elsevier B.V. All. rights reserved.
The aims were to evaluate the levels of bacterial species in saliva and in situ and to assess whether the design of brackets influences the risk of developing periodontal disease. Twenty patients (13.3 mean age) were bonded with self-ligating brackets and a conventional bracket. Saliva was collected before bonding and 30 and 60 days after bonding. One sample of each bracket was removed 30 and 60 days after bonding. The analysis was determined by checkerboard DNA-DNA hybridization. The data was evaluated by the non-parametric test. A significant increase in the levels of bacterial species in the saliva occurred in 15 of the 22 analyzed species. The self-ligating brackets presented the highest incidence percentages for the orange and red complexes 60 days after bonding. In situ analyses showed different patterns according to the bracket design. The levels of Campylobacter rectus showed significant differences (p = 0.011) 60 days after bonding among the three brackets; the highest values were observed in the In-OvationA (R) R bracket. The bracket design seems to influence the levels of bacterial species involved in periodontal disease. Considering the wide variety of bacterial species, additional studies are needed to aid in the establishment of effective protocols to prevent the development of periodontal disease during orthodontic treatment. A dynamic alteration in the oral microbiota may lead to inflammatory reactions in the supporting soft and hard tissues. The different types of brackets interfere with bacterial adherence. Bracket design should be considered in orthodontic treatment.
Background: Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. Material/Methods: We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. Results: We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. Conclusions: Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese.
Microparasites play an important role in the demography, ecology and evolution of Pacific salmonids. As salmon stocks continue to decline and the impacts of global climate change on fish populations become apparent, a greater understanding of microparasites in wild salmon populations is warranted. We used high-throughput, quantitative PCR (HT-qRT-PCR) to rapidly screen 82 adult Chinook salmon from five geographically or genetically distinct groups (mostly returning to tributaries of the Fraser River) for 45 microparasite taxa. We detected 20 microparasite species, four of which have not previously been documented in Chinook salmon, and four of which have not been previously detected in any salmonids in the Fraser River. Comparisons of microparasite load to blood plasma variables revealed some positive associations between Flavobacterium psychrophilum, Cryptobia salmositica and Ceratonova shasta and physiological indices suggestive of morbidity. We include a comparison of our findings for each microparasite taxa with previous knowledge of its distribution in British Columbia.
Purpose of the Review In this review, we will discuss the basic fundamentals of how to perform molecular imaging to better understand the underlyingmechanisms contributing to cardiovascular disease. Report Findings Molecular imaging combines molecular biology with in vivo imaging. Molecular probes are used to target discrete biological processes such as cell death, inflammation, and angiogenesis. These probes emit signals that are detected by traditional imaging systems. Because the same disease processes can manifest in individuals in different ways, molecular imaging may emerge as an important strategy for delivering precision medicine. Summary Molecular imaging is a powerful tool that may help physicians provide more personalized care in the near future.
Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: (1) the development of new statistical methods to address etiologic heterogeneity; (2) the enhancement of causal inference; (3) the identification of previously unknown exposure-subtype disease associations; and (4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields.
Autopsy, histology and cytology have been and histology and cytology still are the main diagnostic tools in surgical pathology. During the last two decades molecular biology gradually has extended the diagnostic armamentarium. In tumor pathology molecular biology techniques are used to diagnose and subclassify tumors, predict response to therapies and identify therapeutic targets. Molecular pathology has evolved into a novel focus of clinical pathology and transforms the historically morphology based discipline. Traditional pathology and molecular pathology combine and guide tumor therapy.
Introduction: Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace.Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy.Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.
The aim of this study was to characterize the ways of spreading of the most common bacterial species isolated from workers as well as from the air and raw materials at the workplaces in power plant utilizing biomass sources. To monitor microbial transmission and identify the source of contamination in the working environment, a combination of molecular and biochemical methods was applied. The study was carried out at workplaces in power plant utilizes biomass as a main fuel source. At each of the studied workplaces, bioaerosol particles were collected on sterile Teflon filters using personal conical inhalable samplers (CIS), and biomass samples (straw pellets and briquettes, corn briquettes, sunflower pellets and wood chips) were directly taken from their storage places. Simultaneously with that, the swab samples from the hands of ten workers and their used respiratory masks (of FFP2 class) were also collected after the work shift to evaluate individual workers' microbial contamination. In all collected samples, total bacterial concentrations were assessed and the most common microbial isolates were identified to the species level using both biochemical (API tests) and molecular polymerase chain reaction (PCR), followed by random amplification of polymorphic DNA (RAPD) typing methods. The mean concentrations of culturable bacteria in the air and in biomass samples at the studied workplaces were high, i.e. 1.2 x 10(6)cfu/m(3) and 3.8 x 10(4)cfu/g, respectively. The number of bacteria in the swab and mask samples also reached a high level of 1.4 x 10(4) cfu/ml and 1.9 x 10(3) cfu/cm(2), respectively. Among the most frequently isolated microorganisms from all types of samples were Gram-positive bacteria of the genus Bacillus and Staphylococcus xylosus. 37 bacterial strains belonging to the genus Bacillus (B. licheniformis 8, B. pumilus 15 and B. subtilis 4) and Staphylococcus (10) were genotyped by the RAPD-PCR method. Based on RAPD-PCR analyses, the genomic similarity among 19 Bacillus strains isolated from biomass, air, protective mask and hand samples as well as 6 S. xylosus strains isolated from air, mask and hand samples exceeded 80%. This study demonstrated that biomass is the primary source of bacteria at power plant workplaces. These results also revealed that biomass-associated bacteria can be easily transferred to workers' hands and mask during their routine activities. To improve health protection at the workplaces, adequate training courses on hand hygiene and how to use and remove respiratory masks correctly for workers should be introduced as a key element of the prevention strategy. From the occupational point of view, the PCR-based methods seem to be an efficient tool for a fast and precise typing of bacterial strains isolated from different sources in the occupational environment. Such methods may help to implement appropriate prophylactic procedures and minimize transmission of infectious agents at workplaces.
Biomineralogy is an inherently interdisciplinary pursuit. This largely stems from the fact that techniques used to investigate a given (bio)mineral should ideally be married with techniques that provide insight into the biological mechanisms that form that mineral (and vice versa). We observe two broad challenges that inhibit a fluent exchange of ideas and information between mineralogists/materials scientists and biologists. First, the smorgasbord of emerging and rapidly evolving techniques available to mineralogists and biologists alike make it difficult not only for an expert to remain contemporary, but can be bewildering to the non-expert. Second, to truly integrate and relate a specific biological insight into the genesis of a biomineral, with the effect that insight has on the properties of the mineral itself, is not trivial. We propose that an evolutionary developmental biology (evo-devo) approach can not only address this challenge, it can also provide deep insight into how the rich diversity of metazoan mineralised structures evolved. While an evo-devo approach to biomineralogy has previously been employed by some groups, recent exciting methodological developments available to the molecular biologist now make this strategy even more attractive. In this short review we aim to outline our perception of the role that evo-devo can play within the field of biomineralogy, taking as a case study the past achievements, recent insights and some future research directions associated with gastropod shell formation. (C) 2016 Elsevier Inc. All rights reserved.
Objective To obtain the full-length cDNA of a novel gene (named yp05) associated with citrinin production-related genes in Monascus aurantiacus. Methods Total RNA was extracted from mycelium, 3' and 5' cDNA end of yp05 gene was amplified using smart (TM) trace cDNA amplification kit, and the full-length cDNA of a novel gene (named yp05) was obtained from the electronic assembly of 3'-RACE and 5'-RACE products. Results This yp05 gene was 787 bp including a 597 bp open reading frame (ORF) and encoded a deduced protein with 199 amino acid residues, and the amino acid sequence of this protein was found similar with the sequences of many fungal manganese-superoxide dismutases in the GenBank with the aid of BLASTp. The transcription of yp05 gene in Monascus strains was analyzed with the aid of Northern blotting. The transcription of yp05 gene was only detected in Monascus strains, provided that citrinin was produced. Conclusion The transcription of yp05 gene belongs to differential expression genes of citrinin yielded from Monascus and has no correlation with the biosynthesis pathway of red pigments.
Although traditional economic models posit that money is fungible, psychological research abounds with examples that deviate from this assumption. Across eight experiments, we provide evidence that people construe physical currency as carrying traces of its moral history. In Experiments 1 and 2, people report being less likely to want money with negative moral history (i.e., stolen money). Experiments 3-5 provide evidence against an alternative account that people's judgments merely reflect beliefs about the consequences of accepting stolen money rather than moral sensitivity. Experiment 6 examines whether an aversion to stolen money may reflect contamination concerns, and Experiment 7 indicates that people report they would donate stolen money, thereby counteracting its negative history with a positive act. Finally, Experiment 8 demonstrates that, even in their recall of actual events, people report a reduced tendency to accept tainted money. Altogether, these findings suggest a robust tendency to evaluate money based on its moral history, even though it is designed to participate in exchanges that effectively erase its origins.
A three year old girl was observed to have bluish marks on her back, arms and legs. The social services initiated an examination on the local hospital, but no conclusion regarding the marks was reached. The girl was institutionalized before a forensic examination after three days concluded that the marks were Mongolian spots. The case stresses the importance of being able to distinguish between Mongolian spots and skin hematomas and the need for a genuine clinical forensic examination in cases where child abuse is suspected. A guide for distinguishing between Mongolian spots and skin hematomas is presented.
Electrochemical monitoring-on-chip (E-MoC)-based approach for rapid assessment of human immunodeficiency virus (HIV)-infection in the presence of cocaine (Coc) and specific drugs namely i.e., tenofovir (Tef), rimcazole (RA) is demonstrated here, for the first time, using electrochemical impedance spectroscopy (EIS). An in-vitro primary human astrocytes (HA) model was developed using a cultureware chip (CC, used for E-MoC) for HIV-infection, Coc exposure and treatment with anti-HIV drug i.e., Tef, and Coc antagonist i.e., RA. The charge transfer resistance (R-ct) value of each CC well varies with respect to infection and treatment demonstrated highly responsive sensitivity of developed chip. The results of E-MoC, a proof-of-the concept, suggested that HIV-infection progression due to Coc ingestion and therapeutic effects of highly specific drugs are measurable on the basis of cell electrophysiology. Though, this work needs various molecular biology-based optimizations to promote this technology as an analytical tool for the rapid assessment of HIV-infection in a patient to manage HIV diseases for timely diagnosis. The presented study is based on using CNS cells and efforts are being made to perform this method using peripheral cells such as monocytes derived dendritic cells. (C) 2016 Elsevier B.V. All rights reserved.
Development of bioinspired devices for energy-efficient computing requires numerical models that can reproduce the global electrical behavior of neurons. We present herein a stochastic model based on the Monte Carlo technique that can reproduce the steady state and the action potential in neurons in terms of the probabilities for different ions to cross the cell membrane. Gating channels for sodium and potassium cations and leakage channels are taken into account following the Hodgkin-Huxley equations in a first stage. We then expand the model to include the time-dependent ion concentrations in the intra- and extracellular space and the related Nernst potentials, and the existence of ion pumps to equilibrate the steady-state currents. The model allows monitoring of the random passage of ions across a biological membrane, and thus includes the influence of ion shot noise. For small membrane areas, results evidence that, when considered alone, shot noise has a discernible effect on spiking in a wide range of excitation currents, not only by leading to the onset of spikes but also by inhibiting their appearance.
In this paper we present a mechanistic model that integrates subneuronal structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain. We also argue that subtle changes in the composition of the membrane's fatty acids may lead to down-stream effects causing dysregulation of the membrane, cytoskeleton and their interface. Such exquisite sensitivity to minor changes is known to occur in physical systems undergoing phase transitions, the simplest and most studied of them is the so-called Ising model, which exhibits a phase transition at a finite temperature between an ordered and disordered state in 2- or 3-dimensional space. We propose this model in the context of neuronal dynamics and further hypothesize that it may involve quantum degrees of freedom dependent upon variation in membrane domains associated with ion channels or microtubules. Finally, we provide a link between these physical characteristics of the dynamical mechanism to psychiatric disorders such as major depression and antidepressant action.
The mechanisms by which childhood socioeconomic status (CSES) affects adult mental health, general health, and well-being are not clear. Moreover, the analytical assumptions employed when assessing mediation in social and psychiatric epidemiology are rarely explained. The aim of this paper was to explain the intermediate confounding assumption, and to quantify differential recall bias in the association between CSES, childhood abuse, and mental health (SCL-10), general health (EQ-5D), and subjective well-being (SWLS). Furthermore, we assessed the mediating role of psychological and physical abuse in the association between CSES and mental health, general health, and well-being; and the influence of differential recall bias in the estimation of total effects, direct effects, and proportion of mediated effects. The assumptions employed when assessing mediation are explained with reference to a causal diagram. Poisson regression models (relative risk, RR and 99% CIs) were used to assess the association between CSES and psychological and physical abuse in childhood. Mediation analysis (difference method) was used to assess the indirect effect of CSES (through psychological and physical abuse in childhood) on mental health, general health, and well-being. Exposure (CSES) was measured at two time points. Mediation was assessed with both cross-sectional and longitudinal data. Psychological abuse and physical abuse mediated the association between CSES and adult mental health, general health, and well-being (616% among men and 714% among women, p < 0.001). The results suggest that up to 27% of the association between CSES and childhood abuse, 23% of the association between childhood abuse, and adult mental health, general health, and well-being, and 44% of the association between CSES and adult mental health, general health, and well-being is driven by differential recall bias. Assessing mediation with cross-sectional data (exposure, mediator, and outcome measured at the same time) showed that the total effects and direct effects were vastly overestimated (biased upwards). Consequently, the proportion of mediated effects were underestimated (biased downwards). If there is a true (unobserved) direct or indirect effect, and the direction of the differential recall bias is predictable, then the results of cross-sectional analyses should be discussed in light of that.
Dopamine levels in the brain influence emotional experiences and empathic responses to others' misfortune. Inspired by roles of Catechol-O-methyltransferase (COMT) in dopamine degradation and the link between moral judgment and empathic responses, this study investigated to what extent the Va1158Met polymorphism of COMTgene contributes to individual differences in moral permissibility and empathic dispositions. One thousand two hundred and seventy-two Chinese Han college students, who were differentiated with the COMT Va1158Met (rs4680) polymorphism, rated permissibility of harm in moral dilemmas and scored their empathic dispositions with Interpersonal Reactivity Index. The results showed a significant association between COMTVa1158Met and the moral permissibility of committing harm. Individuals with the Val/Val genotype, which is associated with lower levels of dopamine, endorsed impersonal harm as more impermissible than those with the Val/Met and Met/Met genotypes. Results also showed that individuals with the Val/Val genotype showed higher empathic concern for others' misfortune. The findings provide the first evidence for the link between COMT gene and the moral permissibility, highlighting the roles of dopamine in social cognition. (C) 2016 Elsevier Ltd. All rights reserved.
Objective: There is increasing recognition that socio-cognitive skills, such as moral reasoning (MR), are affected in a wide range of developmental and neuropsychological conditions. However, the lack of appropriate measures available to neuropsychologists poses a challenge for the direct assessment of these skills. This study sought to explore age-related changes in MR using an innovative visual tool and examine the developmental sensitivity of the task. Method: To address some of the methodological limitations of traditional measures of MR, a novel, visual task, the Socio-Moral Reasoning Aptitude Level (So-Moral), was used to evaluate MR in 216 healthy participants aged 6-20years. Results: The findings show a linear increase in MR from childhood to late adolescence with significant group differences between childhood (6-8years) and preadolescence (9-11years), and between early adolescence (12-14years) and middle adolescence (15-17years). Conclusions: Interpreted in light of current brain development research, the results highlight age-related changes in MR that offer insight into typical MR development and opportunities for comparisons with clinical populations. The findings also provide evidence of the potential of the So-Moral as a developmentally appropriate measure of MR throughout childhood and adolescence.
Neuroscientific evidence indicates that human social functioning is supported by a distributed network of frontal and temporal brain regions that undergoes significant development during childhood and adolescence. Clinical studies of individuals with early brain insults (EBI) to frontotemporal regions suggest that such lesions may interfere with the maturation of sociocognitive skills and lead to increased sociobehavioural problems. However, little attention has focussed on the direct assessment of sociocognitive skills, such as moral reasoning, following focal EBI. In the present study, the performance of 15 patients with focal EBI (8-16 years) was compared to that of 15 demographically matched controls on basic neuropsychological measures (IQ and executive functions), sociocognitive tasks (moral reasoning, moral decision-making and empathy) and parent reports of sociobehavioural problems and social adaptive skills. Patients with focal EBI had significantly lower levels of moral reasoning maturity, moral decision-making, and empathy than their matched controls, but did not differ on more general measures of cognition. Their parents also reported increased sociobehavioural problems. These findings suggest that focal EBI to frontotemporal regions can result in reduced sociocognitive capacities, more specifically moral reasoning, and increased vulnerability to sociobehavioural problems.
Implicit moral evaluations i.e., immediate, unintentional assessments of the wrongness of actions or persons play a central role in supporting moral behavior in everyday life. Yet little research has employed methods that rigorously measure individual differences in implicit moral evaluations. In five experiments, we develop a new sequential priming measure the Moral Categorization Task and a multinomial model that decomposes judgment on this task into multiple component processes. These include implicit moral evaluations of moral transgression primes (Unintentional Judgment), accurate moral judgments about target actions (Intentional judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Speeded response deadlines reduced Intentional Judgment but not Unintentional Judgment (Experiment 1). Unintentional Judgment was stronger toward moral transgression primes than non-moral negative primes (Experiments 2-4). Intentional Judgment was associated with increased error-related negativity, a neurophysiological indicator of behavioral control (Experiment 4). Finally, people who voted for an anti-gay marriage amendment had stronger Unintentional Judgment toward gay marriage primes (Experiment 5). Across Experiments 1-4, implicit moral evaluations converged with moral personality: Unintentional Judgment about wrong primes, but not negative primes, was negatively associated with psychopathic tendencies and positively associated with moral identity and guilt proneness. Theoretical and practical applications of formal modeling for moral psychology are discussed. (C) 2016 Elsevier B.V. All rights reserved.
Recent research has demonstrated impairments in social cognition associated with multiple sclerosis (MS). The present work asks whether these impairments are associated with atypical moral judgment. Specifically, we assessed whether MS patients are able to integrate information about intentions and outcomes for moral judgment (i.e., appropriateness and punishment judgments) in the case of third-party acts. We found a complex pattern of moral judgments in MS patients: although their moral judgments were comparable to controls' for specific types of acts (e.g., accidental or intentional harms), they nevertheless judged behaviors to be less appropriate and endorsed more severe punishment across the board, and they were also more likely to report that others' responses would be congruent with theirs. Further analyses suggested that elevated levels of externally oriented cognition in MS (due to co-occurring alexithymia) explain these effects. Additionally, we found that the distinction between appropriateness and punishment judgments, whereby harmful outcomes influence punishment judgments to a greater extent than appropriateness judgments, was preserved in MS despite the observed disruptions in the affective and motivational components of empathy. The current results inform the two-process model for intent-based moral judgments as well as possible strategies for improving the quality of life in MS patients.
AIM: To clone Delta(12)-fatty acid desaturase gene of Moltierella isabellina and to functionally characterize this gene in vitro and In vivo. METHODS: Reverse transcriptional polymerase chain reaction (RT-PCR) was used to clone the open reading frame of Delta(12)-fatty acid desaturase gene (D12D) of Mortierella isabellina. Plasmids pEMICL12 and pYMICL12 were constructed with it. pEMICL12 was transformed into Escherichia coli (E. coll) strain BL21 using CaCl2 method for expression after induction with IPTG. pTMICL12 was transformed into Saccharomyces cerevisiae strain IN-VSc1 using lithium acetate method for expression under the induction of galactose. Northern blotting method was used to investigate the effect of temperature on the transcriptional level of this gene in S. cerevisiae strain IN-VSc1. RESULTS: Recombinant plasmids pEMICL12 and pTMICL12 were successfully constructed and transformed into E. coli and S. cerevisiae separately with appropriate method. After induction with IPTG and galactose, it was found that expression of Delta(12)-fatty acid desaturase genes in E. coli and S. cerevisiae under appropriate conditions led to the production of active Delta(12)-fatty acid desaturase, which could convert 17.876% and 17.604% of oleic acid respectively to linoleic acid by GC-MS detection in vitro and in vivo. CONCLUSION: Cloning and expression of M. isabellina D12D gene in E. coli and S. cerevisiae is successfully completed. (C) 2006 The WJG Press. All rights reserved.
This paper presents an integrated bandgap reference circuit which is addressing low current consumption and a wide supply voltage range, using a current mode structure. Embedded in a sophisticated Power Management Unit (PMU) for a GNSS receiver, this bandgap reference has an output of 0.60 V and it can reach a temperature coefficient of 33 ppm/degrees C in the range from -40 degrees C to 125 degrees C. With a 1.4 V supply voltage, the power is only 3.5 mu W and the PSRR is 57 dB at DC frequency. Occupying 0.125 mm(2) chip area, this bandgap reference has been implemented in the CMOS 28 nm technology from Globalfoundries and successfully validated in the lab.
In this paper a CMOS operational amplifier is presented. A CMOS operational amplifier is presented here which is operating at 2V power supply and 1microamp input bias current at 0.8micrometer technology using nonconventional mode of MOS transistors and whose input is dependent on bias current. The unique behavior of the MOS transistors in sub threshold region allows a designer to work at low input bias current. It also allows operating at low voltage. While operating the device at weak inversion results low power dissipation but dynamic range is degraded. Optimum balance between power dissipation and dynamic range results when the MOS transistors are operated at moderate inversion. In comparison with the reported low power, low voltage op-amps at 0.8micrometer technology, this op-amp has very low standby power consumption with a high driving capability and operated at low voltage. operating the device in moderate version is a good solution. Also operating the device in sub threshold region not only allows lower power dissipation but also a lower voltage operation is achieved. The proposed op-amp is a simple two stage single ended op-amp. The input stage of the op-amp is a differential amplifier with an NMOS pair. Operational Amplifiers, or Opa-mps as they are more commonly called, are one of the basic building blocks of Analogue Electronic Circuits. Operational amplifiers are linear devices that have all the properties required for nearly ideal DC amplification and are therefore used extensively in signal conditioning, filtering or to perform mathematical operations such as add, subtract, integration and differentiation.
Moso bamboo is characterized by infrequent sexual reproduction and erratic flowering habit; however, the molecular biology of flower formation and development is not well studied in this species. We studied the molecular regulation mechanisms of moso bamboo development and flowering by selecting three key regulatory pathways: plant-pathogen interaction, plant hormone signal transduction and protein processing in endoplasmic reticulum at different stages of flowering in moso bamboo. We selected PheDof1, PheMADS14 and six microRNAs involved in the three pathways through KEGG pathway and cluster analysis. Subcellular localization, transcriptional activation, Western blotting, insitu hybridization and qRT-PCR were used to further investigate the expression patterns and regulatory roles of pivotal genes at different flower development stages. Differential expression patterns showed that PheDof1, PheMADS14 and six miRNAs may play vital regulatory roles in flower development and floral transition in moso bamboo. Our research paves way for further studies on metabolic regulatory networks and provides insight into the molecular regulation mechanisms of moso bamboo flowering and senescence.
Recent theoretical models suggest that repetitive negative thinking might be a key mechanism explaining the negative effects of maternal psychopathology on mother-infant relations. While an emerging body of research largely supports this idea, the relative importance of differences in the trajectory of repetitive negative thinking during and after pregnancy for mother-infant bonding as well as maternal depressive symptoms is currently unknown. Therefore, we investigated associations between the course of maternal repetitive negative thinking during pregnancy and after birth and mother-infant-bonding and maternal depressive symptoms in a longitudinal study. The overall level of repetitive negative thinking was a significant predictor of mother-infant bonding, maternal anxiety and rejection in dealing with her infant four months after birth. Furthermore, differences in the trajectory of repetitive negative thinking predicted bonding, but not anxiety or rejection. The overall levels of repetitive negative thinking as well as the differences in the trajectory of repetitive negative thinking were significant predictors of maternal depressive symptoms. These findings indicate that changes of repetitive negative thinking during and after pregnancy can increase the risk of postpartum depressive symptoms.
Observers frequently form impressions of other people based on complex or conflicting information. Rather than being objective, these impressions are often biased by observers' motives. For instance, observers often downplay negative information they learn about ingroup members. Here, we characterize the neural systems associated with biased impression formation. Participants learned positive and negative information about ingroup and outgroup social targets. Following this information, participants worsened their impressions of outgroup, but not ingroup, targets. This tendency was associated with a failure to engage neural structures including lateral prefrontal cortex, dorsal anterior cingulate cortex, temporoparietal junction, Insula and Precuneus when processing negative information about ingroup (but not outgroup) targets. To the extent that participants engaged these regions while learning negative information about ingroup members, they exhibited less ingroup bias in their impressions. These data are consistent with a model of 'effortless bias', under which perceivers fail to process goal-inconsistent information in order to maintain desired conclusions.
When reflecting on the nature of skilled action, it is easy to fall into familiar dichotomies such that one construes the flexibility and intelligence of skill at the level of intentional states while characterizing the automatic motor processes that constitute motor skill execution as learned but fixed, invariant, bottom-up, brute-causal responses. In this essay, I will argue that this picture of skilled, automatic, motor processes is overly simplistic. Specifically, I will argue that an adequate account of the learned motor routines that constitute embodied skills cannot be given in a purely bottom-up, brute-causal fashion. Rather, motor control is intelligent all the way down. To establish this, I will first review two recent accounts of skill, Stanley and Krakauer (Front Hum Neurosci, 2013. doi and Papineau (R Inst Philos Suppl 73:175-196, 2013), which characterize the automatic motor control responsible for the fine-grained movements constitutive of motor skill as brute, low-level phenomena. I will then isolate five key features that should apply to skilled motor control, if these accounts are correct. Together, the accounts posit that motor control is: (1) ballistic, (2) invariant, (3) independent of general action trajectories, (4) Insensitive to semantic content, and (5) independent of personal-level intentions. In the final section of this paper, I will appeal to optimal control theory for empirical evidence to challenge the commitment to skilled action as qualified by the above features.
This paper proposes an induction motor drive control method which uses a minimal number of sensors, providing only DC-link current as a feedback signal. The improved DC-link current sampling scheme and modified asymmetrical switching pattern cancel the characteristic waveform errors which exist in all three reconstructed motor line-currents. Motor line-current harmonic content is reduced to an acceptable level, eliminating torque and speed oscillations which were inherent for conventional single sensor drives. Consequently, the use of single current sensor and line-current reconstruction technique is no longer acceptable only for low and medium performance drives, but also for the drives where obtaining a highly accurate, stable, and fast response is the priority. The proposed control algorithm is validated using induction motor drive hardware prototype based on TMS320F2812 digital signal processor.
Background: Speech and language impairments are well-established in individuals with amyotrophic lateral sclerosis (ALS). However, knowledge about particular aspects of social communication and everyday conversational abilities is limited. Aims: To investigate self- and informant-report ratings of social communicative abilities in ALS participants and matched healthy controls. Methods & Procedures: Thirty-two participants with ALS and 24 controls completed the La Trobe Communication Questionnaire (LCQ). Participants nominated a close other to provide an informant report on the LCQ. Demographic and clinical information was also collected. Outcomes & Results: Informant ratings indicated greater difficulties in conversational initiation, effectiveness and partner sensitivity for ALS participants compared with controls. ALS participants did not rate their social communicative abilities as poorer than controls and self- reports only differed from informant ratings in the control group. LCQ scores were not significantly correlated with clinical/functional variables. Conclusions & Implications: Social communication can be reduced in ALS and individuals may lack insight into these difficulties. In order to understand and provide targeted interventions for such difficulties, clinical speech and language assessment should incorporate social communication assessment, including both a self- and informant report format.
Mott cells are atypical plasmacytes recognized microscopically by endoplasmic reticulum (ER) distensions (Russell bodies) a result of retained secretory product (antibody). Originally associated with parasitism, they are observed in a broad spectrum of immunopathology, sometimes involving hypergammaglobulinemia. Few descriptions of Mott cells appear in avian literature. The purpose of the manuscript is to provide examples identified by light microscopy in three poultry species. Transmission electron micrographs (TEM) of plasmacytes from the turkey oviduct mucosa are included for comparison with Mott cell light microscopic images. Wright's stained blood and bone marrow from commercial and specific pathogen free (SPF) chickens, ducks, and turkeys are the sources. Mott cell positive samples commonly occurred with leukocytosis or leukemoid reactions, polymicrobial bacteremia, and fungemia. Atypical granulocytes and leukocytes regularly accompanied Mott cells. It is proposed that circulating Mott cells are "sentinels" indicative of stress, dyscrasia, and pathology. Moreover, Mott cells, like other atypia, complicate the interpretation of simple heterophil/lymphocyte (H/L) ratios. As Mott cells are defective plasmacytes these observations address hematology, immunology, pathology, and welfare issues.
The effect of frequent protein malnutrition on liver function has not been intensively examined. Thus, the effects of alternating 5 days of a protein and amino acid-free diet followed by 5 days of a complete diet repeated three times (3 PFD-CD) on female mouse liver were examined. The expression of carbonic anhydrase III (CAIII), fatty acid synthase (FAS), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glutathione S-transferase P1 (GSTP1) in liver were assessed by proteomics, reverse transcriptase-polymerase chain reaction and Northern blotting. The activities of liver GSTs, glutathione reductase (GR) and catalase (CAT), as well as serum glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were also tested. Additionally, oxidative damage was examined by measuring of protein carbonylation and lipid peroxidation. Liver histology was examined by light and electron microscopy. Compared with control mice, 3 PFD-CD increased the content of FAS protein (+90%) and FAS mRNA (+30%), while the levels of CAIII and CAIII mRNAs were decreased (-48% and -64%, respectively). In addition, 3 PFD-CD did not significantly change the content of GSTP1 but produced an increase in its mRNA level (+20%), while it decreased the activities of both CAT (-66%) and GSTs (-26%). After 3 PFD-CD, liver protein carbonylation and lipid peroxidation were increased by +55% and +95%, respectively. In serum, 3 PFD-CD increased the activities of both SGOT (+30%) and SGPT (+61%). In addition, 3 PFD-CD showed a histological pattern characteristic of hepatic damage. All together, these data suggest that frequent dietary amino acid deprivation causes hepatic metabolic and ultrastructural changes in a fashion similar to precancerous or cancerous conditions.
BACKGROUND & AIMS: Mesenchymal stem cells ( MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs ( UCMSCs) were differentiated into hepatocyte-like cells ( hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadrupole time-of-flight mass spectrometry. Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide or CCl4; some mice were then given injections of secretomes or proteins. Liver tissues were collected and analyzed by histology or polymerase chain reaction array to analyze changes in gene expression patterns. We analyzed the effects of MSC secretomes and potential anti-fibrotic proteins on transforming growth factor beta 1 ( TGF beta 1)-mediated activation of human hepatic stellate cell ( HSC) lines ( hTert-HSC and LX2) and human primary HSCs. Liver tissues were collected from 16 patients with liver cirrhosis and 16 individuals without cirrhosis ( controls) in Korea and analyzed by immunohistochemistry and immunoblots. RESULTS: In mice with fibrosis, accumulation of extracellular matrix proteins was significantly reduced 3 days after injecting secretomes from UCMSCs, and to a greater extent from hpUCMSCs; numbers of activated HSCs that expressed the myogenic marker a-smooth muscle actin ( alpha-SMA, encoded by ACTA2 [ actin, alpha 2, smooth muscle]) were also reduced. Secretomes from UCMSCs, and to a greater extent from hpUCMSCs, reduced liver expression of multiple fibrotic factors, collagens, metalloproteinases, TGF beta, and Smad proteins in the TGFb signaling pathways. In HSC cell lines and primary HSCs, TGF beta 1-stimulated upregulation of alpha-SMA was significantly inhibited ( and SMAD2 phosphorylation reduced) by secretomes from UCMSCs, and to a greater extent from hpUCMSCs. We identified 32 proteins in secretomes of UCMSCs that were more highly concentrated in secretomes from hpUCMSCs and inhibited TGF beta-mediated activation of HSCs. One of these, milk fat globule-EGF factor 8 ( MFGE8), was a strong inhibitor of activation of human primary HSCs. We found MFGE8 to downregulate expression of TGFb type I receptor by binding to alpha(v)beta(3) integrin on HSCs and to be secreted by MSCs from umbilical cord, teeth, and bone marrow. In mice, injection of recombinant human MFGE8 had anti-fibrotic effects comparable to those of the hpUCMSC secretome, reducing extracellular matrix deposition and HSC activation. Co-injection of an antibody against MFGE8 reduced the anti-fibrotic effects of the hpUCMSC secretome in mice. Levels of MFGE8 were reduced in cirrhotic liver tissue from patients compared with controls. CONCLUSIONS: MFGE8 is an anti-fibrotic protein in MSC secretomes that strongly inhibits TGF beta signaling and reduces extracellular matrix deposition and liver fibrosis in mice.
Mice and humans branched from a common ancestor approximately 80 million years ago. Despite this, mice are routinely utilized as animal models of human disease and in drug development because they are inexpensive, easy to handle, and relatively straightforward to genetically manipulate. While this has led to breakthroughs in the understanding of genotype-phenotype relationships and in the identification of therapeutic targets, translation of beneficial responses to therapeutics from mice to humans has not always been successful. In a large part, these differences may be attributed to variations in the alignment of protein expression and signaling in the immune systems between mice and humans. Well-established inbred strains of "The Laboratory Mouse'' vary in their immune response patterns as a result of genetic mutations and polymorphisms arising from intentional selection for research relevant traits, and even closely related substrains vary in their immune response patterns as a result of genetic mutations and polymorphisms arising from genetic drift. This article reviews some of the differences between the mouse and human immune system and between inbred mouse strains and shares examples of how these differences can impact the usefulness of mouse models of disease.
Direct eye contact is a powerful social cue to regulate interpersonal interactions. Previous behavioral studies showed a link between eye contact and motor mimicry, indicating that the automatic mimicry of observed hand movements is significantly enhanced when direct eye contact exists between the observer and the observed model. In the present study, we aim to investigate the neurophysiological basis of the previously reported behavioral enhancements. Here, transcranial magnetic stimulation (TMS) was applied to assess changes in cortico-motor excitability at the level of the primary motor cortex (MI) to explore whether and how the motor system is facilitated from observing others' hand movements and, in particular, how this process is modulated by eye contact. To do so, motor evoked potentials (MEPs) were collected from two hand muscles while participants received single-pulse TMS and naturally observed video clips of an actor showing hand opening movements or static hands. During the observation, either direct or averted eye gaze was established between the subject and the observed actor. Our findings show a clear effect of eye gaze on observation-induced motor facilitation. This indicates that the mapping or 'mirroring' of others' movements is significantly enhanced when movement observation is accompanied by direct eye gaze compared to averted eye gaze. Our results support the notion that eye contact is a powerful social signal with the ability to direct human non-verbal social behavior. Furthermore, our findings are important for understanding the role of the mirror motor system in the mapping of socially relevant actions.
Moyamoya disease is a chronic cerebrovascular occlusive disease that is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. The occurrence of Moyamoya disease is related to immune, genetic, and other factors. Though the research of Moyamoya disease has made great strides in the past 60 years, the etiology and pathogenesis are largely unknown. This review will focus on the genetic pathogenic and inflammation factors of Moyamoya disease.
The objectives of Master of Philosophy (MPhil) in Physiological Sciences are: 1) to describe the new ways in which anatomy, biochemistry and physiology on one hand, and microbiology, pathology and pharmacology on other hand meet their functional requirements through multidisciplinary integrated concepts; 2) to elucidate relationships between cell biology, molecular biology and molecular genetics by connecting dots of how cell functions are driven by molecules and being controlled by genes. This forms the basis of cell, molecular and genetics [CMG] module upon which 7 multidisciplinary modules of Physiological Sciences follow; 3) these 24 credit hours provide the physiological basis for PhD studies as well as faculty development to enhance learning abilities of medical student; 4) the modules constitute Cardio-Respiratory Physiological Sciences, GI and Renal Physiological Sciences, Neurosciences, Endo-Reproductive Physiological Sciences.; 5) it has integrated microbiology, pathology and pharmacology in a unique way through CMG of microbes leading to associated pathology and mechanisms of prescribed drugs; 6) it has additional synopsis and thesis friendly course work leading to comprehensive examinations; 7) the year two deals with research work of 6 credit hours leading to defense of thesis; 8) The MPhil in Physiological Sciences is fundamentally different from what is being offered elsewhere. It prepares and offers a good spring board to dovetail PhD studies as well as faculty and institutional development. This is the first study that deals with innovative programmes in research, learning and education in the field of physiological sciences. This broad-based MPhil would make its recipients competent, critical, confident and productive learner. This is a completely unique design of a curriculum that has no comparable examples elsewhere. Our mission is to educate graduate students in the field of Physiological Sciences such that they have a complete grasp over the broad-based integrated concepts of basic health sciences. Upon completion of their education, the students will be able to use the duality of imagination and skepticism. Hence, the students will contribute to their fields by unfolding their creative energy.
We report the expression of the mouse Mpped1 in the telencephalon through embryonic stages to adulthood. Using Northern blotting analysis and RNA in situ hybridization (ISH), our data show that Mpped1 is specifically expressed in the brain and is enriched in the cortical plate of the developing telencephalon. Postnatally, the expression of Mpped1 is reduced in the cerebral cortex relative to its levels in the embryonic dorsal telencephalon. Also, Mpped1 expression is sustained in the hippocampal CA1 region. Examination of the expression of Mpped1 and other cortical layer markers by ISH in a malformed beta-catenin null dorsal telencephalon show that the Mpped1-, Cux2-, and Ror beta-expressing superficial cortical layers are reduced and form patchy patterns, and the Tbr-1-expressing deep-layer neurons are incorrectly located on superficial layers, indicative of a migration defect of cortical neurons in the absence of beta-catenin. Developmental Dynamics 239:1797-1806, 2010. (C) 2010 Wiley-Liss, Inc.
Purpose: In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient. Methods: Hyperpolarized three-dimensional balanced steady state C-13 MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group. Results: A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription. Conclusion: MRI and hyperpolarized [C-13, N-15] urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77: 1650-1655, 2017. (C) 2016 International Society for Magnetic Resonance in Medicine
Purpose: We have previously identified mouse Tarsh as one of the cellular senescence-related genes and showed the loss of expression of TARSH mRNA in four human lung cancer cell lines. TARSH is a presumptive signal transduction molecule interacting with NESH, which is implicated to have some roles in lung cancer metastasis. Methods: The amplification of complete ORF-encoding TARSH cDNA was done with reverse transcription-PCR. Northern blotting was carried out using TARSH cDNA probes. To clarify the relationship between TARSH and lung cancer, we quantified TARSH mRNA expression in 15 human lung cancer cell lines and 32 primary non-small cell lung cancers. Results: We first determined the complete ORF-encoding cDNA sequence which is expressed in the human lung. On the Northern hybridization analysis, TARSH was strongly expressed in the human lung. The expression of TARSH mRNA is remarkably downregulated in all the lung cancer cell lines examined. Furthermore, TARSH expression was significantly low in all of the tumor specimens when compared to the expression in corresponding non-neoplastic lung tissue specimens. Conclusion: The cancer-associated transcriptional inactivation of TARSH suggests that TARSH could be used as a biomarker for lung cancer development as well as a molecular adjunct for lung carcinogenesis in human.
Transcription-export complex 2 (TREX-2 complex) facilitates the localization of actively transcribing genes to the nuclear periphery and also functions to contribute to the generation of export-competent mRNPs through interactions with the general mRNA nuclear export factor Mex67:Mtr2. The TREX-2 complex is based on a Sac3 scaffold to which Thp1, Sem1, Cdc31, and Sus1 bind. TREX-2 can be subdivided into two modules: one, in which Thp1 and Semi bind to the Sac3(M) region (residues similar to 100-551), and the other in which Cdc31 and two Sus1 chains bind to the Sac3(CID) region (residues similar to 710-805). Complementary structural analyses using X-ray crystallography, electron microscopy, and small-angle X-ray scattering of the Saccharomyces cerevisiae TREX-2 complex, expressed using Baculovirus-infected Sf9 cells, have indicated that the TPR-like repeats of the Sac3(M) region extend considerably further towards the N-terminus than previously thought, and also indicate that this region and Sac3(CID):Sus1: Cdc31 region of the S. cerevisiae complex are structurally independent. Although the density visible accounted for only similar to 100 kDa, a 5.3 angstrom resolution cryo-EM reconstruction was obtained of the M-region of TREX-2 that showed an additional three putative a-helices extending towards the Sac3 N-terminus and these helices were also seen in a 4.9 angstrom resolution structure obtained by X-ray crystallography. Summary statement: We describe the expression, purification and structural characterization of the S. cerevisiae TREX-2 complex and demonstrate that the Sac3 TPR-like repeats are more extensive than previously thought and that the M- and CID-regions do not appear to have a defined spatial orientation. (C) 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc.
In the last decade, bioinformatic analyses of high-throughput proteomics and transcriptomics data have enabled researchers to gain insight into the molecular networks that may underlie lasting changes in synaptic efficacy. Development and utilization of these techniques have advanced the field of learning and memory significantly. It is now possible to move from the study of activity-dependent changes of a single protein to modeling entire network changes that require local protein synthesis. This data revolution has necessitated the development of alternative computational and statistical techniques to analyze and understand the patterns contained within. Thus, the focus of this review is to provide a synopsis of the journey and evolution toward big data techniques to address still unanswered questions regarding how synapses are modified to strengthen neuronal circuits. We first review the seminal studies that demonstrated the pivotal role played by local mRNA translation as the mechanism underlying the enhancement of enduring synaptic activity. In the interest of those who are new to the field, we provide a brief overview of molecular biology and biochemical techniques utilized for sample preparation to identify locally translated proteins using RNA sequencing and proteomics, as well as the computational approaches used to analyze these data. While many mRNAs have been identified, few have been shown to be locally synthesized. To this end, we review techniques currently being utilized to visualize new protein synthesis, a task that has proven to be the most difficult aspect of the field. Finally, we provide examples of future applications to test the physiological relevance of locally synthesized proteins identified by big data approaches.
Background: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. Methods: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model. This evaluation was performed using an in vitro model of human innate immunity and in vivo in mice after intradermal injection. Results: Results suggest that immunostimulation from the mRNA vaccine in humans is similar to that in mice and acts through cellular RNA sensors, with genes for RLRs [ddx58 (RIG-1) and ifih1 (MDA-5)], TLRs (tlr3, tlr7, and tlr8-human only), and CLRs (clec4gp1, clec2d, cledl1) all significantly up-regulated by the mRNA vaccine. The up-regulation of TLR8 and TLR7 points to the involvement of both mDCs and pDCs in the response to the mRNA vaccine in humans. In both humans and mice activation of these pathways drove maturation and activation of immune cells as well as production of cytokines and chemokines known to attract and activate key players of the innate and adaptive immune system. Conclusion: This translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models.
Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen emerging in hospitals as well as community and livestock. MRSA is a significant and costly public health concern because it may enter the human food chain and contaminate milk and dairy products causing foodborne illness. This study aimed to determine the occurrence and the characteristics of MRSA isolated from 3760 samples of milk and dairy products in a previous survey conducted in southern Italy during 2008-2014. Overall out of 484 S. aureus strains isolated, 40 (8.3%) were MRSA and were characterized by spa-typing, Multi-Locus Sequence Typing, SCCmec typing, Staphylococcal enterotoxins (SEs) genes, Panton-Valentine Leukocidin (PVL) genes and ability to form biofilm. The most frequently recovered STs were ST152 (t355-67.5%), followed by ST398 (t899, t108-25%), ST1 (t127-5%) and ST5 (t688-2.5%). All isolates harboured the SCCmec type V (92.5%) or IVa (25%). In one isolate (2.5%), ST398/t899, the SCCmec resulted not detected. Three isolates (7.5%) carried one or more enterotoxin encoding genes (one strain had seg, sei, sem, sen and seo genes; two strains had seh gene). The 50% of isolated strains harboured PVL-encoding genes. Molecular analysis for icaA and icaD genes showed: 72.5% icaA and icaD positive, 25% only icaD gene and one icaA and icaD negative. The detection of MRSA in food of animal origin is a potential health hazard, thus it is necessary monitoring of food producing animals and improving hygiene standards in food practices in order to reduce the microbiological risk to minimum. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
Background: Mesenchymal stromal cells (MSC) are a major component of the tumor microenvironment in patients with head and neck squamous cell carcinoma (HNSCC). MSC display innate and regulatory immunologic functions, very similar to many hematopoietic 'classical' immune cells. Conversion of ATP to immunosuppressive adenosine is an immunosuppressive mechanism utilized by other hematopoietic immune cells. The present study explores the adenosine metabolism of tumor derived MSC in comparison to autologous MSC from non-malignant tissue. Methods: From HNSCC patients (n = 10), paired MSC were generated from tumor tissue (tMSC) and autologous healthy control tissue (cMSC). Differentiation properties and phenotype (CD105, CD73, CD39, CD90, CD26, CD29) were compared by flow cytometry. Production of immunosuppressive adenosine (ADO) by functionally active ectonucleotidases, CD39 and CD73, was determined by luminescence and mass spectrometry. Suppressive activity of ADO was tested in CFSE proliferation assays of isolated T-cells. Plasticity of cMSC was explored after incubation with tumor-cell conditioned media. Results: Differentiation into osteogenic, chondrogenic and adipogenic directions was comparable in tMSC and cMSC. Expression of ectonucleotidases, CD39 and CD73, was decreased in tMSC as compared to corresponding cMSC, which correlated with decreased ATP metabolism in mass spectrometry. Proliferation of CD4(+) T-cells was significantly suppressed by exogenous ADO. Tumor-conditioned medium was unable to down-regulate ADO production in cMSC. Conclusion: We identified MSC of the oropharyngeal mucosa as an important producer of exogenous ADO. In patients with HNSCC, reduced expression of ADO may contribute to excessive inflammation and tumor growth. (C) 2016 Elsevier GmbH. All rights reserved.
Because of the limitations of standard culture techniques, the development of new recombinant protein expression systems with biotechnological potential is a key challenge. Ideally, such systems should be able to effectively and accurately synthesize a protein of interest with intrinsic metabolic capacity. Here, we describe such a system that was designed based on a plasmid vector containing promoter elements derived from the metallothionein MTIla promoter, as well as processing and purification elements. This promoter can be induced by heavy metals in a culture medium to induce the synthesis of human prostate-specific antigen (hPSA), which has been modified to insert elements for purification, proteolysis, and secretion. We optimized hPSA production in this system by comparing the effects and contributions of ZnCl2, CdCl2, and CuSO4 in HEK293FT, HeLa, BHK-21, and CHO-K1 cells. We also compared the effectiveness of three different transfection agents: multi-walled carbon nanotubes, Lipofectamine 2000, and X-tremeGENE HP Reagent. hPSA production was confirmed via the detection of enhanced green fluorescent protein fluorescence, and cell viability was determined. The expression of hPSA was compared with that of the native protein produced by LNCaP cells, using enzyme-linked immunosorbent assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis. X-tremeGENE reagent, the BHK-21 cell line, and CuSO4 showed the highest hPSA production rates. Furthermore, BHK-21 cells were more resistant to the oxidative stress caused by 100 mu M CuSO4. These results suggest that the proposed optimized inducible expression system can effectively produce recombinant proteins with desired characteristics for a wide range of applications in molecular biology.
Objective: To study the dynamics of the expression and localization of the mu opioid receptor (MOR) in human endometrium throughout the menstrual cycle. Design: Analysis of human endometrial samples from different menstrual cycle phases (menstrual, early/midproliferative, late proliferative/early secretory, midsecretory, and late secretory) by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Setting: Academic research laboratory. Patient(s): Women from the Human Reproduction Unit of the Cruces University Hospital, fulfilling the following criteria: normal uterine vaginal ultrasound; absence of endometriosis, polycystic ovary syndrome, implantation failure, or recurrent miscarriage; and no history of opioid drug use. Intervention(s): Endometrial samples of 86 women categorized into groups for the menstrual cycle phases: 12 menstrual, 21 early/midproliferative, 16 late proliferative/early secretory, 17 midsecretory, and 20 late secretory. Main Outcome Measure(s): MOR gene and protein expression and localization in the different compartments of the human endometrium at different stages of the menstrual cycle. Result(s): The expression of MOR mRNA and protein changed throughout the cycle in human endometrium. MOR expression increased during the proliferative phase and decreased during the secretory one. Lower values were found at menstruation, and maximum values around the time of ovulation. Small variations for each endometrial compartment were found. Conclusion(s): The presence of MOR in human endometrium and the dynamic changes during the menstrual cycle suggest a possible role for opioids in reproduction events related to the human endometrium or endometriosis. (C) 2017 by American Society for Reproductive Medicine.
The mirror neuron system (MNS) has been mooted as a crucial component underlying human social cognition. Initial evidence based on functional magnetic resonance imaging (fMRI) suggests that the MNS plays a role in emotion classification, but further confirmation and convergent evidence is needed. This study employed electroencephalography (EEG) to examine modulations in the mu rhythm associated with the inference of emotions from facial expressions. It was hypothesised that mu suppression would be associated with classifying the emotion portrayed by facial expressions. Nineteen participants viewed pictures of facial expressions or emotion words and were asked to either match the stimulus to an emotion word or to passively observe. Mu activity following stimulus presentation was localised using a 3-D distributed inverse solution, and compared between conditions. Subtractive logic was used to isolate the specific processes of interest. Comparisons of source localisation images between conditions revealed that there was mu suppression associated with recognising emotion from faces, thereby supporting our hypothesis. Further analyses confirmed that those effects were not due to activity associated with the motor response or the observation of facial expressions, offering further support for the hypotheses. This study provides important convergent evidence for the involvement of the MNS in the inference of emotion from facial expressions.
Theories of neuroaesthetics assume, that looking at traces of actions used in creating artwork (e.g. brush marks) is associated with a simulation of these actions in the observer's sensorimotor-cortex. The aim of the current study is to dissociate the activation of the sensorimotor-cortex by the observation of action traces from associated visual processes. Twenty-eight participants observed handmade graphics (acrylic paint on paper) of different complexity (line, triangle, shape of a house) and computer-generated counterparts. Central mu-activity, as an index of sensorimotor-cortex activity, and occipital alpha-activity, as an index of visual cortex activity were recorded in the 8-13 Hz EEG-band. In line with the hyp5hesis, mu-activity at electrode C4 is sensitive for the complexity of handmade (p = 0.001), but not computer-generated graphics (p >0.500). In contrast, occipital alpha-activity is sensitive for the complexity of both handmade and computer-generated graphics (p <0.001). Furthermore, the more empathic the participants rated themselves, the stronger mu-suppression was induced by handmade graphics compared to computer-generated graphics (electrode C4; r=0.612, p = 0.001). These results support the involvement of the sensorimotor-cortex in the recognition of action traces and strengthen evidence that individuals scoring high in emotional empathy feature a particularly responsive mirror neuron system. (C) 2017 Elsevier B.V. All rights reserved.
Mucin glycan is the primary determinant of mucin functions. These functions are expanded by three branch structures, including core 2, core 4, and blood group 1, which are synthesized by core 2 beta 1,6 N-acetylglucosaminyltransferase-M (C2GnT-M). Alteration of C2GnT-M gene expression is expected to have a profound effect on mucin functions, which prompted us to study the regulation of this gene. Quantitative real-time PCR analysis of the expression of this gene in 24 human tissues and airway epithelial cells showed that this gene was expressed primarily in mucus-secretory tissues. 5 ' Rapid amplification of cDNA ends analysis, coupled with sequence alignment with human genome database, revealed that this gene was comprised of three exons and two introns. Northern blotting using exon I probe showed the presence of this exon in all transcripts, suggesting the presence of cis-regulatory elements in the proximal region upstream of and/or near the transcription initiation site (+1). Analysis of this DNA region (-417/+187) by a promoter-reporter transient transfection assay, coupled with serial deletion and linker scanning mutagenesis, revealed two positive regulatory regions, including -291/-282, and -62/-43. Further, the promoter activity was enhanced by all-trans retinoic acid (ATRA) and IL-13. Thus the promoter region is specific to hC2GnT-M gene and subject to regulation by ATRA and IL-13. These cis-regulatory elements may be useful for construction of a mucus cell-specific vector for therapy of mucus hypersecretory diseases.
Anti-tumor necrosis factor (TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases (IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each anti-TNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membrane-bound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with anti-TNF antibodies in chronic intestinal inflammation, by predicting response to therapy. (C) The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound mucins that have both barrier and signaling functions. The family of transmembrane mucins consists of diverse members that share a few characteristics. The highly glycosylated extracellular mucin domains inhibit invasion by pathogenic bacteria and can form a tight mesh structure that protects cells in harmful conditions. The intracellular tails of transmembrane mucins can be phosphorylated and connect to signaling pathways that regulate inflammation, cell-cell interactions, differentiation, and apoptosis. Transmembrane mucins play important roles in preventing infection at mucosal surfaces, but are also re-nowned for their contributions to the development, progression, and metastasis of adenocarcinomas. In general, transmembrane mucins seem to have evolved to monitor and repair damaged epithelia, but these functions can be highjacked by cancer cells to yield a survival advantage. This review presents an overview of the current knowledge of the functions of transmembrane mucins in inflammatory processes and carcinogenesis in order to better understand the diverse functions of these multifunctional proteins. (C) 2017 S. Karger AG, Basel
Cartilage injuries are one of the most common musculoskeletal disorders. Although a number of techniques have been designed to treat cartilage lesions, current research is focused on tissue engineering methods. Recent advances in molecular biology, biotechnology, and polymer science have led to both the experimental and clinical application of various cell types and biomaterials in the treatment of cartilage injuries. This study reports an exceptionally good growth of chondrocytes on a 3D scaffold, based on multiwalled carbon nanotubes (MWCNTs). The MWCNT-based nanostructural scaffold was fabricated employing a plasma enhanced chemical vapor deposition technique. Articular cartilage specimens were taken from the distal femur of adolescent New Zealand White rabbits and chondrocytes were obtained by collagenase digestion. The scaffolds were characterized using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Cell-seeded constructs were visualized with SEM. Chondrocytes adhered to the MWCNT surfaces and were evenly distributed. After one week of culturing, the number of cells was tripled on the MWCNT scaffolds in respect to the culturing in a plastic flask. These cells displayed multiple cytoplasmic extensions that interact with the MWCNTs. The nanotubes were bent by the cells and the cell morphology was altered through the nanostructured surface. Our study confirms that MWCNT-based surfaces provide a very good scaffold that can be used to stimulate the formation of cartilage tissue.
International organizations, ranging from large MNCs to small born global firms, are increasingly recognizing that multicultural employees can help them operate across countries and across cultures. However, multiculturals individuals who identify with and internalize more than one culture - are a diverse group, and organizations seeking to leverage their potential can benefit from a deeper understanding of the resources they possess and the challenges they face. We conducted three studies with a total of 1196 participants to test relationships between multicultural identity patterns and personal, social and task outcomes. Consistent results across studies indicated that individuals with more cultural identities (higher identity plurality) had more social capital and higher levels of intercultural skills than those with fewer cultural identities, while individuals who integrated their cultural identities (higher identity integration) experienced higher levels of personal well-being than those who separated them. Based on these results we advocate for two directions in future research on multicultural employees: moving beyond cognitive mechanisms alone, and examining monocultural and multicultural individuals simultaneously along the spectrum of identity plurality.
The space-filling visualization model was first invented by Ben Shneiderman [28] for maximizing the utilization of display space in relational data (or graph) visualization, especially for tree visualization. It uses the concept of Enclosure which dismisses the "edges" in the graphic representation that are all too frequently used in traditional node-link based graph visualizations. Therefore, the major issue in graph visualization which is the edge crossing can be naturally solved through the adoption of a space filling approach. However in the past, the space-filling concept has not attracted much attention from researchers in the field of multidimensional visualization. Although the problem of 'edge crossing' has also occurred among polylines which are used as the basic visual elements in the parallel coordinates visualization, it is problematic if those 'edge crossings' among polylines are not evenly distributed on the display plate as visual clutter will occur. This problem could significantly reduce the human readability in terms of reviewing a particular region of the visualization. In this study, we propose a new Space-Filling Multidimensional Data Visualization (SFMDVis) that for the first-time introduces a space-filling approach into multidimensional data visualization. The main contributions are: (1) achieving the maximization of space utilization in multidimensional visualization (i.e. 100% of the display area is fully used), (2) eliminating visual clutter in SFMDVis through the use of the non-classic geometric primitive and (3) improving the quality of visualization for the visual perception of linear correlations among different variables as well as recognizing data patterns. To evaluate the quality of SFMDVis, we have conducted a usability study to measure the performance of SFMDVis in comparison with parallel coordinates and a scatterplot matrix for finding linear correlations and data patterns. The evaluation results have suggested that the accuracy of SFMDVis is better than both in terms of perceiving linear correlations and also that the SFMDVis is more efficient (less time is required) than both when recognizing data patterns. 2015 Elsevier Inc. (C) All rights reserved.
Introduction: The dissemination of multi-drug resistant bacteria (MDRB) has become a major public health concern worldwide because of the increase in infections caused by MDRB, the difficulty in treating them, and expenditures in patient care.Areas covered: We have reviewed challenges and contemporary opportunities for rapidly confronting infections caused by MDRB in the 21st century, including surveillance, detection, identification of resistance mechanisms, and action steps.Expert commentary: In this context, the first critical point for clinical microbiologists is to be able to rapidly detect an abnormal event, an outbreak and/or the spread of a MDRB with surveillance tools so that healthcare policies and therapies adapted to a new stochastic event that will certainly occur again in the future can be implemented.
A multifunctional platform based on the microhotplate was developed for applications including a Pirani vacuum gauge, temperature, and gas sensor. It consisted of a tungsten microhotplate and an on-chip operational amplifier. The platform was fabricated in a standard complementary metal oxide semiconductor (CMOS) process. A tungsten plug in standard CMOS process was specially designed as the serpentine resistor for the microhotplate, acting as both heater and thermister. With the sacrificial layer technology, the microhotplate was suspended over the silicon substrate with a 340 nm gap. The on-chip operational amplifier provided a bias current for the microhotplate. This platform has been used to develop different kinds of sensors. The first one was a Pirani vacuum gauge ranging from 10(-1) to 10(5) Pa. The second one was a temperature sensor ranging from -20 to 70 degrees C. The third one was a thermal-conductivity gas sensor, which could distinguish gases with different thermal conductivities in constant gas pressure and environment temperature. In the fourth application, with extra fabrication processes including the deposition of gas-sensitive film, the platform was used as a metal-oxide gas sensor for the detection of gas concentration.
In this paper, we consider the balancing problem in a hierarchical market-based structure for smart energy grids that is based on the Universal Smart Energy Framework. The large-scale introduction of renewable, intermittent energy sources in the power system can create a mismatch between the forecasted (day ahead) and the actual supply and demand. Without a proper control strategy, this deviation could lead to network overloads and commercial losses. We present a multilevel distributed optimal control formulation to the problem, in which the appliances of prosumers that can provide flexibility are optimally dispatched based on local information. The control strategy takes the capacity limitations of the distribution network into account. We provide example simulation results, obtained by distributed model predictive control.
The Multi-Material Arbitrary Lagrangian Eulerian (MMALE) method is an effective way to simulate the multi-material flow with severe surface deformation. Comparing with the traditional Arbitrary Lagrangian Eulerian (ALE) method, the MMALE method allows for multiple materials in a single cell which overcomes the difficulties in grid refinement process. In recent decades, many researches have been conducted for the Lagrangian, rezoning and surface reconstruction phases, but less attention has been paid to the multi-material remapping phase especially for the three-dimensional problems due to two complex geometric problems: the polyhedron subdivision and the polyhedron intersection. In this paper, we propose a "Clipping and Projecting" algorithm for polyhedron intersection whose basic idea comes from the commonly used method by Grandy (1999) [29] and Jia et al. (2013) [34]. Our new algorithm solves the geometric problem by an incremental modification of the topology based on segment plane intersections. A comparison with Jia et al. (2013) [34] shows our new method improves the efficiency by 55% to 65% when calculating polyhedron intersections. Moreover, the instability caused by the geometric degeneracy can be thoroughly avoided because the geometry integrity is preserved in the new algorithm. We also focus on the polyhedron subdivision process and describe an algorithm which could automatically and precisely tackle the various situations including convex, non-convex and multiple subdivisions. Numerical studies indicate that by using our polyhedron subdivision and intersection algorithm, the volume conversation of the remapping phase can be exactly preserved in the MMALE simulation. (C) 2017 Elsevier Inc. All rights reserved.
Preclinical molecular imaging is an emerging field. Improving the ability of scientists to study the molecular basis of human pathology in animals is of the utmost importance for future advances in all fields of human medicine. Moreover, the possibility of developing new imaging techniques or of implementing old ones adapted to the clinic is a significant area. Cardiology, neurology, immunology and oncology have all been studied with preclinical molecular imaging. The functional techniques of photoacoustic imaging (PAT), fluorescence molecular tomography (FMT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in association with each other or with the ana-tomic reference provided by computed tomography (CT) as well as with anatomic and functional information provided by magnetic resonance (MR) have all been proficiently applied to animal models of human disease. All the above -mentioned imaging techniques have shown their ability to explore the molecular mechanisms involved in animal models of disease. The clinical translatability of most of the techniques motivates the ongoing study of their possible fields of application. The ability to combine two or more techniques allows obtaining as much information as possible on the molecular processes involved in pathologies, reducing the number of animals necessary in each experiment. Merging molecular probes compatible with various imaging technique will further expand the capability to achieve the best results.
Objective: This study identified the prevalence of and relationship between mood disorders and multimorbidity in middle-aged and older veterans. Method: Cross-sectional data were obtained from veterans who received primary care services at VA Pittsburgh Healthcare System from January 2007 to December 2011 (n = 34,786). Results: Most veterans had three or more organ systems with chronic disease (95.3%), of which 4.1% had a depressive disorder, 2.5% had an anxiety disorder, and 0.7% had co-occurring depression and anxiety. The odds of having a mood disorder increased with each additional organ system with chronic disease, with odds being the greatest in those with 10 to 13 organ systems with chronic disease. Younger age, female gender, non-married marital status, and having a service connected disability were also significant predictors of having a mood disorder. Discussion: These findings suggest a need to integrate mental health assessment and treatment in chronic health care management for veterans.
The investigation on antimicrobial mechanisms is a challenging and crucial issue in the fields of food or clinical microbiology, as it constitutes a prerequisite to the development of new antimicrobial processes or compounds, as well as to anticipate phenomenon of microbial resistance. Nowadays it is accepted that a cells population exposed to a stress can cause the appearance of different cell populations and in particular sub-lethally compromised cells which could be defined as viable but non-culturable (VBNC). Recent advances on flow cytometry (FCM) and especially on multi-parameter flow cytometry (MP-FCM) provide the opportunity to obtain high-speed information at real time on damage at single-cell level. This review gathers MP-FCM methodologies based on individual and simultaneous staining of microbial cells employed to investigate their physiological state following different physical and chemical antimicrobial treatments. Special attention will be paid to recent studies exploiting the possibility to corroborate MP-FCM results with additional techniques (plate counting, microscopy, spectroscopy, molecular biology techniques, membrane modeling) in order to elucidate the antimicrobial mechanism of action of a given antimicrobial treatment or compound. The combination of MP-FCM methodologies with these additional methods is namely a promising and increasingly used approach to give further insight in differences in microbial sub-population evolutions in response to antimicrobial treatments.
This work describes the practical implementation of an interleaved multi-phase, multiswitch boost converter for fuel cell applications. The paper aims to validate the concept of digitally-controlled Multi-Interleaving Boost Converter pisq for fuel cell applications, from two-phase, four-legs per phase, synchronous boost converter, abbreviated as 2-4MIBC. Compared with the Interleaved Boost Converter (IBC), MIBC exhibits interesting performance in terms of magnetics, input and output current ripple, part count and distributed power losses. A potential field of application is indeed medium and higher power fuel cell front-end converters, where minimizing input current ripple is significant but also redundancy and reliability are crucial. Actually, this approach covers all these aspects since provide module and device redundancy with real-time and flexible digital control reconfiguration. Relevant aspects related to design, modeling, simulation and experimental verification of 1 kW, FPGA-controlled, 2-4-MIBC are treated in this paper. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.
Branch and bound is a well-known generic method for computing an optimal solution of a single objective optimization problem. Based on the idea "divide to conquer", it consists in an implicit enumeration principle viewed as a tree search. Although the branch and bound was first suggested by Land and Doig (1960), the first complete algorithm introduced as a multi-objective branch and bound that we identified was proposed by Kiziltan and Yucaoglu (1983). Rather few multi-objective branch and bound algorithms have been proposed. This situation is not surprising as the contributions on the extensions of the components of branch and bound for multi-objective optimization are recent. For example, the concept of bound sets, which extends the classic notion of bounds, has been mentioned by Villarreal and Karwan (1981). But it was only developed for the first time in 2001 by Ehrgott and Gandibleux, and fully defined in 2007. This paper describes a state-of-the-art of multi-objective branch and bound, which reviews concepts, components and published algorithms. It mainly focuses on the contributions belonging to the class of optimization problems who has received the most of attention in this context from 1983 until 2015: the linear optimization problems with zero-one variables and mixed 0-1/continuous variables. Only papers aiming to compute a complete set of efficient solutions are discussed. (C) 2017 Elsevier B.V. All rights reserved.
Digitally controlled permanent-magnet synchronous motors (PMSMs) exhibit bandwidth limitations imposed by delay. In high power applications such as rail transit, the negative impact of delay is particularly serious due to the low switching frequency of the inverter. In this paper, the causes and effects of time delay are analyzed, and the sampling delay is greatly reduced by using multiple sampling method. Test results are given to verify the effectiveness and reliability of the proposed method.
The objective of this study is to evaluate the relationship between social cognition (SC) and cognitive impairment in persons with multiple sclerosis (PwMS). A prospective study was conducted in 60 PwMS, 30 with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS) and 15 with primary progressive MS (PPMS), and in healthy subjects (HS). All subjects were assessed by the Bordeaux Social Cognition Evaluation Protocol (PECS-B) (facial emotion recognition, theory of mind, emotional awareness and cognitive and affective alexithymia), by a large neuropsychological battery and by questionnaires (depression and anxiety). 43.3% of PwMS were impaired for at least one SC test. The proportion of PwMS with at least two impaired SC tests was similar in all three phenotypes (20%). Mean scores differed significantly between PwMS and HS only for the Reading the Mind in the Eyes Test, a test of Theory of Mind (ToM). ANOVA analyses showed an effect of phenotype on emotional awareness scores with lower scores in PPMS as compared to RRMS. ToM performance was significantly correlated (r (2) = 0.56) with executive functions, working memory and episodic memory scores. SC impairment was found in all phenotypes and was more prominent in cognitively impaired MS patients. Executive functions, and working and episodic memory performance accounts for approximately 50% of ToM performance. Emotional awareness is more impaired in progressive MS.
Background: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. Objective: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients. Methods: sVCAM-1 serum concentrations and whole blood mRNA expression were measured in blood samples from untreated RRMS-patients and from two independent groups of natalizumab-treated patients. Results: sVCAM-1 serum concentrations and whole blood expression of HLX1 and IL1B mRNA were lower, whereas expression of EBI3 mRNA was higher in natalizumab-treated MS-patients. Five genes were differentially expressed in clinically unstable natalizumab-treated MS-patients in the discovery but not in the validation group. Conclusion: Decreased serum concentrations of sVCAM-1 and altered whole blood mRNA expression levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HIX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status in natalizumab-treated MS. (C) 2016 Elsevier B.V. All rights reserved.
Background: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis. Objectives: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis. Methods: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease. A lectin-based assay was used to investigate potential galactosylation modifications of immunoglobulin G. Results and conclusion: Galactosylation of immunoglobulin G isolated from cerebrospinal fluid of control patients was found to be age- and gender-dependent. In addition, immunoglobulin G galactosylation was significantly altered in cerebrospinal fluid but not in serum of multiple sclerosis patients. Furthermore, this modification was correlated with an active progression of multiple sclerosis. Finally, the loss of galactosyl moieties was not simply associated with inflammation as no such change was detected in viral meningitis patients characterized by brain inflammation.
Background: No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. Objectives and methods: To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. Results: In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Conclusion: Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS.
Non-invasive molecular imaging techniques can enhance diagnosis to achieve successful treatment, as well as reveal underlying pathogenic mechanisms in disorders such as multiple sclerosis (MS). The cooperation of advanced multimodal imaging techniques and increased knowledge of the MS disease mechanism allows both monitoring of neuronal network and therapeutic outcome as well as the tools to discover novel therapeutic targets. Diverse imaging modalities provide reliable diagnostic and prognostic platforms to better achieve precision medicine. Traditionally, magnetic resonance imaging (MRI) has been considered the golden standard in MS research and diagnosis. However, positron emission tomography (PET) imaging can provide functional information of molecular biology in detail even prior to anatomic changes, allowing close follow up of disease progression and treatment response. The recent findings support three major neuroinflammation components in MS: astrogliosis, cytokine elevation, and significant changes in specific proteins, which offer a great variety of specific targets for imaging purposes. Regardless of the fact that imaging of astrocyte function is still a young field and in need for development of suitable imaging ligands, recent studies have shown that inflammation and astrocyte activation are related to progression of MS. MS is a complex disease, which requires understanding of disease mechanisms for successful treatment. PET is a precise non-invasive imaging method for biochemical functions and has potential to enhance early and accurate diagnosis for precision therapy of MS. In this review we focus on modulation of different receptor systems and inflammatory aspect of MS, especially on activation of glial cells, and summarize the recent findings of PET imaging in MS and present the most potent targets for new biomarkers with the main focus on experimental MS research.
This paper presents a new approximated integer delayed modeling and control technique for Continuous-time Fractional Delay Differential Equations (CFDDEs). Using the impulse response sequences of the CFDDE and the balanced model-reduction method, a delay-free discrete-time state-space model is constructed. Then, an equivalent Discrete-time Integer Delay Difference Equation (DIDDE) is obtained by transforming the obtained discrete-time state-space model into a controller-type block companion form. Furthermore, based on the obtained DIDDE, an equivalent Continuous-time Integer Delay Differential Equation (CIDDE) is determined by means of the newly developed Chebyshev's bilinear approximation method. For digital control of the CFDDE, an optimal Discrete-time Integer Delayed Control Law (DIDCL) is designed using the conventional discrete-time LQR approach together with the obtained delay-free discrete-time state-space model. On the other hand, for continuous-time control of the CFDDE, a Continuous-time Integer Delayed Control Law (CIDCL) is determined from the designed DIDCL by means of the inverse Chebyshev's bilinear approximation method. Finally, digital and analog integer delayed observers are constructed for the implementations of the developed DIDCL and CIDCL, respectively. An illustrative example is given to demonstrate the effectiveness of the proposed method. (C) 2015 Elsevier Inc. All rights reserved.
Genomic DNA is dynamically associated with protein factors and folded to form chromatin fibers. The 3-dimensional (3D) configuration of the chromatin will enable the distal genetic elements to come into close proximity, allowing transcriptional regulation. Noncoding RNA can mediate the 3D structure of chromatin. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a valuable and powerful technique in molecular biology which allows the study of unbiased, genome-wide de novo chromatin interactions with paired-end tags. Here, we describe the standard version of ChIA-PET and a Multiplex ChIA-PET version.
Gibel carp Carassius auratus gibelio (Bloch), a commercially important freshwater-cultured fish in China, is threatened by myxosporeans, particularly Thelohanellus wuhanensis, Myxobolus honghuensis, M. wulii and M. turpisrotundus. Here, we developed a multiplex PCR assay for simultaneous detection of these 4 myxosporeans. The specific primers for each species were designed based on the 28S rDNA gene of T. wuhanensis, the ITS-5.8S rDNA of M. honghuensis and M. wulii, and the 18S rDNA gene of M. turpisrotundus. Specificity testing confirmed that the 4 primer sets have no cross-reactivity with other related myxosporean species tested. Detection limits of the multiplex PCR assay were 0.2, 0.3, 3.1 and 3.8 spores for T. wuhanensis, M. honghuensis, M. wulii and M. turpisrotundus, respectively. Following screening of 104 field samples, the analytical sensitivity of the present multiplex PCR assay was found to be similar to the sensitivity obtained by the singleplex PCR assays and was higher than that of microscopic examination. Moreover, Kappa analysis showed a strong agreement between the results of the singleplex and multiplex PCR assays, indicating that the developed multiplex PCR assay was an efficient approach for the diagnosis of the 4 myxosporeans infecting gibel carp.
Multiplex reverse transcription-polymerase chain reaction (RT-PCR) and PCR protocols were developed and subsequently evaluated for its effectiveness in detecting simultaneously single and mixed infections in sheep and goats. Specific primers for three DNA viruses and three RNA viruses, including foot and mouth disease virus (FMDV), Bluetongue virus (BTV), peste des petits ruminants virus (PPRV), sheeppox virus (SPPV), goatpox virus (GTPV) and orf virus (ORFV) were used for testing procedure. A single nucleic acid extraction protocol was adopted for the simultaneous extraction of both RNA and DNA viruses. The multiplex PCR consisted with two-step procedure which included reverse transcription of RNA virus and multiplex PCR of viral cDNA and DNA. The multiplex PCR assay was shown to be sensitive because it could detect at least 100 pg of viral genomic DNA or RNA from a mixture of six viruses in a reaction. The assay was also highly specific in detecting one or more of the same viruses in various combinations in specimens. Thirty seven clinical samples collected from sheep and goats were detected among forty three samples tested by both uniplex and multiplex PCR, showing highly identification. As results of the sensitivity and specificity, the multiplex PCR is a useful approach for clinical diagnosis of mixed infections of DNA and RNA viruses in sheep and goats with a reaction. (C) 2017 Elsevier B.V. All rights reserved.
Multiplex reverse transcription (RT)-polymerase chain reaction (PCR)-based assays involving fluorescent dye-labeled primers were modified to detect 10 types of gastroenteritis viruses by adding two further assays to a previously developed assay. Then, these assays were applied to clinical samples, which were collected between January 2006 and December 2013. All 10 types of viruses were effectively detected in the multiplex RT-PCR-based assays. In addition, various viral parameters, such as the detection rates and age distributions of each viral type, were examined. The frequency and types of mixed infections were also investigated. Among the 186 virus-positive samples, genogroup II noroviruses were found to be the most common type of virus (32.7%), followed by group A rotaviruses (10.6%) and parechoviruses (10.3%). Mixed infections were observed in 37 samples, and many of them were detected in patients who were less than 2 years old. These observations showed that the multiplex RT-PCR-based assays involving fluorescent dye-labeled primers were able to effectively detect the viruses circulating among pediatric acute gastroenteritis patients and contributed to the highly specific and sensitive diagnosis of gastroenteritis. (C) 2016 Wiley Periodicals, Inc.
In the present paper, we investigate the stationary probability distribution(SPD) and the mean treatment time of a time-delayed cancer growth system induced by cross-correlated intrinsic and extrinsic noises. Our main results show that the resonant-like phenomenon of the mean first-passage time (MFPT) appears in the tumor cell growth model due to the interaction of all kinds of noises and time delay. Due to the existence of the resonant-like peak value, by increasing the intensity of multiplicative noise and time delay, it is possible to restrain effectively the development of the cancer cells and enhance the stability of the system. During the process of controlling the diffusion of the tumor cells, it contributes to inhibiting the development of cancer by increasing the cross-correlated noise strength and weakening the additive noise intensity and time delay. Meanwhile, the proper multiplicative noise intensity is conducive to the process of inhibition. Conversely, in the process of exterminating cancer cells of a large density, it can exert positive effects on eliminating the tumor cells by increasing noises intensities and the value of time delay. (C) 2016 Elsevier Ltd. All rights reserved.
It is well known that the existence of unstable zero dynamics is recognized as a major barrier in many control systems. When the usual digital control with zero-order hold (ZOH) or fractional-order hold (FROH) input is used, unstable zero dynamics inevitably appear in the discrete-time model even though the continuous-time system with relative degree more than two is of minimum phase. This paper investigates the zero dynamics, as the sampling period tends to zero, of sampled-data models composed of a generalized sample hold function (GSHF), a continuous-time nonlinear plant and a sampler in cascade. More precisely, we show how an approximate sampled-data model can be obtained for nonlinear systems with two special GSHF cases such that sampled zero dynamics of the resulting model can be arbitrarily placed. Further, two GSHFs with appropriate parameters provide nonlinear zero dynamics as stable as possible, or with improved stability properties even when unstable, for a given continuous-time plant. It is also shown that the intersample behavior arising from the multirate input can be localised by appropriately selecting the design parameters based on the stability condition of the zero dynamics. The results presented here generalize well-known ideas from the linear to nonlinear cases.
This paper concerns the net effects of promoting renewable energies on value added and disposable income in Germany, as well as their distribution among regions and income brackets. Since its entry into force, the German Renewable Energy Sources Act (EEG) has stimulated tremendous investments in renewable energy capacities by guaranteeing investors a fixed price per kWh as well as a preferred feed into the grid over electricity from conventional sources. The policy measures are financed by a surcharge on electricity prices. In recent years, a controversy has arisen about potentially negative regional and social distribution effects. In this paper, multiregional price and quantity input-output models with endogenous heterogeneous households are used to trace the indirect impacts of the EEG on value added and disposable income through the complex network of regional value chains. Our findings suggest that the generation of electricity from renewable sources itself leads to small positive impacts on industries, but leads to a significant drain on household income and'has regressive distributive effects. However, investment in new capacities may possibly transform these negative impacts into a positive direction for the majority of households. (C) 2017 Elsevier B.V. All rights reserved.
Nowadays, many works have been presented regarding the modeling, simulation and circuit realization of different kinds of continuous-time multi-scroll chaotic attractors. However, very few works describe the experimental realization of attractors having high maximum Lyapunov exponent (MLE) and high entropy, which are desirable characteristics to guarantee better chaotic unpredictability. For instance, two chaotic oscillators having the same MLE values can behave in a very different way, e.g. showing different entropy values. That way, we describe the experimental realization of an optimized multi-scroll chaotic oscillator with both high MLE and entropy. First, the MLE is optimized by applying an evolutionary algorithm, which provides a set of feasible solutions. Second, the associated entropy is evaluated for each feasible solution. In this chapter, experimental results are shown for the electronic implementation of a chaotic oscillator generating 2-, 5- and 10-scrolls. Finally, the experimental results show that by increasing the number of scrolls both the MLE and its associated
The current-feedback operational amplifier (CFOA) allows us to implement any kind of circuit useful in analogue signal processing applications. However, it has limited performance in implementing nonlinear circuits. That way, this investigation highlights the experimental results of implementing a multi-scroll chaotic oscillator by using the commercially available CFOA AD844. The chaotic oscillator is based on saturated nonlinear function (SNLF) series, and we show and discuss its frequency limitations to generate 3- to 10-scrolls from 1 kHz to 100 kHz. Finally, we conclude that the frequency limitations are due to the nonideal characteristics of the CFOA-based SNLF block, imposed by the AD844.
Based on the characteristics and teaching problems of electronic technology courses, this paper proposed to use the multisim simulation software in the whole process of analog electronic technology teaching, integrating theory and practice of teaching, which strengthen the theory teaching and make up for the lack of hardware in experimental teaching. The teaching practice of basic amplifier and integrated operational amplifier that are core components in analog electronics, for example, the analysis based on the integration of theory and practice in teaching methods of multisim stimulate students' interest in learning, improve learning initiative, and enhance understanding of the content students learned as well as their practical abilities, developing sense of innovation and achieving ideal teaching effect.
This paper studies the control of coexisting attractors in an impacting system via a recently developed control law based on linear augmentation. Special attention is given to two control issues in the framework of multistable engineering systems, namely, the switching between coexisting attractors without altering the system's main parameters and the avoidance of grazing-induced chaotic responses. The effectiveness of the proposed control scheme is confirmed numerically for the case of a periodically excited, soft impact oscillator. Our analysis shows how path-following techniques for non-smooth systems can be used in order to determine the optimal control parameters in terms of energy expenditure due to the control signal and transient behavior of the control error, which can be applied to a broad range of engineering problems. (C) 2017 Elsevier B.V. All rights reserved.
This paper presents the design of a 4th-order mult-istage feedforward operational amplifier (op amp) for applications in continuous-time bandpass delta-sigma modulators. On the system-level, a design procedure is proposed to determine the transconductance of each stage. On the transistor-level, curren-treusing is emphasized to achieve power efficiency. Simulated in a 65 nm CMOS process, the op amp achieves over 40 dB gain up to 500 MHz and over 10 dB gain up to 2 GHz with 10 mW power consumption.
The paper presents a four-stage operational amplifier (OPA) with high DC gain and large bandwidth by combining no capacitor feedforward compensation and reversed nested indirect compensation. The proposed OPA is simulated in TSMC 65 nm 1.2 V CMOS process, achieving 100 dB DC gain, 330 MHz gain-bandwidth product, 266.25 V/mu s slew rate and 1.56 mW power dissipation with 1.2 V supply voltage.
A simple and high sensitive cholesterol amperometric biosensor, which is based on in situ electropolymerization of multi-walled carbon nanotube-polyaniline (MWCNT-PANI) nanocomposite and electrodeposition of platinum nanoparticle (nano-Pt) films onto the glassy carbon electrode surface for cholesterol oxidase immobilization, was constructed in this study. The preparation process of the modified electrode was characterized by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, and chronoamperometry. Because of the synergistic electrocatalytic activity between MWCNT-PANI nanocomposites and nano-Pt, the cholesterol biosensor exhibited an excellent performance with a linear range of 2.0-510.0 mu M, a detection limit of 0.8 mu M (signal-to-noise ratio = 3), a high sensitivity of 109.9 mu A mM(-1), and a short response time within 5 Sec. Moreover, the reproducibility, stability, and selectivity of the biosensor were also investigated. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 757-764, 2016
Rearing in darkness slows the time course of the visual cortical critical period, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, while at 20 weeks dark-reared cats are more plastic [Mower GD (1991) The effect of dark rearing on the time course of the critical period in cat visual cortex. Dev Brain Res 58:151-158]. Thus, genes that are important for visual cortical plasticity should show differences in expression between normal and darkreared visual cortex that are of opposite direction in young versus older animals. Previously, we showed by differential display polymerase chain reaction and northern blotting that mRNA for Munc13-3, a mammalian homologue of the C. elegans uncoordinated (unc) gene, shows such bidirectional regulation in cat visual cortex [Yang CB, Zheng YT, Li GY, Mower GD (2002) Identification of Munc13-3 as a candidate gene for critical period neuroplasticity in visual cortex. J Neurosci 22:8614-8618]. Here, the analysis is extended to Munc13-3protein in mouse visual cortex, which will provide the basis for gene manipulation analysis. In mice, Munc13-3 protein was elevated 2.3-fold in dark-reared compared with normal visual cortex at 3.5 weeks and 2.0-fold in normal compared with dark-reared visual cortex at 9.5 weeks. Analysis of variance of protein levels showed a significant interaction, indicating that the effect of dark rearing depended on age. This bidirectional regulation was restricted to visual cortex and did not occur in frontal cortex. Bidirectional regulation was also specific to Munc13-3 and was not found for other Munc13 family members. Munc13 proteins serve a central priming function in synaptic vesicle exocytosis at glutamatergic and GABAergic synapses and this work contributes to the growing evidence indicating a role of Munc13 genes in synaptic plasticity. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
Activity-dependent changes in synapses rely on functional changes in resident proteins and on gene expression. We addressed the relationship between synapse activity and the expression of synaptic genes by comparing RNA levels in the neocortex of normal mice versus secretion-deficient and therefore synaptically silent munc18-1 (mammalian homologue of Caenorhabditis elegans uncoordinated locomotion-18) null mutants, using microarray expression analysis, real-time quantitative PCR and northern blotting. We hypothesized that genes under the control of synaptic activity would be differentially expressed between mutants and controls. We found that few synaptic genes were differentially expressed. However, most neuropeptide genes with detectable expression on the microarray were differentially expressed, being expressed 3-20-fold higher in control cortex. Several other secreted proteins were also differentially expressed, but genes encoding their receptors and many other synaptic components were not. Differential expression was confirmed by real-time quantitative PCR analysis. In situ hybridization indicated that the difference in neuropeptide expression was uniform and not due to the loss of specific cells in the mutant. In primary sensory neurons, which do not depend on synaptic activity for their input, the differential expression of neuropeptides was not observed. These data argue against a general relationship between the activity of synapses and the expression of their resident proteins, but suggest a link between secretion and the expression of genes encoding the secreted products.
An improved method for Southern DNA and Northem RNA blotting using the Mupide (R)-2 Mini-Gel System is described. We get sharp and clear bands in Southern and Northern blotting after only 30 min short gel electrophoresis instead of the several hours large gel electrophoresis of conventional methods. The high electrical voltage with a pulse-like current of the Mupid (R)-2 Mini-Gel System also allows reduction of the amount of formaldehyde, a harmful reagent, from the gel running buffer in RNA blotting. This minor modification of DNA and RNA blotting technique enables us to perform the complete experimental procedure more quickly economically in less space, than conventional Southern and Northern blotting, as well as using an extremely small amount of formaldehyde in RNA blotting. (c) 2006 Elsevier B.V All rights reserved.
Background: Rickettsiosis is a potential life threatening infectious disease in travelers. Clinical recognition is not always straightforward, as typical manifestations such as rash and/or eschar may be absent. Definite diagnosis is based on seroconversion and therefore often delayed until the convalescent phase of disease. Case presentation: In this case report, we describe four patients with severe travel-related rickettsiosis (two patients with murine-and two patients with scrub typhus), in whom acute-phase diagnosis was possible by real-time polymerase chain reaction on serum or blood. Conclusions: Despite its limitations, we think that polymerase chain reaction can contribute significantly to the early diagnosis and treatment of rickettsial disease in travelers.
Striated muscles exhibit a wide range of metabolic activity levels. Heart and diaphragm are muscles with continuous contractile performance, which requires life-long function. In contrast, skeletal muscles like longissimus muscle can adapt metabolism from resting to different stages of exercise. The aim of this study was to compare the morphological features of these three muscles and the expression of genes that are important for energy metabolism. Therefore, histochemical studies were performed for determination of muscle fibre type composition. Oxidative and glycolytic capacity was assessed by measuring isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH) activities. The mRNA expression of glucose transporter 4 (GLUT 4), growth hormone receptor (GHR) and AMP-activated kinase (AMPK) alpha(1) and alpha(2) subunits was studied by semiquantitative Northern blotting. Heart, and to a slightly lesser extent diaphragm were highly oxidative muscles characterised by high expression of oxidative muscle fibres and ICDH activity. Longissimus muscle exhibited the highest percentage of glycolytic fibres and LDH activity. GLUT 4 mRNA was lowest in heart reflecting the dependency of heart muscle on fatty acids as major energy source. Higher expression of GLUT 4 in diaphragm indicated that glucose is an important energy substrate in this oxidative muscle. Highest GLUT 4 expression in longissimus should be essential for the refilling of glycogen stores after exercise. AMPK subunits, which are important stimulators of GLUT 4 protein insertion into the sarcolemma, are also highest expressed in longissimus muscle indicating the strong capacity to adapt energy metabolism to large changes in energy demand. Interestingly, AMPK alpha(1) subunit expression on protein level is strongly restricted to muscle fibres containing type I myosin in this muscle. GHR mRNA expression was also highest in longissimus muscle indicating that an enhanced effect of growth hormone, which is described to be diabetogenic, could be involved in the lower insulin sensitivity of glycolytic muscles.
Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright (C) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively. These Muse cells differentiated into melanocytes in differentiation medium. The SSEA-3-positive cells were scattered in the basement membrane zone and the dermis, with comparatively more in the sebaceous glands, vascular and sweat glands, as well as the outer root sheath of hair follicles, the dermal papillae, and the hair bulbs. Muse cells, which have the ability to self-renew, were obtained from scalp dermal fibroblasts by flow cytometry sorting with an anti-SSEA- 3 antibody. The results of RT-PCR, Western blot, and immunofluorescence staining showed that the expression levels of Oct4, Nanog, Sox2, and Klf4 mRNAs and proteins in Muse cells were significantly different from their parental dermal fibroblasts. Muse cells differentiated into melanocytes when cultured in melanocyte differentiation medium, and the Muse cell-derived melanocytes expressed the melanocyte-specific marker HMB45. Muse cells could be obtained by flow cytometry from primary cultures of scalp dermal fibroblasts, which possessed the ability of pluripotency and self-renewal, and could differentiate into melanocytes in vitro.
Despite the increasing use of portable tablets in learning, their impact has received little attention in research. In five different projects, this media-ethnographic and design-based analysis of the use of portable tablets as a learning resource in science museums investigates how young people's learning with portable tablets matches the intentions of the museums. By applying media and information literacy (MIL) components as analytical dimensions, a pattern of discrepancies between young people's expectations, their actual learning and the museums' approaches to framing such learning is identified. It is argued that, paradoxically, museums' decisions to innovate by introducing new technologies, such as portable tablets, and new pedagogies to support them conflict with many young people's traditional ideas of museums and learning. The assessment of the implications of museums' integration of portable tablets indicates that in making pedagogical transformations to accommodate new technologies, museums risk opposing didactic intention if pedagogies do not sufficiently attend to young learners' systemic expectations to learning and to their expectations to the digital experience influenced by their leisure use.
Objectives: The purpose was to examine the effectiveness of music care on cognitive function, depression, and behavioral problems among elderly people with dementia in long-term care facilities in Taiwan. Methods: The study had a quasi-experimental, longitudinal research design and used two groups of subjects. Subjects were not randomly assigned to experimental group (n = 90) or comparison group (n = 56). Based on Bandura's social cognition theory, subjects in the experimental group received Kagayashiki music care (KMC) twice per week for 24 weeks. Subjects in the comparison group were provided with activities as usual. Results: Results found, using the control score of the Clifton Assessment Procedures for the Elderly Behavior Rating Scale (baseline) and time of attending KMC activities as a covariate, the two groups of subjects had statistically significant differences in the mini-mental state examination (MMSE). Results also showed that, using the control score of the Cornell Scale for Depression in Dementia (baseline) and MMSE (baseline) as a covariate, the two groups of subjects had statistically significant differences in the Clifton Assessment Procedures for the Elderly Behavior Rating Scale. Conclusion: These findings provide information for staff caregivers in long-term care facilities to develop a non-invasive care model for elderly people with dementia to deal with depression, anxiety, and behavioral problems.
BackgroundAlthough music therapy (MT) is considered an effective intervention for young people with mental health needs, its efficacy in clinical settings is unclear. We therefore examined the efficacy of MT in clinical practice. MethodsTwo hundred and fifty-one child (8-16years, with social, emotional, behavioural and developmental difficulties) and parent dyads from six Child and Adolescent Mental Health Service community care facilities in Northern Ireland were randomised to 12 weekly sessions of MT plus usual care [n=123; 76 in final analyses] or usual care alone [n=128; 105 in final analyses]. Follow-up occurred at 13weeks and 26weeks postrandomisation. Primary outcome was improvement in communication (Social Skills Improvement System Rating Scales) (SSIS) at 13weeks. Secondary outcomes included social functioning, self-esteem, depression and family functioning. ResultsThere was no significant difference for the child SSIS at week 13 (adjusted difference in mean 2.4; 95% CI -1.2 to 6.1; p=.19) or for the guardian SSIS (0.5; 95% CI -2.9 to 3.8; p=.78). However, for participants aged 13 and over in the intervention group, the child SSIS communication was significantly improved (6.1, 95% CI 1.6 to 10.5; p=.007) but not the guardian SSIS (1.1; 95% CI -2.9 to 5.2; p=.59). Overall, self-esteem was significantly improved and depression scores were significantly lower at week 13. There was no significant difference in family or social functioning at week 13. ConclusionsWhile the findings provide some evidence for the integration of music therapy into clinical practice, differences relating to subgroups and secondary outcomes indicate the need for further study. ISRCTN Register; ISRCTN96352204.
Evidence shows that music therapy aids in symptom management and improves quality of life for palliative medicine and hospice patients. The majority of previous studies have addressed patient needs, while only a few addressed the needs of family members. The primary purpose of this study was to understand family members' perceptions of music therapy experienced by a relative in palliative medicine or hospice. Patient self-reported scales and music therapist assessment of change were also investigated. Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after music therapy sessions. One family member present during the session assessed perceived effect on the patient's pain, anxiety, depression, shortness of breath, stress level, restlessness, comfort level, mood, and quality of life. The effect on family member's stress level, quality of life, and mood and helpfulness of the music therapy session for the patient and self were studied. Recommendations about future patient participation in music therapy and qualitative comments were also solicited. Fifty family member/patient dyads participated in the study. Family member perceptions were positive, with 82% of responders indicating improvement for self and patient in stress, mood, and quality of life; 80% rating the session as extremely helpful; and 100% of 49 recommending further music therapy sessions for the patient. Patients reported statistically significant improvement in pain, depression, distress, and mood scores. Family members of patients in palliative medicine and hospice settings reported an immediate positive impact of music therapy on the patient and on themselves. More research needs to be conducted to better understand the benefits of music therapy for family members.
Understanding the rates, spectra, and fitness effects of spontaneousmutations is fundamental to answering key questions in evolution, molecular biology, disease genetics, and conservation biology. To estimate mutation rates and evaluate the effect of selection on new mutations, we propagated mutation accumulation (MA) lines of Daphnia pulex for more than 82 generations and maintained a non-MA population under conditions where selection could act. Both experiments were started with the same obligate asexual progenitor clone. By sequencing 30 genomes and implementing a series of validation steps that informed the bioinformatic analyses, we identified a total of 477 single nucleotide mutations (SNMs) in the MA lines, corresponding to a mutation rate of 2.30 x 10(-9) (95% CI 1.90-2.70 x 10(-9)) per nucleotide per generation. The high overall rate of loss of heterozygosity (LOH) of 4.82 x 10(-5) per site per generation was due to a large ameiotic recombination event spanning an entire arm of a chromosome (similar to 6Mb) and several hemizygous deletion events spanning similar to 2 kb each. In the non-MA population, we found significantly fewer mutations than expected based on the rate derived from the MA experiment, indicating purifying selection was likely acting to remove new deleterious mutations. We observed a surprisingly high level of genetic variability in the non-MA population, which we propose to be driven by balancing selection. Our findings suggest that both positive and negative selection on new mutations is powerful and effective in a strictly clonal population.
Human MutT homolog 1 (MTH1) detoxifies the oxidized DNA precursor 8-oxo-2' -deoxyguanosine-5' triphos-phate and serves a tumor suppressive role in distinct types of cancer. In the present study, the expression of MTH1 was examined in various subtypes of breast cancer, and the effect of its suppression on breast cancer growth was characterized in vitro and in vivo. MTH1 mRNA and protein levels were assessed using the reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. The effect of MTH1 expression on the proliferation of breast cancer cells was investigated in vitro using Cell Counting Kit-8 and colony formation assays, and in vivo using breast cancer cell line xenografts in mice. The toxicity of the MTH1 inhibitor TH588 was investigated in nude mice. A marked increase in MTH1 protein and mRNA levels was demonstrated in breast cancer tissues compared with the non-cancerous control. However, no apparent differences in MTH1 expression were observed between distinct molecular subtypes of breast cancer. MTH1 overexpression was demonstrated to be independent of patient age, tumor size and lymph node metastasis. Inhibition of MTH1 decreased cancer cell viability and the clonogenic potential of cancer cells in a dose-dependent manner. These results were confirmed by decreased in vivo proliferation of MCF7, MDA-MB-231 and MDA-MB-453 cancer cell lines, representing distinct subtypes of breast cancer. Although inhibition of MTH1 activity decreased xenograft growth in mice, no major adverse effects of TH588 were detected on the basis of blood biochemistry, and liver and kidney function. The results of the present study suggested that MTH1 is overexpressed in the majority of breast cancers, independent of the molecular identity and clinicopathological features of the tumor, including patient age, tumor size and lymph node metastasis. Inhibition of MTH1 activity suppressed the growth of three subtypes of breast cancer, including luminal, basal-like and human epidermal growth factor receptor 2posi-tive, in vitro and in vivo. Treatment with the MTH1 inhibitor appears to be safe; however, further studies are required prior to the clinical use of MTH1 inhibitors.
Introduction: Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease.Areas covered: PubMed searches were conducted for the term myasthenia gravis' cross-referenced with the terms immunology', subgroups', antibody', ocular', thymoma', treatment' and thymectomy'. Additionally, we summarized the current state of immunopathology and therapy.Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.
Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified, and selected for more human virulent characteristics by amoeba species in aquatic bioffirns. However, a quantitative microbial risk assessment (QMRA) has not been performed due to the lack of dose response models resulting from significant heterogeneity within even a single species or subspecies of MAC, as well as the range of human susceptibilities to mycobacterial disease. The primary human-relevant species and subspecies responsible for the majority of the human disease burden and present in drinking water, biofilms, and soil are M. avium subsp. hominissuis, M. intracellulare, and M. chimaera. A critical review of the published literature identified important health endpoints, exposure routes, and susceptible populations for MAC risk assessment. In addition, data sets for quantitative dose-response functions were extracted from published in vivo animal dosing experiments. As a result, seven new exponential dose response models for human-relevant species of MAC with endpoints of lung lesions, death, disseminated infection, liver infection, and lymph node lesions are proposed. Although current physical and biochemical tests used in clinical settings do not differentiate between M. avium and M. intracellulare, differentiating between environmental species and subspecies of the MAC can aid in the assessment of health risks and control of MAC sources. A framework is proposed for incorporating the proposed dose response models into susceptible population-and exposure route-specific QMRA models. (C) 2016 Elsevier Ltd. All rights reserved.
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads that were produced in both Escherichia coli and Lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities, which we hypothesized to have the potential to induce immunity. In this study, we aimed to develop PHA beads produced in mycobacteria (mycobacterial PHA biobeads [MBB]) and test their potential as a TB vaccine in a mouse model. As a model organism, nonpathogenic Mycobacterium smegmatis was engineered to produce MBB or MBB with immobilized mycobacterial antigens Ag85A and ESAT-6 on their surface (A:EMBB). Three key enzymes involved in the poly(3-hydroxybutyric acid) pathway, namely, beta-ketothiolase (PhaA), acetoacetyl-coenzyme A reductase (PhaB), and PHA synthase (PhaC), were engineered into E. coli-Mycobacterium shuttle plasmids and expressed in trans. Immobilization of specific antigens to the surface of the MBB was achieved by creating a fusion with the PHA synthase which remains covalently attached to the polyester core, resulting in PHA biobeads displaying covalently immobilized antigens. MBB, A: E-MBB, and an M. smegmatis vector control (MVC) were used in a mouse immunology trial, with comparison to phosphate-buffered saline (PBS)-vaccinated and Mycobacterium bovis BCG-vaccinated groups. We successfully produced MBB and A: E-MBB and used them as vaccines to induce a cellular immune response to mycobacterial antigens. IMPORTANCE Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. In this study, we produced polyhydroxyalkanoate (PHA) biobeads in mycobacteria and used them as vaccines to induce a cellular immune response to mycobacterial antigens.
The outcome of infection with Mycobacterium tuberculosis (MTB) is largely influenced by the host-pathogen interaction in which both the human host and the MTB genetic backgrounds play an important role. Whether this interaction also influences the selection and expansion of drug-resistant MTB strains is the primary focus of this review. We first outline the main and recent findings regarding MTB determinants implicated in the development of drug resistance. Second, we examine data regarding human genetic factors that may play a role in TB drug resistance. We highlight interesting openings for TB research and therapy. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
The latest probable scenario in vaccination strategies is to prime one live attenuated vaccine candidate followed by boost dose of second vaccine candidate. In the present study, we primed the mice with a recombinant Bacille Calmette-Guerin (BCG) comprising Ag85B and ESAT-6 followed by boost doses of Ag85B, ESAT-6 and Ag85B-ESAT-6 fusion protein in the DDA adjuvant, separately. After boost doses of 8 and 12 weeks, the levels of antigen-stimulated T cells secreting interferon (IFN)-gamma, the content of the IFN-gamma, tumor necrosis factor-a and interleukin-4 in the splenocytes in vitro culture supernatant, the antigen-specific immunoglobulin (Ig)G titer from mouse serum, IgG subclass and the population of antigen-specific CD4(+) and CD8(+) T cells were detected. The present study showed that recombinant BCG along with boost doses of Ag85B or ESAT-6 individually did not induce efficient T-helper (Th) 1-type immune response. On the other hand, recombinant BCG with boost doses of Ag85B-ESAT-6 fusion protein enhanced longer lasting predominant Thl immune response. This result suggested that Ag85B might synergize with ESAT-6 protein in order to produce better as well as effective immune response. Thus, the present study concluded recombinant BCG with boost doses of Ag85B-ESAT-6 fusion protein could be a good strategy to improve the immune protective efficacy.
Tuberculosis is one of the most common infectious diseases in China, while delayed patient finding obstructed disease control, especially for smear-negative patients. The current study was undertaken to evaluate the diagnostic accuracy of GeneXpert MTB/RIF compared with conventional methods in the detection of pulmonary tuberculosis patients. A total of 295 spot sputum samples from confirmed pulmonary tuberculosis patients were evaluated from September 2014 to June 2015. Each sample was examined by acid-fast bacillus smear microscopy, culture and GeneXpert MTB/RIF. The sputum culture onLowenstein-Jensen (L-J)was considered as the gold-standard. After testing by smear, 68.81% (203/ 295) was negative and 31.19% (92/295) was positive. As thegold-standard,L-J culture detected 37.97% (112/295) positive of all specimens, while the positivity for GeneXpert MTB/RIF was 46.44% (137/295). Compared with L-J culture, the combined sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for GeneXpert MTB/RIF were 94.64%, 82.97%, 77.37% and 96.18% respectively. For smear-negative specimens, the sensitivity, specificity, PPV and NPV for GeneXpert MTB/ RIF were 96.00%, 83.05%, 44.44% and 99.32%; while for smear-positive specimens, the corresponding accuracy values were 94.25%, 80.00%, 98.80% and 44.44%. The findings of study indicated that GeneXpert MTB/RIF assay demonstrated a high sensitivity in detecting Mycobacterium tuberculosis compared to smear method and a high NPV among smear negative patients. (C) 2017 Elsevier Ltd. All rights reserved.
Mycoplasma ovipneumoniae (MO) is main responsible for pleuropneumonia in sheep. The disease is spreading in the world, and has caused great suffering and losses to the sheep husbandry. Current methodologies for detecting and identifying MO are somehow time consuming, complicated, expensive. Herein, a powerful biosensing platform for effective MO detection has been explored based on manganese dioxide (MnO2) microsphere absorbing Cy5 labeled single strand DNA (Cy5-ssDNA) probe, in which different base number of the complementary of MO conserved sequence was employed. The results demonstrated that the fluorescence enhancement exhibited a good linear relationship with MO plasmid added over a concentration range of 10(2)-10(6) copies/mu L, with the detection limit of 1.042 copies/mu L. This biosensing platform has been finally employed as the feasible probe for MO plasmid and detection with good reproducibility and stability, which exhibited a good performance to discriminate perfect complementary target MO and the base mismatched DNA sequence, illustrated that using MnO2 microsphere absorbing Cy5-ssDNA probe as biosensor can detect MO in simple, rapid, economical, selective and sensitive way, and showed significantly potential in more extensive biochemical application. (C) 2017 Elsevier B.V. All rights reserved.
Magnaporthe oryzae chrysovirus 1 strain A (MoCV1-A) is the causal agent of growth repression and attenuated virulence (hypovirulence) of the rice blast fungus, Magnaporthe oryzae. We previously revealed that heterologous expression of the MoCV1-A ORF4 protein resulted in cytological damage to the yeasts Saccharomyces cerevisiae and Cryptococcus neoformans. Since the ORF4 protein is one of the components of viral particles, we evaluated the inhibitory effects of the purified virus particle against the conidial germination of M. oryzae, and confirmed its suppressive effects. Recombinant MoCV1-A ORF4 protein produced in Pichia pastoris was also effective for suppression of conidial germination of M. oryzae. MoCV1-A ORF4 protein sequence showed significant similarity to 6 related mycoviral proteins; Botrysphaeria dothidea chrysovirus 1, two Fusarium graminearum viruses, Fusarium oxysporum f. sp. dianthi mycovirus 1, Penicillium janczewski chrysovirus and Agaricus bisporus virus 1 in the Chrysoviridae family. Multiple alignments of the ORF4-related protein sequences showed that their central regions (210-591 aa in MoCV1-A ORF4) are relatively conserved. Indeed, yeast transformants expressing the conserved central region of MoCV1-A ORF4 protein (325-575 aa) showed similar impaired growth phenotypes as those observed in yeasts expressing the full-length MoCV1-A ORF4 protein. These data suggest that the mycovirus itself and its encoded viral protein can be useful as anti-fungal proteins to control rice blast disease caused by M. oryzae and other pathogenic fungi. (C) 2016 Elsevier B.V. All rights reserved.
The tumor microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages of differentiation and expanded in response to a variety of tumor factors. MDSCs exert diverse effects in modulating the interactions between immune effector cells and the malignant cells. An increased presence of MDSCs is associated with tumor progression, poorer outcomes, and decreased effectiveness of immunotherapeutic strategies. In this article, we will review our current understanding of the mechanisms that underlie MDSC expansion and their immune-suppressive function. Finally, we review the preclinical studies and clinical trials that have attempted to target MDSCs, in order to improve responses to cancer therapies.
Myeloid-derived suppressor cells (MDSCs) weaken the antitumor immune response through the inhibition of effector T cell activity and the production of immunosuppressive factors in pathological sites. It is well established that interleukin-17A (IL-17A) has a remarkable role on the promotion of inflammation and tumor formation, and IL-17 has been implicated in the enhancement of immunosuppression of MDSCs, which consequently promotes tumor progression. A detailed study of this relationship remains elusive. In our study, we not only confirmed the promotion of IL-17 on Lewis lung carcinoma (LLC) development but also surprisingly showed that IL-17 could extend the fate and enhance the immunosuppressive effect of MDSCs through activating ERK1/2. Additionally, the effect of IL-17 on MDSCs was reversed, even in tumors by blocking ERK1/2. Interdicting the signaling molecule ERK1/2 could increase the apoptosis of MDSCs and weaken the suppressive activity of MDSCs, so that thereafter, the antitumor immunity could be restored partly. Therefore, these findings offer new insights into the importance of IL-17 and the downstream signaling factor ERK1/2 for MDSCs.
In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+ Foxp3(-)(forkhead box P3) IFN-gamma(+) T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.
Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)-induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra-cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3-induced myocarditis. One day post CVB3 infection, C57BL/6 mice were intravenously injected with 1 x 10(6) MSC and sacrificed 6 days later for molecular biology and flow cytometry analysis. MSC application reduced the severity of myocarditis, and heart and blood pro-inflammatory Ly6C(high) and Ly6C(middle) monocytes, while those were retained in the spleen. Anti-inflammatory Ly6C(low) monocytes increased in the blood, heart, and spleen of MSC-treated CVB3 mice. CVB3 infection induced splenic myelopoiesis, while MSC application slightly diminished the spleen myelopoietic activity in CVB3 mice. Left ventricular (LV) mRNA expression of the chemokines monocyte chemotactic protein-1 (MCP)-1, MCP-3, CCL5, the adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, the pro-inflammatory cytokines interleukin-6, interleukin-12, tumor necrosis factor-, the pro-fibrotic transforming growth factor1, and circulating MCP-1 and MCP-3 levels decreased in CVB3 MSC mice, while LV stromal cell-derived factor-1 RNA expression and systemic levels of fractalkine were increased in CVB3 MSC mice. MSC application in CVB3-induced myocarditis modulates monocytes trafficking to the heart and could be a promising strategy for the resolution of cardiac inflammation and prevention of the disease progression.
Background: Fibroblasts are key players in maintaining skin homeostasis and in orchestrating physiological tissue repair and skin regeneration. Dysfunctions in fibroblasts that occur with aging and the senescent process lead to the delayed healing observed in elderly people. The molecular mechanisms leading to fibroblast dysfunction during aging and the senescent process have not yet been clarified. Previously, changes in patterns of glycosylation were observed in fibroblasts in aging and the senescent process, but the effect of these changes on the function of fibroblasts has not been well documented. Here, we investigated whether changes in glycosylation during the process to senescence may have functional effects on fibroblasts. Methods: The changes in cell surface glycans on skin fibroblasts during the process to senescence were examined in early-passage (EP) and late-passage (LP) skin fibroblasts by fluorescence-activated cell sorting analysis using lectins. The contributors to the changes in cell surface glycans were examined by real-time polymerase chain reaction or Western blot analysis. The effects of changes in glycosylation on proliferation, migration, induction of cellular senescence, and myofibroblast differentiation induced by transforming growth factor (TGF)-beta 1 stimulation were examined in EP fibroblasts. The changes in glycosylation were performed by GalNAc-alpha-O-benzyl or sialidase treatment. Results: A decrease in sialylation of glycoproteins and an increase in sialidase NEU1 were observed in LP fibroblasts. The reduction of sialylation did not have any effect on proliferation, migration, or induction of cellular senescence. On the other hand, myofibroblast differentiation was inhibited by the reduction of sialylation, indicating that sialylation is important for myofibroblast differentiation. The localization of CD44 in lipid rafts, which is required for myofibroblast differentiation, was inhibited by the reduction of sialylation. Furthermore, reduced myofibroblast differentiation in LP fibroblasts was restored by a sialidase inhibitor. Conclusions: Desialylation of CD44 with increased sialidase during the process to senescence reduced the localization of CD44 in lipid rafts after TGF-beta 1 stimulation, leading to the inhibition of myofibroblast differentiation. Thus, regulation of sialylation may be an attractive strategy for the prevention and regenerative therapy of age-related skin diseases, cosmetic skin alterations, and chronic wounds caused by delayed healing in elderly people.
PURPOSE. The purpose of this study was to determine the endogenous regulation pattern of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the tree shrew sclera during myopia development and investigate the capacity of exogenous TIMP-2 to inhibit matrix metalloproteinase-2 (MMP-2) in vitro and both scleral collagen degradation and myopia development in vivo. METHODS. TIMP-2 expression in the sclera during myopia development was assessed using polymerase chain reaction. In vitro TIMP-2 inhibition of MMP-2 was investigated using a gelatinase activity plate assay and zymography. Tree shrews were injected with a collagen precursor before undergoing monocular form deprivation and concurrent daily subconjunctival injections of either TIMP-2 or vehicle to the form-deprived eye. In vivo ocular biometry changes were monitored, and scleral tissue was collected after 12 days and assayed for collagen degradation. RESULTS. The development of myopia was associated with a mean reduction in TIMP-2 mRNA expression after 5 days of form deprivation (P < 0.01). Both activation and activity of MMP-2 were inhibited by TIMP-2 with an IC50 of 10 to 20 and 2 nM, respectively. In vivo exogenous addition of TIMP-2 significantly reduced myopia development (P < 0.01), due to reduced vitreous chamber elongation (P < 0.01). In vivo TIMP-2 treatment also significantly inhibited posterior scleral collagen degradation relative to vehicle-treated eyes (P < 0.01), with levels similar to those in control eyes. CONCLUSIONS. Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased degradative activity in the sclera. It follows that replenishment of this TIMP-2 significantly reduced the rate of both scleral collagen degradation and myopia development.
Myxoid/round cell liposarcoma are characterized by typical chromosomal translocations. This genetic alteration might result in specific gene-expression profiles in this tumor entity. To identify over-expressed genes in myxoid/round cell liposarcoma DNA microarray analysis was performed on four tumors and four samples of adult fat tissue. Genes ret, cdk4, cyclin D2 and c-myc showed over-expression by means of microarray analysis and Northern blotting. Immunohistochemistry demonstrated cytoplasmic localization of associated proteins in 36 different tumors. The localization of ret was seen in endothelial cells of plexiform vasculature in addition to its accumulation in tumor cells (25% of cases). The results show an over-expression of cdk4, cyclin D2, c-myc and ret on both the transcriptional and protein level in myxoid/round cell liposarcoma. For cyclin D2 and ret this finding has not been reported in this tumor type. The increase of ret on transcriptional level might be explained by its expression in endothelium in intratumoral plexiform blood vessels. For the molecular pathogenesis of myxoid/round cell liposarcoma our findings imply the involvement of these four genes in the deregulation of the cell cycle, especially as cdk4 and cyclin D2 are target genes of c-myc.
The green peach aphid, Myzus persicae Sulzer (Hemiptera, Aphididae), is an important cosmopolitan pest. Real time qRT-PCR has been used for target gene expression analysis on M. persicae. Using real time qRT-PCR, the expression levels are normalized on the basis of the reliable reference genes. However, to date, the stability of available reference genes has been insufficient. In this study, we evaluated nine candidate reference genes from M. persicae under diverse experimental conditions. The tested candidate genes were comprehensively ranked based on five alternative methods (RefFinder, geNorm, Normfinder, BestKeeper and the comparative Delta C-t method). 18s, Actin and ribosomal protein L27 (L27) were recommended as the most stable reference genes for M. persicae, whereas ribosomal protein L27 (L27) was found to be the least stable reference genes for abiotic studies (photoperiod, temperature and insecticide susceptibility). Our finding not only sheds light on establishing an accurate and reliable normalization of real time qRT-PCR data in M. persicae but also lays a solid foundation for further studies of M. persicae involving RNA interference and functional gene research.
For more than 15 years, motor interference paradigms have been used to investigate the influence of action observation on action execution. Most research on so-called automatic imitation has focused on variables that play a modulating role or investigated potential confounding factors. Interestingly, furthermore, a number of functional magnetic resonance imaging (fMRI) studies have tried to shed light on the functional mechanisms and neural correlates involved in imitation inhibition. However, these fMRI studies, presumably due to poor temporal resolution, have primarily focused on high-level processes and have neglected the potential role of low-level motor and perceptual processes. In the current EEG study, we therefore aimed to disentangle the influence of low-level perceptual and motoric mechanisms from high-level cognitive mechanisms. We focused on potential congruency differences in the visual N190 - a component related to the processing of biological motion, the Readiness Potential - a component related to motor preparation, and the high-level P3 component. Interestingly, we detected congruency effects in each of these components, suggesting that the interference effect in an automatic imitation paradigm is not only related to high-level processes such as self-other distinction but also to more low-level influences of perception on action and action on perception. Moreover, we documented relationships of the neural effects with (autistic) behavior.
Representing an important greenhouse gas, nitrous oxide (N2O) emission from cultivated land is a hot topic in current climate change research. This study examined the influences of nitrogen fertilisation, temperature and soil moisture on the ammonia monooxygenase subunit A (amoA) gene copy numbers and N2O emission characteristics. The experimental observation of N2O fluxes was based on the static chamber-gas chromatographic method. The ammonia-oxidising bacteria (AOB) and ammonia-oxidising archaea (AOA) gene copy numbers in different periods were measured by real-time polymerase chain reaction (PCR). The results indicated that rain-fed potato field was a N2O source, and the average annual N2O emission was approximately 0.46 +/- 0.06 kgN(2)O-N/ha/year. N2O emissions increased significantly with increase in fertilisation, temperatures below 19.6 A degrees C and soil volumetric water content under 15%. Crop rotation appreciably decreases N2O emissions by 34.4 to 52.4% compared to continuous cropping in rain-fed potato fields. The significant correlation between N2O fluxes and AOB copy numbers implied that N2O emissions were primarily controlled by AOB in rain-fed potato fields. The research has important theoretical and practical value for understanding N2O emissions from rain-fed dry farmland fields.
Plants are exposed to all types of abiotic stresses during the process of growth and development, which could adversely affect the productivity and postharvest storage quality of plants. In the current study, the expression of SNAC4-9 and the changes of physiological parameters were analyzed in tomato seedlings under various abiotic conditions and hormone treatments. The results demonstrate that all six genes were induced by these stresses at differential induction levels and that SNAC4-9 gene expression profiles were likely to be related to the ABA, SA, and MeJA signaling pathways. In addition, all of the stress- and hormone-treated seedlings exhibited significant increases in their proline content and antioxidant enzyme activities. MDA was significantly increased in seedlings exposed to stress and decreased in hormone-treated seedlings. These data collectively suggest that SNAC4-9 might function through ABA, SA, and JA signaling pathways and the regulation of proline and antioxidant systems. This study combines molecular biology and physiology to provide valuable information for further exploring the functional roles of NAC genes in response to environmental stresses and indicates that these genes may exhibit potential for enhancing stress tolerance of transgenic tomato plants and further improving the postharvest storage quality of tomato plants.
The aim of this study is to investigate antibacterial effects of immunodominant proteins isolated from the venom of Naja Naja Oxiana snake against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. The innate immune system is an important line of defense against bacterial diseases. Antibacterial peptides and proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial diseases and the potential of being converted into new therapeutic agents. Identification of immunodominant proteins of the venom of Naja Naja Oxiana snake was performed by SDS-PAGE and western blot analysis. Identified proteins were isolated directly from preparative gel electrophoresis by Electro-elution. In the next step, antibacterial effects of immunodominant proteins were tested against several strains of clinical isolates, including S. aureus, B. subtilis (Gram-positive bacteria) P. aeruginosa and E. coli (Gram-negative bacteria) using broth microdilution and disc-diffusion assays. In order to compare the results of the discdiffusion assay, antibacterial effects of several antibiotics (Gentamicin, Ampicillin, Penicillin, Amoxicillin and Ciprofloxacin) were also examined using the same conditions. Results showed that immunodominant proteins of (14, and 65kDa) with high immunogenicity were very effective in inhibiting the growth of two Gram-positive bacteria (S. aureus, B. sub) that were tested. However, they were only moderately effective in inhibiting the growth of the two tested Gram-negative bacteria (P. aeruginosa and E. coli). However, immunodominant proteins of 22 kDa and 32kDa with high immunogenicity, showed slight effectiveness in inhibiting the growth of two; the Gram-positive and Gram-negative bacteria that were tested. To the best of our knowledge, these immunodominant proteins are novel antigens for potent antimicrobial effects against two gram-positive bacteria (S. aureus, B. subtilis) and less antimicrobial effect against two gram-negative bacteria (E. coli, P. aeruginosa) that were prepared.
Being a proven photocatalyst, nano-anatase is capable of undergoing electron transfer reactions under light. In previous studies, we had proven that nano-anatase improved photosynthesis and greatly promoted spinach growth. However, the molecular mechanisms of carbon reaction promoted by nano-anatase are still not clearly understood. In the present paper, reverse transcription polymerase chain reaction and Northern blotting were carried out, and the results showed that the expression of ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) small subunit (rbcS) and Rubisco large subunit (rbcL) messenger RNA (mRNA) in the nano-anatase-treated spinach were obviously promoted, respectively, while the effects of bulk TiO2 were not so significant. Accordingly, the protein expression of Rubisco from the nano-anatase-treated spinach was increased by 40% compared with control. Further analysis indicated that the activity of Rubisco in the nano-anatase-treated spinach was significantly higher than the control, by up to 2.33 times, and bulk TiO2 treatment had no such significant effects. Together, one of the molecular mechanisms of carbon reaction promoted by nano-anatase is that the nano-anatase treatment results in the enhancement of Rubisco mRNA amounts, the protein levels, and activity of Rubisco, thereby leading to the improvement of Rubisco carboxylation and the high rate of photosynthetic carbon reaction.
Hydrochloric acid doped thin film of poly-o-methyl aniline (POMANI)-Mn3O4 nanocomposites have been fabricated on glass substrate. The nanocomposite films showed RT-NTC characteristics in the temperature range of 35-185 degrees C with repeatability in the temperature range of 75-185 degrees C. The cut off temperature of the thermistor fabricated from the nanocomposite material was found to be between 165 and 170 degrees C. Synthesised nanocomposite material has been characterized using FT-IR, XRD, TEM for structure, morphology and TGA/DTC for thermal stability. Thermistor constant (beta) observed from RT characteristics are in the range of 7363 K-10,188 K and activation energy (Delta E) was calculated which was in the range 0.634 eV-0.878 eV. Further linearization of thin film based NTC thermistors was carried out using an low cost analog circuit by adding parallel (R-P), series resistance (R-S) and operational amplifier (OP-AMP). It has been observed that these thin film based temperature sensors have repeatable temperature sensing behavior on linearization with high sensitivity and low power dissipation (P-diss)2015 (C) Elsevier B.V. All rights reserved.
Organic-inorganic nano-materials have attracted growing attention due to their potential applications for optoelectronic devices, sensors, and heterogeneous catalysts. We reported here on the preparation of polynary nanocomposites composed of poly(4-vinylpyridine) (P4VP) functionalized multi-walled carbon nanotubes (MWNTP4VP), silica nanoparticles (nano-SiO2), viologens, and/or phosphomolybdic acid (PMA), in which the MWNTP4VP, nano-SiO2, and viologens were covalently connected while PMA was electrostatically adsorbed. Thermogravimetric analysis revealed that the nanocomposites were composed of about 40-45% MWNTs, 40-45% nanoSiO(2), as well as 10-15% organic species and others. The preparation processes and compositions of the nanocomposites were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Field emission transmission electron microscopic images revealed that the nano-SiO(2)BenV particles were strongly attached to the MWNTP4VP surfaces to form MWNTP4VP@nano-SiO(2)BenV triad nano-cores. Cyclic voltammo-grams of the MWNTP4VP@nano-SiO(2)BenV casting films showed three couples of redox waves in the potential range between -0.8 and 0 V (vs Ag/AgCl), designated to the electron transfer process of viologen substituents of MWNTP4VP@nano-SiO(2)BenV(2+)MWNTP4VP@nano-SiO(2)BenV(+center dot) and their dimers. Further, three couples of redox waves were recorded for the casting films of MWNTP4VP@nanoSiO(2)BenV/PMA polynary nanocomposites in the potential range between -0.2 and 0.8 V, designated to three successive electron transfer processes of PMA. Finally, it was revealed that the present MWNTPVP@nano-SiO(2)BenV/PMA polynary composites could act as efficient heterogeneous catalysts for the electrocatalytic reduction of bromate. (C) 2017 Elsevier B.V. All rights reserved.
Nano-fibrillated cellulose (NFC), an abundant renewable bio-macromolecule, has received much attention in the research community. The study detailed herein is related to the preparation of photocatalytic nanocomposites consisting of nano-fibrillated cellulose/magnetite/titanium dioxide nanoparticles (NFC@Fe3O4@TNP). The aim of this study is to improve the photocatalytic efficiency of NFC-TNP composites and to improve their recyclability during the photocatalytic hydrogen generation. The NFC@Fe3O4@TNP nanocomposites were characterized by TEM, EDX, SAED, XRD, XPS, FTIR, Raman spectra and VSM techniques, The results showed that Fe3O4 NP and TNP were Well-distributed on the surface of NFC. The photocatalytic efficiency study showed that NFC@Fe3O4@TNP nanocomposites represented a higher photocatalytic hydrogen generation rate in comparison with that of NFC-TNP sample. In addition, the NFC@Fe3O4@TNP nanocomposites can be readily recovered from the system using a magnet due to their stable superparamagnetic properties, and they had only a marginal loss of TNP and photocatalytic efficiency after fifteen cycles. (C) 2017 Published by Elsevier B.V.
Gas sensors play a vital role on many aspects in our society, and have gained much progress, propelled by the development of nanoscience and nanotechnology. In this regard, metal oxides with heterojunctions have attracted tremendous attention owing to their enhanced gas sensing properties. Herein, belt-tooth shape ZnO/In2O3 nano-heterostructures has been achieved through a chemical vapor deposition process. The gas sensor fabricated from the as-prepared nano-heterostructures exhibits superior sensing performances for C2H2 gas at low operating temperature (90 degrees C). Moreover, the Au decorated ZnO/In2O3 nano-heterostructures (Au-ZnO/In2O3) exhibit enhanced C2H2 sensing properties such as higher response, less response time, better selectivity and smaller deviation from the ideal value of power exponent. More significantly, the response to C2H2 gas is maintained well in 30 days, indicating good long-term stability. In addition, both the potential-barrier-controlled carrier transport model combining with the surface depletion model and the unique properties of Au are presented to describe the C2H2 gas sensing mechanism of Au-ZnO/In2O3. This study offers an innovative methodology to design novel gas sensing materials and enhance gas sensing performances. (C) 2016 Elsevier B.V. All rights reserved.
Polymeric nanoparticulate carriers play an important role and holding a significant potential for the development of novel immunomodulatory agents as easily they are taken up by antigen presenting cells. They allow an enhanced antigen stability, better immunogenicity and immunostimulatory effect with sustained and controlled release of the antigen to the target sites. Better information and vital understanding of mechanism of action, interaction of such vectors with the APCs and dendritic cells and antigen release kinetics in immunomodulatory effects, and improved knowledge of their in vivo fate and distribution are now needed, those collectively would speed up the rational strategies of nanoparticles as carriers for vaccines and other protein antigens. The evolution of such innovative adjuvants for protein and DNA immunizations are an exciting and growing zone in immunology, which may enhance the clinical outcomes in many infectious and non-infectious diseases. This review summarizes the recent advances in nano-vaccinology with polymeric (especially biodegradable) carriers, their methods of preparation, surface modification, their interaction with antigen presenting cells, release of antigens, its kinetics and mechanism in the delivery of vaccines via non-invasive routes.
In recent years, the change of biological effects in tumor cells triggered by nanoparticles had become a new breakthrough in cancer therapy. Especially, it was widely accepted that various drug loaded nanoparticles induced tumor cell death by encapsulating more drugs and depending on EPR effects to enhance the concentration of drugs in tumor sites. Nanoparticles as a useful new approach had attracted increasing attention to treat cancer. In fact, nanoparticles also played an important role on tumor cell invasion and metastasis. We used chitosan nanoparticles as a module to explore the internalization of chitosan nanoparticles on the effects of invasion and metastasis in tumor cells. Our new finding demonstrated that chitosan nanoparticles were shown to have the ability of inducing reactive oxygen species and believed to significantly enhance cell invasion and metastasis.
Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response. (C) 2016 Elsevier B.V. All rights reserved.
Optical methods to manipulate and detect nanoscale objects are highly desired in both nanomaterials and molecular biology fields. Optical tweezers have been used to manipulate objects that range in size from a few hundred nanometres to several micrometres. The emergence of near-field methods that overcome the diffraction limit has enabled the manipulation of objects below 100 nm. A highly free manipulation with signal-enhanced real-time detection, however, remains a challenge for single sub-100-nm nanoparticles or biomolecules. Here we show an approach that uses a photonic nanojet to perform the manipulation and detection of single sub-100-nm objects. With the photonic nanojet generated by a dielectric microlens bound to an optical fibre probe, three-dimensional manipulations were achieved for a single 85-nm fluorescent polystyrene nanoparticle as well as for a plasmid DNA molecule. Backscattering and fluorescent signals were detected with the enhancement factors up to similar to 10(3) and similar to 30, respectively. The demonstrated approach provides a potentially powerful tool for nanostructure assembly, biosensing and single-biomolecule studies.
The potency of conventional antivenom (AV) conjugated to soy protein nanoparticles (NPs) (C-AV) was compared with the free AV in neutralizing the systemic toxicity of Naja naja venom. The effective dose (ED50) of AV and C-AV to neutralize the venom-induced toxicity in mice was found to be 19.89 and 9.50 mg, respectively. The histopathological examination of heart, liver, and kidney indicated that the systemic toxicity induced by the venom was effectively neutralized by lower concentrations of C-AV than compared with AV. In addition, C-AV was found to be more effective in neutralizing the edema forming activity of N. naja venom compared with the AV. Thus, the results of this study indicate that the potency of commercially available AV could be improved by conjugating it to soy protein NPs. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 827-833, 2016
With the development of nanotechnology, understanding of intermolecular interactions on a single molecule level by atomic force spectroscopy (AFM) has played an important role in molecular biology and biomedical science. In recent years, some research suggested that the presence of metal cations is an important regulator in the processes of misfolding and aggregation of the amyloid beta-protein (A beta), which may be an important etiological factor of Alzheimer's disease. However, the knowledge on the principle of interactions between A beta and metal cations at the single molecule level is still poor understood. In this paper, the amyloid beta-protein (A beta) was fabricated on substrate of mixed thiol-modified gold nanoparticles using self-assembled monolayer method and the adhesion force in the longitudinal direction between metal cations and A beta 42 were investigated by AFM. The role of metal ions on A beta aggregation is discussed from the perspective of single molecular force. The force results showed that the specific adhesion force F-i and the nonspecific force F-0 between a single A beta-A beta pair in control experiment were calculated as 42 +/- 3 and 80 pN, respectively. However, Fi between a single A beta-A beta pair in the presence of Cu2+, Zn2+, Ca2+ and Al3+ increased dramatically to 84 +/- 6, 89 +/- 3, 73 +/- 5, 95 +/- 5 pN successively, which indicated that unbinding between A beta proteins is accelerated in the presence of metal cations. What is more, the imaging results showed that substoichiometric copper cations accelerate the formation of fibrils within 3 days. The combined atomic force spectroscopy and imaging analysis indicate that metal cations play a role in promoting the aggregating behavior of A beta 42.
In the last two decades, a lot of progress has been made in Nanotechnology and Nanoscience, an exploitation of matter on atomic, molecular and supermolecular scale. Nanotechnology because of its size is widely used in such varied fields as surface science, molecular biology, organic chemistry, semi-conductor physics, micro fabrication, medical sciences, electronics, biomaterials, energy production, etc. Using nanotechnology, Researchers have been able to develop new materials with nanoscale dimensions to directly control matter on the atomic or molecular scale. Due to the range of many potential applications, both industrial and military, many governments boast invested billions of dollars in nanotechnology and nanoscience research. This brief review deals with the fundamentals of nanotechnology and nanoscience and its application in various fields. It also discusses the future of nanotechnology and the risks involved in it.
With increasing demand for energy and advances in exploration and development technologies, more attention is being devoted to exploration and development of deep oil and gas reservoirs. The Nanpu Sag contains huge reserves in deep oil and gas reservoirs and is a promising area. In this paper, the physico-chemical and mechanical properties of hard brittle shales from the Shahejie Formation in the Nanpu Sag in the Bohai Bay Basin of northern China were investigated using a variety of methods, including x-ray diffraction analysis, cation exchange capacity (CEC) analysis, contact angle measurements, scanning electron microscope observations, immersion experiments, ultrasonic testing and mechanical testing. The effects of the physico-chemical properties of the shales on wellbore instability were observed, and the effects of hydration of the shales on wellbore instability were also examined. The results show that the major mineral constituents of the investigated shales are quartz and clay minerals. The clay mineral contents range from 25.33% to 52.03%, and the quartz contents range from 20.03% to 46.45%. The clay minerals do not include montmorillonite, but large amounts of mixed-layer illite/smectite were observed. The CEC values of the shales range from 90 to 210 mmol kg(-1), indicating that the shales are partly hydrated. The wettability of the shales is strongly water-wetted, indicating that water would enter the shales due to the capillary effect. Hydration of hard brittle shales can generate cracks, leading to changes in microstructure and increases in the acoustic value, which could generate damage in the shales and reduce their strength. With increasing hydration time, the shale hydration effect gradually becomes stronger, causing an increase in the range of the acoustic travel time and decreases in the ranges of cohesion and internal friction angles. For the hard brittle shales of the Nanpu Sag, drilling fluid systems should aim to enhance sealing ability, decrease drilling fluid filter loss and increase the amount of clay-hydration inhibitor used.
Phytoene synthase (PSY), as a key regulatory enzyme for carotene biosynthesis, plays an important role in regulating color formation in many species. In the present study, a protocol was developed for the transformation of Narcissus tazzeta var chinensis using Agrobacterium tumefaciens strain LBA4404 harboring a binary vector pCAMBIA1301 plasmid which contained an antisense phytoene synthase gene, a reporter beta-glucuronidase gene and a selectable marker hygromycin phosphotransferase gene. Effects of some factors on efficiency of transformation and regeneration were examined. Preculture of the explants for 6 days before inoculation enhanced the transient GUS expression. The addition of acetosyringone (AS) at 100 mu mol l(-1) stop for inoculation and a period of 3 days co-cultivation yielded efficient transient GUS expression. Transformants were obtained through selection on MS medium containing 5 mg l(-1) 6-benzylaminopurine(BA), 0.1 mg l(-1) alpha-naphthalene acetic acid (NAA) and 40 mg l(-1) hygromycin (.) under bar The transformation frequency was 1.24% based on PCR analysis of gus gene. One or two copies of transgene were demonstrated in different transformations by Southern blotting analyses. Northern blotting results confirmed that the transcription of the endogenous psy gene in transgenic plants was inhibited or silenced. The method reported here provides new opportunities for improvement of quality traits of Narcissus tazzeta via genetic transformation.
Differences in people's beliefs can substantially impact their interpretation of a series of events. In this functional MRI study, we manipulated subjects' beliefs, leading two groups of subjects to interpret the same narrative in different ways. We found that responses in higher-order brain areas-including the default-mode network, language areas, and subsets of the mirror neuron system-tended to be similar among people who shared the same interpretation, but different from those of people with an opposing interpretation. Furthermore, the difference in neural responses between the two groups at each moment was correlated with the magnitude of the difference in the interpretation of the narrative. This study demonstrates that brain responses to the same event tend to cluster together among people who share the same views.
This meta-analysis investigates the extent to which people's leisure reading may produce better social-cognitive abilities. Researchers have hypothesized that experiences of fiction (more so than nonfiction) will improve readers' empathy and theory of mind. To capture the size of this effect, we aggregated correlations between measures of lifetime reading habits for both fiction and nonfiction with measures of empathy and theory of mind. Consistent with previous evidence, fiction reading had a larger correlation with the social-cognitive measures compared to nonfiction reading. However, the effects were small in magnitude. Heterogeneity analyses indicated that the effect sizes were consistent across studies. We also examined gender, publication status, and design as moderators. However, none of the moderators reached significance. We suggest that the results of this meta-analysis sanction a shift in research agenda toward understanding causal mechanisms.
Nattokinase (NK) is a health product for the prevention and potential control of thrombosis diseases. To explore the possibility of enhancing NK production in Bacillus subtilis by altering the promoter of NK gene (PaprN), we tested several methods. We substituted the wild-type -10 box (TACAAT) of PaprN with the consensus sequence (TATAAT) of sigma(A)-dependent promoters, mutated the original -35 box (TACTAA) to a partial consensus sequence (TACACA), and expressed aprN from two tandem promoters, respectively. The efficacies of these changes were monitored by fibrinolytic activity, SDS-PAGE, and northern blotting analyses. Fibrinolytic activity analysis showed that altering the -10 region of PaprN could increase NK production by 136%. This production is significantly higher than those reported in the literatures. Similar results were obtained in SDS-PAGE and northern blotting analyses. This engineered promoter was also able to enhance the expression of beta-glucuronidase (GUS) by 249%. Partial alteration of the -35 element could slightly improve the production of NK by 13%, while two tandem promoters just had marginal effects on the production of NK. Our study showed that alteration of -10 or -35 elements in PaprN, especially -10 element, is an effective way to enhance the production of heterologous proteins in B. subtilis.
Overlapping sense/antisense RNAs transcribed in opposite directions from the same genomic locus are common in vertebrates. The impact of antisense transcription on gene regulation and cell biology is largely unknown. We show that sense/antisense RNAs of an evolutionarily conserved phosphate transporter gene (Slc34a2a) are coexpressed in a short time window during embryonic development of zebrafish at 48 hours postfertilization (hpf). To address the mechanism by which coexpressed sense/antisense transcripts are processed, we injected sense/antisense RNAs in various combinations into Xenopus oocytes. In the cytoplasm RNAs were stable in whatever combination expressed. In the nucleus coinjected sense/antisense transcripts were degraded into short RNAs of similar to 23 bases within 4 h. A homologous transcript from toad or another isoform (Slc34a2b) from zebrafish failed to trigger processing. In oocytes that were primed with nuclear sense/antisense RNA coinjections, a reporter RNA was rapidly degraded. We produced evidence that the observed processing of complementary transcripts was not restricted to Xenopus oocytes, because Slc34a-related short RNAs were detected in zebrafish embryos by Northern blotting. Signals were observed at stages that showed coexpression of sense/antisense transcripts. Remarkably, strand-specific probes revealed that the orientation of short RNAs was developmentally regulated. In addition, RNA from zebrafish embryos 48 hpf was able to induce degradation of reporter constructs in Xenopus oocytes. Our findings may give important clues to understanding the physiological role of the widespread antisense transcription.
High-throughput sequencing has identified a large number of sense-antisense transcriptional pairs, which indicates that these genes were transcribed from both directions. Recent reports have demonstrated that many antisense RNAs, especially IncRNA (long non-coding RNA), can interact with the sense RNA by forming an RNA duplex. Many methods, such as RNA-sequencing, Northern blotting, RNase protection assays and strand-specific PCR, can be used to detect the anti sense transcript and gene transcriptional orientation. However, the applications of these methods have been constrained, to some extent, because of the high cost, difficult operation or inaccuracy, especially regarding the analysis of substantial amounts of data. Thus, we developed an easy method to detect and validate these complicated RNAs. We primarily took advantage of the strand specificity of RT-PCR and the single-strand specificity of S1 endonuclease to analyze sense and antisense transcripts. Four known genes, including mouse beta-actin and Tsix (Xist antisense RNA), chicken LXN (latexin) and GFM1 (G elongation factor, mitochondrial 1), were used to establish the method. These four genes were well studied and transcribed from positive strand, negative strand or both strands of DNA, respectively, which represented all possible cases. The results indicated that the method can easily distinguish sense, antisense and sense-antisense transcriptional pairs. In addition, it can be used to verify the results of high-throughput sequencing, as well as to analyze the regulatory mechanisms between RNAs. This method can improve the accuracy of detection and can be mainly used in analyzing single gene and was low cost.
The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44, and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have classically been defined as activating receptors that trigger cytotoxicity and cytokine responses by NK cells upon engaging with ligands on tumor cells. Several new findings, however, have challenged this model and identified alternative mechanisms regulating the function of NCRs. Recent reports indicate that ligand matters, since the interaction of NKp44 with distinct ligands on target cells can either activate or inhibit NK cells. Also, the NCRs have been found to interact with distinct specificities to various heparan sulfate glycosaminoglycans, which are complex polysaccharides found in extracellular matrix or on cell surface heparan sulfate proteoglycans (HSPGs). The NCRs can engage with HSPGs in trans as a co-ligand on the target cells or in cis on the NK cell surface to regulate receptor-ligand interactions and NK cell activation. A number of splice variants of ncr2 and ncr3 have also been identified, and a predominant expression of certain variants results in inhibitory signaling through NKp44 and NKp30. Several recent studies have found that the selective expression of some of these inhibitory splice variants can significantly influence outcome in the contexts of cancer, infection, and pregnancy. These findings establish that NCR functions are more diverse than originally thought, and better understanding of their splice variant expression profiles and ligand interactions are needed to establish their functional regulation in the context of human health.
We propose a two-stage mixed-integer linear stochastic optimization model to analyze the scheduling of electricity-production units under natural gas-supply uncertainty due to pipeline congestion and natural gas-price variability. The first stage of this stochastic optimization model represents the day-ahead scheduling (i.e., unit commitment) stage, while the second stage represents actual real-time operations through a number of scenarios. We use this model to analyze the effect on unit commitment and dispatch of two types of natural gas-supply conditions. First, we analyze a case involving low-cost natural gas supply with natural gas-transmission issues related to potential gas-pipeline congestion. We then examine a case involving higher-cost natural gas, which is used solely to attain feasibility with fast-ramping events. The first case mimics situations in the ISO New England system, in which relatively low-cost natural gas supply is uncertain in cold-weather conditions due to natural gas-transmission bottlenecks. The second case is reminiscent of situations in the California ISO system, in which relatively expensive but flexible natural gas-fired units need to be used to handle rapid changes in net demand in the early mornings and late afternoons.
Natural killer cells (NK cells) are traditionally attributed to the innate immune system. It is considered that previously received stimuli have little effect on the functioning of these immune cells. Indeed, NK cells even without prior sensitization provide a rapid effector response against tumor, virus-infected, or otherwise damaged cells. They have a limited repertoire of receptors, the expression of which does not require somatic recombination. However, recent data indicate that NK cells may acquire the properties specific to adaptive immune cells. In particular, NK cells have been shown to possess the features of immunological memory, namely, the ability to more quickly and effectively respond to a repeated stimulus. The mechanisms of memory acquisition in NK cells differ from those implemented in T and B lymphocytes and are still rather vague. Presumably, some of these mechanisms underlie the significant phenotypic and functional NK cell diversity emerging during their differentiation. The recent data accumulated in this area considerably change the existing immunology paradigm, which postulates a clear delineation of the adaptive and innate immune cells. The published data on phenotypic and functional characteristics of NK cells and particular changes in these characteristics during NK cell differentiation and generation of memory-like NK cells are reviewed.
Both proponents and opponents of the claim that mental disorders are natural kinds compare mental disorders to paradigmatic examples of natural kinds, to inquire into a set of properties that achieve three scientific tasks: explanation, prediction, and intervention. I argue that the comparative strategy fails to take us to any intervention-related properties of mental disorders. I replace it with what I call a trilateral strategy-a strategy guided by first-person accounts of individuals with mental disorders, and the relevant clinical and scientific work on psychopathology. I illustrate how the trilateral strategy works with a focus on schizophrenia-an example used by both sides of the debate.
The fact that the CD30 molecule can mediate signals for cell proliferation or apoptosis prompted us to perform a systematic investigation of CD30 antigen expression in embryonal tissues during proliferation and differentiation stages. We first targeted the foetal human intestinal cryptae cells with positive results. The epidermis is a dynamic epithelium that is constantly renewed throughout life. The basal layer, attached to the basement membrane, contains the dividing cells of the skin and as cells move up from this layer they undergo differentiation, ending in the formation of a terminally differentiated anucleate cell called squame. It is intriguing to find out if cells in the basal layer can express the CD30 antigen. We investigated the immunohistochemical expression of CD30 antigen in 15 paraffin-embedded tissue samples representing epidermis and epidermal buds from foetuses after spontaneous abortion in the 8th, 10th and 12th weeks of gestation, respectively, using the monoclonal antibody NCL-CD30. A Northern blotting analysis was additionally performed. The results showed that: (1) the epithelial cells of the epidermis in the developing skin express the CD30 antigen; (2) CD30 expression in these epithelial cells is higher in cases of hormonal administration than in normal gestation; (3) a similar positive reaction involved the epidermal buds associated with the development of the skin appendages. Northern blots of tissue sections using a CD30 cDNA probe detected mRNAs of the same molecular mass and variety similarly to those in the positive control cell line HUT 102.
The relatively new field of microRNA (miR) has experienced rapid growth in methodology associated with its detection and bioanalysis as well as with its role in -omics research, clinical diagnostics, and new therapeutic strategies. The breadth of this area of research and the seemingly exponential increase in number of publications on the subject can present scientists new to the field with a daunting amount of information to evaluate. This review aims to provide a collective overview of miR detection methods by relating conventional, established techniques [such as quantitative reverse transcription polymerase chain reaction (RT-qPCR), microarray, and Northern blotting (NB)] and relatively recent advancements [such as next-generation sequencing (NGS), highly sensitive biosensors, and computational prediction of microRNA/targets] to common miR research strategies. This should guide interested readers toward a more focused study of miR research and the surrounding technology.
In two studies, we examine how need for cognitive closure (NFC), referring to an individual's tendency to reduce uncertainty via rigid processing style, relates to the way attentional resources are distributed while multitasking. Previous studies show that NFC is related to focused, rather than distributed, attention. High NFC individuals should thus process tasks serially rather than in parallel. That is, in order to maintain performance on an additional task, they would need to shift attentional focus to this task more often. Low NFC individuals, on the other hand, should be able to process both tasks in parallel, i.e. they would maintain performance on the additional task with fewer attentional shifts. To test our hypotheses, we asked participants to perform a main and additional task simultaneously. During task performance participants' eyes were tracked. In line with our predictions, the interest area analysis showed that NFC was related to more fixations and longer dwell time on the additional task. It was also associated with more runs to this task (Studies 1 and 2). The effects were stronger in difficult, compared to easy, condition (Study 2). The paper is the first one to directly test attention allocation during multitasking depending on NFC levels. (C) 2017 Elsevier Ltd. All rights reserved.
Negative symptoms have long been conceptualized as a core aspect of schizophrenia. They play a key role in the functional outcome of the disorder, and their management represents a significant unmet need. Improvements in definition, characterization, assessment instruments and experimental models are needed in order to foster research aimed at developing effective interventions. A consensus has recently been reached on the following aspects: a) five constructs should be considered as negative symptoms, i.e. blunted affect, alogia, anhedonia, asociality and avolition; b) for each construct, symptoms due to identifiable factors, such as medication effects, psychotic symptoms or depression, should be distinguished from those regarded as primary; c) the five constructs cluster in two factors, one including blunted affect and alogia and the other consisting of anhedonia, avolition and asociality. In this paper, for each construct, we report the current definition; highlight differences among the main assessment instruments; illustrate quantitative measures, if available, and their relationship with the evaluations based on rating scales; and describe correlates as well as experimental models. We conclude that: a) the assessment of the negative symptom dimension has recently improved, but even current expert consensus-based instruments diverge on several aspects; b) the use of objective measures might contribute to overcome uncertainties about the reliability of rating scales, but these measures require further investigation and validation; c) the boundaries with other illness components, in particular neurocognition and social cognition, are not well defined; and d) without further reducing the heterogeneity within the negative symptom dimension, attempts to develop successful interventions are likely to lead to great efforts paid back by small rewards.
Background. Dental health care professionals play an important role as mandated advocates when health care neglect is suspected in children; however, there is some confusion around what constitutes child neglect. Methods. The authors reviewed the dental literature for descriptors and definitions of neglect. They studied the individual state statutes to learn the protection afforded for both victims of neglect and for health care providers acting on behalf of such children. They also reviewed methods of action to address suspected neglect. Results. The authors found confusion around what is or is not child neglect. Yet, dental professionals are tasked by the law, and by a moral code, to protect children from neglect. The authors offer a definition of neglect and suggested practice guidelines to assist the practitioner acting as a child's advocate. Conclusions. Clinicians can use strategies to address the problem of child neglect. A digital data treatment registry may provide additional views of a child's health status. Practical Implications. With a better understanding of the definition of neglect, strategies can be implemented for use by the dental team to address this problem of neglect and reduce its incidence.
Early life neglect increases risk for the development of psychopathologies during childhood and adulthood, including depression and anxiety disorders. We recently reported epigenetic changes in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3 (ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting Protein (TPPP). To validate the role of these genes in depression risk, secondary analyses were conducted of gene expression data obtained from medial prefrontal cortex (mPFC) tissue of mice subjected to a model of maternal neglect which included maternal separation and early weaning (MSEW). Anxiety and depression-like phenotype data derived using the elevated plus maze (EPM) and forced swimming test (FST), respectively, were also available for secondary analyses. Behavioral tests were conducted in MSEW and control adult male mice when they were between 65 and 80 days old. ID3, GRIN1 and TPPP gene expression in the mPFC were found to significantly predict behavioral differences in the EPM and FST. These results further support the role of these genes in the etiology of depressive and anxiety phenotypes following early life stress. (C) 2016 Published by Elsevier B.V.
Parenting behaviors are influenced by numerous factors, including individual, family, and community contexts. Ecological systems theory suggests that these systems as well as interactions among the systems coalesce to influence the parent/child relationship in multiple ways. When challenges exist within and across these systems, child abuse and neglect can occur. While a significant body of research has delved into parsing the relative importance of neighborhood-level versus individual-level predictors, little is known about the complex ways in which interactions across ecological systems might enhance or hinder parenting behaviors. The current study seeks to fill this gap by answering the following research question: (1) Are there interactive effects of individual and neighborhood poverty on the risk of child maltreatment? Structural equation modeling was used to analyze data from 946 parents at Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics in Franklin County, Ohio. Living in higher poverty neighborhoods is associated with higher levels of maltreatment irrespective of individual poverty status, but there is not a corresponding decrease for those living in lower poverty neighborhoods. These findings suggest that both individual poverty status and neighborhood poverty matter for child maltreatment and that there does not appear to be a compounding effect of being both poor and in a poor neighborhood, nor is there a protective effect when poor but living in a nonpoor neighborhood. (C) 2016 Elsevier Ltd. All rights reserved.
Parents interact with their environment in important ways that may impact their ability to parent their children positively. The current study uses data from the age 3 wave of the Fragile Families and Child Wellbeing study to investigate whether neighborhood processes and community participation relate to internal control, and whether these three variables are associated with child maltreatment behaviors. Using structural equation modeling, the direct and indirect effects of the environment (neighborhood disorder, social control, and social cohesion) and community participation on child maltreatment are tested. The mediating variable tested is internal control. The results show that neighborhood processes and community participation are associated with child neglect, physical child abuse, and psychological aggression but that these associations are driven through their effect on internal control. (C) 2016 Elsevier Ltd. All rights reserved.
The complete coding sequence of manganese superoxide dismutase (Mn-SOD) of Trichinella pseudospiralis (Tp) was obtained and characterized for the first time by degenerative reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of complementary DNA ends (RACE) reactions. The open reading frame of Tp Mn-SOD contained 663 nucleotides, encoding 220 amino acid residues. This included the conserved histidine and aspartate residues for metal binding, cysteine residues for disulfide bond formation, and arginine residue for directing the superoxide ion to the protein. The presence of mitochondrial transit peptides and maturation cleavage site suggest that the cloned Tp Mn-SOD gene is a mitochondrial enzyme. It is a single copy gene containing three introns. Northern blotting suggested that the expression level of Mn-SOD is lower than Cu/Zn SOD in infective stage larvae. Semi-quantitative RT-PCR demonstrated that a single dominant transcript of Tp Mn-SOD was highly expressed in the infective-stage larvae but not in adult worms. The information provides a better understanding of the highly compartmentalized superoxide dismutases of adenophorean nematodes.
The neoliberal direction of social policy under New Zealand's fifth National government (2008-) is demonstrated in its 2012 White Paper for Vulnerable Children. This document advocates increased monitoring and policing of welfare populations and the downgrading of child protection policy to a technical administrative system for managing risky' families. The White Paper's release came soon after the coroner's report into the deaths of the Kahui twins', which were treated by the media as a shocking case of child abuse, and exemplified the media's use of a fantasy of a savage' Maori welfare underclass in reporting cases of child abuse. Drawing on Isin's analysis of governing through neurosis', this article explores how these media and policy discourses reinforce normative patterns of neoliberal citizen subjectivity by offering compelling pathways out of anxiety that re-route citizens' anxiety over child abuse in support of neoliberal modes of citizen subjectivity.
The death of a neonate is devastating for all involved. Each year, critically ill neonates present to emergency departments across the United States. These infants require acute medical interventions with a goal of stabilization. Despite these efforts, hundreds of infants die every year in emergency departments across the United States. Emergency care providers, unaccustomed to providing neonatal end-of-life care, may feel unsure about how to best care for families during resuscitative measures and after neonates die. There is literature to suggest that increased knowledge and advance preparation can calm fears of providers caring for patients in such tragic situations. We aim to provide in this article a broad overview of a variety of topics related to neonatal death and bereavement care.
Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRG). However, specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. Growth hormone modulates homeostasis and tissue repair after injury, but how GH affects nociception in neonates is not known. To determine whether GH played a role in modulating sensory neuron function and hyperresponsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-DRG-spinal cord preparation. Results show that inflammation of the hairy hind paw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated through an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that after GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced painlike behaviors, possibly by suppressing the upregulation of IGFr1 within DRG.
Renal cell carcinoma (RCC) is one of the most common kidney malignancies. An upgraded comprehension of the molecular biology implicated in the development of cancer has stimulated an increase in research and development of innovative antitumor therapies. The aim of the study was to analyze the medical literature for hypertension and renal toxicities as the adverse events of the vascular endothelial growth factor (VEGF) signaling pathway inhibitor (anti-VEGF) therapy. Relevant studies were identified in PubMed and ClinicalTrials.gov databases. Eligible studies were phase III and IV prospective clinical trials, meta-analyses and retrospective studies that had described events of hypertension or nephrotoxicity for patients who received anti-VEGF therapy. A total of 48 studies were included in the systematic review. The incidence of any grade hypertension ranged from 17% to 49.6%. Proteinuria and increased creatinine levels were ascertained in 8% to 73% and 5% to 65.6% of patients, respectively. These adverse events are most often mild in severity but may sometimes lead to treatment discontinuation. Nephrotoxicity and hypertension are related to multiple mechanisms; however, one of the main disturbances in those patients is VEGF inhibition. There is a significant risk of developing hypertension and renal dysfunction among patients receiving anti-VEGF treatment; however, there is also some evidence that these side effects may be used as biomarkers of response to antiangiogenic agents.
Aim: Recent studies have demonstrated that netrin-1 plays a vital role in bone metabolism. Previous studies have shown that osteoblasts produce netrin-1 which affects osteoclast differentiation. However, the role of netrin-1 in osteoblast differentiation is not well understood. In this study, we explored the roles of netrin-1 in osteoblasts. Materials and Methods: Quantitative reverse-transcriptase polymerase chain reaction (qPCR), RNA interference for netrin receptors, the generation of netrin-1 plasmid, transfection of plasmids, and cell proliferation assay were performed. Results: During osteoblast differentiation by ascorbic acid, netrin-1 expression was significantly decreased. Gene expression related with osteoblast differentiation was down-regulated by netrin-1 treatment. We also found that osteoblast differentiation by bone morphogenetic protein-4 (BMP-4) was inhibited in the presence of recombinant netrin-1. Forced expression of both BMP-4 and netrin-1 significantly decreased alkaline phosphatase expression. On the other hand, Unc5b, neogenin, and A2b which belong to netrin receptors were expressed by osteoblasts. Moreover, alkaline phosphatase expression was significantly decreased by knockdown for the combination of two receptors among these receptors. Conclusion: Netrin-1 is involved in the regulation of osteoblast differentiation.
With the wealth of data accumulated from completely sequenced genomes and other high-throughput experiments, global studies of biological systems, by simultaneously investigating multiple biological entities (e.g. genes, transcripts, proteins), has become a routine. Network representation is frequently used to capture the presence of these molecules as well as their relationship. Network biology has been widely used in molecular biology and genetics, where several network properties have been shown to be functionally important. Here, we discuss how such methodology can be useful to translational biomedical research, where scientists traditionally focus on one or a small set of genes, diseases, and drug candidates at any one time. We first give an overview of network representation frequently used in biology: what nodes and edges represent, and review its application in preclinical research to date. Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. These types of inhibitors have the potential to be more specific, resulting in high efficacy treatments with less side effects, compared to the conventional treatments such as chemotherapy. Global analysis may provide better insight into the overall picture of human diseases, as well as identify previously overlooked problems, leading to rapid advances in medicine. From the clinicians' point of view, it is necessary to bridge the gap between theoretical network biology and practical biomedical research, in order to improve the diagnosis, prevention, and treatment of the world's major diseases.
This article presents basic concepts and recent research directions about the stability of sampled-data systems with aperiodic sampling. We focus mainly on the stability problem for systems with arbitrary time-varying sampling intervals which has been addressed in several areas of research in Control Theory. Systems with aperiodic sampling can be seen as time-delay systems, hybrid systems, Input/Output interconnections, discrete-time systems with time-varying parameters, etc. The goal of the article is to provide a structural overview of the progress made on the stability analysis problem. Without being exhaustive, which would be neither possible nor useful, we try to bring together results from diverse communities and present them in a unified manner. For each of the existing approaches, the basic concepts, fundamental results, converse stability theorems (when available), and relations with the other approaches are discussed in detail. Results concerning extensions of Lyapunov and frequency domain methods for systems with aperiodic sampling are recalled, as they allow to derive constructive stability conditions. Furthermore, numerical criteria are presented while indicating the sources of conservatism, the problems that remain open and the possible directions of improvement. At last, some emerging research directions, such as the design of stabilizing sampling sequences, are briefly discussed. (C) 2016 Elsevier Ltd. All rights reserved.
Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social-network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe the Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy-to-use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines, and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs in which nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and metadata on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic; they can be modified during the computation at low cost. SNAP is provided as an open-source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms.
BACKGROUND: Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown. OBJECTIVE: To compare the differences in gene expression between normal embryos and those with neural tube defects. DESIGN, TIME AND SETTING: A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007. MATERIALS: Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group (n = 30) and a normal control group (n=30). The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA. METHODS: Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similarly administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic (E) day 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray. MAIN OUTCOME MEASURES: Morphological changes and differential gene expression between the normal control group and the retinoic acid group. RESULTS: Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of the cranium and abnormal changes of the metencephalon and face. cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of Nek7, lgfbp5, Zw10, Csf3r, Psmc6 and Rb 1, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting. CONCLUSION: Cdk5, Nek7, lgfbp5, Zw10, Csf3r, Psmc6, Rb 1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.
Despite it has not been formally included in DSM-5 as a disorder, 'Internet addiction (IA)' has become a worldwide issue. It can be broadly defined as a non-chemical, behavioral addiction, which involves human-machine interaction. We pinpoint it as an "instrumental" form of social interaction (i.e. mediated by machines), a notion that appears useful for the sake of possible preclinical modeling. The features of Internet use reveals as addictive when this comes at the expense of genuine real-life sociability, with an overlap towards the hikikomori phenomenon (i.e., extreme retreat to one's own room). Due to the specific neuro-developmental plasticity in adolescence, IA poses risks to youths' mental health, and may likely produce negative consequences in everyday life. The thwarted development of adolescents' identity, self-image and adaptive social relationships is discussed: the IA adolescents often suffer loss of control, feelings of anger, symptoms of distress, social withdrawal, and familial conflicts. Further, more severe clinical conditions are also associated to IA, such as dysthymic, bipolar, affective, social-anxiety disorders, as well as major depression. This paper overviews the literature on IA, from neuro-biological, psychosocial and clinical standpoints, taking into account recent debates on diagnostic criteria, nosographic label and assessment tools. Neuroimaging data and neurochemical regulations are illustrated with links to pathogenetic hypotheses, which are amenable to validation through innovative preclinical modeling. (C) 2016 Elsevier Ltd. All rights reserved.
Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells. A tumor xenograft model using SCID-Beige mice was utilized to detect the metastasis of NB tumors in vivo. Inhibitors of PI3K, MAPK, Akt, and mTOR were used. Western blotting was performed to study the expressions of P-Akt, P-Erk, and P-mTOR. Our results showed that in TrkB-expressing NB cells, BDNF treatment significantly increased gap closing (P < 0.01) in scratch wound healing assay, also significantly enhanced the numbers of migrating cells (P < 0.01) and invading cells (P < 0.01) in the Boyden chamber migration and invasion assays. In vivo, NB distant metastases were significantly increased in mice with TrkB-expressing xenograft tumors compared to those with non-TrkB-expressing tumors (P < 0.05). Pre-treatment with any of the inhibitors for PI3K (LY294002), MAPK (PD98059), Akt (perifosine), or mTOR (rapamycin) blocked the BDNF/TrkB-induced increases of cell migration and invasion in TB3 cells, and also blocked the BDNF/TrkB-induced expressions of P-Akt, P-Erk, and P-mTOR. These data indicated that BDNF/TrkB increased metastasis in NB via PI3K/Akt/mTOR and MAPK pathways, and BDNF/TrkB and the downstream targets may be potential targets for the treatment of NB metastasis.
Introduction: Treatment for children with clinically aggressive, high-risk neuroblastoma remains challenging. Less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities. Here, we review new and evolving treatments that may ultimately improve outcome for children with high-risk neuroblastoma with decreased potential for late adverse events.Areas covered: New strategies for treating high-risk neuroblastoma are reviewed including: radiotherapy, targeted cytotoxics, biologics, immunotherapy, and molecularly targeted agents. Recently completed and ongoing neuroblastoma clinical trials testing these novel treatments are highlighted. In addition, we discuss ongoing clinical trials designed to evaluate precision medicine approaches that target actionable somatic mutations and oncogenic cellular pathways.Expert opinion: Advances in genomic medicine and molecular biology have led to the development of early phase studies testing biologically rational therapies targeting aberrantly activated cellular pathways. Because many of these drugs have a wider therapeutic index than standard chemotherapeutic agents, these treatments may be more effective and less toxic than current strategies. However, to effectively integrate these targeted strategies, robust predictive biomarkers must be developed that will identify patients who will benefit from these approaches and rapidly match treatments to patients at diagnosis.
Objective: Neurocognition is known to impact functioning in individuals at ultrahigh risk (UHR) for psychosis, but studies investigating potential mediators of this relationship are scarce. Building on evidence from schizophrenia spectrum disorders, the study tested whether negative symptoms and social skills act as mediators between neurocognition and functional outcome in UHR individuals. Methods: Ultrahigh risk participants (N = 84) underwent neurocognitive testing using the Brief Assessment of Cognition in Schizophrenia. Social skills and negative symptoms were assessed using the High-Risk Social Challenge task and the Scale for the Assessment of Negative Symptoms respectively. Four instruments were used to assess overall functioning, and one instrument assessed quality of life encompassing social functioning. Results: The cross-sectional analyses revealed that neurocognition was related to the measures of functioning. Negative symptoms mediated the relationship between neurocognition and four of the five measures of functioning. We did not find social skills to mediate between neurocognition and functioning. Conclusion: Negative symptoms appear to mediate the relationship between neurocognition and functional outcome in UHR individuals, but the finding needs to be confirmed and extended to longitudinal studies. This underscores the importance of focusing on both neurocognition and negative symptoms when aiming at improving the functional outcome of UHR individuals.
Background: There is little information on the application and impact of revised criteria for diagnosing dementia and mild cognitive impairment (MCI), now termed major and mild neurocognitive disorders (NCDs) in the DSM-5. We evaluate a psychometric algorithm for diagnosing DSM-5 NCDs in a community-dwelling sample, and characterize the neuropsychological and functional profile of expert-diagnosed DSM-5 NCDs relative to DSM-IV dementia and International Working Group criteria for MCI. Methods: A population-based sample of 1644 adults aged 72-78 years was assessed. Algorithmic diagnostic criteria used detailed neuropsychological data, medical history, longitudinal cognitive performance, and informant interview. Those meeting all criteria for at least one diagnosis had data reviewed by a neurologist (expert diagnosis) who achieved consensus with a psychiatrist for complex cases. Results: The algorithm accurately classified DSM-5 major NCD (area under the curve (AUC) = 0.95, 95% confidence interval (CI) 0.92-0.97), DSM-IV dementia (AUC = 0.91, 95% CI 0.85-0.97), DSM-5 mild NCD (AUC = 0.75, 95% CI 0.70-0. 80), and MCI (AUC = 0.76, 95% CI 0.72-0.81) when compared to expert diagnosis. Expert diagnosis of dementia using DSM-5 criteria overlapped with 90% of DSM-IV dementia cases, but resulted in a 127% increase in diagnosis relative to DSM-IV. Additional cases had less severe memory, language impairment, and instrumental activities of daily living (IADL) impairments compared to cases meeting DSM-IV criteria for dementia. DSM-5 mild NCD overlapped with 83% of MCI cases and resulted in a 19% increase in diagnosis. These additional cases had a subtly different neurocognitive profile to MCI cases, including poorer social cognition. Conclusion: DSM-5 NCD criteria can be operationalized in a psychometric algorithm in a population setting. Expert diagnosis using DSM-5 NCD criteria captured most cases with DSM-IV dementia and MCI in our sample, but included many additional cases suggesting that DSM-5 criteria are broader in their categorization.
Cell fate determination and differentiation during neurogenesis and myogenesis involve the sequential expression of several basic helix-loop-helix (bHLH) transcription factors. The expression of NeuroD1/2 and the expression of NSCL(Nh1h)1/2 are closely related in many developing peripheral and central neuronal cells, suggesting an epistatic relationship between these two bHLH transcription factor families during neurogenesis. To investigate this relationship, a murine neuroblastoma cell culture system and single/double knock-out (KO) mice of NeuroD1 and NeuroD2 were utilized for the gain-of-function and loss-of-function approaches, respectively. Both NeuroD1 and NeuroD2 were able to induce the transcription of NSCL1 in vitro: however, they were not able to activate NSCL2 transcription. The DNA-binding ability of NeuroD1 was essential for NSCL1 induction. To examine the epistatic relationship in vivo, we examined the expression of NSCL1 and NSCL2 in NeuroD1 and NeuroD2 KO mice and NeuroD1/2 compound MO mice by in situ hybridization, RT-PCR and Northern blotting. The expression of NSCL1 was lower in the NeuroD1 KO mice and was not further decreased in the double KO mice. However, the expression of NSCL2 did not change in either the single KO or double KO mice. These results demonstrate that NeuroD1 is an upstream regulator of the NSCL1 gene but not the NSCL2 gene in mice. In addition, NeuroD2 is not involved in this regulatory pathway in vivo. (C) 2012 Elsevier Inc. All rights reserved.
Most neurodegenerative diseases are characterized by intracellular aggregates of insoluble proteins. As for the majority of these disorders, aetiology and pathogenesis are only poorly understood; current nosological concepts are largely based on these molecular signatures of protein aggregates which also provide valuable tools for neuropathological differential diagnosis. The microtubule associated protein tau is one of these proteins that form intracellular fibrillary deposits in neurons and glial cells of a large variety of disorders today collectively referred to as tauopathies. While dysfunction of tau has unequivocally been shown to be able to cause neurodegeneration, the precise mechanisms of how tau is involved in neurodegenerative disorders is still poorly understood. After research has focused for several decades on the axonal function of tau and on the fibrillar tau aggregation, more recent cell biological studies have opened up new insights into the role of tau at the synapse and in the nucleus. According to currently emerging cell biological concepts, tau might play a role in the regulation of neuronal plasticity in a wide array of neuronal networks. In addition, it might be involved in regulating genome stability. The most intriguing question relevant both to physiological and pathophysiological function of tau is the biological meaning of the large heterogeneity of isoforms of tau which apparently is a rather promiscuous molecule. The present review is divided into two parts. First, we give an overview on the molecular biology and cell biology of tau and its physiological functions. The second part deals with the pathophysiology of tau and description of tauopathies which comprise more than 20 disorders including Alzheimer's disease, progressive supranuclear palsy, cortico basal degeneration, Pick's disease and others. (C) 2016 Elsevier Inc. All rights reserved.
Neurodegenerative diseases affect the neurons of the human brain and decline the neural activities causing neurocognitive dysfunctions and brain and behavioral disorders. An intensive immunotherapy is used to alter the course of multiple sclerosis, a common form of neurodegeneration, by controlling oxidative stress, recovering mitochondrial injury, and rehabilitating channelopathy dysfunctions. However, little is known about how the epigenetic factors can regulate atrophy genesis at hippocampal region, which prevents neurodegeneration. Further, traumatic brain injury leads to neurodegeneration. However, the onset of the later is not yet successfully monitored. Simultaneously, discrimination between neurodegeneration due to ageing and traumatic brain injury has not been addressed in the existing literature. Therefore, we present different forms of traumatic brain injury that trigger neurotoxicity, leading to the classification of onset stage of neurodegenerative pathways. We discuss how the immune system orchestrates changes in neurogenesis in presence of physiological stimuli. In our view, the epigenetic mode of treatment successfully intervenes all forms of neurodegenerative disease in both ageing and traumatic condition. Here, we establish a cross talk between epigenetic factors and neural immunology to balance oxidative stress at hippocampal regions.
Frontal alpha asymmetry has been proposed to underlie the balance between approach and withdrawal motivation associated to each individual's affective style. Neurofeedback of EEG frontal alpha asymmetry represents a promising tool to reduce negative affect, although its specific effects on left/right frontal activity and approach/withdrawal motivation are still unclear. The present study employed a neurofeedback training to increase frontal alpha asymmetry (right - left), in order to evaluate discrete changes in alpha power at left and right sites, as well as in positive and negative affect, anxiety and depression. Thirty-two right-handed females were randomly assigned to receive either the neurofeedback on frontal alpha asymmetry, or an active control training (N = 16 in each group). The asymmetry group showed an increase in alpha asymmetry driven by higher alpha at the right site (p < 0.001), as well as a coherent reduction in both negative affect and anxiety symptoms (ps < 0.05), from pre-to post-training. No training-specific modulation emerged for positive affect and depressive symptoms. These findings provide a strong rationale for the use of frontal alpha asymmetry neurofeedback for the reduction of negative affect and anxiety in clinical settings. (C) 2017 Elsevier Ltd. All rights reserved.
The importance of neuro-immune interactions in both physiological and pathophysiological states cannot be overstated. As our appreciation for the neuroimmune nature of the brain and spinal cord grows, so does our need to extend the spatial and temporal resolution of our molecular analysis techniques. Current imaging technologies applied to investigate the actions of the neuroimmune system in both health and disease states have been adapted from the fields of immunology and neuroscience. While these classical techniques have provided immense insight into the function of the CNS, they are however, inherently limited. Thus, the development of innovative methods which overcome these limitations are crucial for imaging and quantifying acute and chronic neuroimmune responses. Therefore, this review aims to convey emerging novel and complementary imaging technologies in a form accessible to medical scientists engaging in neuroimmune research. (C) 2016 Elsevier Inc. All rights reserved.
Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.
An approximately 3,000 finishing swine operation in the United States experienced an outbreak of an atypical neurologic disease in 11-weeks-old pigs with an overall morbidity of 20% and case fatality rate of 30%. The clinical onset and progression of signs in affected pigs varied but included inappetence, compromised ambulation, ataxia, incoordination, mental dullness, paresis, paralysis and decreased response to environmental stimuli. Tissues from affected pigs were submitted for diagnostic investigation. Histopathologic examination of the cerebrum, cerebellum and spinal cord revealed severe lymphoplasmacytic and necrotizing polioencephalomyelitis with multifocal areas of gliosis and neuron satellitosis, suggestive of a neurotropic viral infection. Bacterial pathogens were not isolated by culture of neurologic tissue from affected pigs. Samples tested by polymerase chain reaction (PCR) were negative for pseudorabies virus and atypical porcine pestivirus. Immunohistochemistry for porcine reproductive and respiratory syndrome virus, porcine circovirus and Listeria was negative. Porcine sapelovirus (PSV) was identified in spinal cord by a nested PCR used to detect porcine enterovirus, porcine teschovirus and PSV. Next-generation sequencing of brainstem and spinal cord samples identified PSV and the absence of other or novel pathogens. In addition, Sapelovirus A mRNA was detected in neurons and nerve roots of the spinal cord by in situ hybridization. The PSV is genetically novel with an overall 94% amino acid identity and 86% nucleotide identity to a recently reported sapelovirus from Korea. This is the first case report in the United States associating sapelovirus with severe polioencephalomyelitis in pigs.
Addictive disorders are a major public health concern, associated with high relapse rates, significant disability and substantial mortality. Unfortunately, current interventions are only modestly effective. Preclinical studies as well as human neuroimaging studies have provided strong evidence that the observable behaviours that characterize the addiction phenotype, such as compulsive drug consumption, impaired self-control, and behavioural inflexibility, reflect underlying dysregulation and malfunction in specific neural circuits. These developments have been accompanied by advances in neuromodulation interventions, both invasive as deep brain stimulation, and non-invasive such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. These interventions appear particularly promising as they may not only allow us to probe affected brain circuits in addictive disorders, but also seem to have unique therapeutic applications to directly target and remodel impaired circuits. However, the available literature is still relatively small and sparse, and the long-term safety and efficacy of these interventions need to be confirmed. Here we review the literature on the use of neuromodulation in addictive disorders to highlight progress limitations with the aim to suggest future directions for this field.
In recent years, advances in light-based technology have driven an ongoing optical revolution in neuroscience. Synergistic technologies in laser microscopy, molecular biology, organic and synthetic chemistry, genetic engineering and materials science have allowed light to overcome the limitations of and to replace many conventional tools used by physiologists to record from and to manipulate single cells or whole cellular networks. Here we review the different optical techniques for stimulating neurons, influencing neuronal growth, manipulating neuronal structures and neurosurgery.
Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving N-methyl-d-aspartate and a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.
In Parkinson's Disease (PD) there is widespread neuronal loss throughout the brain with pronounced degeneration of dopaminergic neurons in the SNc, leading to bradykinesia, rigidity, and tremor. The identification of living dopaminergic neurons in primary Ventral Mesencephalic (VM) cultures using a fluorescent marker provides an alternative way to study the selective vulnerability of these neurons without relying on the immunostaining of fixed cells. Here, we isolate, dissociate, and culture mouse VM neurons for 3 weeks. We then identify dopaminergic neurons in the cultures using eGFP fluorescence (driven by a Tyrosine Hydroxylase (TH) promoter). Individual neurons are harvested into microcentrifuge tubes using glass micropipettes. Next, we lyse the harvested cells, and conduct cDNA synthesis and transposon-mediated "tagmentation" to produce single cell RNA-Seq libraries(1,2,3,4,5). After passing a quality-control check, single-cell libraries are sequenced and subsequent analysis is carried out to measure gene expression. We report transcriptome results for individual dopaminergic and GABAergic neurons isolated from midbrain cultures. We report that 100% of the live TH-eGFP cells that were harvested and sequenced were dopaminergic neurons. These techniques will have widespread applications in neuroscience and molecular biology.
The preg gene encodes a cyclin-like protein that is implicated in the derepression of nucleases and phosphatases that scavenge phosphate from the environment. To better understand the regulatory role of the preg gene product, the differential display reverse transcriptase - polymerase chain reaction was used to isolate transcripts differentially expressed in the preg(c) mutant strain of the mold Neurospora crassa grown under phosphate starvation, at pH 7.8. Two transcripts, whose differential expressions were confirmed by Northern blotting, were downregulated in a strain of N. crassa carrying a loss-of-function mutation in the preg gene (preg(c) allele). These transcripts revealed genes coding for enzymes involved in the thymidine salvage pathway (iso-orotate decarboxylase) and in the biosynthesis of coenzyme Q (ubiquinone C-methyltransferase), which may be relevant to a further understanding of the molecular events involved in the phosphorus sensing in N. crassa.
Introduction: Bacterial infection and bile flow retardation form a vicious cycle which promotes stone formation and recurrence, and it seems that mucin overexpression plays an important role in this process. However, the mechanism of increased mucus secretion in the biliary tract by bacterial infection and its treatment remain unclear. Material and methods: Human biliary epithelial cells were induced by neutrophil elastase (NE), and H2O2 production in the cell supernatants was detected by a specific kit, and then cells were pretreated with a H2O2 inhibitor, and expression of MUC5AC was detected by real-time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Moreover, selective PKC and Nox inhibitors, apocynin and bisindolylmaleimide I, were used to pretreat cells and detect H2O2, MUC5AC mRNA and protein expression. Then, we pretreated cells with selective inhibitors or NE, and detected transforming growth factor alpha (TGF-alpha) using an ELISA kit. Results: H2O2 production increased in an NE dose-dependent manner (p < 0.001), and NE upregulated MUC5AC expression at both mRNA and protein levels, while DMTU, could reduce this high expression (p < 0.01 at mRNA level, p < 0.001 at grey analysis for western blot and p < 0.01 at mean density for immunohistochemical staining at protein level). Moreover, apocynin and bisindolylmaleimide I could reduce the H2O2 production stimulated by NE (p < 0.05), and reduce MUC5AC high expression (p < 0.01 at mRNA level, p < 0.001 at both grey analysis for western blot and mean density for immunohistochemical staining at protein level). In addition, NE induced TGF-alpha production, and any of the three selective inhibitors could reduce it (p < 0.05). Conclusions: NE-induced reactive oxygen species participated in the up regulation of MUC5AC production. Moreover, protein kinase C and NADPH oxidase (Nox) regulate MUC5AC production in NE-challenged human biliary epithelial cells.
Neutrophils, the most abundant leukocyte in human circulation are being more and more recognized as part of the immune reaction to cancer. In the last years, the understanding that neutrophils possess a dual role in cancer development has emerged. During tumor progression the number of neutrophils increase, and their phenotype change. In advanced cancer, we can find several sub-populations of circulating neutrophils possessing different characteristics of maturity, tumor cytotoxicity and immune suppression. One important sub-population of circulating neutrophils is the granulocytic myeloid derived suppressor cells (G-MDSC). Differencing G-MDSC from other sub-populations of neutrophils in the circulation is a complex and controversial task, as there are no clear definitions of the differences between these granulocytic sub-populations. Herein we review the differences described thus far between G-MDSC and other circulating neutrophils. We then compare the morphology, surface markers, function and prognostic importance of the different tumor-related circulating neutrophils, as described by us and others, and discuss the possible relations between the different sub-populations, their source and fate. Lastly, we suggest a nomenclature to try and encompass the full range of circulating neutrophils in cancer. (C) 2016 Elsevier GmbH. All rights reserved.
A total of similar to 38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon- inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3, IL-18 and hemagglutinin neuraminidase (HN), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3, IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro.
This paper presents a system modeling method for an multi-stage operational amplifier circuit based on the step response experiment. By taking an step voltage signal as the input, the measure data are collected for estimating the system parameters. By defining and minimizing an output error criterion function, a Newton iterative estimation algorithm is derived. In order to show the accuracy of the estimated circuit model, we use a proportional integral controller and construct a closed-loop operational amplifier circuit in terms of the estimated circuit model. Moreover, we take a step experiment to test the tracking performance of the operational amplifier circuit. The simulation results indicate that the proposed method can generate the parameter estimates of the multi-stage operational amplifier circuit system.
Whether specific T-cell clones are present in tumor infiltrating lymphocytes (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T-cell receptor (TCR) chains - and to characterize the repertoire of TILs in BCC. V and J gene-usage and CDR3 length were computed to determine the clonality of TCR and degree of overlap in TCR repertoires between skin resident T-cells and TILs. We found high diversity of the TCR repertoire in BCC and control skin with random V-J gene usage and similar CDR3-length distribution. Lack of TCR repertoire restriction indicates absence of tumor-specific TIL clones in BCC.
Transcriptome analysis has been a key area of biological inquiry for decades. Over the years, research in the field has progressed from candidate gene-based detection of RNAs using Northern blotting to high-throughput expression profiling driven by the advent of microarrays. Next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution.
The identification of mutations that are present at low frequencies in clinical samples is an essential component of precision medicine. The development of molecular barcoding for next-generation sequencing has greatly enhanced the sensitivity of detecting such mutations by massively parallel sequencing. However, further improvements in specificity would be useful for a variety of applications. We herein describe a technology (BiSeqS) that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA; its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. We show here that BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among >10,000 wild-type molecules.
Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.
Background: Nuclear factor-kappaB (NF-kappa B), a transcription factor, is abundantly expressed in many tumors and regulates many tumor-relative genes such as c-myc and caspase-8, which NF-kappa B-mediated genes activation serves as an anti-tumor pathway by regulating expression of these tumor-relative genes. Given the important roles of these genes in tumor control, the present study was to test the hypothesis that NF-kappa B decoy ODNs transfected into tumor cells in vitro and in vivo might affect growth and apoptosis. Methods: First, NF-kappa B decoy oligodeoxynucleotides were designed according to the NF-kappa B elements in the promoter region of c-myc gene. Then, supression effects of decoy ODNs on proliferation of five carcinoma cell lines were assessed by MTT assay. Apoptosis of carcinoma cells was determined by chromosome DNA ladder and flow cytometric analysis (FCM). Thirdly, suppression effects of NF-kappa B decoy ODNs on proliferation of carcinoma in vivo were investigated in nude mice. To confirm mechanisms of action, a pGL3-C-MYC luciferase expression vector containing a fragment of the c-myc promoter was constructed and co-transfected with NF-kappa B decoy ODNs into SKOV-3 cells by lipofectamineTM2000. Expression levels of endogenous c-myc and caspase-8 genes were assessed by northern blotting. Lastly, nuclear extracts were prepared from SKOV-3 cells and DNA-protein interactions were examined by electrophoretic mobility shift assay (EMSA). Results: Treatment of cancer cell lines with NF-kappa B decoy ODNs resulted in strong suppression of proliferation, especial of the SKOV-3 ovarian cancer cell line in vitro and in vivo. Induction of apoptosis of SKOV-3 was observed in DNA gel electrophoresis and FCM. Activity of luciferase was significantly reduced in the NF-kappa B decoy-transfected cells, but not in cells transfected with a control decoy. Furthermore, we found that transcripts of endogenous c-myc gene were reduced, while caspase-8 transcripts were induced. EMSA demonstrated specific binding of the NF-kappa B decoy to NF-kappa B protein. Conclusions: These findings indicatd that NF-kappa B activation plays an important role in proliferation in many cancers, esspecially ovarian carcinomas. Inhibitors of NF-kappa B may thus offer promise as a therapeutic approach for the treatment of tumors via manipulating expression of desired target genes. NF-kappa B decoy ODNs may allow development of therapeutic and investigative tools for human malignancies.
The development of efficient visible-light-driven photocatalysts for water splitting has drawn much attention. Herein, we demonstrated a novel H-2-producing photocatalytic system that employed nitrogen doped graphene quantum dots (NGQDs)-ZnNb2O6/g-C3N4 heterostructures as the hydrogen evolving catalysts. The as-prepared NGQDs-ZnNb2O6/g-C3N4 heterostructures were favorable for light harvesting and charge separation, and showed highly efficient photocatalytic performance for water splitting into hydrogen. Results showed that both the ZnNb2O6/g-C3N4 (Zn/CN) mole ratio and the amount of NGQDs displayed important influence for H-2 production. Moreover, the optimum synthesis conditions of the Zn/CN mole ratio (1/7) and the amount of NGQDs (5%) were both obtained, and the corresponding 5%NGQDs-Zn/7CN sample performed a much higher hydrogen-evolution rate of 340.9 mu mol h(-1) g(-1). By the further studies, the enhanced photocatalytic activity could be ascribed to the crucial roles of NGQDs and heterojunction photocatalytic system, which resulted in an efficient charge separation and the largely enhanced photocatalytic activity. Meanwhile, the possible photocatalytic mechanism of NGQDs-ZnNb2O6/g-C3N4 was also proposed. We envision that this work creates new opportunities for constructing and designing efficient visible-light-driven photocatalysts for hydrogen evolution reaction. (C) 2017 Published by Elsevier B.V.
Wine originally emerged as a serendipitous mix of chemistry and biology, where microorganisms played a decisive role. From these ancient fermentations to the current monitored industrial processes, winegrowers and winemakers have been continuously changing their practices according to scientific knowledge and advances. A new enology direction is emerging and aiming to blend the complexity of spontaneous fermentations with industrial safety of monitored fermentations. In this context, wines with distinctive autochthonous peculiarities have a great acceptance among consumers, causing important economic returns. The concept of terroir, far from being a rural term, conceals a wide range of analytical parameters that are the basis of the knowledge-based enology trend. In this sense, the biological aspect of soils has been underestimated for years, when actually it contains a great microbial diversity. This soil-associated microbiota has been described as determinant, not only for the chemistry and nutritional properties of soils, but also for health, yield, and quality of the grapevine. Additionally, recent works describe the soil microbiome as the reservoir of the grapevine associated microbiota, and as a contributor to the final sensory properties of wines. To understand the crucial roles of microorganisms on the entire wine making process, we must understand their ecological niches, population dynamics, and relationships between 'microbiome-vine health' and 'microbiome-wine metabolome.' These are critical steps for designing precision enology practices. For that purpose, current metagenomic techniques are expanding from laboratories, to the food industry. This review focuses on the current knowledge about vine and wine microbiomes, with emphasis on their biological roles and the technical basis of next-generation sequencing pipelines. An overview of molecular and informatics tools is included and new directions are proposed, highlighting the importance of -omics technologies in wine research and industry.
The research "Behavior Change and Energy Use" (US Department of Energy and Climate Change, 2011) [1] shows that with better information in the monthly electricity bill, the Energy Performance Certificate (EPC) can encourage people to reduce their energy usage. That is why smart meters - the emerging technology to help people to know their monthly energy consumption, are gradually replacing mechanical power meters. In this paper, we investigate a special energy monitoring process named Non-Intrusive Appliance Load Monitoring (NIALM), which is potentially the best method to give consumers pertinent information with respect to power consumption. However, real-time feedback feature in a low cost NIALM system is still a big challenge in such technology because of the complication in NIALM's algorithms. System on Chip (SoC) technology can solve this challenge. Besides including high-speed interconnection and multi-processors, integrating Field-Programmable Gate Array (FPGA) into SoCs may be the most important evolution, which provides developers a powerful tool to develop a low cost but high performance system. Therefore, in this paper we proposed a development of a real-time NIALM system based on the SoC with FPGA acceleration. (C) 2017 Elsevier Ltd. All rights reserved.
In this work we investigate the influence that nicotine exerts on attention focusing, modeling the coupling of reward and thalamocortical circuits. Each neuron in the neural networks that replicate such circuits is described by a carefully designed coupled system of nonlinear differential equations that details essential neurophysiological properties. Computer simulations of the reward-attention circuit reflects the spiking behavior of each individual neuron in the network, under the presence or absence of nicotine. It becomes clear that changes in the dopaminergic levels in the reward circuit due to nicotine strongly influences the nigral dopaminergic activity, that modulates the thalamocortical filtering mechanism. Our results indicate that nicotine strengthens the attentional focus on a particular stimulus, decreasing the smoker's mental flexibility. Also, the simulations highlight aspects of clinical inattention symptoms, particularly in the attention deficit hyperactivity disorder. They show why patients suffering from attentional lability might improve the attentional focus when exposed to nicotine. (C) 2017 Elsevier B.V. All rights reserved.
Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The specific roles individual nAChR subunits perform in Drosophila melanogaster and other insects are relatively uncharacterized. Of the 10 D. melanogaster nAChR subunits, only three have described roles in behavioral pathways; D alpha 3 and D alpha 4 in sleep, and D alpha 7 in the escape response. Other subunits have been associated with resistance to several classes of insecticides. In particular, our previous work has demonstrated that an allele of the D alpha 1 subunit is associated with resistance to neonicotinoid insecticides. We used ends-out gene targeting to create a knockout of the D alpha 1 gene to facilitate phenotypic analysis in a controlled genetic background. To our knowledge, this is the first report of a native function for any nAChR subunits known to be targeted by insecticides. Loss of D alpha 1 function was associated with changes in courtship, sleep, longevity, and insecticide resistance. While acetylcholine signaling had previously been linked with mating behavior and reproduction in D. melanogaster, no specific nAChR subunit had been directly implicated. The role of D alpha 1 in a number of behavioral phenotypes highlights the importance of understanding the biological roles of nAChRs and points to the fitness cost that may be associated with neonicotinoid resistance.
China's rapid economic development greatly affected not only the global economy but also the entire environment of the Earth. Forecasting China's economic growth has become a popular and essential issue but at present, such forecasts are nearly all conducted at the national scale. In this study, we use nighttime light images and the gridded Landscan population dataset to disaggregate gross domestic product (GDP) reported at the province scale on a per pixel level for 2000-2013. Using the disaggregated GDP time series data and the statistical tool of Holt-Winters smoothing, we predict changes of GDP at each 1kmx1km grid area from 2014 to 2020 and then aggregate the pixel-level GDP to forecast economic growth in 23 major urban agglomerations of China. We elaborate and demonstrate that lit population (brightness of nighttime lightsxpopulation) is a better indicator than brightness of nighttime lights to estimate and disaggregate GDP. We also show that our forecast GDP has high agreement with the National Bureau of Statistics of China's demographic data and the International Monetary Fund's predictions. Finally, we display uncertainties and analyze potential errors of this disaggregation and forecast method.
Serrano-Nascimento C, Calil-Silveira J, Nunes MT. Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration. Am J Physiol Cell Physiol 298: C893-C899, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00224.2009.-Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-beta increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of Wolff-Chaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 mu g/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplification of cDNA ends-poly(A) test (RACE-PAT). We observed that NIS mRNA abundance and poly(A) tail length were significantly reduced in all periods of iodide treatment. Perchlorate reversed these effects, indicating that iodide was the agent that triggered the modifications observed. Since the poly(A) tail length of mRNAs is directly associated with their stability and translation efficiency, we can assume that the rapid decay of NIS mRNA abundance observed was due to a reduction of its stability, a condition in which its translation could be impaired. Our data show for the first time that iodide regulates NIS mRNA expression at posttranscriptional level, providing a new mechanism by which iodide exerts its autoregulatory effect on thyroid.
Nitrate cycling is essential in sustaining soil systems. Excessive application of N-fertilizers and the associated underground water contamination have attracted a great deal of research attention. Sorption is efficient and environmentally friendly in nitrate fixation. A debate was noted in literature regarding whether biochars have potential to fix nitrate through sorption. In this study, biochars produced from different biomasses as well as biomass compositions were chosen as the absorbents to evaluate their potential efficiencies in nitrate fixation. Increased sorption to nitrate was observed for biochars with increased pyrolysis temperature, but the increasing extent varied with biomass. The surface base functional groups and surface charges of biochars could not well explain nitrate sorption. The significant positive correlation between nitrate sorption and biochar surface areas suggested that surface area was the controlling parameter for nitrate sorption. The pre-coating of tannic acid (TA) on biochars decreased but did not completely inhibit nitrate sorption. This observation suggested that nitrate sorption on biochars may be further decreased after their interactions with natural organic matter. Nitrate sorption was compared among various adsorbents, including biochars, soil particles, clay minerals, engineered particles, as well as humic substances. Soil particles generally showed high sorption to nitrate over biochars. This result suggested that biochars investigated in this work may play a limited role in nitrate fixation through sorption after their massive application. Nitrogen fixation through nitrate adsorption on biochars should be carefully evaluated taking into consideration of biochar feedstocks and properties. (C) 2016 Elsevier B.V. All rights reserved.
Nitrate pollution of groundwater, which is mainly caused by the application of nitrogen-based fertilizers in intensive agriculture, is a widespread problem all over the world and a potential risk for public health. Reverse osmosis, ion exchange and electrodialysis are currently used for water denitrification, yielding a highly concentrated reject water that requires economic and environmental costs for disposal. Nitrate reduction technologies that are able to convert nitrate into inert nitrogen gas have appeared that are promising, cost effective and environmentally friendly. Among these technologies, attention has been focused on i) the chemical reduction over mono-and bimetallic catalysts with hydrogen as the reducing agent and ii) electrocatalytic reduction processes over metallic anodes. Although selectivity values towards N-2 of greater than 90% are achieved with both technologies, the undesired formation of ammonium as a reaction by-product is still the main drawback preventing their implementation at larger scales. For this reason, the development of new catalytic and electrodic materials as well as novel reactor configurations to avoid ammonium formation have been extensively investigated in the last few years to increase the effectiveness and competitiveness of both technologies. In this paper, an overview of the current state-of-the-art of both catalytic reduction and electroreduction of nitrates is presented, highlighting their potential and their main drawbacks along with guidelines for future research. (C) 2017 Elsevier B.V. All rights reserved.
Nitrobenzene (NB) is widely used in the manufacturing of different types of products and other aromatic chemicals. Moreover, it is highly toxic and environmental pollutant compound. Therefore, the detection of nitro aromatic compounds (NACs) has gained more attention in the field of sensor. This article describes the green reduction utilized to preparation of green reduced graphene oxide/nickel tetraphenyl porphyrin (GRGO/Ni-TPP) nanocomposite modified electrode for the determination of nitrobenzene (NB). The GRGO was prepared by environmentally friendly method and using caffeic acid (CA) as a reducing agent. Moreover, the GRGO/Ni-TPP nanocomposite was prepared via the pi-pi stacking interaction between the RGO and Ni-TPP. In addition, the prepared material was confirmed by the UV-Visible spectroscopy (UV), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The structural morphology and elemental composition of the prepared nanocomposite was confirmed by the scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX). Besides, the electrochemical studies of the prepared nanocomposite was characterized by the CV and DPV technique. The DPV studies displayed the linearity response of the proposed sensor about 0.5-878 mu M with the sensitivity of 1.277 mu A mu M-1 cm(-2) and the limit of detection (LOD) is 0.14 mu M. Furthermore, the GRGO/Ni-TPP nanocomposite modified electrode shows good selectivity towards the detection of NB. In addition, the real sample analysis exhibited appreciable recovery towards the determination of NB using various types of water samples. (C) 2017 Elsevier Inc. All rights reserved.
This study applied different concentration of NaNO3 solution to simulate the effect of inorganic nitrogen (N) deposition/pollution on carbon (C) storage in coastal mangrove sediment through observing the changes of enzyme activity and microbial abundance. Sediment collected from mangrove forest (MG) and intertidal zone (IZ) were incubated with different N rates (0 (control), 5 (low-N) and 20 (high-N) N g(-1) dry sediment, respectively). After incubation, the activities of phenol oxidase (PHO) and acid phosphatase (ACP) were enhanced, but beta-glucosidase (GLU) and N-beta-acetyl-glucosaminidase (NAG) activities were reduced by N addition. The altered enzymatic stoichiometries by N input implied that microbial phosphorus (P) limitation was increased, whereas C and N limitation were alleviated. Besides, N input decreased the bacterial abundance but increased fungal abundance in both types of sediment. The increased pH and soluble phenolics along with the exacerbated P limitation by N addition might explain these changes. Furthermore, sediment with N addition (except high-N treated MG sediment) showed a trend of C sequestration, which might be largely caused by the decrease of bacterial abundance and GLU activity. However, MG sediment with high-N suggested a trend of C loss, and the possible reason for this discrepancy might be the relatively higher increase of PHO and ACP activity. To better understand the influence of N deposition/pollution on C cycling, the long-term N effect on microorganisms, enzymes, and thus C storage should be paid more attention in the future. (C) 2017 Elsevier Ltd. All rights reserved.
Ammonia (NH3) is a key commodity chemical of vital importance for fertilisers. It is made on an industrial scale via the Haber Bosch process, which requires significant infrastructure to be in place such that ammonia is generally made in large, centralized facilities. If ammonia could be produced under less demanding conditions, then there would be the potential for smaller devices to be used to generate ammonia in a decentralized manner for local consumption. Electrochemistry has been proposed as an enabling technology for this purpose as it is relatively simple to scale electrolytic devices to meet almost any level of demand. Moreover, it is possible to envisage electrosynthetic cells where water could be oxidised to produce protons and electrons at the anode which could then be used to reduce and protonate nitrogen to give ammonia at the cathode. If this nitrogen were sourced from the air, then the only required infrastructure for this process would be supplies of water, air and electricity, the latter of which could be provided by renewables. Hence an electrosynthetic cell for ammonia production could allow NH3 to be generated sustainably in small, low-cost devices requiring only minimal facilities. In this review, we describe recent progress towards such electrosynthetic ammonia production devices, summarizing also some of the seminal literature in the field. Comparison is made between the various different approaches that have been taken, and the key remaining challenges in the electrosynthesis of ammonia are highlighted. (C) 2016 Elsevier B.V. All rights reserved.
While the initial treatment of non-small cell lung cancer (NSCLC) usually relies on surgical resection followed by systemic cytotoxic chemotherapy and/or radiation therapy, recent advances in understanding of NSCLC biology and immunology have spurred the development of numerous targeted therapies. In particular, a class of immune modulatory drugs targeting the immune checkpoint pathways has demonstrated remarkable durable remissions in a select minority of advanced NSCLC patients, potentially heralding the elusive "cancer cure". This review focuses on the clinical evidence for one of these agents, nivolumab, and clarifies the role of this drug in the context of the other targeted therapies currently available for the treatment of NSCLC. We also discuss the impact of nivolumab on patient quality of life and health economics.
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56(bright)CD16(-) phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy. However, there is a tendency for pregnancy immunology to reflect transplantation immunology regarding the assumption that the maternal immune system should be suppressed. This tendency is misleading. We discuss how the immune system is formed in early deciduas and the interactions between maternal NK cells and fetal growth. We propose that the maternal immune response must not be fully suppressed and is even necessary for the local response of uterine NK cells.
NK cell cytotoxicity in Chediak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NI(cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-gamma production, could be restored up to normal levels by in vitro IL-2 treatment. This cytokine also caused the appearance of smaller lysosomal granules and their orientation towards the NK-target cell contact area, thus suggesting that IL-2 had a more general capacity to restore NK cell effector functions. Moreover after the transplant, although the successful engraftment, NK cell cytotoxicity resulted still partially impaired at one year, almost normal at ten years and, anyhow, fully recovered by in vitro IL-2 treatment. Taken together, our results indicate that IL-2 had a wide capacity to restore NK cell effector functions, being able to reverse the altered cytotoxic activity, lytic granule pattern, and cytokine production observed in the CHS patient. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Dysregulation of NKD1 has been identified in several solid tumors. However, the status of NKD1 expression and its clinical implication in acute myeloid leukemia remain largely elusive. NKD1 transcript level in bone marrow mononuclear cells was detected by real-time quantitative polymerase chain reaction in 126 de novo acute myeloid leukemia patients and 30 controls. Clinical significance of NKD1 expression was obtained by the comparison between the patients with low and high NKD1 expression. NKD1 messenger RNA level was significantly decreased in acute myeloid leukemia patients compared with controls (p = 0.019). There were no significant differences between patients with low and high NKD1 expression in sex, age, peripheral blood cells, bone marrow blasts, French-American-British/World Health Organization subtypes, and karyotypes/karyotypic classifications (p >0.05). Although no significant difference was observed in complete remission rate between NKD1(low) and NKD1(high) patients (p >0.05), Kaplan-Meier analysis revealed that NKD1(low) patients showed shorter overall survival time than NKD1(high) patients in whole-cohort acute myeloid leukemia, non-M3 acute myeloid leukemia, and cytogenetically normal acute myeloid leukemia (p = 0.014, 0.063, and 0.020). Multivariate analyses disclosed the low NKD1 expression was an independent risk factor in cytogenetically normal acute myeloid leukemia patients (hazard ratio = 0.397, p = 0.017). Moreover, the prognostic value of NKD1 expression was confirmed by gene expression profile data in cytogenetically normal acute myeloid leukemia patients (p = 0.028 and 0.011). NKD1 showed significantly increased level after induction chemotherapy achieved complete remission in follow-up paired acute myeloid leukemia patients (p < 0.001). These findings indicated that reduced NKD1 expression is associated with unfavorable clinical outcome in cytogenetically normal acute myeloid leukemia.
Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbic-prefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level=100 ng/ml) to 21 healthy volunteers in a within-subject placebo controlled crossover design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontal-parahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valence-specific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia.
Skeletal surveys are currently considered standard-of-care for the evaluation of fractures in infants with suspected abuse. It has been well described that subtle fractures may be missed and soft tissue and visceral injuries are often undetected using this radiographic modality in Whole body MRI (WB-MRI) is mainly used in oncology and infectious disease, however, its application in the field of child abuse pediatrics has not been well studied. We present a case that illustrates the potential utility of WB-MRI using a 3 T magnet in evaluating infants with suspected child abuse. (C) 2015 Elsevier Ltd. All rights reserved.
This article presents an overview of nonaccidental trauma in children, including common clinical presentation, evaluation, and diagnosis.
Non-accidental trauma is a significant source of morbidity and mortality in the pediatric population. Given the vulnerable state of the child, the radiologist can often provide valuable diagnostic information in the setting of suspected abuse. This review focuses on common findings of abusive trauma and serves as a guide to aid in clinical decision-making for providers of emergency medicine and pediatrics. Amid this discussion is an assessment of modern controversies regarding reported mimicking pathologies, recapitulation of the current state of evidence with respect to radiologic findings of abuse, and examination of the contribution that spine imaging may add to the diagnosis of possible abusive head trauma in the acutely injured child. Recommendations for avoiding pitfalls regarding the dating of intracranial injuries are discussed, and illustrated depictions of perpetrator-induced pathology are provided to aid in the understanding of these injuries. Through the use of the appropriate approach to imaging and evidence-based guidelines regarding radiologic findings, the role of radiology is to provide fundamental clues to diagnose and prevent recurrence of abusive injury in patients who cannot speak for themselves.
[Objective] To investigate the effect of cordyceps sinensis (CS) on expression of uncoupling protein-2 (UCP2) and so to elucidate the role of UCP2 in development of nonalcoholic fatty liver diseases (NAFLD). [Methods] Rats were administrated with high-fat diet to produce NAFLD animal model and intervened by cordyceps sinensis. Triglyceride (TG), total cholesterol (TC) in liver were measured by biochemistry, adenosine triphosphate (ATP) by luciferin-luciferinase, and UCP2 expression by Northern blotting and immunohistochemistry. Liver histopathology was evaluated. [Results] High-fat diet fed rats developed obesity and showed a gradual increase in body weight, liver index, and a decrease in ATP level. More advanced liver disease was found histopathologically for longer high-fat diet. Up-regulation of liver UCP2 by high-fat diet stopped after week 12. However codyceps sinensis induced UCP2 up-regulation continuously, and kept liver ATP a relatively high level. [Conclusion] NAFLD rat models were produced successfully. Liver UCP2 up-regulation in NAFLD rats may be a definite beneficial adaptation to lipid exposure. Cordyceps sinensis may serve a protective role to prevent NAFLD from progression. One of the possible mechanisms involves in modulating UCP2 expression and thereby, regulating fat metabolism, energy homeostasis.
BACKGROUND: Therapeutic options for pain management are restricted in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced or NSAID-exacerbated urticaria because strong cyclooxygenase (COX)-I inhibiting NSAID cannot be used. Alternative NSAID such as weak COX-I inhibitors or selective COX-II inhibitors are sometimes not sufficiently effective or have potentially troublesome adverse effects. OBJECTIVE: To date, prophylactic premedication with H-1-antihistamines is rarely practiced in patients concurrently suffering from recurrent pain and NSAID-associated urticaria. Our data analysis aims to clarify whether prophylactic premedication before the intake of NSAID is effective, safe, and practicable. METHODS: Data of 21 patients with NSAID-induced or NSAID-exacerbated urticaria who underwent single dose NSAID provocation 30 minutes after premedication with 5 mg desloratadine were retrospectively evaluated. RESULTS: After H-1-antihistamine premedication, 17 patients tolerated 16 single dose provocation tests with strong COX-I inhibitors and 2 tests with weak COX-I inhibitors. Despite H1-antihistamine premedication, 2 patients developed acute urticaria after intake of 400 mg ibuprofen. Another 2 patients with acute urticaria after intake of 800 mg ibuprofen tolerated 400 mg ibuprofen and 1000 mg paracetamol, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In the majority of patients with NSAID-induced or NSAID-exacerbated urticaria concurrently suffering from intermittent pain, a premedication regimen with 5 mg desloratadine 30 minutes before intake of a strong COX-I inhibitor seems to be effective, safe, and practicable. (C) 2016 American Academy of Allergy, Asthma & Immunology
The decline of species richness with altitude is one of the most obvious patterns in ecology and results from the combination of ecological and evolutionary mechanisms. In harsh high-altitude environments, the effect of altitude usually overrules other environmental variables related to biodiversity. Studies using species richness along altitude gradients in high altitude are relatively numerous for lakes, but not for ponds. However, due to their special features, such as small size, high isolation and regional variability, ponds have been proved to be different systems compared to lakes. In high-altitude waterbodies, species of the family Chironomidae often dominate in benthic invertebrate communities and thus serve as an ideal model to study aquatic community changes along an altitude gradient. However, due to the time-consuming processing and expertise needed to identify the species, chironomids are often excluded from regular surveys. In the present study, we sampled 66 Tatra ponds over a 1100-m altitude gradient for benthic invertebrates, with special attention to chironomids. Out of the total 122 taxa collected, Chironomidae constituted the richest group with 58 taxa, being present in all the study ponds. The most diverse pond supported 13 chironomid taxa, and mean diversity was 6 taxa/pond. While total invertebrate richness decreased with altitude, chironomid richness showed only a weak negative response to altitude. The proportion of total chironomid diversity made up of Tanypodinae and Chironominae subfamilies decreased with altitude, while the opposite trend was recorded for the proportion of Diamesinae and Orthocladiinae.
Oral squamous cell carcinoma is the most aggressive cancer that is associated with high recurrence, metastasis, and poor treatment outcome. Dysregulation of long non-coding RNAs has been shown to promote tumor growth and metastasis in several cancers. In this study, we investigated the expression of 11 selected long non-coding RNAs that are associated with cell proliferation, metastasis, and tumor suppression in oral squamous cell carcinomas and normal tissues by quantitative real-time polymerase chain reaction. Out of the 11 long non-coding RNAs profiled, 9 were significantly overexpressed in tumors with tobacco chewing history. Moreover, the long non-coding RNA profile was similar to the head and neck cancer datasets of The Cancer Genome Atlas database. Linc-RoR, a regulator of reprogramming, implicated in tumorigenesis was found to be overexpressed in undifferentiated tumors and showed strong association with tumor recurrence and poor therapeutic response. In oral squamous cell carcinomas, for the first time, we observed linc-RoR overexpression, downregulation of miR-145-5p, and overexpression of c-Myc, Klf4, Oct4, and Sox2, suggesting the existence of linc-RoR-mediated competing endogenous RNA network in undifferentiated tumors. Taken together, this study demonstrated the association of linc-RoR overexpression in undifferentiated oral tumors and its prognostic value to predict the therapeutic response.
Human mitochondrial long noncoding RNAs (lncRNAs) have not been described to date. By analysis of deep-sequencing data we have identified three lncRNAs generated from the mitochondrial genome and confirmed their expression by Northern blotting and strand-specific qRT-PCR. We show that the abundance of these lncRNAs is comparable to their complementary mRNAs and that nuclear-encoded mitochondrial proteins involved in RNA processing regulate their expression. We also identify the 5' and 3' transcript ends of the three lncRNAs and show that mitochondrial RNase P protein 1 (MRPP1) is important for the processing of these transcripts. Finally, we show that mitochondrial lncRNAs form intermolecular duplexes and that their abundance is cell-and tissue-specific, suggesting a functional role in the regulation of mitochondrial gene expression.
Collecting representative data on sensitive issues has long been problematic and challenging in public health prevalence investigation (e.g. non-suicidal self-injury), medical research (e.g. drug habits), social issue studies (e.g. history of child abuse), and their interdisciplinary studies (e.g. premarital sexual intercourse). Alternative data collection techniques that can be adopted to study sensitive questions validly become more important and necessary. As an alternative to the famous Warner randomized response model, non-randomized response triangular model has recently been developed to encourage participants to provide truthful responses in surveys involving sensitive questions. Unfortunately, both randomized and non-randomized response models could underestimate the proportion of subjects with the sensitive characteristic as some respondents do not believe that these techniques can protect their anonymity. As a result, some authors hypothesized that lack of trust and noncompliance should be highest among those who have the most to lose and the least to use for the anonymity provided by using these techniques. Some researchers noticed the existence of noncompliance and proposed new models to measure noncompliance in order to get reliable information. However, all proposed methods were based on randomized response models which require randomizing devices, restrict the survey to only face-to-face interview and are lack of reproductivity. Taking the noncompliance into consideration, we introduce new non-randomized response techniques in which no covariate is required. Asymptotic properties of the proposed estimates for sensitive characteristic as well as noncompliance probabilities are developed. Our proposed techniques are empirically shown to yield accurate estimates for both sensitive and noncompliance probabilities. A real example about premarital sex among university students is used to demonstrate our methodologies.
Infrared thermography is a well-established technique for the non-destructive characterisation of various materials. This technique relies on the analysis of acquired temperature profile over the test sample to evaluate the presence of surface and sub-surface anomalies within the material. Over past decade coded thermal excitation schemes and associated post processing (signal/video processing) schemes have gained vital attention in infrared thermographic community in various fields. However, in thermal non-destructive testing the usage of coded excitations are still relatively uncommon. This paper explores the feasibility of using complementary Golay coded excitation in active thermography. The newly developed technique is shown to be effective in increasing temporal signal to noise ratio by suppressing side lobes of the compressed pulse. The present experimental investigation emphasises the defect detection capabilities of Golay coded thermal wave imaging to characterise a carbon fibre reinforced plastic material having blind holes and inclusions as defects. An investigation of spatial signal to noise ratio is also presented.
The theory of computer science is based around universal Turing machines (UTMs): abstract machines able to execute all possible algorithms. Modern digital computers are physical embodiments of classical UTMs. For the most important class of problem in computer science, non- deterministic polynomial complete problems, non- deterministic UTMs (NUTMs) are theoretically exponentially faster than both classical UTMs and quantum mechanical UTMs (QUTMs). However, no attempt has previously been made to build an NUTM, and their construction has been regarded as impossible. Here, we demonstrate the first physical design of an NUTM. This design is based on Thue string rewriting systems, and thereby avoids the limitations of most previous DNA computing schemes: all the computation is local (simple edits to strings) so there is no need for communication, and there is no need to order operations. The design exploits DNA's ability to replicate to execute an exponential number of computational paths in P time. Each Thue rewriting step is embodied in a DNA edit implemented using a novel combination of polymerase chain reactions and site- directed mutagenesis. We demonstrate that the design works using both computational modelling and in vitro molecular biology experimentation: the design is thermodynamically favourable, microprogramming can be used to encode arbitrary Thue rules, all classes of Thue rule can be implemented, and non- deterministic rule implementation. In an NUTM, the resource limitation is space, which contrasts with classical UTMs and QUTMs where it is time. This fundamental difference enables an NUTMto trade space for time, which is significant for both theoretical computer science and physics. It is also of practical importance, for to quote Richard Feynman ` there's plenty of room at the bottom'. This means that a desktop DNA NUTM could potentially utilize more processors than all the electronic computers in the world combined, and thereby outperform the world's current fastest supercomputer, while consuming a tiny fraction of its energy.
In this paper, a nonlinear current-output digital to analog converter (DAC) employing a pseudo-exponential transconductance amplifier is presented. The proposed transconductance amplifier makes use of the code-dependent body-biasing to realize the exponential relationship of the output current to the input digital signal in the CMOS technology. A digital control unit is designed to provide a linearly code-dependent voltage to feed into the transconductance amplifier by charging a capacitor for a period determined by a counter which is loaded by the input digital code. The proposed DAC is simulated in a 180 nm standard CMOS technology. The accuracy of the exponential input-output characteristic is verified by the curve fitting of the simulation results where R-squared value of the fitted functions is greater than 0.999 in all process and temperature corners. The presented DAC consumed 79 mu W in the worst-case.
Digital control in switching power converters has been proposed and researched in recent years. However, one of the problems which arise in these circuits is that of quantization-induced limit cycle oscillations, which are generally considered to be undesirable. In this work, we investigate the addition of new control terms in the feedback loop of the system, in order to actively prevent these limit cycles from occurring. Firstly, the addition of a sinusoidal signal is considered, and then a more complicated signal which focuses on interrupting how the system switches between duty cycle levels is presented. The methods are effective in removing the limit cycle oscillations which arise in the system. Copyright (c) 2013 John Wiley & Sons, Ltd.
Oscillators are essential to fuel autonomous behaviours in molecular systems. Artificial oscillators built with programmable biological molecules such as DNA and RNA are generally easy to build and tune, and can serve as timers for biological computation and regulation. We describe a new artificial nucleic acid biochemical reaction network, and we demonstrate its capacity to exhibit oscillatory solutions. This network can be built in vitro using nucleic acids and three bacteriophage enzymes, and has the potential to be implemented in cells. Numerical simulations suggest that oscillations occur in a realistic range of reaction rates and concentrations.
It is well known that the existence of unstable sampled zero dynamics is recognised as a major barrier in many control problems. When the usual digital control with zero-order hold (ZOH) or fractional-order hold (FROH) input is used, unstable sampled zero dynamics inevitably appear in the discrete-time model even though the continuous-time system with relative degree more than or equal to three is of minimum phase. In this paper, we show how an approximate sampled-data model can be obtained for nonlinear systems by the use of multirate input and hold such as a generalised sample hold function (GSHF) in order that discrete zero dynamics of the resulting model can be arbitrarily placed. Furthermore, the properties of sampled zero dynamics are studied and the conditions for ensuring the stability of sampling zero dynamics of the desired model are derived. The results presented here generalise well-known notion of sampling zero dynamics from the linear case to nonlinear systems, and GSHF can provide some advantages over ZOH or FROH in terms of stability of discrete system zero dynamics.
Vibration energy harvesting converts mechanical energy from ambient sources to electricity to power remote sensors. Compared to linear resonators that have poor performance away from their natural frequency, nonlinear vibration energy harvesters perform better because they use vibration energy over a broader spectrum. We present a hybrid nonlinear energy harvester that combines bi-stability with internal resonance to increase the frequency bandwidth. A two-fold increase in the frequency bandwidth can be obtained compared to a bi-stable system with fixed magnets. The harvester consists of a piezoelectric cantilever beam carrying a movable magnet facing a fixed magnet. A spring allows the magnet to move along the beam and it provides an extra stored energy to further increase the amplitude of vibration acting as a mechanical amplifier. An electromechanically coupled mathematical model of the system is presented to obtain the dynamic response of the cantilever beam, the movable magnet and the output voltage. The perturbation method of multiple scales is applied to solve these equations and obtain approximate analytical solutions. The effects of various system parameters on the frequency responses are investigated. The numerical approaches of the long time integration (Runge-Kutta method) and the shooting technique are used to verify the analytical results. The results of this study can be used to improve efficiency in converting wasted mechanical vibration to useful electrical energy by broadening the frequency bandwidth. (C) 2016 Elsevier Ltd. All rights reserved.
The recent development in nanotechnology resulted in growing of various nanoplate like structures. High attention was devoted to graphene sheet nanostructure, which enforced the scientist to start developing various theoretical models to investigate its physical properties. Magnetic field effects on nanoplates, especially graphene sheets, have also attracted a considerable attention of the scientific community. Here, by using the nonlocal theory, we examine the influence of in-plane magnetic field on the viscoelastic orthotropic multi-nanoplate system (VOMNPS) embedded in a viscoelastic medium. We derive the system of m partial differential equations describing the free transverse vibration of VOMNPS under the uniaxial in-plane magnetic field using the Eringen's nonlocal elasticity and Kirchhoffs plate theory considering the viscoelastic and orthotropic material properties of nanoplates. Closed form solutions for complex natural frequencies are derived by applying the Navier's and trigonometric method for the case of simply supported nanoplates. The results obtained with analytical method are validated with the results obtained by using the numerical method. In addition, numerical examples are given to show the effects of nonlocal parameter, internal damping, damping and stiffness of viscoelastic medium, rotary inertia and uniaxial in-plane magnetic force on the real and the imaginary parts of complex natural frequencies of VOMNPS. This study can be useful as a starting point for the research and design of nanoelectromechanical devices based on graphene sheets. (C) 2017 Elsevier Masson SAS. All rights reserved.
Most research on ethnicity has focused on visual cues. However, accents are strong social cues that can match or contradict visual cues. We examined understudied reactions to people whose one cue suggests one ethnicity, whereas the other cue contradicts it. In an experiment conducted in Germany, job candidates spoke with an accent either congruent or incongruent with their (German or Turkish) appearance. Based on ethnolinguistic identity theory, we predicted that accents would be strong cues for categorization and evaluation. Based on expectancy violations theory we expected that incongruent targets would be evaluated more extremely than congruent targets. Both predictions were confirmed: accents strongly influenced perceptions and Turkish-looking German-accented targets were perceived as most competent of all targets (and additionally most warm). The findings show that bringing together visual and auditory information yields a more complete picture of the processes underlying impression formation.
Non-orthogonal multiple access (NOMA) has attracted a significant attention to the research community as a potential candidate for 5G or future radio access. This article presents a NOMA-based cooperative network where a transmitter considered as a base station communicates simultaneously with two users treating as a far user and a near user via the help of a half-duplex decode-and-forward relay. We investigate the outage probability and the outage capacity of the proposed network over independent Rayleigh slow fading channels. Closed-form expressions of the outage probabilities are derived for both users. Approximate outage capacity of the users are also investigated at high signal to noise ratio regime. It has been shown that the proposed cooperative NOMA can achieve superior performance compared to the non-cooperative NOMA in terms of outage probability. The tightness between the simulation and theoretical results confirms the efficiency of the proposed protocol.
Objective: Lung cancer is one of the most common leading causes of cancer related death in the worldwide, thus its early detection might be a critical strategy to improve patients' prognosis and survival. The present study was designed to assess if microRNAs expression profiling of bronchoalveolar lavage cell fraction and sputum could help to non-small cell lung cancer early detection. Materials and methods: Relative expression of 3 selected microRNAs (miR-10b, miR-1 and miR-30a) were quantified using Real-time polymerase chain reaction in bronchoalveolar lavage cell fraction and sputum samples from non-small cell lung cancer cases (n = 30) and cancer-free group (n = 30). Written informed consent from all enrolled individuals was obtained. So, the Ethical and Scientific Committees of the participating institution confirmed the present study in accordance with the ethical standards (as laid down in 1964 Declaration of Helsinki). Results: miR-1 and miR-30a were significantly downregulated in non-small-cell lung cancer patients, bronchoalveolar lavage and sputum while miR-10b was significantly upregulated. Overexpression of miR-10b has a positive strong correlation with clinical stages of cancer. ROC curve analysis of miR-10b (as oncomir) and miR-1 (as tumor suppressor) in bronchoalveolar lavage and sputum samples showed that miR-10b with 0.931 and 0.927 AUC values and miR-1 with 0.786 and 0.788 AUC values, could be an excellent and a fair candidate microRNA to distinguish non-small-cell lung cancer patients from cancerfree subjects, respectively. Conclusion: This study reported significant differences in microRNAs expression in bronchoalveolar lavage and sputum samples of lung cancer patients compared to cancer-free subjects which represent a potential role as a highly specific and sensitive test to Improved early detection of non-small cell lung cancer. (C) 2017 Elsevier Masson SAS. All rights reserved.
In this study, we conducted a case-control study to explore the association between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of rs1550117 A>G variant was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA genotype carriers. Further stratified analysis showed that rs1550117 A>G was significantly related to age ( >60 years), male, smoking and drinking. In vivo detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays consistently showed that the allele G significantly decreased DNMT3A transcription. Additional functional analysis revealed that the increased binding affinity of transcription repressor SP1, which was associated with allele G of rs1550117, led to the significant decreased expression of DNMT3A. Collectively, our results propose a suppression role of DNMT3A in NSCLC development and emphasize the dual roles of DNMT3A in tumorigenesis.
Despite better understanding of it's molecular biology, non-small cell lung cancer (NSCLC) remains a challenging disease to treat. Unfortunately, treatment options are still very limited and prognosis for advanced disease is poor. Immune surveillance plays a crucial role in a host's defence against tumour cells, and this is particular relevant for lung cancer due to it's high somatic mutational load, which increases the chances for the immune system to recognize cancer cells as 'non-self'. Novel immunotherapies are emerging as an effective treatment for this disease. In this review, we present the data on immune checkpoint inhibitors for NSCLC, describing their mechanism of action, data efficacy from recent clinical trials, and strategies to select patients more likely to benefit from these agents.
In this study, we evaluated the prognostic potential and functional regulation of human nature antisense, brain-derived neurotrophic factor antisense, in non-small cell lung cancer. Non-small cell lung cancer carcinoma and adjacent non-carcinoma lung tissues were extracted from 151 patients. Their endogenous brain-derived neurotrophic factor antisense expression levels were compared by quantitative reverse transcription polymerase chain reaction. Clinical relevance between endogenous brain-derived neurotrophic factor antisense expression level and patients' clinicopathological variances or overall survival was analyzed. The potential of brain-derived neurotrophic factor antisense being an independent prognostic factor in non-small cell lung cancer was also evaluated. In in vitro non-small cell lung cancer cell lines, brain-derived neurotrophic factor antisense was upregulated through forced overexpression. The effects of brain-derived neurotrophic factor antisense upregulation on non-small cell lung cancer in vitro survival, proliferation, and migration were evaluated by viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and transwell assays. Brain-derived neurotrophic factor antisense is lowly expressed in non-small cell lung cancer carcinoma tissues and further downregulated in late-stage carcinomas. Brain-derived neurotrophic factor antisense downregulation was closely associated with non-small cell lung cancer patients' advanced tumor, lymph node, metastasis stage, and positive status of lymph node metastasis, and confirmed to be an independent prognostic factor for patients' poor overall survival. In non-small cell lung cancer A549 and H226 cell lines, forced overexpression of brain-derived neurotrophic factor antisense did not alter cancer cell viability but had significantly tumor suppressive effect in inhibiting in vitro non-small cell lung cancer proliferation and migration. Endogenous brain-derived neurotrophic factor antisense in non-small cell lung cancer carcinoma could be a potential biomarker for predicting patients' prognosis. Overexpressing brain-derived neurotrophic factor antisense may also have a therapeutic potential in inhibiting non-small cell lung cancer tumor growth.
Radiation treatment remains one of the major modalities in the treatment of lung cancer. Although the majority of patients initially respond to treatment with radiation, resistance inevitably develops and leads to treatment failure. Therefore, the identification of the underlying molecular mechanisms of radiation resistance may facilitate the development of novel approaches for overcoming resistance, and enhance the efficacy of treatment with radiation in lung and other types of cancer. In the present study we established three radiation-resistant sub-cell lines derived from the radiation-sensitive lung cancer cell line HCC827. Using a polymerase chain reaction microRNA (miRNA) array, multiple miRNAs were identified to be markedly downregulated in radiation-resistant cells, including miRNA (miR)-124, miR-191 and miR-205. It was observed that overexpression of miR-124 sensitized the resistant cells to treatment with radiation and that thioredoxin reductase 1 (TXNRD1) is a novel target of miR-124. Furthermore, it was demonstrated that knockdown of TXNRD1 using small interfering RNA increased the basal level of reactive oxygen species and sensitized the cells to radiation treatment. The results of the present study demonstrated that multiple miRNAs are downregulated in radiation-resistant lung cancer cells and that downregulation of miR-124 mediates radiation resistance through the targeting of TXNRD1 mRNA expression. The present study revealed a novel molecular mechanism of miRNA-mediated radiation resistance and identified miR-124-regulated TXNRD1 as a novel therapeutic target for overcoming radiation resistance in the treatment of lung cancer.
Advanced non-small cell lung cancer (NSCLC) has long been a diagnosis with few treatment options and poor outcomes. However, recent discoveries about the molecular biology of NSCLC are changing the way it is treated. Driver mutations that cause uncontrolled cancer cell proliferation have been discovered in some types of NSCLC. This has led to the discovery of therapies that can target a specific driver mutation in advanced NSCLC and halt cancer progression. This article reviews standard treatment of NSCLC and explores the targetable mutations of NSCLC, available targeted treatments, treatment obstacles, and the future of targeted therapy in NSCLC.
In recent years, major advances in our understanding of the molecular biology of lung cancer, together with significant improvements in radiotherapy technologies, have revolutionized the treatment of non-small cell lung cancer (NSCLC). This has led to the development of new therapies that target molecular mutations specific to each tumor type, acting on the cell surface antigens or intracellular signaling pathways, or directly affecting cell survival. At the same time, ablative dose radiotherapy can be delivered safely in the context of metastatic disease. In this article, the GOECP/SEOR (Oncological Group for Study of Lung Cancer/Spanish Society of Radiation Oncology) reviews the role of new targeted therapies used in combination with radiotherapy in patients with locally advanced (stage III) NSCLC and in patients with advanced, metastatic (stage IV) NSCLC.
This paper presents a novel approach to non-standard timber assembly - Robotic Timber Construction (RTC) where robotic fabrication is used to expand additive digital fabrication techniques towards industrial full scale dimensions. Featuring robotic systems that grasp, manipulate, and finally position building components according to a precise digital blueprint, RTC combines robotic assembly procedures and advanced digital design of nonstandard timber structures. The resulting architectural morphologies allow for a convergence of aesthetic and functional concerns, enabling structural optimisation through the locally differentiated aggregation of material. Initiated by the group of Gramazio Kohler Research at ETH Zurich, this approach offers a new perspective on automated timber construction, where the focus is shifted from the processing of single parts towards the assembly of generic members in space. As such, RTC promotes unique advantages over conventional approaches to timber construction, such as, for example, CNC joinery and cutting: through the automated placement of material exactly where it is needed, RTC combines additive and largely waste-free construction with economic assembly procedures, it does not require additional external building reference, and it offers digital control across the entire building process, even when the design and assembly information are highly complex. This paper considers 1) research parameters for the individual components of RTC (such as computational design processes, construction methods and fabrication strategies), and 2) the architectural implications of integrating these components into a systemic, unifying process at the earliest stages of design. Overall, RTC leads to profound changes in the design, performance and expressive language of architecture and thus fosters the creation of architecture that profoundly reinvents its constructive repertoire. (C) 2015 Elsevier B.V. All rights reserved.
ObjectiveThe functional variant within the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene c.677C>T, producing alterations in folate metabolism, has been associated with the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). We assessed this association in a Chilean population using a combined analysis of case-control and case-parent trio samples. Subjects and methodsSamples of 165 cases and 291 controls and 121 case-parent trios (sharing the cases) were genotyped. Odds ratio (OR) was estimated for case-control (allele and genotype frequency differences), and this result was confirmed by allele transmission distortion in trios. Due to that these samples are not independent, a combined OR was also computed. Maternal genotype effect was additionally evaluated based on a log-linear method. ResultsBorderline but not significant OR (1.28; CI 0.97-1.69) was observed for risk allele (T) in the case-control sample. However, triad sample showed a significant association (OR 1.56: CI 1.09-2.25) which was confirmed by the combined OR (1.37; CI 1.11-1.71). Maternal genotype has been also associated with the phenotype (P=0.002). ConclusionsIn contrast to previous reports considering Chilean subjects, our results demonstrated that the offspring and maternal genotypes for MTHFR c.677C>T variant are strongly associated with NSCL/P in this Chilean population.
Non-tuberculous mycobacteria (NTM) are not only emerging and opportunistic pathogens of both humans and animals, but from a veterinary point of view some species induce cross-reactive immune responses that hamper the diagnosis of bovine tuberculosis (bTB) in both livestock and wildlife. Little information is available about NTM species circulating in wildlife species of South Africa. In this study, we determined the diversity of NTM isolated from wildlife species from South Africa as well as Botswana. Thirty known NTM species and subspecies, as well as unidentified NTM, and NTM closely related to Mycobacterium goodii/Mycobacterium smegmatis were identified from 102 isolates cultured between the years 1998 and 2010, using a combination of molecular assays viz PCR and sequencing of different Mycobacterial house-keeping genes as well as single nucleotide polymorphism (SNP) analysis. The NTM identified in this study include the following species which were isolated from tissue with tuberculosis-like lesions in the absence of Mycobacterium tuberculosis complex (MTBC) implying their potential role as pathogens of animals: Mycobacterium abscessus subsp. bolletii, Mycobacterium gastri, Mycobacterium species closely related to Mycobacterium goodii/Mycobacteriurn smegmatis, Mycobacterium brasiliensis, Mycobacterium sinense JMD 601, Mycobacterium avium subsp. avium, Mycobacterium sp. GR-2007, Mycobacterium bouchedurhonense, and Mycobacterium septicum/M. peregrinum. Mycobaterium brasiliensis, Mycobacterium gastri, Mycobacterium sp. GR-2007, and a potential novel Mycobacterium species closely related to Mycobacterium goodii were found for the first time in this study to be potential pathogens of animals. Mycobacterium simiae was isolated from a sample originating from a tuberculin skin test positive reactor, demonstrating its potential to elicit inappropriate immune responses in animals that may interfere with diagnosis of tuberculosis by immunology. Mycobacterium abscessus subsp. bolletti was the most frequently detected NTM identified in 37 of the 102 isolates. Other NTM species were also isolated from animals not showing any pathological changes. Knowledge gained in this study contribute to the understanding of NTM species circulating in wild animals in South Africa and the pathogenic potential of certain species, whose role in disease causation need to be examined, as well as to a certain extent the potential of M. simiae to hamper the diagnosis of bTB.
Noroviruses are the leading cause of acute gastroenteritis in humans. Real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) is a promising molecular method for the detection of noroviruses. In this study, the performance of three TaqMan real-time RT-PCR assays was assessed, which were one commercially available real-time RT-PCR kit (assay A: Norovirus Real Time RT-PCR kit) and two in-house real-time RT-PCR assays (assay B: LightCycler RNA Master Hybprobe and assay C: RealTime ready RNA Virus Master). Assays A and B showed higher sensitivity than assay C for norovirus GI, while they all had the same sensitivity (103 DNA copies/mL) for GII DNA standard controls. Assay B had the highest efficiency for both genogroups. No cross-reactivity was observed among GI and GII noroviruses, rotavirus, hepatitis A virus, and poliovirus. The detection rates of these assays in GI and GII norovirus-positive fecal samples were not significantly different. However, the mean quantification cycle (Cq) value of assay B for GII was lower than assays A and C with statistical significance (P-value, 0.000). All three real-time RT-PCR assays could detect a variety of noroviruses including GI. 2, GII. 2, GII. 3, GII. 4, GII. 6, GII. 12, GII. 17, and GII. 21. This study suggests assay B as a suitable assay for the detection and quantification of noroviruses GI and GII due to good analytical sensitivity and higher performance to amplify norovirus on DNA standard controls and clinical samples.
Sewage samples have been investigated to study the norovirus concentrations in sewage or the genotypes of noroviruses circulating in human populations. However, the statistical relationship between the concentration of the virus and the number of infected individuals and the clinical importance of genotypes or strains detected in sewage are unclear. In this study, we carried out both environmental and clinical surveillance of noroviruses for 3 years, 2013 to 2016. We performed cross-correlation analysis of the concentrations of norovirus GI or GII in sewage samples collected weekly and the reported number of gastroenteritis cases. Norovirus genotypes in sewage were also analyzed by pyrosequencing and compared with those identified in stool samples. The cross-correlation analysis found the peak coefficient (R = 0.51) at a lag of zero, indicating that the variation in the GII concentration, expressed as the log10 number of copies per milliliter, was coincident with that in the gastroenteritis cases. A total of 15 norovirus genotypes and up to 8 genotypes per sample were detected in sewage, which included all of the 13 genotypes identified in the stool samples except 2. GII. 4 was most frequently detected in both sample types, followed by GII. 17. Phylogenetic analysis revealed that a strain belonging to the GII. 17 Kawasaki 2014 lineage had been introduced into the study area in the 2012-2013 season. An increase in GI. 3 cases was observed in the 2015-2016 season, and sewage monitoring identified the presence of GI. 3 in the previous season (2014-2015). Our results demonstrated that monitoring of noroviruses in sewage is useful for sensitive detection of epidemic variants in human populations. IMPORTANCE We obtained statistical evidence of the relationship between the variation in the norovirus GII concentration in sewage and that of gastroenteritis cases during the 3-year study period. Sewage sample analysis by a pyrosequencing approach enabled us to understand the temporal variation in the norovirus genotypes circulating in human populations. We found that a strain closely related to the GII. 17 Kawasaki 2014 lineage had been introduced into the study area at least 1 year before its appearance and identification in clinical cases. A similar pattern was observed for GI. 3; cases were reported in the 2015-2016 season, and closely related strains were found in sewage in the previous season. Our observation indicates that monitoring of noroviruses in sewage is useful for the rapid detection of an epidemic and is also sensitive enough to study the molecular epidemiology of noroviruses. Applying this approach to other enteric pathogens in sewage will enhance our understanding of their ecology.
The updated RIDA (R) QUICK (N1402) immunochromatographic assay (R-Biopharm) for detection of norovirus was evaluated during a prospective, multicenter study using 771 stool samples from patients with gastroenteritis. Compared to real-time reverse transcriptase polymerase chain reaction (RT-rtPCR) as gold standard, the RIDA (R) QUICK had an overall sensitivity of 72.8% (91/125) and a specificity of 99.5% (640/643). Genotype analysis of the polymerase (ORF1) and capsid (ORF2) region of the genome indicated that the RIDA (R) QUICK assay could detect a broad range of genotypes including new variants (15 of 125 positive samples) which were detected by an in-house SYBR (R) Green RT-rtPCR, but not by the RIDA (R) GENE PCR PG1415 (R-Biopharm) and mostly not by the RIDA (R) GENE PCR PG1405 and the Xpert (R) Norovirus assay (Cepheid). The RIDA (R) QUICK can be used to reliably confirm norovirus in stool samples, but a negative result does not definitively exclude the presence of norovirus. (C) 2017 Elsevier Inc. All rights reserved.
Silver nanoparticles (AgNP) have strong broad-spectrum antimicrobial activity and gained increased attention for the development of AgNP based products, including medical and food applications. Initially, the efficacy of AgNP and silver nitrate (AgNO3) was evaluated for inactivating norovirus surrogates, the feline calicivirus (FCV) and the murine norovirus (MNV). These norovirus surrogates were exposed to AgNO3 and AgNP solutions for 24 h at 25 degrees C and then analyzed by cell-culture assays. Both AgNP and silver ions significantly decreased FCV and MNV infectivity in a dose-dependent manner between concentrations of 2.1 and 21 mg/L. Furthermore, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) films were prepared by depositing a coating of thermally post-processed electrospun PHBV18/AgNP fiber mats over compression moulded PHBV3 films. After 24 h exposure at 37 degrees C and 100% RH, no infectious FCV were recovered when in contact with the AgNP films while MNV titers decreased by 0.86 log. The morphology of the PHBV18 and PHBV18/AgNP fibers studied by SEM showed smooth and continuous fibers in both cases and the EDAX analysis confirmed the homogeneously distribution of AgNP into the coating and onto the PHBV3/PHBV18 layer. This study showed, for the first time, the suitability of the PHBV18/AgNP electrospun coating for antiviral surfaces. (C) 2017 Elsevier Ltd. All rights reserved.
Successful detection of very small RNAs (tiny RNA, similar to 14 nt in length) by Northern blotting is dependent on improved Northern blot protocols that combine chemical crosslinking of RNA with 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide (EDC) to positively charged membranes, the use of native polyacrylamide gels, and the development of highly sensitive and specific probes modified with locked nucleic acids (LNA). In this protocol, we show that Northern blot detection of tiny RNAs with 5'-digoxigenin-labeled DNA/LNA mixmer probes is a highly sensitive and specific method and, in our hands, more sensitive than using a corresponding DNA/LNA mixmer probe with a 5'-P-32-end label.
This protocol describes how to perform northern blot analyses to detect microRNAs and their precursors with single-nucleotide resolution, which is crucial for analyzing individual length variants and for evaluating relative quantities of unique microRNAs in cells. Northern blot analysis consists of resolving RNAs by gel electrophoresis, followed by transferring and fixing to nylon membranes as well as detecting by hybridization with radioactive probes. Earlier efforts to improve this method focused mainly on altering the sensitivity of short RNA detection. We have enhanced the resolution of the northern blot technique by optimizing the electrophoresis step. We have also investigated other steps of the procedure with the goal of enhancing the resolution of RNAs; herein, we present several recommendations to do so. Our protocol is applicable to analyses of all kinds of endogenous and exogenous RNAs, falling within length ranges of 20-30 and 50-70 nt, corresponding to microRNA and pre-microRNA lengths, respectively.
A medium selectivity notch filter has been proposed. The active RC filter has only one operational amplifier and three resistors with one floating capacitor as passive components. Two floating resistors provide the positive feedback and one grounded resistor is used for independent tuning of Q factor. The amplifier pole frequency is used for designing the circuit and amplifier used is in both positive and negative feedback configuration. The filter can be tuned for a wide frequency range between 10 kHz-250 kHz and a medium Q factor upto 25 is achievable by proposed configuration. The circuit shows low passive parameter sensitivity which is characteristic of a single pole model. PSpice simulations have been presented to verify theoretical analysis.
AIM To explore the exact interaction between Notch and transforming growth factor (TGF)-beta signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells (PBMCs) were isolated from the modeled rats, and cultured with.-secretase inhibitor DAPT and TGF-beta inhibitor for 24 h. The mRNA levels of Notch and TGF-beta signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-beta proteins was analyzed by western blotting. RESULTS Compared to control rats, Notch and TGF-beta signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-beta inhibitor suppressed Notch and TGF-beta signal transducer in PBMCs of model rats. DAPT reduced mRNA and protein expression of TGF-beta signaling, such as TGF-beta 1 and Smad3. TGF-beta inhibitor also downregulated Notch1, Hes1 and Hes5, and mRNA and protein expression of the Notch signaling pathway. CONCLUSION Notch and TGF-beta signaling play a role in liver fibrosis. TGF-beta signaling upregulates Notch signaling, which promotes TGF-beta signaling.
Fourteen novel miniature inverted-repeat transposable element (MITE) families are found in the Florida carpenter ant genome, Camponotus floridanus. They constitute approximately 0.63 % of the entire genome. Analysis of their insertion time showed that most members of these MITEs were inserted into their host genome in less than 8 million years ago. In addition, the association between MITEs and the noncoding regions of genes in C. floridanus is random. Interestingly, an autonomous partner (named CfTEC) responsible for the amplification of these MITEs was also found in C. floridanus. Meanwhile, we present evidence, based on searches of publicly available databases, that this autonomous element was widespread in animals. Moreover, structure and phylogenetic analyses supported that TECs might represent a novel cade of transposons intermediate between the classic CACTA transposon and TRCs. Finally, their transposition mechanism and impact on host genome evolution were also discussed.
With the rapid development of the space technology, operational amplifier is widely used as the basic liner circuit in a satellite system. There are many charged particles trapped in the earth's magnetosphere, most of the particles are protons and electrons. In BJTs, the damage caused by electrons causes both bulk recombination and surface recombination to increase and subsequently current gain to decrease. Transistor gain degradation is the primary cause of parametric shifts and functional failures in linear bipolar circuits. The severity of electron radiation response correlates with electron's energy and flux, therefore it is important to understand the electron radiation response in different conditions. In this paper, the tested devices used in this study are NPN-input bipolar operational amplifiers commercial-off-the-shelf (COTS) manufactured by Texas Instruments (TI). NPN-input bipolar operational amplifiers LM108 are irradiated with different energy and different beam current electrons respectively under different bias conditions to study the electron radiation damage effect. Experiment using Co-60 gamma-ray radiation is conducted to compare the different radiation damages between Co-60 gamma-ray and electron radiation. The total radiation experiments are carried out with the Co-60 gamma-ray source (Xinjiang Technical Institute of physics and chemistry). The radiation dose rates for the test samples are 1 Gy (Si)/s, and the total accumulated dose is 1000 Gy (Si). Subsequently, room temperature and high temperature annealings are conducted to analyze the parametric failure mechanism of LM108 caused by a total dose radiation for different biases. Result shows that 0.32 Gy(Si)/s beam current electrons can induce more damage than that caused by 1.53 Gy(Si)/s electrons with the same energy; 1.8 MeV electrons can induce more damages than 1 MeV electrons with the same electron beam current because the former produces more displacement damage than the latter. Comparison between zero and forward biased devices shows that different biased devices have different radiation sensibility, and radiation produces more damages in zero biased devices than in forward biased devices with the same electron energy and beam current. This is because forward biased BJT will suppress the edge electric field, thus leading to the decrease of oxide-trapped charge and interface-trapped charge. During high-temperature annealing, degradation of the devices obviously can be recovered and almost return to the initial value finally. This result indicates that the 1.8 MeV and 1 MeV electron radiation mainly induces ionization damage in bipolar operational amplifier LM108.
The aim of this study was to investigate the therapeutic effect of Angelica sinensis on a rat model of diffuse interstitial pulmonary fibrosis induced by bleomycin A5. The mechanism by which A. sinensis exerts its effect is also discussed. A diffuse interstitial pulmonary fibrosis model was established in 36 male Wistar rats by an endotracheal injection of bleomycin A5 (5mg/kg). Then, these rats were randomly divided into the model group (n = 18) and the treatment group (treated with A. sinensis after modelling, n = 18). Control rats (n = 6) received an equal volume of saline. Hematoxylin-eosin (HE) staining was performed to analyse alveolitis and Masson staining, to observe pulmonary fibrosis. Collagen content was determined by hydroxyproline assay. Nuclear factor kappa B (NF-kappa B) activity was measured by electrophoretic mobility shift assay. Transforming growth factor-beta (TGF-beta) expression at mRNA level was detected by northern blotting and at protein level by enzyme-linked immunosorbent assay. The results obtained showed that the alveolitis and pulmonary fibrosis of the rats treated with A. sinensis was significantly alleviated compared with that of the rats in the model group. Treatment with A. sinensis also lowered the content of collagen, decreased NF-kappa B activity in alveolar macrophages and reduced the TGF-beta expression at the mRNA and protein level. These results indicated that A. sinensis is effective in treating and alleviating interstitial pulmonary fibrosis, possibly by lowering collagen, inhibiting the activity of NF-kappa B and reducing the TGF-beta expression.
Requiring only simple heating devices, isothermal nucleic acid-based amplification (NASBA) is a potential detection platform to be developed for on-site diagnosis of aquaculture pathogens. In this report, an NASBA assay has been developed for the Taura syndrome virus (TSV), one of the most devastating RNA virus pathogens for several penaeid shrimp species. The NASBA amplicons were detected by agarose gel electrophoresis and confirmed by Northern-blotting and dot-blotting analysis, using a biotinylated TSV-specific primer. The sensitivity of the TSV NASBA coupled with dot-blotting detection was approximately 5-fold less sensitive than that of the commercially available RT-nested, PCR-based IQ2000 TSV Detection and Prevention System that was also confirmed to be more sensitive than the RT-PCR-based TSV detection protocol recommended by the OIE (Office International des Epizooties). The specificity of the TSV NASBA reaction was substantiated by the results that RNA of non-target viruses did not generate any signals. Furthermore, a simple colorimetric microtiter plate assay employing TSV-specific capture and detection primers was developed as a simple alternative approach for the detection of NASBA amplicons. Taken together, the combination of the isothermal NASBA and colorimetric solid phase-based assays should allow sensitive, straightforward, and speedy on-site detection of TSV.
5-Bromouracil is a nucleobase analogue that can replace thymine in DNA strands and acts as a strong radiosensitizer, with potential applications in molecular biology and cancer therapy. Here, the deactivation of 5-bromouracil after ultraviolet irradiation is investigated in the singlet and triplet manifold by accurate quantum chemistry calculations and non-adiabatic dynamics simulations. It is found that, after irradiation to the bright pp* state, three main relaxation pathways are, in principle, possible: relaxation back to the ground state, intersystem crossing (ISC) and C-Br photodissociation. Based on accurate MS-CASPT2 optimizations, we propose that ground-state relaxation should be the predominant deactivation pathway in the gas phase. We then employ different electronic structure methods to assess their suitability to carry out excited-state dynamics simulations. MRCIS (multi-reference configuration interaction including single excitations) was used in surface hopping simulations to compute the ultrafast ISC dynamics, which mostly involves the (1)n(O)pi* and (3)pi pi* states. This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.
Nucleophosmin (NPM) and human epidermal growth factor receptor-2 (Her-2) are abnormally expressed in various types of human malignant tumors, including gastric cancer, and have been closely associated with cancer chemoresistance. However, their interaction and roles in oxaliplatin resistance are not fully understood. Therefore, the present study aimed to elucidate the relationship between NPM and Her-2 in gastric cancer cell lines and clinical samples, and further investigated their role in the resistance of gastric cancer to oxaliplatin. Western blotting and reverse transcription-quantitative polymerase chain reaction confirmed that NPM and Her-2 expression were significantly upregulated in gastric cancer cells and clinical samples, and that their expression levels were strongly correlated. However, Her-2 expression was not affected by upregulation or downregulation of NPM expression in gastric cancer cells. Cell counting kit-8 assays demonstrated that the cell sensitivity to oxaliplatin decreased simultaneously with an increase in NPM expression. Furthermore, inhibition of Her-2 expression using trastuzumab significantly increased the sensitivity of the cells to oxaliplatin, which occurred simultaneously with the downregulation of NPM. These results indicated that inhibition of NPM, as a Her-2 downstream signal, may be a novel strategy to overcome oxaliplatin-resistant gastric cancer, and that trastuzumab and oxaliplatin may exhibit a synergistic antitumor effect in Her-2-positive gastric cancer cells.
It is acknowledged that knowledge and knowledge bases are an important part of coach and athlete learning and that the coach - athlete relationship is crucial to knowledge created, shared and used. This said knowledge about nutrition as constructed by elite gymnasts would seem particularly important in a culture long associated with weight control practices and disordered eating. This paper provides an insight into the ways that 10 Brazilian Olympic gymnasts construct ideas pertaining to nutritional knowledge across generational periods (between 1980 and 2004) where significant organisational change in Women's Artistic Gymnastics in Brazil occurred and included the introduction of dieticians. Drawing upon different knowledge types and paying attention to the coaching context, the life histories of 10 Olympic gymnasts were used to open a window on knowledge construction pertaining to nutrition by three generations of gymnasts. The findings draw attention to two main illustrative themes. Firstly, coaches' personal knowledge, whilst perceived as incomplete by gymnasts, reinforced a narrative of weight loss for gymnasts regardless of generation. Secondly, the younger generations of gymnasts perceived that the introduction of dieticians into structured provision enabled them to use better structured knowledge, and with it a sense of increased autonomy and corporeal learning via the construction of tacit embodied knowledge leading to healthier practices. Reflections are given to the role of the coach, dieticians and pedagogical actions, and the continued reshaping of knowledge in elite gymnastics.
Background: The early postnatal period is critical for immunity, and feeding docosahexaenoic acid (DHA) has been demonstrated to affect immune development. Objective: The objective of this study was to determine the importance of feeding DHA during suckling and/or weaning on immune function and oral tolerance (OT). Methods: Sprague-Dawley rats were randomly assigned to 1 of 2 nutritionally adequate diets throughout lactation (21 d): a control (n = 12, 0% DHA) diet or a DHA (n = 8, 0.9% DHA) diet. At 11 d, suckled pups from each dam were randomly assigned to a mucosal OT challenge: placebo or ovalbumin. At week 5, all pups systemically received ovalbumin + adjuvant to induce systemic immunization. At 21 d, pups from each dam were randomly assigned to 1 of the 2 diets for 21 d in a factorial design after which immune function and OT were assessed. Results: Feeding dams DHA during lactation resulted in a 40-60% higher splenocyte production of interleukin (IL)-10 when stimulated with concanavalin A, lipopolysaccharide (LPS), or ovalbumin and a 100% higher production of interferon (IFN)-gamma with LPS (P< 0.05) than feeding the control diet to the pups. In comparison with pups fed the control diet, feeding DHA at weaning resulted in a 25% lower type 1 T helper (IL-1 beta) and type 2 T helper (IL-6) response by splenocytes after LPS stimulation and a 33% lower plasma concentration of ovalbumin-specific immunoglobulin (Ig) G (P < 0.05). Pups that did not receive additional DHA during the study had a 70% higher plasma concentration of ovalbumin-specific IgE than did the pups that received DHA at suckling and/or weaning (P< 0.05). Conclusions: Feeding additional DHA during suckling had a beneficial programming effect on the ability of immune cells to produce IFN-gamma and IL-10, and feeding DHA during weaning resulted in a lower inflammatory response. Providing no dietary DHA in either of the critical periods of immune development prevented the establishment of OT in female rat offspring.
The staggering prevalence of obesity and obesity-related health conditions takes exorbitant tolls on health care resources. This cross-sectional study with private evaluations of 636 adult inmates in a southern state prison was conducted with regressions comparing obese (body mass index [BMI] >= 30) to nonobese individuals to define obesity risk factors. Obese individuals more likely were female, were victims of childhood sexual abuse, suffered greater severity of childhood sexual abuse, attempted suicide, reported drug dependency, were non-Caucasian, and were older than nonobese. Psychopathy predicted lower BMI. Though obesity might be expected in victims of childhood physical abuse, traumatic brain injury, or other mental health conditions due to mobility or decision-making deficits, neither were significant. Adjusting for related variables, childhood sexual abuse remained significant. Females attempted suicide more frequently and suffered greater childhood sexual abuse.
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57B1/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57BI/6 background strain), at three months of age (n = 10/group). At euthanasia, animals had their interscapular BATweighed, and prepared for analysis (Western blot, and RTqPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1). The ob/ob group also showed impaired gene expression for lipid utilization (perilipin was increased, while other markers were diminished: carnitine palmitoyltransferase-1b, CPT-lb; cluster of differentiation 36, CD36; fatty acid binding protein 4, FABP4; fatty acid synthase, FAS, and sterol regulatory element-binding protein 1c, SREBP1c), and altered protein expression of insulin signaling (diminished pAKT, TC10, and GLUT-4). Lastly, the ob/ob group showed increased gene expression of markers of inflammation (interleukin 1 beta, IL-1beta; IL-6, tumor necrosis factor alpha, TNFalpha; and monocyte chemotactic protein-1, MCP-1). In conclusion, the ob/ob mice have decreased thermogenic markers associated with reduced gene expression related to fatty acid synthesis, mobilization, and oxidation. There were also alterations in insulin signaling and protein and gene expressions of inflammation. The findings suggest that the lack of substrate for thermogenesis and the local inflammation negatively regulated thermogenic signaling in the ob/ob mice. (C) 2016 Elsevier GmbH. All rights reserved.
This study explores whether object relations (OR) functioning improves over the course of psychodynamic psychotherapy, and whether this improvement is related to symptom decrease as well as therapist technique. The sample consisted of 75 outpatients engaged in short-term psychodynamic psychotherapy at a university-based psychological service clinic. OR functioning was assessed pre- and post-treatment by independent raters using the Social Cognition and Object Relations Scale from in-session patient relational narratives. The Comparative Psychotherapy Process Scale was used to assess therapist activity and psychotherapy techniques early in treatment. Independent clinical ratings of global OR and psychotherapy techniques were conducted, and rater agreement was found to be in the excellent range. Regarding the results, global OR (overall quality and level of interpersonal functioning) significantly improved with large effect size after psychodynamic therapy. Change in global OR functioning was significantly and positively related to the incidence of psychodynamic techniques in early sessions, as were number of psychotherapy sessions attended. Patient self-reported reliable change in symptomatology and reliable change in global OR were significantly related as well. Multilevel model analyses confirmed pairwise correlations accounting for therapist effects on a variety of process-outcome measures, number of sessions attended, initial levels of psychiatric symptoms, employment of therapeutic techniques as well overall OR functioning at outcome. Limitations of the present study, future research directions and implications for clinical practice are also discussed. Copyright (c) 2016 John Wiley & Sons, Ltd.
Research on the risk factors for SI in adults with OC tendencies is limited, and it is still unclear whether the association between OC tendencies and SI in non-clinical individuals exists. The goal of the present study was to test the associations between OC tendencies, self/other perception, personality traits, depressive symptoms and SI among a non-clinical adult population. We investigated an Italian sample of 337 adults, who were administered a set of self-report questionnaires to assess obsessive-compulsive tendencies, depression, self/other perception, personality traits, and hopelessness. Confirmatory factor analyses (CFA) were performed. In the final model we found that personality, obsessive-compulsive factor and suicidal ideation were significantly correlated with each other: personality correlated negatively with obsessive-compulsive factor and suicidal ideation, while obsessive-compulsive factor and suicidal ideation resulted as strongly positively associated. Our results highlight the importance of assessing OC tendencies, negative self/other perception and SI. Understanding their role and interplay will allow for the development and implementation of more advanced prevention and treatment policies.
Background. The perception of patients' needs of support and sensitive communication about psychosocial stress all represent new, exacting tasks for nursing staff, midwives, social workers and physicians in obstetrics. As part of Good Start into the Family (GuStaF), a learning and teaching project in a university hospital, we were able to interview parents about their experiences with the intervention. Objective. Evaluation of the process of establishing contacts, the communication with professionals in obstetrics and the support offered from the perspective of parents. Methods. Qualitative guided interviews with seven families one year after the delivery. Results. Problem areas reported by parents were predominately related to increased parental care and the feeling of being overwhelmed in addition to social stress. Core themes in communication addressed the entry into conversations, which was remembered negatively when advice was perceived as improper, patronizing or stigmatizing, and positively when professionals had listened sensitively and had provided tangible support. Some conversations increased stress. Relating to assistance and support, parents reported both positive and negative experiences. Justness and reliability emerged as particularly important topics. Discussion. The attendance of families around the time of the delivery poses varying demands upon the hospital staff, not necessarily in keeping with traditional professional attitudes and competencies. Careful attention to the personal physical and emotional well-being of mothers and newborns, non-stigmatizing entry into the conversations, justness of the support and avoiding inconsistencies within the institution and the network all appear to be of great importance.
In contrast with other high-resource countries, maternal mortality has seen an increase in the United States. Caring for pregnant women in cardiac arrest may prove uniquely challenging given the rarity of the event coupled by the physiological changes of pregnancy. Optimization of resuscitative efforts warrants special attention as described in the 2015 American Heart Association's Scientific Statement on Maternal Cardiac Arrest. Current recommendations address a variety of topics ranging from the basic components of chest compressions and airway management to some of the logistical complexities and operational challenges involved in maternal cardiac arrest.
Electricity generation from moving currents without using dams (i.e., in-stream hydrokinetic electricity) has the potential to introduce multiple GW of renewable power to U.S. grids. This study evaluates a control system designed to regulate the generator rotor rate (rpm) to improve power production from in-stream hydrokinetic turbines. The control algorithm is evaluated using numerical models of both a rigidly mounted tidal turbine (TT) and a moored ocean current turbine (OCT) coupled to an induction electric machine model. The moored simulation utilizes an innovative approach for coupling a multiple degrees-of-freedom (DOF) nonlinear hydrodynamic/mechanical turbine model with a nonlinear electromechanical generator model. Based on the turbine torque-speed characteristic, as well as the asynchronous machine features, a proportional-integral (PI) controller is used to generate a correction term for the frequency of the three-phase sinusoidal voltages that are supplied to the asynchronous generator. The speed control of the induction generator through the supply frequency is accomplished by a simplified voltage source inverter (VSI). The simplified VSI consists of control voltage sources (CVSs), while the comparison with a real VSI using diodes and transistors, which are controlled by pulse width modulation (PWM) technique, is also presented. Simulations are used to evaluate the developed algorithms showing that rpm fluctuations are around 0.02 for a tidal turbine operating in a wave field with a 6m significant wave height and around 0.005 for a moored ocean current turbine operating in a wave field with a 2m significant wave height.
BACKGROUND: Polymorphisms in genes encoding tumor necrosis factor-alpha (TNF-alpha) and its receptor TNF-R1 have been shown to affect one person's susceptibility to develop certain neoplastic diseases. The aim of the present association study was to investigate whether single nucleotide polymorphisms (SNPs) in TNF-alpha (-308G>A) and TNF-R1 (36A>G) genes modulate the susceptibility for keratocystic odontogenic tumors (KCOTs) development in Serbian patients. METHODS: Genotyping was performed in 60 KCOT patients and 125 healthy individuals, using polymerase chain reaction/restriction fragment length polymorphism analysis. RESULTS: A significant difference in genotype and allele frequencies was found between patients and controls for both SNPs (P < 0.05). Carriers of the TNF-alpha A variant had an eightfold increase of KCOT risk (OR = 8.12, 95% CI = 3.98-16.56, P < 0.0001), while carriers of the TNF-R1 G variant had approximately a fourfold increase of KCOT risk (OR= 3.65, CI: 1.60-8.40, P = 0.001). CONCLUSIONS: Our findings suggest that the two polymorphisms are strong risk factors for KCOT development in Serbian population.
The article suggests an evaluation method of offset voltage of BiJFet differential difference operational amplifiers (DDAs), based on the theory of autonomous multiport circuit. The static error of DDA, connected with the offset voltage (V-io), can be presented by the current autonomous parameter I-p connected with the highimpedance node, entered into its classical equivalent circuit. The parameter I-p is determined by the DDA circuitry and ideally it must have zero value. The conditions for the synthesis of the main functional nodes of DDA are obtained, whereby V-io approximate to 0 is provided in the range of low temperatures and radiation effect. An example of construction of BiJFet-DDA with small V-io and its drift is given.
Large Wind Parks (WPs) are an essential priority, mainly in non-residential districts. Especially the offshore WPs, in areas with valuable energy potential, without legislation prohibits and without causing disturbance to the nearby community, could release enormous land for other uses (culture, recreation areas, tourism, etc.). The aim of this paper is to present a methodology for the sustainable siting of an offshore WP based on legal limitations, with a particular respect of ecological and economic resources using as example the island of Crete. It will also be considered the visual, acoustic and aesthetic disturbance of the coastal area residents and visitors and integrate them into the context. One of the essential issues that make the region unique is the undersea relief, which makes difficult the numerous and large-scale intervention, because some areas are strictly protected by the EU. Three steps have been followed: (i) exception of unsuitable areas (geological restrictions, visual and acoustical disturb and safety and of course due to environmental conditions); (ii) evaluation of environmental impacts on birdlife, Special Protection Areas and Sites of Community Importance; (iii) assessment of wind potential and needs of electricity in the regional unit of Chania, in the Western Crete. (C) 2017 Elsevier Ltd. All rights reserved.
Improvement of cultivar resistance is the key strategy to control the host-specialized pathogen Verticillium longisporum in oilseed rape (OSR). A special feature of this pathogen is its systemic, non-homogenous and delayed colonization of the plant xylem resulting in an extended symptomless period of latency. As a result, severity of infection in the field is difficult to score as it becomes apparent only at crop maturity stages when it may be confused with natural senescence. Assessment of Verticillium disease severity in OSR by visual scoring of microsclerotia on harvested stubbles unsatisfactorily reflects genotypic resistance as it is strongly affected by the ripening stage of the plant. To overcome these limitations, we developed a qPCR method, which unambiguously differentiates levels of quantitative resistance to V. longisporum in OSR genotypes under field conditions. The specificity and sensitivity of two primer pairs targeting ITS or tubulin loci in the V. longisporum genome were tested. While tubulin primers showed a high specificity to V. longisporum isolates, ITS primers exhibited a significantly higher sensitivity in detecting fungal DNA in stem tissue (limit of quantification =0.56 fg DNA) of field-grown pre-symptomatic plants. The best discrimination of resistant and susceptible OSR cultivars based on fungal DNA analysis in stem tissue was achieved at growth stage 80, at the transition of fungal vascular growth in viable plants to saprotrophic colonization of senescent stem tissues. Field screening data obtained with qPCR at growth stage 80 confirmed results from greenhouse testing thus corroborating the relevance and reliability of seedling assays for determining cultivar responses to V. longisporum in the field, as a useful tool for breeders in first selection of elite OSR genotypes with improved resistance to Verticillium.
Background and objectives: Older adults are characterized by an attentional preference for positive over negative information. Since this positivity effect is considered to be an emotion regulation strategy, it should be more pronounced when emotion regulation is needed. In contrast to previous studies that focused on the effects of sad mood on attention, we used a stressor to activate emotion regulation and evaluate the effects of different types of mood state changes. Moreover, we evaluated mood effects on attentional processes using a paradigm that allows disentangling between different attentional engagement and disengagement processes. Methods: Sixty older adults were randomly assigned to receive a stressor or a control task. Before and after this manipulation, mood state levels (happy, sad, nervous, calm) were assessed. Next, attentional processing of happy, sad, and angry faces was investigated using an eye-tracking paradigm in which participants had to either engage their attention towards or disengage their attention away from emotional stimuli. Results: Changes in different mood state levels were associated with different attentional disengagement strategies. As expected, older adults who increased in sad mood level showed a larger positivity effect as evidenced by a longer time to disengage attention from happy faces. However, older adults who received the tension induction and who decreased in calm mood level were characterized by longer times to disengage attention from sad faces. Limitations: The stressor was only partially effective as it led to changes in calm mood, but not in nervous mood. Conclusions: These results suggest that older adults may deploy a positivity effect in attention (i.e., longer times to disengage from positive information) in order to regulate sad mood, but that this effect may be hampered during the confrontation with stressors. (C) 2016 Elsevier Ltd. All rights reserved.
The aim of the present study was to provide descriptive dietary patterns of home-living older adults, and to examine their association with sociodemographic and 'diet-related' variables, and health and psychological factors. Dietary patterns were analyzed using separately cluster analysis for men (N = 151, M-age = 72.72, SD = 8.80, range = 56-97) and women (N = 251, M-age = 76.74, SD = 9.95, range = 55-97) in 402 older adults aged 55 years and over. Cluster analyses showed four distinct dietary profiles for each gender. In older men, the four distinct dietary clusters were associated with any differences in sociodemographic and diet-related variables, cognitive function, and health and psychological factors. Likewise, in older women, the four distinct dietary clusters were associated with any differences in sociodemographic and 'diet-related' variables'. However in older women, results showed that the cluster 1 "high fish-fruit-vegetable" was associated with a better cognitive function, a better self-rated health and no depressive symptoms, whereas cluster 3 "moderate ready meals" was associated with cognitive decline, slight depression, and poor perceived health. Results emphasize the interest to take into consideration health and psychological factors associated with dietary patterns to better target the vulnerability of individuals and enable an effective prevention. (C) 2017 Elsevier B.V. All rights reserved.
We present a case of sarcoma occurring at a site of resected oligodendroglioma without preceding radiotherapy or chemotherapy. Oligosarcoma occurring at sites of resected oligodendroglioma or anaplastic oligodendroglioma with sarcomatous components are rare. Although meningioma or sarcoma-like lesions are sometimes reported after glioma-targeted radiotherapy, those without preceding radiotherapy are quite rare. Moreover, cases of sarcoma without oligodendroglial components occurring at a site of resected oligodendroglioma have never been reported. In this case, fluorescent in situ hybridization analysis revealed 1p/19q co-deletion in both the first tumor and second tumors. Additionally, immunohistochemistry revealed mutated isocitrate dehydrogenase 1 in both tumors. Taken together, these findings suggest a monoclonal tumor origin. Consequently, this case may indicate a new mechanism of development of sarcomatous lesions occurring at the site of a resected glioma.
Olive flounder (Paralichthys olivaceus) is an economically important cultured marine fish in China, Korea, and Japan. Controlling and managing the breeding of olive flounder in captivity is an imperative step toward obtaining a sustainable supply of this fish in aquaculture production systems. Therefore, investigation on the molecular regulatory mechanism of gonadal development and gametogenesis in this species is of great significance in aquaculture. Furthermore, identification of the expression profile of numerous sex-related genes is the first step to primarily understand such molecular regulatory mechanism. Six female and six male gonads obtained from 2-year-old olive flounders were sequenced using Illumina, which produced 6.68 and 6.24 GB data for ovary and testis, respectively. The reads were mapped to the draft genome of olive flounder, and then the reads per kilobase per million (FPKM) for each gene were calculated. The female-/male-biased expressed genes were investigated based on the FPKM values. Overall, 3086 female-biased and 5048 male-biased genes were screened out. GO enrichment analysis showed that the GO terms "male meiosis," "gamete generation," "fertilization," "spermatogenesis," and "germ plasma" were enriched in male-biased genes. In addition, the GO terms "cell morphogenesis involved in differentiation," "embryonic morphogenesis," "plasma membrane," "steroid hormone receptor activity," and "aromatase activity" were enriched in female-biased genes. Moreover, 373,369 single nucleotide polymorphisms and 32,993 indels were identified in the transcriptome. This work is the largest collection of gonad transcriptome data for olive flounder and provides an extensive resource for future gonadal development and gametogenesis molecular biology studies in this species.
Advanced chemical remediation strategies (advanced oxidation processes, AOPs) have turned out as a feasible solution for the treatment of bio-refractory effluents, as in the case of olive mill wastewater (OMW). In this review paper, a focus on the relevant state-of-the art on advanced physico-chemical processes- including ozonation, wet oxidation, Fenton's reagent, photocatalysis, coagulation-flocculation, as well as electrochemical, solar-driven and hybrid processes- for the treatment of OMW is presented. In particular, the extent of recalcitrant organic pollutants abatement efficiency and the grade of mineralization achieved by the various treatments available up to today is addressed. Special attention is given to the different configurations and treatment line sequences, some important effect parameters and novel materials for implementation at real industrial scale. The latter includes the latest advances and applications for OMW treatment with biopolymers for coagulation-flocculation, ferromagnetic nanocatalyst for ease of recovery and multiple long-term use, low-cost catalysts, doped nanocatalysts for enhanced sunlight activation, zeolite-based catalysts, mixed and doped electrodes, among others. Solutions reported for the management of the secondary sludge by-produced in some treatment processes are also discussed. Moreover, a glance at the specific energy consumption and associated costs comparison of the different processes proposed is also given. (C) 2017 Elsevier B.V. All rights reserved.
Rio de Janeiro's inner and coastal waters are heavily impacted by human sewage pollution for decades. Enteric viruses, including human adenoviruses (HAdV), human enterovirus (EV), group A rotavirus (RV) and hepatitis A virus (HAV) are more likely to be found in contaminated surface waters. The present work aimed to assess the frequency and loads of EV, HAdV-C and -F species, RV and HAV in sand and water samples from venues used during the 2016 Summer Olympics and by tourists attending the event. Sixteen monthly collections were carried out from March 2015 to July 2016 in 12 different sites from Rio de Janeiro, Brazil. Total and thermotolerant coliform counting was performed along molecular detection of virus was performed using quantitative polymerase chain reaction (qPCR). Analyses of all samples were further investigated by integrated cell culture PCR to check about the presence of HAdV infectious virus particles. The results show that 95.9% of water samples showed contamination with at least one type of virus. Regarding the viruses individually (% for water and sand respectively): HAdV-C (93.1%-57.8%), HAdV-F (25.3%-0%), RV (12.3%-4.4%), EV (26.7%-8.8%) and HAV (0%). The viral loads ranged from 103 gc/L up to 10(9) gc/L (water), and 10(3) gc/g to 10(6) gc/g (sand). In the phylogenetic tree, were classified into four main clusters, referring to species C, D, F and BAdV. And up to 90% of sites studied presented at least once presence of infectious HAdV-C. The most contaminated points were the Rodrigo de Freitas Lagoon, where Olympic rowing took place, and the Marina da Gloria, the starting point for the sailing races, demonstrating serious problem of fecal contamination of water resources and threatens the health of Olympic athletes, tourists and residents. (C) 2017 Elsevier B.V. All rights reserved.
Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. One solution would be to match patients to existing compounds based on in silico modeling. However, optimization of complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production, perhaps achievable in the future by three-dimensional (3D) printing. Indeed, 3D printing is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. Companies are already endeavoring to develop affordable 3D printers for home use. An attractive, but as yet scantily explored, application is to place chemical design and production under digital control. This could be accomplished by utilizing a 3D printer to initiate chemical reactions, and print the reagents and/or the final compounds directly. Of interest, the Food and Drug Administration (FDA) has recently approved a 3D printed drug-levetiracetam-indicated for seizures. Further, it is now increasingly clear that biologic materials-tissues, and eventually organs-can also be "printed." In the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine.
Objectives. Retinoic acid (RetA) and oncostatin M (OSM) have both been shown to mediate potent effects with respect to extracellular matrix integrity. This study assesses the effects of a RetA + OSM combination on cartilage catabolism. Methods. Animal and human cartilage samples were used to assess the ability of RetA + OSM to promote the release of collagen and proteoglycan fragments, which was determined by measuring glycosaminoglycan and hydroxyproline, respectively. Total collagenolytic and tissue inhibitor of metalloproteinases (TIMP) inhibitory activities were determined by bioassay, whilst gene expression of matrix metalloproteinases (MMPs) and TIMP-1 were determined by northern blotting. Immunohistochemistry was used to assess the presence of MMP-1 and -13 in resorbing cartilage explants. Results. Both agents alone induced proteoglycan release from bovine cartilage, whilst RetA-induced collagen release was variable. Reproducible and synergistic collagenolysis was observed with RetA + OSM, which appeared to be due to MMP-13. Similar collagen release was observed from porcine cartilage. Conversely, no collagen release was seen with human articular cartilage. In primary human chondrocytes, RetA + OSM failed to induce MMP-1 or -13 but caused a significant increase in TIMP-1 expression. Conclusions. These novel observations show that the combination of RetA + OSM has profound effects on cartilage matrix turnover, but these effects are species-specific. A better understanding of the mechanism by which this combination differentially regulates MMP and TIMP expression in human chondrocytes could provide valuable insight into new therapeutic strategies aimed at the prevention of cartilage destruction.
Nowadays, thermoelectric (TE) materials have gained considerable attention due to their unique ability to directly convert waste heat to electricity and vice versa. For a long time, researchers have mainly focused on developing high-performance inorganic TE materials, e.g., Bi-Te, Pb-Te, and Si-Ge based alloys, etc. However, inorganic TE materials have various disadvantages, such as high-cost, heavy metal contamination, as well as relatively poor processability, etc. Compared to inorganic TE materials, poly(3,4-ethylenedioxythiophene) (PEDOT) has great potential to be used for TE materials, due to its low thermal conductivity, low-cost, and low-density, etc. Therefore, more and more attention has been focused on the preparation and TE properties of PEDOT and PEDOT based nanocomposites, especially one-dimensional (1-D) PEDOT and 1-D PEDOT based nanocomposites, due to 1-D nanostructures always have enhanced TE properties. This article presents an overview of the synthesis of PEDOT nanoparticles, 1-D PEDOT nanostructures and their corresponding nanocomposites, as well as TE properties. (C) 2017 Elsevier B.V. All rights reserved.
The carbon dots have got much attention recently. Considering the environment protection, "green" materials are urgent. In this paper, nitrogen-and sulfur-co-doped carbon dots (N, S-CDs) were prepared through one-pot simple and convenient hydrothermal carbonization approach with "green" ginkgo leaves as the materials. The synthesized carbon dots were successfully doped with nitrogen and sulfur elements. The fluorescence intensities of carbon dots were rather stable in different pH and ionic strength. Furthermore, the "green" N, S-CDs were successfully applied in bioimaging as fluorescent probes due to its excellent optical properties and low cytotoxicity. (C) 2017 Elsevier B. V. All rights reserved.
A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems.
To find a balance between food and energy security, this research presents the design of an energy self-sufficient farm in electricity, heat and bioethanol, which is produced by energy crops and agricultural residues. The farm proposed is evaluated by two models: Land Optimization and Cost Optimization. Due to the food-fuel debate over land and the detriment of food security, this research proposes utilizing the current abandoned land and increasing the food self-sufficiency ratio (FSSR) of the crops analyzed (rice, wheat and maize). The farm is optimized for several food and fuel demands, with a maximum farm unit size of 100 ha. The result is a myriad of farms of different sizes, each optimized for a certain demand. Subsequently, the amount and variety of such farms are optimized maximizing the food and fuel produced for each city of the case study (Miyagi Prefecture, Japan). The results suggest that the establishment of energy self-sufficient farms in the abandoned land can stimulate the biofuel industry and increase food security simultaneously. The FSSR of maize and wheat can be improved in approximately 10-25 and 7-9 %, respectively. The estimated bioethanol potential is 3.2-3.8 ML. Additionally, a surplus of electricity and heat, approximately 61-65 GWh and 60-165 MJ, respectively, is obtained. As the Land Optimization model proposed is sensitive to crop yields, a simultaneous evaluation is recommended. The results also suggest that the farms must be larger than 8 ha to achieve self-sufficiency; therefore, the policies involved need further evaluation.
A strategy for growing online biochemistry courses is presented based on successes in ecampus at Oregon State University. Four free drawing cards were key to the effortYouTube videos, iTunes U online free course content, an Open Educational Resource textbookBiochemistry Free and Easy, and a fun set of educational songs known as the Metabolic Melodies. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):25-30, 2017.
While online interventions are increasingly explored as an alternative to therapist-based interventions for cancer-related distress, limitations to efficacy potentially include low uptake and adherence. Few predictors of uptake or adherence to online interventions have been consistently identified, particularly in individuals with cancer. This study examined rates and predictors of uptake and adherence to Finding My Way, a RCT of an online intervention versus an information-only online control for cancer-related distress. Participants were adults with cancer treated with curative intent. Adherence was assessed by login frequency, duration and activity level; analyses examined demographic, medical and psychological predictors of uptake and adherence. The study enrolled 191 adults (aged 26-94 years) undergoing active treatment for cancer of any type. Uptake was highest for females and for individuals with ovarian (80%) and breast cancer (49.8%), and lowest for those with melanoma (26.5%). Adherence was predicted by older age and control-group allocation. Baseline distress levels did not predict adherence. High adherers to the full intervention had better emotion regulation and quality of life than low adherers. Uptake of online intervention varies according to age, gender and cancer type. While uptake was higher amongst younger individuals, once enrolled, older individuals were more likely to adhere to online interventions for cancer-related distress.
Despite the sustained media attention surrounding internet trolling, academic studies investigating its occurrence are rare. This study aimed to provide a case study analysis of the behaviours and strategies of a group of alleged Twitter trolls referred to as the anti-McCanns due to their continual abuse of Kate and Gerry McCann as well as those who support them and thus identify as pro-McCann. The way in which language was used to construct the anti-McCanns group identity, enhance in-group cohesion and facilitate out-group disassociation from the pro-Mccann group was additionally explored, given that previous research has implicated group processes in the propagation of aggressive online conduct. A multi-method approach involving a combination of ethnographic observations and the collection of online commentary was employed. The data was then analysed using quantitative content analysis and discourse analysis, which indicated that language was utilised in a variety of ways by the anti-McCanns to construct a salient group identity and negatively stereotype and disassociate from the pro-McCann group. Findings additionally revealed that several strategies were employed by the anti-McCann trolls to provoke and derogate members of the pro-McCann group, supporting previous findings which have linked trolling to both western media culture and the characteristics of anti-social personality disorder. The implications of these findings both theoretical and practical are discussed, alongside recommendations for future research. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: Phthalates, which are commonly used to render plastics into soft and flexible materials, have also been determined as developmental and reproductive toxicants in human and animals. The purpose of this study was to evaluate the effect of mono-(2ethylhexyl) phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) oral administrations on maturation of mouse oocytes, apoptosis and gene transcription levels. Materials and Methods: In this experimental study, immature oocytes recovered from Naval Medical Research Institute (NMRI) mouse strain (6-8 weeks), were divided into seven different experimental and control groups. Control group oocytes were retrieved from mice that received only normal saline. The experimental groups I, II or III oocytes were retrieved from mice treated with 50, 100 or 200 mu l DEHP (2.56 mu M) solution, respectively. The experimental groups IV, V or VI oocytes were retrieved from mouse exposed to 50, 100 or 200 mu l MEHP (2.56 mu M) solution, respectively. Fertilization and embryonic development were carried out in OMM and T6 medium. Apoptosis was assessed by annexin V-FITC/Dead Cell Apoptosis Kit, with PI staining. In addition, the mRNA levels of Pou5f1, Ccna1 and Asah1 were examined in oocytes. Finally, mouse embryo at early blastocyst stage was stained with acridine-orange (AO) and ethidium-bromide (EB), in order to access their viability. Results: The proportion of oocytes that progressed up to metaphase II (MII) and 2-cells embryo formation stage was significantly decreased by exposure to MEHP or DEHP, in a dose-dependent manner. Annexin V and PI positive oocytes showed greater quantity in the treated mice than control. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) revealed that expression levels of Pou5f1, Asah1 and Ccna1 were significantly lower in the treated mouse oocytes than control. The total cell count for blastocyst developed from the treated mouse oocytes was lower than the controls. Conclusion: These results indicate that oral administration of MEHP and DEHP could negatively affect mouse oocyte meiotic maturation and development in vivo, suggesting that phthalates could be risk factors for mammalians' reproductive health. Additionally, phthalate-induced changes in Pou5f1, Asah1 and Ccna1 transcription level could explain in part, the reduced developmental ability of mouse-treated oocytes.
Phytophthora capsici inflicts damage on numerous crop plants by secreting a series of pectinase including pectate lyase (PEL). Here, we report a pectate lyase gene (Pcpel1) from a genomic library of a highly virulent P.capsici strain SD33. Pcpel1 was identified as an open reading frame of 1233bp encoding a protein of 410 amino acids with a predicted amino-terminal signal sequence of 21 amino acids. The predicted protein of Pcpel1 has a calculated molecular mass of 43.8kDa and a pI value of 6.8. Analysis of the amino acid sequence suggested that it was a member of the polysaccharide lyase family 1 that shows pectate lyase activity. Moreover, heterologous expression of Pcpel1 in Pichia pastoris produced proteins with molecular mass 66kDa, very likely due to differential glycosylation by the yeast. By western blotting and northern blotting analysis, Pcpel1 was strongly expressed during interaction of P.capsici with the host plant, suggesting its involvement in the process of host infection. The role of Pcpel1 in cell wall disassembly and host/parasite interaction is discussed.
Phytophthora species are highly destructive phytopathogens, associated with massive damage in natural ecosystems and agriculture. Citrus production is also affected, mainly by the hemibiothrophic oomycete Phytophthora parasitica, which causes root rot and gummosis. Poncirus trifoliata and Citrus sunki (two rootstocks widely used in citrus orchards) pose a resistance and a susceptible interaction with P. parasitica, respectively, which makes them suitable models to study plant defense mechanisms. Gene expression analysis is a very important tool in this type of study, in particular PCR (RT-qPCR). Hence, it is crucial to use appropriate reference genes for expression normalization. Our aim was to evaluate the stability of several candidate reference genes to determine which set is best suited for normalization in citrus infected with P. parasitica. We evaluated five candidate reference genes selected from the database CitEST. GeNorm and NormFinder algorithms were used to assess the best reference genes. We found that the more stable genes to be used for RT-qPCR analysis in P. trifoliata plants were GAPC2 and F-BOX, while EGIDH and GAPC2 were more suitable to C. sunki. These four genes were found to be excellent normalizers, being stable throughout the infection regardless of pathogen attack or symptom development.
Investigation of magnetic properties and microwave resonance phenomena in nanocomposites based on opal matrices containing the particles of intermetallide of Fe3Ni2 and FeNi3 is carried out. The interactions which lead to the resonance changes of transmission and reflection coefficients are determined. Electromagnetic properties are measured in the millimeter frequency range. Special attention is paid to comparison between static and dynamic magnetic properties of nanocomposites. Frequency dependences of magnitude of lines of resonance features are obtained. Spectra of resonance and antiresonance are studied. The conditions when the magnetic antiresonance is observed are clarified. The X-ray phase analysis of the nanocomposites is performed and their structure is studied. (C) 2017 Elsevier B. V. All rights reserved.
A low voltage and low power Operational amplifier (Opamp) using Process, temperature insensitive current source has been presented. The design methodology of the addition based current source and the Opamp implementation using this current source is presented. The spice simulations are carried out in GPDK 90 nm technology at 0.6 V supply. The results of addition based current source Opamp are compared with the MOSFET current source Opamp. The proposed Opamp shows better gain of 80.6db, GBW of 3MHz and low power consumption of 54 uW.
Negative feedback technique employing high DC gain operational amplifier (op-amp) is one of the most important techniques in analog circuit design. However, high DC gain op-amp is difficult to realize in scaled technology due to a decrease of intrinsic gain. In this paper, high DC gain op-amp using common-gate topology with high power efficiency is proposed. To achieve high DC gain, large output impedance is required but input transistors' drain conductance decreases output impedance of conventional topology such as folded cascode topology with complementary input. This is because bias current of the output side transistors is not separated from the bias current of the input transistors. On the other hand, proposed circuit can suppress a degradation of output impedance by inserting common-gate topology between input and output side. This architecture separates bias current of the input transistors from that of the output side, and hence the effect of the drain conductance of input transistors is reduced. As the result, proposed circuit can increase DC gain about 10 dB compared with the folded cascode topology with complementary input in 65 nm CMOS process. Moreover, power consumption can be reduced because input NMOS and PMOS share bias current. According to the simulation results, for the same power consumption, in the proposed circuit gain-bandwidth product (GBW) is improved by approximately 30% and noise is also reduced in comparison to the conventional topology.
A new gain enhancement technique for an operational amplifier (opamp) using a replica amplifier is presented to reduce a sensitivity of a gain mismatch between the main amplifier and the replica amplifier which limits a gain-enhancement factor in the conventional replica-amp techniques. In the proposed technique, the replica amplifier is used to only amplify an error voltage of the main amplifier. The outputs of the main amplifier and the replica amplifier are added to cancel the error voltage of the main amplifier. The proposed technique can also achieve a higher output voltage swing because the replica amplifier amplifies only the error voltage. In case of using a fully-differential common-source opamp for the main amplifier and a telescopic opamp for the replica amplifier, Monte Carlo simulation at 100 iterations shows that the proposed amplifier has almost the same gain variation with 15.5 dB gain enhancement and about five times output voltage swing expanding for a supply voltage of 1.2V compared with the single closed-loop amplifier using the telescopic opamp.
Due to continuous decrease in channel length of the transistor and reduction in the supply voltages, design of operational amplifier (opamp) poses new challenges [1]. Because of the short channel effects limitations in the planar MoS technologies, alternative device structures have been developed and among those FinFET is the most prominent one. Hence, in this study we wanted to explore those advantages of FinFET over MosFET for analog IC design and hence we have designed Miller compensated opamp using 90nm MoS and 32nm FinFET devices. These were evaluated for parameters like power, voltage gain, phase margin, Gain Bandwidth Product (GBW), and slew rate. The results show that FinFET based opamp is better than MoS based opamp in many aspects, about which we have briefed in the comparison and conclusion section of the paper i.e. Section V of the paper.
The operational amplifiers are the versatile and significant modules in the field of electronic circuits. Two-stage Op-Amp is a multistage amplifier which is widely useful for on-chip applications. The proposed circuit is a two stage operational amplifier designed using differential architecture, implemented in CMOS technology. The circuit gives best results such as high gain of 1,960 dB and low power consumption of 1.320 mW at 180 nm technology.
This paper proposes a technique to build SPICE micromodels of integrated circuits in bipolar technology appropriate to simulate single event transients. First of all, we will show how to obtain SPICE models of the internal transistors from texts in the scientific and academic literature. Next, several strategies to figure out the internal structure of the integrated circuits and bias point will be shown. Finally, simulation results will be compared to data issue from experiments, either performed by the authors or by other researchers. As the simulations do not require expensive software or hardware, this paper can be a start point for research groups with small budget or for academic purposes at universities.
An accurate design of low power Voltage Controlled Oscillator (VCO) enabled quantizer in Continuous Time Sigma Delta ADC in 180nm CMOS technology using Tanner EDA tools is done. The proposed architecture consists of the loop filter, VCO quantizer and the DAC in the feedback side of model. The Operational Amplifier (OPAMP) used in designed of loop filters offers 40dB gain, 70 degree phase margin and unity gain bandwidth of 79.06MHz that consuming power of 3 mW. Even order harmonics of VCO are reduced by VCO quantizer loop structures. The Higher order loop filter is designed using an active Resistance and Capacitive based integrators and VCO quantizer is implemented using 15 multiple stage ring oscillator and register of DFF which provides an added advantage of low phase noise with frequency of 100 KHz rang. Remarkable power dissipation of overall circuit is 3mW.
A chip design of novel chopper stabilized operational amplifier was presented, chopper-wave modulation and demodulation was used in this architecture, and its 1/f noise was decreased largely. To extend input common mode voltage range, a novel rail-to-rail differential amplifier was adapted in the input stage. The range of input common mode voltage was from zero to power supply, and it only consumed about 22 mu A current. When input signal frequency was 1 KHz, and the output signal THD was only 0.01%.
Oscillation test methodology (OTM) has been very effective in detecting physical defects such as open, shorts and bridging defects in low-voltage CMOS VLSI analog and mixed signal circuits. This paper discusses the OTM for low voltage two-stage operational amplifier using N-well 1 mu m CMOS technology with high fault coverage and minimum area overhead. Five bridging faults and one open fault have been detected. Discrete practical realizations and extensive simulations based on CMOS 1 mu m technology parameters using PSPICE affirm that the test technique presented for MOSFET circuits ensures high fault coverage and requires a negligible area overhead.
A rail-to-rail operational amplifier is designed with minimum variation in the input stage transconductance (g(m)) in standard 0.18 mu m CMOS technology. In this design, transconductance is maintained approximately constant independent of the operation region of the input transistors (i.e., saturation or weak inversion regions). Unlike conventional methods in rail-to-rail designs in which two complementary differential pairs are used, in this work, by using a single input pair, the sensitivity to mismatches between PMOS and NMOS input transistors is eliminated. A Monte-Carlo simulation with n=300 was run to ensure mismatch insensitivity. Simulation results show that the input stage transconductance deviation as the input common-mode voltage varies from rail-to-rail is less than +/- 0.81%, in typical conditions and at 27 degrees C. When the temperature varies from -20 degrees C to 120 degrees C, the variation does not exceed +/- 1.28%. Furthermore, the variations of g(m) two long-channel (L=1 mu m) and short-channel (L=0.18 mu m) cases are +/- 0.85% and +/- 0.9%, respectively. This proves that the introduced circuit works properly regardless of the channel length of the input pair. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents a further development of an improved frequency compensation method for a two-stage operational amplifier with indirect feedback current, which is beneficial for large capacitive load applications. It describes the case when a nulling resistor is added at the output in such a way that it is residing outside the outer feedback loop of the amplifier. Compared to the case when the nulling resistor is placed outside inner frequency compensation loop but it is inside of the outer feedback loop of the amplifier, the driving capability can be substantially improved or for the same capacitive load it can improve the stability by gaining up to 45 degree of extra phase margin. A prototype has been implemented with the STMicroelectronics 28 nm CMOS technology and simulated with Cadence Virtuoso. Simulations at room temperature show an improvement of the unity gain frequency from 741.57 MHz to 1.047 GHz and an extra phase margin gain of 38 degree. The simulation of the temperature effect showed that the phase margin gain remains for temperature range [-20, 150] degrees C.
The article discusses automated test complex based on the PXI devices basis for monitoring parameters and functioning of integrated opamp during radiation experiments. Need of measurements and input signals high accuracy support is specified.
Output voltage and an inverting input voltage of inverting amplifier circuit are measured when conducted disturbance is injected to power supply pin by DPI measurement. Correlation between output voltage and inverting input voltage is shown.
A receiver front-end supporting contiguous and non-contiguous intra-band carrier aggregation scenarios with a fully integrated spectrum sensor that can detect both in-gap and out-of-band blockers has been implemented in 65nm CMOS technology. An NF of 2.5dB is achieved using a noise canceling LNTA, and linearized OTAs are used to achieve an IIP3 improvement of up to 6.5dB in-band and 11dB at the filter band edge. The spectrum sensor can detect blocker levels in 22 steps of 9MHz between -100MHz and 100MHz IF. The system consumes between 36.6mA and 57.6mA from a 1.2V supply.
In this paper, using Lab VIEW graphical programming environment are made a number of virtual instruments which are used at the demo/study of low power active filters with operational amplifiers (op-amp). There are analyzed the active first order low pass, high pass and band pass filters. The results are included in two papers. The first one contains the simulation of active filters. The different values of passive components (feedback or input resistor and capacitors) around the op-amp can be selected with numerical controls for each type of filter. The effect is seen using the Bode characteristic (frequency response curve for filter). The AC (alternating current) frequency characteristic is best described in term of a Bode plot where the gain is plotted on a log scale on the vertical axis and the frequency is plotted on a log scale on the horizontal axis. The op-amp ideal frequency response curve (Open Loop) it is also displayed in the chart. The values of Open Loop Gain and Frequency Cut-Off are also set with numerical control. The validity of the program is done by comparing simulation results with data obtained by calculation using the theory. The program is designed in a modular manner and it can be used successfully in education and training courses.
Three methods of operational amplifier (Op amp) slew rate verification are considered. These methods are illustrated through the example of SPICE macro models of Op amp LMH6642 by Texas Instruments and OP37 by Analog Devices.
This work presents a fully differential operational amplifier (opamp) design architecture, that achieves a high gain bandwidth at a low power consumption. For verification, the architecture is implemented in a low cost 180 nm bulk CMOS technology. The chip achieves a high gain bandwidth of 2.03 GHz at 55 degrees phase margin with a low power consumption of only 2.25 mW. Of course even better results are possible if more sophisticated technologies like BiCMOS or massively scaled technologies are available. The opamp is used in analog baseband filters of communication systems and enables real time ability.
This work attempts to reduce component count in Low, High, and All Pass active Filters. It also uses a lower order filter to achieve same results as higher order ones in terms of the frequency response. The optimizers used are Nelder-Mead, GA and PSO. The filters are transformed into small signal analysis while nodal analysis is used to translate a circuit to matrix form. Three different examples are presented to illustrate the effectiveness of the approach. Results have revealed that with a computer program, a lower order operational amplifier filter can be used to achieve same results as a higher order one. Also, PSO can achieve the best results as regard frequency response for the three examples, followed by GA while Nelder-Mead has the worst result.
Processing the results of measurements of operational amplifier parameters using the virtual instrumentations technology of LabVIEW development environment is considered. The method for the automated processing of the operational amplifier parameters measurements results is proposed. Formulas of operational amplifier Spice-model parameters calculations are given.
Operational amplifier is the basis of analog circuit technology, whose reliability is very important for circuit system. In order to collect parameters online and to assess working life of operational amplifier, a parameters online testing system was designed. This system is consisted of a typical operating circuit and a electrical connection of the test circuit for device under test(DUT). Besides, parameters which are tested by the test circuit can be collected by a data acquisition system. And values of parameters can be displayed on Pc. And an accelerated degradation test(ADT) is designed, a heat source and thermocouple were pasted on the back of the heat sink so that the temperature of heat source can be controlled. Finally, the life of this operational amplifier operating under normal stresses can be assessed by mathematical methods. The results indicate that the proposed method is valid for online life assessment of operational amplifier.
A very high gain (137 dB) two stage CMOS operational amplifier having structural simplicity of classical Widlar architecture has been presented. The differential input stage of proposed operational amplifier has been modified by incorporating inverse aspect ratio self cascode structures biased to operate in subthreshold region, to minimize the classical compensation capacitor to 0.1 pF and results in considerable saving in occupied chip area. P-SPICE simulations in 0.25 mu m CMOS technology at +/- 1 V supply have been carried out to compare the performance of proposed operational amplifier with previously reported designs. The proposed operational amplifier demonstrated better gain-bandwidth product of 1.37 MHz, low power consumption of 21 mu W and occupied smaller chip area of < 400 (mu m)(2).
This paper shows that the classical square/triangular wave generator can also provide sinusoidal oscillations. Thus, a square/triangular/sinusoidal oscillator can be obtained from the same topology by changing a resistance. A new sinusoidal oscillator using two operational amplifiers, one resistor, and one capacitor is also shown. Experimental results that confirm the operation of the proposed circuits in different regimes are included.
This work focuses on the subthreshold design of ultra low-voltage low-power operational amplifiers. A well-defined procedure for the systematic design of subthreshold operational amplifiers (op-amps) is introduced. The design of a 0.5-V two-stage Miller-compensated amplifier fabricated with a 0.18-mu m complementary metal-oxide-semiconductor process is presented. The op-amp operates with all transistors in subthreshold region and achieves a DC gain of 70dB and a gain-bandwidth product of 18kHz, dissipating just 75nW. The active area of the chip is approximate to 0.057mm(2). Experimental results demonstrate that well-designed subthreshold op-amps are a very attractive solution to implement sub-1-V energy-efficient applications for modern portable electronic systems. A comparative analysis with low-voltage, low-power op-amp designs available in the literature highlights that subthreshold op-amps designed according to the proposed design procedure achieve a better trade-off among speed, power, and load capacitance. Copyright (c) 2013 John Wiley & Sons, Ltd.
This paper present a virtual instrumentation system for learning the Operational Amplifiers (Op Amps) circuits function, design and analysis. By combining the schematic diagram and simulation tools with the multifunction data acquisition board (DAQ) and measurement features provided by LabVIEW, the real analog signals are easily sampled and then compared with the signals of simulated Op Amp circuits. With the proposed system can be studied Op Amp circuits in different configurations: inverting, adder and integrator amplifier. With minimal modifications can be added other circuits' configurations as: no inverting, subtraction, differential or other nonlinear circuits. Simulated Op Amp circuits have models that are based on the electrical characteristics of their components. Experimental platform consists of integrated circuit Op Amp, related components configured diagram and power supply. Voltage signals applied to the input of the circuit come from an external source or signal generator or are generated using DAQ module. The generated signals from DAQ module can be in the form of DC voltage, sinusoidal, triangular or rectangular; these signals parameters can easily be adjusted by software. All parameter values are measured using DAQ module and specially designed virtual instruments. The output signal values from DAQ module may be manually applied, point by point to the input of the circuit test or can be applied automatically.
The paper suggests an novel architecture of the operational amplifier (OA) using the circuit method to increase the high-speed response. It is provided due to special circuit of nonlinear correction and the extension of the active operational range of the input differential stage (DS) of OA. At static current of the common circuit of the source of DS 10 mu A. the maximum slew rate of OA increases more than 20 times - up to the level of 10 V/mu S (process technology XFab XB06).
This paper describes conditions and simple circuit modifications that eliminate undesired complex conjugate poles in two-stage operational amplifiers that are based on current buffer Miller compensation. The complex conjugate poles have been the main problem of this frequency compensation topology since its first introduction more than 30 years ago. It is shown that a resistor added between the second stage and the amplifier output creates a zero that improves stability and reduces the circuit to a second-order system. This greatly simplifies the design of an otherwise complex topology and at the same time retains the valued benefits of current buffer based frequency compensation. In addition, for the case where a short channel transistor is used for the current buffer, conditions that create sufficient phase margin for the inner loop of the amplifier without the nulling resistor are formulated.
This paper presents a low-power, low-noise and high precision operational amplifier for a tracking system containing the intelligent medical device, and is an extended version of paper previously published by Nenadovic et al. in proc. of ICECS 2014. The accuracy of the tracking system strongly depends on the accurate amplitude acquisition of the received signal. Therefore, an operational amplifier with precise gain control and effective temperature compensation has been designed and fabricated. The operational amplifier provides linear and temperature independent signal amplification at frequencies between 0.2 and 20 kHz at a body temperature. The amplifier shows measured gain over temperature sensitivity as low as 32 ppm/A degrees C in temperature range from 20 to 40 A degrees C and consumes 300 mu A from a supply voltage of 2.5 V. Furthermore, the measured gain over temperature sensitivity in the range from -40 to 130 A degrees C is only 60 ppm/A degrees C. Simulated linearity for signal amplitudes up to 10 mV is 0.4 % and the input-referred noise at 1 kHz is 32 nV/aeHz. An open-loop gain of 46 dB at 1 kHz and bandwidth-gain product of 4.8 MHz is measured. The operational amplifier was designed in IHPs 250 nm SiGe BiCMOS technology and occupies an area of 0.2 mm(2).
Frequency compensation of a multistage operational amplifier (op-amp) is normally performed through solving nodal equations of an equivalent circuit to obtain the op-amp's final transfer function. The process is often very tedious and offers little insight into the roles of the selected compensation scheme. In this paper, we present a graphical design approach for two-stage and three-stage op-amps with active feedback Miller compensation. By viewing frequency compensation as a standard feedback problem, we can utilize the well-known graphical tools such as the root locus and Bode plot to understand the effects of the compensation and to estimate the locations of the closed-loop poles and zeros of the op-amp. Intuitive graphical design procedures for two-stage and three-stage op-amps are also formulated. To show its effectiveness, we illustrate our design approach through the design of a three-stage op-amp in a standard 0.18-m complementary metal-oxide-semiconductor (CMOS) process. With a load capacitance of 500pF, post-layout simulations show that the op-amp achieves a low-frequency gain of 144dB, a phase margin of 58, and a unity-gain frequency of 1.38MHz while consuming a total bias current of 31A from a 1.8-V supply voltage. Comparisons with the published amplifiers show that our op-amp achieves the figure of merits comparable to those of the state of the art. Copyright o 2015 John Wiley & Sons, Ltd.
This paper reveals that logistics make up at least 17% of annual operational expenditure costs for offshore wind farms. Annual operational expenditure is found to vary by a factor of 9.5, making its share of levelized cost of energy for offshore wind range from 13% to 57%. These are key findings of a 20-month research project targeting cost reduction initiatives for offshore wind systems. The findings reveal that cost-out measures are difficult to implement due to cultural differences. Implementation efforts are rendered by personnel located offshore in a harsh sea environment which is in stark contrast to the shore-based office personnel who develop studies directing cost reduction efforts. This paper details the company motivation to join industry-wide cost reduction initiatives. A business case for offshore wind operations and maintenance logistics yielding 1% savings in levelized cost of energy is included on how to expand working hours from daytime to also work at night.
This paper presents a single-stage ultra-low-power fully differential operational transconductance amplifier (FD-OTA) with rail-to-rail linear input range operating in weak inversion region. The input core of the OTA is comprised of source degenerated, flipped voltage follower (FVF)-based bulk-driven class AB input pair, into which a regenerative feedback loop has been inserted to boost its bulk transconductance (gib). The proposed FD-OTA has utilized selfcascode current mirror (SC-CM) loads, which increase its open loop gain from nominal intrinsic value of 42 dB to 70.4 dB. It has provided 9.24 kHz gain bandwidth (GBW), consuming 64 nW of quiescent power from a 0.51 V single power supply at 15 pF load. The proposed OTA in unity gain configuration has ensured reduced total harmonic distortion (THD) of 52.4 dB at 200 Hz frequency and 1 Vp-p signal swing. Its fully differential class AB input and output structures have ensured increased gain, GBW, slew rates and output swings with reduced nonlinearity and common mode substrate noise. The Cadence Virtuoso environment using GPDK 180 nm standard n-well CMOS process technology has been used to simulate the proposed circuit.
Parents who use opioids and are involved in the child welfare system are less likely to retain custody of their children than parents who use other drugs. No previous studies have described medication-assisted treatment (MAT) utilization and child permanency outcomes for this population. The Sobriety Treatment and Recovery Team (START) model is a child welfare-based intervention focused on families with co-occurring substance use and child abuse / neglect issues. This study examined the prevalence and correlates of MAT utilization among parents in the START program with a history of opioid use, and compared child outcomes for families who received MAT services to those who did not. Of the 596 individuals with a history of opioid use in the START program, 55 (9.2%) received MAT. Receipt of MAT services did not differ by gender, age, county of residence, or drug use, though individuals who identified as White were more likely to participate in MAT. In a multiple logistic regression model, additional months of MAT increased the odds of parents retaining custody of their children. To address barriers to MAT, results-focused educational interventions may be needed for the child welfare workforce, as well as programs to improve collaboration and decision-making between the child welfare workforce, court personnel, and drug addiction treatment providers. (C) 2016 Elsevier Inc. All rights reserved.
PurposeThe purpose of this study is to assess positive predictive value (PPV), relative to medical chart review, of International Classification of Diseases (ICD)-9/10 diagnostic codes for identifying opioid overdoses and poisonings. MethodsData were obtained from Kaiser Permanente Northwest and Northern California. Diagnostic data from electronic health records, submitted claims, and state death records from Oregon, Washington, and California were linked. Individual opioid-related poisoning codes (e.g., 965.xx and X42), and adverse effects of opioids codes (e.g., E935.xx) combined with diagnoses possibly indicative of overdoses (e.g., respiratory depression), were evaluated by comparison with chart audits. ResultsOpioid adverse effects codes had low PPV to detect overdoses (13.4%) as assessed in 127 charts and were not pursued. Instead, opioid poisoning codes were assessed in 2100 individuals who had those codes present in electronic health records in the period between the years 2008 and 2012. Of these, 10/2100 had no available information and 241/2100 were excluded potentially as anesthesia-related. Among the 1849 remaining individuals with opioid poisoning codes, 1495 events were accurately identified as opioid overdoses; 69 were miscodes or misidentified, and 285 were opioid adverse effects, not overdoses. Thus, PPV was 81%. Opioid adverse effects or overdoses were accurately identified in 1780 of 1849 events (96.3%). ConclusionsOpioid poisoning codes have a predictive value of 81% to identify opioid overdoses, suggesting ICD opioid poisoning codes can be used to monitor overdose rates and evaluate interventions to reduce overdose. Further research to assess sensitivity, specificity, and negative predictive value are ongoing. Copyright (c) 2017 John Wiley & Sons, Ltd.
This Letter reports a lead (II) ion sensor composed of a tapered multimode fibre (MMF) coated with chitosan. The diameter and length of the tapered fibre region is 20 mu m and 1 cm, respectively. Tapered MMF is used because it is more flexible and compact compared with plastic clad silica. Chitosan is chosen as the sensing layer because it can absorb heavy metal ions due to its unique properties as polyelectrolyte and chelating agent. The refractive index of the chitosan layer changes as it absorbs lead (II) ion and this leads to an increase in the absorbance measured by the spectrophotometer. This is tested by immersing the sensor in a solution that contains lead (II) ion with different concentrations, from 0.2 to 1 ppm. The results show that the absorbance measured by the spectrophotometer increased as the concentration of the lead (II) ion increased. The sensor's average sensitivity is measured as 40.554 abs/ppm. This sensor is simpler compared with surface plasmon resonance-based lead (II) ion sensor because it does not require metal coating prior to the sensing layer coating.
Genome packaging of double-stranded RNA (dsRNA) phages has been widely studied using biochemical and molecular biology methods. We adapted the existing in vitro packaging system of one such phage for single-molecule experimentation. To our knowledge, this is the first attempt to study the details of viral RNA packaging using optical tweezers. Pseudomonas phage phi 6 is a dsRNA virus with a tripartite genome. Positive-sense (+) single-stranded RNA (ssRNA) genome precursors are packaged into a preformed procapsid (PC), where negative strands are synthesized. We present single-molecule measurements of the viral ssRNA packaging by the phi 6 PC. Our data show that packaging proceeds intermittently in slow and fast phases, which likely reflects differences in the unfolding of the RNA secondary structures of the ssRNA being packaged. Although the mean packaging velocity was relatively low (0.07-0.54 nm/sec), packaging could reach 4.62 nm/sec during the fast packaging phase.
We consider linear-quadratic optimal sampled-data control problems, where the state evolves continuously in time according to a linear control system and the control is sampled, i.e., is piecewise constant over a subdivision of the time interval, and the cost is quadratic. As a first result, we prove that, as the sampling periods tend to zero, the optimal sampled-data controls converge pointwise to the optimal permanent control. Then, we extend the classical Riccati theory to the sampled-data control framework, by developing two different approaches: the first one uses a recently established version of the Pontryagin maximum principle for optimal sampled-data control problems, and the second one uses an adequate version of the dynamic programming principle. In turn, we obtain a closed-loop expression for optimal sampled-data controls of linear-quadratic problems. (C) 2017 Elsevier Ltd. All rights reserved.
The term smart grid refers to a modernization of the electrical network consisting in the integration of various technologies such as dispersed generation, dispatchable loads, communication systems and storage devices which operates in grid-connected and islanded modes. As a result, traditional optimization techniques in new power systems have been seriously influenced during the last decade. One of the most important technical and economical tools in this regard is the Optimal Power Flow (OPF). As a fundamental optimization tool in the operation and planning fields, OPF has an undeniable role in the power system. This paper reviews and compares the OPF approaches mainly related to smart distribution grids. In this work, the main OPF approaches are compared in terms of their objective functions, constraints, and methodologies. Furthermore, computational performances, case study networks and the publication date of these methods are reported. Finally, some basic challenges arising from the new OPF methodologies in smart grids are addressed.
Many cities around the world have reached a critical situation when it comes to energy and water supply, threatening the urban sustainable development. From an engineering and architecture perspective it is mandatory to design cities taking into account energy and water issues to achieve high living and sustainability standards. The aim of this paper is to develop an optimization model for the planning of residential urban districts with special consideration of renewables and water harvesting integration. The optimization model is multi-objective which uses a genetic algorithm to minimize the system life cycle costs, and maximize renewables and water harvesting reliability through dynamic simulations. The developed model can be used for spatial optimization design of new urban districts. It can also be employed for analyzing the performances of existing urban districts under an energy-water-economic viewpoint. The optimization results show that the reliability of the hybrid renewables based power system can vary between 40 and 95% depending on the scenarios considered regarding the built environment area and on the cases concerning the overall electric load. The levelized cost of electricity vary between 0.096 and 0.212 $/kW h. The maximum water harvesting system reliability vary between 30% and 100% depending on the built environment area distribution. For reliabilities below 20% the levelized cost of water is kept below 1 $/m(3) making competitive with the network water tariff. (C) 2016 Elsevier Ltd. All rights reserved.
A new method is implemented in designing of self-oscillating loop for driving piezoelectric transformers. The implemented method is based on combining both analog and digital control systems. Digitized delay, or digitized phase shift through the self-oscillating loop results in a very precise frequency control and ensures an optimum operation of the piezoelectric transformer in terms of voltage gain and efficiency. In this work, additional time delay is implemented digitally for the first time through 16 bit digital-to-analog converter to the self-oscillating loop. Delay control setpoints updates at a rate of 417 kHz. This allows the control loop to dynamically follow frequency changes of the transformer in each resonant cycle. The operation principle behind self-oscillating is discussed in this paper. Moreover, experimental results are reported.
Optogenetics is a rapidly developing new technique that combines optical methods with techniques that are used in molecular biology. It can be used for monitoring various optical processes in cells and controlling their activity using light. The technique is based on bacterial opsin expression in mammalian neurons. In this review, the use of optogenetics for controlling the activity of specific neuronal populations in different regions of the human brain is considered in detail. The paper also presents information on light-sensitive proteins, genetically encoded optical instruments, and their use for activation or inhibition of neurons and investigation of the causal relationship between neural networks and pathological symptoms.
Many of the existing electricity markets are of the mixed type, which has pool auction and bilateral contracts between producers and distributors. In this case, the problem faced by a Generation Company (GenCo) is that of maximizing the revenues from participating in the market through the pool auction while honoring the bilateral contracts agreed, for which the revenue is fixed. The extension to mixed markets of a medium-term model, successfully employed for auction-only markets, is presented. It results in a non-convex expected revenue function to be maximized subject to constraints, for which the currently available direct global-optimization solvers prove not to be efficient enough. A heuristic procedure based on a sequence of solutions by a nonlinear solver is presented, and numerical results obtained with several realistic cases show satisfactory results. The test cases presented have dispatchable and non-dispatchable renewables and consider medium-term pumping together with conventional units by all GenCos participating in the mixed market. The advantages for GenCos of employing medium-term results as those produced by the model presented, include, among others, the evaluation of the expected profitability of their bilateral contracts. (C) 2017 Elsevier B.V. All rights reserved.
As a special case of the quay crane scheduling problem, the unidirectional quay crane scheduling problem has been received more and more attention. In this paper, we analyze the computational complexity of the unidirectional quay crane scheduling problem and propose a tighter mixed integer programming formulation. Next, we develop three makespan-constrained models to obtain risk-averse solutions to mitigate the impacts of ship instability and solution infeasibility (thus, need to revamp or even reschedule the plans). Comprehensive numerical experiments are designed to investigate the benefits of the tighter formulation and the three optimization models for risk-aversion. (C) 2017 Elsevier B.V. All rights reserved.
Background: Oral cancer is one of the most common malignant lesions of the head and neck. This cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades. Moreover, the incidence of oral HPV-positive tumors is rising, especially in young people. This oral neoplasm develops through numerous molecular imbalances that affect key genes and signaling pathways; however, the molecular mechanisms involved in the pathogenesis and progression of oral tumors are still to be fully determined. In order to improve the quality of life and long-term survival rate of these patients, it is vital to establish accurate biomarkers that help in the early diagnosis, prognosis and development of target treatments. Such biomarkers may possibly allow for selection of patients that will benefit from each therapy modality, helping in the optimization of intensity and sequence of the treatments in order to decrease side effects and improve survival. Conclusion: In this review we discuss the current knowledge of oral cancer and the potential role of omics approaches to identify molecular biomarkers in the improvement of early diagnosis, treatment and prognosis. The pursuit to improve the quality of life and decrease mortality rates of the oral patients needs to be centralized on the identification of critical genes in oral carcinogenesis. Understanding the molecular biology of oral cancer is vital for search new therapies, being the molecular-targeted therapies the most promising treatment for these patients.
Transcription factor activator protein-1 (AP-1) super-family is known to modulate expression of array of genes during development of many cancers and considered as an important target for modern therapeutics. But the role of AP-1 during development of human oral cancers is still poorly understood. Because oral cancer is one of the most common cancers in India and south-east Asia, we studied the activation and expression pattern of AP-1 family of proteins and mRNA in different stages of oral carcinogenesis. Get-shift assay, western blotting, immunohistochemistry and northern blotting have been used to assess the binding activity and expression pattern of AP-1 family (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) proteins and mRNA transcripts in a total of 100 fresh oral tissue specimens comprising precancer (n = 40), cancer (n = 50) and healthy control (n = 10). Constitutive activation of AP-1 with concomitant upregulated expression of majority of AP-1 family of proteins and mRNA was observed in cancer cases. Interestingly, almost all precancerous cases showed JunD homodimers, whereas c-Fos/JunD was the most prevalent complex found in cancer tissues. The overexpression of EGFR mRNA, p50:p50/NF-kappa B homodimer formation, together with overexpression of pERK and c-Fos proteins in this study suggests an interesting cross talk between AP-1 and NF-kappa B pathways in oral cancers. Thus, this study demonstrates differential expression and activation of AP-1 super-family proteins in relation to severity of lesion and their crucial role in human oral carcinogenesis.
Aim: To review the literature on the oral health status of the population, evidence-based understanding of epigenetic mechanisms, and its significant role in diseases occurring in the oral cavity. Background: Epigenetics is the study of heritable changes in gene expression that does not involve changes to the underlying DNA sequence. In other words, it is a change in phenotype without a change in genotype, which in turn affects the way cells read genes. Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. The field of epigenetics is quickly growing, and it is believed that both the environment and lifestyle can interact with the genome to influence epigenetic change. These changes may be reflected at various stages throughout a person's life and even in later generations. Conclusion: Epigenetic codes help us understand the biological phenotype that arises from the interaction of the human genome with the environment in health and in disease. Epigenetics is a major turn away from molecular biology. Current epigenetics not only offers new insights into gene regulation and heredity, but also it challenges the way we think about evolution, genetics, and development. Most interestingly, it suggests testable mechanisms whereby environmental factors (ranging from stress to infection) can influence genetic expression.
Epithelial cells from oral mucosa (EOM) are responsible for important functions, like the primary protection of oral mucosa against external aggressions building a mechanical barrier against microorganisms, mechanical damage, toxic material, thermal regulation and secretion of different classes of inflammatory mediators. EOM could be an interesting tool for cellular and molecular biology research. Usually, EOM are collected by a painful and invasive process. In this study, we propose an alternative method to cultivate EOM collected by non-invasive scraping method of oral mucosa. Papanicolaou staining showed mainly two kinds of epithelial cell population after EOM scraping. As result of the five culture methods tested here, our results revealed that the EOM were successfully cultured on a murine feeder layer. In addition, EOM could be frozen and thawed, without morphology changes and loss of viability. Our findings suggest that EOM can be considered as a good cell source for many purposes, such as genetic studies, diagnosis and cell therapy.
Kruppel-like factor 7 (KLF7) is a member of the KLF family of zinc finger transcription factors, and was the first KLF cloned using complementary DNA and polymerase chain reaction (PCR) techniques with human vascular endothelial cells as a template. In addition, KLF7 is known as the ubiquitous Kruppel-like factor, as it is widely expressed in numerous human tissues at low levels. In the present study, the function of KLF7 in migration and epithelialmesen-chymal transition (EMT), which are associated with tumor progression, was investigated in human oral squamous cell carcinoma (OSCC) cells. Genes that were differentially expressed in normal vs. OSCC tissue were identified in the Gene Expression Omnibus database, which identified upregulation of KLF7 in OSCC. The expression and subcellular location of KLF7 was then analyzed using immunohistochemistry. KLF7 expression was measured in three OSCC cell lines, and the two cell lines with the highest (HN13) and lowest (CAL27) KLF7 expression were selected for further analysis. Subsequently, HN13 cells with reduced KLF7 expression (sh-HN13) and CAL27 cells overexpressing KLF7 (OE-CAL27) were constructed. Transwell migration and wound healing assays were then used to analyze the migration of the cells. In addition, mRNA and protein expression levels of the EMT markers E-cadherin, N-cadherin, vimentin and snail were detected using reverse transcription-quantitative PCR and western blotting. KLF7 overexpression in OSCC was validated using tissue immunohistochemistry, which identified moderate to high cytoplasmic staining of KLF7 in OSCC cells. KLF7 knockdown and overexpression altered the migration ability of sh-HN13 and OE-CAL27 cells, which decreased and increased significantly respectively. Expression of E-cadherin, N-cadherin, vimentin and snail was markedly altered in sh-HN13 and OE-CAL27 cells, indicating changes in EMT status. The results of the present study suggest that KLF7 overexpression changes the migratory behavior of OSCC cells, and induces EMT and lymph node metastasis through the expression of snail.
Although significant advances have been established in molecular biology of Oral squamous cell carcinoma (OSCC), innovative strategies are still required to further understand detailed molecular mechanisms. Using bioinformatic approach, we aim to explore the potential miRNA-mRNA pairs in cancer related inflammatory response and investigate their potential roles as signature miRNA and proteins in the signaling pathway. Firstly, the differentially expressed genes of OSCC were selected which then underwent gene ontology to identify genes engaged in inflammatory response and its regulation. Validated miRNAs were retrieved and miRNAs with complete complementarily with their targets were visualized for miRNA-mRNA regulatory network. Protein-protein interactions of inflammatory and its regulatory genes were analyzed for interacting genes involved in signaling pathway. Eight universal miRNAs were obtained for inflammation and its regulation. miRNA-19a/b showed significant influence in controlling inflammatory response in OSCC. Therefore, micronome on deregulated genes in inflammation identifies miRNA-mRNA pairs which have high potential to be targeted for diagnostic and treatment applications in OSCC. ( C) 2016 Elsevier B.V. All rights reserved.
Although numbers of cancer cell lines have been shown to be successfully reprogrammed into induced pluripotent stem cells (iPSCs), reprogramming Oral Squamous Cell Carcinoma (OSCC) to pluripotency in relation to its cancer cell type and the expression pattern of pluripotent genes under later passage remain unexplored. In our study, we reprogrammed and characterised H103 and H376 oral squamous carcinoma cells using retroviral OSKM mediated method. Reprogrammed cells were characterized for their embryonic stem cells (ESCs) like morphology, pluripotent gene expression via quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence staining, embryoid bodies (EB) formation and directed differentiation capacity. Reprogrammed H103 (Rep-H103) exhibited similar ESCs morphologies with flatten cells and clear borders on feeder layer. Reprogrammed H376 (Rep-H376) did not show ESCs morphologies but grow with a disorganized morphology. Critical pluripotency genes Oct4, Sox2 and Nanog were expressed higher in Rep-H103 against the parental counterpart from passage 5 to passage 10. As for Rep-H376, Nanog expression against its parental counterpart showed a significant decrease at passage 5 and although increased in passage 10, the level of expression was similar to the parental cells. Rep-H103 exhibited pluripotent signals (Oct4, Sox2, Nanog and Tra-1-60) and could form EB with the presence of three germ layers markers. Rep-H103 displayed differentiation capacity into adipocytes and osteocytes. The OSCC cell line H103 which was able to be reprogrammed into an iPSC like state showed high expression of Oct4, Sox2 and Nanog at late passage and may provide a potential iPSC model to study multi-stage oncogenesis in OSCC.
APETALA2 plays critical roles in establishing meristem and organ identity during plant floral development. In this study, we obtained a CeAP2-like gene by using the mRNA differential display technique to analyze the wild type and a multitepal mutant of the orchid Cymbidium ensifolium. The full-length cDNA encoding the CeAP2-like transcription factor shows significant similarity to the cDNA of AP2 from Erycina pusilla and contains nucleotides complementary to miR172. Using a transient gene expression system of Arabidopsis protoplasts, we found that the accumulation of CeAP2-like protein and transcripts was negatively regulated by miR172, indicating this gene as a putative target of miR172. Northern blotting revealed that CeAP2-like is dominantly expressed in the sepals and petals of the wild-type flower, and shows low expression in the gynostemium. In contrast, the accumulation of CeAP2-like transcripts decreased significantly, especially in the central part of the mutant flower, corresponding to its abnormal petals and the absence of the gynostemium. Furthermore, we found an antagonistic expression pattern between CeAP2-like and AGAMOUS in the wild type, representing A-and C-class genes that specify floral organ fate. However, this antagonistic distribution was modified in the multitepal mutant, and both genes showed lower expression than that in the wild type. This result suggested that the balance between CeAP2-like and AGAMOUS activity was important for the regulation of floral patterning in C. ensifolium. This study represents the first report on a class A gene and its regulatory role for floral development in the orchid C. ensifolium.
Order Batching and Picker Routing Problems arise in warehouses when items specified by customer orders have to be retrieved from their storage locations. The Order Batching Problem includes the grouping of a given set of customer orders into feasible picking orders such that the total length of all picker tours is minimized. In order to calculate the length of a picker tour, the sequence has to be determined according to which the items contained in the picking order will be picked. This problem is known as the Picker Routing Problem. Although quite sophisticated heuristics and even efficient exact solution approaches exist to the Picker Routing Problem in warehouse with up to two blocks, the routing problem does not get much attention when dealing with the Order Batching Problem. Instead, the order pickers are assumed to follow a certain, simple routing strategy when making their ways through the warehouse. The advantage of this approach can be seen in the fact that-in particular for single-block warehouse layouts-the corresponding picker tours are very straightforward and can be memorized easily by the order pickers. This advantage diminishes, however, when more complex, multi-block layouts have to be dealt with. Furthermore, in such case, the approach may result in picker tours which are far from optimal. For multi-block layouts, we integrate different routing algorithms into an iterated local search approach for the batching in order to demonstrate what the benefits are from solving the Order Batching and the Picker Routing Problem in a more integrated way. By means of numerical experiments it is shown that paying more attention to the Picker Routing Problem results in a substantial improvement of the solution quality without increasing computing times.
Background/Alms: Differences in hepatic organic anion transporters were compared in rats to identify a causative factor for early stage acute hepatic failure after 70% or 90% hepatectomy (Hx). Methodology: Male Wistar rats (8 weeks, 250-330g) were randomly assigned to one of two groups for 70% Hx or 90% Hx, and sacrificed at 0, 6, 12, 24, 48, or 72 hours after Hx. Posthepatectomy expression of the bile salt export pump (Bsep), multidrug resistance proteins 2 and 3 (Mrp2, Mrp3), sodium-dependent taurocholate co-transporting polypeptide (Ntcp), and organic anion transporting polypeptides 1 and 2 (Oatp1, Oatp2) were analyzed by Northern blotting. Serum liver function tests were also performed. Results: Postoperative survival rates at 72 hours after 70% and 90% Hx were 100% and 50%, respectively. mRNA expression of Bsep and Mrp3 was increased after 90% Hx, while decreased after 70% Hx. These values were significantly greater at 12 and 24 hours after 90% Hx than after 70% Hx (p<0.05). In contrast, Mrp2 expression was down-regulated to a half of the preoperative level after 90% Hx, while increased after 70% Hx. mRNA expression of uptake transporters (Ntcp, Oatp1, Oatp2) was decreased after 70% Hx and 90% Hx with a similar extent. Total serum bilirubin and bile acid levels were significantly increased after both hepatectomy procedures with a greater extent after 90% Hx. Conclusions: Alteration of mRNA expression of Bsep, Mrp2 and Mrp3 may be characteristic behavior in the early stage of acute liver failure.
Organic Rankine Cycles (ORCs) are nowadays a valuable technology to produce electricity from low and medium temperature heat sources, e.g., in geothermal, biomass and waste heat recovery applications. Dynamic simulations can help improve the flexibility and operation of such plants, and guarantee a better economic performance. In this work, a dynamic model for a multi-pass kettle evaporator of a geothermal ORC power plant has been developed and its dynamics have been validated against measured data. The model combines the finite volume approach on the tube side and a two-volume cavity on the shell side. To validate the dynamic model, a positive and a negative step function in heat source flow rate is applied. The simulation model performed well in both cases. The liquid level appeared the most challenging quantity to simulate. A better agreement in temperature was achieved by increasing the volume flow rate of the geothermal brine by 2% over the entire simulation. Measurement errors, discrepancies in working fluid and thermal brine properties and uncertainties in heat transfer correlations can account for this. In the future, the entire geothermal power plant will be simulated, and suggestions to improve its dynamics and control by means of simulations will be provided.
Many industrial processes inevitably produce excess heat as by-product. Recovering this heat is a matter of waste management and provides opportunities to improve the energy use efficiency. The excess heat can be used for heating purposes (e.g., in processes, or delivered to district heating systems or buildings) or to generate electricity. An increasingly applied technology for industrial excess heat recovery is the organic Rankine cycle (ORC), suitable to recover low-grade heat from 90 degrees C onwards. Although ORCs are studied intensively, few studies have examined the economics of commissioned ORC systems. This paper investigates a 375 kWgross ORC system employed for flue gas heat recovery from an industrial kiln in Flanders, Belgium. The purpose of the study is twofold: providing insight into a practical ORC case; and evaluating the financial feasibility while taking the specific policy circumstances into account. The financial appraisal takes account of the specific technical setup, the diverse costs of the system, the external economic parameters, and the policy circumstances in Europe, Belgium and Flanders. A sensitivity analysis illustrates the influence of each parameter on the results. The analysis demonstrates the dominance of the investment costs (4217 (sic)(2013)/kW(gross)) in the expenses. Under the valid conditions the investment has a positive financial return, but the financial support from the government is indispensable. Finally, the sensitivity analysis reveals the importance of attaining sufficient load hours and the influence of electricity prices on the financial feasibility of ORC projects. The results suggest that ORC systems are suitable for industrial excess heat electricity production under certain conditions, but financial support remains necessary. Reducing the investment costs of the ORC itself could alleviate these conditions. (C) 2017 Elsevier Ltd. All rights reserved.
Organophosphorus ester-induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken, which results in mild ataxia in 714 days and severe paralysis as the disease progresses with a single dose. White leghorn layer hens were treated with DFP (1.7 mg/kg, sc) after prophylactic treatment with atropine (I mg/kg, sc) in normal saline and eserine ( I mg/kg, so in dimethyl sulfoxide. Control groups were treated with vehicle propylene glycol (0.1 mL/kg, SC), atropine in normal saline and eserine in dimethyl sulfoxide. The hens were sacrificed at different time points Such as 2, 4, and 8 h, as well as 1, 2, 5, 10 and 20 days, and the tissues from cerebrum, midbrain, cerebellum brainstem and spinal cord were quickly dissected and frozen for protein (western) and mRNA (northern) Studies. Subcellular fractionation, SDS-PAGE and immunoblotting of the nuclear and Supernatant fractions using standard protocols from spinal cord and cerebrum showed differential expression of protein levels of PKA, CREB and phosphorylated CREB (p-CREB). There was an increase in PKA level in spinal cord nuclear fraction after 4 h ( 130 +/- 5%) and 8 h (133 +/- 6%), while cerebrum nuclear fraction showed decrease (77 5%) at 4 h and remained at the same level at 8 h. No change was seen in either spinal cord or cerebrum soluble fraction at any time points. There was an increase in CREB level in the spinal cord supernatant (133 +/- 3%) after 5 days, while nuclear and supernatant fraction of the cerebrum did not show any alterations at any time point. p-CREB was induced in the spinal cord nuclear fraction at I day (150 3%) and 5 days (173 +/- 7%) of treatment, in contrast to the decreased levels p-CREB (72 +/- 4%) at 10 days in cerebrum nuclear fraction. Supernatant fraction of spinal cord and cerebrum did not show any changes in pCREB at time points studied. Similarly another set of animals were treated with DFP and perfused using standard protocols and immunohistochemistry for p-CREB in the brain and spinal cord confirmed the overall protein expression pattern identified by western analysis. Expression Of beta-tubulin subtypes (1, 2, 3, and 4), studied by Northern blotting showed complex and differential pattern, while immunohistochemistry of the anti-beta-tubulin for the entire period of OPIDN developmental stages showed early induction and persistence even in the disintegrating axonal and non-neuronal structures of the CNS. These data thus strongly suggest that early cytoskeletal damage at molecular level mediated by PKA/p-CREB pathways leads to the culmination of gross (microscopically observable) level cytoskeletal changes in various components of central nervous system (CNS), consistent with our earlier findings. Thus, the differential protein expression of PKA, CREB. p-CREB and beta-tubulin subtypes appear to contribute to the initiation, progression and development of OPIDN, probably by recruiting other molecular pathways specific to various components of nervous system. (C) 2009 Elsevier Inc. All rights reserved.
Organophosphorus (OPs) compounds are widely used in many pesticides, insecticides, and chemical nerve agents. These compounds are hazardous for humans and the environment. There are many reports on detoxification of these compounds, among them enzymatic cleavage of these compounds with organophosphorus hydrolase (OPH) has been taken into more consideration. Several studies have been performed to improve OPH secretion in Escherichia coli by different signal peptides, but have not been successful. In this study, to achieve the extracellular secretion of OPH in E. coli, the complete opd gene along with its native signal peptide was codon optimized and expressed in E. coli BL21(DE3)pLysS. The culture medium showed OPH activity after 2, 4, and 6 H of induction time. The extracellular secretion of OPH was also confirmed by SDS-PAGE and Western blot analysis. The effects of different factors in growth medium were also investigated regarding expression and extracellular secretion of OPH. It appears that the secretion of OPH into the extracellular medium is highly affected by culture conditions. Therefore, our results revealed that the recombinant OPH was successfully secreted into the extracellular medium. This secretion system can be considered as a high efficiency biocatalyst for detoxification of OPs compounds. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 870-876, 2016.
Background: Oridonin, the major terpene found in Rabdosia rubescens (Henmsl.) Hara, is widely used as a dietary supplement and therapeutic drug. Oridonin has been proven to possess good anti-tumour activity, but little is known about its effect on angiogenesis. The aim of this study was to investigate the antiangiogenic effects of oridonin in vivo and in vitro and prove that oridonin anti-tumour activity is based on suppressing angiogenesis. Methods: In vitro, the antiangiogenesis effect was studied by proliferation, apoptosis, migration, invasion, and tube formation experiments on human umbilical vascular endothelial cells (HUVECs). In vivo, using the Tg (fli1: GFP) zebrafish model, the embryonic vasculogenesis and postnatal regeneration were evaluated. The vascular endothelial growth factor (VEGF) signalling pathway gene expressions were assessed by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the inhibition effects on tumour growth and metastasis were observed using a xenograft zebrafish tumour model and xenograft nude mouse tumour model. Angiogenesis was assayed by immunostaining with cluster of differentiation 31. Importantly, the proteins were identified as being differentially expressed in an in vivo model by two-dimensional electrophoresis-mass spectrometry (2D-MS) and western blot (WB). Results: The results indicated that oridonin inhibited HUVEC proliferation, migration, invasion, and tube formation and induced cell apoptosis. Oridonin inhibited zebrafish angiogenesis during embryonic development and tail fin regeneration. RT-PCR showed that oridonin decreased the VEGFA, VEGFR2, and VEGFR3 expressions in zebrafish, while the TP53 expression increased. Moreover, oridonin had strong effects on tumour growth and metastasis in vivo. 2D-MS identified a total of 50 proteins differentially expressed (17 up-expressed, 28 down-expressed). Lastly, WB showed that Claudin 1, Claudin 4, and Claudin 7 were closely related to tumour growth and metastasis. Conclusion: This study demonstrated that oridonin could inhibit tumour growth and metastasis, which mainly based on oridonin antiangiogenic effects. Claudin 1, Claudin 4, and Claudin 7 were the main contributors to the mechanism.
Scrub typhus, caused by Orientia tsutsugamushi, is a common cause of acute undifferentiated febrile illness in the Asia-Pacific region. However, its nonspecific clinical manifestation often prevents early diagnosis. We propose the use of PCR and serologic tests as diagnostic tools. Here, we developed a multiplex real-time PCR assay using hydrolysis (TaqMan) probes targeting O. tsutsugamushi 47-kDa, groEL, and human interferon beta (IFN-beta gene) genes to improve early diagnosis of scrub typhus. The amplification efficiency was higher than 94%, and the lower detection limit was 10 copies per reaction. We used a human gene as an internal DNA quality and quantity control. To determine the sensitivity of this PCR assay, we selected patients with confirmed scrub typhus who exhibited a clear 4-fold increase in the level of IgG and/or IgM. The PCR assay result was positive in 45 of 52 patients, indicating a sensitivity of 86.5% (95% confidence interval [CI]: 74.2 to 94.4). The PCR assessment was negative for all 136 non-scrub typhus patients, indicating a specificity of 100% (95% CI: 97.3 to 100). In addition, this test helped diagnose patients with inconclusive immunofluorescence assay (IFA) results and using single blood samples. In conclusion, the real-time PCR assay proposed here is sensitive and specific in diagnosing scrub typhus. Combining PCR and serologic tests will improve the diagnosis of scrub typhus among patients presenting with acute febrile illness.
By focusing on the case of the Jarso and the Girhi in eastern Ethiopia, this article seeks to contribute to comparative studies on the social, territorial and relational effects of the effort at political and administrative decentralization in multi-ethnic settings. The article analyses the political and social implications of the elements that constitute impediments to social cohesion and socio-economic interaction in the study area. The data required for the study were collected through fieldwork that involved interviews, focus group discussions and field observations. On the basis of the analysis, the article recommends what should be done to create a relational politics of place in which places and spaces that connect people remain open, discontinuous, relational and internally diverse.
The last decade has brought about an unexpected rise in oropharyngeal squamous cell carcinoma (OPSCC) primarily in white males from the ages of 40-55 years, with limited exposure to alcohol and tobacco. This subset of squamous cell carcinoma (SCC) has been found to be associated with human papillomavirus infection (HPV). Other Head and Neck Squamous Cell carcinoma (HNSCC) subtypes include oral cavity, hypopharyngeal, nasopharyngeal, and laryngeal SCC which tend to be HPV negative. HPV associated oropharyngeal cancer has proven to differ from alcohol and tobacco associated oropharyngeal carcinoma in regards to the molecular pathophysiology, presentation, epidemiology, prognosis, and improved response to chemoradiation therapy. Given the improved survival of patients with HPV associated SCC, efforts to de-intensify treatment to decrease treatment related morbidity are at the forefront of clinical research. This review will focus on the important differences between HPV and tobacco related oropharyngeal cancer. We will review the molecular pathogenesis of HPV related oropharyngeal cancer with an emphasis on new paradigms for screening and treating this disease. Published by Elsevier B.V.
Trehalose is not only an important disaccharide, but also a key stress resistance factor in the development of many organisms, including plants, bacteria, fungi, and insects. To study the potential function of trehalose in development and behaviour, cDNA for a trehalose-6-phosphate synthase from Catantops pinguis (CpiTPS) was cloned and sequenced. Results revealed that the CpiTPS cDNA sequence contains an open reading frame of 2430 nucleotides encoding a protein of 809 amino acids with a predicted molecular weight of 91.13 kDa and a pI value of 6.25. Northern blot and RT-PCR analyses showed that CpiTPS mRNA expression was high in the fat body and testes, ovaries, Malpighian tubules, brain, trachea, rectum, and posterior extensor of C. pinguis. Northern blotting revealed that CpiTPS mRNA was expressed in the fat body at different developmental stages and was present at a high level in first instar larvae and adults. The results demonstrate that CpiTPS is a key gene in C. pinguis development.
P>Oryza meyeriana Baill was found immune to Xanthomonas oryzae pv. oryzae (Xoo). However, the genes responsible for the strong resistance are unknown. In this study, suppression subtractive hybridization (SSH) was utilized to identify genes differentially expressed in O. meyeriana after Xoo infection. Oryza meyeriana plants inoculated with high pathogenicity races were used as 'tester' and non-inoculated plants as 'driver'. Analysis of the SSH library revealed genes responsible for cell wall lignifications, which may function to block pathogen invasion. Also identified are genes involved in secondary metabolism systems to eliminate damage caused by chemicals such as peroxides in cells. One of the response genes, ME281 encoding a protein with leucine-rich repeats which has high similarity with those of other reported disease resistance genes, was further analysed by RT-PCR and Northern blotting, which showed its expression peaked at 48-72 h after Xoo infection, suggesting that it may function at the later stage of the plant's responses. This study would help demonstrate the molecular mechanism of O. meyeriana's strong resistance to Xoo and find new disease resistance candidate genes.
Many studies use strategies that allow for the identification of a large number of genes expressed in response to different stress conditions to which the plant is subjected throughout its cycle. In order to obtain accurate and reliable results in gene expression studies, it is necessary to use reference genes, which must have uniform expression in the majority of cells in the organism studied. RNA isolation of leaves and expression analysis in real-time quantitative polymerase chain reaction (RT-qPCR) were carried out. In this study, nine candidate reference genes were tested, actin 11 (ACT11), ubiquitin conjugated to E2 enzyme (UBC-E2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta tubulin (beta-tubulin), eukaryotic initiation factor 4 alpha (eIF-4 alpha), ubiquitin 10 (UBQ10), ubiquitin 5 (UBQ5), aquaporin TIP41 (TIP41-Like) and cyclophilin, in two genotypes of rice, AN Cambara and BRS Querncia, with different levels of soil moisture (20%, 10% and recovery) in the vegetative (V5) and reproductive stages (period preceding flowering). Currently, there are different softwares that perform stability analyses and define the most suitable reference genes for a particular study. In this study, we used five different methods: geNorm, BestKeeper, Delta Ct method, NormFinder and RefFinder. The results indicate that UBC-E2 and UBQ5 can be used as reference genes in all samples and softwares evaluated. The genes beta-tubulin and eIF-4 alpha, traditionally used as reference genes, along with GAPDH, presented lower stability values. The gene expression of basic leucine zipper (bZIP23 and bZIP72) was used to validate the selected reference genes, demonstrating that the use of an inappropriate reference can induce erroneous results.
We investigated the expression pattern of zinc finger protein gene in rice (Oryza sativa L.) under various abiotic stresses. This gene contains an open reading frame encoding a zinc-finger protein of 171 amino acids and is induced by various stresses, namely salinity, drought, and cold. Phylogenetic analysis based on deduced amino acid sequences of OsZFP cDNA revealed a significant sequence similarity to the zinc finger protein from diverse families of plant species. Southern blot analysis of rice genomic DNA suggested that OsZFP is encoded by a multiple-copy gene. The steady-state levels of OsZFP transcripts were found to increase in response to salinity, drought, and cold stresses. A rice zinc-finger protein gene, OsZFP, encoding the Cys2/His2-type zinc-finger transcription factor was isolated from rice using RT-PCR. The expression profiling indicated that OsZFP was constitutively expressed in leaves and roots. The Northern blotting showed that OsZFP was strongly induced by high salinity and drought, but only slightly regulated by low temperature (4 degrees C). These results suggested that the OsZFP may play an important role in rice responses to salinity, drought, and cold as a transcription factor.
Objective. To conduct a replication study and meta-analysis involving the study of mtDNA variants in the radiographic progression of OA in different cohorts worldwide, including Cohort Hip and Cohort Knee (CHECK), the OA Initiative and a cohort from Spain. Methods. The influence of the haplogroups in the rate of radiographic progression at 96 months in 431 subjects from CHECK was assessed in terms of Kellgren and Lawrence (KL) grade. Progression was defined as a change from KL >= 1 at baseline to any higher grade during the follow-up. Extended Cox proportional hazard models were used to analyse the influence of mtDNA variants in the rate of radiographic knee OA progression. A subsequent meta-analysis of 1603 subjects following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted to combine the data of individual studies. A sensitivity analysis was performed to validate the stability of the results. Results. CHECK subjects carrying the haplogroup T showed the lowest rate of radiographic knee OA progression [hazard ratio (HR) 0.645 (95% CI 0.419, 0.978); P < 0.05]. When pooled, subjects within the superhaplogroup JT showed the same trend [HR 0.707 (95% CI 0.501, 0.965); P < 0.05]. BMI [HR 1.046 (95% CI 1.018, 1.073); P < 0.05] and bilateral OA [HR 2.266 (95% CI 1.733, 2.954); P < 0.05] at baseline are risk factors for radiographic knee OA progression as well. In the meta-analysis there was a reduced rate of radiographic progression in subjects with haplogroup T [HR 0.612 (95% CI 0.454, 0.824); P = 0.001] or in the superhaplogroup JT [HR 0.765 (95% CI 0.624, 0.938); P = 0.009]. Sensitivity analysis revealed that the results were robust. Conclusion. The mtDNA variants in the superhaplogroup JT associate with a reduced rate of radiographic OA progression. The mtDNA polymorphisms in the superhaplogroup JT emerge as potential complementary genetic biomarkers for disease progression.
Current treatments for acute or degenerative chondral and osteochondral lesions are in need of improvement, as these types of injuries lead to disability and worsen the quality of life in a high percentage of patients. The aim of this study was to develop a new bi-layered scaffold for osteochondral tissue regeneration through a "biomimetic" and "bioinspired" approach. For chondral regeneration, the scaffold was realized with an organic compound (type I collagen), while for the regeneration of the subchondral layer, bioactive magnesium-doped hydroxyapatite (Mg/HA) crystals were co-precipitated with the organic component of the scaffold. The entire scaffold structure was stabilized with a cross-linking agent, highly reactive bis-epoxyde (1,4-butanediol diglycidyl ether - BDDGE 1 wt%). The developed scaffold was then characterized for its physico-chemical characteristics. Its structure and adhesion strength between the integrated layers were investigated. At the same time, in vitro cell culture studies were carried out to examine the ability of chondral and bone scaffold layers to separately support adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes and osteoblasts, respectively. Moreover, an in vivo study with nude mice, transplanted with osteochondral scaffolds plain or engineered with undifferentiated hMSCs, was also set up with 4 and 8-week time points. The results showed that chondral and bone scaffold layers represented biocompatible scaffolds able to sustain hMSCs attachment and proliferation. Moreover, the association of scaffold stimuli and differentiation medium, induced hMSCs chondrogenic and osteogenic differentiation and deposition of extracellular matrix (ECM). The ectopic implantation of the engineered osteochondral scaffolds indicated that hMSCs were able to colonize the osteochondral scaffold in depth. The scaffold appeared permissive to tissue growth and penetration, ensuring the diffusion of nutrients and oxygen, as also suggested by the presence of a neo-angiogenesis process, especially at 4 weeks. Moreover, the in vivo results further confirmed the great potential of the scaffold in tissue engineering, as it was able to support the initial formation of new bone and chondral tissue, confirming the importance of combined and innovative strategies to improve the available therapeutic strategies for chondral and osteochondral regeneration. (C) 2016 Elsevier B.V. All rights reserved.
Child abuse is a major public health concern that can explain a proportion of fractures in children. Osteogenesis imperfecta (OI) is the most common inherited syndrome that predisposes to skeletal fractures. We conducted a retrospective analysis of data from clinical, laboratory, and radiographic information from children evaluated for child abuse in which molecular testing for COL1A1 and COL1A2 genes was conducted. A total of 43 patients underwent molecular testing for OI. Pathogenic variants predicted to result in a mild form of OI were found in two patients (5%), both clinically suspected to have this diagnosis. None of the cases in whom OI molecular testing was ordered when maltreatment concerns were thought to be more likely (0/35) were identified to have pathogenic variants. After reviewing each individual case, the final diagnosis was child abuse for 34 cases (77%), and additional radiographic and laboratory studies did not identify any with inherited metabolic predisposition to fracture or rickets. We conclude that routine testing for OI in the setting of child abuse when no other suggestive clinical findings are present has a low yield. A careful review of the medical history and a detailed clinical evaluation help identify those at risk for genetic alterations. (C) 2016 Wiley Periodicals, Inc.
Patients with lung cancer still have high mortality, recurrence rate after adjuvant treatment, and poor five-year survival rates, despite of advances in multidisciplinary anti-cancer therapies, e.g. chemotherapy, radiotherapy and targeted therapies, It depends upon the presence of intratumoral heterogeneity and complexity of lung cancer. There is growing evidence to suggest that osteopontin (OPN) may play a critical role in tumor progression and metastasis. The present review briefly describes the structure and molecular biology of OPN, highlights the role of OPN in the development and metastasis of lung cancer, and summarizes potential mechanisms of OPN heterogeneity in tumor to underline some of these inconsistencies. The article will emphasize the importance to understand the role of OPN in cancer evolution and heterogeneity and explore the potential of OPN as a therapeutic target. (C) 2016 Published by Elsevier Ltd.
Background and purpose: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is involved in the progress of atherosclerosis. We chose a gene polymorphism locus, OPG rs3102735, to explore how OPG gene polymorphisms relate to the occurrence of ischemic stroke and microembolic signals and to evaluate their relationship with the severity of neurologic deficits at admission and the degree of vascular stenosis. Methods: We studied 251 patients diagnosed with large artery atherosclerosis (LAA) stroke and 121 controls. The LAA stroke patients were divided into clinical subgroups according to the presence of microembolic signals, severity of neurologic deficits at admission, and the degree of vascular stenosis. The OPG rs3102735 gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism. The microembolic signals (MES) were monitored by transcranial Doppler (TCD) for 60 min within 72 h of stroke onset. The severity of neurologic deficits at admission was evaluated by the National Institutes of Health Stroke Scale (NIHSS). Results: The CC + CT genotypes and allele C frequencies of the rs3102735 gene polymorphism were significantly higher in the LAA group than in the control group (39% vs. 25.6%, P = 0.026; 21.7% vs.13.2%, P = 0.006), higher in MES-positive compared to MES-negative patients (58.7% vs. 32.4%, P < 0.01; 34.1% vs.17.6%, P= 6) than in those with an NIHSS Score (0.05). Conclusion: Our findings suggest that the OPG rs3102735 gene polymorphism might be related to the occurrence of LAA ischemic stroke, microembolic signals and stroke severity and not the degree of vascular stenosis. (C) 2017 Elsevier B.V. All rights reserved.
Background: Osteosarcoma is the most common malignancy of bone. Intratumoral hypoxia occurs in many solid tumors, where it is associated with the development of aggressive phenotype. ANRIL has been shown to be a long noncoding RNA that facilitates the progression of a number of malignancies. Yet, few studies have explored the expression pattern of ANRIL in osteosarcoma and the effect of hypoxia on ANRIL. Methods: We evaluated the expression levels of ANRIL in osteosarcoma tissues, adjacent normal tissues and cells with quantitative real-time polymerase chain reaction. Multiple approaches including luciferase reporter assay with nucleotide substitutions, chromatin immunoprecipitation assay and electrophoretic mobility shift assay were used to confirm the direct binding of HIF-1 alpha to the ANRIL promoter region. SiRNA-based knockdown and other molecular biology techniques were employed to measure the effect of HIF-1 alpha on the expression of ANRIL. Results: We found that the expression of ANRIL was upregulated in 15 pairs of osteosarcoma compared with adjacent normal tissues. We found that hypoxia is sufficient to upregulate ANRIL expression in osteosarcoma cells (MNNG and U2OS). HIF-1 alpha directly binds to the putative hypoxia response element in the upstream region of ANRIL. What's more, siRNA and small molecular inhibitors-mediated HIF-1 alpha suppression attenuated ANRIL upregulation under hypoxic conditions. Upon hypoxia, ANRIL promoted cancer cell invasion and suppressed cell apoptosis. Conclusion: Taken together, these data suggest that HIF-1 alpha may contribute to the upregulation of ANRIL in osteosarcoma under hypoxic conditions. ANRIL is involved in hypoxia-induced aggressive phenotype in osteosarcoma.
Osteosarcoma (OS) is the most common form of bone malignancy in children and adolescents. A class of molecules known as microRNAs (miRNAs) have been routinely associated in the development and progression of OS. The present study was centered on the less well-known miRNA, miRNA (miR)-150, and its role in OS was investigated. The levels of miR-150 were examined in 40 tissue specimens from patients with OS and adjacent normal tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. In addition the expression levels of miR-150 were examined in three OS cell lines and a normal osteoblast cell line. Cell proliferation, migration and invasion assays were performed to establish the correlation between miR-150 and metastasis. The potential targets of miR-150 were theoretically predicted and one high-scoring target, Rho-associated kinase 1 (ROCK1), was established to be a direct target using RT-qPCR and western blot analyses and Pearson's correlation analysis. The results indicated that miR-150 was downregulated in tissues from patients with OS and cell lines. Secondly, it was shown that the overexpression of miR-150 was inversely correlated with OS cell proliferation, migration and invasion. It was also shown that miR-150 negatively regulated the gene expression of ROCK1 in the OS cell lines. Finally, the interaction between miR-150 and ROCK1 was established and it was shown that miR-150 directly targeted ROCK1. In conclusion, miR-150 was found to be a tumor suppressor, and the suppression of miR-150 resulted in elevation in the levels of ROCK1. This interaction between miR-150 and ROCK1 may be key in the progression of OS. Furthermore, miR-150 or ROCK1 may be potential therapeutic targets for the treatment of OS.
To study the effects of miR-22 on the proliferation and the apoptosis of osteosarcoma MG-63 cell line and to explore the potential molecular mechanism that miR-22 regulates this biological process. Quantitive real-time polymerase chain reaction (RT-qPCR) was performed to explore the miRNA level of miR-22. The MG-63 cell line was infected with miR-22 mimics for establishment of miR-22 overexpression. Non-infected cells were in blank group and cells infected with empty vector were served as negative control (NC group). MTT assay was conducted to measure cell viability. The cell cycle and apoptosis were explored using flow cytometry and the apoptosis-related markers were detected by western blotting. RT-qPCR results revealed that the miR-22 miRNA level in the MG-63 cells was significantly lower than that in osteoblasts (P<0.05). MTT assay showed that the MG-63 cells infected with miR-22 mimics exhibited markedly decreased proliferation ability compared with blank and empty vector (NC) groups. Next, we found that overexpression of miR-22 remarkably increased the apoptosis of the MG-63 cells, evidenced from the flow cytometry results and elevated Bax and reduced Bcl-2. Furthermore, results revealed that percentage of the cells at G0/G1 phase in miR-22 mimic group (66.75 +/- 3.67%) was significantly higher than blank (52.9 +/- 2.58%) and NC (50.5 +/- 2.45%) groups. miR-22 attenuated the proliferation and induced the apoptosis of the MG-63 cells via promoting G0/G1 cell cycle arrest. Thus, miR-22 may have the potential to be a novel therapeutic in treatment of osteosarcoma.
Previous Northern blotting analyses of rice seedlings have screened several WRKY genes among the transcripts that are differentially regulated in the following treatments: high salinity, cold stress, polyethylene glycol (PEG) and heat shock. Here, we report characterization of a WRKY gene, OsWRKY08, in rice, which was found to be inducible by PEG NaCl, Abscisic acid (ABA), and naphthalene acetic acid (NAA) as its ortholog AtWRKY28 in Arabidopsis. To determine whether overexpression of OsWRKY08 alters abiotic stress tolerance, 35S::OsWRKY08 recombinant was generated and transformed into Arabidopsis. Physiological tests indicated that 35S::OsWRKY08 transgenic Arabidopsis displayed increased tolerance to mannitol stress through increasing the lateral root number and primary root length during seeding root development. Further, semi-quantitative RT-PCR showed that AtCOR47 and AtRD21, two ABA-independent abiotic stress responded genes, were induced in 35S::OsWRKY08 transgenic plants. These results suggest OsWRKY08 improves the osmotic stress tolerance of transgenic Arabidopsis through an ABA-independent signaling pathway.
Oral tolerance (OT) towards antigens encountered in the gut is a vital immune function of gut immunity. Experimental models can demonstrate OT efficacy by feeding of a protein followed by peripheral immunization and measuring the specific antibody titer. We had previously shown that exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), a xenobiotic high-affinity aryl hydrocarbon receptor (AhR)-ligand, destabilized OT against ovalbumin ( OVA) in mice. AhR is involved in the development, differentiation and function of immune cells, and highly expressed in gut epithelial cells and gut immune cells. We here used AhR-deficient mice to study the role of AhR in OT further. We show that complete AhR-deficiency undermines the stability of oral tolerance against OVA upon multiple immunizations, despite no renewed oral encounter with the antigen. This OT destabilization is accompanied by significant changes in IL10 and TGF. RNA in the gut tissue. Using conditional AhR-deficient mouse lines, we identify T cells as the major responsible immune cell type in this context. Our findings add to knowledge that lack of AhR signaling in the gut impairs important gut immune functions.
In this paper a slew rate enhancement method using some extra paths in recycling folded cascode (RFC) amplifier is presented. The added transistors are in cut-off region in the small-signal operation and will be automatically turned on during slewing phase. Therefore, negative and positive slew rates are improved without increasing power dissipation in the small-signal operation. Simulation results in 90 nm CMOS technology show a 2.4 times enhancement in the average slew rate and a 69 % reduction in the settling time without affecting the gain bandwidth and power dissipation compared to the conventional RFC structure.
By using compensation technique with feed-forward path, an improved folded cascode operational transconductance amplifier (OTA) that operates in weak inversion region is designed. The proposed configuration consists of composite transistors, recycling structure and feed-forward compensation path. In comparison with the typical folded cascode CMOS Miller amplifier, this design has higher DC gain, unity gain frequency and slew rate without adversely affecting the noise and offset performance. The presented OTA is simulated in 0.18 mu m CMOS technology and the simulation results confirm the theoretical analyses. Finally, the proposed amplifier has a 104.5 dB open-loop DC gain and 69.4 kHz unity gain frequency @ 0.6 V supply voltage while the power consumption is 300 nW.
This study investigated baseline client characteristics that predicted long-term treatment outcomes among adolescents referred from school and community sources and enrolled in usual care for conduct and substance use problems. Predictor effects for multiple demographic (age, sex, race/ethnicity), clinical (baseline symptom severity, comorbidity, family discord), and developmental psychopathology (behavioral dysregulation, depression, peer delinquency) characteristics were examined. Participants were 205 adolescents (52 % male; mean age 15.7 years) from diverse backgrounds (59 % Hispanic American, 21 % African American, 15 % multiracial, 6 % other) residing in a large inner-city area. As expected, characteristics from all three predictor categories were related to various aspects of change in externalizing problems, delinquent acts, and substance use at one-year follow-up. The strongest predictive effect was found for baseline symptom severity: Youth with greater severity showed greater clinical gains. Higher levels of co-occurring developmental psychopathology characteristics likewise predicted better outcomes. Exploratory analyses showed that change over time in developmental psychopathology characteristics (peer delinquency, depression) was related to change in delinquent acts and substance use. Implications for serving multiproblem adolescents and tailoring treatment plans in routine care are discussed.
Objectives: To investigate characteristics of nine carbapenem-non-susceptible (CP-NS) Escherichia coli isolates collected between 1999 and 2005 at a Taiwanese university hospital. Methods: Genetic relatedness was analysed by PFGE. beta-Lactamases were characterized by PCR and isoelectric focusing. Outer membrane proteins and transcripts were investigated by SDS-PAGE and northern blotting. Cloning experiments were performed to investigate the role of membrane permeability in carbapenem non-susceptibility. Results: The nine CP-NS isolates were found to produce the CMY-2 AmpC enzyme (n = 8), the CTX-M-14-type extended-spectrum beta-lactamase (ESBL) (n = 1), the SHV-12 ESBL (n = 1) and the IMP-8-type metallo-beta-lactamase (n = 1) alone or in combination. All CP-NS isolates revealed a decrease in the transcription and protein expression of ompC, and susceptibility to carbapenems was restored in one isolate by introducing the cloned ompC gene. PFGE revealed genetic diversity among the nine isolates. All patients with the CP-NS isolates had been treated with carbapenems (six patients) and/or extended-spectrum cephalosporins (five patients) before isolation. Conclusions: Our study suggests that the decreased susceptibility to carbapenems in E. coli in the hospital might arise by the stepwise accumulations of multiple drug-resistance determinants in different clones.
The current study aimed to investigate the potential role of miR-9 in the inhibition of ovarian cancer progression through the stromal cell-derived factor-1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) pathway and to provide a theoretical basis for the diagnosis and treatment of ovarian cancer. Human ovarian cancer OVCAR-3 cells were transfected with miR-9 short hairpin RNA (shRNA). The effect of miR-9 on the mRNA expression levels of CXCR4 were analyzed using reverse transcription-quantitative polymerase chain reaction. The effects of miR-9 on OVCAR-3 cell proliferation, invasion and apoptotic ability were detected using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay, Matrigel method, and Annexin V-fluorescein isothiocyanate flow cytometry, respectively. In addition, expression levels of SDF-1/CXCR4 pathway associated proteins were determined by western blot analysis. mRNA expression levels of CXCR4 in OVCAR-3 cells transfected with miR-9 shRNA was significantly downregulated compared with the blank and control groups (P<0.05). Furthermore, compared with the two control groups, the current results revealed that miR-9 inhibited cell proliferation, suppressed invasive ability and induced cell apoptosis in OVCAR-3 cells (P<0.05). Finally, it was observed that miR-9 functioned as a tumor inhibitor through the SDF-1/CXCR4 pathway by suppressing the expression levels of extracellular signal-regulated kinase 1 (ERK1), ERK2 and matrix metalloproteinase-9 proteins. The present study suggested that miR-9 may function as a promising tumor inhibitor for ovarian cancer through targeting the SDF-1/CXCR4 pathway.
MicroRNAs are a class of small non-coding, endogenous RNAs involved in cancer development and progression. MicroRNA-221 (mir-221) has been reported to have both an oncogenic and tumor-suppressive role in human tumors, but the role of miR-221 in ovarian cancer is poorly understood. In the present study, the expression levels of miR-221 and the apoptosis protease activating factor 1 (APAF1) protein in 63 samples of ovarian cancer tissues and the cell lines, IOSE25, A2780, OVCAR3, SKOV3 and 3AO were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Cell proliferation was measured using Cell Counting kit-8 (CCK-8); cell migration and invasion were detected using a Transwell assay; cell apoptosis was evaluated by flow cytometry and Hoechst staining, and a luciferase assay was performed to verify a putative target site of miR-221 in the 3'-UTR of APAFI mRNA. Expression of miR-221 was upregulated in ovarian cancer tissues. Patients with increased miR-221 expression levels had a reduced disease-free survival (P=0.0014) and overall survival (P=0.0058) compared with those with low miR-221 expression. Transfection of SKOV3 and A2780 cell lines with miR-221 inhibitor induced APAF1 protein expression, suppressed cell proliferation and migration and promoted tumor cell apoptosis. In conclusion, the APAF1 gene was confirmed as a direct target of miR-221 and overexpression of APAF1 suppressed ovarian cancer cell proliferation and induced cell apoptosis in vitro. These findings indicate that miR-221-APAF1 should be studied further as a potential new diagnostic or prognostic biomarker for ovarian cancer.
Despite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer (OC) is the first cause of death due to gynecological cancer and the fifth cause of death for cancer in women in Spain. The aim of this guideline is to summarize the current evidence and to give evidence-based recommendations for clinical practice.
When imitating novel actions, typically developing preschoolers often copy components of the demonstration that are unrelated to the modeled action's goal, a phenomenon known as 'overimitation'. According to the social motivation account, overimitation fulfills social affiliation motives (i.e., the imitator's drive to experience social connectedness with the demonstrator and the social context). Conversely, according to the social-cognitive account, overimitation reflects overattribution of causal relevance (i.e., the imitator's failure to appreciate that some components of the demonstration are not relevant to the action's outcome). Autism Spectrum Disorder (ASD) and William syndrome (WS) are characterized by reduced and enhanced spontaneous social motivation, respectively, as well as similar impairments in social-cognition, thus providing helpful test cases to understand the nature of overimitation. Using a novel eye-tracking paradigm, we examined overimitation in 31 preschoolers with ASD, 18 age-and IQ-matched peers with WS, and 19 age-matched typically developing children. We found that children with WS and typically developing children were more likely to overimitate, and to increase their attention to the model's face during demonstration of causally irrelevant actions, compared to those with ASD. These findings will be discussed in the context of support for the social-motivational account of overimitation. (C) 2017 Elsevier B.V. All rights reserved.
Microsporidia are a group of intracellular parasites characterized by highly reduced and compact genomes. The presence of a high gene density had several consequences for microsporidian genomes, including a high frequency of overlap between transcripts of adjacent genes. This phenomenon is apparently widespread in microsporidia, and strongly correlated with gene density. However, all analyses to date have focused on one or a few transcripts from many loci, so it is unclear how diverse the pool of transcripts at a given locus may be. To address this question, we characterized initiation and termination points from 62 transcripts in gene-dense regions in Antonospora locustae spores using both conventional and fluorescence-based RACE-PCR procedures. In parallel, we investigated the abundance and nature of transcripts along a 6 kb region surrounding the actin locus of A. locustae using northern blotting, RACE-PCR and previously characterised EST sequences. Overall, we confirmed previous suggestions that most transcripts in A. locustae spores overlap with the downstream gene, but that at the 5' end untranslated regions are very short and overlap is rare. From fluorescence-based RACE-PCR we show that transcription of most genes (31 out of 34) initiates at a single position, whereas 35% of loci analyzed with 3' RACE polyadenylate mRNA at several sites. Finally, we identified the presence of previously unsuspected and very large transcripts in A. locustae spores. Those transcripts were found to overlap up to four open reading frames in different strands, adding a novel layer of complexity in the mRNA transcription of this microsporidian species.
The rapid expansion of variable renewable energy (e.g., wind and solar) can make it more difficult to balance electricity supply and demand at a grid-scale. While much attention has focused on the risk of unexpected generation shortfalls, periods of oversupply (when supply is greater than demand) also present challenges that can lead to financial losses for utilities and/or consumers when renewable energy is "curtailed". A unique form of oversupply occurs in hydro-dominated systems. Although hydropower is thought to offer a highly flexible resource that can complement variable renewable energy, seasonal variability in streamflows and the presence of environmental regulations can create complex oversupply conditions if renewable energy is plentiful. In this study, an integrated hydro-economic model is developed to assess the frequency and severity of financial losses arising from oversupply in the U.S. Pacific Northwest, a hydro-dominated system with rapidly growing wind power generation. Present value losses over 25 years (2016-2040) are evaluated under several future scenarios including increased wind capacity, electricity price uncertainty, and expanded transmission capacity for moving excess electricity to export markets. Results indicate that oversupply losses will increase as a function of installed wind capacity, with the extent of this increase sensitive to future electricity prices. In the case of adding transmission capacity to alleviate oversupply losses, the cost of this infrastructure is substantially more than the associated reduction in losses and is therefore difficult to justify. (C) 2017 Elsevier Ltd. All rights reserved.
Ovis ammon darwini: has been listed as a nearthreatened species by IUCN-World Conservation Union due to over-hunting and poaching, competition with domestic livestock, and habitat destruction. Study on molecular biology research provides the scientific basis for the protection and sustainable utilization of key endangered species. Mitochondrial genome is very useful for researches in ecology, systematics and conservation biology. In this study, the complete mitochondrial genome sequence of O. a. darwini was determined by next-generation sequencing data, which is 16,618 bp in length and contains 13 proteincoding genes(PCGs), 2 rRNAs genes, 22 tRNAs genes and a non-coding control region. Base composition of genome is A(33.7 %), C(25.8 %), G(13.1 %), T(27.4 %) with an A + T content of 61.1 %. Phylogenetic analysis suggested that the systematic status of O. a. darwini was more closed related to O. a. hodgsoni clustered with O. ammon. The mitogenome of O. a. darwini offered significant information for molecular genetic research of O. ammon.
We report two experiments supporting the theory that children's understanding of ownership rights is related to their notions of body rights. Experiment 1 investigated 4- to 7-year-olds' (N = 123) developing sensitivity to physical contact in their judgments about the acceptability of behaving in relation to owned objects and body parts. Experiment 2 used a simpler design to investigate this in 3- and 4-year-olds (N = 112). Findings confirmed two predictions of the theory. First, in both experiments, children's judgments about ownership and body rights were similarly affected by physical contact. Second, judgments about both kinds of rights were yoked in development; age-related changes in judgments about ownership rights were paralleled by changes in judgments about body rights. Our findings have additional import for theories of ownership rights because they suggest that physical contact may be a crucial factor in whether behaviors targeting property are judged to be permissible. (C) 2016 Elsevier Inc. All rights reserved.
Group ownership is ubiquitous-property is owned by countries, corporations, families, and clubs. However, people cannot understand group ownership by simply relying on their conceptions of ownership by individuals, as group ownership is subject to complexities that do not arise when property is individually owned. We report 6 experiments investigating whether children ages 3 to 6 (N = 540) understand group ownership. In Experiments 1 and 2 children were asked who different objects belong to, and they appropriately judged that certain objects are more likely to belong to a group than to individual people. Experiments 3 and 4 investigated whether children understand the limits of group ownership. Children saw vignettes where agents modified or depleted property. Children ages 3 and older understood that individual members of a group should not deplete group-owned property, and children ages 5 and 6 understood that individual members should not modify group-owned property. Finally, Experiments 5 and 6 investigated whether children understand the benefits of group ownership. Children ages 5 and 6 judged that it is more acceptable for a group member to take group property than for a nonmember to do this, and children ages 4 to 6 judged that group members can take more group resources than can nonmembers. Together, these results are informative about how children conceive of group ownership rights, and about children's conceptions of groups.
Selenium (Se) is an essential nutrient for antioxidant defenses in fish because of its role in preventing immunosuppression caused by oxidative stress. In this study it was demonstrated the relation between the oxidative stress and immune status after a long Se supplementation period, as a result of the evaluation of immunological, hematological and antioxidant responses, as well as growth performance of pacu fed diets supplemented with different concentrations of organic selenium (0, 0.3, 0.6, 0.9, and 1.8 mg Se-yeast/kg, but the final analyzed selenium concentrations were 0.72, 0.94, 1.15, 1.57 and 2.51 mg/kg, respectively) for 65 days. Dietary Se supplementation at 1.15 mg Se-yeast/kg (analyzed value) restored the production of antioxidant enzymes (glutathione peroxidase (GPx) and glutathione S-transferase (GST)), and consequently allowed the increased of some immunological parameters (leukocyte respiratory burst activity and lysozyme activity), hematological parameters (red blood cell count (RBC), hematocrit (HTC), mean corpuscular volume (MCV), and white blood cell count (WBC)). Se supplementation in pacu diets at 1.15 mg Se-yeast/kg for 65 days improved immune response and antioxidant defenses, suggesting that oxidative stress impairs immune system response to prevent excessive reactive oxygen species in cells and indicating the occurrence of a physiological trade-off between immune and antioxidant systems. Higher Se levels, such as 1.57 mg Se-yeast/kg increased the leukocyte respiratory burst activity, the WBC and thrombocyte counts, the RBC and HTC, and the GST and GPx enzymes. However, 2.51 mg Se-yeast/kg decreased the lysozyme levels, the WBC and thrombocyte counts, the RBC, HTC and MCV, and the GST and GPx enzymes. Those findings are important to future studies because showed the negative effect of oxidative stress on immunity, and may help to prevent any inhibition of the expected immune response after immunomodulators administration and vaccination. Also it was possible to meet the dietary selenium requirement of pacu, that was estimated to be 1.56 mg/kg. (C) 2016 Elsevier Ltd. All rights reserved.
Oxygen reduction reaction (ORR) is at the core of various applications, such as fuel cells, metal-air batteries and H2O2 electro-generation. Depending on the targeted application, catalysts that follow a "direct four-electron (4e(-))" pathway or "two-electron (2e(-))" pathway are envisaged. We have systematically investigated the impact of the electrocatalyst loading on the rotating ring-disk electrode (RRDE), on their activity and selectivity towards ORR in alkaline medium (0.1 M and 1M KOH). Four representative catalysts, including a noble metal catalyst (commercial 20 wt% Pt/C, ETEK), metal-free catalysts (Printex carbon black and graphene), and non-noble metal catalyst (Fe/N/C), were selected because they exhibit different behaviours for ORR following a "direct four-electron (4e-)" pathway, "two-electron (2e-)" pathway, or a "series 2e(-) + 2e(-)" pathway. The results confirmed that the catalyst loading influences the activity and the selectivity of the catalysts, with lower loadings favoring the H2O2 electrogeneration, and researchers should pay attention to it. Moreover, in order to make possible comparison between results coming from different research groups, we recommend reasonable loading ranges for each type of catalyst. (C) 2017 Elsevier B.V. All rights reserved.
Low oxygen pressure or hypoxia is often an obstacle in pathological conditions, including during cancer development and metastatic dissemination. The main family of transcription factors involved in the adaptation to inappropriate oxygen levels are the 'Hypoxia-Inducible Factors' (HIFs) that together with HIF prolyl hydroxylases (PHDs) regulate many different processes, during physiological as well pathological conditions. Additionally, the entire HIF transcription cascade is involved in the 'seventh' hallmark of cancer; tumor promoting inflammation. Previous work revealed that HIF-pathway proteins influence tumor associated immune cells in their action toward proliferation, differentiation, vessel normalization and tumor dissemination. These changes are not necessarily analogous to the role of these proteins in non-tumor related immune responses, where hypoxia often encourages a strong inflammatory response. Recently, Clever et al. demonstrated that T-cell intrinsic inhibition of all three PHDs (PHD1-3) is necessary but sufficient to limit CD4(+)-regulatory T (T-reg) cell induction and stimulates CD8(+) T cell effector function. Interestingly, this resulted in the inhibition of local tolerance in the lung but reduced tumor colonization. In this perspective, we discuss the effect of targeting HIF-pathway proteins in tumor-associated cell lineages, their therapeutic prospective and possible pitfalls.
Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 III of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social >size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin.
Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli.
It has been suggested that dogs' ability to comprehend human pointing gestures evolved as a by-product of the socio-emotional changes associated with domestication. Given the large role played by the oxytocin system in socio-emotional processes, it is possible to hypothesize a role for oxytocin in modulating dogs' socio-communicative skills. Indeed, it has been shown that intranasal oxytocin enhances dogs' ability to use human pointing cues in an object choice task, a classic paradigm used to assess the ability to follow a pointing gesture. We further tested this hypothesis in another sample of dogs and replicated the above findings. We also provided a novel explanation to the above findings, suggesting that oxytocin released during human-dog interactions increases the positive expectations about human behaviour via emotion and reward processes and thus facilitates the interpretation of pointing as leading to positive events. Given the large and deep homology across mammals in the neural mechanisms involved in emotions, oxytocin could be involved in the acquisition of socio-communicative skills during human typical as well as pathological development.
Schizophrenia is a heterogeneous disorder in which psychiatric symptoms are classified into two general subgroups positive and negative symptoms. Current antipsychotic drugs are effective for treating positive symptoms, whereas negative symptoms are less responsive. Since the neuropeptide oxytocin (OT) has been shown to mediate social behavior in animals and humans, it has been used as an experimental therapeutic for treating schizophrenia and in particular negative symptoms which includes social deficits. Through eight randomized controlled trials (RCTs) and three meta-analyses, evidence for an effect of intranasal OT (IN-OT) has been inconsistent. We therefore conducted an updated meta-analysis that offers several advantages when compared to those done previously: (1) We used a multivariate analysis which allows for comparisons between symptoms and accounts for correlations between symptoms; (2) We controlled for baseline scores; (3) We used a fully Bayesian framework that allows for assessment of evidence in favor of the null hypothesis using Bayes factors; and (4) We addressed inconsistencies in the primary studies and previous meta-analyses. Eight RCTs (n = 238) were included in the present study and we found that oxytocin did not improve any aspect of symptomology in schizophrenic patients and there was moderate evidence in favor of the null (no effect of oxytocin) for negative symptoms. Multivariate comparisons between symptom types revealed that oxytocin was not especially beneficial for treating negative symptoms. The effect size estimates were not moderated, publication bias was absent, and our estimates were robust to sensitivity analyses. These results suggest that IN-OT is not an effective therapeutic for schizophrenia. (C) 2016 Elsevier Ltd. All rights reserved.
The formation of the primary shell is a vital process in marine bivalves. Ocean acidification largely influences shell formation. It has been reported that enzymes involved in phenol oxidation, such as tyrosinase and phenoloxidases, participate in the formation of the periostracum. In the present study, we cloned a tyrosinase gene from Crassostrea angulata named Ca-tyrA1, and its potential function in early larval shell biogenesis was investigated. The Ca-tyrA1 gene has a full-length cDNA of 2430 bp in size, with an open reading frame of 1896 bp in size, which encodes a 631-amino acid protein that includes a 24-amino acid putative signal peptide. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that Ca-tyrA1 transcription mainly occurs at the trochophore stage, and the Ca-tyrA1 mRNA levels in the 3000 ppm treatment group were significantly upregulated in the early D-veliger larvae. WMISH and electron scanning microscopy analyses showed that the expression of Ca-tyrA1 occurs at the gastrula stage, thereby sustaining the early D-veliger larvae, and the shape of its signal is saddle-like, similar to that observed under an electron scanning microscope. Furthermore, the RNA interference has shown that the treatment group has a higher deformity rate than that of the control, thereby indicating that Ca-tyrA1 participates in the biogenesis of the primary shell. In conclusion, and our results indicate that Ca-tyrA1 plays a vital role in the formation of the larval shell and participates in the response to larval shell damages in Crassostrea angulata that were induced by ocean acidification. (C) 2017 Elsevier Inc. All rights reserved.
The double stranded small active RNA (saRNA)-p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322. The expression of P21 protein and p21 mRNA were measured using the Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA-322 on cancer cells was evaluated in vitro; and furthermore, a xenograft colorectal tumor mode in mice was established to estimate the tumor suppressing ability of p21-saRNA-322 in vivo. The results showed that in all three colorectal cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused apoptosis and cell cycle arrest at the G(0)/G(1). Furthermore, anti-proliferation effect, reduction of colonies formation and cell senescence were observed in p21-saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment significantly inhibited the HT-29 tumor growth and facilitated p21 activation in vivo. These results indicated that, p21-saRNA-322-induceded up-regulation of p21 might be a promising therapeutic option for the treatment of colorectal cancer.
P23k is a 23 kDa protein involved in sugar translocation in the scutellum of germinating barley seeds. The present study was carried out to provide the genomic characterization for P23k gene in terms of copy number, chromosome mapping, genetic mapping and expression analysis in germinating sculletum in two major Triticeae crops, barley and wheat, and their relatives. Southern blotting showed that a variable copy number with different restriction fragment sizes was found among 15 Hordeum accessions, while low copy number were found to be conserved in 23 Triticum and 3 Aegilops accessions. Genetic and physical mapping study identified that the P23k gene is duplicated in wild and cultivated barley on chromosomes 1H, 2H, and 3H, and further tandem duplication on chromosomes 1H and 3H. In contrast, the wheat P23k is located on chromosome 3A of durum wheat and at the distal portion of the long arms of 3A and 3D chromosomes of bread wheat. Northern blotting showed remarkably high accumulation of P23k transcript in the germinating scutellum in cultivated and wild barley, whereas very few or no accumulation was detected in diploid, tetraploid, and hexaploid wheat accessions. The present study suggests a simple scenario where the ancestral P23k is encoded on the distal portion of an ancestral chromosome of homoeologous chromosome 3. Beside of polyploidy, dispersed and tandem duplications could trigger generation of the P23k family in the Hordeum lineage, while an ancestral P23k has been conserved in homoeologous 3A and 3D chromosomes in the wheat lineage.
Mast cells (MCs) are long-lived resident cells known for their substantial role in antigen-induced anaphylaxis and other immunoglobulin E-mediated allergic reactions as well as tumor promotion. MCs' activation results in the release of pro-inflammatory factors such as histamine, tryptase, tumor necrosis factor or carboxypeptidase A stored in secretory granules. IgE-dependent hypersensitivity has been thought to be the major pathway mediating degranulation of mast cells, but the P2Y14 nucleotide receptor activated by UDP-glucose (UDPG) may also enhance this process. In this study we identified thymidine 5'-O-monophosphorothioate (TMPS) as a molecule inhibiting UDPG-induced degranulation in a rat mast cell line (RBL-2H3). Additionally, TMPS diminished UDPG-evoked intracellular calcium mobilization in a stable HEK293T cell line overexpressing the P2Y14 receptor. Therefore, we demonstrate that the use of thymidine 5'-O-monophosphorothioate might be a novel anti-inflammatory approach based on preventing mast cell activation.
Ependymomas are the third commonest paediatric central nervous system (CNS) tumour, accounting for 6-12% of brain tumours in children. The management of these tumours has seen considerable changes over the last two decades, leading to a significant improvement in outcomes. However, despite advances in neurosurgical, neuroimaging and postoperative adjuvant therapy, management of these tumours remain challenging, and recurrence occurs in over 50% of cases, particularly when complete resection is not achieved prior to conformal radiotherapy. To-date no chemotherapeutic regimen has proven to be of significant clinical benefit. Predicting tumour behaviour and defining robust correlates of disease outcome based on histopathology and clinical characteristics remains suboptimal. Paucity of cell lines, failure to develop ideal animal models of these tumours, have precluded better understanding of the oncogenic drivers, undermining development of targeted therapies. Over the last few years breakthrough in the understanding of the molecular biology, are now providing clues to therapeutic insights. It is clear that even with histopathological similarities, these are genetically heterogeneous tumours with diverse clinical outcomes. Rapid evolution of data based on genome-wide DNA methylation patterns, have now identified nine molecular subgroups in these tumours, across three anatomic compartments which include supratentorial (ST), posterior fossa (PF) and the spinal locations. More recently based on transcriptome profiling, two subgroups (group A and B) of PF ependymoma have been identified with distinct molecular, clinical characteristics and specific chromosomal aberrations. This review includes current management, evolving molecular biology and the shifting paradigm of treatment profile that targets molecular alterations in paediatric ependymoma. (C) 2016 Elsevier Ltd. All rights reserved.
Background: Suspected child physical abuse, sexual abuse and neglect are not uncommon presentations. As part of the assessment of these cases, a forensic medical history may be taken. This forensic history is used not only to determine the steps necessary to address the child's wellbeing but also to direct the forensic examination. Currently, there is no clear consensus on whether or not a forensic medical history should consistently be considered an integral element within the paediatric forensic evaluation. This study examines the value derived by the medical practitioner taking a forensic medical history rather than relying on hearsay evidence when a child presents for an assessment. Methods: A retrospective review of paediatric cases seen by the Victorian Forensic Paediatric Medical Service (VFPMS) between 2014 and 2015 was undertaken. 274 forensic case reports were reviewed and the data was entered into an Excel spread sheet and analysed using chi squared tests within STATA (R). Results: With increasing age of the child, a forensic medical history is significantly more likely to be taken. Additional information is made available to the medical practitioner what would otherwise have been provided if the medical practitioner relied only on the interview conducted by the police. Discrepancies observed between the official third parties (police or child protection) report of what a child has said and what the child says to the medical practitioner decrease with age, as do discrepancies observed between the child's version of events and a third party's (eg. parents, caregivers, friends) version of events. Conclusions: The study showed that by taking a forensic medical history from the child additional information can be obtained. Further, that there is a value in the examining medical practitioner taking a forensic medical history from children in cases of child physical and sexual abuse and neglect. (C) 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
The definitive treatment of paediatric femoral diaphyseal fractures remains controversial. Modalities of treatment vary mostly according to age, with fracture pattern and site having a lesser impact. Current evidence is reflective of this variation with most evidence cited by the American Academy of Orthopedic Surgeons being level 4 or 5. The authors present a review of the most up-to-date evidence relating to the treatment of these fractures in each age group. In an attempt to clarify the current trends, we have produced an algorithm for decision-making based on the experience from our own tertiary referral level 1 major trauma centre.
The negative affects of this violent occupationfear, threat, humiliationquell hope, setting limits on the potentials of political agency. This article documents the corporeality of the Occupation in Hebron, evoking the body as materially contingent to explore agential capacities within the delimiting affects of the violent sensorium. Drawing on fieldwork with Palestinian activists engaged in providing political tours of Hebron, I argue that by reappropriating the violent affects of occupation, this form of activism demonstrates agency that resists political depression. Theoretically, I argue further, at hand is an empirical account of the autonomy of affect giving rise to critical hope amid a sensorium of fear. The research presented, therefore, contributes to addressing a key question for resistance in Palestine (and beyond): how feara predominant affective register of contemporary politicsmight be harnessed towards (renewed) political agency and resistance to oppression.
The detection of biomarkers is of crucial importance in reducing the morbidity and mortality of complex diseases. Thus, there is a great desire to develop highly efficient and simple sensing methods to fulfill the different diagnostic and therapeutic purposes. Herein, using tumor suppressor p53 gene as model target DNA, we developed a novel palindromic fragment-incorporated molecular beacon (P-MB) that can perform multiple functions, including recognition element, signal reporter, polymerization template and primer. Upon specific hybridization with target DNA, P-MBs can interact with each other and are extended by polymerase without any additional probes. As a result, hybridized targets are peeled off from P-MBs and initiate the next round of reactions, leading to the unique strand displacement amplification (SDA). The newly-proposed enzymatic amplification displays the detection limit as low as 100 pM and excellent selectivity in distinguishing single-base mutation with the linear response range from 100 pM to 75 nM. This is the simplest SDA sensing system so far because of only involving one type of DNA probe. This impressive sensing paradigm is expected to provide new insight into developing new-type of DNA probes that hold tremendous potential with important applications in molecular biology research and clinical diagnosis.
Objectives: Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. Materials and methods: Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient (SCID) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20). Results: Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 (JNK3) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase (MAPK)/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68 ng/kg to 83 ng/kg) while no tumor regression occurred in control animals. Conclusions: These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.
Intergroup conflict is evident throughout the history of our species, ubiquitous across human societies, and considered crucial for the evolution of humans' large-scale cooperative nature. Like humans, chimpanzee societies exhibit intragroup coordination and coalitionary support during violent intergroup conflicts. In both species, cooperation among group members is essential for individuals to gain access to benefits from engaging in intergroup conflict. Studies suggest that a contributive mechanism regulating in-group cooperation during intergroup conflicts in humans involves the neuropeptide hormone oxytocin, known to influence trust, coordination, and social cognition, although evidence from natural settings is lacking. Here, applying a noninvasive method, we investigate oxytocinergic system involvement during natural intergroup conflicts in wild chimpanzees. We found that chimpanzees of both sexes had significantly higher urinary oxytocin levels immediately before and during intergroup conflict compared with controls. Also, elevated hormone levels were linked with greater cohesion during intergroup conflicts, rather than with the level of potential threat posed by rival groups, intragroup affiliative social interactions, or coordinated behavior alone. Thus, the oxytocinergic system, potentially engendering cohesion and cooperation when facing an out-group threat, may not be uniquely human but rather a mechanism with evolutionary roots shared by our last common ancestor with chimpanzees, likely expediting fitness gains during intergroup conflict.
The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas-complement interaction covers complex pro-and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting.
Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various human cancers. However, its expression and role in pancreatic cancer (PC) are not well understood. The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC. First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro. The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinoma patients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60-5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro. Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.
Objectives: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). Methods: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles. Results: Significantly better median survival times were found for high/moderate expression levels of hENT1 (27.9 vs 12.4 months, P = 0.001) and dCK (19.7 vs 10.5 months, P = 0.003), as well as low expression of RRM1 (23.4 vs 11.4 months, P = 0.027). A Cox proportional hazards model identified low expression of hENT1 (hazard ratio [HR], 3.38; 95% confidence intervals [CI], 2.28-10.50) and dCK (HR, 2.24; 95% CI, 1.63-3.39), and high/moderate levels of RRM1 (HR, 1.65; 95% CI, 1.23-2.45) as negative prognostic factors. Conclusions: Expression of hENT, RRM1, and dCK genes provides important prognostic information for PDAC patients treated with adjuvant gemcitabine.
We explored the expression and function of miR-181d (microRNA-181d) in human pancreatic cancer. Quantitative real-time polymerase chain reaction was used to probe miR-181d expression in both pancreatic cancer cell lines and human pancreatic carcinoma. Pancreatic cancer cell lines, PANC-1 and AsPC-1 cells, were engineered to stably downregulate endogenous miR-181d through lentiviral transduction. The mechanistic effects of miR-181d downregulation on pancreatic cancer development were tested by proliferation, migration, fluorouracil chemosensitivity assays in vitro, and explant assay in vivo. Possible miR-181d downstream gene, NKAIN2 (Na+/K+ transporting ATPase interacting 2), was tested by dual-luciferase activity assay and quantitative real-time polymerase chain reaction. Functional involvement of NKAIN2 in miR-181d-regulated pancreatic cancer development was tested by small interfering RNA-mediated NKAIN2 knockdown in miR-181d-downregulated PANC-1 and AsPC-1 cells. MiR-181d was upregulated in both pancreatic cancer cell lines and human pancreatic carcinoma. Lentivirus-induced miR-181d downregulation decreased pancreatic cancer proliferation, migration, and fluorouracil resistance in vitro and inhibited the growth of cancer explant in vivo. NKAIN2 was directly targeted by miR-181d in pancreatic cancer. Small interfering RNA-mediated NKAIN2 knockdown reversed the inhibition of miR-181d downregulation on pancreatic cancer development. MiR-181d is aberrantly overexpressed in pancreatic cancer. Inhibiting miR-181d may suppress pancreatic cancer development, possibly through the inverse regulation on NKAIN2.
Aims In cystic and solid pancreatic lesions, KRAS mutational status refines the diagnosis of uncertain endoscopic ultrasound (EUS) aspirates. This test should have a fast turnaround time and ideally be performed at the centre where the patient is diagnosed. The Idylla KRAS Mutation Test enables standardisation even in units without molecular expertise. Methods The Idylla test was designed for use with formalin-fixed paraffin-embedded (FFPE) sections. However, we directly pipetted 3 mu L (corresponding to 1/10th of a DNA preparation from the aspirate sample) in the cartridge, which was automatically run as if an FFPE sample had been inserted. The performance was compared with Sanger sequencing, Allele Specific Locked Nucleic Acid PCR (ASLNAqPCR), and 454 Next Generation Sequencing (454-NGS) in light of clinicopathological end points. Results Idylla yielded valid results in 49/52 (94.2%) cases, in 2h. A total of 18/49 cases showed mutation either in KRAS exon 2 (14/18) or in exon 3 (4/18). Idylla KRAS test had 100% specificity and a sensitivity (55.1%) higher than Sanger sequencing (41.3%) and identical to ASLNAqPCR (55.1%). When the low-abundant mutant allele (<5%) cases were excluded from the analysis, the Idylla KRAS Mutation Test clinical sensitivity increased to 61.9% approaching that of 454-NGS (66.6%). Conclusions This is the first study that applied the novel Idylla KRAS test to the clinical setting of pancreatic cancer. In particular, this system can be easily implemented in the routine assessment of pancreatic EUS-fine-needle aspiration-derived DNA samples to quickly provide information on KRAS mutational status to supplement cytological evaluation.
Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
Pancreatic lipase is a potential therapeutic target to treat diet-induced obesity in humans, as obesity-related diseases continue to be a global problem. Despite intensive research on finding potential inhibitors, very few compounds have been introduced to clinical studies. In this work, new chemical scaffold 1H-indene-(1,3,5,6)-tetrol was proposed using knowledge-based approach, and 36 inhibitors were derived by modifying its functional groups at different positions in scaffold. To explore binding affinity and interactions of ligands with protein, CDOCKER and AutoDock programs were used for molecular docking studies. Analyzing results of rigid and flexible docking algorithms, inhibitors C_12, C_24, and C_36 were selected based on different properties and high predicted binding affinities for further analysis. These three inhibitors have different moieties placed at different functional groups in scaffold, and to characterize structural rationales for inhibitory activities of compounds, molecular dynamics simulations were performed (500 nSec). It has been shown through simulations that two structural fragments (indene and indole) in inhibitor can be treated as isosteric structures and their position at binding cleft can be replaced by each other. Taking into account these information, two lines of inhibitors can further be developed, each line based on a different core scaffold, that is, indene/indole. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 765-778, 2016
Papaya (Carica papaya) is a relevant tropical crop and physico-chemical changes take place very quickly, as a consequence of activation of biochemical pathways by de nova synthesis of several proteins. Thus, in order to have information on the changes in gene expression in ripening papaya, transcripts from the pulp of unripe and ripe fruit were profiled by differential-display RT-PCR (DDRT-PCR). Seventy transcript derived fragments (TDFs) isolated from gels were re-amplified by PCR and differential expression of 40 papaya genes was confirmed by reverse northern blotting. Twenty-nine positively cloned TDFs were sequenced, and 17 were putatively identified by homology search. Ten of these genes were downregulated during ripening and UDP-glucose glucosyltransferase, alpha-2 importin, RNase L inhibitor-like protein, and a syntaxin protein were identified. Among the up-regulated genes there was a carboxylesterase, an integral membrane Yip1 family protein, a glycosyl hydrolase family-like protein and an endopolygalacturonase. Considering their relatedness to papaya quality, the fragments of genes potentially implicated in carbohydrate metabolism and pulp softening may be considered of interest for further studies. According to the results, differential display was a feasible approach to investigate differences in gene expression during fruit ripening, and can provide interesting information about those fruits whose genomic data is scarce, as is the case of papayas. (c) 2009 Elsevier B.V. All rights reserved.
The existing European Regulation (EC n(o) 51/2013) prohibits the use of animals meals in feedstuffs in order to prevent Bovine Spongiform Encephalopathy infection and diffusion, however the legislation is rapidly moving towards a partial lifting of the "feed ban" and the competent control organisms are urged to develop suitable analytical methods able to avoid food safety incidents related to animal origin products. The limitations of the official methods (i.e. light microscopy and Polymerase Chain Reaction) suggest exploring new analytic ways to get reliable results in a short time. The combination of spectroscopic techniques with optical microscopy allows the development of an individual particle method able to meet both selectivity and sensitivity requirements (0.1% w/w). A spectroscopic method based on Fourier Transform micro-Raman spectroscopy coupled with Discriminant Analysis is here presented. This approach could be very useful for in-situ applications, such as customs inspections, since it drastically reduces time and costs of analysis. (C) 2017 Published by Elsevier Ltd.
Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals. Among non-immune compromised adults, hPIV infection typically causes mild disease manifested as upper respiratory tract symptoms and is infrequently associated with severe croup or pneumonia. Moreover, hPIV infection may be associated with viral exacerbations of chronic airway diseases, asthma or COPD or chronic rhinosinusitis. In this review, we summarized the basic epidemiology and immunology of hPIVs and addressed the more recent data implicating the role of parainfluenza viruses in the exacerbation of chronic airway disorders.
Method for estimation of structural defects density over whole wafer area by parametric wafer map creation is considered. This technique allows fast and accurate estimation of defects density over wafer area and in wafer batch. Input offset voltage of operational amplifier (op-amp) is calculated as a function of structural defects density and an example of corresponding parametric map is shown. The opportunity to localize the origin of structural defects on technological route is discussed.
Avian paramyxoviruses (APMVs) have been reported from a wide variety of avian species around the world. Avian paramyxoviruses are economically significant because of the huge mortality and morbidity associated with it. Twelve different serotypes of APMV have been reported till date. Avian paramyxoviruses belong to the family Paramyxoviridae under genus Avulavirus. Newcastle disease virus (APMV-1) is the most characterized members among the APMV serotypes. Complete genome sequence of all twelve APMV serotypes has been published recently. In recent years, APMV-1 has attracted the virologists for its oncolytic activity and its use as a vaccine vector for both animals and humans. The recombinant APMV-based vaccine offers a pertinent choice for the construction of live attenuated vaccine due to its minimum recombination frequency, modular nature of transcription and lack of DNA phase during its replication. Although insufficient data are available regarding other APMV serotypes, our understanding about the APMV biology is expanding rapidly because of the availability of modern molecular biology tools and high-throughput complete genome sequencing.
Introduction: Although social cognition skills and biases are well-studied in paranoia, "mind perception" - perceiving the extent to which someone even possesses a thinking, feeling mind - is not. We sought to better characterise the profile of mind perception for individuals with paranoia. Methods: We examined links between mind perception and paranoia in a large (n = 890) subclinical sample. Participants completed measures of paranoia, schizotypy, mind perception, and dispositional empathy. These assessments were examined for their relationships to one another, as well as the possibility that mind perception partially mediates the relationship between paranoia and empathy. Results: Analyses revealed that increased paranoia was linked to less mind perception towards people. This distorted mind perception partially explained the link between paranoia and both perspective taking and empathic concern. Conclusions: In paranoia - and psychopathology more broadly understanding and addressing distorted mind perception may be one component of restoring social functioning.
Time-dependent diffusion equations with fractional Laplacian have received considerable attention in recent years, for which numerical methods play an important role because a simple and analytic solution is often unavailable. We analyze in this paper a parareal algorithm for this kind of problem, which realizes parallel-in-time computation. The algorithm is iterative and uses the 3rd-order SDIRK (singly diagonally implicit Runge-Kutta) method with a small step-size Delta t as the F-propagator and the implicit-explicit Euler method with a large step-size Delta T as the G-propagator. The two step-sizes satisfy Delta T/Delta t = J with J >= 2 being an integer. Using the implicit-explicit Euler method as the G-propagator potentially improves the parallel efficiency, but complicates the convergence analysis. By employing some technical analysis, we provide a sharp estimate of the convergence rate, which is independent of the mesh ratio J and the distribution of the eigenvalues of the coefficient matrix. An extension of the results to problems with time-periodic conditions is also given. Several numerical experiments are carried out to verify the theoretical results. (C) 2017 Elsevier Inc. All rights reserved.
Interleukin-9 is a cytokine classically related to type 2 immune responses whose cellular identity has been recently reevaluated to identify a new specialized T helper subset called Th9 and an innate source referred as innate lymphoid cell type 2. Over the past years, IL-9 has been associated with allergic responses, tumor immunology, and autoimmunity; however, in this review, we will specifically focus on the role of IL-9 and Th9 cells in the context of parasitic infections. We will summarize and discuss all the evidence relating IL-9 expression and function in parasitic infections with a particular emphasis in helminth infections, an important health issue in developing countries; we will also provide a general description and classification of parasites, the immune response and cellular compartments activated in this context, and its implications and future directions towards a complete understanding of this interesting new T helper subset and its potential therapeutic use.
Background: Leishmania (Viannia) braziliensis is the main etiological agent of tegumentary leishmaniasis in the Americas. Parasite molecular diversity and host immune status contribute to extensive variations in its clinical presentation within endemic areas of Brazil. Pentavalent antimonials have been used for more than 60 years as the first-line drug for all cases, despite the potential for severe side effects and refractoriness. In Rio de Janeiro, Brazil, most L. (V.) braziliensis infections are benign with a scarcity of parasites, although metastasis and refractory infections can arise. In this scenario, the use of novel molecular tools can be useful for diagnosis and to assess tissue parasitism, and is of benefit to clinical and therapeutic management. Methods: In this study, parasite load was assessed by real-time PCR based on the leishmanial small subunit ribosomal RNA gene. Results and conclusion: The data revealed a tendency to higher tissue parasitism in the skin compared to mucous lesion sites and a reduction with disease progression. Parasite load was lower in poor compared to good responders to antimonials, and was also reduced in recurrent lesions compared to primary ones. However, parasite load became higher with sequential relapses, pointing to an immune system inability to control the infection. Therefore the parasite burden does not seem to be a good predictor of disease progression. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Parasitic worms of the genus Trichinella (phylum Nematoda; class Enoplea) represent a complex of at least twelve taxa that infect a range of different host animals, including humans, around the world. They are foodborne, intracellular nematodes, and their life cycles differ substantially from those of other nematodes. The recent characterization of the genomes and transcriptomes of all twelve recognized taxa of Trichinella now allows, for the first time, detailed studies of their molecular biology. In the present study, we defined, curated, and compared the protein kinase complements (kinomes) of Trichinella spiralis and T. pseudospiralis using an integrated bioinformatic workflow employing transcriptomic and genomic data sets. We examined how variation in the kinome might link to unique aspects of Trichinella morphology, biology, and evolution. Furthermore, we utilized in silico structural modeling to discover and characterize a novel, MOS-like kinase with an unusual, previously undescribed N-terminal domain. Taken together, the present findings provide a basis for comparative investigations of nematode kinomes, and might facilitate the identification of Enoplea-specific intervention and diagnostic targets. Importantly, the in silico modeling approach assessed here provides an exciting prospect of being able to identify and classify currently unknown (orphan) kinases, as a foundation for their subsequent structural and functional investigation.
Arctic wildlife can be exposed to high mercury (Hg) levels, and are also naturally exposed to gastrointestinal parasites that can reduce condition and negatively affect reproductive output and/or survival in similar ways. Importantly, both Hg and parasites are increasing in wildlife in some Arctic regions. We studied the northern common eider duck (Somateria mollissima) to explore how Hg in association with both natural levels and experimentally reduced parasitic infections, affect reproduction and survival. Female eiders were measured, banded, and blood sampled to determine blood Hg burdens, prior to breeding. Propensity to nest, clutch size, nest survival, nest attendance, and return rates were assessed in relation to both Hg burden and parasite treatment. Neither reproduction nor return rates of females varied with Hg concentrations, but females arriving late to the colony, or in low body condition, showed increased nesting propensity when given the anti-parasite treatment as compared to placebo treatment. Our results suggest that parasites can play a critical role in decisions to invest in avian breeding annually, particularly among individuals with a late onset to breeding, and in poor condition. Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved.
Johne's disease, caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic wasting disease of ruminants. Hallmark symptoms of clinical Johne's disease include diarrhea, progressive weight loss, and premature death; symptoms due largely to chronic inflammation in the small intestine. MAP colonizes resident macrophages within the ileum of the small intestine, subsequently establishing a persistent infection in the host. It has been proposed that regulatory T cells may play a role in the progression of Johne's disease, either through promotion of tolerance to MAP or via a loss in homeostasis that subsequently allows widespread inflammation. In this report, we evaluated the presence of Tregs, as well as other immune parameters, in the ileum and draining lymph nodes of MAP associated lesions. A lesion classification scheme was developed to categorize severity of MAP-induced lesions within infected tissues and subsequently regulatory T cell presence and overall immune activity were assessed corresponding to lesions of varying severity, in comparison to tissues from healthy control animals. Our results revealed a relationship between animal health and overall lesion severity within the infected tissues, as well as a relationship between bacterial burden and severity of pathology. Regulatory T cell abundance was shown to decrease with increasing lesion severity. Within the ileum, the expression of many Th1, Th2, and Treg-associated genes increased in mild lesions and decreased in severe lesions, whereas in the lymph nodes the expression of these genes tended to increase with increasing lesion severity. Based on our results, we conclude that a local loss of T cell (including Treg) activity occurs within severe Heal lesions associated with MAP, resulting in a loss of homeostasis that ultimately leads to the progression of clinical Johne's disease. (C) 2016 Elsevier B.V. All rights reserved.
Negative parental attributions are related to parent and family stressors and are thought to be important predictors of subsequent disciplinary actions and, potentially, abusive parenting. We examined if negative parental attributions mediate the relation between daily stressors (i.e., low SES, parenting stress, partner-related stress) parents' own history of child maltreatment, and harsh and abusive parenting. Mothers (n = 53) completed a computerized attribution task and reported on daily stressors, their own history of child maltreatment and their discipline strategies. Mothers' negative parental attributions mediated the association between parenting stress (but not the other stressors) and harsh and abusive discipline. These finding implicate that interventions to decrease (the risk of) child abuse should not only focus on reducing abuse-related stressors, but also target negative parental attributions. (C) 2016 Elsevier Ltd. All rights reserved.
Parental depressive symptoms are an important public health concern because they have been linked, in numerous previous studies, to negative parenting behaviors including dysfunctional discipline and child abuse and neglect. Taking this into consideration, parental depressive symptoms warrant particular attention among families with child maltreatment allegations-a group at high risk of dysfunctional discipline and future physical abuse. The current study sought to examine relations between parental depressive symptoms and dysfunctional discipline in an ethnically diverse sample of 234 families who were referred for psychological services due to concerns of child maltreatment. Referrals were made by school, medical, or child welfare personnel. 59.8 % of children were male and the average age was 7.05 years. Results indicated that parental depressive symptoms were significantly correlated with dysfunctional discipline including laxness, over-reactivity, and hostility. However, all three relations lost statistical significance after controlling for parental stress. The findings of this study suggest that well-documented relations between parental depression and negative parenting behavior may be driven by elevated parental stress rather than reflecting risks uniquely associated with depressive pathology.
Family structure as a risk for child maltreatment has long been viewed as a static state in the child maltreatment literature. Drawing on data from the Fragile Families and Child Wellbeing Study, the author uses a series of individual fixed-effects models to investigate whether particular types of relationship transitions over children's first decade of life are associated with increased risk for maternal and paternal child abuse and maternal neglect. Findings question and confirm a number of long-standing theoretical and empirical findings from the child maltreatment literature. Results indicate that transitions to being single are associated with increased risk for maternal child abuse and neglect. In addition, the frequency and severity of paternal harsh parenting may be closely linked with the nature of fathers' relationship transitions. Last, results largely do not provide support for the theory that the presence of social (nonbiological) fathers increases mothers' risk for engaging in child abuse or neglect.
Background Parenting by people with intellectual disability is attracting increasing attention, and policymakers and service providers require empirical evidence to develop sound policy and service responses. The purpose of the study was to identify prevalence and demographic data on parents with ID in Australia compared with parents with other disabilities and the population of parents without disability.Method The Survey of Disability, Ageing and Carers, 2009, was identified as the most suitable survey, and design-weighted analysis was performed.Results An estimated 0.41% of Australian parents had intellectual disability, equating to 17,000 parents with ID. Parents with ID were more likely to have only 1 child and to reside outside a capital city compared with parents without disability.Conclusions These findings provide benchmark data for monitoring, over time, the prevalence of parents with ID and point to policy and service responses for parents with only 1 child and for those in outer urban, regional, and rural areas of Australia.
Introduction: Depressive symptoms are very common in patients with Parkinson's disease (PD) and have a significant impact on the quality of life. Methods: The present study analyzed the correlations between over-time changes in depressive symptoms and gray matter parameters of cortical thickness and subcortical volumes in non-demented PD patients. Results: A significant correlation was observed, between increased scores for depression over time and lower cortical thickness over time in the right temporo-parietal junction, right occipital medial region, right dorsolateral prefrontal cortex, right posterior cingulate region, left middle temporal as well as left supplementary motor area. Furthermore, the presence of depressive symptoms at baseline predicted increased cortical thinning over time in the left middle temporal, left anterior cingulate, right posterior cingulate and right parahippocampal cortices. Finally, a statistically significant negative correlation has been revealed between the thalamus' volume changes over time and the change in depressive symptoms scores. All other analyzed subcortical structures didn't reveal any significant correlations. Conclusion: These results suggest that depressive symptoms in PD patients are associated with gray matter cortical thinning and thalamus volume shrinkage over time and higher scores of depressive symptoms at baseline correlate with a higher rate of cortical thinning longitudinally. The present study highlights the importance of addressing depressive symptoms in PD patients early in the disease. (C) 2016 Elsevier Inc. All rights reserved.
Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.
This paper discusses counterfactual scripting to critically inquire and give form to Participatory Design (PD) processes in an age of ubiquitous participation. In its often superficial application in various societal domains, the processes and instruments for participation are often cut loose from their political context. The stories of what has happened in a PD process are told through a clear storyline that develops logically via different design moves towards a well-defined plot; leaving out any alternative narratives. Inspired by counterfactual history, we reject this teleological perspective and explore counterfactual scripting as a way to give renewed attention to the political context in PD. We do this by giving form to the design process as a pluralistic process that not only focuses on the future, but creates alternatives for the past to speculate about the future. We evaluate counterfactual thinking in a participatory architecture and urban planning process.
The advent of nanotechnology has increasingly influenced all research fields -covering also the food area. The awareness of the peculiar properties of matter at the nanoscale level has stimulated investigations down to submicron (less than 1 mu m) and nanosize (1-100 nm). The appealing possibility to evidence interactions among nanostructures in foodstuff is strictly related to both functional and organoleptic properties of food. Besides the most common techniques known well before the advent of nanotechnology, such as light scattering and electron microscopy, Nanoparticle Tracking Analysis (NTA) has come up almost ten years ago. Although the technique is new, the basic principles rely on a well consolidated theoretical knowledge, such as the Stokes-Einstein and the dynamic scattering equations. The aim of this review is to provide an overview of the techniques commonly used to characterize food structures focusing the attention to NTA. Therefore, a literature survey is provided taking into account the many different situations that can occur in food products, spanning from emulsions and protein aggregates to individual nanoparticles, either added to improve food properties or derived from food contamination. A comparison of NTA with the classical dynamic light scattering (DLS) is also included, focusing the attention on the strength and weakness of both techniques. The current increasing interest in NTA is foreseen to expand its use also in food area, by stimulating research in the perspective of a conscious food managing approach. (C) 2016 Elsevier Ltd. All rights reserved.
Ambient particulate matter (PM) is known to induce inflammation in the respiratory tract of exposed subjects. The aim of the present study was to detect, in bronchial epithelial cells, candidate inflammatory genes exhibiting transcriptional modifications following urban PM2.5 exposure. Paris urban PM2.5 sampled either at a curbside or a background station in winter and in summer was tested in comparison with diesel exhaust particles (DEP) at 10 microg/cm(2) on human bronchial epithelial (16-HBE) cells (18 h of exposure). The gene profiling study performed using a 375 cDNA cytokine expression array highlighted the differential expression of certain genes, three of which were selected as genes of interest: the IL-1 alpha cytokine, the GRO-alpha chemokine, and amphiregulin, a ligand of the EGF receptor. Their increased expression was confirmed by RT-PCR and/or by Northern blotting in bronchial epithelial cells. In the culture medium of particle-treated cultures, increased release of GRO-alpha and amphiregulin was shown. The particle component responsible for protein release varied for the two genes. The organic extract seemed to be mainly involved in amphiregulin expression and secretion, whereas both the aqueous and organic extracts induced GRO-alpha release. In conclusion, in bronchial epithelial cells, Paris PM2.5 increased mRNA and protein expression of GRO-alpha and AR involved in the chemoattraction process and bronchial remodeling, respectively.
Positive energy residential buildings are houses that generate more energy from renewable sources than they consume while maintaining appropriate thermal comfort levels. However, their design, construction and operation present several critical challenges. In particular, the considerable load reductions are not always compatible with the increased level of comfort expected in modern houses. Tropical climates, meanwhile, should be more amenable to the implementation of positive energy houses for two reasons. Firstly, negligible heating is generally required as compared to colder climates, where the heating energy requirements are considerable. Then, renewable energy resources are usually abundant in tropical climates. This paper investigates the feasibility of positive energy residential buildings in the tropical island of Mauritius. A baseline model representing a typical Mauritian house is designed using DesignBuilder software. The energy efficiency of the model is then optimised by investigating a whole range of passive building design strategies, many of them adapted from vernacular architecture. Results reveal that the application of passive strategies such as shading, insulation and natural ventilation have precluded the need for artificial cooling and ventilation in the positive energy (PE) house. The resulting electricity consumption of the house decreases from 24.14 to 14.30 kWh/m(2)/year. A 1.2 kW photovoltaic system provides the most cost-effective solution to exceed the annual electricity requirements of the house.
Objective: The aim of this study is to trace the possible relations between the hygienic status of slicing utensils and the microbiological quality of pastrami. Study Design: A total of 75 pastrami retail markets were visited in Kayseri, Turkey, where the pastrami (a ready-to-eat meat product) is commonly produced and consumed. Sliced pastrami, the cutting board and knife surface swabs were collected from each pastrami retail point to trace possible sources of contamination. Methods: Samples were analysed for the presence of total viable counts (TVC), total coliforms, Escherichia coli, members of Enterobacteriaceae, Staphylococcus aureus and Listeria spp. In addition, pastrami samples were analysed for sulphite-reducing Clostridium spp. and Toxoplasma gondii. Results: When compared with the target values of related literatures, a total of 6 (8%) pastrami samples were found unsatisfactory as a result of TVC (5.3%), Enterobacteriaceae (5.3%), E. coli (2.6%), S. aureus (2.6%), Listeria spp. (2.6%) and Listeria monocytogenes (1.3%) contaminations. No T. gondii positivity was observed among the pastrami samples. None of the cutting board and knife surface swabs were found to harbour TVC level >10(3) cfu/cm(2), E. coli and L. monocytogenes. For the total coliforms, 7 (9.3%) and 5 (6.6%) of cutting board and knife surface swabs were found to exceed the target value (<2.5 cfu/cm(2)), respectively. No statistically significant correlation was detected between the organisms on pastrami and slicing utensils indicating that pastrami were not cross-contaminated by the contact surfaces. Conclusion: More emphasis needs to be placed for training of food handlers and to apply good hygienic practices at the point of pastrami sale. The conditions at retail points must be monitored and inspections should be tightened to protect public health. (C) 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Pogostemon cablin (Blanco) Benth. is an important medicinal plant; however, its molecular biology remains largely unexplored. Here, we report the results of whole transcriptome-wide analyses of P. cablin using next-generation sequencing technology. In the present study, we generated 108,996 unigenes using RNA sequencing data. Among these unigenes, 65,536 were annotated in the NR database. There were 40,670 intact open reading frames (ORFs), which accounted for 69 % of the 58,820 predicted ORFs, demonstrating that our assembled transcriptome was of high quality. Gene expression levels in the leaf and stem were quantified, and 18,481 unigenes (17 %) were determined to be significantly differentially expressed. The patchouli alcohol (PA) and pogostone (PO) metabolic pathway of P. cablin was also reconstructed, and among the 17 putative homologs to PA and PO biosynthesis-related genes, seven were significantly upregulated in the stems, and three genes were significantly upregulated in the leaves. The correlation between the essential oil contents of P. cablin and the potentially pivotal genes for PA and PO production were identified. Considering that the contents of PA and PO in leaves and stems are markedly different in the same plant and we did not detect any pattern in the expression levels of candidate genes between leaves and stems, we speculate that after the biosynthesis, more PA probably accumulates in the leaves, and more PO in the stems of P. cablin. The transcriptome of P. cabin will facilitate further researches on the molecular system biology of the Pogostemon genus, as well as the in-depth studyies of PA and PO biosynthesis and its potential applications for genetic engineering.
Infected organisms can resist or tolerate infection, with tolerance of infection defined as minimizing per-parasite reductions in fitness. Although tolerance is well studied in plants, researchers have only begun to probe the mechanisms and transmission consequences of tolerance in animals. Here we suggest that research on tolerance in animals would benefit from explicitly incorporating behavior as a component of tolerance, given the importance of behavior for host fitness and parasite transmission. We propose two distinct manifestations of tolerance in animals: tissue-specific tolerance, which minimizes fitness losses due to tissue damage during infection, and behavioral tolerance, which minimizes fitness losses by maintaining normal, fitness-enhancing behaviors during infection. Here we briefly review one set of potential immune mechanisms underlying both responses in vertebrate animals: inflammation and its associated signaling molecules. Inflammatory responses, including broadly effective resistance mechanisms like the production of reactive oxygen species, can incur severe costs in terms of damage to a host's own tissues, thereby reducing tissue-specific tolerance. In addition, signaling molecules involved in these responses facilitate stereotypical behavioral changes during infection, which include lethargy and anorexia, reducing normal behaviors and behavioral tolerance. We consider how tissue-specific and behavioral tolerance may vary independently or in conjunction and outline potential consequences of such covariation for the transmission of infectious diseases. We put forward the distinction between tissue-specific and behavioral tolerance not as a definitive framework, but to help stimulate and broaden future research by considering animal behavior as intimately linked to the mechanisms and consequences of tolerance in animals. (c) 2016 Elsevier Inc. All rights reserved.
Objective: Advanced statistical tools have created the opportunity to systematically examine the effect of early trajectories in predictors of therapeutic change, such as early alliance development patterns, on outcome. To date, however, these methods have been used almost exclusively to examine the effect of the development of early symptoms on later ones. Development patterns of alliance early in treatment, and their association with treatment outcome, have received much theoretical attention, but few systematic examinations have been conducted so far. Method: We integrated exploratory cluster analysis with the accumulated theoretical and empirical knowledge on patterns of alliance development to identify distinct patterns of early alliance development across the 1st 4 sessions of treatment in a sample of 166 patients receiving psychotherapy. Results: Three patterns of early alliance development were identified: early gradual strengthening, early repaired rupture, and early unrepaired rupture. The gradual strengthening and the repaired rupture patterns early in treatment predicted alliance strengthening later in treatment, whereas the unrepaired rupture pattern early in treatment predicted alliance stability later in treatment. The effect of early alliance development patterns on treatment outcome was moderated by pretreatment interpersonal problems: For patients with better interpersonal functioning at intake, the gradual strengthening and the repaired rupture patterns showed better outcomes, whereas for those with poorer interpersonal functioning at intake, the early unrepaired rupture pattern showed better outcomes. Conclusions: Findings suggest that early alliance development patterns affect treatment process and outcome.
Introduction: Pneumocystis jirovecii is a ubiquitous fungus, which causes pneumonia in humans. Diagnosis was hampered by the inability to culture the organism, and based on microscopic examination of respiratory samples or clinical presentation. New assays can assist in the diagnosis and even aid with the emergence of resistant infections. Areas covered: This manuscript will provide background information on Pneumocystis pneumonia (PcP). Diagnosis, from radiological to non-microbiological (e.g. Lactate dehydrogenase) and microbiological investigations (Microscopy, PCR, beta-D-Glucan) will be discussed. Recommendations on prophylactic and therapeutic management will be covered. Expert commentary: PcP diagnosis using microscopy is far from optimal and false negatives will occur. With an incidence of 1% or less, the pre-test probability of not having PcP is 99% and testing is suited to excluding disease. Microscopy provides a high degree of diagnostic confidence but it is not infallible, and its lower sensitivity limits its application. Newer diagnostics (PCR, beta-D-Glucan) can aid management and improve performance when testing less invasive specimens, such as upper respiratory samples or blood, alleviating clinical pressure. Combination testing may allow PcP to be both diagnosed and excluded, and molecular testing can assist in the detection of emerging resistant PcP.
Diazotrophs are one of the most important microbial communities which play a key role in rhizosphere to enhance plant growth-promotion by supplying fixed nitrogen to the plants. The aim of present study was to analyze the frequency and diversity of diazotrophs in the rhizospheres of five genotypes of aromatic rice (Oryza sativa cultivars Nua Kalajeera, Ketekijoha, Nua Desheri, Nua Chandan and Kala Namak) grown in ten years old long-term aromatic rice-rice (LARR) cropping system under sub-humid tropical condition. In this study, it was observed that very less frequency of active diazotrophs (0-14.28%) in the rhizosphere of aromatic rice genotypes based on polymerase chain reaction (PCR)-based nifH gene amplification, dot blot hybridization and acetylene reduction assay (ARA). The following five isolates (B10, B12, B29, BK16, NKR16) from rhizosphere of aromatic rice and the reference strain Azospirillum brasilence showed nifH amplification and positive signal for dot blot. None of these isolates showed positive in ARA test except A. brasilence. Basic local alighnment search tool (BLAST) homology of nifH sequences of B10, B12, B29, BK16 and NKR16 matched with Gluconoacetobacter diazotrophicus, Pseudomonas stutzeri, Klebsiella sp., Klebsiella pneumoniae and Sinorhizobium meliloti, respectively. Whereas, isolates B10, B12 and BK16 were identified as Bacillus cereus, Enterobacter sp., and Lysinibacillus sp., respectively based on 16S-rDNA sequencing. As per nifH sequences, these diazotrophs (B10, B12, B29, BK16, NKR16) fall under alpha and gamma-proteobacter, whereas 16S-rDNA sequences revealed that they belonged to firmicutes and gamma-proteobacter. Multiple sequence alignment of nifH gene sequences showed wider variation among diazotrophs, however 3D structure of NifH protein revealed the less diversity among isolates. Moreover, restriction digestion of 16S-rDNA using tetracutters (Mspl, Mbol and HaeIII) deciphered a unique pattern among small population of diazotrophs. The results of this finding provided an interesting data and novel information of diazotroph diversity in LARR cropping system. Finally, the present study indicated that the continuous application of high dose of inorganic nitrogenous fertilizers (nitrogen at the rate of 60 & 80 kg N ha(-1) year(-1) wet and dry seasons, respectively) limit the frequency and diversity of rhizospheric diazotrophs in the LARR cropping system. (C) 2017 Elsevier B.V. All rights reserved.
Molecular diagnosis of congenital toxoplasmosis or disseminated toxoplasmosis is based mainly on PCR. The repeated DNA element rep529 has become the main DNA target used in most PCR methods, whether laboratory developed or commercial. In this multicenter study, we evaluated the Toxoplasma ELITe MGB (Elitech) commercial kit by comparison with three reference quantitative PCR assays (RAs) used routinely in three proficient laboratories of the French National Reference Center for Toxoplasmosis network, using Toxoplasma calibrated suspensions diluted to obtain a range of concentrations from 0.1 to 10,000 parasites/ml. These suspensions were extracted with either the DNA extraction kit (EXTRAblood; Elitech) recommended by the manufacturer or the QIAamp DNA minikit (Qiagen). The Toxoplasma ELITe MGB assay was also evaluated on a panel of 128 clinical samples, including 56 amniotic fluid samples, 55 placenta samples, and various other samples, of which 95 originated from patients with proven toxoplasmosis. The ELITe MGB assay amplified low-concentration replicates (<10 parasites/ml) of calibrated suspensions less frequently than the RAs of 2/3 laboratories. Additionally, the combination of EXTRA blood and Toxoplasma ELITe MGB yielded poorer sensitivity than the combination of QIAamp DNA minikit and ELITe MGB for low parasite concentrations (P < 0.001 for 1 parasite/ml). On clinical samples, the sensitivity and the specificity of the commercial assay were 89% and 100%, respectively. The sensitivity ranged from 79% (placenta samples) to 100% (amniotic fluid samples). Overall, this study shows that the Toxo-plasma ELITe MGB assay is suitable for the diagnosis of toxoplasmosis from non-cell-rich or non-hemoglobin-rich samples and that the EXTRAblood kit is not optimal.
Immunotherapy has recently emerged as the fourth pillar of cancer treatment, joining surgery, radiation, and chemotherapy. While early immunotherapies focused on accelerating T-cell activity, current immune-checkpoint inhibitors take the brakes off the anti-tumor immune responses. Successful clinical trials with PD-1 monoclonal antibodies and other immune-checkpoint inhibitors have opened new avenues in cancer immunology. However, the failure of a large subset of cancer patients to respond to these new immunotherapies has led to intensified research on combination therapies and predictive biomarkers. Here we summarize the development of PD-1-blockade immunotherapy and current issues in its clinical use.
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (T-Regs). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1: PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.
The Addendum Guidelines for the Prevention of Peanut Allergy in the United States-Report of the NIAID-Sponsored Expert Panel were developed to build on previous food allergy guidelines after several key studies demonstrated the benefit of early introduction of allergenic foods. These landmark studies including the Learning Early about Peanut ( LEAP), LEAP-On and Enquiring about Tolerance trials created a paradigm shift in food allergy prevention. The "take home" messages of this guideline include that peanut should be introduced early in the first year of life, and for the majority of infants, peanut can be introduced at home. The only group of infants for which medical assessment is recommended is those with severe eczema, egg allergy or both. Here we summarize the Guideline recommendations, endorsed by the Canadian Society of Allergy and Clinical Immunology, and highlight important aspects relevant to Canadian practitioners.
The present review examines how macromolecular structure and functional groups of pectin affect its functionality with particular focus on its interfacial activity. We venture into a description of the particularly complex pectin structure and describe the major building blocks and their properties. In the following section, the role of each structural parameter is discussed with particular attention to protein, degree of acetylation and methylation, molecular weight, and branching. Finally, we discuss how modification of the extraction conditions could be tailored to obtain pectin with the desired emulsification properties. It is proposed that pectin with protein content in the range of 3%, with degree of acetylation greater than 10%, molecular weight between 100 and 200 x 10(3) g mol(-1) and enriched in RG-I segments is more likely to perform well as an emulsifier. To tailor such a structure, an aqueous extraction protocol with low pH values (between 2.5 and 3.5) with a strong monoprotic acid (e.g., HCl) and one-step solvent precipitation should be selected. The proposed set of extraction conditions could be used as a first step towards rational design of pectin with desirable interfacial functionality. (C) 2016 Elsevier Ltd. All rights reserved.
Objective: Traumatic stressors, including child abuse and/or interpersonal violence over a woman's lifecourse, can affect the health of her children. This study examines the associations between maternal lifetime interpersonal trauma (IPT) and children's asthma by age 6 years (n = 857). Methods: Pregnant women completed the Revised Conflict Tactics Scale; IPT exposure was categorized as unexposed (55%), early (childhood and/or teen years only, 25%), late (adulthood and/or index pregnancy, 7%), and chronic (early and late, 13%). Clinician-diagnosed asthma in children was reported by mothers at each follow-up visit until the child reached age 6 years. We examined the effects of maternal IPT categories and child's asthma using logistic regression. Using structural equation models, we also examined indirect relationships between maternal chronic IPT and child asthma operating through active asthma in pregnancy, prepregnancy BMI, prenatal smoking, and/or increased exposure to other adverse life events or environmental toxins prenatally. Effect modification by the child's sex was examined. Results: Mothers were primarily Hispanic (55%) or black (30%) with less than high school education (62%). In logistic regression models, chronic maternal IPT (compared with unexposed) was associated with asthma in boys (odds ratio = 2.87, 95% confidence interval = 1.48-5.57) but not girls (odds ratio = 0.69, 95% confidence interval = 0.23-2.12; p(interaction) = .042). In structural equation models, chronic IPT was associated with maternal active asthma in pregnancy (beta = 0.59, p < .001), maternal active asthma was associated with children's asthma (beta = 0.20, p = .009), and the total indirect effect for this path was significant (beta = 0.12, p = .031). Associations were most evident among boys. Conclusions: Mothers' history of chronic IPT was associated with asthma in boys. This association was mediated through active maternal asthma in pregnancy.
Background: Probiotic supplementation to women during pregnancy and lactation can modulate breast milk composition, with immune benefits being transferred to their infants. Aim: The aim of the study was to evaluate the effect of high-dose probiotic supplementation to women during late pregnancy and lactation on cytokine profile and secretory IgA (sIgA) in breast milk and thus to study if differences in breast milk composition can affect lactoferrin and sIgA levels in stool samples of newborns. The safety of maternal probiotic administration on neonatal growth pattern and gastrointestinal symptoms were also evaluated. Methods: In a double-blind, placebo-controlled, randomized trial, 66 women took either the probiotic (n = 33) or a placebo (n = 33) daily. Levels of interleukins (IL-6, IL-10 and IL-1 beta), transforming growth factor-beta 1 (TGF-beta 1), and sIgA in breast milk; and the level of sIgA and lactoferrin in newborn stool samples were analyzed at birth and then again at one month of life. Antropometrical evaluation and analysis of gastrointestinal events in newborns was also performed. Results: Probiotic maternal consumption had a significant impact on IL6 mean values in colostrum and on IL10 and TGF-beta 1 mean values in mature breast milk. Fecal sIgA mean values were higher in newborns whose mothers took the probiotic product than in the control group. Probiotic maternal supplementation seems to decrease incidence of infantile colic and regurgitation in infants. Conclusion: High-dose multi-strain probiotic administration to women during pregnancy influences breast milk cytokines pattern and sIgA production in newborns, and seems to improve gastrointestinal functional symptoms in infants.
Background: Although fibrosis seems to be prognostic for adverse outcomes in adults with idiopathic dilated cardiomyopathy (IDC), little is known about the prevalence and development of fibrosis in pediatric IDC hearts. We hypothesized that there is less activation of fibrosis at a molecular level in pediatric IDC hearts than in failing adult hearts. Methods and Results: Pediatric hearts were analyzed histologically to determine the prevalence of fibrosis. Left ventricular tissue from adult and pediatric IDC hearts and adult and pediatric nonfailing (NF) hearts were subjected to quantitative reverse-transcription polymerase chain reaction to study the expression of important mRNAs that affect fibrosis. We found age-specific differences between IDC and NF hearts in the regulation of noncoding galectin-3, Corin, matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitor of metalloproteinase (TIMP) 2, and TIMP-3. We also found markers that were similarly altered in both adult and pediatric IDC hearts (interleukin-1 receptor like 1 receptor, TIMP-1, and TIMP-4). Finally, microRNAs 29a-c were significantly decreased in the pediatric IDC patients. Conclusions: Pediatric IDC patients demonstrate age-specific differences in the molecular pathways implicated in fibrosis in the adult heart. At the ultrastructural level the unique gene expression pattern appears to limit fibrosis in the failing pediatric heart.
Objectives Childhood obesity prevention and treatment depends, in part, on parents acting as agents of change for their children. Our objective was to measure the associations between parenting self-efficacy, parent depressive symptoms, and preschool child behaviors that support healthy growth. Methods We performed a cross-sectional analysis of baseline data from a randomized controlled trial. Parenting self-efficacy was measured using a 5-item version of the Parenting Sense of Competence (PSOC-5) scale (alpha= 0.8). Parent depressive symptoms were measured using the Center for Epidemiological Studies-Depression (CESD) scale. Child outcomes included diet (24 h diet recall), physical activity (accelerometry), sleep (parent-report), and media use during meals (parent-report). We performed separate multiple linear regressions for each outcome controlling for other covariates. Results The sample consisted of 601 parent-child pairs. Median child age was 4.3 (IQR 3.6-5.1) years; median child body mass index (BMI) percentile was 79.1% (IQR 66.8-88.5%); 90% of children were Hispanic/Latino, and 6% of children were non-Hispanic Black. Median parent age was 31.5 (IQR 27.6-36.0) years; 22% of parents met criteria for depression. Parenting self-efficacy (median PSOC-5 25; IQR 24-28) was negatively correlated with depressive symptoms (rho = -0.16; p < 0.001). In adjusted models, higher parenting self-efficacy was associated with duration of child's sleep and fewer meals eaten in front of a TV (p < 0.001). There was a significant interaction of parenting self-efficacy and parental depressive symptoms on child sleep duration (p < 0.001). Parenting self-efficacy and depressive symptoms were not significantly associated with child physical activity or child diet. Conclusions In this minority population, higher parenting self-efficacy was associated with longer child sleep and fewer meals in front the TV, but parent depressive symptoms mitigated that protective effect for child sleep duration.
Over 700,000 children are victims of abuse and neglect each year in the United States. Effective screening programs that entail broad capture of suspected non:accidental trauma (NAT) may help to identify sentinel injuries. This can facilitate earlier detection and psychosocial interventions in hopes of decreasing recurrent NAT, which confers a higher mortality rate. The purpose of this article is to outline essential components of hospital-based NAT screening tools and highlight existing programs. In general, these tools should include several components: education sessions for healthcare providers on how to identify signs of NAT, automated notes or checklists within the electronic medical record to prompt specialty referrals, and a multidisciplinary team of experts that can address the needs of these children in the acute care setting. (C) 2017 Elsevier Inc. All rights reserved.
Introduction: Pediatric burns due to abuse are unfortunately relatively common, accounting for 5.8-8.8% of all cases of abuse annually. Our goal was to evaluate our 36-year experience in the evaluation and management of the victims of abuse in the North Texas area. Methods: A prospectively maintained database containing records on all admissions from 1974 through 2010 was queried for all patients aged less than 18 years. Patients admitted for management of a non-burn injury were excluded from the analysis. Results: Of 5,553 pediatric burn admissions, 297 (5.3%) were due to abuse. Children with non accidental injuries tended to be younger (2.1 vs. 5.0 years, p < 0.0001) and male (66.0 vs. 56.5%, p = 0.0008). Scald was the most common mechanism of injury overall (44.8%), and was also the predominant cause of inflicted burns (89.6 vs. 42.3%, p < 0.0001). Multivariate logistic regression identified age, gender, presence of a scald, contact, or chemical burn, and injury to the hands, bilateral feet, buttocks, back, and perineum to be significant predictors of abuse. Victims of abuse were also found to have worse outcomes, including mortality (5.4 vs. 2.3%, p = 0.0005). After adjusting for age, mechanism of injury, and burn size, abuse remained a significant predictor of mortality (OR 3.3, 95% CI 1.5-7.2) Conclusions: Clinicians should approach all burn injuries in young children with a high index of suspicion, but in particular those with scalds, or injuries to the buttocks, perineum, or bilateral feet should provoke suspicion. Burns due to abuse are associated with worse outcomes, including length of stay and mortality. (C) 2016 Published by Elsevier Ltd.
As therapeutic and supportive care interventions become increasingly effective, growing numbers of childhood and adolescent cancer survivors face a myriad of physical and psychological sequelae secondary to their disease and treatment. Mental health issues, in particular, present a significant problem in this unique patient population, with depression affecting a sizable number of childhood and adolescent cancer survivors. Multiple key determinants impact a survivor's risk of developing depression, with variables traversing across biologic, individual, family, community, and global levels, as well as spanning throughout the life course of human development from the preconception and prenatal periods to adulthood. A multi-level life course conceptual model offers a valuable framework to identify and organize the diverse variables that modulate the risk of developing depression in survivors of childhood and adolescent cancer. This review describes the first multi-level life course perspective applied to development of depression in childhood and adolescent cancer survivors. This conceptual framework may be used to guide the investigation of mental health interventions for SCACs to ensure that key determinants of depression occurrence are adequately addressed across various levels and throughout the life trajectory.
Mother-son incest as well as female pedophilic disorder remain underrecognized and misdiagnosed. This is the case of a female child abuser who suffered from hypersexual disorder and mental retardation and whose son was viewed as a substitute transitional sexual partner. Our clinical case shared some common features with female sex offenders previously described in the literature but the association of sexual gratification and hypersexuality without pedophilic fantasies is quite uncommon in female child abusers.
A third to half of penile invasive squamous cell carcinomas are human papillomavirus (HPV) related. Warty (condylomatous), warty-basaloid, and basaloid carcinomas are the most common subtypes associated with HPV. Less frequent are clear cell and lymphoepithelioma-like carcinomas. Here we report a novel penile tumor associated with HPV. Twelve cases were selected from 1010 penile carcinomas, part of an international HPV detection study conducted at the Institut Catala d'Oncologia, Barcelona, Spain. Immunostaining with p16(INK4a) was performed on all cases, and HPV-mRNA detection was also performed. En bloc full tumor staining was the utilized criteria for positivity of p16(INK4a). For HPV-DNA detection, wholetissue section polymerase chain reaction analysis was performed by SPF10-DEIA-LiPA(25) (version 1). The patients' ages ranged from 42 to 92 years (average, 71 y). The tumor was most commonly located in the glans. A characteristic microscopic finding was the presence of a moderate to dense tumor-associated inflammatory cell infiltrate composed of neutrophils, lymphocytes, plasma cells, or eosinophils. Tumors grew in large solid sheets, nests, or had a trabecular pattern. Cells were large and poorly differentiated or anaplastic. Keratinization was minimal or absent. Nuclei were large with prominent nucleoli. Mitoses were numerous. Tumor necrosis was common. Deep invasion of the corpora cavernosa was frequent. p16(INK4a) and HPV-DNA were positive in all cases, whereas mRNA detection was positive in 9 cases only. The prevalent genotype was HPV16 (9 cases, 75%). Other genotypes were HPVs 58, 33, and 66. Medullary carcinomas of the penis are morphologically distinctive HPV-related high-grade neoplasms affecting older individuals. More studies are necessary to delineate the epidemiological, clinical, and molecular features of this unusual penile neoplasm.
Peptide nucleic acids (PNAs) have stronger affinity and greater specificity than do oligonucleotides for binding to DNA and RNA and, as such, have potential utility as probes in molecular biology applications. In this study, a novel approach for labeling the PNA with radioiodine that avoided solubility issues and poor labeling encountered when trying to radioiodinate PNAs directly in solution was developed. For this approach, a purpose-designed prosthetic group that incorporated both a radioiodinatable tyrosine and a tripbenylphosphonium (TPP) moiety was synthesized. The latter is an organic cation that combines the properties of good solubility in both aqueous and organic solvents with a strong retention by reverse phase HPLC. Following radioiodination of the TPP-based prosthetic group in phosphate buffer, the prosthetic group was purified and coupled to the terminal amine of 15-mer PNA on the solid phase resin. After cleavage and deprotection of the PNA from the resin, the presence of the TPP group resulted in a clean separation of radioiodinated PNA from unlabeled PNA, yielding a high-specific activity probe in a single HPLC run. As an example of a potential molecular biology application of the resultant I-125-labeled PNA probe, it was used to detect mRNA for the Lcn2 gene in Northern blotting. (c) 2006 Elsevier Inc. All rights reserved.
Peptide-major histocompatibility complex (pMHC) multimers enable the detection, characterization, and isolation of antigen-specific T-cell subsets at the single-cell level via flow cytometry and fluorescence microscopy. These labeling reagents exploit a multivalent scaffold to increase the avidity of individually weak T-cell receptor (TCR)-pMHC interactions. Dextramers are an improvement over the original streptavidin-based tetramer technology because they are more multivalent, improving sensitivity for rare, low-avidity T cells, including self/tumor-reactive clones. However, commercial pMHC dextramers are expensive, and in-house production is very involved for a typical biology research laboratory. Here, we present a simple, inexpensive protocol for preparing pMHC dextramers by doping in biotinylated dextran during conventional tetramer preparation. We use these pMHC dextramers to identify patient-derived, tumor-reactive T cells. We apply the same dextran doping technique to prepare TCR dextramers and use these novel reagents to yield new insight into MHC I-mediated antigen presentation.
Grounded in the tripartite model of perfectionism and previous empirical support, the current study explored qualitatively different types of perfectionists and their well-being. A total of 276 college students responded to measures of perfectionism, conscientiousness, neuroticism, and well-being. Latent Profile Analysis identified three distinct latent classes of perfectionists: adaptive, maladaptive, and non-perfectionists. Adaptive perfectionists exhibited highest levels of presence of meaning, subjective happiness, and life satisfaction; maladaptive perfectionists showed the highest levels of search for meaning. Findings call attention to the value of exploring the heterogeneity of perfectionists and their well-being. (C) 2017 Elsevier Ltd. All rights reserved.
In this study, a model is presented to obtain the parameters of penalty and reward scheme (PRS) in performance-based regulation (PBR) for each electricity distribution company (EDC) using analytical hierarchy process (AHP) and fuzzy c-means clustering (FCM). In the FCM algorithm, similar companies were categorized into clusters. By using AHP, score of effective factor in reliability index was obtained. In this model, external factors affecting EDCs performance were considered to reduce the risk of PBR implementation for companies and customers. The proposed model was applied on the EDCs in Iran. The results, including AHP score, parameters of PRS and PRS cost were calculated. (C) 2017 Elsevier Ltd. All rights reserved.
AIM To explore the functional role of cullin 4A (CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma (PHCC). METHODS The expression of CUL4A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry (IHC) was adopted to investigate the relationship between CUL4A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival (OS) and progression-free survival (PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition (EMT) markers was verified in cells with CUL4A knockdown or overexpression. The relationship between CUL4A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays. RESULTS CUL4A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4A expression; as well as three related to PFS: N stage, TNM stage and high CUL4A expression. Further multivariate logistic regression analysis identified high CUL4A expression as the only independent prognostic factor for PHCC. Moreover, CUL4A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4A in promoting the EMT and metastasis. CONCLUSION CUL4A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4A may be a potential therapeutic target for PHCC.
Objective. The aim of this study was to develop in vitro biofilms on SLA titanium (Ti-SLA) and zirconium oxide (ZrO2) surfaces and to evaluate the effect of antiseptic agents on the number of putative periodontal pathogenic species. Methods. An in vitro biofilm model was developed on sterile discs of Ti-SLA and ZrO2. Three antiseptic agents [chlorhexidine and cetyl-pyridinium-chloride (CHX/CPC), essential oils (EEOOs) and cetyl-peridinium-chloride (CPC)] were applied to 72-h biofilms, immersing discs during 1 min in the antiseptic solution, either with or without mechanical disruption. Viable bacteria [colony forming units (CFU/mL)] were measured by quantitative polymerase chain reaction (qPCR) combined with propidium monoazide. A generalized lineal model was constructed to determine the effect of the agents on the viable bacterial counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum on each surface. Results. The exposure to each antiseptic solution resulted in a statistically significant reductions in the number of viable target species included in the in vitro multi-species biofilm, on both Ti-SLA and ZrO2 (p < 0.001) which was of up to 2 orders for A. actinomycetemcomitans, for P. gingivalis 2 orders on Ti-SLA and up to 3 orders on ZrO2, and, for F. nucleatum up to 4 orders. No significant differences were found in counts of the tested bacteria between in vitro biofilms formed on both Ti-SLA and ZrO2, after topically exposure to the antimicrobial agents whether the application was purely chemical or combined with mechanical disruption. Significance. A. actinomycetemcomitans, P. gingivalis and F. nucleatum responded similarly to their exposure to antiseptics when grown in multispecies biofilms on titanium and zirconium surfaces, in spite of the described structural differences between these bacterial communities. (C) 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
Fimbriae are protein-based filamentous appendages that protrude from the bacterial cell surface and facilitate host adhesion. Two types of fimbriae, FimA and Mfa1, of the periodontal pathogen Porphyromonas gingivalis are responsible for adherence to other bacteria and to host cells in the oral cavity. Both fimbrial forms are composed of 5 proteins, but there is limited information about their polymerization mechanisms. Here, the authors evaluated the function of Mfa5, one of the Mfa1 fimbrial accessory proteins. Using mfa5 gene disruption and complementation studies, the authors revealed that Mfa5 affects the incorporation of other accessory proteins, Mfa3 and Mfa4, into fibers and the expression of fimbriae on the cell surface. Mfa5 is predicted to have a C-terminal domain (CTD) that uses the type IX secretion system (T9SS), which is limited to this organism and related Bacteroidetes species, for translocation across the outer membrane. To determine the relationship between the putative Mfa5 CTD and the T9SS, mutants were constructed with in-frame deletion of the CTD and deletion of porU, a C-terminal signal peptidase linked to T9SS-mediated secretion. The CTD-expressing strain presented a similar phenotype to the mfa5 disruption mutant with reduced expression of fimbriae lacking all accessory proteins. The porU mutants and the CTD-expressing strain showed intracellular accumulation of Mfa5. These results indicate that Mfa5 function requires T9SS-mediated translocation across the outer membrane, which is dependent on the CTD, and subsequent incorporation into fibers. These findings suggest the presence of a novel polymerization mechanism of the P. gingivalis fimbriae.
Regeneration of periodontal tissues, particularly cementum, is key to regaining periodontal attachment and health. Human periodontal ligament stem cells (hPDLSCs) have been shown to be a good cell source to regenerate periodontal tissues. However, their subpopulations and the differentiation induction in relation to cementogenic lineages is unclear. Thus, we aim to examine the expression of cementum-associated genes in PDLSC subpopulations and determine the effect of broadly used osteogenic stimulus or vitamin C (VC) on the expression of cementogenic and osteogenic genes in PDLSCs. Our real-time quantitative polymerase chain reaction (qPCR) analysis showed that cementogenic marker cementum attachment protein (CAP) expressed only slightly higher in STRO-1(+)/CD146(+), STRO-1(-)/CD146(+) and STRO-1(-)/CD146(-) subpopulations than in the original cell pool, while cementum protein 1 (CEMP1) expression in these subpopulations was not different from the original pool. Notably, under the stimulation with osteogenic differentiation medium, CAP and CEMP1 were downregulated while osteogenic markers bone sialoprotein (BSP) and osteocalcin (OCN) were upregulated. Both CAP and CEMP1 were upregulated by VC treatment. Transplantation of VC-treated PDLSCs into immunocompromised mice resulted in forming significantly more ectopic cementum- and bone-like mineral tissues in vivo. Immunohistochemical analysis of the ectopic growth showed that CAP and CEMP1 were mainly expressed in the mineral tissue and in some cells of the fibrous tissues. We conclude that osteogenic stimulation is not inductive but appears to be inhibitory of cementogenic pathways, whereas VC induces cementogenic lineage commitment by PDLSCs and may be a useful stimulus for cementogenesis in periodontal regeneration.
Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions. We randomly assigned 63 male Fischer344 rats to three consecutive experiments of 21 animals each (cone-beam computed tomography; histology/serology; reverse-transcription quantitative real-time polymerase chain reaction) in three experimental groups (n = 7; control; orthodontic tooth movement [OTM] of the first/second upper left molars [NiTi coil spring, 0.25 N]; OTM with a daily oral meloxicam dose of 3 mg/kg). In vitro, we stimulated human periodontal ligament fibroblasts (hPDL) with orthodontic pressure (2 g/cm(2)) with/without meloxicam (10 mu M). In vivo, meloxicam significantly reduced serum C-reactive protein concentration, tooth movement velocity, orthodontically induced dentine root resorption (OIRR), osteoclast activity and the relative expression of inflammatory/osteoclast marker genes within the dental-periodontal tissue, while presenting good gastric tolerance. In vitro, we observed a corresponding significant decrease of prostaglandin E-2/interleukin-6/RANKL(-OPG) expression and of hPDL-mediated osteoclastogenesis. By inhibiting prostaglandin synthesis, meloxicam seems to downregulate hPDL-mediated inflammation, RANKL-induced osteoclastogenesis and, consequently, tooth movement velocity by about 50%, thus limiting its suitability for analgesia during orthodontic therapy. However, its protective effects regarding OIRR and good tolerance profile suggest future prophylactic application, which merits its further investigation.
BACKGROUND: Correct diagnosis of cefazolin hypersensitivity is not straightforward, mainly because of the absence of in vitro tests and uncertainties concerning the optimal cefazolin concentration for skin testing. Cross-reactivity studies suggest cefazolin hypersensitivity to be a selective hypersensitivity. OBJECTIVE: The first objective was to confirm that the application of a higher than 2 mg/mL test concentration could increase skin test sensitivity. A second part aimed at investigating the cross-reactivity between cefazolin and other beta-lactam antibiotics. METHODS: A total of 66 patients referred to our clinic after experiencing perioperative anaphylaxis, and exposed to cefazolin, underwent skin testing with cefazolin up to 20 mg/mL. Patients exhibiting a positive skin test with cefazolin had a panel of skin tests with other beta-lactams and, if indicated, graded drug challenges to study cross-reactivity. RESULTS: Increasing skin test concentration from the recommended 2 mg/mL to 20 mg/mL identified an additional 7 of 19 (27%) patients, who would otherwise have displayed negative skin testing. The concentration was proven nonirritating in 30 cefazolin-exposed control individuals in whom an alternative culprit for perioperative anaphylaxis was identified. Graded challenge testing, after negative skin testing, displayed that all patients tolerated alternative beta-lactam antibiotics (ie, amoxicillin, cephalosporins, monobactams, and carbapenems). Of them, 11 individuals also tolerated an alternative cephalosporin, suggesting that cefazolin hypersensitivity (generally) is a selective allergy. CONCLUSIONS: Increasing cefazolin concentration for skin tests up to 20 mg/mL benefits the sensitivity of diagnosis. Furthermore, our data confirm that cefazolin hypersensitivity seems to be a selective allergy with good tolerance to other b-lactam antibiotics. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p, 146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.
Long-term peritoneal dialysis (PD) leads to ultrafiltration failure (UFF). Peritoneal mesothelial cells, which form the innermost monolayer of the peritoneal cavity, have been shown to regulate various responses, including inflammation, in UFF. The present study was designed to investigate the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, on peritoneal dialysis solution (PDS)-induced injuries in rat peritoneal mesothelial cells (RPMCs). RPMCs were cultured for different durations and with different concentrations of PDS. The gene expression levels of aquaporin-1 (AQP-1) and zonula occluden-1 (ZO-1) were determined using reverse transcription-quantitative polymerase chain reaction analysis. The protein levels of AQP-1, ZO-1 and PPAR-gamma were measured using western blot analysis. Interleukin (IL)-6 and IL-8 were detected using ELISA. The RPMCs were damaged by stimulation with 4.25% PDS for 72 h. The expression levels of AQP-1 and ZO-1 were increased, and the secretion of IL-6 and IL-8 were decreased by rosiglitazone. The use of the PPAR-gamma inhibitor, GW-9662, completely prevented the effects of rosiglitazone. These results indicated that PDS exposure stimulated an inflammatory response in the RPMCs. The PPAR-gamma activator, rosiglitazone, appeared to relieve the injury by inhibiting inflammation, and regulating the expression of AQP-1 and ZO-1, however further investigations are required to elucidate the potential underlying mechanism.
Purpose To evaluate the characteristic multidetector CT findings of peritoneal tuberculous (TB) cold abscesses. Patients and methods The morphological characteristics of 48 peritoneal TB cold abscesses in 29 patients (male:female = 13:16; age range 16-75 years) were retrospectively evaluated. TB infection was histologically proven by acid fast bacilli (AFB) smear or culture, TB-polymerase chain reaction (PCR), or histopathological specimen diagnosis. Results Seventeen abscesses (35.4%) were present in the right perihepatic space, 10 (20.8%) in the left subphrenic space, 6 (12.5%) in the right subphrenic space, 4 (8.3%) in the pelvic cavity, 3 (6.3%) in the left perihepatic space, 3 (6.3%) in the right lower quadrant, and so on. The abscess contents ranged from 10.4 to 61.4 Hounsfield units. Internal septa (64.6%), central necrotic lymphadenopathy (55.2%), and TB coinfections in other organs (65.5%) were observed. TB infection was histopathologically confirmed from the surgical specimens in 17 patients and other 4 patients revealed the positive TB-PCR results from the peritoneal fluid. Ten patients (34.5%) had a recent history of TB peritonitis with ascites. Conclusion Peritoneal TB cold abscesses were commonly found in the right perihepatic and subphrenic spaces and revealed higher density of internal content, frequent internal septa, central necrotic lymphadenopathy, and high TB coinfections in other organs.
Viable bacterial cells and its genetic material can be stably maintained in Arctic permafrost for a long geological time. Because of the seasonal melting of permafrost strata, it cannot be excluded an access to the surface of ancient highly invasive species with increased pathogenicity. Mycoplasmas are very successful pathogens in humans, mammals, birds, insects, and plants, with high genome plasticity and ability to avoid immune response of host organism. The metagenomic approach allowed us to predict mycoplasma diversity in the Arctic permafrost. The number of mycoplasma DNA fragments in soil deposits of comparable age (similar to 30,000 years) and origin (the late Pleistocene Ice Complexes) is not so abundant compared with other microorganisms, but it is enough for a chance in the presence of living mycoplasmal cells in permafrost. DNA fragments of human, animal, insect, and plant pathogens were identified. The "ubiquitous" mycoplasma Acholeplasma laidlawii is the undisputed leader in the number of identified sequences in all three metagenomes. It may indicate a higher adaptive capacity and more powerful metabolic potential of A. laidlawii among Mollicutes.
LaMnO3 has attracted significant attention as energy conversion and storage materials, and especially as a promising noble-metal-free oxide catalyst and a new kind of electrode material for supercapacitors. However, the poor electronic transport ability of LaMnO3 hinders its application. Thus, improvement of its electronic transport ability is essential to enhance the electron transfer from catalyst active sites to an electrode, which is effective to avoid ohmic potential drop and consequently energy loss. In this work, the high-quality epitaxial growth La-deficiency La0.9MnO3 films were obtained by a simple and low cost polymer assisted deposition method. It is found that the room-temperature conductivity (sigma) of doping La0.9MnO3 increases nearly ten times compared to that of the parent LaMnO3. The oxygen-content-driven enhancement of the conductivity is discussed for the oriented La0.9MnO3 film. It is suggested that the existence of the LaAlO3 substrate is beneficial to stabilize the La-deficiency La0.9MnO3 compound and A-site La-deficiency extends the range of oxygen content. Both strain (including epitaxial strain and doping induced chemical strain) and annealing temperature are cooperating on the oxygen content, resulting in the oxygen stoichiometry independence of ambient conditions and the high conductivity. Following this process, conductivity and electronic state of the perovskite-related material can be tuned for the practical application.
Manufacturing cost analysis is becoming an increasingly important tool in the photovoltaics industry to identify research areas that need attention and enable progress towards cost reduction targets. We describe a method to estimate manufacturing cost that is suitable for use during an early stage of technology development, delivering both the manufacturing cost estimate as well as an uncertainty analysis that quickly highlights the opportunities for greatest cost improvement. We apply the technique to three process sequences for the large-scale production of organic-inorganic hybrid perovskite photovoltaic modules. A process sequence that combines two demonstrated perovskite module sequences is estimated to cost $107/m(2) (uncertainty range $87 to 140/m(2)), comparable with commercial crystalline silicon and cadmium telluride technologies (on a US $/m(2) basis). A levelized cost of electricity calculation shows that this perovskite technology would be competitive in 2015 with incumbent photovoltaic technologies if a module power conversion efficiency of 18% and lifetime of 20 years can be achieved. Further analysis shows that even if the cost of the active layers and rear electrode were reduced to zero, a module power conversion efficiency of 18% and lifetime of 20 years would be required to meet the 2020 SunShot levelized cost of electricity targets. Copyright (C) 2017 John Wiley & Sons, Ltd.
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in the formation and development of hepatocellular carcinoma and that peroxisome proliferator-activated receptor gamma coactivator-1 alpha may be a potential therapeutic target for hepatocellular carcinoma.
The regulation of postharvest treatment with propylene and 1-MCP on ethylene release rate and expressions of 1-aminocyclopropane-1-carboxylic acid synthase (ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes in Fuping Janshi persimmon (Diospyros kaki L.) fruit were investigated. Fruits were treated with propylene and 1-MCP, then stored at 20 degrees C, ethylene release rate of the treated fruits was measured at regular intervals and RNA was extracted for Northern blotting analysis. The results suggested that treatment with propylene accelerated the expressions of ACS and ACO genes and then enhanced the ethylene biosynthesis, while treatment with 1-MCP inhibited the expressions of two genes and their ethylene biosynthesis. Furthermore, different effects on expressions caused by treatments with propylene and 1-MCP existed in various fruit tissues, the inhibitory effect on ACS and ACO genes by 1-MCP was the strongest in pericarp, followed by pulp and core tissues, in the area near fruit stalk, the inhibitory effect was the weakest. While the enhanced effect on ACS and ACO genes by propylene increased from pulp, core, and pericarp to the area near fruit stalk. Expression of each member of ACS and ACO families in various tissues was also completely different, in control and propylene treatment, DKACS3 gene just expressed in the area near fruit stalk and did not express in other tissues, but DKACS2 gene expressed in four tissues by treatment with propylene.
While much of the person perception literature has focused solely on the representation of superordinate social categories (e.g., race and age), these superordinate social categories may be organized into smaller subcategories (i.e., subtypes and subgroups) that can be distinguished by their perceived typicality. Based on the logic that atypical subcategories represent subtypes and typical subcategories represent subgroups, we hypothesized that some subcategory labels would elicit greater perceived stereotypicality compared to others. In Experiment 1, participants listed stereotypic traits and rated the perceived typicality of subcategories of Black and White men. In Experiment 2 we used a reverse correlation image classification procedure to estimate participants' visual representations of the faces of Black and White superordinate category and subcategory members. Results indicated that representations of Black subgroups reflected traits and features more prototypical of Black men compared to representations of Black subtypes. Similarly, representations of White subgroups reflected traits and features more prototypical of White men compared to representations of White subtypes. The current experiments further clarify the nature of subcategory representations as subgroups and subtypes within the superordinate category. Implications for stereotype maintenance and change are considered. (C) 2017 Elsevier Inc. All rights reserved.
The present study sought to understand the perceived well-being value of future goals as a possible explanation for why persons who are suicidal remain attached to goals that are seen as unattainable. Deliberate self-harm patients (DSH; N = 24) were compared with matched hospital controls (N = 24) on a range of measures including current well-being and perceived future well-being in the context of imagined goal attainment. Despite the DSH group having substantially lower current levels of well-being, there was no difference between the groups when forecasting their future well-being in the context of imagined attainment. For DSH participants the thought of achieving an important future goal is seen as necessary and sufficient for attaining normal levels of future well-being, which may function to keep them attached to goals that are perceived as relatively unattainable.
Asthma is a chronic inflammatory and heterogeneous disease developing mostly through allergic inflammation, which modifies the expression of various cytokines and neurotrophins. Previous studies suggest the involvement of interleukin (IL)-15 in the regulation of immune response in asthma. Brain-derived neurotrophic factor (BDNF) II plays an important role as a regulator of development and survival of neurons as well as maintenance of their physiological activity. Chronic stress associated with asthma and elevated IL-15 mRNA and BDNFII mRNA levels may affect the mood and a subjective sensation of dyspnoea-inducing anxiety. Psychopathological variables and numerous cytokine/neurotrophin interactions influence the formation of temperament and strategies of coping with stress. The aim of the study was to identify the role of IL-15 mRNA and BDNFII mRNA expressions and their effect on components of temperament and strategies of coping with stress in asthmatics. A total of 352 subjects (176 healthy volunteers and 176 asthmatic patients) participated in the study. The Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale were applied in all the subjects. The expression of IL-15 and BDNFII gene was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Different levels of IL-15 and BDNFII expressions between healthy volunteers and patients were revealed in the study. IL-15 enhanced the BDNFII mRNA expression among patients with bronchial asthma. The depression level negatively correlated with the BDNFII mRNA expression. This neurotrophin modified the temperament variable. BDNFII significantly affected (proportional relationship) the level of briskness in asthmatic patients. BDNFII might influence the level and style of coping with stress (emotion-oriented style). This hypothesis requires further studies on protein functional models. The obtained data confirms the role of IL-15 and BDNFII in the pathomechanisms of depression and formation of selected traits defining the temperament in asthmatics.
Every day, we primarily experience actions as agents, by having a concrete perspective on our actions, their means and goals. This peculiar perspective is what allows us to successfully plan and execute our actions in a dense social environment. Nevertheless, in this environment actions are also perceived from an observer's perspective. Adopting such a perspective helps us to understand and respond to other's people actions and their outcomes. Importantly, similar experiences of being agent and observer occur also when actions are not physically acted/perceived but are merely linguistically shared. In this paper we present two exploratory studies, one in Italian and one in German, in which we applied a direct comparison of three singular perspectives in combination with different verb categories. First, second and third person pronouns were combined with action and interaction verbs, i.e., verbs implying an interaction with an object e.g., grasp-or an interaction with an object and another person -e.g., give. By means of kinematics recording, we analyzed participants' reaching-grasping responses to a mouse while they were presented with the different combinations of linguistic stimuli (pronouns and verb type). Results of Experiment 1 on reaching show that, when they are preceded by YOU, interaction verbs reached the velocity peak earlier than action verbs, since a further motor act will follow. Thus pronouns influence perspective taking and while comprehending language we are sensitive to the motor chain organization of verbs. The absence of the same effects in Experiment 2 is likely due to the fact that, being the pronoun in German mandatory, it is perceived as less salient than in Italian. Overall our result supports the idea that language is grounded in the motor system in a flexible way, and highlights the need for cross- linguistic studies in the field of embodied language processing.
Background: Pertussis infection can be severe in unvaccinated infants. A case-control study was conducted to investigate the potential role of breast-feeding in protecting young, unvaccinated infants from pertussis. Methods: Hospitalized infants <6 months of age with positive real time polymerase chain reaction for pertussis on nasopharyngeal aspirate were enrolled as cases; healthy controls were enrolled among patients admitted for ultrasound screening. Vaccinated infants were excluded. Socio-demographic, clinical and feeding information were collected. The effect of breastfeeding on pertussis was investigated through multivariable analysis. Breast milk and blood samples were obtained from mothers of patients. IgA and bacterial binding against Bordetella pertussis and other bacteria were tested in breast milk. IgG against pertussis toxin (PT) was tested in serum. Results: We enrolled 296 patients (61 cases and 235 controls). Exclusive breastfeeding was not associated with pertussis compared with partial breastfeeding/artificial feeding [odds ratio: 1.2; 95% confidence interval (CI): 0.31-4.67]. Children with siblings were at higher risk for pertussis (odds ratio: 2.5; 95% CI: 1.21-5.35). IgA against pertussis antigens were not higher in cases (IgA anti-PT median = 0.24 optical density) compared with controls (IgA anti-PT median = 0.21 optical density). Though bacterial binding to B. pertussis, measured in breast milk, was higher in cases (median = 4.35%) compared with controls (median = 2.8%; P = 0.004), bacterial binding to B. pertussis was low compared with other pathogens. IgG titers were higher in mothers of cases, but no correlation was found between serum IgG and breast milk IgA. Conclusion: Breastfeeding remains a mainstay of prevention for numerous diseases, though it does not seem to play a role against pertussis. Alternative strategies to protect unvaccinated infants from pertussis should be considered.
Nowadays, the significant increase in noise has become a major problem in urban areas. Using pervious concrete pavement is recommended to reduce the noise. Unfortunately, standard materials used to produce pervious concrete are not completely environmental friendly. As a result, many researchers have devoted their attention towards identifying eco-friendlier substitutions to be used in the manufacturing of pervious concrete. In this respect, this current paper discussed the efficiency of two different sizes of oil palm kernel shell (KS) and cockle shell (CS) as partial replacement of natural coarse aggregate for sound absorption of pervious concrete. Thirteen mixtures were made, which replaced 6.30 mm limestone with 0, 25, 50 and 75% of 6.30 mm and 4.75 mm of both shells. The specimens were cured in a fog room and void content and compressive strength were tested. The replacement of both KS and CS as the natural aggregate decreased the compressive strength, although the range was still acceptable for pervious concrete at 28 days. However, the angular shape of both shells caused high void content. The maximum increase in void content compared to that of the control pervious concrete (CPC) was achieved with the use of 75% of 6.30 mm KS at 28 days. Moreover, by increasing sound absorption with the application of both shells, particularly KS, the concrete could be used as silent road pavement. It was therefore concluded that the use of both KS and CS to produce cleaner and quitter pervious concrete pavement is practical, both mechanically and environmentally. (C) 2017 Elsevier Ltd. All rights reserved.
The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine-the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil) of the pesticide chlorpyrifos (CPF) on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME (R) model (six reactors, representing the different parts of the gastrointestinal tract). The last three reactors (representing the colon) were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts) and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i) CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses); (ii) the changes are "SHIME (R)-compartment" specific; and (iii) the changes are associated with minor alterations in the production of short-chain fatty acids and lactate.
Introduction. - Prostate cancer is the most frequent cancer in men in France and it is a public health issue. This cancer is heterogenous. There is a clinical need of an accurate non-invasive imaging method to improve diagnosis, guide the choice of therapy and evaluate its efficacy. We undertook to critically review the different molecular imaging probes, currently used or in clinical trial. Method. - A systematic review of the literature was performed in Pubmed/Medline database by searching for articles in French or English published on PET tracer in prostate cancer in clinical application. Results. - Several PET tracers are under investigation because of the low performance of the FDG in prostate cancer. In France, only two new PET tracers have the marketing authorization: the NaF and choline, but these tracers have several limitations. The NaF analyses only bone metastasis. The choline has changed the recurrence of prostate cancer but is not effective for recurrence with low PSA, furthermore its sensitivity is low for the detection of lymph nodes metastasis in initial disease. Several tracers in trial including the PSMA offer encouraging prospects in initial staging and for recurrences. Conclusion. - An accurate knowledge in molecular biology allowed to develop the metabolic imagery. Many new tracers are under evaluation in prostate cancer. The indication of each of them needs to be established. (C) 2016 Elsevier Masson SAS. All rights reserved.
The long-day plant Petunia x hybrida 'Fantasy Red' was found to produce a considerable number of premature abortive flower buds when placed under short light period stress. Suppression subtractive hybridization (SSH) was performed to compare the gene expression profiles between normal and abortive petunia flower buds as induced by short light periods. Using reverse northern blotting, a total of 912 positive clones were successfully identified and sequenced, and 289 non-redundant, differentially expressed transcripts were obtained. According to the Blast2GO and KEGG pathway analyses, the significant distinct cellular component was identified as mitochondrion, and the notable different metabolic pathways were ascribed to carbohydrate metabolism and lipid metabolism. The quality of the SSH libraries was verified through quantitative real-time reverse transcription-PCR (qRT-PCR) analysis of 14 genes. In addition, six of these genes were demonstrated to be of temporal and/or spatial specificity using qRT-PCR, implying that they might be responsible for the premature flower abortion. Furthermore, Phms2 (KC465381), a sequence sharing a high degree of similarity with male sterility 2 gene was characterized, and its inconsistent expression pattern predicted a novel role for Phms2 in flower bud abortion. The data presented here provide insight into the molecular mechanisms of premature flower abortion under short light periods and, hence, may be of value for assessing candidate genes with potential for creating novel germplasms with enhanced photoperiod stress tolerance. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
The multidrug resistance 1 gene (MDR1) encodes for P-glycoprotein (P-gp), which plays a pathophysiological role in the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Herein, we aimed to investigate the relationship between MDR1 gene polymorphisms and SLE susceptibility in the Chinese Guangxi population. The genotypes of rs1128503 and rs1045642 in MDR1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 283 SLE patients and 247 healthy controls from Guangxi. Direct sequencing method was used to verify the results. Binary logistic regression analyses adjusting for gender and age indicated that subjects carrying the rs1128503 T-allele and TT genotype were at increased risk of SLE when compared to carriers of the C allele and CC genotype, with adjusted ORs of 1.36 (95% CI 1.07-1.74; P = 0.014) and 1.77 (95% CI 1.08-2.88; P = 0.022), respectively. In addition, the risk allele T had a recessive effect (OR 1.49, 95% CI 1.04-2.14, P = 0.029). Subgroup analyses revealed effect modification by age for the presence of the rs1128503 T allele, yielding a significant positive association with SLE in older (ae40 years) subjects (T vs. C allele: OR 1.41, 95% CI 1.01-1.96; P = 0.041; TT vs. CC genotype: OR 1.74, 95% CI 1.07-2.79; P = 0.021). For the first time, we demonstrated that MDR1 rs1128503 polymorphisms were associated with SLE susceptibility in Chinese Guangxi population.
Different iron-based cathode catalysts have been studied for oxygen reduction reaction (ORR) in neutral media and then applied into microbial fuel cells (MFC). The catalysts have been synthesized using sacrificial support method (SSM) using eight different organic precursors named Niclosamide, Ricobendazole, Guanosine, Succinylsulfathiazole, Sulfacetamide, Quinine, Sulfadiazine and Pyrazinamide. Linear Sweep Voltammetry (LSV) curves were obtained for the catalysts using a O-2 saturated in 0.1 M potassium phosphate buffer and 0.1 M KCl solution and a Rotating Ring Disk Electrode (RRDE) setup in order to study the ORR characteristics. Additionally, we analyze the peroxide yield obtained for each catalyst which helps us determine the reaction kinetics. Those catalysts have been mixed with activated carbon (AC), carbon black (CB) and PTFE and pressed on a metallic mesh forming a pellet like gas diffusion electrode (GDE). Results showed that Fe-Ricobendazole, Fe-Niclosamide and Fe-Pyrazinamide had the highest cathode polarization curves and highest power densities output that was above 200 mu Wcm(-2). Fe-Ricobendazole, Fe-Niclosamide, Fe-Pyrazinamide, Fe-Guanosine Fe-Succinylsulfathiazole and Fe-Sulfacetamide outperformed compared to Pt cathode. Fe-Sulfadiazene and Fe-Quinine performed better than AC used as control but less than Pt. Correlation of surface composition with performance showed that power density achieved is directly related to the total amount of nitrogen, and in particularly, N coordinated to metal and pyridinic and pyrrolic types while larger amounts of graphitic nitrogen result in worse performance. (C) 2017 The Authors. Published by Elsevier B.V.
Phaeodactylum tricornutum is a widely used model organism for studying diatom biology. We created a P. tricornutum-specific literature database, or bibliome, that can be interactively annotated by users to improve the relevance and accuracy of search queries. A bibliome represents the current knowledge about a specific organism or biological process and is the foundation for genome-scale computation models. The bibliome of P. tricornutum was assembled from literature searches of 'P. tricornutum' (as topic) in two different existing databases, the Web of Knowledge and PubMed resulting in 2497 independent articles. We manually curated the bibliome for relevance to biochemical, physiological, and molecular biology studies. Literature that described the use of P. tricornutum as feed source and ecotoxicology studies were excluded from the bibliome. This process resulted in a final list of 1124 entries -20% of which received additional classification in the form of notes or keywords. We present the bibliome in an HTML format that is easily searched and that can be customized according to the interests of individual researchers. This HTML tool can also easily be adapted for other algal species or specific research topics. (C) 2016 Elsevier B.V. All rights reserved.
Objective: Phagocyte function of neutrophil granulocytes and monocytes is decreased in healthy pregnancy and further decreased in preeclampsia. The cause of the declined function is unknown. Decreased phagocyte function can lead to the higher infection rate in healthy pregnancy and may also be responsible for the increased susceptibility to infections and high trophoblast concentration in preeclampsia. The aim of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes. Methods: Monocytes and neutrophil granulocytes were separated from the peripheral circulation of six nonpregnant patients and incubated in plasma samples from six healthy pregnant, six preeclamptic pregnant, and six nonpregnant patients. The cells were marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosan molecules. Results: Phagocyte function of neutrophils as well as monocytes from nonpregnant patients were decreased significantly when the cells were incubated in plasma samples from healthy pregnant patients, and further decreased when incubated in plasma samples from preeclamptic pregnant women. Conclusion: The decreased phagocyte function of neutrophil granulocytes and that of monocytes in healthy pregnancy and the further decreased phagocyte function in preeclampsia is caused by factor(s) in the maternal circulation.
Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of prescribed medication for the improvement of cognitive functioning and academic performance. Although there are some studies about PCE prevalence, it is less clear how users and non-users of PCE substances differ with respect to their positive and negative student experiences (e.g. academic burnout and engagement with studies) and in social cognitive variables that relate to decision-making and self-regulation of PCE use. The present study assessed whether students with different experiences of PCE substance use displayed differences in academic burnout, study engagement, and social cognitive variables relevant to PCE use. Three hundred and forty-seven university students (mean age (M) = 22.15years, SD = 1.69; 54% females) completed a battery of anonymous questionnaires on academic burnout, engagement with studies, social cognitive variables relevant to PCE use, and self-reported use of PCE substances and non-prescribed nutritional supplements. Three user groups emerged, namely non-users (51.9%, n = 180), single users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate analysis of variance indicated significant differences among the three user groups in intentions, attitudes, social norms, and anticipated regret toward PCE use. No significant differences were observed with respect to academic burnout and work engagement. The findings show that university students may engage in PCE use independent of their student experiences. Rather, a chemically assisted performance enhancement mindset seems to differentiate users from non-users of PCE substances.
Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. We have earlier shown that a novel antioxidant from the bamboo leaves constituent 3-O-caffeoyl-1-methylquinic acid (MCGA3) induces heme oxygenase-1 (HO-1) and protects endothelial cells from ROS-induced endothelial injury. The purpose of this study was to elucidate the induction mechanism of HO-1 and other phase II genes by MCGA3 in human umbilical vascular endothelial cells (HUVECs). Using Northern blotting and RT-PCR, we found that treatment of HUVECs with MCGA3 increased, in a dose and time-dependent manner, steady-state mRNA levels of the selected phase II genes including HO-1, ferritin, gamma-glutarriylcysteine lygase, glutathione reductase, and glutathione transferase, which were dependent on Nrf2 nuclear translocation. The observed phase II gene induction by MCGA3 was found to be associated with MCGA3-inediated cytoprotective activity, ROS-scavcnging potency, and the increase in the cellular levels of both reduced (GSH) and oxidized glutathione (GSSG). Interestingly, exposure to MCGA3 resulted in a decreased ratio of GSH/GSSG, which was negatively related with mRNA level of phase II genes. By employing N-acetylcysteine and GSH biosynthetic enzyme inhibitors as well as prooxidants, hemin and H2O2, we show that a decreased intracellular GSH/GSSG homeostasis, at least in part, may be involved in the MCGA3-rnediated phase If gene induction and Nrf2 translocation, although the attenuation of HO-1 expression with SP 600125 supports a partial involvement of JNK signaling. (c) 2005 Elsevier Inc. All rights reserved.
Repetitive control strategies have been commonly applied in pulse-width-modulated (PWM) voltage source inverters (VSIs) for many industrial applications. This paper presents a repetitive controller for voltage harmonic mitigation of VSI-based islanded microgrids. The phase delay in the overall control system, e.g., the delay caused by the digital duty cycle calculation, PWM generation, and repetitive controller, has to be compensated by elaborately designed phase lead filters in order to prevent control performance deterioration and system instability. Nevertheless, quantificational analysis and practical design of the time advance unit in such filters are hardly found in existing literature works. In view of this, this paper proposes an explicit analysis of the phase lead filters and a novel design method of the time advance unit in repetitive controllers to ensure system stability. Moreover, with the help of the proposed method, the overall system stability margin is predictable and improved controller performance is achieved as well. The proposed method is implemented experimentally to show the accurate stability margin calculation as well as the excellent steady state and dynamic performances of the repetitive control scheme.
Synchronization with the utility voltage is naturally carried out by a diode bridge stage in single-phase active rectifiers, while an active synchronization is included in the control algorithms applied to modern bridgeless topologies. Sensorless line current rebuilding algorithms also need synchronization with the line voltage to compensate at least for part of the current estimation error. The phase-locked-loop (PLL) circuits employed in single-phase ac-dc converters are reviewed and a new digital PLL algorithm, based on the synchronous reference frame, is proposed. It is implemented in a field-programmable gate array to utilize the parallelism and superior time resolution. Considering a restricted frequency variation of the line voltage around the central frequency, the orthogonal signal is obtained by a discrete differential operator designed to ensure unity gain at the central frequency. Its performance, including the memory and computational cost, versus previously consolidated algorithms implemented in the same device is analyzed. Simulations and experimental results prove its suitable behavior in steady state at different line frequencies and under line voltage and frequency transients.
This article deals with an electronic implementation of a 3-D dynamical system that comprises multiple scrolls and is regarded as unstable dissipative system. Such a system is dissipative in one of its components but unstable in the other two. The proposed electronic circuit is implemented with resistors, capacitors and comparators and has the capability to generate two or three scrolls
The macromolecular crystallography P13 beamline is part of the European Molecular Biology Laboratory Integrated Facility for Structural Biology at PETRA III (DESY, Hamburg, Germany) and has been in user operation since mid-2013. P13 is tunable across the energy range from 4 to 17.5 keV to support crystallographic data acquisition exploiting a wide range of elemental absorption edges for experimental phase determination. An adaptive Kirk-patrick-Baez focusing system provides an X-ray beam with a high photon flux and tunable focus size to adapt to diverse experimental situations. Data collections at energies as low as 4 keV (lambda = 3.1 angstrom) are possible due to a beamline design minimizing background and maximizing photon flux particularly at low energy (up to 10(11) photons s(-1) at 4 keV), a custom calibration of the PILATUS 6M-F detector for use at low energies, and the availability of a helium path. At high energies, the high photon flux (5.4 x 10(11) photons s(-1) at 17.5 keV) combined with a large area detector mounted on a 2 theta arm allows data collection to sub-atomic resolution (0.55 angstrom). A peak flux of about 8.0 x 10(12) photons s(-1) is reached at 11 keV. Automated sample mounting is available by means of the robotic sample changer 'MARVIN' with a dewar capacity of 160 samples. In close proximity to the beamline, laboratories have been set up for sample preparation and characterization; a laboratory specifically equipped for on-site heavy atom derivatization with a library of more than 150 compounds is available to beamline users.
Prophenoloxidase (ProPO) cascade is a principal defense system in crustaceans, which consists of a variety of pattern recognition proteins (lipopolysaccharide and beta-glucan-binding protein [beta-GBP], beta-GBP, and beta-glucan recognition protein), proteases (serine protease), and protease inhibitors (alpha 2-macroglobulin and pacifastin) to regulate the protection mechanism in crustaceans. In the prophneoloxidase pathway, the protein-protein interactions (PPIs) and other immune-related analyses still have not been reported. Moreover, the structural features of ProPO cascade proteins have not yet been reported, hence we constructed the three-dimensional structural features for all ProPO pathway proteins. Their PPIs were studied through an in silico approach. Laminarin has been identified as a triggering activator and it showed energetic binding with homology modeled beta-GBP and activated the beta-GBP, followed by the protein-protein complex formation leading to phenoloxidase synthesis. These findings provided a novel view of the ProPO mechanism and enhanced our knowledge of the innate immune system in crustaceans via computation. In conclusion, we propose a combined experimental and computational approach to analyze the mechanism of ProPO cascade proteins. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 779-788, 2016
Phenytoin, a voltage-gated sodium channel (Na-V channel) antagonist, reportedly inhibits arginine vasopressin (AVP) release from an isolated rat neurohypophysis. So far, it is uncertain whether phenytoin has a direct action on ectopic AVP-producing neuroendocrine tumors. We studied the effect of phenytoin on the release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP gene in the human small cell lung cancer cell line Lu-165. Cells were maintained in RPMI1640 medium with 10% fetal bovine serum and were used within the fifth passage. Copeptin was detected using a new sandwich immunoassay, and AVP mRNA levels were measured using real-time reverse transcription polymerase chain reaction. Treatment with phenytoin at a concentration of 25 mu g/mL, but not at 5 or 10 mu g/mL, had an inhibitory effect on copeptin levels in the medium at 48 h. At the same concentration, AVP mRNA levels in Lu-165 cells also decreased. Although a sodium challenge with added sodium at 20 mEq/L increased copeptin levels in the medium, a sodium challenge with added sodium at 10 and 20 mEq/L had no effect on AVP mRNA levels. Phenytoin at a concentration of 25 mu g/mL suppressed copeptin levels in the medium under the sodium challenge with added sodium at 10 and 20 mEq/L. Phenytoin at a concentration of 25 mu g/mL also decreased AVP mRNA levels in Lu-165 cells under the sodium challenge with added sodium at 10 mEq/L, but not at 20 mEq/L. Among five tested NaV channel subunits, Na-V 1.3 was highly expressed in Lu-165 cells. However, phenytoin significantly decreased Na-V 1.3 mRNA levels under the sodium challenge with added sodium at 10 and 20 mEq/L. These results suggest that Lu-165 cells are sensitive to phenytoin and sodium to control of AVP release and its gene expression. Phenytoin might have a direct action on ectopic AVP-producing tumors, suggesting the importance of NaV channels in AVP-producing neuroendocrine tumors.
To gain a better understanding of the dimensions, characteristics and phenomenon of child maltreatment and its policy responses in the Philippines, this article provides a systematic review of the peer reviewed literature. This review provides a summary and analysis of the core child maltreatment issues in the Philippines and examines child protection policy responses. It takes a systematic approach, identifying 31 peer reviewed articles from a diverse range of scholarship that met its criteria, and subjected to a quality appraisal tool. Its findings provide important details about child maltreatment and child protection arrangements in the Philippines. It recommends further research into policy and programmatic approaches to child maltreatment, a greater focus on the social, cultural and structural influences on child maltreatment, and investigation into child maltreatment, particularly child sexual abuse, in contexts outside of the home, such as in institutions.
This study reports for the first time the full charging of a state-of-the-art mobile smartphone, using Microbial Fuel Cells fed with urine. This was possible by employing a new design of MFC that allowed scaling-up without power density losses. Although it was demonstrated in the past that a basic mobile phone could be charged by MFCs, the present study goes beyond this to show how, simply using urine, an MFC system successfully charges a modern-day smartphone. Several energy-harvesting systems have been tested and results have demonstrated that the charging circuitry of commercially available phones may consume up to 38% of energy on top of the battery capacity. The study concludes by developing a mobile phone charger based on urine, which results in 3 h of phone operation (outgoing call) for every 6 h of charge time, with as little as 600 mL (per charge) of real neat urine. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.
Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. (C) 2016 Elsevier B.V. All rights reserved.
The objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in most specimens at all anatomic sites, and their levels were strongly positively related (P < .001 for effusions and solid lesions). PLD2 messenger RNA (mRNA) expression was significantly higher in effusions compared with both carcinomas in the ovary and solid metastases (P < .001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P < .001), and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P = .021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A(2) pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role in mediating progression to effusions and chemoresistance in this cancer. (C) 2017 Elsevier Inc. All rights reserved.
The phosphorylated fullerene/sulfonated polyvinyl alcohol (PFSP) cation exchange membrane was prepared, characterized and its applications were studied in microbial fuel cell (MFC) for copper removal along with the power generation. The phosphorylation of fullerene was confirmed by UV and Fourier Transform Infrared Spectroscopy (FTIR). The composite membrane was prepared by solution casting method and characterized by FTIR, Scanning Electron Microscopy (SEM) and Thermo Gravimetric Analysis (TGA) methods. The proton conductivity, water uptake and ion exchange capacity (IEC) of the prepared membrane were observed to be 11.7 x 10(-2) S/cm, 120% and 1.67 meq/g respectively. Open circuit voltage (OCV) and power density obtained were 801 mV and 499.1 mW/m(2) respectively for the composite membrane. The maximum Cu++ removal was 73.2% as compared to 63.2% for Ultrex CMI 7000; a commercial membrane. This prepared membrane is expected to offer vital and constructive properties for its application in fuel cell technology and to remove copper ions from wastewater. (C) 2016 Elsevier B.V. All rights reserved.
Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 angstrom in the dark and 48.8 angstrom under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 angstrom long, 80 angstrom wide, and 50 angstrom thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2.
Photobiomodulation (PBM) describes light-induced photochemical reactions achieved by the application of red or near infrared lasers/LED light with low energy densities. This noninvasive and painless method has been used in some clinical areas but controversial outcomes demand a skeptical look for its promising and potential effects. In this detailed in vitro study, the osteoblast cells were irradiated with 635 and 809 nm diode lasers at energy densities of 0.5, 1, and 2 J/cm(2). Cell viability, proliferation, bone formation, and osteoblast differentiation were evaluated by methylthiazole tetrazolium (MTT) assay, Alamar Blue assay, acridine orange/propidium iodide staining, alkaline phosphatase (ALP) activity, Alizarin red staining, and reverse-transcription polymerase chain reaction (RT-PCR) to test the expression of collagen type I, ALPL, and osteocalcin. The results indicate that studied energy doses have a transient effect (48 h after laser irradiation) on the osteoblast viability and proliferation. Similarly, laser irradiation did not appear to have any effect on ALP activity. These results were confirmed by RT-PCR analysis of osteoblast markers. This study suggests that several irradiation parameters and variations in the methods should be clearly established in the laboratory before laser treatment becomes a postulated application for bone tissue regeneration in clinical level.
As promising photocatalyst driven by visible-light, BiOI has attracted more and more attention in the past years. However, the surface structure and properties of BiOl that is the most important place for the photocatalytic have not been investigated in details. To this end, density functional theory was performed to calculate the structural and electronic properties of four low-index stoichiometric surfaces of BiOI. It is found that the relaxation of the low-index BiOI surfaces are relatively small, especially the (001) surface. Thus, the surface energies of BiOl are very relatively small. Moreover, there are a few surface states below the bottom of conduction band in the first layer except the (001) surface, which maybe capture the photo-excited carriers. In all of the most stable terminated planes, all the dangling bonds are cleaved from the broken Bi-O bonds. In the case of (001) surface, the dangling bond density of Bi atoms for the (001) surface is zero per square nano. Therefore, the (001) surface is thermodynamically lowest energy surface of BiOl, and it is the predominant surface (51.4%). As a final remark, the dangling bonds density of bismuth atoms determines not only the surface energy, but also the surface relaxation. Finally, the equilibrium morphology of BiOI was also proposed and provided, which is determined through the Wulff construction. These results will help us to better understand the underlying photocatalytic mechanism that is related to BiOI surfaces, and provide theoretical support for some experimental studies about BiOI-based photocatalyst in future. (C) 2017 Elsevier B.V. All rights reserved.
One-dimensional bimetallic nanowires were introduced into TiO2-based matrix to enhance their photocatalysis efficiency and expand their light absorption range in this work. Recently, metal nanowires have attracted many attention in photocatalyst research fields because of their favorable electronic transmission properties and especially in the aspect of surface plasmon resonance effects. Moreover, Cu-Ni bimetallic nanowires (Cu-Ni NWs) have shown better chemical stability than ordinary monometallic nanowires in our recent works. Interestingly, it has been found that Ni sleeves of the bimetallic nanowires also can modify the Schottky barrier of interface between TiO2 and metallic conductor, so that be beneficial to the separation of photogenerated carriers in the Cu-Ni/TiO2 network topology. Hence, a novel heterostructured photocatalyst composed of Cu-Ni NWs and TiO2 nanoparticles (NPs) was fabricated by one-step hydrolysis approach to explore its photocatalytic performance. TEM and EDX mapping images of this TiO2 NPs @Cu-Ni NWs (TCN) hybrid displayed that Cu-Ni NWs were wrapped by compact TiO2 layer and retained the one-dimensional structure in matrix. In experiments, the photocatalytic performance of the TCN nanocomposite was significantly enhanced comparing to pure TiO2. Acetaldehyde, as a common gas pollutant in the environment, was employed to evaluate the photodegradation efficiency of a series of TCN nanocomposites under continuous feeding. The TCN exhibited excellent potodegradation performance, where the dynamic photocatalytic efficiency of TCN containing 3 wt% Cu-Ni NWs was about 88% and 56% (continuous 500 ppm CH3CHO feeding, 20 SCCM) under UV and visible light, respectively. ESR results proved that the recombination of photo -generated electron -hole pairs was inhibited significantly in TCN nanocomposite. Finally, the mechanism for electron -hole pairs' separation and transmission at Schottky barrier interface between Cu-Ni NWs and TiO2 layers has been proposed based on the above analyses. (C) 2017 Elsevier B.V. All rights reserved.
Controllable synthesis and surface modification of TiO2 crystals with specific exposed facets using fluoride as a shape directing agent have drawn a great deal of attention in the photocatalytic field. Both the exposed facets and surface F ions are known to have a great influence on the phOtocatalytic performance of TiO2 crystals, while these two factors are usually considered and discussed separately. Here, we investigated the influence of surface F ions on the carrier migration when the surface F ions are present on anatase TiO2 crystals with predominant {001} or {101} facets by using the H2O photo-oxidation and NH3 photo oxidation as the probe reactions. We observed a remarkable synergistic effect between {001} facets and surface F ions on the photogenerated hole migration. The {001} facets provide hole-trapping sites and the electrostatic effect of surface F anions attract and accelerate the holes migration to {001} facets, which synergistically promote the electron-hole pair separation and thus significantly enhance the photo oxidation activity. However, no synergistic effect was detected between {101} facets and the surface F ions. This finding provides a new insight into the photogenerated charge migration on fluorinated TiO2 with specific exposed facets. (C) 2017 Elsevier B.V. All rights reserved.
A novel hybrid system composed of a photocatalytic fuel cell (PFC) and Fenton reactor was developed with the aim to degrade the azo dye Reactive Black 5 (RB5) and generate electricity. Compared to previously established system of bioelectro-Fenton system, microbial fuel cell (MFC) system has significant challenge in the development and operation system. Therefore, PFC is used instead of MFC to generate electrons for the Fenton system. The effect of azo dye (RB5) on each PFC and Fenton reactor was investigated. The experimental results showed that maximum power output was achieved in the absence of dye in the Fenton reactor of this hybrid system. Furthermore, higher degradation efficiency of RB5 could also be observed in the PFC reactor in this hybrid system. (C) 2016 Elsevier B.V. All rights reserved.
Inorganic photochromic materials have attracted growing attention in recent years. Here, a reversible white-purple photochromic powder material Sr3GdLi(PO4)(3)F:Eu2+ was synthesized by conventional solid-state method. The surface color shows reversible white-purple changes after irradiated alternatively by UV and visible light (or thermal treat). Diffuse reflectance spectra were used to characterize the photochromic properties including coloring and bleaching. The results indicated that the optimal Eu2+ doping concentration was found to be about 0.5 mol%. Several cycles measurements including photo- and thermal-induced bleaching indicates that Sr3GdLi(PO4)(3)F:Eu2+ posses high fatigue resistance in photochromism performance. Based on thermoluminescence curves, the photochromism property related factors that the critical role of traps and the motion of charge carriers between traps were discussed. Finally, a schematic diagram for illustrating the photochromic mechanism was proposed. (C) 2017 Elsevier B.V. All rights reserved.
Activatable photosensitizers that can be activated by cancer-associated stimuli have drawn increasing attention for simultaneous fluorescence imaging and photodynamic ablation of cancer cells. Here, we developed a cancer-cell specific photosensitizer nano-delivery system by synthesizing protoporphyrin IX (PplX)-conjugated pullulan (P) with reducible disulfide bonds. The amphiphilic P-s-s-PpIX conjugate self-assembled in aqueous condition to form core-shell structured nanoparticles (P-s-s-PpIX NPs) with average size of 166 nm, showing reduction-controllable stability. In in vitro, the photoactivity of P-s-sPpIX NPs in an aqueous environment was significantly suppressed by the self-quenching effect, which kept P-s-s-PpIX NPs in a photo-inactive and quenched state. But in the presence of GSH, P-s-s-P-pIX NPs quickly dissociated by reductive breakage of disulfide linkers, followed by the significant recovery of fluorescent emission and singlet oxygen generation. In MCF-7 cells, compared to non-reducible P-PpIX NPs with stable amide linkages, P-s-s-PpIX NPs displayed higher cytotoxicity and induced higher apoptosis rate of tumor cells with light irradiation treatment. As a result, the P-s-s-PpIX NPs may serve as an effective smart nanomedicine platform for specific light-up and reduction-triggered cancer imaging and photodynamic therapy with the prominently reduced damage to normal tissues and cells. (C) 2017 Elsevier Inc. All rights reserved.
The first step to improving public health is by the assessment of vital signs, which are valuable indicators of overall health. In the present day there are a number of complex, albeit expensive instruments that can measure various parameters accurately. However, these instruments often tend to be bulky, expensive and difficult to operate. Hence it is difficult to use these instruments in isolated locations such as rural or disaster stricken areas, for bedside monitoring or even in military camps. The objective of this paper is to introduce the concept of a user friendly modular system which can be used to monitor various physiological parameters efficiently. In the proposed system different sensing circuits are attached to a common MicroController Unit (MCU) which can be updated with the associated firmware. Any general computing system such as a laptop is connected to the MCU via a USB-UART bridge. After the connection is established the controller starts sending data to the computer. A JavaScript is run on the laptop using open-source software called Processing 2.0, which initiates a customized display of the various parameters using the incoming data. For data logging we store the serial data in text files. As proof of principle we have measured two parameters, namely the body temperature using the LM35 sensor and the heart rate using photoplethysmography. Such a switchable system can be used as a tool to measure various parameters like oxygen saturation, blood pressure, ECG etc. on the computer screen.
Background: Psoriasis is mediated by a T helper 17 (Th17) cell inflammatory process. This study describes the changes in serum levels of IL-17, 22 and 23 in patients of psoriasis vulgaris treated with narrow band ultraviolet B (NBUVB).Methods: The serum levels of IL-17, 22 and 23 were compared with a control group (n=30) before and after NBUVB. In addition, post-NBUVB levels were compared with healthy controls. Psoriasis Area Severity Score (PASI) and Body Surface Area scoring were used to evaluate severity of disease.Results: When compared with the non-psoriasis control group, IL-17, 22 and 23 were higher in psoriasis patients (p<0.05, p<0.001, p<0.001, respectively). The serum levels of all three interleukins strongly correlated with severity of disease. Although IL-17, 22 and 23 decreased after NBUVB, decline in IL-17 was not significant after phototherapy as compared to controls (p=0.634). IL-22 and 23 continued to remain elevated post-phototherapy when compared with control group (p<0.05, p<0.0001, respectively).Conclusions: The serum levels of IL-17, 22 and 23 decrease after phototherapy in psoriasis. Post-phototherapy only the IL-17 levels decrease to that of non-psoriasis controls. Our study supports the role of T helper 17 cell specific cytokines in psoriasis and a possible mechanism of action of NBUVB via inhibition of these cytokines.
In recent years, with the development of photovoltaic system and photo-thermal system technology, hybrid photovoltaic-thermal (PVT) technology has been a breakthrough in many aspects. This paper describes the movable hybrid PVT system from the aspects of appearance structure, energy flow, and control circuit. The system is equipped with rolling wheels and the simulated light sources also can be removed so that the system can be used in the outdoor conditions. The movable system is also suitable for the PVT system and its related applications without any external power supply. This system combines two technologies: photovoltaic power generation and photo-thermal utilization. The first part of the power supply is for the systems own output power supply, and the second part is for generating thermal energy. The two separate parts can be controlled and monitored respectively through the control circuits and the touch screens. The experimental results show that the system can generate 691 kWh electric energy and 3047.8 kWh thermal energy each year under normal working conditions. The efficiency of the proposed movable hybrid PVT system is calculated to be approximately 42.82% using the revised equations that are proposed in this paper. Therefore, the movable hybrid PVT system can meet the daily demands of hot water and electricity power in remote areas or islands and other non-grid areas. It also can be used to conduct experiment tests for the PVT system.
This paper assesses how different levels of geographical disaggregation of wind and photovoltaic energy resources could affect the outcomes of an energy system model by 2020 and 2050. Energy system models used for policy making typically have high technology detail but little spatial detail. However, the generation potential and integration costs of variable renewable energy sources and their time profile of production depend on geographic characteristics and infrastructure in place. For a case study for Austria we generate spatially highly resolved synthetic time series for potential production locations of wind power and PV. There are regional differences in the costs for wind turbines but not for PV. However, they are smaller than the cost reductions induced by technological learning from one modelled decade to the other. The wind availability shows significant regional differences where mainly the differences for summer days and winter nights are important. The solar availability for PV installations is more homogenous. We introduce these wind and PV data into the energy system model JRC-EU-TIMES with different levels of regional disaggregation. Results show that up to the point that the maximum potential is reached disaggregating wind regions significantly affects results causing lower electricity generation from wind and PV. (C) 2017 The Authors. Published by Elsevier Ltd.
Photovoltaic arrays are the means to convert solar power into electricity, and a significant way to generate renewable and clean energy. To be efficient, a photovoltaic must generate constantly the maximum possible power and under different environmental conditions. Finding the maximum generated power has been a known issue in the industry using methods of classic control theory with very good results. However, those solutions are case-specific resulting to increased set-up effort. This work proposes a universal RLMPPT control method based on a reinforcement learning (RL) method that tracks and adjusts the maximum power point of a photovoltaic source without any prior knowledge. A Markov Decision Process (MDP) model for the Maximum Power Point Tracking (MPPT) photovoltaic process is defined and an RL algorithm is proposed and evaluated on a number of photovoltaic sources. The proposed RLMPPT control method has the advantage of being applicable to different PV sources with minimum set-up time. To evaluate the RLMPPT control method performance, a number of simulations run under different environmental and operating conditions and a comparison with the conventional method of Perturb and Observe (P&O) is performed. Results show quick response and close to optimal behavior without requiring any prior knowledge. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a fast and novel method to determine the optimal capacity of a battery and a hydrogen system for a grid-connected photovoltaic (PV) system based on the required grid dependency (GD) and the minimum Levelized Cost of Energy (LCE). The GD is calculated from the weather data at 9 locations throughout Japan during 25 years considering different sizing of PV, battery, and hydrogen system. Based on the results, the relationship between the GD and the capacities of the devices and the weather parameter is established. The results show that the GD depends on the annual total solar insolation and the devices' capacities as well. The empirical GD formula is then examined at a different location in Japan. The proposed GD calculation agrees well with the GD obtained from the real 25 - year weather data and shows great advantages over the conventional method in the simplicity and calculation time. In addition, the optimal capacity of the system can be obtained directly from the GD formula and the objective function of the LCE. (C) 2017 Elsevier Ltd. All rights reserved.
Risk analysis is essential for attracting investment to solar projects. This paper measures risk as the variability in internal rate of return (IRR) and estimates it from the uncertainty in (i) future systems prices, (ii) operations costs and (iii) revenues based on energy yield, irradiance and electricity prices. We quantify these risks for photovoltaic (PV) and concentrated photovoltaic (CPV) projects starting in 2016, 18 and 20 for customers selling solar-generated electricity under a fixed feed-in tariff (FIT) and for large business customers displacing electricity loads that they would pay for according to variable market rates. An international comparison of results is provided. Uncertainty in future systems prices causes on average 45% (PV) and 93% (CPV) variation in IRR, which is important to a developer's planning process but is resolvable with negotiated system prices from suppliers. Uncertainty in future operations costs impacts the IRR by on average 17% (PV) and 20% (CPV). Uncertainty in revenues impacts the IRR by at most 3.6%. Furthermore, the analysis shows that overall percentage variability in a project's IRR is much less than the percentage variability in operations costs and revenues, which are the two factors at play once the system is operating. (C) 2017 Elsevier Ltd. All rights reserved.
Although child maltreatment medical research has benefited from several multi-center studies, the new specialty of child abuse pediatrics has not had a sustainable network capable of pursuing multiple, prospective, clinically-oriented studies. The Child Abuse Pediatrics NetWork (CAPNET) is a new multi-center research network dedicated to child maltreatment medical research. In order to establish a relevant, practical research agenda, we conducted a modified Delphi process to determine the topic areas with highest priority for such a. network. Research questions were solicited from members of the Ray E. Helfer Society and study authors and were sorted into topic areas. These topic areas were rated for priority using iterative rounds of ratings and in-person meetings. The topics rated with the highest priority were missed diagnosis and selected/indicated prevention. This agenda can be used to target future multi-center child maltreatment medical research. (C) 2017 Elsevier Ltd. All rights reserved.
Cognitive deficits are pervasive among people with schizophrenia and treatment options are limited. There has been an increased interest in the neurocognitive benefits of exercise, but a comprehensive evaluation of studies to date is lacking. We therefore conducted a meta-analysis of all controlled trials investigating the cognitive outcomes of exercise interventions in schizophrenia. Studies were identified from a systematic search across major electronic databases from inception to April 2016. Meta-analyses were used to calculate pooled effect sizes (Hedges g) and 95% CIs. We identified 10 eligible trials with cognitive outcome data for 385 patients with schizophrenia. Exercise significantly improved global cognition (g = 0.33, 95% CI = 0.13-0.53, P = .001) with no statistical heterogeneity (I-2 = 0%). The effect size in the 7 studies which were randomized controlled trials was g = 0.43 (P < .001). Meta-regression analyses indicated that greater amounts of exercise are associated with larger improvements in global cognition (beta = .005, P = .065). Interventions which were supervised by physical activity professionals were also more effective (g = 0.47, P < .001). Exercise significantly improved the cognitive domains of working memory (g = 0.39, P = .024, N = 7, n = 282), social cognition (g = 0.71, P = .002, N = 3, n = 81), and attention/vigilance (g = 0.66, P = .005, N = 3, n = 104). Effects on processing speed, verbal memory, visual memory and reasoning and problem solving were not significant. This meta-analysis provides evidence that exercise can improve cognitive functioning among people with schizophrenia, particularly from interventions using higher dosages of exercise. Given the challenges in improving cognition, and the wider health benefits of exercise, a greater focus on providing supervised exercise to people with schizophrenia is needed.
The purpose of this study was to evaluate the relationship between daytime activity (sedentary time, moderate- to vigorous-intensity physical activity [MVPA]) and indices of polysomnographically (PSG) assessed sleep, including sleep-disordered breathing (SDB). One hundred and thirty-six adults (65% female, 59.8 +/- 9.1 years, body mass index [BMI] 30.3 +/- 6.9 kg m(-2)) provided daily estimates of time spent in light-, moderate-, and vigorous-intensity activity for 6-14 days (mean 9.9 +/- 1.8 days) prior to laboratory PSG. Daily sedentary time was calculated as the amount of time spent awake and not in light-, moderate-, or vigorous-intensity activity; time spent in moderate- and vigorous-intensity activity were combined for MVPA. Indices of PSG sleep included timing (sleep midpoint), duration (total sleep time), continuity (sleep efficiency), depth (% slow-wave sleep), and SDB (apnea-hypopnea index [AHI]). Using median splits of sedentary time and MVPA, analyses of covariance examined their relationship with sleep following adjustment for age, sex, race, employment, education, BMI, existing cardiovascular disease, depression history, and mean daily wake time. Binary logistic regression examined the odds of having at least mild-severity SDB (AHI ae 5) according to sedentary time, MVPA, and their combination. Adults with above-median sedentary time (i.e., >841.9 min/day) had significantly greater AHI (P = .04) and lower odds of mild SDB (P = .03) compared to adults with low sedentary time; adults with high MVPA (>30.5 min/day) had significantly lower AHI compared to adults with low MVPA (P = .04). When examined in the same model, adults with high sedentary time and low MVPA had significantly higher AHI (P < .01) and higher odds of having mild SDB (P = .03) than all the other groups. No other sleep measures were related to sedentary time, MVPA, or their combination. Sedentary time and MVPA were associated with SDB. Whether reducing sedentary time leads to lower SDB severity deserves future exploration.
The vast majority of research on child abuse potential has concentrated on women demonstrating varying levels of risk of perpetrating physical child abuse. In contrast, the current study considered factors predictive of physical child abuse potential in a group of 70 male intimate partner violence offenders, a group that would represent a likely high risk group. Elements of Social Information Processing theory were evaluated, including pre-existing schemas of empathy, anger, and attitudes approving, of parent-child aggression considered as potential moderators of negative attributions of child behavior. To lend methodological rigor, the study also utilized multiple measures and multiple methods, including analog tasks, to predict child abuse risk. Contrary to expectations, findings did not support the role of anger independently predicting child abuse risk in this sample of men. However, preexisting beliefs approving of parent-child aggression, lower empathy, and more negative child behavior attributions independently predicted abuse potential; in addition, greater anger, poorer empathy, and more favorable attitudes toward parent-child aggression also exacerbated men's negative child attributions to further elevate their child abuse risk. Future work is encouraged to consider how factors commonly considered in women parallel or diverge from those observed to elevate child abuse risk in men of varying levels of risk. (C) 2016 Elsevier Ltd. All rights reserved.
The current investigation evaluated whether cognitive processes characteristic of the Social Information Processing model predicted parent-child aggression (PCA) risk independent of personal vulnerabilities and resiliencies. This study utilized a multimethod approach, including analog tasks, with a diverse sample of 203 primiparous expectant mothers and 151 of their partners. Factors considered in this study included PCA approval attitudes, empathy, reactivity, negative child attributions, compliance expectations, and knowledge of non-physical discipline alternatives; additionally, vulnerabilities included psychopathology symptoms, domestic violence victimization, and substance use, whereas resiliencies included perceived social support, partner relationship satisfaction, and coping efficacy. For both mothers and fathers, findings supported the role of greater approval of PCA attitudes, lower empathy, more overreactivity, more negative attributions, and higher compliance expectations in relation to elevated risk of PCA. Moreover, personal vulnerabilities and resiliencies related to PCA risk for mothers; however, fathers and mothers differed on the nature of these relationships with respect to vulnerabilities as well as aspects of empathy and PCA approval attitudes. Findings provide evidence for commonalities in many of the factors investigated between mothers and fathers with some notable distinctions. Results are discussed in terms of how findings could inform prevention programs.
How helpful legal punishment and neighbor help are in preventing parents' physical child abuse in the real-life setting has been uncertain and suspicious. The question is of concern considering prevailing advocacy for preventing child abuse in the community. To address this question, the study examines the preventive effects with a survey of 1956 high school students in the Chinese metropolis of Shanghai. Results reveal the significant preventive effects of legal punishment and neighbor help on physical abuse by the father and mother respectively. In addition, legal punishment on the mother tended to reduce the father's physical abuse in the presence of neighbor help. These results support ecological theory, which posits the joint contribution of complementary resources obtained from different sources. The results imply the merit of orchestrating support from parents, neighbors, and legal authorities for preventing child abuse. (C) 2016 Elsevier Ltd. All rights reserved.
Rapid changes in modern medicine along with advances in the science of learning and memory have necessitated a shift in the way physician knowledge is assessed. Physician recertification beyond initial certification has historically consisted of retaining large amounts of knowledge over a long time span. The adult learning theory has shown that the maintenance and improvement of our knowledge base is more effective by being exposed to new concepts at regular intervals throughout one's career and reinforcing these concepts on an ongoing basis. These philosophies have spurred several American Board of Medical Specialties member boards to embark on a variety of continuous assessment models that are designed to keep physicians up to date with the use of new technologies and innovative and flexible question formats. This article describes the new American Board of Allergy and Immunology (ABAI) Continuous Assessment Program. As the ABAI departs from the traditional secure examination/test center model and embarks on its new pilot, the focus remains firmly rooted in the core competencies that patients and the public demand and deserve. Through surveys, the ABAI has laid the groundwork for initial program design by asking its diplomates to rank the most relevant aspects of a sound clinical assessment. Periodic surveys to follow will enable the ABAI to adjust program design to provide the most pertinent content to practicing physicians to improve patient care, promote professionalism, and ensure public trust. (C) 2016 American Academy of Allergy, Asthma & Immunology.
The mouse isolated perfused kidney (MIPK) is a technique for keeping a mouse kidney under ex vivo conditions perfused and functional for 1 hr. This is a prerequisite for studying the physiology of the isolated organ and for many innovative applications that may be possible in the future, including perfusion decellularization for kidney bioengineering or the administration of anti-rejection or genome-editing drugs in high doses to prime the kidney for transplantation. During the time of the perfusion, the kidney can be manipulated, renal function can be assessed, and various pharmaceuticals administered. After the procedure, the kidney can be transplanted or processed for molecular biology, biochemical analysis, or microscopy. This paper describes the perfusate and the surgical technique needed for the ex vivo perfusion of mouse kidneys. Details of the perfusion apparatus are given and data are presented showing the viability of the kidney's preparation: renal blood flow, vascular resistance, and urine data as functional, transmission electron micrographs of different nephron segments as morphological readouts, and western blots of transport proteins of different nephron segments as molecular readout.
The mRNA differential display technique was used to identify genes from Habanero pepper (Capsicum chinense Jacq.) seedlings whose expression is modified systemically by infection with the oomycete Phytophthora capsici L. Experiments with different oligonucleotide primer combinations revealed that no single gene was synthesised de nova. Instead, the quantitative accumulation of multiple transcripts was found. From these transcripts, levels of a nitrate reductase (Capsicum chinense nitrate reductase, CcNR), which has a high percentage of identity with other Solanaceae NRs, showed a consistent increase a few hours after inoculation (hai) with P capsici. Reverse northern blotting revealed the existence of basal levels of CcNR transcripts in different adult tissues; however, systemic levels rose dramatically after spraying seedlings with salicylic acid (SA) and ethephon (ET) but not with methyl jasmonate (MeJa). Both P capsici and defence phytohormones (DP) also modified NR enzymatic activity (nitrite:NAD(+) oxidoreductase; EC 1.7.1.1) with similar kinetics. Because the application of DP induced and activated the CcNR differentially, it is possible that the activity of CcNR is related to a specific host defence response. (C) 2011 Elsevier Masson SAS. All rights reserved.
Lateral gene transfer (LGT) can facilitate the acquisition of new functions in recipient lineages, which may enable them to colonize new environments. Several recent publications have shown that gene transfer between prokaryotes and eukaryotes occurs with appreciable frequency. Here we present a study of interdomain gene transfer of cutinases - well documented virulence factors in fungi - between eukaryotic plant pathogens Phytophthora species and prokaryotic bacterial lineages. Two putative cutinase genes were cloned from Phytophthora brassicae and Northern blotting experiments showed that these genes are expressed early during the infection of the host Arabidopsis thaliana and induced during cyst germination of the pathogen. Analysis of the gene organisation of this gene family in Phytophthora ramorum and P sojae showed three and ten copies in tight succession within a region of 5 and 25 kb, respectively, probably indicating a recent expansion in Phytophthora lineages by gene duplications. Bioinformatic analyses identified orthologues only in three genera of Actinobacteria, and in two distantly related eukaryotic groups: oomycetes and fungi. Together with phylogenetic analyses this limited distribution of the gene in the tree of life strongly support a scenario where cutinase genes originated after the origin of land plants in a microbial lineage living in proximity of plants and subsequently were transferred between distantly related plant-degrading microbes. More precisely, a cutinase gene was likely acquired by an ancestor of P brassicae, P sojae, P infestans and P ramorum, possibly from an actinobacterial source, suggesting that gene transfer might be an important mechanism in the evolution of their virulence. These findings could indeed provide an interesting model system to study acquisition of virulence factors in these important plant pathogens. (c) 2007 Elsevier B.V. All lights reserved.
PID controller has been widely used in many different areas such as power systems, drives control, automotive mechatronics, aerospace, process control, and robotics. Recently, FPGA (field programmable gate array) has become an alternative solution for the realization of digital control algorithm systems. In this paper FPGA-based incremental PID (Proportional, Integral, Derivative) controller is designed and simulated. After the analysis of PID control algorithm, VerilogHDL language is used to design the software programs. Simulation results show the effectiveness and feasibility of the proposed method.
Piezoelectric bending actuators, also known as bimorphs, are characterized by very good dynamic properties and by displacements in a range of a few millimeters. Therefore these actuators are used in a wide range of applications. However their usage is limited because they require supplying amplifiers with output voltage of about 200 V, which are rather expensive. This paper presents investigation results of such amplifiers with high voltage output. The model of a piezobending actuator is proposed and implemented in Matlab-Simulink software in order to simulate the behavior of the actuator supplied by the amplifiers. The simulation results are presented and compared with investigation results of high voltage amplifier used for supplying a piezoactuator. The influence of current limitation of operational amplifier on the actuator current is tested. Finally, a low cost audio power amplifier is proposed to control the piezobender actuator (as a cheaper alternative to the high-voltage amplifier) and its investigations results are presented in the paper. (C) 2016 Elsevier Ltd. All rights reserved.
This paper presents the design and the realisation of a technique to attenuate the hysteresis nonlinear phenomenon of piezoelectric actuators. Piezoelectric actuator are widely utilised for deformable mirrors used for MOAO and power laser beam shaping techniques. The nonlinearities of piezo are usually iteratively compensated using closed-loop set-ups. In open-loop control, the hysteresis and the creep of the piezo cannot be corrected, thus this nonlinearities must be removed or at least minimised. The concept has been demonstrated on high displacement Amplified Piezoelectric Actuators (APA) mounted in a Fabry-Perot interferometer. The hysteresis attenuation technique aims to assist the Fabry-Perots nano-positioning control system to attain its main scientific specification. In such system, each APA has a maximum stroke of 270 pm within a 170 V (-20 V to +150 V) range and is used to position a high reflective mirror plate. The Fabry-Perots nano-positioning control system is specified to limit the APAs positioning steady-state noise to 3nm rms, but the hysteresis limits the positioning accuracy. In order to attenuate hysteresis, a hybrid amplifier circuit built with a high power operational amplifier has been designed and applied for each APA. The experiments results show that the hysteresis effect has almost been eliminated, and consequently the positioning steady-state noise can significantly been reduced. Because of the excellent results of this hybrid amplifier, a patent application has been introduced in June 12, 2015 under number N 1555381 and is being reviewed now.
This paper studies and implements a 15-W driver for piezoelectric actuators. The discussed driver is mainly composed of a flyback converter and a power operational amplifier (P-OPA). The flyback converter produces a variable DC voltage to supply the P-OPA, which outputs an amplified sinusoidal signal with a DC bias of 100V to drive the piezoelectric actuator. The power losses can be reduced because the supply voltage of the P-OPA varies with the peak of the input signal. The power conversion efficiency of the driver can thus be promoted up to more than 30%. From the experimental results, the implemented prototype possesses some advantageous features, such as a nearly constant output-to-input voltage gain, a high slew rate, a high input impedance, a low output impedance, and low output voltage ripples. Copyright (c) 2016 John Wiley & Sons, Ltd.
Foxol plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes preadipocyte differentiation of clonal cell lines from rodents. We isolated the full-length cDNA of porcine FoxO1 gene using RACE, confirmed by visual Northern blotting. The deduced amino acids indicated 94% and 90% identities with the corresponding human and mice aa. Analysis of the aa sequence, showed that it included a Forkhead domain (aa 167-247), a transmembrane structure domain (aa 90-113), a LXXLL motif (aa 469-473), and 51 Ser, 8 Thr, and 4 Tyr phosphorylation sites, indicating a potential important role for FoxO1 transcriptional activity in vivo. Using the IMpRH panel, we mapped FoxO1 gene to chromosome 11p13. Our data provide basic molecular information useful for the further investigation on the function of FoxO1 gene. Time-course analysis of FoxO1 expressions indicated that levels of mRNA and protein gradually increased from day 0 to 3, and it reached almost maximal level at day 3, then decreased from day 5 to 7 in porcine primary preadipocyte differentiation. After induction by IGF-1, GPDH activity and accumulation of lipid increased, however, expressions of FoxO1 mRNA and protein were inhibited in a dose dependent manner. These results suggest that FoxO1 takes part in porcine preadipocyte differentiation and expressions of FoxO1 were regulated by IGF-1.
Maturation of cumulus-oocyte complexes (COCs) is crucial for further successful monospermic fertilization, embryo growth, and implantation. All these events are accompanied by proliferation and differentiation of cumulus cells. The migration of COCs to the oviduct after ovulation and the interaction between female gametes and/or embryos with maternal tissues are still poorly recognized on the molecular level. This study was aimed to first demonstrate themRNAexpression profile of cell migration markers during different stages of porcine oocytes maturation and developmental capability in vitro. The COCs were collected from a total of 45 pubertal crossbred Landrace gilts, brilliant cresyl blue (BCB) stained, and analyzed before (n = 150) or after (n = 150) in vitro maturation (IVM). Using the Affymetrix((R)) Porcine Gene 1.1 ST Array, the expression profile of 12,258 porcine transcripts was examined. We found nine genes involved in cell migration mechanisms, that is, PLD1, KIT, LAMA2, MAP3K1, VEGFA, TGFBR3, INSR, TPM1, and RTN4. These genes were upregulated in porcine oocytes before IVM as compared with post-IVM expression analysis. Moreover, important mechanisms of biological interaction between VEGFA-KIT and VEGFA-INSR were also observed. The upregulation and/or downregulation of selected mRNAs expression after microarray assays was checked and approved by real-time quantitative polymerase chain reaction. We suggest that several genes, including LAMA2 or TPM1, encode proteins participating in the formation of the oocyte's protein architecture such as microtubules and kinetochore reorganization. As the expression of all `` migration regulatory genes'' investigated in this study was significantly upregulated in oocytes before IVM, we conclude that they may contribute to the maturational capability of porcine oocytes. However, migration potency of COCs is not accompanied by achievement of the MII stage by porcine oocytes in vitro. The investigated genes such as PLD1, KIT, LAMA2, MAP3K1, VEGFA, TGFBR3, INSR, TPM1, and RTN4 may be recognized as a new marker of porcine oocytes maturational competence during in vitro culture.
The ability to engineer cells to express a protein of interest in an inducible manner and stably for a long period is a valuable tool in molecular biology and also one that holds promise for regenerative medicine in the future. CCN proteins have been suggested to be involved in tissue regeneration. In this chapter, we describe an in vitro method for stable and inducible expression of CCN protein in a chondroprogenitor cell line and in chondrocytes in primary culture that does not involve the use of any viral vector.
Objectives: We aimed to study the antitumor effects of the PPAR gamma agonist pioglitazone on human retinoblastoma. Methods: The effects of pioglitazone on cell proliferation and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hoechst 33258 staining assay. The apoptosis related protein levels were detected by western blot. Inflammationary factors analysis was evaluated by western blot and ELISA. The effect of pioglitazone on nuclear factor-kappa B (NF-kappa B)-dependent reporter gene transcription induced by LPS was analyzed by NF-B-luciferase assay. Then human retinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice and the animals were treated with pioglitazone to verify its antitumor effect in vivo. Results: Our data revealed that pioglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that pioglitazone could affect the apoptosis and inflammation related signal via modulating the activity of NF-kappa B signal. Also we found that pioglitazone could markedly reduce the growth of Y79 cells transplanted into the mice without causing significant side effects. Conclusions: Our results suggested that pioglitazone demonstrated antitumor activity against the human retinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and modulating NF-kappa B pathway, and thus delayed tumor growth in vivo.
A fast Fourier transform (FFT)-based digital calibration method for 1.5 bit/stage pipeline analog-to-digital converter (ADC) is proposed in this paper. Capacitor mismatch and finite gain of the operational amplifier (OPAMP) can be overcome by the proposed calibration method. Given that the capacitor mismatch and the finite OPAMP gain cause the radix of all the stages of 1.5 bit/stage pipeline ADC to become unequal to 2, the FFT processor can be adopted to evaluate the actual radixes of all the stages and then generate new digital output to compensate for error caused by these non-ideal effects. Moreover, as capacitor mismatch and the finite gain of OPAMP can be compensated, low-gain OPAMP can be used in high-performance ADC to reduce power dissipation; a small capacitor can then be adopted to save on space. An example of a 10 bit 1.5 bit/stage pipelined ADC with only an 8 bit circuit performance is implemented in 0.18 mu m TSMC CMOS process. Circuit measurement result reveals that the signal-to-noise-and-distortion ratio of 51.03 dB with 11 dB improvement after calibration can be achieved at the sample rate of 1 MHz. Copyright (c) 2013 John Wiley & Sons, Ltd.
This design pays much attention on analyzing and calculating Miller capacitor in operational amplifier to optimist OP (Operational Amplifier). The design for a 8-bit high speed, low power pipeline ADC is based on standard 0.18um CMOS technology, with 3.3 power supply. The results show that the dc gain of the operational amplifier is 96dB, the gain-bandwidth is 167MHZ, and the ADC can achieve 8bits resolution and 10M samples/s.
A 14-bit 50-MS/s pipelined analog-to-digital converter (ADC) is presented. Operational amplifier (op-amp) sharing technique, 1.5 bit redundant stages based on switched capacitor circuits with inverter-based comparators and digital gain error calibration are used to reduce power consumption of the ADC and relax op-amp requirements. Simulation results in MATLAB/Simulink (structure level) and Cadence Virtuoso (schematic level, 180 nm 1.8 V CMOS) are provided. The pipelined ADC achieves 70 dB SINAD/80 dB SFDR and consumes 135 mW at 1.8 V supply, FoM is 1.04 pJ/conv.
In this paper the main aspects in construction of the low-power CMOS pipelined analog-to-digital converters (ADCs) are discussed. The main requirements for a 1.5 bit redundant stage of the pipeline ADC are defined. Examples of the digital and the analog error correction mechanisms for the pipelined ADC in conjunction with the power reduction mechanisms are considered.
Black pepper (Piper nigrum L.), member of the family Piperaceae is indigenous to India and is one of the most widely used spices in the world. In this paper we report the results of our attempts to identify a set of genes differentially expressed in the leaves of Piper nigrum, which could facilitate targeted engineering of this valuable crop. A PCR-based Suppression Subtractive Hybridization (SSH) technique was used to generate a leaf-specific subtracted cDNA library of Piper nigrum. A tester population of leaf cDNA was subtracted with a root derived driver cDNA. The efficiency of subtraction was confirmed by PCR analysis using the housekeeping gene actin. On sequence analysis, almost 30% of the clones showed homology to metallothionein type-2 gene. The predominance of metallothionein transcripts in the leaf was further confirmed using Real-Time PCR analyses and Northern blot. The possible role of metallothionein type-2 homologues in the leaf is discussed along with the feasibility of using SSH technique for identification of more number of tissue-specific genes from Piper nigrum.
The study examined whether the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised Edition (DC: 0-3R; ZERO TO THREE, 2005) Parent-Infant Relationship Global Assessment Scale (PIR-GAS) is applicable to six European countries and contributes to the identification of caregiver-infant/toddler dyads with abusive relationship patterns. The sample consisted of 115 dyads with children's ages ranging from 1 to 47 months. Sixty-four dyads were recruited from community settings without known violence problems, and 51 dyads were recruited from clinical settings and already had been identified with violence problems or as being at risk for violence problems. To classify the dyads on the PIR-GAS categories, caregiver-child interactions were video-recorded and coded with observational scales appropriate for child age. To test whether the PIR-GAS allows for reliable identification of dyads with abusive relationship patterns, PIR-GAS ratings were compared with scores on the the International Society for the Prevention of Child Abuse and Neglect's (ISPCAN) Child Abuse Screening Tool-Parental Version (ICAST-P; D.K. Runyan etal., ), a questionnaire measuring abusive parental disciplinary practices. It was found that PIR-GAS ratings differentiated between the general and the clinical sample, and the dyads with abusive patterns of relationship were identified by both the PIR-GAS and the ICAST-P. Interrater reliability for the PIR-GAS ranged from moderate to excellent. The value of a broader use of tools such as the DC: 0-3R to promote early identification of families at risk for infant and toddler abuse and neglect is discussed.
Piwi-interacting RNAs (piRNAs) are 26 to 31-nt small non-coding RNAs that have been reported mostly in germ line cells and cancer cells. However, the presence of piRNAs in the whitespotted bamboo shark liver has not yet been reported. In a previous study of microRNAs in shark liver, some piRNAs were detected from small RNAs sequenced by Solexa technology. A total of 4857 piRNAs were predicted and found in shark liver. We further selected 17 piRNAs with high and significantly differential expression between normal and regenerative liver tissues for subsequent verification by Northern blotting. Ten piRNAs were further identified, and six of these were matched to known piRNAs in piRNABank. The actual expression of six known and four novel piRNAs was validated by qRT-PCR. In addition, a total of 401 target genes of the 10 piRNAs were predicted by miRanda. Through GO and pathway function analyses, only five piRNAs could be annotated with eighteen GO annotations. The results indicated that the identified piRNAs are involved in many important biological responses, including immune inflammation, cell-specific differentiation and development, and angiogenesis. This manuscript provides the first identification of piRNAs in the liver of whitespotted bamboo shark using Solexa technology as well as further elucidation of the regulatory role of piRNAs in whitespotted bamboo shark liver. These findings may provide a useful resource and may facilitate the development of therapeutic strategies against liver damage. (C) 2016 Elsevier B.V. All rights reserved.
The labelled of pistachio on food products is mandatory and, as a consequence, the development of suitable analytical methodologies to detect this nut in processed foods is advisable. In this work, two different qPCR assays to detect pistachio, SYBR (R) Green and locked nucleic acid (LNA) probes, are tested and compared. Pis v allergen coding sequences have been amplified and cloned in different pistachio varieties, and specific primers and probes for each allergen have been designed. According to our results, LNA probe-real time PCR appears to be the most sensitive and specific method, reaching 10 mg/kg of pistachio. The effect of temperature and/or pressure on pistachio DNA detection was also analysed by LNA probe-based qPCR. Data showed a reduced amplificability of pistachio after thermal treatment under pressure, nevertheless, this effect was not observed after boiling. The applicability of this method has been studied by analysing 14 food products and by comparison with a commercial ELISA kit. (C) 2016 Elsevier Ltd. All rights reserved.
The PKI55 protein was identified in our laboratory as specific protein kinase C inhibitor. We previously demonstrated that PKI55 is poorly translated in vivo and acts promoting PKC degradation and establishing a feedback loop of inhibition. However, our understanding of mechanisms by which the expression of PKI55 is regulated, is limited. In the present work we investigated the mRNA expression of PKI55 in human tissues by Northern blotting and RT-PCR, demonstrating that it is highly expressed in brain tissue. Moreover, since the computational analysis of the gene promoter region showed two sites (Box I and Box 2) similar to consensus sequences for AP1 and GAGA factors, we investigated their ability to bind to these proteins. Electrophoretic mobility shift assays showed that GAGA factors preferentially interacted with Box 2, while AP1 elements linked preferentially Box I sequence. We suggest that the interaction of these transcription factors with Box 1 and Box 2 could regulate the transcription of the PKI55 gene and, consequently, the expression of PKC. (C) 2008 Elsevier Masson SAS. All rights reserved.
The PLAGL1 gene encodes a homonymous zinc finger protein that promotes cell cycle arrest and apoptosis through multiple pathways. The protein has been implicated in metabolic, genetic, and neoplastic illnesses, but the molecular mechanisms by which the protein PLAGL1 participates in such diverse processes remains to be elucidated. In this review, we focus mainly on the molecular biology of PLAGL1 and the relevance of its abnormalities to several pathological processes.
The total environment includes 5 closely-linking circles, in which biosphere and lithosphere are the active core. As global population increases and urbanization process accelerates, arable land is gradually decreasing under global climate change and the pressure of various types of environmental pollution. This case is especially for China. Land is the most important resources for human beings' survival. How to increase and manage arable land is the key for sustainable agriculture development. China has extensive marshy land that can be reclamated for the better potential land resources under the pre- condition of protecting the environment, which will be a good way for enlarging globally and managing arable land. Related studies have been conducted in China for the past 30years and now many results with obvious practical efficiency have been obtained. For summarizing these results, salt-soil will be the main target and related contents such as nutrient transport, use types, biodiversity and interactions with plants from molecular biology to ecology will be covered, in which the interactions among biosphere, lithosphere, atmosphere and anthroposphere will be focused on. (C) 2016 Elsevier B.V. All rights reserved.
Infectious plant diseases are caused by pathogenic microorganisms such as fungi, bacteria, viruses, viroids, phytoplasma and nematodes. Worldwide, plant pathogen infections are among main factors limiting crop productivity and increasing economic losses. Plant pathogen detection is important as first step to manage a plant disease in greenhouses, field conditions and at the country boarders. Current immunological techniques used to detect pathogens in plant include enzyme-linked immunosorbent assays (ELISA) and direct tissue blot immunoassays (DTBIA). DNA-based techniques such as polymerase chain reaction (PCR), real time PCR (RTPCR) and dot blot hybridization have also been proposed for pathogen identification and detection. However these methodologies are time-consuming and require complex instruments, being not suitable for in-situ analysis. Consequently, there is strong interest for developing new biosensing systems for early detection of plant diseases with high sensitivity and specificity at the point-of-care. In this context, we revise here the recent advancement in the development of advantageous biosensing systems for plant pathogen detection based on both antibody and DNA receptors. The use of different nanomaterials such as nanochannels and metallic nanoparticles for the development of innovative and sensitive biosensing systems for the detection of pathogens (i.e. bacteria and viruses) at the point-of-care is also shown. Plastic and paper-based platforms have been used for this purpose, offering cheap and easy-to-use really integrated sensing systems for rapid on-site detection. Beside devices developed at research and development level a brief revision of commercially available kits is also included in this review.
Introduction: Endarterectomized human atherosclerotic plaques are a valuable basis for gene expression studies to disclose novel imaging biomarkers and therapeutic targets, such as the cannabinoid receptor type 2 (CB2). In this work, CB2 is expressed on activated immune cells, which are abundant in inflamed plaques. We evaluated the CB2-specific radiotracer [C-11]RS-016 for imaging vascular inflammation in human and mouse atherosclerotic lesions. Methods: The differential gene expression of microscopically classified human carotid plaques was evaluated using quantitative polymerase chain reaction. In addition, CB2 expression levels in human plaques were investigated by in vitro autoradiography. As an appropriate animal model we used apolipoprotein E knockout mice (ApoE KO) with shear stress-induced atherosclerosis to evaluate CB2 levels in vivo. Positron emission tomography (PET) was performed with both the CB2 radioligand [C-11]RS-016 and the metabolic radiotracer [F-18]fluorodeoxyglucose ([F-18]FDG) at various time points. Retrospectively, carotids were dissected for histopathology and gene expression analysis. Results: We identified 28 human genes differentially expressed in atherosclerotic plaques compared to normal arteries of which 12 were upregulated preferentially in vulnerable plaques. The latter group included members of matrix metalloproteinase family and the T-lymphocyte activation antigens CD80 and CD86. CB2 was upregulated by 2-fold in human atherosclerotic plaques correlating with CD68 expression levels. Specific in vitro binding of [C-11]RS-016 was predominantly observed to plaques. In vivo PET imaging of ApoE KO mice revealed accumulation of[C-11]RS-016 and [F-18]FDG in atherosclerotic plaques. Development of advanced plaques with elevated CB2 and CD68 levels were found in vitro in ApoE KO mice resembling human vulnerable plaques. Conclusion: We identified human genes associated with plaque vulnerability, which potentially could serve as novel imaging or therapeutic targets. The CB2-specific radiotracer [C-11]RS-016 detected human plaques by in vitro autoradiography and accumulated in vivo in plaques of ApoE KO mice, however not exclusively in vulnerable plaques. (C) 2017 Elsevier Inc All rights reserved.
The tractability of the budding yeast genome has provided many insights into the fundamental mechanisms regulating cellular life. With the advent of synthetic biology and single-cell measurements, novel tools are required to manipulate the yeast genome in a more controlled manner. We present, here, a new family of yeast shuttle vectors called single integration vectors (pSIV). Upon transformation in yeast, these plasmids replace the entire deficient auxotrophy marker locus by a cassette containing an exogenous marker. As shown using flow cytometry, this complete replacement results in a unique integration of the desired DNA fragment at the marker locus. In addition, a second transcriptional unit can be inserted to achieve the simultaneous integration of two constructs. The selection marker cassettes, present in the pSIV, were also used to generate a complete set of gene tagging plasmids (pGT) encompassing a large palette of fluorescent proteins, from a cyan fluorescent protein to a near-infrared tandem dimer red fluorescent protein. These tagging cassettes are orthogonal to each other thanks to the use of different TEF promoter and terminator couples, thereby avoiding marker cassette switching and favoring integration in the desired locus. In summary, we have created two sets of robust molecular tools for the precise genetic manipulation of the budding yeast.
pSK41 is a prototypical 46-kb conjugative multiresistance plasmid of Staphylococcus aureus. The pSK41 replication initiation protein (Rep) is rate-limiting for plasmid replication, and its expression is negatively regulated by a small, non-coding antisense transcript, RNAI, that is complementary to the rep mRNA leader region. In this study, enzymatic probing was used to verify the predicted secondary structures of RNAI and its target RNA. We demonstrated that two stem-loop structures of RNAI, SLRNAI-II and SLRNAI-III, were important for inhibition. A putative U-turn motif detected in the loop of SLrep-I (5'-UUGG-3') was analysed for its significance to RNAI-mediated inhibition in vivo and Northern blotting suggested that rep mRNA was processed. Taken together, these observations support our previously proposed model but also raise new questions about the replication control mechanism. (C) 2015 Elsevier Inc. All rights reserved.
For malaria transmission, Plasmodium parasites must develop in the mosquito vector. Oxidative stress in the insect midgut, triggered by environmental changes (e.g., pH and temperature), influences the cellular signaling involved in differentiation from gametocytes to mobile ookinetes for the purpose of parasite survival. Oxidative stress activates the homeostatic response to stress characterized by the phosphorylation eIF2 alpha, the attenuation of protein synthesis, and the transcription of genes participating in the unfolded protein response and antioxidant processes, forming a part of an integrated stress response (ISR). We hypothesized that ISR operates during the differentiation of gametocytes to ookinetes to assure Plasmodium survival. Using in-vitro conditions resembling the mosquito midgut conditions, we cultured Plasmodium berghei gametocytes to ookinetes and evaluated the redox balance by detecting reactive oxygen species and superoxide dismutase activity. Additionally, we evaluated the phosphorylation of eIF2 alpha, the attenuation of the global protein synthesis, and the gene expression of cellular stress markers (e.g., endoplasmic reticulum chaperones and antioxidant molecules, measured by reverse-transcription quantitative polymerase chain reaction), finding that these processes were all taking place, probably to improve survival during the differentiation of Plasmodium berghei ookinetes.
Malaria is caused by parasites of the genus Plasmodium, which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum, it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1(42)) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in Aotus monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP142 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the P. vivax plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP1(42) in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and this regimen for further development.
A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 x 10(5) PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ- specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.
Background: Alloimmunization against human platelet antigens (HPAs) can occur prenatally and induce fetal/neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to identify placental histological features associated with platelet alloimmunization and their clinical significance. Methods: This study examined 21 placentas from FNAIT-affected pregnancies and 42 age-matched control cases, all collected from pathology departments in the Rhone-Alpes region. Clinical and laboratory findings were collected for each FNAIT case. Two pathologists reviewed the placental slides of each FNAIT and control case. Histological features, with special emphasis on chronic inflammatory lesions, were evaluated. Differences between the two groups were calculated with odds ratios (ORs) and assessed with Wald's chi-square. Results: FNAIT was associated with a significantly higher frequency of chronic chorioamnionitis (CC) (OR 14, 95%Cl 1.7-113.8), basal chronic villitis (BCV) (OR 17, 95%CI 2-145.6) and chronic intervillositis (CIV). Chronic villitis (CV) (OR 3.7, 95%CI 0.9-15.2) and chronic deciduitis (CD) (OR 4.7, 95%CI 0.79-28.2) were also more frequent in the FNAIT than the control group, but these differences were not statistically significant. Conclusions: FNAIT is significantly associated with CC, BCV, and CIV. This chronic inflammatory reaction is preferentially localized on the maternofetal interface. Anti-HPA alloimmunization may trigger an immunological conflict similar to graft-versus-host disease. (C) 2016 Elsevier Ltd. All rights reserved.
Immunization against human platelet alloantigens (HPAs) is associated with a number of clinical complications. The detection and identification of clinically relevant platelet antibodies are important for the diagnosis and management of patients affected with immune-mediated thrombocytopenias. Human platelet alloantigen frequencies and the characteristics of antiplatelet antibodies vary widely between ethnic groups. Since 2008, the importance of platelet immunology in the field of transfusion medicine has gained greater recognition by clinical laboratories in China. Laboratories in China have established and improved methods for platelet antibody detection and HPA genotyping techniques, which are used for the diagnosis of alloimmune platelet disorders in clinic and research environments. Research has revealed the frequencies of HPA alleles in different Chinese ethnic groups and compared the differences in HPA gene frequencies between the Chinese Han and other ethnic groups of the world. Production of anti-CD36 isoantibodies is an important risk factor for immune-mediated thrombocytopenia in the Chinese population. Advances in research and clinical application of platelet immunology have significantly improved the clinical diagnosis, treatment including transfusion support, and prevention of alloimmune platelet disorders in the Chinese population.(C)2017 Published by Elsevier Inc.
Phospholipase D (PLD) and phosphatidylcholine (PC) were implicated in apoptosis and cancer. However, direct evidence on the role of PLD in the cause of apoptosis remains obscure. It was recently reported that apoptosis and necrosis could be induced in the cerebellum and brainstem after focal cerebral hypoxic-ischemic (HI) injury. It was found that apoptosis could be enhanced by farnesol inhibition of PLD signal transduction. Whereas it was shown that highly invasive cancer cell line depends on PLD activity for survival when deprived of serum growth factors. Based on these reports, it is postulated that apoptosis in the cerebellum and brainstem induced after focal cerebral HI treatment may be caused by faulty PLD expression. This is consistent with a report that PLD1 activity and mRNA levels were down-regulated during apoptosis. To test this hypothesis, Northern blotting was used to examine PLD2 mRNA expression after focal cerebral HI. The results show that both PLD2 mRNA 10.8 and 3.9 kb transcripts were significantly decreased by as much as 37% in the brainstem and cerebellum areas 3 h after HI compared to the control, concur with previous report of decreasing PLD activity after ischemia. These PLD2 transcripts, however, were not significantly different from the control 3 days after HI, indicating that the decrease in PLD2 transcription after HI maybe a transient phenomenon. This is the first report to show that the loss of membrane integrity resulting from deprivation of energy and growth factors after HI could cause decrease in PLD2 transcription that promotes apoptosis. The hypothetic role of PLD2 and the mechanism leading to apoptosis remains to be further elucidated.
Energy management strategies (EMSs) are critical for the improvement of fuel economy of plug-in hybrid electric vehicles (PHEVs). However, conventional EMSs hardly consider the influence of uphill terrain on the fuel economy and battery life, leaving vehicles with insufficient battery power for continuous uphill terrains. Hence, in this study, an optimal control strategy for a PHEV based on the road grade information is proposed. The target state of charge (SOC) is estimated based on the road grade information as well as the predicted driving cycle on uphill road obtained from the GPS/GIS system. Furthermore, the trajectory of the SOC is preplanned to ensure sufficient electricity for the uphill terrain in the charge depleting (CD) and charge sustaining (CS) modes. The genetic algorithm is applied to optimize the parameters of the control strategy to maintain the SOC of battery in the CD mode. The pre-charge mode is designed to charge the battery in the CS mode from a reasonable distance before the uphill terrain. Finally, the simulation model of the powertrain system for the PHEV is established using MATLAB/Simulink platform. The results show that the proposed control strategy based on road-grade information helps successfully achieve better fuel economy and longer battery life.
Application of nanocomposite pour point depressants to improve the rheology of waxy crude oil is a novel and efficient technique and receives much attention. However, the effects of nano and microparticles alone on the rheology of waxy crude oil are unclear up to now. In this paper, monodispersed PMSQ microspheres with different sizes (200 nm-10 mm) were successfully synthesized through a two-step solgel route. Then the effect of the PMSQ microspheres on the flow behavior of two typical waxy crude oils was studied. The results showed that the PMSQ microspheres disperse well in oil phase as single spheres. A small dosage of the PMSQ microspheres significantly decreases the gelation point, elastic modulus G', viscous modulus G", apparent viscosity and yield stress of the two oil samples, indicating that the PMSQ microspheres improve the flow behavior of waxy crude oil at temperatures below the wax appearance temperature. The flow improving efficiency of the PMSQ microspheres is greatly influenced by the size and dosage of the microspheres. Moreover, adding PMSQ microspheres in the oil samples also inhibits asphaltenes precipitation because the PMSQ microspheres are capable of adsorbing part of the asphaltenes. However, the PMSQ microspheres have little influence on the exothermic character and microstructure of the two oil samples. Similar tests on a model waxy oil further confirmed that the PMSQ microspheres cannot participate in wax precipitation process and change the morphology of precipitated wax crystals, but can impede the interactions of the precipitated wax crystals through spacial hindrance effect, which inhibits the development of wax crystal network structure and thus improves the flow behavior of the oil. This mechanism brings a new way to improve the flow behavior of waxy crude oil and favors the development of new-generation flow improvers based on nano or microparticles. (C) 2017 Elsevier Ltd. All rights reserved.
Pneumocystis carinii (Pc) adhesion to alveolar epithelial cells is well established and is thought to be a prerequisite for the initiation of Pneumocystis pneumonia. Pc binding events occur in part through the major Pc surface glycoprotein Msg, as well as an integrin-like molecule termed PcInt1. Recent data from the Pc sequencing project also demonstrate DNA sequences homologous to other genes important in Candida spp. binding to mammalian host cells, as well as organism binding to polystyrene surfaces and in biofilm formation. One of these genes, flo8, a transcription factor needed for downstream cAMP/PKA-pathway-mediated activation of the major adhesion/flocculin Flo11 in yeast, was cloned from a Pc cDNA library utilizing a partial sequence available in the Pc genome database. A CHEF blot of Pc genomic DNA yielded a single band providing evidence this gene is present in the organism. BLASTP analysis of the predicted protein demonstrated 41 % homology to the Saccharomyces cerevisiae Flo8. Northern blotting demonstrated greatest expression at pH 6.0-8.0, pH comparable to reported fungal biofilm milieu. Western blot and immunoprecipitation assays of PcFlo8 protein in isolated cyst and tropic life forms confirmed the presence of the cognate protein in these Pc life forms. Heterologous expression of Pcflo8 cDNA in flo8 Delta-deficient yeast strains demonstrated that the Pcflo8 was able to restore yeast binding to polystyrene and invasive growth of yeast flo8 Delta cells. Furthermore, Pcflo8 promoted yeast binding to HEK293 human epithelial cells, strengthening its functional classification as a Flo8 transcription factor. Taken together, these data suggest that PcFlo8 is expressed by Pc and may exert activity in organism adhesion and biofilm formation.
Background: Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-beta 1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. Methods: The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-beta 1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. Results: TGF-beta 1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-beta 1. Conclusion: We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.
Background: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. Methods: Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH(2)O, and FiO(2) = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. Results: In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2. 0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0. 025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). Conclusion: In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.
Podcasts are digital files very popular in several and very distinct areas. In higher education, they have been explored in a multitude of ways mainly to support teaching and learning processes. The study here described focuses the integration of podcasts in Heredity and Evolution, a course from the Biology and Geology Degree Program at University of Minho, Portugal. It aimed to introduce podcasts in the teaching/learning context, to empirically study different dimensions of podcasting, and to evaluate students' acceptance and receptiveness to the pedagogical use of this technology. Five informative podcasts and three with feedback were produced and delivered. All the students listened to the audio files and considered the episodes audible and clear, their preference going to episodes of short or moderate length and containing summaries, study guidelines or syllabus contents. Students judged extremely valuable the integration of this technology in learning and showed receptiveness to podcasting in other courses. Curiously, in spite of owning mobile devices, students clearly favored the use of personal computers to listen to the podcasts. This student acceptance and openness to podcasting has been encouraging its pedagogical application in other teaching courses. The episodes produced often maintain the characteristics identified as the best by the students of this study but the pedagogical approach has been moving to a more student-centered learning situation, with students as podcasts producers. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
Electrochemical Impedance Spectroscopy (EIS) is a label-free method of molecular detection of particular interest for biomedical applications. We aim to create a hand-held, easy to use EIS measurement device, for biomolecular detection. Electrochemical cyclic voltammetry systems help millions of diabetics monitor their blood glucose levels 2-8 times per day, but their use is very limited due to the poor lower limit of detection. The EIS technique can be used to detect a much larger array of biomolecules at very low concentration. Our EIS system generates the magnitude and phase of the impedance from test samples via MATLAB, which provides the real and imaginary components of the impedance. The circuit was integrated on a single chip and fabricated in a standard 0.5 mu m CMOS technology. A hand-held EIS measurement system was built using the chip and an Arduino Uno to measure a Randles circuit equivalent over the frequency range from 1 Hz to 2 kHz, the measurement and simulation results show excellent agreement.
Advances in microfluidics and the introduction of isothermal nucleic acid amplification assays have resulted in a range of solutions for nucleic acid amplification tests suited for point of care and field use. However, miniaturisation of instrumentation for such assays has not seen such rapid advances and fluorescence based assays still depend on complex, bulky and expensive optics such as fluorescence microscopes, photomultiplier tubes and sensitive lens assemblies. In this work we demonstrate a robust, low cost platform for isothermal nucleic acid amplification on a microfluidic device. Using easily obtainable materials and commercial off-the-shelf components, we show real time fluorescence detection using a low cost photodiode and operational amplifier without need for lenses. Temperature regulation on the device is achieved using a heater fabricated with standard printed circuit board fabrication methods. These facile construction methods allow fabrications at a cost compatible with widespread deployment to resource poor settings.
Intentional childhood poisoning is an uncommon formof child abuse but has a very high risk of morbidity and mortality. Patients present with four main categories of illness: metabolic derangements (salt and water ingestion), gastrointestinal symptoms (laxative and ipecac poisoning), hemorrhagic disease (warfarin and superwarfarin exposures), and neurologic symptoms (central nervous systemdepression or excitation). While widely available, routine urine drug screens are of limited value so clinicians must have a high index of suspicion to make these diagnoses.
Transformation of pokeweed antiviral protein gene (PAP) into plants was shown to improve plant resistance to several viruses or fungi pathogens with no much negative effect on plant growth. The non-virulent defective PAP inhibits only the virus but does not interfere with the host. A non-virulent defective PAP gene (PacPAP) from Phytolacca acinosa was introduced into cucumber successfully by agrobacterium mediated method. Southern blotting and northern blotting analyses indicated that, 5 stable transgenic cucumber lines with PacPAP were obtained and PacPAP showed different expression levels in transgenic plants. The identification of resistances to disease was performed by artificial inoculation of cucumber mosaic virus (CMV) and Fusarium oxysporum fsp. cucumerinum on T-0 and T-1 transgenic plants. Compared with the non-transgenic susceptible plants, all transgenic plants with PacPAP showed resistance in different degree to CMV and the CMV-resistance of progeny (T-1) from transgenic lines could inherit stably, but the transgenic plants did not resist to Fusarium wilt of cucumber, the PacPAP was not resistant to Fusarium oxysporum fsp. cucumerinum. This work provides a new virus resistant cucumber breeding resource.
The enrichment of specific pollutant-reducing consortium is usually required prior to the startup of bio-cathode bioelectrochemical system (BES) and the whole process is time consuming. To rapidly establish a non-specific functional biocathode, direct polar inversion from bioanode to biocathode is proposed in this study. Based on the diverse reductases and electron transfer related proteins of anode-respiring bacteria (ARB), the acclimated electrochemically active biofilm (EAB) may catalyze reduction of different aromatic pollutants. Within approximately 12 d, the acclimated bioanodes were directly employed as biocathodes for nitroaromatic nitrobenzene (NB) and azo dye acid orange 7 (AO7) reduction. Our results indicated that the established biocathode significantly accelerated the reduction of NB to aniline (AN) and AO7 to discolored products compared with the abiotic cathode and open circuit controls. Several microbes possessing capabilities of nitroaromatic/azo dye reduction and bidirectional electron transfer were maintained or enriched in the biocathode communities. Cyclic voltammetry highlighted the decreased over-potentials and enhanced electron transfer of biocathode as well as demonstrated the ARB Geobacter containing cytochrome c involved in the backward electron transfer from electrode to NB. This study offers new insights into the rapid establishment and modularization of functional biocathodes for the potential treatment of complicated electron acceptors-coexisting wastewaters. (C) 2017 Elsevier B.V. All rights reserved.
Plants employ RNA silencing as a natural defense mechanism against viruses. As a counter-defense, viruses encode silencing suppressor proteins (SSPs) that suppress RNA silencing. Most, but not all, the P0 proteins encoded by poleroviruses have been identified as SSP. In this study, we demonstrated that cotton leafroll dwarf virus (CLRDV, genus Polerovirus) P0 protein suppressed local silencing that was induced by sense or inverted repeat transgenes in Agrobacterium co-infiltration assay in Nicotiana benthamiana plants. A CLRDV full-length infectious cDNA clone that is able to infect N. benthamiana through Agrobacterium-mediated inoculation also inhibited local silencing in co-infiltration assays, suggesting that the P0 protein exhibits similar RNA silencing suppression activity when expressed from the full-length viral genome. On the other hand, the P0 protein did not efficiently inhibit the spread of systemic silencing signals. Moreover, Northern blotting indicated that the P0 protein inhibits the generation of secondary but not primary small interfering RNAs. The study of CLRDV P0 suppression activity may contribute to understanding the molecular mechanisms involved in the induction of cotton blue disease by CLRDV infection. (C) 2013 Elsevier B.V. All rights reserved.
Poliovirus (PV) is typically transmitted by the fecal-oral route, which means that the risk of infection and virus distribution could be achieved by exposure to the virus contaminated in food and water. The aim of this study was to determine the occurrence of PV strains by detecting the virus in pediatric patients who admitted to the hospitals with diarrhea in Chiang Mai, Thailand during 2010-2015. By applying a reverse transcription-polymerase chain reaction and nucleotide sequencing analysis of 1,300 stool specimens collected from pediatric patients, PVs were detected at 0.61% (8 out of 1,300 specimens). Among eight PV positive samples, mixed infection with norovirus or human bocavirus was detected in one each out of eight cases. All PV strains detected in this study were characterized further by phylogenetic analysis of 343 bp of the 5' UTR and 315 bp of the partial VP1 sequences. The results revealed that eight PV strains detected in the present study two of each were PV1 and PV2, and four were PV3 serotypes of the Sabin vaccine strains. The data demonstrated the presence of PV1, PV2, and PV3 Sabin vaccine strains in children with acute gastroenteritis in Chiang Mai, Thailand. (C) 2016 Wiley Periodicals, Inc.
Research on adult populations has widely investigated the deep differences that characterize individuals who embrace either conservative or liberal views of the world. More recently, research has started to investigate these differences at very early stages of life. One major goal is to explore how parental political ideology may influence children's characteristics that are known to be associated to different ideological positions. In the present work, we further investigate the relations between parents' ideology and children cognitive processing strategies within the framework of political ideology as motivated social cognition (Jost et al., 2003) and the dual process model of political ideology (Duckitt et al., 2002). Specifically, epistemic (implicit attitudes toward order vs. chaos), existential (negativity and threat bias), and relational needs (conformity measure) were assessed in pre-school children (N = 106; 46 years). For each child at least one parent completed both the Social Dominance Orientation (SDO) and the Right Wing Authoritarianism (RWA) measures. Interestingly, results indicated that mothers' and fathers' responses had unique associations with children's socio-cognitive motivations, and different findings emerged in relation to the two facets of parental authoritarianism, namely dominance (i.e., SDO) and submission (i.e., RWA). More specifically, children's existential needs appeared to be more related to mothers' RWA scores, whereas children's epistemic needs appeared to be more related to fathers' SDO. Finally, parents' RWA and SDO scores appeared to have opposite effects on children's relational needs: children's conformity increased at increasing levels of mothers' RWA and decreased at increasing levels of fathers' SDO. Overall, however, results were relatively weak and several links between the responses of parents and their children were not significant, suggesting caution in drawing strong conclusions about the impact of parents' ideology. Limitations and future developments will be discussed.
An ergodic semi-Markov process with the structure represented by the full graph with loops, which simulates a digital control algorithm that generated transactions onto an object, is investigated. Elementary simplifications for reduction of semi-Markov processes are defined. Recursive procedure for reduction of initial semi-Markov process structure till the model, which includes selected states with its links only, is proposed. Formulae for recalculation of probabilities, weighted densities and expectations of time of switching to linked states are obtained. It is shown that recursive procedure may be used also for calculation of time expectation of return the process to one of selected states that simplified the task of evaluation of time intervals between transactions in polling procedure.
This chapter describes a method for the isolation of intact polyadenylated mRNA using LNA oligo(T) capture. The method enables efficient isolation of poly(A)(+) RNA directly from guanidinium thiocyanate (GuSCN)-containing cell or tissue extract: by combining the design of biotinylated LNA oligo(T) capture probes with subsequent immobilization of the captured poly(A)(+) RNA onto streptavidin-coated magnetic particles. In contrast to DNA oligo-dT and polyT PNA based mRNA isolation techniques, the LNA oligo(T) capture method allows poly(A) selection in the presence of 4 M GuSCN cell lysis buffer, which is needed for efficient inactivation of endogenous RNases. In addition, LNA oligo(T) facilitates highly efficient poly(A)(+) isolation at elevated temperatures compared to standard oligo(dT) technology. The successful use of the LNA oligo(T) capture method in recovery of mRNA from human cells and the subsequent use of the mRNA in northern blotting analysis, RT-PCR and qRT-PCR are demonstrated.
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.
Polymeric carriers are ubiquitously studied in vaccine and drug delivery to control the encapsulation, kinetics, and targeting of cargo. Recent research reveals many polymers can cause immunostimulatory and inflammatory responses, even in the absence of other immune signals. However, the extent to which this intrinsic immunogenicity evolves during degradation is understudied. Here we synthesized a small library of poly(beta amino esters) (PBAEs) that exhibit different starting molecular weights (MWs), but with similar and rapid degradation rates. Primary dendritic cells (DCs) treated with free PBAEs, either intact or degraded to form low MW fragments, were not activated. In contrast particles formed from PBAEs at different extents of degradation caused differential expression of classical DC activation markers (for example, CD40, CD80, CD86, MHCII), as well as antigen presentation. During degradation, activation levels changed with changing physicochemical properties (for example, MW, concentration, size, charge). Of note, irrespective of starting MW, immunogenicity peaked when the MW of degrading PBAEs decreased to a range of similar to 1500-3000 Da. These findings could help inform design of future carriers that exploit the dynamic interactions with the immune system as materials degrade, leading to carriers that deliver cargo but also help direct the immune responses to vaccine or immunotherapy cargo. (C) 2017 Wiley Periodicals, Inc.
A simple and cost effective synthesis of nanomaterials with advanced physical and chemical properties have received much attention to the researchers, and is of interest to the researchers from different disciplines. In the present work, we report a simple and one pot electrochemical synthesis of poly(melamine) entrapped gold nanoparticles (PM-AuNPs) composite. The PM-AuNPs composite was prepared by a single step electrochemical method, wherein the AuNPs and PM were simultaneously fabricated on the electrode surface. The as-prepared materials were characterized by various physicochemical methods. The PM-AuNPs composite modified electrode was used as an electrocatalyst for oxidation of catechol (CC) due to its well-defined redox behavior and enhanced electro-oxidation ability towards CC than other modified electrodes. Under optimized conditions, the differential pulse voltammetry (DPV) was used for the determination of CC. The DPV response of CC was linear over the concentration ranging from 0.5 to 175.5 mu M with a detection limit of 0.011 mu M. The PM-AuNPs composite modified electrode exhibits the high selectivity in the presence of range of potentially interfering compounds including dihydroxybenzene isomers. The sensor shows excellent practicality in CC containing water
Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor B (NF-B) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1, IL-6, and tumor necrosis factor . Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-B in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-B signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.
Fermentation of herb Polygonum hydropiper L. (PHL) and cassava pulp (CP) for feed additive production with simultaneous flavonoid dissolution was investigated, and a two-stage response surface methodology (RSM) based on Plackett-Burman factorial design (PB design) was used to optimize the flavonoid dissolution and protein content. Using the screening function of PB design, four different significant factors for the two response variables were acquired: factors A (CP) and B (PHL) for the flavonoid dissolution versus factors G (inoculum size) and H (fermentation time) for protein content. Then, two RSMs were used sequentially to improve the values of the two response variables separately. The mutual corroboration of the experimental results in the present study confirmed the validity of the associated experimental design. The validation experiment showed a flavonoid dissolution rate of 94.00%, and a protein content of 18.20%, gaining an increase in 21.20% and 199.10% over the control, respectively. The present study confirms the feasibility of feed additive production by Saccharomyces cerevisiae with CP and PHL and simultaneous optimization of flavonoid dissolution and protein content using a two-stage RSM. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc. Volume 64, Number 2, Pages 290-300, 2017
In this research, the morphologies, isothermal-crystallization kinetics, and spherulite growth of aliphatic polyketone/polyamide-6 blends were studied. A single glass-transition temperature (T (g)) was determined, and the composition dependence of T (g) for these blends was well described by the Kwei equation. The strong intermolecular interaction between the two polymer components was confirmed by melting-point depression. The isothermal-crystallization kinetics were analyzed on the basis of the Avrami approach. A linear increase in the radii of the spherulites with time was observed for all compositions. All the spherulites continued to grow at nearly identical growth rates. With increasing polyamide-6 content, the size of the spherulites in the polyketone/polyamide-6 blends gradually decreased, and the number of spherulites in the blends increased.
We presented the integration of polymerase chain reaction (PCR) microdevice and surface plasmon resonance (SPR) optical fiber sensor into an inline all-in-one device for fluorophore-free detection of PCR amplification. The proposed integrated device consisted of the microfluidic PCR reactor that used channel position-dependent temperature change and the optical fiber SPR sensor with bimetallic (Ag/Al) coating. This all-in-one device performed not only the amplification of DNA of Salmonella spp. (injected volume of 20 microlitter) within 30 min, but also the immediately subsequent measurement of the DNA amplicon by the SPR fiber sensor part. Results showed that the SPR sensor signal increased with the cycle number due to the amplicon refractive index smaller than the sum of its constituent dNTP molecules and its minimum resolvable DNA amplicon was that generated at the 15th cycle. The integrated device could serve as a DNA amplification to-detection instrument. Both the label-free nature that could allow reusability of the presented device and further miniaturization of the whole system can find use in a point-of-care testing with early diagnosis genetic analysis. (C) 2016 Elsevier B.V. All rights reserved.
The polymerase chain reaction (PCR) is considered an excellent technique and is widely used in both molecular biology research and various clinical applications. However, the presence of byproducts and low output are limitations generally associated with this technique. Recently, the use of nanoparticles (NPs) has been shown to be very effective at enhancing PCR. Although mechanisms underlying this process have been suggested, most of them are mainly based on PCR results under certain situations without abundant systematic experimental strategy. In order to overcome these challenges, we synthesized a series of polyethylene glycol (PEG)-modified polyethylenimine (PEI)-entrapped gold nanoparticles (PEG-Au PENPs), each having different gold contents. The role of the synthesized NPs in improving the PCR technique was then systematically evaluated using the error-prone two-round PCR and GC-rich PCR (74% GC content). Our results suggest a possible mechanism of PCR enhancement. In the error-prone two-round PCR system, the improvement of the specificity and efficiency of the technique using the PEG-Au PENPs mainly depends on surface-charge-mediated electrostatic interactions. In the GC-rich PCR system, thermal conduction may be the dominant factor. These important findings offer a breakthrough in understanding the mechanisms involved in improving PCR amplification, as well as in the application of nanomaterials in different fields, particularly in biology and medicine.
The dideoxynucleoside triphosphates (ddNTPs) terminate the bio-polymerization of DNA and become essential chemical component of DNA sequencing technology which is now basic tool for molecular biology research. In this method the radiolabeled or fluorescent dye labeled ddNTP analogues are being used for DNA sequencing by detection of the terminated DNA fragment after single labeled ddNTP incorporation into DNA under PCR conditions. This report describes the syntheses of rationally designed novel amino-functionalized ddNTP analogue such as Pyrrolidine nucleoside triphosphates (prNTPs), and their polymerase activities with DNA polymerase by LC-MS and Gel-electrophoretic techniques. The Mass and PAGE analyses strongly support the incorporation of prNTPs into DNA oligonucleotide with Therminator DNA polymerase as like control substrate ddNTP. As resultant the DNA oligonucleotide are functionalized as amine group by prNTP incorporation with polymerase. Hence prNTPs provide opportunities to prepare demandable conjugated DNA with other biomolecules/dyes/fluorescence molecule without modifying nucleobase structure. (C) 2016 Elsevier Ltd. All rights reserved.
Different from monomeric substrate, polymeric substrate (PS) needs to undergo slow hydrolysis process before becoming available for consumption by bacteria. Hydrolysis products will be available for the heterotrophs in low concentration, which will reduce competitive advantages of heterotrophs to nitrifiers in mixed culture. Therefore, some links between PS and nitrification process can be expected. In this study, three lab-scale sequencing batch reactors with different PS/total substrate (TS) ratio (0, 0.5 or 1) in influent were performed in parallel to investigate the influence of PS on nitrification process in activated sludge system. The results showed that with the increase of PS/TS ratio, apparent sludge yields decreased, while NOT-N concentration in effluent increased. The change of PS/TS ratio in influent also altered the cycle behaviors of activated sludge. With the increase of PS/TS ratio from 0 to 0.5 and 1, the ammonium and nitrite utilization rate increased 2 and 3 times, respectively. The q-PCR results showed that the abundance of nitrifiers in activated sludge for PS/TS ratio of 0.5 and 1 were 0.7-0.8 and 1.4-1.5 orders of magnitude higher than that for PS/TS ratio of 0. However, the abundance of total bacteria decreased about 0.5 orders of magnitude from the former two to the latter. The FISH observation confirmed that the nitrifiers' microcolony became bigger and more robust with the increase of PS/TS ratio. This paper paves a path to understand the role of PS/TS in affecting the nitrification process in biological wastewater treatment systems. (C) 2017 Elsevier Ltd. All rights reserved.
DNA vaccine is a third generation vaccine type based on concepts and techniques of molecular biology. It can closely mimic live infections and induce both antibody and cell mediated immune responses and thus has much potential for treating chronic viral infection and cancer. How do we transport the DNA vaccine to the right target cells in lymphoid tissues and organs? How do we achieve high and robust gene transfection efficiency while simultaneously inducing DC maturation and antigen presentation? These questions pose significant challenges and addressing them may require serious efforts in developing better biomaterials as carriers. This review is dedicated to the discussion of polymers as nanoscale carriers for the DNA vaccine. We summarize recent advances in polymer science and engineering to overcome multilevel hurdles for DNA vaccine delivery and conclude with thoughts on challenges and opportunities that may shape the future of polymers in DNA vaccination.
Exportin 5 (XPO5) is a microRNA (miRNA)-related nuclear export protein, and its disorder may lead to the dysregulation of miRNAs. Recent studies have demonstrated that the aberrant expression of XPO5 might participate in carcinogenesis in certain cancers. However, there is only limited information of XPO5 in thyroid cancer (TC) development. In our study, we quantified the expression level of XPO5 by real-time polymerase chain reaction (PCR) in 64 TC patients' cancer tissues and adjacent normal tissues. After confirming the XPO5 expression, we evaluated the association between XPO5 potential functional single-nucleotide polymorphisms (SNPs) and risk of TC in a Chinese population (1140 cases vs 1230 controls). Finally, luciferase assays were performed to investigate the function of the SNP in XPO5 3' untranslation region. The message ribonucleic acid (RNA) levels of XPO5 were significantly lower in cancer tissues than normal tissues (P=0.004). In SNPs screening, only 1 noble SNP rs11077 was identified in XPO5 functional region. The results in our case-control study also confirmed that XPO5 rs11077 was significantly associated with onset of TC (GT/GG vs TT P=0.035, adjusted odds ratio = 1.25, 95% confidence interval = 1.02-1.54). The adverse influence of this polymorphism was mainly observed in age >45 years (P=0.028), female (P=0.020), T1 staging (P=0.026), N1 (P=0.038), metastasis (P=0.031 M0, and P=0.035 for M1), and early stage (I+II) (P=0.021). A following luciferase test revealed the critical role of rs11077 for triggering the XPO5 expression. Furthermore, patients with G allele of rs11077 showed lower XPO5 expression level. XPO5 SNP rs11077 influences the expression of XPO5, and this SNP could also be a potential biomarker for the diagnosis of TC in clinical, especially in Chinese population.
This review aimed to investigate possible protective or deleterious effects of polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in pregnant women, along with their antioxidant and anti-inflammatory action. A great variety of foods and beverages, such as herbal teas, grape and orange derivatives, dark chocolate, and many others contain high concentrations of flavonoids and are freely consumed by the general population. In humans, PRF consumption reduces lipid peroxidation, and several studies have shown a positive correlation between an increased consumption of PRF and a decrease in the incidence of cardiovascular disease. On the other hand, current studies have suggested that maternal ingestion of PRF, especially during the third trimester of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses exposed to this type of diet show higher ductal velocities and lower pulsatility indexes, as well as larger right ventricles than those exposed to minimal amounts of these substances. The underlying mechanism involved in these conditions has not been entirely elucidated, but it seems to be a result of the antioxidant and anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking into account the deleterious effect in late-pregnancy against the numerous positive effects associated to polyphenols, this dual behavior deserves attention particularly to control the dietary ingestion of PRF during gestation. In this line, same PRF, natural constituents of human diet, may represent risk to fetal in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs.
Using cell lines and primary cells, it has been shown that translation control plays a key role regulating gene expression during physiological and pathological conditions. The relevance of this type of regulation in vivo (tissues, organs) remains to be elucidated, due to the lack of an efficient method for polysome-bound fractionation of solid tissue RNA samples. A simple and efficient method is described, in which tissue samples were pulverized in liquid nitrogen and lysed with NP40-lysis buffer in the presence of the RNAse inhibitors RNAsin and vanadyl-ribonucleoside complex. After cell lysis, the cytoplasmic extract was loaded into sucrose gradients, fractionated, and RNA prepared from each fraction. The obtained RNA was reverse transcribed with a low efficiency, a problem that was overcome by purifying polyA(+) RNA. Aiming to use small quantities of solid tissue samples (10-20 mg/sample), polyA(+) RNA purification was discarded, and the different components were individually screened for a negative effect on reverse transcription. The polysaccharide heparin, which is present as a nonspecific RNAse inhibitor, inhibits reverse transcriptase activity, and must be removed from RNA samples for an efficient reaction. Heparin was successfully removed by precipitation of the RNA with lithium chloride, as demonstrated by the reversal of the inhibition on RT-PCR reactions. In summary, we present a reliable method allowing us to prepare high-quality polysome-bound mRNA from small quantities of liquid-nitrogen-frozen solid tissue samples from both human and mouse origin, amenable for Northern blotting, RT-PCR reactions, and expression profiling analyses.
In this study, we used data from life histories of 424 non-incarcerated (n = 266) and incarcerated (n = 158) women to examine the extent to which women are exposed to multiple forms of victimization, including child abuse, intimate partner violence, sexual assault, and traumatic life events. We assessed the effects of polyvictimization (e. g., multiple victimizations) on women's healthrelated outcomes (e. g., attempted suicide, drug and alcohol problems) as well as whether the prevalence rates and effects of victimization were significantly different between the subsamples of women. Results indicate that incarcerated women experience significantly more victimization than non-incarcerated women, and while polyvictimization was associated with a higher likelihood of alcohol problems, drug problems, and attempted suicide among non-incarcerated women, it was only marginally associated with an increased likelihood of alcohol problems among incarcerated women. Finally, low levels of polyvictimization affected alcohol and drug problems among incarcerated and non-incarcerated women differently.
Porcine CFL2b gene play an important role in the muscle development and myofibrillar formation in pig. To explore whether CFL2b expression affects muscle fiber trait, the porcine CFL2b full-length cDNA was amplified using homology based cDNA cloning and SMART RACE. Then the full length cDNA of porcine CFL2b was inserted into pEGFP-N1 and transfected into C2C12 cells. The cells stably expressing CFL2b were selected by G418. We examined the expression of MyHC 2x, MyHC 2b and MyHC1/slow in C2C12 cells stably expressing CFL2b. The results showed that the level of MyHC 2x and MyHC 2b mRNA were dramatically increased compared with control cells, while the level of MyHC1/slow mRNA is not changed. To identify the transcription events of CFL2b, the porcine CFL2b mRNA was detected by Northern blotting, two transcripts, long transcript (3,012 bp) and short transcript (1,466 bp) were found in porcine skeletal muscles. The nucleotide sequence of CFL2b shares 88.1 and 74.9% homology with the CFL2b gene in human and mouse. The deduced amino acid sequence of CFL2b (166 amino acids) in pig shares 100, 99.1% identity with the CFL2b in human and mouse, respectively. Taken together, our research revealed that porcine CFL2b may be involved in the regulation muscle fiber trait by affecting the expression of MyHC.
Background: Recently identified porcine circovirus-like virus P1 has the smallest DNA viral genome. In this study, we identified the viral genes and their corresponding mRNA transcripts. Results: The RNAs of P1, synthesized in porcine kidney cells, were examined with northern blotting and PCR analyses. Eight virus-specific RNAs were detected. Four mRNAs (open reading frames (ORFs) 1, 2, 4, and 5) are encoded by the viral (-) strand and four (ORFs 3, 6, 7, and 8) are encoded by the viral (+) strand. All proteins encoded by the ORFs of the P1 virus are less than 50 amino acids in length, except that encoded by ORF1 (113 amino acids). Conclusions: We show a very complex viral transcription pattern in P1-infected cells.
Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-beta), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-beta production by targeting the NF-kappa B essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses.
Porcine epidemic diarrhea virus (PEDV), which is the causative agent of porcine epidemic diarrhea in China and other countries, is responsible for serious economic losses in the pork industry. Inactivated PEDV vaccine plays a key role in controlling the prevalence of PEDV. However, consistently low viral titers are obtained during the propagation of PEDV in vitro; this represents a challenge to molecular analyses of the virus and vaccine development. In this study, we successfully isolated a PEDV isolate (strain NJ) from clinical samples collected during a recent outbreak of diarrhea in piglets in China, using porcine intestinal epithelial cells (IEC). We found that the isolate was better adapted to growth in IECs than in Vero cells, and the titer of the IEC cultures was 10(4.5) TCID50/0.1 mL at passage 45. Mutations in the S protein increased with the viral passage and the mutations tended towards attenuation. Viral challenge showed that the survival of IEC-adapted cultures was higher at the 45th passage than at the 5th passage. The use of IECs to isolate and propagate PEDV provides an effective approach for laboratory-based diagnosis of PEDV, as well as studies of the epidemiological characteristics and molecular biology of this virus.
Background: The effectiveness of biosecurity methods to mitigate the transmission of porcine epidemic diarrhea virus (PEDV) via farm personnel or contaminated fomites is poorly understood. This study was undertaken to evaluate the effectiveness of biosecurity procedures directed at minimizing transmission via personnel following different biosecurity protocols using a controlled experimental setting. Results: PEDV RNA was detected from rectal swabs of experimentally infected (INF) and sentinel pigs by real-time reverse transcription polymerase chain reaction (rRT-PCR). Virus shedding in INF pigs peaked at 1 day post infection (dpi) and viral RNA levels remained elevated through 19 dpi. Sentinel pigs in the low biosecurity group (LB) became PEDV positive after the first movement of study personnel from the INF group. However, rectal swabs from pigs in the medium biosecurity (MB) and high biosecurity (HB) groups were negative during the 10 consecutive days of movements and remained negative through 24 days post movement (dpm) when the first trial was terminated. Viral RNA was detected at 1 dpm through 3 dpm from the personal protective equipment (PPE) of LB personnel. In addition, at 1 dpm, 2 hair/face swabs from MB personnel were positive; however, transmission of virus was not detected. All swabs of fomite from the HB study personnel were negative. Conclusions: These results indicate that indirect PEDV transmission through contaminated PPE occurs rapidly (within 24 h) under modeled conditions. Biosecurity procedures such as changing PPE, washing exposed skin areas, or taking a shower are recommended for pig production systems and appear to be an effective option for lowering the risk of PEDV transmission between groups of pigs.
Type 2 porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) was first isolated in Korea in 1994. The commercial PRRS modified live vaccine (Ingelvac (R) PRRS MLV, Boehringer Ingelheim Vetmedica Inc., St. Joseph, Missouri, USA) based on type 2 PRRSV, was first licensed for use in 3- to 18-week-old pigs in Korea in 1996. The objective of the present study was to evaluate the efficacy of this 20 year old commercial PRRS modified live vaccine (MLV) against two recent PRRSV isolates. Two genetically distant type 2 PRRSV strains (SNUVR150004 for lineage 1 and SNUVR150324 for lineage 5), isolated in 2015, were used as challenge virus. Regardless of the challenge virus, vaccination of pigs effectively reduced the level of viremia, the lung lesions, and of the PRRSV antigen within the lung lesions. The induction of virus specific interferon-gamma secreting cells by the PRRS vaccine produced a protective immune response, leading to the reduction of PRRSV viremia. There were no significant differences in efficacy against the two recently isolated viruses by the PRRS MLV based on virological results, immunological responses, and pathological outcomes. This study demonstrates that the PRRS MLV used in this study is still effective against recently isolated heterologous type 2 PRRSV strains even after 20 years of use in over 35 million pigs (C) 2016 Elsevier B.V. All rights reserved.
Porcine rotavirus-A (PoRVA) is one of the common causes of mild to severe dehydrating diarrhea, leading to losses in weaning and postweaning piglets. A rapid, highly specific, and sensitive antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) was developed for detection of PoRVA, by using VP6 (a highly conserved and antigenic protein of group-A rotavirus)-directed rabbit polyclonal antibodies (capture antibody) and murine monoclonal antibodies (detector antibody). The detection limit of AC-ELISA was found to be equal to that of conventional reverse transcription-polymerase chain reaction (RT-PCR; about 10(2.5) TCID50/mL). For validation of the in-house AC-ELISA, 295 porcine fecal/diarrhea samples, collected from different provinces of China, were evaluated and compared with conventional RT-PCR and TaqMan RT-quantitative PCR (qPCR). The sensitivity and specificity of this in-house AC-ELISA relative to RT-qPCR were found to be 91.67% and 100%, respectively, with the strong agreement (kappa = 0.972) between these two techniques. Total detection rate with AC-ELISA, conventional RT-PCR, and RT-qPCR were found to be 11.2%, 11.5%, and 12.2%, respectively, without any statistical significant difference. Moreover, AC-ELISA failed to detect any cross-reactivity with porcine epidemic diarrhea virus, transmissible gastroenteritis virus, pseudorabies virus, and porcine circovirus-2. These results suggested that our developed method was rapid, highly specific, and sensitive, which may help in large-scale surveillance, timely detection, and preventive control of rotavirus infection in porcine farms.
Porous organic polymers (POPs), a new class of porous materials constructed by organic molecular building blocks, have attracted much attention. To design POPs with both good porosity and specific-task functionalization is still a critical challenge. In this work, using a simple Friedel-Crafts one-step reaction, one of the most common organic compound methylbenzene monomers were polymerized through the cross linker formaldehyde dimethyl acetal (FDA) to produce a cost-effective non-functionalized porous polymer (POP-CH3). Moreover, amine groups were further incorporated into the network by the post synthetic modification method. The resulted porous polymer POP-NH2 presented highly effective in removing Pb(II) from aqueous solution. The maximum Pb(Il) adsorption capacity, q(max) evaluated from the Langmuir model was 523.6 mg g(-1). The combination of FT-IR experimental results and the theoretical quantum calculations illustrated that the amine groups (-NH2) can easily form coordination complexes with Pb(II), which were responsible for efficient adsorption. The generated POP-NH2 could be regenerated effectively and recycled at least four times without significant loss of adsorption efficiency. Hence, the outstanding Pb(II) adsorption capacity, excellent reusability as well as low cost of synthesis create potential polymer POP-NH2 to be an attractive adsorbent for removing toxic metal ions from aqueous solution. (C) 2017 Elsevier B.V. All rights reserved.
The act-and-wait concept is a recently developed type of controller, which is receiving growing interest because of its promising features with respect to the control of systems with feedback delay. Although most of its advantages have been widely discussed and verified experimentally, a detailed analysis of the nonlinear behavior of this type of controller is still missing. In this paper, we apply the act-and-wait controller to the digital position control of a single-degree-of-freedom system. The analysis shows both the linear stability and the post-bifurcation behavior of the system, comparing the system with a regular proportional-differential controller and with the act-and-wait controller. The performed investigation confirms most of the advantages of the act-and-wait controller, already known in the literature, regarding the enlargement of the stable region and the possibility of achieving deadbeat control, also in the presence of delay. On the other hand it shows some drawbacks of this controller, related to the post-bifurcation behavior, which presents unbounded motions, and to the robustness of the stability, which appears to be limited.
In this paper we present an analysis of the stability of a two-degree-of-freedom system, modeling a robotic arm connected to the actuator through an elastic joint and subject to digital position control. The system consists of two lumped masses connected to each other through a spring and a damper. In the model there is only one actuator, so the system is underactuated in a certain sense; two cases are considered, referring to a collocated and a noncollocated configuration. Stability analysis is presented using both a continuous and a discrete time approach. The discrete time approach is related to the case of a digital controller, typical in real applications. This samples the position and the velocity signals at discrete time intervals and, therefore, it generates a piecewise constant control force, introducing a delay in the control system as well. The stability charts are presented in the parameter space of the sampling time and the control gains. Their differences highlight the role played by the resonances between the finite sampling frequency and the natural frequency of the system in achieving robust stability with respect to parameter variations.
Cognitive control enables successful goal-directed behavior by resolving a conflict between opposing action tendencies, while emotional control arises as a consequence of emotional conflict processing such as in irony. While negative emotion facilitates both cognitive and emotional conflict processing, it is unclear how emotional conflict processing is affected by positive emotion (e.g., humor). In 2 EEG experiments, we investigated the role of positive audiovisual target stimuli in cognitive and emotional conflict processing. Participants categorized either spoken vowels (cognitive task) or their emotional valence (emotional task) and ignored the visual stimulus dimension. Behaviorally, a positive target showed no influence on cognitive conflict processing, but impeded emotional conflict processing. In the emotional task, response time conflict costs were higher for positive than for neutral targets. In the EEG, we observed an interaction of emotion by congruence in the P200 and N200 ERP components in emotional but not in cognitive conflict processing. In the emotional conflict task, the P200 and N200 conflict effect was larger for emotional than neutral targets. Thus, our results show that emotion affects conflict processing differently as a function of conflict type and emotional valence. This suggests that there are conflict- and valence-specific mechanisms modulating executive control.
Research on positive emotion disturbance has gained increasing attention, yet it is not clear which specific positive emotions are affected by mood symptoms, particularly during the critical period of adolescence. This is especially pertinent for identifying potential endophenotypic markers associated with mood disorder onset and course. The present study examined self-reported discrete positive and negative emotions in association with clinician-rated manic and depressive mood symptoms in a clinically and demographically diverse group of 401 outpatient adolescents between 11 and 18 years of age. Results indicated that higher self reported joy and contempt were associated with increased symptoms of mania, after controlling for symptoms of depression. Low levels of joy and high sadness uniquely predicted symptoms of depression, after controlling for symptoms of mania. Results were independent of age, ethnicity, gender and bipolar diagnosis. These findings extend work on specific emotions implicated in mood pathology in adulthood, and provide insights into associations between emotions associated with goal driven behavior with manic and depressive mood symptom severity in adolescence. In particular, joy was the only emotion associated with both depressive and manic symptoms across adolescent psychopathology, highlighting the importance of understanding positive emotion disturbance during adolescent development.
Research over the last two decades on the role of positive emotions and cognitions in psychological functioning is leading to conceptual changes regarding the nature of mental disorders and the mechanisms underlying their onset and maintenance. This introduction to the latest breakthrough research on positive emotions and cognition offers a brief description of the emerging presence of positivity in current diagnostic systems like the DSM5 and Research Domain Criteria (RDoC). It also analyzes some select findings from the literature on experimental psychopathology supporting the relevance of examining positive aspects of functioning in clinical psychology. In addition, the study of positive aspects of psychological functioning adds a more conceptually complex understanding of psychopathology. The multiple perspectives encompassed in this special issue shed light on our understanding of the different roles that positive emotions and cognitions play in mediating normal and abnormal human functioning and their importance to improving research methods and interventions in psychopathology.
In this paper, a novel operational amplifier is demonstrated which is established on the folded cascode Op-amp structure. A new technique of positive feedback is proposed to increase the open loop gain of Op-amp while not limiting its linearity. The proposed structure is simulated by HSPICE software using level 49 parameters (BSIM3V3) in a typical 0.18 A mu m CMOS technology. HSPICE simulation verifies the theoretical estimated improvements.
Traditionally, treatments for depression have been primarily focused on reducing patients' symptoms or deficits and less concerned with building positive resources. This study aims to compare the efficacy of a manualized protocol of empirically-validated positive psychology interventions (PPI) with a cognitive-behavioral therapy (CBT) protocol. This controlled clinical trial included 96 adult women with a DSM-IV diagnosis of major depression or dysthymia. Participants were blindly allocated to a 10-session PPI (n = 47) or CBT (n = 49) group therapy condition. Intention to treat analysis showed that both interventions were effective in reducing clinical symptoms and increasing well-being. There were no significant differences between groups in either main outcomes (i.e., severity of depressive symptoms and clinical diagnosis) or secondary outcomes (e.g., positive and negative affect, and satisfaction with life). Even within the most severely depressed participants, no differences between PPI and CBT emerged. If further clinical studies confirm these results, this would widen treatment choice for both patients and professionals.
Background: In Posner-Schlossman syndrome (PSS), which is characterized by recurrent unilateral attacks of ocular hypertension. Surgical treatment is sometimes necessary because intraocular pressure (IOP) cannot be controlled with anti-glaucoma medications. To identify the clinical features of Posner-Schlossman syndrome (PSS) indicative of the need for intraocular pressure (IOP)-controlling surgery. Methods: This study was a retrospective case-series analysis of the clinical charts of 33 patients diagnosed with PSS, who underwent surgery to control IOP or received medication only. Various clinical factors were compared between the surgical and medication groups. Results: The surgical group had a higher corneal endothelial cell (CEC) density loss (p < 0.05), higher maximum IOP (p < 0.01), greater visual field loss (p < 0.01) and higher positive number for cytomegalovirus (CMV) (p < 0.001) than the non-surgical group. Eighteen of the 33 patients had a high CEC reduction ratio. Of these 18, 16 required glaucoma surgery. Conclusions: PSS patients with a higher CEC reduction ratio, higher maximum IOP, greater visual field loss and higher positive number for CMV in the aqueous humor tended to be more likely to require progressive treatment, such as glaucoma surgery.
Posner-Schlossman syndrome, or glaucomatocyclitic crisis, is a unilateral ocular condition characterized by recurrent attacks of nongranulomatous anterior uveitis and raised intraocular pressure that can result in chronic secondary glaucoma. This relatively rare disease is most likely the result of recurrent cytomegalovirus infection and affects predominantly middle-aged males. Diagnosis is largely clinical, with aqueous and blood sampling aiding the identification of any underlying infectious cause. Successful disease management is often achieved by topical treatment, although systemic therapy and even surgical intervention may be required. We discuss our current understanding of Posner-Schlossman syndrome, from its pathophysiology through to recommended treatment options. (C) 2016 Elsevier Inc. All rights reserved.
The link between education and crime is a topic that requires special attention with respect to the converging influence of individual, social, and environmental factors. This article will investigate the educational pathways followed by students in a higher education program for formerly incarcerated individuals at a large state university in the northeastern United States. Specifically, it will explore the extent to which their postincarceration educational experiences served as a hook for change and also related impediments tied to street influences, financial constraints, stigma, academic and social development. Data were collected from a sample of 34 current and former students in the program, each of whom participated in a face-to-face interview. The higher education program played a key role in propelling the desistance process for research participants. This article will discuss how personal agency can be sustained through participation in higher education post release and the implications for future research on crime avoidance.
Postpartum depression affects approximately 15 % of mothers; however, its pathological mechanisms still remain unclear. Ovariectomized adult mice received the administration of estrogen (E2) and progesterone with a subsequent alone E2, termed hormone-simulated pregnancy (HSP). Affective behaviors as assessed by forced swim and tail suspension tests, hippocampal neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic AMP (cAMP) response element binding protein (CREB) phosphorylation (phosphor-CREB), and neurosteroidogenesis were examined before E2 withdrawal (EW; HSP mice) and on days 2-4 (early-EW mice) and days 8-10 (late-EW mice) after EW. Depressive-like behaviors were observed in early-EW mice but not in late-EW mice. Levels of nNOS, NO, and phosphor-CREB were increased in HSP mice followed by a significant decline in early-EW mice with a subsequent restoration in late-EW mice. The treatment of early-EW mice with NO donor alleviated depressive-like behaviors and decline of phosphor-CREB. The nNOS inhibitor and NO scavenger caused depressive-like behaviors and reduced phosphor-CREB in HSP mice and late-EW mice. Notably, the levels of steroidogenic enzymes StAR and P450scc were elevated in late-EW mice. The sigma-1 receptor (sigma R-1) agonist could alleviate depressive-like behaviors and decline of nNOS-NO-CREB in early-EW mice. The pharmacological blockade or deficiency of sigma R-1 in late-EW mice caused depressive-like behaviors with decline of nNOS-NO-CREB. The reduction of hippocampal brain-derived neurotrophic factor (BDNF) or N-methyl-d-aspartic acid (NMDA) receptor NR2B phosphorylation in early-EW mice could recover in late-EW mice, which was sensitive to the blockade of sigma R-1. The NMDA receptor agonist, but not TrkB receptor activator, could correct the decline of nNOS-NO-CREB in early-EW mice. The findings indicate that the activation of sigma R-1 can alleviate postpartum "depression" through increasing nNOS-NO-CREB activities.
This study examines the main and moderating effects of childhood abuse or neglect severity, income, and family social support on the presence of postpartum depressive symptoms (PDS). Participants included 183 postpartum mothers who endorsed a history of childhood maltreatment (CM) and enrolled in a longitudinal study of mother and child outcomes. Participants completed questionnaires to assess CM severity, associated societal and maternal characteristics, and depressive symptom severity. The results confirm previously identified links between CM severity and PDS. Further, hierarchical linear regression analyses indicate the interaction of household income and interpersonal support from the family attenuates the relationship between CM severity and PDS. The final model accounted for 29% of the variance of PDS scores, a large effect size. This study is the first to demonstrate interrelationships between income and social support on resilience to postpartum psychopathology in childhood trauma-surviving women. Social support appeared to protect against PDS for all mothers in this study while income only conferred a protective effect when accompanied by family support. For clinicians, this implies the need to focus on improving family and other relationships, especially for at-risk mothers.
Postpartum depression (PPD) has been described as the most common complication experienced postpartum, affecting about 10-15 % of all new mothers. Factors like a history of mental illness, and experienced recent adverse life events has been associated with an increased risk for developing PPD. Immigrant women in Western countries have been found to have a marked higher prevalence of PPD compared to the general population. In Norway the prevalence of PPD in the general population has been found to be around 8-10 %, and among Pakistani immigrants a rate of 7.6 % was found. Somali people in Norway are the second largest immigrant group in Norway with a non-Western background. No study on PPD and associated factors among Somali women has been found in the literature. The aim of the study was to assess PPD and associated factors among Somali women in greater Oslo region, Norway. A cross-sectional survey was conducted; recruiting new mothers through all maternity wards in the Oslo region. Data was collected with interview-administrated questionnaires. PPD was assessed using Edinburgh Postnatal Depression Scale (EPDS), defining those scoring >= 10 to have a possible PPD. Of the 80 eligible women identified, 39 (49 %) consented to participate, and completed the study. Of the 39 respondents 3 (7.7 %) were assessed to have a possible PPD. Most important associated factors found were history of mental illness, having experienced technical assistance during delivery, self-rated health and experienced economical problems last 12 months. A low prevalence of PPD was found, and both the prevalence and its associated factors should be interpreted with caution. The associated factors do not have enough power to give any strength to the associations. However, some of the results can be used in develop new hypotheses with regard to PPD among Somali women as immigrants in a Western society.
Introduction: Postpartum depression is a prevalent disorder affecting many women of reproductive age. Despite increasing public awareness, it is frequently underdiagnosed and undertreated leading to significant maternal morbidity and adverse child outcomes. When identified, postpartum depression is usually treated as major depressive disorder. Many studies have identified the postpartum as a period of high risk for first presentations and relapses of bipolar disorder.Areas covered: This article reviews the acute and prophylactic treatment of postpartum major depressive disorder, bipolar depression and major depressive disorder with mixed features. The safety of antidepressant and mood stabilizing medications in pregnancy and breastfeeding will also be reviewed.Expert commentary: Differentiating postpartum major depressive disorder and postpartum bipolar depression can be difficult given their clinical similarities but accurate identification is vital for initiating proper treatment. Antidepressants are the mainstay of drug treatment for postpartum major depressive disorder, yet randomized controlled trials have shown conflicting results. A paucity of evidence exists for the effectiveness of antidepressant prophylaxis in the prevention of recurrences of major depressive disorder. Mood stabilizing medications reduce the risk of postpartum bipolar depression relapse but no randomized controlled trials have examined their use in the acute or prophylactic treatment of postpartum bipolar depression.
The magnitude of postprandial lipemia has been identified as independent risk factor for the development of coronary artery disease. To test the effect of postprandial versus postabsorptive low-density lipoproteins (LDL) on the expression of adhesion molecules, LDL were isolated from healthy subjects before and 4 h after ingestion of a standardized fatty test meal. We used flow cytometry and Northern blotting to quantify cell adhesion molecules in human aortic endothelial cells (HAEC). The adherence of leukocytes to HAEC was analyzed using a monocyte adhesion assay. Incubation of HAEC with postprandial, but not postabsorptive LDL induced a two-fold increase in the surface expression of intercellular adhesion molecule-1 (ICAM-1), but not of E-selectin or vascular cell adhesion molecule-1. In addition, increased amounts of ICAM-1 transcripts were found in HAEC treated with postprandial LDL. The adhesion of monocytes to HAEC was enhanced after pretreatment with postprandial, but not with postabsorptive LDL. We conclude that postprandial, but not postabsorptive LDL increase the surface expression of ICAM-1 in HAEC apparently by de novo protein synthesis leading to increased adhesion of monocytes. The upregulation of ICAM-1 by postprandial LDL may explain part of the proatherogenic effect of high postprandial lipemia. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
This meeting report highlights key trends that emerged from a conference entitled Post-Transcriptional Gene Regulation in Plants, which was held 14-15 July 2016, as a satellite meeting of the annual meeting of the American Society of Plant Biologists in Austin, Texas. The molecular biology of RNA is emerging as an integral part of the framework for plants' responses to environmental challenges such as drought and heat, hypoxia, nutrient deprivation, light and pathogens. Moreover, the conference illustrated how a multitude of customized and pioneering omics-related technologies are being applied, more and more often in combination, to describe and dissect the complexities of gene expression at the post-transcriptional level.
Piwi-interacting RNAs (piRNA) are fully modified by 2'-O -methylation at their 3'-termini. This terminal methylation is required to prevent 3'-nucleotide addition, which serves as a tag for destabilization. In this chapter, we describe biochemical and mass spectrometric analyses of 2'-O -methylation at 3'-termini of piRNAs.
BackgroundFew efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). MethodsTwenty-nine youth (8-17years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2-6months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n=14) or waiting list (WL; n=15) for 10weeks. ResultsSignificantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04-.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safety-seeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. ConclusionsThis trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of watchful waiting' into the 2- to 6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required.
ObjectiveTo assess the association between parental post-traumatic stress disorder (PTSD) and offspring PTSD and its specificity for other disorders in a non-clinical epidemiological cohort of Australian Vietnam veterans, their partners and their sons and daughters. MethodVeterans were interviewed twice, in 1992-1994 and 2005-2006; partners were interviewed in 2006-2007, and their offspring in 2012-2014. A total of 125 sons and 168 daughters were interviewed from 197 families, 137 of which also included partners who were the mothers of the children. Statistical analysis used multi-level modelling to compute odds ratios and 95% confidence intervals while controlling for clustering effects within families. Parent PTSD diagnoses were examined for associations with offspring trauma exposure, PTSD and other psychiatric diagnoses. ResultsVeteran PTSD increased the risk of PTSD and no other disorder in both sons and daughters; partner PTSD did not. Veteran depression was also a risk factor for sons' PTSD, and alcohol disorder was linked to alcohol dependence in sons and PTSD in daughters, but not when controlling for veteran PTSD. ConclusionWe conclude that PTSD in a Vietnam veteran father increases the risk specifically for PTSD in his sons and daughters.
Posttraumatic stress disorder (PTSD) is a psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective for treating PTSD, but whether different frequencies have different effects remains controversial. We conducted this systematic review and meta-analysis to address this question. We searched the literature for studies written in English or Chinese in 9 electronic databases from the databases' inception to August 1, 2016. Additional articles were identified from the reference lists of identified studies and from personal reference collections. Eighteen articles were included, and 11 were suitable for the meta-analysis (Combined sample size was 377 (217 in active rTMS groups, 160 in sham-controlled groups)). Low-frequency (LF) rTMS resulted in a significant reduction in the PTSD total score and the depression score (1. PTSD total score: pooled SMD, 0.92; Cl, 0.11-1.72; 2. Depression: pooled SMD, 0.54; CI, 0.08-1.00). High-frequency (HF) rTMS showed the following results: 1. PTSD total score: pooled SMD, 3.24; CI, 2.24-4.25; 2. re-experiencing: pooled SMD, -1.77; CI, -2.49(-1.04); 3. Avoidance: pooled SMD, -1.57; CI, -2.50-(-0.84); 4. hyperarousal: pooled SMD, -1.32; CI, -2.17-(-0.47); 5. depression: pooled SMD, 1.92; CI, 0.80-3.03; and 6. Anxiety: pooled SMD, 2.67; CI, 1.82-3.52. Therefore, both HF and LF rTMS can alleviate PTSD symptoms. Although the evidence is extremely limited, LF rTMS can reduce overall PTSD and depression symptoms. HF rTMS can improve the main and related symptoms of PTSD. However, additional research is needed to substantiate these findings. (C) 2017 Elsevier Ltd. All rights reserved.
Trauma, especially early life trauma, is a risk factor for the development of both posttraumatic stress disorder and psychosis. The goal of the present study was to determine specific associations between exposure to childhood abuse, PTSD symptoms, and current psychotic disorder. Subjects were recruited from a public, urban hospital (N = 328, >90% African American). Psychotic disorders were measured using the MINI International Neuropsychiatric Interview, PTSD was measured using the Clinician Administered PTSD Scale, child abuse was measured with the Childhood Trauma Questionnaire, and lifetime trauma exposure was measured with the Traumatic Events Inventory. Logistic regression analyses showed that both child abuse and current PTSD were statistically significant predictors of psychotic disorder beyond the effects of lifetime trauma load. When PTSD symptom clusters were examined, avoidance and numbing symptoms showed unique association with psychotic disorder independent of demographic variables and trauma exposure. Using bootstrapping techniques, we found a full indirect effect of PTSD on the association between child abuse and, suggesting a particularly important role of PTSD symptoms in relation to psychotic disorder in the presence of early life trauma. Because this is a cross-sectional study, continued research is needed to determine causality of such models. Identifying co-occurring psychosis and PTSD, particularly in populations with high levels of trauma exposure, is critical and will likely aid in more successful treatment interventions. (C) 2016 The Authors. Published by Elsevier Ltd.
Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of Na+, K+, Ca2+ and Cl- ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons' behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular K+, which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.
The present review work is devoted to potentiometric sensors based on high-temperature proton conducting ceramic materials. The technology developments and possible application of such sensors for the determination of concentration of hydrogen-containing components in gases, solids and melts are described and thoroughly discussed. A special attention is devoted to the analysis of experimental data already appeared in international literature and their adequacy to the basic operation principles. On the base of this analysis, the existing problems and future trends are revealed and discussed. (C) 2017 Elsevier B.V. All rights reserved.
Electrochemical biosensing is used to detect specific analytes in fluids, such as bacterial and chemical contaminants. A common implementation of an electrochemical readout is a potentiostat, which usually includes potentiometric, amperometric, and impedimetric detection. Recently several researchers have developed small, low-cost, single-chip silicon-based potentiostats. With the advances in heterogeneous integration technology, low-power potentiostats can be implemented on paper and similar low cost substrates. This paper deals with the design of a low-power paper-based amperometric front-end for a low-cost and rapid detection environment. In amperometric detection a voltage signal is provided to a sensor system, while a small current value generated by an electrochemical redox reaction in the system is measured. In order to measure low current values, the noise of the circuit must be minimized, which is accomplished with a pre-amplification front-end stage, typically designed around an operational amplifier core. An appropriate circuit design for a low-power and low-cost amperometric front-end is identified, taking the heterogeneous integration of various components into account. The operational amplifier core is on a bare custom CMOS chip, which will be integrated onto the paper substrate alongside commercial off-the-shelf electronic components. A general-purpose low-power two-stage CMOS amplifier circuit is designed and simulated for the ams 350 nm 5 V process. After the layout design and verification, the IC was submitted for a multi-project wafer manufacturing run. The simulated results are a bandwidth of 2.4 MHz, a common-mode rejection ratio of 70.04 dB, and power dissipation of 0.154 mW, which are comparable with the analytical values.
Accurate identification of plant pathogens is crucial towards developing sustainable control strategies to ensure sustainable economic agricultural production. The aim of this study was to detect and characterize Potato virus Y (PVY) isolates infecting potato (Solanum tuberosum L.) in the Msinga district in the Province of KwaZulu-Natal, South Africa. Potato leaf samples exhibiting virus-like symptoms were collected from four different areas in the district. Initial detection of PVY in the leaf samples was done using triple antibody sandwich ELISA. PVY-positive samples were further tested using antibodies specific to PVY serotypes O and N. Nicotiana tabacum cv Samsun plants were individually mechanically inoculated with all 32 PVY-ELISA positive samples. Symptoms on inoculated tobacco plants were monitored over a 4-week period. They consisted of vein clearing, faint mosaic patterns, and the veinal necrosis, symptoms characteristic of PVYN, PVY(N)Wilga and PVYNTN strains. Reverse transcription-polymerase chain reaction, using primers specific to the coat protein gene of PVY, was performed as a confirmation test on total RNA of four randomly selected PVY-ELISA positive samples, each sample representing each of the four areas surveyed. Strains PVYN and PVYO were identified. The second part of the study aimed to analyse the full genome sequences of the PVY isolates A4, KD2, MOD1 and SneP3, in order to understand the evolution of the virus in Msinga. To achieve this, total RNA, extracted from tobacco leaves (N. tabacum cv Samsun) that had been inoculated with the selected four PVY isolates, was used as a template for next generation sequencing (NGS). NGS was run on Illumina HiSeq using paired-end chemistry 125 x 125bp reads. de novo assembly of the generated reads was performed. The resulting contigs were subjected to BLAST on the GenBank database in order to identify PVY genomes. The PVY isolates were aligned with closely related non-recombinant PVY sequences comprising of the following strains: PVYN, PVYO, PVYNTN, and PVYC. Recombination events were assessed using RDP4 software. Phylogenetic results revealed that PVY isolate SneP3 belonged to the PVYNTN strain while isolate PVYMOD1 to the PVY N Wilga strain group. Recombination analyses confirmed the occurrence of PVY recombinant strains in the Msinga district. The widespread presence of PVY and occurrence of recombinant strains in Msinga has serious implications on the management of PVY diseases by small-scale farmers growing potato for a livelihood. (C) 2017 Elsevier Ltd. All rights reserved.
A multiWatt RF power amplifier operating in the frequency range 0.5 to 1.2 GHz is reported, whose output amplitude is determined by digital input words ("RF Power DAC operation"). The amplifier employs a CMOS IC for digital control, directly connected to a GaN FET operating in common-gate mode. The use of the GaN FET allows power supply voltages in excess of 15 V to be used. A load resistance of 50 ohms can be directly connected to the GaN FET, thereby avoiding bandwidth limitations from output matching networks. Output power in the range 2 to 3 W and drain efficiencies above 50% are obtained over more than an octave of bandwidth.
Owning to the current or voltage can be artificially controlled, programmable DC electronic load plays an essential role in current and future power source testing. In this paper, we propose an electronic load which is easy to operate. The core of the design is power control module, where the compared result of current or voltage is used to control the current through the NMOS power transistor IRF540 or the voltage between the two ports of the electronic load. The keyboard and LCD based on MSP430 provide a friendly man-machine interactive interface. By establishing a feedback network using an operational amplifier, it can maintain the stability of the current or the voltage. The voltage follower and the differential amplifiers are utilized to sample the voltage and current signal. Moreover, overcurrent protection function is integrated in this design to enhance the robustness.
Switched power electronic converters involve different control actions for different system events. A local control strategy may be developed which reacts only to some local information available to each component without any communication between the different system components located far away in real time. The purpose of this paper is to present a low cost memory based control strategy in a dc-dc boost converter. The control employed in this work is based on a sliding-mode hysteretic control strategy where the sliding manifold is derived a priori and stored as a look-up table in digital memory hardware. The proposed control implementation strategy is low cost and offers a robust dynamic response that is used to mitigate many disturbances in the system. (C) 2016 Elsevier Ltd. All rights reserved.
As China's largest CO2 emission source, power sector has a large scale of power exchange, which results in the issue of interprovincial CO2 emissions transfer embodied in power transmission. Based on interprovincial detailed power exchange data, a bottom-up method which takes into account the fuel mix of exported electricity is developed to calculate provincial CO2 emissions embodied in power transmission. Provincial CO2 emissions from power sector associated in consumption perspective in 2007, 2010 and 2012 are analyzed and compared with those in production based perspective. The calculation shows that total CO2 emissions embodied in interprovincial power exchange is 532 Tg in 2012, accounting for 14% of total emissions from power sector. The embodied emissions have risen by 94% between 2007 and 2012. The general transfer pathway of embodied CO2 emissions is from eastern China to western China with long-range power transmission. The disparities between consumption and production based CO2 emissions are significant in some provinces. The production based CO2 emissions from power sector of Inner Mongolia are 195 Tg higher than those of the consumption based, while the consumption based emissions of Beijing are 484% larger than those of the production based. This study also reveals an increasing trend of CO2 emissions from both production and consumption principles for most provinces over the period 2007-2012. (C) 2016 Elsevier B.V. All rights reserved.
A simple and novel predictive duty cycle control strategy for boost PFC converter is proposed. The duty cycle is calculated based on input current, input voltage and output voltage for every cycle. The operating principles and control scheme are analyzed and discussed in detail. Experimental results of a 120 W boost power PFC prototype point out that high power factor and low input current THD are achieved over the entire output power range using proposed control strategy. The results prove to be satisfactory.
Continuous conduction mode power factor correction AC-DC converters are widely employed as the front stage in power supplies with medium or high output power. The second-order reactive input power in single-phase systems causes second-order ripple in the DC-link voltage. The speed of voltage regulation is thus limited by the second-order frequency in seeking to achieve low distorted input current. This study presents a fast second-order voltage estimation method, wherein an integrator is used for the estimation of second-order voltage ripple to obtain rapid voltage feedback without ripple and thereby cope with the limitations imposed by the second-order frequency. This approach greatly expands the bandwidth of the voltage control loop beyond the second-order frequency while reducing the total harmonic distortion associated with the input current. This also makes it possible to reduce the DC capacitance to reduce costs. The authors opted for full digital control using a TI F28335 DSP IC, in conjunction with feedback plus feedforward control to facilitate the design of the current loop. A feedback current corrector is used to reduce distortion associated with the input current over a wide load range. The effectiveness of the proposed control method was confirmed with some simulation and experimental results.
This study proposes the application and implementation of a new power factor correction (PFC) with a variable slope ramp for a small wind power system without any input voltage sensing circuits or external control components in the current shaping loop. The hardware description of the variable slope ramp simplifies the complexity of integrated circuit realization with low resolution analog-to-digital converters, and achieves a high power factor for multi and three-phase AC/DC converters such as wind power systems. Up to 1 kW small wind power system is tested to verify the performance of the proposed PFC control. The highest achieved power factor reaches 99.5%.
A new digital predictive control strategy for a single-phase boost power factor correction (PFC) converter is presented in this paper, to reduce the harmonic distortion and improve the dynamic response. Based on the converter circuit structure, the values of output voltage and inductor current of next switching cycle are predicted in advance. The steady-state algorithm and the dynamic-state algorithm are implemented respectively, the duty cycle is calculated only via the predicted output voltage and inductor current values during the steady process, and the optimized duty cycle is predicted during the dynamic process, to improve the characters of PFC converter. The single-phase boost PFC converter with the proposed digital predictive control strategy has been implemented via the field programmable gate array (FPGA). The experimental results indicate that the proposed digital control strategy can improve the power factor and the dynamic response of PFC converter simultaneously.
The power factor correction (PFC) converter is commonly used in many applications nowadays. For high power applications, boost PFC converter operated in continuous conduction mode is usually employed. However, at high-line light-load condition, the converter operates in discontinuous conduction mode. This leads to erroneous input current sampling which results in low power factor (PF) and high total harmonic distortion (THD). Moreover, the effect of EMI filter capacitor causes the displacement between the input current and input voltage. This paper proposes a digital control method to improve PF and reduce THD by using the current sample correction algorithm, duty ratio feed forward for current controller and EMI filter capacitance current injection algorithm. The increase of PF and reduction of THD are demonstrated by experiments on a 400W boost PFC converter.
This paper presents an integrated maximum power point tracking system for use with a thermophotovoltaic portable power generator. The design, implemented in 0.35-mu m CMOS technology, consists of a low-power control stage and a dc-dc boost power stage with soft-switching capability. With a nominal input voltage of 1 V, and an output voltage of 4 V, we demonstrate a peak conversion efficiency under nominal conditions of over 94% (overall peak efficiency over 95%), at a power level of 300 mW. The control stage uses lossless current sensing together with a custom low-power time-based analogto- digital converter to minimize control losses. The converter employs a fully integrated digital implementation of a peak power-tracking algorithm, and achieves a measured tracking efficiency above 98%. A detailed study of achievable efficiency versus inductor size is also presented, with the calculated and measured results.
This article presents a single-phase series active power filter for mitigation of the load voltage harmonic content while maintaining the voltage on the DC side regulated without the support of a voltage source. The proposed series active power filter control algorithm eliminates the additional voltage source to regulate the DC voltage, and with the adopted topology, a coupling transformer is not used to interface the series active power filter with the electrical power grid. The article describes the control strategy that encapsulates the grid synchronization scheme, compensation voltage calculation, damping algorithm, and dead-time compensation. The topology and control strategy of the series active power filter have been evaluated in simulation software, and simulations results are presented. Experimental results, obtained with a developed laboratorial prototype, validate the theoretical assumptions and are within the harmonic spectrum limits imposed by the international recommendations of IEEE Standard 519.
The article introduces an innovative PWM current-mode technique to control the switched-mode power supplies for regulating the output of the power supply. The proposed technique can be used to control the most common offline power supply topologies and to control any dc-dc converter. Using the new methodology, it is possible to greatly simplify the internal architecture of any integrated IC controller, reducing its complexity and costs and greatly simplifying the overall system's design process.
High penetration of renewable generation will increase the requirement for both operating reserve (OR) and frequency response (FR), due to its variability, uncertainty, and limited inertia capability. Although the importance of optimal scheduling of OR has been widely studied, the scheduling of FR has not yet been fully investigated. In this context, this paper proposes a computationally efficient mixed integer linear programming formulation for a full stochastic scheduling model that simultaneously optimizes energy production, OR, FR, and underfrequency load shedding. By using value of lost load (VOLL) as the single security measure, the model optimally balances the cost associated with the provision of various ancillary services against the benefit of reduced cost of load curtailment. The proposed model is applied in a 2030-GB system to demonstrate its effectiveness. The impact of installed capacity of wind generation and setting of VOLL is also analyzed.
The combination of wind turbines with fuel cells (FC) and electrolyzers (ELY) is an option for balancing fluctuating grid power injections from renewable energy sources. The conversion of electricity to hydrogen via ELY is often called "power to gas", while transforming hydrogen to electricity via FC is referred to as re-electrification. The application of these technologies currently faces high costs and finding a positive business case is challenging. This study quantifies the economic potential of marketing FC/ELY systems' flexibility. Their potential to reduce wind farm forecast errors as well as the system's ability to provide secondary control reserve (SCR) in Germany is investigated. For this purpose, data for the year 2013 is used. Different root mean squared errors and a probability density function (PDF) for forecast errors are considered. SCR dispatch power in high temporal resolution is approximated and different bidding strategies (SCR market) are taken into account. Results show that both applications can be economically viable, also when being combined. However, profitability is highly dependent on the system's configuration as well as its operating strategy. (C) 2016 Elsevier Ltd. All rights reserved.
This paper presents the realization of Fuzzy Logic Controller concepts using operational amplifiers as a tool to teach students about design and modeling. Design of a FLC is performed because this path provides a good background for the student to experience a complete process approach that goes from verbal description of a problem throughout the final practical implementation, passing through the process of mathematical modeling and the understanding of what a realization of a function means. All the basic blocks consist of operational amplifier circuits that are taught in a first circuit course, just pushing the application a little beyond but still within the reach of the already acquired background.
We present a mini-review of cognition in Prader-Willi syndrome. Studies cited include findings on general ability (IQ), IQ correlates with family members, strengths and weaknesses in cognitive profiles in genetic subtypes, attainment in literacy and numeracy, language, comprehension, modality preferences, executive functions, and social cognition. The latter includes investigations of theory of mind, emotion recognition, face processing and knowledge of social norms. Results from research on mouse models and brain imaging studies relevant to cognition are briefly discussed. The importance of these studies to understanding and managing education and behaviour in PWS and the limitations of the studies in terms of small numbers, non-representativeness, and lack of replication is also touched upon. (C) 2016 Elsevier Ltd. All rights reserved.
Pragmatics has historically played a relatively peripheral role in language evolution research. This is a profound mistake. Here I describe how a pragmatic perspective can inform language evolution in the most fundamental way: by making clear what the natural objects of study are, and hence what the aims of the field should be.
Purpose Prolactin regulatory element-binding protein (PREB), a member of the WD-repeat protein family, has been recognized as a transcriptional factor that regulates prolactin promoter activity in the anterior pituitary of rats. PREB is expressed not only in the pituitary but also in various other tissues, including the adipose tissue. Previous studies have shown that PREB acts as a transcriptional regulator and suppresses the expression of the adiponectin gene in cultured 3T3L1 preadipocytes. The aim of this study was to further examine the potential role of PREB in adipose tissue in vivo. Methods Transgenic mice that overexpressing PREB (PREB transgenic mice) were generated. Insulin resistance was evaluated in PREB transgenic mice using glucose and insulin tolerance tests. Adiponectin expression in the adipose tissue was examined by western blot analysis and quantitative polymerase chain reaction (qPCR). The expression levels of stearoyl-CoA desaturase (Scd) and adiponectin receptor 2(ADIPOR2) were quantified by qPCR. Results Glucose and insulin tolerance tests revealed insulin resistance in PREB transgenic mice. Serum adiponectin and leptin concentrations were decreased. Adiponectin gene expression was decreased in the adipose tissue, which was confirmed by the downregulation of the adiponectin-dependent hepatic Scd gene and upregulation of the ADIPOR2 gene in the liver of PREB transgenic mice. We also found that pioglitazone, an agonist for the peroxisome proliferator-activated receptor-r, improved the insulin resistance in the PREB transgenic mice after a 10-day feeding period. Conclusions These results demonstrated that PREB might contribute to the regulation of adiponectin gene expression in vivo.
The developmental needs of infants during the first year of life have been emphasised by recent research from a variety of sources highlighting the crucial role that early parent-infant interaction plays. Infants identified as being at significant risk of maltreatment need adequate protection within a time frame consistent with their developmental needs. This briefing paper describes a new care pathway established within a UK-based social care team, which aims to provide early identification, intensive support, timely assessment and decision making for a group of highly vulnerable, pregnant women, their partners and their infants. The pathway of care is described and a case study is presented to illustrate this care pathway. A mother is referred at eighteen weeks of pregnancy and supported post birth for six months. The combination of supporting structured professional judgement by the inclusion of standardised tools and training in a programme specifically developed for high-risk families suggests that this pre-birth risk-assessment process warrants further evaluation.
A new operational amplifier cell for high voltage current sensing applications is presented in this paper. The proposed structure employs a fully low voltage input stage capable of tracking input common modes (CMs) ranging from GND rail to above the supply rail. Furthermore, a solution for ensuring the linearity of the amplifier over the entire operating voltages is discussed. The proposed circuit was implemented in a typical 0.25 mu m CMOS BCD technology and its performances were confirmed by simulations and silicon measurements.
Decision support methodologies in precision agriculture should integrate the different dimensions composing the added complexity of operational decision problems. Special attention has to be given to the adequate knowledge extraction techniques for making sense of the collected data, processing the information for assessing decision makers and farmers in the efficient and sustainable management of the field. Focusing on weed management, the integration of operational aspects for weed spraying is an open challenge for modeling the farmers' decision problem, identifying satisfactory solutions for the implementation of automatic weed recognition procedures. The objective of this paper is to develop a decision support methodology for detecting the undesired weed from aerial images, building an image-based viewpoint consisting in relevant operational knowledge for applying precision spraying. In this way, it is possible to assess the potential herbicide cost reductions of increased precision at the spraying device, selecting the appropriate weed precision spraying technology. Findings from this study indicate that the potential gains and marginal cost reductions of herbicides decrease significantly with increased precision in spraying.
The role of prediction error (PE) in driving learning is well-established in fields such as classical and instrumental conditioning, reward learning and procedural memory; however, its role in human one-shot declarative encoding is less clear. According to one recent hypothesis, PE reflects the divergence between two probability distributions: one reflecting the prior probability (from previous experiences) and the other reflecting the sensory evidence (from the current experience). Assuming unimodal probability distributions, PE can be manipulated in three ways: (1) the distance between the mode of the prior and evidence, (2) the precision of the prior, and (3) the precision of the evidence. We tested these three manipulations across five experiments, in terms of peoples' ability to encode a single presentation of a scene-item pairing as a function of previous exposures to that scene and/or item. Memory was probed by presenting the scene together with three choices for the previously paired item, in which the two foil items were from other pairings within the same condition as the target item. In Experiment 1, we manipulated the evidence to be either consistent or inconsistent with prior expectations, predicting PE to be larger, and hence memory better, when the new pairing was inconsistent. In Experiments 2a-c, we manipulated the precision of the priors, predicting better memory for a new pairing when the (inconsistent) priors were more precise. In Experiment 3, we manipulated both visual noise and prior exposure for unfamiliar faces, before pairing them with scenes, predicting better memory when the sensory evidence was more precise. In all experiments, the PE hypotheses were supported. We discuss alternative explanations of individual experiments, and conclude the Predictive Interactive Multiple Memory Signals (PIMMS) framework provides the most parsimonious account of the full pattern of results. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.
The co-occurrence of psychotic and autism spectrum disorder (ASD) symptoms represents an important clinical challenge. Here we consider this problem in the context of a computational psychiatry approach that has been applied to both conditions-predictive coding. Some symptoms of schizophrenia have been explained in terms of a failure of top-down predictions or an enhanced weighting of bottom-up prediction errors. Likewise, autism has been explained in terms of similar perturbations. We suggest that this theoretical overlap may explain overlapping symptomatology. Experimental evidence highlights meaningful distinctions and consistencies between these disorders. We hypothesize individuals with ASD may experience some degree of delusions without the presence of any additional impairment, but that hallucinations are likely indicative of a distinct process.
Predictive control has attracted much attention and has been widely used in power electronics and electric drives. However, further developments for applications in the field of renewable energy systems are still under investigation. In this paper, the principles of predictive control are studied with a focus on model predictive control (MPC) and vector-sequence-based predictive control (VPC). Based on these techniques, two control strategies for flexible power supply are developed. They are implemented in the most promising renewable energy systems, namely solar photovoltaic (PV) systems and wind generators, respectively. The experimental results based on a laboratory prototype show that the active and reactive powers supplied by the PV and wind generator can be controlled flexibly with excellent steady-state and transient performance. As the penetration level of the renewable energy sources in electricity network continues to rise, predictive control tends to be an attractive and powerful technique for power electronics converters in renewable energy systems.
Well-controlled trophoblast invasion at the maternal-fetal interface is crucial for normal placentation and successful pregnancy, otherwise pathological conditions of pregnancy occur, such as preeclampsia. In previous studies, it has been demonstrated that unique long 16 binding protein (ULBP)1, a ligand for the natural-killer group (NKG)2D receptor on uterine natural killer (uNK) cells, is upregulated in the placenta in patients with preeclampsia. As they are present on the majority of the decidua, uNK have an important role in pregnancy. The aim of the present study was to determine the role of ULBP1 in trophoblast cell invasion, which is closely associated with the occurrence of preeclampsia. In the present study, ULBP1 expression levels in placentas collected after cesarean section from women with preeclampsia and normal pregnant women were determined by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting. The effects of ULBP1 on extravillous trophoblast cell line (HTR-8/SVneo) invasion mediated via uNK cells and the underlying mechanisms were investigated. mRNA and protein expression levels of ULBP1 were significantly upregulated (P<0.05) in preeclamptic placentas compared with normal controls. ULBP1 inhibited HTR-8/SVneo cells via the regulation of biological functions of uNK cells, including the downregulation of NKG2D expression on uNK cells and the stimulation of production of cytokines and chemokines that affect extravillous cytotrophoblast invasion by uNK cells. ULBP1 may have an important role in the pathophysiology of preeclampsia through the modification of biological functions of uNK cells, which may affect trophoblast invasion.
Background & Objective: Rehabilitation focuses brain-behavior relationship which highlights interaction between psychological and neurobiological factors for better patient care. There is a missing link in the literature about socio-cognitive aspects of frontal lobe epilepsy. Our objective was to examine prefrontal cortical functioning (PCF) and empathic abilities in patients with frontal lobe epilepsy (FLE). Further, we analyzed whether any relationship between components of dispositional empathy and PCF exists in patients with FLE. Methods: The study was designed in an experimental paradigm. Sixty patients with FLE were recruited from Sheikh Zayed and Jinnah hospital, Pakistan. Sixty healthy individuals in response to an advertisement took part in the study as control subjects. Participants completed interpersonal reactivity index. Following they performed clock drawing test and word-color identification task switching experiment. Result: Patients with FLE demonstrated weaker PCF (i.e., cognitive flexibility and executive function) as compared to healthy control subjects. Patients with FLE scored lesser on cognitive empathy as compared to healthy control subjects. On contrary, there was no significant difference between patient and control group on affective empathy. Cognitive not affective empathy was potential predictor of PCF. Conclusion: Cognitive empathy is a significant marker of prefrontal cortical functioning (PCF) in FLE. Higher cognitive empathy would lead to efficient PCF.
We sought to identify relationship and individual psychological factors that related to four profiles of intimate partner violence (IPV) among pregnant adolescent couples: no IPV, male IPV victim only, female IPV victim only, mutual IPV, and how associations differ by sex. Using data from a longitudinal study of pregnant adolescents and partners (n = 291 couples), we used a multivariate profile analysis using multivariate analysis of covariance with between and within-subjects effects to compare IPV groups and sex on relationship and psychological factors. Analyses were conducted at the couple level, with IPV groups as a between-subjects couple level variable and sex as a within-subjects variable that allowed us to model and compare the outcomes of both partners while controlling for the correlated nature of the data. Analyses controlled for age, race, income, relationship duration, and gestational age. Among couples, 64% had no IPV; 23% male IPV victim only; 7% mutual IPV; 5% female IPV victim only. Relationship (F = 3.61, P < .001) and psychological (F = 3.17, P < .001) factors differed by IPV group, overall. Attachment anxiety, attachment avoidance, relationship equity, perceived partner infidelity, depression, stress, and hostility each differed by IPV profile (all P < .01). Attachment anxiety, equity, depression and stress had a significant IPV profile by sex interaction (all P < .05). Couples with mutual IPV had the least healthy relationship and psychological characteristics; couples with no IPV had the healthiest characteristics. Females in mutually violent relationships were at particularly high risk. Couple-level interventions focused on relational issues might protect young families from developing IPV behaviors. (C) 2016 Wiley Periodicals, Inc.
Purpose: The purpose of this study was to explore the association between sexual orientation and teen pregnancy (before age 20 years) in a U.S. nationally representative cohort of young adult females aged 24-32 years. Methods: A total of 5,972 participants in Waves I and IV of the National Longitudinal Study of Adolescent to Adult Health were included. Self-reported sexual orientation identity was categorized as heterosexual, and three sexual minority (SM) groups: mostly heterosexual, bisexual, and lesbian (combining "mostly homosexual" and "100% homosexual"). Stepwise multivariate regression models were fit to compare odds of teen pregnancy and relative risk ratios of timing of teen pregnancy, between heterosexual and SM groups, adjusting for sociodemographic characteristics, sexual victimization history, and sexual risk behaviors. Results: After adjusting for sociodemographics and sexual victimization, bisexual women had significantly higher odds than heterosexual peers of teen pregnancy (odds ratio [OR] = 1.70; 95% confidence interval [CI] = 1.05-2.75); this association was marginally significant after adjusting for sexual risk behaviors. Bisexuals were also more likely to have an early (before age 18 years) teen pregnancy (OR = 2.04; 95% CI = 1.17-3.56). In contrast, lesbian women were significantly less likely to have a teen pregnancy than heterosexual (OR = .47; 95% CI = .23-.97), mostly heterosexual (OR = .46; 95% CI = .21-.99), and bisexual (OR = .29; 95% CI = .12-.71) women in final models. Conclusions: Expanding on extant literature, we found opposing risk patterns for teen pregnancy between bisexual and lesbian women, likely due to distinct patterns of sexual risk taking. Findings suggest that SM-inclusive teen pregnancy prevention efforts tailored to meet the unique needs of SM young women, particularly bisexuals, are needed. (C) 2016 Society for Adolescent Health and Medicine. All rights reserved.
Introduction: Pregnancy anxiety is an important psychosocial risk factor that may be more strongly associated with adverse birth outcomes than other measures of stress. Better understanding of the upstream predictors and causes of pregnancy anxiety could help to identify high-risk women for adverse maternal and infant outcomes. The objective of the present study was to measure the associations between five past pregnancy outcomes (live preterm birth (PTB), live term birth, miscarriage at <20 weeks, stillbirth at 20 weeks, and elective abortion) and pregnancy anxiety at three trimesters in a subsequent pregnancy.Methods: Analyses were conducted using data from the 3D Cohort Study, a Canadian birth cohort. Data on maternal demographic characteristics and pregnancy history for each known previous pregnancy were collected via interviewer-administered questionnaires at study entry. Pregnancy anxiety for the index study pregnancy was measured prospectively by self-administered questionnaire following three prenatal study visits.Results: Of 2366 participants in the 3D Study, 1505 had at least one previous pregnancy. In linear regression analyses with adjustment for confounding variables, prior live term birth was associated with lower pregnancy anxiety in all three trimesters, whereas prior miscarriage was significantly associated with higher pregnancy anxiety in the first trimester. Prior stillbirth was associated with greater pregnancy anxiety in the third trimester. Prior elective abortion was significantly associated with higher pregnancy anxiety scores in the first and second trimesters, with an association of similar magnitude observed in the third trimester.Discussion: Our findings suggest that the outcomes of previous pregnancies should be incorporated, along with demographic and psychosocial characteristics, into conceptual models framing pregnancy anxiety.
Background: There is increasing understanding of the significance of early neurodevelopment in establishing risk for the range of mental disorders. Models of the early aetiology of mental disorders are complex with a range of potential factors from genetic and epigenetic to environmental influencing neurological and psychological development. Whilst the mechanisms are not fully understood, this paper provides an overview of potential biological and neurobiological factors that might be involved. Method: An aetiological model is presented and discussed. The discussion includes a range of risk factors for mental disorder. Maternal anxiety disorder is presented and reviewed as an example of the interaction of placental, epigenetic and early parenting factors elevating risk of poor neonatal outcome. Results: Available evidence points to the importance of in-utero influences as well as the role of early attachment and emotional care. Transgenerational mechanisms such as the impact of maternal mental disorder on foetal development are important models for examination of early risk. Maternal anxiety, as an example, is a significant risk factor for compromised mental health. Conclusions: Development of models for understanding the early origins of mental disorder is an important step in elaborating risk reduction strategies. Comprehensive early identification of risk raises the possibility of preventive interventions.
The objective of this study was to estimate whether maternal history of childhood maltreatment was associated with pre-pregnancy obesity or excessive gestational weight gain. Pregnant women (n = 472) reported pre-pregnancy weight and height and gestational weight gain and were followed up to 16 years post-partum when they reported maltreatment on the Childhood Trauma Questionnaire (CTQ). CTQ score ranged from no maltreatment (25) to severe maltreatment (125). Prenatal mental health modified the association between CTQ score and maternal weight (P= 75th percentile on the State Trait Anxiety Inventory) [relative risk, RR (95% confidence interval, CI): 1.45 (1.12, 1.88)], but was not associated among less anxious (<75th percentile) women [RR (95% CI): 1.10 (0.81, 1.51)]. Risk of excessive gestational weight gain was higher [adjusted RR (95% CI): 1.21 (1.07, 1.37)] with every 1 SD increase in CTQ score for anxious women. No association was observed for less anxious women [adjusted RR (95% CI): 0.89 (0.78, 1.02)]. Prenatal depression similarly modified the association between maltreatment and weight gain. Factors such as psychological status and traumatic experiences in early childhood may contribute to pre-pregnancy obesity and excessive gestational weight gain.
During human pregnancy, paternally inherited antigens expressed by the fetal-placental unit can elicit expansion of antigen-specific CD8(+) T cells. These cells can persist for years asmemory T cells, but their effects on long-term maternal health are unknown. Shared placenta/tumor-associated antigens are expressed by placenta and tumors, but areminimally expressed or absent in normal adult tissues. We hypothesized that maternal T cells elicited against these antigens can alter risk of cancers expressing the same antigen after pregnancy, and tested this inmice using chicken ovalbumin (OVA) as a surrogate shared placenta/tumor antigen. Hemizygous OVA transgenicmales were bred to wild-type C57BL/6 females (H2b haplotype) such that the fetuses inherited and expressed OVA. Maternal OVA/H2Kb-specific CD8(+) T cells became detectable during gestation, and persisted in some animals for up to 24 weeks. To determine whether these cells might influence growth of OVA-expressing tumors in OVA-bred females, E. G7-OVA thymoma cells were inoculated subcutaneously in OVA-bred, wild-type bred, and virgin females, and monitored for growth. OVA-bred mice had prolonged survival as compared to virgin mice and the progression of tumors was delayed in comparison to wild-type bred and virgin females. Thus, paternally inherited OVA antigen elicited a CD8(+) T cell response during pregnancy that was associated with delayed growth of OVAexpressing tumors following pregnancy. These data suggest a possible role of antigen-specific T cells in protecting parous females against tumors bearing shared placenta/tumor antigens. Summary Sentence Gestational exposure of shared placenta/tumor-associated antigen may induce antigen-specific T cells, which may lower cancer risk against tumors bearing same antigen.
Objectives: Exposure to child abuse (CA) is associated with an increased risk of developing asthma and allergies; it is unknown if that risk is present across generations. This study investigated if 2-year-old children born to mothers with a history of CA were at an increased risk of receiving a diagnosis of asthma or allergies. Methods: Data from 1,551 participants were collected as part of the All Our Babies (AOB) study, a prospective pregnancy cohort. During pregnancy, each woman provided information about her own history of CA, and at 24 months postpartum, she provided information about her child's medical diagnoses. Symptoms of maternal depression and anxiety were assessed during pregnancy and at 24 months postpartum. Results: Unadjusted models showed that compared to children born to mothers without a history of CA, 2-year-old children born to mothers with a history of CA were more likely to have had a diagnosis of asthma (7.4% vs 4.2%, p = .016) or allergy (15.6% vs 9.2%, p < .001). Maternal symptoms of depression assessed in late pregnancy and symptoms of depression and anxiety at 24 months postpartum were significant mediators of the relationship between maternal CA and 2-year-old asthma diagnosis. Maternal symptoms of depression and anxiety assessed in late pregnancy were also significant mediators of the relationship between maternal CA and 2-year-old allergy diagnosis. Conclusions: The results indicate that maternal exposure to CA is associated with increased risk of asthma and allergy in their 2-year-old children; symptoms of maternal depression and anxiety were identified as pathways linking the variables.
The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.
In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother's immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother's exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data.
A lack of longitudinal studies impedes the understanding of whether visual processing skills significantly influence reading performance. The present study assessed if multi element processing (MEP), a visual processing task comprising only non-verbal stimuli, was predominantly related with decoding or sight-word reading. One hundred Spanish pre-reading children were evaluated on their MEP, naming speed (RAN), phonemic awareness (PA), letter knowledge (LK) and IQ. Early reading level was measured in first grade. In third grade, four reading lists consisting of short and long, high- and low-frequency words were administered. Results from path analyses revealed that, after controlling for RAN, PA, LK, IQ and early reading level, MEP was a significant predictor of the reading of long low frequency words only. This result suggests that, in the transparent Spanish orthography, pre-reading MEP is significantly linked to future decoding skill. This is the first study to provide empirical evidence that pre-reading MEP predicts future reading. (C) 2016 Elsevier Inc. All rights reserved.
Background: Despite concerns about rising treatment of psychiatric patients with psychotropic medications and declining treatment with psychotherapy, actual treatment profiles of psychiatric patients are largely unknown.Aims: To describe patterns in the treatment of patients in a large psychiatric university hospital department.Methods: A descriptive mapping of treatment of in- and outpatients in a psychiatric department at Aarhus University Hospital Risskov, Denmark. Information was collected by healthcare staff using a 25-item survey form. The p-value was calculated with a chi-squared test and p<0.05 was considered significant. The study was preceded by a pilot study on 41 patients.Results: Over a 1 month period, a total of 343 consecutive patients were assessed and hereof 200 were included in the age range 18-90 years (mean 53.76); 86 men and 114 women. One-hundred and eighty-eight patients (94%) used psychotropic medication, 37 (19%) as monotherapy, and 148 (74%) in combination with non-pharmacological therapy. Ninety-seven (49%) had psychotherapy and 104 (52%) social support. Among inpatients, 21 (64%) had physical therapy, and 10 (30%) electroconvulsive therapy. In total, 163 (82%) had non-pharmacological therapy. Fifty-two (26%) patients had monotherapy, and 148 (74%) polytherapy. Mean number of treatment modalities used per patient was 2.07 for all patients and 3.23 for inpatients.Conclusions: In this department, polytherapy including non-pharmacological modalities is applied widely across all settings and patient categories. However, psychotropic medication clearly dominates as the most frequently applied treatment.
Psychiatric disorders and in particular depression have increased during the "Great Recession". The aim of this study was to investigate the consumption of psychotropic drugs in people who lost their permanent employment, using administrative data. The study considered all of the subjects domiciled in Lombardy, Northern Italy, who lost a permanent employment between 2008 and 2010, not assuming psychotropic drugs and who did not find a new job within the following 12 months. The control group included people who did not lose permanent job in the study period, matched to the cases for gender, age, nationality, skill level, education and economic sector, using propensity score matching. The subjects who lost their permanent employment were 17 % more likely to receive one or more drug prescriptions than the controls, but the difference was significant only for males. Females, subjects aged >50 years, low skill level workers and Italians were more likely to have received a prescription for psychotropic drugs than respectively males, subjects aged 20-29 years or aged 30-39 years, low skill level workers and non-Italians. The average number of drugs prescribed for those who lost their job and those who continued working was respectively 2.9 and 3.1. In conclusion, losing a permanent job increases significantly psychotropic drugs consumption in males but not in females.
The electrode distance variance and capacitance style pressure sensor is talked about. The change rate of the pressure is treated as judging basis of whether the fault is existed. Make the bridge output signal as the sensor's output signal and one of the detection signal, also make the operational amplifier output signal as another detection signal. The expressions of each element in drift failure when in changeless input signal are obtained. and the change laws of them are analyzed. On the basis of these works it is verified that different elements' failure can be distinguished and solved. After such works the fault location and the fault evaluation are realized. The simulation tells that the value of the fault diagnosis's results are relatively close to the true value of the fault.
Pressure-retarded osmosis is a renewable method of power production from salinity gradients which has generated significant academic and commercial interest but, to date, has not been successfully implemented on a large scale. In this work, we investigate lower bound cost scenarios for power generation with PRO to evaluate its economic viability. We build a comprehensive economic model for PRO with assumptions that minimize the cost of power production, thereby conclusively identifying the operating conditions that are not economically viable. With the current state-of-the art PRO membranes, we estimate the minimum levelized cost of electricity for PRO of US$1.2/kWh for seawater and river water pairing, $0.44/kWh for reverse osmosis brine and wastewater, and $0.066/kWh for nearly saturated water (26% wt) and river water, all for a 2 MW production system. Only a pairing of extremely high salinity (greater than 18%) water and freshwater has the potential to compete with wind power currently at $0.074/kWh. We show two methods for reducing this cost via economies of scale and reducing the membrane structural parameter. We find that the latter method reduces the levelized cost of electricity significantly more than increasing the membrane permeability coefficient. (C) 2017 Elsevier B.V. All rights reserved.
In Korea, an amendment to the Child Welfare Act was made in 2008 that required a national study estimating the occurrence rate of child abuse and neglect every 5 years. The present study reports the major findings of the first national study conducted after the 2008 amendment. The aim of the study is to estimate the prevalence of child physical and psychological maltreatment (CPPM) in Korea and to explore the basic characteristics associated with such incidents. Household surveys were administered to caregivers and focal children who were school age and older. We estimated the prevalence of CPPM using the Parent-child Conflict Tactic Scale, which was developed by Straus et al. (1998). The occurrence rate of CPPM was 25.3 % in Korea, with instances differing by household income, poverty status, and size of the region. Children who experienced physical and psychological maltreatment were more likely to witness the abuse of their siblings and domestic violence. The implications of the findings are discussed and recommendations made for further research.
The prevalence of depression and anxiety in the Chinese male population with infertility is still uncertain. The prevalence of depression, anxiety, and a combination of both psychological symptoms was 20.8%, 7.8%, and 15.4%, respectively in 771 infertile Chinese men in the current study by the Mental Health Inventory-5 and the State-Trait Anxiety Inventory-Short Form questionnaires. Differences in demographics (age, education, and income) had no noticeable impact on the development of psychological symptoms. Clinical factors such as concomitant disorders (varicocele, epididymal cyst, and erectile dysfunction) were identified as risk factors associated with depressive symptoms (OR = 1.47; 95% CI [1.14, 1.90]; p < .001) and both depressive and anxiety symptoms (OR = 1.56; 95% CI [1.17, 2.08]; p < .001). An infertility duration over 2 years was associated with a high risk of anxiety symptoms (OR = 3.94; 95% CI [1.20, 12.93], p < .02). Other clinical conditions such as type of treatment and quality of sperm were not significant risk factors for psychological symptoms. This study provides evidence that Chinese men of reproductive age who suffer from infertility are vulnerable to psychological distress.
Background: Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria, Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the distributions of host, pathogen and vector overlap. Many of these diseases threaten livestock production and some also represent a concern to human public health. The primary aim of this study was to determine the prevalence of the above-mentioned pathogens in a large number of blood samples (n = 1979) collected from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to assess the diagnostic sensitivity of a number of species-specific polymerase chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples were screened using species-specific PCR for the presence of Theileria ovis, Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis, Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The diagnostic sensitivity of these two approaches was then compared in terms of their ability to detect single species and mixed infections. Results: Overall, 84 and 74.43% of the small ruminants sampled were identified as hosting one or more pathogen(s) by species-specific PCR and RLB respectively. The presence of Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the first time while the presence of Babesia motasi, B. crassa and T. separata in Turkish small ruminants was confirmed using molecular methods. A high prevalence of mixed infection was evident, with PCR and RLB approaches indicating that 52.24 and 35.42% of animals were co-infected with multiple species, respectively. More than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB approach was found to be capable of detecting mixed infections with species such as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp. Conclusion: The results indicated that pathogens causing TBHDs are highly prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species-specific single PCR was generally higher than that of RLB. However, the latter approach was still capable of identifying a high proportion of individuals containing mixed-species infections. The use of species-specific single PCR is recommended to accurately estimate pathogen prevalence and to identify co-infected hosts.
Burgeoning research has documented high rates of maltreatment during the first 3 years of life. Early exposure to maltreatment is related to a host of negative physical, developmental, and mental health outcomes in childhood and adulthood. Scientists have documented the biological embedding of maltreatment, including alterations in the structures and processes of the young brain. Maltreatment is a complex phenomenon, which manifests in contexts of family poverty, inadequate parental knowledge and skill regarding child development and caregiving, social isolation of parents, disruptions in parent-child relationships, compromised parental psychological functioning, and concrete issues that affect parenting. Capitalizing on research on young child maltreatment, interventions have been designed to ameliorate infant/toddler maltreatment, buffer young children against the effects of maltreatment, and promote the well-being of maltreated young children. There is a growing empirical base on interventions to address early maltreatment within the context of a public health prevention framework. Primary prevention programs aim to reduce the incidence of maltreatment and related outcomes for infants, toddlers, and their families through the implementation of population-based programs, such as home visiting and early care and education programs. Secondary prevention models target families with specific risk factors associated with maltreatment, such as maternal depression. Tertiary programs generally entail involuntary services, designed to prevent maltreatment recurrence and to improve parenting skills through therapeutic approaches targeting the parent-child dyad. Empirical knowledge about maltreated young children and their families and interventions to support them can inform the design and delivery of child welfare services.
Contemporary approaches to child protection are dominated by individualized forensically focused interventions that provide limited scope for more holistic preventative responses to children at risk and the provision of support to struggling families and communities. However, in many jurisdictions, it is frequently shown, often through public inquiries and program reviews, that investigatory and removal approaches are failing in critically important ways, particularly regarding reducing the inequities that underpin neglect and abuse. Consequently, there have been increasing calls for a public health model for the protection of children, although there is often a lack of clarity as to what exactly this should entail. Yet, there are opportunities to learn from public health approaches successfully used in the field of injury prevention. Specifically, we advocate for the use of Haddon's Matrix, which provides a detailed theoretical and practical framework for the application of a comprehensive and integrated public health model to guide intervention program design and responses to child protection risk factors. A broad overview of the application of Haddon's Matrix's principles and methods is provided with examples of program and intervention design. It is argued that this framework provides the range of interventions necessary to address the complex social and structural factors contributing to inequity and the maltreatment of children. It also provides the foundation for a holistic and integrated system of prevention and intervention to contribute to system-level change and address child maltreatment.
Inadequate access to prevention and medical treatment for female sex workers (SW) represents a challenge for the German health system. Accessibility and care for SW in Bochum (Germany) through a cooperation between the Interdisciplinary Immunology Outpatient Clinic, Center for Sexual Health and Medicine of St. Josef's Hospital, the Bochum health department and the Madonna e.V. was the focus of this work. Medical outreach services were provided for the diagnosis of sexually transmitted infections (STI) in SW in brothels in Bochum between August 2013 and January 2014. After clarification and verbal consent from the SW, free HIV, syphilis, chlamydia, gonorrhea and trichomoniasis tests were offered and carried out using pseudonyms for the SW. A total of 112 SW were reached (up to 55.4 % within the framework of the STI Outreach Study). Of the SW, 94.6 % had an immigrant background. The majority (61.3 %) of SW were between 20 und 29 years old. Only 19.0 % of the collective had health insurance. The following STIs were diagnosed: 12.5 % chlamydia, 6.2 % syphilis, 3.6 % gonorrhea, 3.6 % trichomoniasis, and 0.9 % HIV. These results were compared with results from STI studies in SW in Germany. Treatment was performed in accordance with the standards of the German STI Society. The offer improved the accessibility and the utilization of medical services by SW in Bochum. A further improvement of services is urgently needed.
We consider a linear-state dynamic game played over an event tree and determine analytically the price of anarchy (PoA), which is given by the ratio of player's outcome in the cooperative game to her outcome in the noncooperative game. Next, we illustrate our findings in the context of a pollution control problem. We conduct a sensitivity analysis to assess the impact on PoA, and its lower and upper bounds, of varying the different parameter values. (C) 2016 Elsevier B.V. All rights reserved.
Introduction: Respiratory tract infections constitute the most frequent manifestation of X-linked agammaglobulinemia (XLA). There are not many papers elucidating gastrointestinal (GI) disorders, including inflammatory bowel disease (IBD), in such patients. The aim of the study was to evaluate the occurrence of gastrointestinal disorders and IBD compared to respiratory tract infections in XLA individuals. Material and methods: Of 1563 patients with primary immunodeficiencies diagnosed in the Department of Immunology, the Children's Memorial Health Institute (CMHI), 66 boys had a provisional diagnosis of agammaglobulinemia. Forty-four subjects fulfilled definitive ESID (European Society for Immunodeficiencies) diagnostic criteria of XLA. A retrospective analysis of medical history of XLA patients was undertaken. Results: Recurrent respiratory tract infections, particularly bronchitis (73%) and pneumonia (59%), were the most common symptoms of XLA. The GI disorders constituted the next main manifestation (63.6%), followed by upper respiratory tract infections. Twenty-six of 28 XLA patients with GI disorders complained of diarrhea, which was resolved generally after immunoglobulin therapy introduction. Single but prolonged episodes of Campylobacter jejuni diarrhea were reported in two individuals. Inflammatory bowel disease of mild to moderate activity was diagnosed in 1 patient, and local enteritis of mild activity in another one. Conclusions: Gastrointestinal disorders were one of the main manifestations of XLA, reported almost as often as lower respiratory tract infections. The most common GI symptom was diarrhea, which usually resolved after immunoglobulin therapy was started. Infections caused by Giardia lamblia were reported occasionally. Inflammatory bowel disease was diagnosed quite exceptionally, which presumably may be connected with normal T cell immunity.
In bioethics and health policy, we often discuss the appropriate boundaries of public funding; how the interface of public and private purchasers and providers should be organized and regulated receives less attention. In this paper, I discuss ethical and regulatory issues raised at this interface by three medical practice models (concierge care, executive wellness clinics, and block fee charges) in which physicians provide insured services (whether publicly insured, privately insured, or privately insured by public mandate) while requiring or requesting that patients pay for services or for the non-insured services of the physicians themselves or their associates. This choice for such practice models is different from the decision to design an insurance plan to include or exclude user fees, co-payments and deductibles. I analyze the issues raised with regards to familiar health care values of equity and efficiency, while highlighting additional concerns about fair terms of access, provider integrity, and fair competition. I then analyze the common Canadian regulatory response to block fee models, considering their extension to wellness clinics, with regards to fiduciary standards governing the physician-patient relationship and the role of informed consent. I close by highlighting briefly issues that are of common concern across different fundamental normative frameworks for health policy.
Lymphoma usually forms solid tumours in patients, and high expression levels of adhesion 1 molecules are observed in these tumours. However, Kaposi's sarcoma-associated herpesvirus (KSHV)-related primary effusion lymphoma (PEL) does not form solid tumours and adhesion molecule expression is suppressed in the cells. Inoculation of a KSHV-associated PEL cell line into the peritoneal cavity of severe combined immunodeficiency mice resulted in the formation of effusion and solid lymphomas in the peritoneal cavity. Proteomics using two-dimensional difference gel electrophoresis and DNA microarray analyses identified 14 proteins and 105 genes, respectively, whose expression differed significantly between effusion and solid lymphomas. Five genes were identified as having similar expression profiles to that of lymphocyte function-associated antigen 1, an important adhesion molecule in leukocytes. Among these, coronin 1A, an actin-binding protein, was identified as a molecule showing high expression in solid lymphoma by both DNA microarray and proteomics analyses. Western and northern blotting showed that coronin 1A was predominantly expressed in solid lymphomas. Moreover, KSHV-encoded lytic proteins, including viral interleukin-6, were highly expressed in effusion lymphoma compared with solid lymphoma. These data demonstrate that effusion and solid lymphomas possess distinctive gene and protein expression profiles in our mouse model, and suggest that differences in gene and protein expression between effusion and solid lymphomas may be associated with the formation of effusion lymphoma or invasive features of solid lymphoma. Furthermore, the results obtained using this combination of proteomics and DNA microarray analyses indicate that protein synthesis partly reflects, but does not correlate strictly with, mRNA production. Copyright (D 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
System inertia reduction, driven by the integration of renewables, imposes significant challenges on the primary frequency control. Electrification of road transport not only reduces carbon emission by shifting from fossil fuel consumption to cleaner electricity consumption, but also potentially provide flexibility to facilitate the integration of renewables, such as supporting primary frequency control. In this context, this paper develops a techno-economic evaluation framework to quantify the challenges on primary frequency control and assess the benefits of EVs in providing primary frequency response. A simplified GB power system dynamic model is used to analyze the impact of declining system inertia on the primary frequency control and the technical potential of primary frequency response provision from EVs. Furthermore, an advanced stochastic system scheduling tool with explicitly modeling of inertia reduction effect is applied to assess the cost and emission driven by primary frequency control as well as the benefits of EVs in providing primary frequency response under two representative GB 2030 system scenarios. This paper also identifies the synergy between PFR provision from EVs and "smart charging" strategy as well as the impact of synthetic inertia from wind turbines. (C) 2016 Elsevier Ltd. All rights reserved.
A broad spectrum of autoimmunity is now well described in patients with primary immunodeficiencies (PIDs). Management of autoimmune disease in the background of PID is particularly challenging given the seemingly discordant goals of immune support and immune suppression. Our growing ability to define the molecular underpinnings of immune dysregulation has facilitated novel targeted therapeutics. This review focuses on mechanism-based treatment strategies for the most common autoimmune and inflammatory complications of PID including autoimmune cytopenias, rheumatologic disease, and gastrointestinal disease. We aim to provide guidance regarding the rational use of these agents in the complex PID patient population. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma& Immunology. This is an open access article under the CC BY-NC-ND license.
The large majority of classified primary immune deficiency (PID) diseases present in childhood. Yet, most patients with PID are adults, with a large proportion experiencing onset of symptoms beyond their childhood years. Most of these are diagnosed predominantly with antibody defects, but cellular and other disorders are increasingly being identified in older patients as well. Moreover, advances in clinical immunology are allowing pediatric patients, even those with severe disease, to reach adulthood. Because of differences in the physiology and pathophysiology of children and adults, the presentation, diagnosis, and management of a complex chronic disease could differ significantly between these patient populations and therefore require modifications in approach. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Immunocompromised patients have increased susceptibility to vaccine-preventable infections. Thus, vaccination is a critical issue in this population. Vaccines are usually classified as live versus inactivated or subunit (nonviable) vaccines. In general, inactivated vaccines are safe in immunocompromised patients and should be given per the routine schedule except when they are unlikely to have any benefit as in severe antibody deficiency or combined immunodeficient patients and patients receiving immunosuppressive therapy or immunoglobulin replacement. However, viable vaccines usually carry the risk of causing disease, especially in severely immunocompromised patients. Therefore, much greater caution must be exercised with the use of viable vaccines and administration is individualized on the basis of the estimated risk of infections if not vaccinated versus the potential adverse effects of the vaccine itself. In this review, we make clear recommendations on the basis of available evidence regarding both routine and specialized vaccines, viable and nonviable, and the degree of immune compromise in all the categories of immunodeficiency disorders. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Bluetongue virus (BTV) is a member of the genus Orbivirus within the family Reoviridae and causes a non-contagious, insect-transmitted disease in domestic and wild ruminants, mainly in sheep and occasionally in cattle and some species of deer. Virus infection can trigger the changes of the cellular microRNA (miRNA) expression profile, which play important post-transcriptional regulatory roles in gene expression and can greatly influence viral replication and pathogenesis. Here, we employed deep sequencing technology to determine which cellular miRNAs were differentially expressed in primary sheep testicular (ST) cells infected with BTV. A total of 25 known miRNAs and 240 novel miRNA candidates that were differentially expressed in BTV-infected and uninfected ST cells were identified, and 251 and 8428 predicted target genes were annotated, respectively. Nine differentially expressed miRNAs and their mRNA targets were validated by quantitative reverse transcription-polymerase chain reaction. Targets prediction and functional analysis of these regulated miRNAs revealed significant enrichment for several signaling pathways including MAPK, PI3K-Akt, endocytosis, Hippo, NF-kB, viral carcinogenesis, FoxO, and JAK-STAT signaling pathways. This study provides a valuable basis for further investigation on the roles of miRNAs in BTV replication and pathogenesis. (C) 2017 Elsevier B.V. All rights reserved.
Introduction: Primary Sjogren's Syndrome (pSS) is one of the autoimmune diseases characterized by polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is an important negative regulator of p53. Our previous study indicated that autoantibody to MDM2 can be detected in systemic lupus erythematosus patients. The purpose of this study is to study anti-MDM2 autoantibody in pSS patients. Methods: Anti-MDM2 autoantibody in sera from 100 pSS patients and 74 normal controls was investigated by ELISA. Positive samples were further confirmed by western blotting. Expression of MDM2 in labial gland tissue from pSS patients and normal controls was checked by immunohistochemistry. The difference in clinical characteristics and laboratory findings between anti-MDM2 positive and anti-MDM2 negative pSS patients was analyzed. Results: The presence of anti-MDM2 autoantibody in pSS patients was 21.0%, significantly higher than normal controls (5.40%). MDM2 was overexpressed in labial gland from pSS patients. pSS patients with positive anti-MDM2 were characterized by longer disease duration and more lymphocytes focal gathering in labial gland. Prevalence of anemia, thrombocytopenia and anti-SSB was significantly higher in pSS patients with anti-MDM2 autoantibody. Titer of anit-MDM2 was negatively associated with hemoglobin level, platelet count, complement 3 level and complement 4 level, positively associated with European Sjogren's syndrome disease activity index (ESSDAI) and level of IgG. Conclusions: Anti-MDM2 autoantibody may be used as a potential serological biomarker in pSS disease activity evaluation. Study on the role of anti-MDM2 or MDM2 in pSS may help us know the pathogenesis mechanism of pSS better.
This article described a novel digital multi-mode control strategy for primary-side controlled flyback converter to improve the efficiency within full-load range. The working modes of different load ranges were chosen according to the main power losses analysis and other constraint. Especially, a novel pulse skip mode control method which could reduce the number of actual switching cycles was proposed to improve the light load efficiency. A prototype with field-programmable gate array control has been made to verify the proposed digital multi-mode control strategy.
The often touted attractive attributes of printed/organic electronics are its mechanically flexible form-factor, low-cost, green, on-demand printing, scalability, low-power operation, and intelligence (signal processing) ideally, the creation of intelligent lightweight electronics printed by simple ubiquitous printing processes, and integrated into new ways to exploit its mechanically flexible form-factor. Printed/Organic Electronics, now an industry on its own right and recognized as one of the key technological enablers for the Internet of Things, is largely complementary to silicon because the printed transistors are slow and the printed elements are large. The sanguine projected growth of the $29 B market today to $73 B by 2027 assumes that `intelligence' (analog, mixed-signal and digital signal processing) would be realizable. Nevertheless, many of the said attributes of printed/organic electronics remain a challenge. In this paper, we exemplify this with a comprehensive and critical review and tabulation of the state-of-the art printed digital, analog, and mixed-signal circuits. We further review the application space of printed/organic electronics and the supply chain, including their classifications and delineate the associated challenges in each constituent chain. These challenges, largely unresolved, are indeed formidable, and are discussed with a critical circuits and systems perspective. Our review depicts that contemporary design philosophies and methodologies for silicon are largely inadequate for printed/organic electronics. To this end, we discuss esoteric analog and digital design philosophies and methodologies, with emphasis on co-design and co-optimization between the different constituent supply chains that may potentially circumvent the said formidable challenges, and discuss the associated penalties thereto.
Fibrolamellar carcinoma is a unique type of hepatocellular carcinoma with a distinctive predilection for young patients without underlying liver disease, characteristic large neoplastic cells with intervening, dense fibrosis, co-expression of keratin 7 and CD68 and activation of protein kinase A (most often by formation of DNAJBI-PRKACA). Fibrolamellar carcinoma has a similar prognosis to conventional hepatocellular carcinomas arising in non-cirrhotic livers. The current American Joint Cancer Committee staging system does not provide optimal stratification of patients with fibrolamellar carcinoma and an alternate systems should be considered in the future. The only effective treatment for fibrolamellar carcinoma is complete resection. Novel therapies may be on the horizon as investigation into the molecular biology of fibrolamellar carcinoma continues. (C) 2017 Elsevier Inc. All rights reserved.
Recent evidence suggests that the PRL-1 and -2 phosphatases may be multifunctional enzymes with diverse roles in a variety of tissue and cell types. Northern blotting has previously shown widespread expression of both transcripts; however, little is known about the cell type-specific expression of either gene, especially in human tissues. Therefore, we investigated expression patterns for PRL-1 and -2 genes in multiple normal, adult human tissues using in situ hybridization. Although both transcripts were ubiquitously expressed, they exhibited strikingly different patterns of expression. PRL-2 was expressed heavily in almost every tissue and cell type examined, whereas PRL-1 expression levels varied considerably both between tissue types and between individuals. Widespread expression of PRL-1 and -2 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis. In addition, the variable patterns of expression for these genes may provide distinct activities in each tissue or cell type.
AIM: To analyze the ability of nine different potentially probiotic bacteria to induce maturation and cytokine production in human monocyte-derived dendritic cells (moDCs). METHODS: Cytokine production and maturation of moDCs in response to bacterial stimulation was analyzed with enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis (FACS), respectively. The kinetics of mRNA expression of cytokine genes was determined by Northern blotting. The involvement of different signaling pathways in cytokine gene expression was studied using specific pharmacological signaling inhibitors. RESULTS: All studied bacteria induced the maturation of moDCs in a dose-dependent manner. More detailed analysis with S. thermophilus THS, B. breve Bb99, and L. lactis subsp. cremoris ARH74 indicated that these bacteria induced the expression of moDC maturation markers HLA class H and CD86 as efficiently as pathogenic bacteria. However, these bacteria differed in their ability to induce moDC cytokine gene expression. 5. thermophilus induced the expression of pro-inflammatory (TNF-alpha, IL-12, IL-6, and CCL20) and Th1 type (IL-12 and IFN-gamma) cytokines, while 8, breve and L. lactis were also potent inducers of anti-inflammatory IL-10. Mitogen-activated protein kinase (MAPK) p38, phosphatidylinositol 3 (PI3) kinase, and nuclear factor-kappa B (NF-kappa B) signaling pathways were shown to be involved in bacteria-induced cytokine production. CONCLUSION: Our results indicate that potentially probiotic bacteria are able to induce moDC maturation, but their ability to induce cytokine gene expression varies significantly from one bacterial strain to another. (C) 2008 The WJG Press. All rights reserved.
Spray drying is a process widely applied in the food industry due its reduced operation time and low cost. The use of probiotic bacteria in non-dairy products has receiving much attention and its application in dry food products can be an alternative for its consumption. Thus, the aim of this study was to evaluate the effect of gum arabic, maltodextrin and gelatin on the survival of Lactobacillus reuteri LR92 in fermented jucara pulp after dehydration by spray-drying and the influence on the physical properties of the powders obtained therefrom. Spray-dried powders were produced using 10% of carrier agents, and analyses of cell viability, moisture content, sorption isotherms, solubility, morphological characteristics and colour were conducted. After dehydration, the viability of L. reuteri was above 6.0 log CFU/g for all of the tested carriers, and the powders produced with gelatin presented higher bacterial survival after drying (8.63 +/- 0.11 log CFU/g). Higher yield and solubility were obtained with gum arabic and maltodextrin and the moisture content was around 2-4% (w/w). These results demonstrate that gelatin is a promising material for drying probiotic bacteria, however, technological properties of the powders need to be improved to be used as a dehydrated product. (C) 2017 Elsevier Ltd. All rights reserved.
AIM: To investigate the capacity of potentially probiotic strains from six bacterial genera to induce cytokine production alone or in combinations in order to identify potential enhancing or synergistic effects in order to select probiotic bacteria for in vivo purposes. METHODS: Cytokine production in human peripheral blood mononuclear cells (PBMC) in response to stimulation with eleven different potentially probiotic bacterial strains from streptococcus, Lactobacillus, Bifidobacterium, Lactococcus, Leuconostoc and Propionibacterium genera was analysed. Production and mRNA expression of TNF-alpha, IL-12, IFN-gamma and IL-10 were determined by ELISA and Northern blotting, respectively. RESULTS: All tested bacteria induced TNF-alpha production. The best inducers of Th1 type cytokines IL-12 and IFN-gamma were Streptococcus and Leuconostoc strains. All Bifidobacterium and Propionibacterium strains induced higher IL-10 production than other studied bacteria. Stimulation of PBMC with any bacterial combinations did not result in enhanced cytokine production suggesting that different bacteria whether gram-positive or gram-negative compete with each other during host cell interactions. CONCLUSION: The probiotic S. thermophilus and Leuconostoc strains are more potent inducers of Th1 type cytokines IL-12 and IFN-gamma than the probiotic Lactobacillus strains. Bacterial combinations did not result in enhanced cytokine production. (c) 2008 WJG. All rights reserved.
The goal of this study was to determine whether differences exist in problematic substance use and receipt of services by nativity (U.S. born, foreign born) and legal status (U.S. citizen, legal resident, undocumented) among Latino parents reported for child abuse and neglect. We used data from the National Survey of Child and Adolescent Well-Being II and weighted bivariate chi-square tests to compare rates of problematic substance use and services receipt by nativity and legal status. Weighted logistic regression models estimated the effect of immigrant status on the odds of service receipt. Rates of problematic substance use were not significantly different by nativity or legal status. Service receipt was significantly lower for foreign-born (2.1%) versus U.S.-born (9.4%) parents. Compared to U.S. citizens (8.1%) and legal residents (4.3%), services receipt was least likely for undocumented parents (0.3%). Adjusting for covariates, nativity did not affect services receipt but undocumented legal status reduced the odds of receiving services by 95%. Data indicate that disparities do exist in receipt of substance use services among immigrant parents, especially undocumented parents, compared to U.S. born parents. Findings also suggest that the protective effect of immigrant status on problematic substance use, i.e., the immigrant paradox, may not apply to child-welfare-involved families. (C) 2016 Elsevier Ltd. All rights reserved.
Purpose A blended web-based intervention, "eHealth module embedded in collaborative occupational health care" (ECO), aimed at return to work, was developed and found effective in sick-listed employees with common mental disorders. In order to establish the feasibility of ECO, a process evaluation was conducted. Methods Seven process components were investigated: recruitment, reach, dose delivered, dose received, fidelity, satisfaction and context. Quantitative and qualitative methods were used to collect data: an online questionnaire for the employees, website data, telephonic interviews with occupational physicians (OPs) and observations of the researchers. Results Recruitment was uncomplicated for the employees, but required several steps for the OPs. Reach was 100 % at the OP level and 76.3 % at the employee level. Dose delivered and received for OPs: 91.6 % received minimally one email message. Dose delivered and received for the employees: finishing of the different modules of ECO varied between 13 and 90 %. Fidelity: the support of the OP to the employee in ECO was lower than anticipated. Satisfaction: both employees and OPs were satisfied with the intervention. However, employees reported a need for more support in ECO. The context showed that OPs had limited time to support the employees and it was impossible for the employee to contact the OP outside their regular contacts. Conclusion Feasibility of ECO and satisfaction of employees and OPs with ECO were good. Fidelity of OPs was limited. For further implementation in the occupational health setting, especially contextual barriers regarding time limitation and accessibility of OPs for employees should be addressed.
It is important to identify effective emotion regulation strategies to increase positive emotion experience in the general population and in clinical conditions characterized by anhedonia. There are indications that engaging in experiential processing (direct awareness of sensory and bodily experience) bolsters positive emotion experience but this has not been extensively tested during memory recall. To further test this notion, 99 community participants recalled two positive autobiographical memories. Prior to the second recall, participants either underwent an experiential, analytical, or distraction induction (n = 33 per condition). Subjective happiness and sadness ratings and heart rate variability (HRV) response were measured during each recall. Greater spontaneous use of experiential processing during the first memory was associated with greater happiness experience, but was unrelated to HRV and sadness experience. Inducing experiential processing increased happiness experience relative to both the analytical and distraction conditions (but had no impact on sadness experience). There was a significant difference in HRV between conditions. The experiential condition led to a trend-significant increase, and the other conditions a non-significant decrease, in HRV from the first to the second memory. These results suggest that engaging in experiential processing is an effective way to up-regulate positive emotion experience during positive memory recall. (C) 2017 The Authors. Published by Elsevier Ltd.
Procrastination refers to the delay or postponement of a task or decision and is often conceptualised as a failure of self-regulation. Recent research has suggested that procrastination could be delineated into two domains: intentional and unintentional. In this two-study paper, we aimed to develop a measure of unintentional procrastination (named the Unintentional Procrastination Scale or the 'UPS') and test whether this would be a stronger marker of psychopathology than intentional and general procrastination. In Study 1, a community sample of 139 participants completed a questionnaire that consisted of several items pertaining to unintentional procrastination that had been derived from theory, previous research, and clinical experience. Responses were subjected to a principle components analysis and assessment of internal consistency. In Study 2, a community sample of 155 participants completed the newly developed scale, along with measures of general and intentional procrastination, metacognitions about procrastination, and negative affect. Data from the UPS were subjected to confirmatory factor analysis and revised accordingly. The UPS was then validated using correlation and regression analyses. The six-item UPS possesses construct and divergent validity and good internal consistency. The UPS appears to be a stronger marker of psychopathology than the pre-existing measures of procrastination used in this study. Results from the regression models suggest that both negative affect and metacognitions about procrastination differentiate between general, intentional, and unintentional procrastination. The UPS is brief, has good psychometric properties, and has strong associations with negative affect, suggesting it has value as a research and clinical tool.
Progesterone (PG) as a neuroprotective reagent has been used for the treatment of spinal cord injury (SCI) in experimental animal models. However, its effect and mechanism on axonal dieback at the early stage of SCI remain unclear. Here, we investigate the dynamics of injured axons and the effect of PG on the axonal dieback, glial response, and behavioral recovery in a mouse model of SCI. Two-photon intravital imaging combined with a simplified imaging window chamber were used to image axons in hemisected spinal cords over a period of 3 days. Repeated imaging showed that axonal dieback distance in mice treated with PG after SCI was significantly reduced than that in mice treated with vehicle after SCI (P < 0.05) at the time point of 24 h, 48 h, and 72 h after SCI. The densities of astrocytes and microglia in the SCI-vehicle treated group were significantly higher than those in mice treated with PG after SCI (P < 0.05). Real time polymerase chain reaction assay indicated that administration of PG after SCI down regulated the expression of pro-inflammatory cytokines MCP-1, NOS2, and IL-1 beta (P < 0.05). PG treatment also improved the behavioral performance post injury. These findings suggested that PG exerted a neuroprotective effect by attenuating axonal dieback, reducing the accumulation of astrocytes and microglia and inhibiting the release of pro-inflammatory cytokines. (C) 2016 Elsevier Ltd. All rights reserved.
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide. However, the therapy with this antibody harbors significant toxicity. Meanwhile, other targets such as PD-1, also expressed on (late) activated T cells, were identified, and therapies with antibodies inhibiting PD-1/PD-L1 are less toxic. Although these antibodies show response only in a minority of patients, the benefit seems durable in some of these patients. In solid tumors such as melanoma or non-small cell lung cancer (NSCLC), treatment with PD-1 inhibitors has resulted in a significant prolongation of survival, even in first-line treatment. As these drugs have been approved in many indications, it is important to know the drugs and side effects. Resistance towards these drugs are caused by low expression of the natural ligand, PD-L1, in the tumor tissue, as well as acquired loss of signal transduction of interferon-related genes such as JAK1 or JAK2, respectively. Also new in cancer therapy are bispecific T cell engager monoclonal antibodies (BiTEs) such as blinatumomab, and autologous chimeric antigen receptor-modified T cells (CAR-Ts). The later have proven their efficacy mainly in hematological neoplasias such as precursor-B-ALL. The dramatic costs of all these new drugs will have an enormous impact on the health care systems in the near future.
Empathy involves being able to understand and respond to others' emotional experiences. Whilst deficits in empathy have been observed in frontotemporal dementia, the extent to which empathy is disrupted in dementia syndromes with predominant language impairment remains unclear. The current study investigated cognitive and affective empathy in the two non-fluent primary progressive aphasia syndromes: progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia (LPA). Informants of 23 PNFA and 16 LPA patients completed the Interpersonal Reactivity Index (IRI), regarding patients' capacity for empathy preand post-disease onset. Twenty-four healthy control participants completed the self-rated IRI for comparison of post-disease empathy capabilities. Within-group analyses revealed reduced cognitive empathy and increased personal distress in both patient groups. In addition, lowered affective empathy was reported in PNFA, with a similar trend observed in LPA. Interestingly, reduced affective empathy was associated with greater carer burden in LPA. Between-group analyses revealed reduced cognitive empathy in both patient groups relative to controls. The current study is the first to document empathy changes in PNFA and LPA, offering insight into the social cognitive deficits experienced in these syndromes. Future neuroimaging studies are needed to identify the underlying neural correlates and mechanisms driving empathy deficits in PNFA and LPA.
The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.
RNA interference (RNAi) involves the degradation of homologous mRNA sequences in organisms and is induced by double-stranded RNA (dsRNA). We have constructed three hairpin RNA (hpRNA) prokaryotic expression vectors derived from the 5' region, the middle region and the 3' region of the Nuclear inclusion protein b (NIb) gene, and then expressed these in M-JM109lacY. Resistance analyses and Northern blotting showed that different hpRNAs had different abilities to protect tobacco plants from infection with Potato virus Y (PVY) and that this resistance was RNA-mediated.
Aim: Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C ->G and 580C ->T) and mouse double minute 2 (MDM2) (SNP309T ->G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma. Patients and Methods: A total of 74 patients with prolactinoma and 100 age-and gender-matched healthy individuals were enrolled in the study. Serum prolactin levels were measured by enzyme-linked immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis. Results: p16 540C. G genotype distribution was found to be: CC: 66.2%, CG: 28.4%, GG: 5.4%; p16 580C ->T genotype distribution was found to be: CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT: 31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (r=0.719, pG was significantly higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95% confidence interval(CI)=0.06-0.58; p=0.003). Conclusion: This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.
The prophenoloxidase (proPO)-activating system in crustaceans and other arthropods is regarded as a constituent of the immune system and plays an important role in defense against pathogens. Hitherto in crustaceans, only one proPO gene per species has been identified. Here we report the identification of a novel proPO-2 (LvproPO-2) from the hemocytes of Litopenaeus vannamei, which shows 72% identity to proPO-1 (LvproPO-1) cloned previously. Northern blotting analysis and quantitative real-time PCR reveal that LvproPO-2 is mainly expressed in the hemocytes, and its expression is down-regulated in shrimp challenged with white spot syndrome virus (WSSV). Western blotting analysis shows that most LvproPO-2/LvPO-2 (L vannamei phenoloxidase-2) exists in the hemocytes, but not in plasma of L vannamei. LvproPO-2/LvPO-2 could be detected on the hemocyte surface and the nucleus of hemocytes by indirect immunofluorescence assay (IFA). These findings provide insight into the molecular biological basis for further studying on the defense mechanism of shrimp innate immunity, especially on the proPO-activating system and melanization cascade of shrimp. (C) 2008 Elsevier Ltd. All rights reserved.
Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis. (c) 2005 Wiley-Liss, Inc.
In these days, three degree of freedom (3DOF) cranes are considered as backbone in most of industries. It is mostly used for picking and placing of heavy objects from one place to another place. The common part in mostly cranes is jib system. Two main tasks of jib system are movement of the trolley and loading/unloading of the payload. The safety of crane mostly depends upon these sub tasks. In most cases, number of unwanted vibrations due to undesirable initial jerks of trolley results uneven operation of crane. These jerks are usually happened during acceleration in the start and deceleration in the end of crane operation. So, it is desirable to develop a control technique that tries to reduce theses initial trolley jerks by providing a reasonable input to the trolley. Moreover, reduction of jerks reduce the payload vibrations. So, it results smooth operation of crane. In this research work, we have implemented PD control technique for payload vibration and trolley position control of jib system of three 3DOF crane. The gains of PD controllers have been found through two methods namely LQR and pole placement. The performance of controllers have been investigated on Matlab/Simulink. The results shows the effectiveness of PD tune by LQR as compared to PD tune by pole placement in context of settling time and rise time of both trolley position and payload vibrations. The former technique is also helpful in reduction of payload vibrations or payload load anti-swing. It has also improved the overshoot of the trolley.
Sampling and computational delay are necessary in digital control, though they may alter the characteristics of the actual controlled plant when considered in the discrete domain. Accordingly, this article establishes a mathematical model of a single-phase grid-connected inverter with an LCL filter in the discrete domain. Three active damping control delay times: 0, [GRAPHICS] , [GRAPHICS] are analysed, considering the influences introduced by digital control of the plant. Further, the range of the capacitor current feedback coefficient used in active damping control is derived to guarantee that the controlled plant does not have poles outside the unit circle. Using Nyquist diagrams, the proper proportional-resonant (PR) controller parameters can be intuitively determined. The theoretical analysis is verified using MATLAB and a 3kW laboratory prototype based on a digital signal processor (TMS320F2808).
In this manuscript, we report the synthesis, NMR and single-crystal structures of three propylene linking dimers related with the hydrolytic degradation of one 5,6-dehydronorcantharimide dimer. Special attention was paid to the conformation of propylene linkers in order to understand their changes in the reaction. Statistical analysis of CSD database revealed that a-a, g-a and g-g conformations may have similar stability in most cases and various complicated unpredictable non-covalent interactions may play important role in the formation of final rotamers. In order to reproduce all stable conformations and the energy barriers separating them, full range two-dimensional fully relaxed potential-energy surfaces (PES) scans of six 'propylene linker' dimers were calculated starting from the most stable crystal structures. The PES were scanned along both bridge C-C single bond torsional angles (denoted as theta(1) and theta(2)), while all other internal coordinates were optimized at the DFT/B3LYP/3-21G* level in gas phase. Then all energy minima were re-optimized again at the DFT/B3LYP/6-311 + G(d,p) level both in gas and ethanol solutions in order to evaluate the really stable rotamers. At last, 1D or 2D relaxed PES scans were performed between local stable rotamers to get reliable energy barriers. This method represents a less time-consuming and more reliable approach to the determination of conformational stability of propanediyl bridging chains. The combination of experimental, statistical and theoretical results shows that the observed conformation is jointly determined by the energy levels of the minima, energy barriers separating them, non covalent interactions and somewhat randomness. (C) 2017 Elsevier B.V. All rights reserved.
Background: Early childhood is a crucial period for language development and building social skills. While distinct, these two processes may impact upon each other.Aims: The current study aimed to identify the directional associations between expressive language ability and prosocial behaviour between three and five years of age.Methods: Participants included 14, 004 children and their families enrolled in the UK Millennium Cohort Study. Children's expressive language and prosocial behaviour were assessed at three and five years of age utilizing standardized assessments and parent reports. Cross-lagged models were used for data analysis.Results: Better expressive language at three years was associated with increased prosocial behaviour by five years. No support for the inverse direction of association was found.Conclusions: Children's early ability to effectively express themselves with others may help in building better social relationships by entry into formal schooling. Programming efforts that are tailored towards enhancing positive behavioural growth and social skills in the toddler years are likely to be effective when expressive language is also a targeted component of the toddler's skill development.
Therapeutic interventions for advanced prostate cancer (PCa) center on inhibiting androgen receptor (AR) and downstream signaling pathways. Resistance to androgen deprivation therapy and/or AR antagonists is inevitable and molecular mechanisms driving castration-resistant PCa (CR-PCa) primarily involve alterations in AR expression and activity. Detailed molecular biology work over the past decade, discussed at length in this review article, has revealed several AR transcripts that result from alternative splicing. These AR splice variants are increased in cell and mouse models of CR-PCa and in CR-PCa tumors. Several AR variants lack the ligand binding domain, but retain their ability to bind DNA and activate transcription-linking constitutive AR function and therapeutic failure. ARV7 is the only variant endogenously detected at the protein level and thus has undergone more thorough molecular characterization. Clinical trials in PCa are currently investigating ARV7 utility as a biomarker and new therapeutics that inhibit ARV7. Overall, this review will illustrate the historical perspectives of AR splice variant discovery using fundamental molecular biology techniques and how it changed the clinical approach to both therapeutic decisions and strategy. The body of work investigating AR splice variants in PCa represents a true example of translational research from bench to bedside.
Prostate cancer is the most common cancer of men in the UK and accounts for a quarter of all new cases. Although treatment of localised cancer can be successful, there is no cure for patients presenting with invasive prostate cancer and there are less treatment options. They are generally treated with androgen ablation therapies but eventually the tumours become hormone resistant and patients develop castration-resistant prostate cancer (CRPC) for which there are no further successful or curative treatments. This highlights the need for new treatment strategies. In order to prevent prostate cancer recurrence and treatment resistance, all the cell populations in a heterogeneous prostate tumour must be targeted, including the rare cancer stem cell (CSC) population. The ETS transcription factor family members are now recognised as a common feature in multiple cancers including prostate cancer; with aberrant expression, loss of tumour suppressor function, inactivating mutations and the formation of fusion genes observed. Most notably, the TMPRSS2-ERG gene fusion is present in approximately 50% of prostate cancers and in prostate CSCs. However, the role of other ETS transcription factors in prostate cancer is less well understood. This review will describe the prostate epithelial cell hierarchy and discuss the evidence behind prostate CSCs and their inherent resistance to conventional cancer therapies. The known and proposed roles of the ETS family of transcription factors in prostate epithelial cell differentiation and regulation of the CSC phenotype will be discussed, as well as how they might be targeted for therapy. (C) 2016 Elsevier Ltd. All rights reserved.
The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.
Prostate cancer (PCa) has become the second leading cause of male cancer-related mortality in the United States. Mesenchymal stem cells (MSCs) are able to migrate to tumor tissues, and are thus considered to be novel antitumor carriers. However, due to their immunosuppressive nature, the application of MSCs in PCa therapy remains limited. In this study, we investigated the effect of MSCs overexpressing an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1) on prostate tumor growth, and we analyzed the underlying mechanisms. Our results show that MSCs accelerate prostate tumor growth, whereas MSCs-Sirt1 significantly suppresses tumor growth. Natural killer (NK) cells and macrophages are the prominent antitumor effectors of the MSCs-Sirt1-induced antitumor activity. IFN-gamma and C-X-C motif chemokine ligand 10 (CXCL10) are highly expressed in MSCs-Sirt1 mice. The antitumor effect of MSCs-Sirt1 is weakened when CXCL10 and IFN-gamma are inhibited. These results show that MSCs-Sirt1 can effectively inhibit prostate cancer growth recruiting NK cells and macrophages in a tumor inflammatory microenvironment.
The aim of this study is to evaluate the effect of the variation of miR-221 on the prostate cancer cells' NE differentiation and invasive function and to examine the function of miR-221 in plasma as a blood-based miRNA biomarker candidate for CaP. The expression of 7 miRNAs in LNCaP, LNCaP-AI, and PC3 prostate cancer cell lines was detected by Northern blotting. LNCaP and LNCaP-AI cells cultured in androgen-depleted medium were transfected with different synthetic miRs. The ability of invasiveness was evaluated by a Matrigel invasion assay. Cell growth was assessed by using the CCK-8 cell proliferation assay at different times. The expression of NSE and DVL2 during the neuroendocrine phenotype and migration were measured by qRT-PCR and Western blot. The level of miR-221 in the prostate cancer samples was measured by qRT-PCR. MiR-221 was significantly increased compared AIPC with ADPC cell lines. Overexpression of miR-221 in LNCaP cells significantly increased the level of NSE expression and induced NE differentiation. Knocking down the level of miR-221 expression with antagonist miR-221 in the LNCaP-AI cell line increased migration and invasion (P < 0.01). DVL2 protein level was up-regulated after transfection of anti-miR-221. MiR-221 was up-regulated in CaP plasma (P < 0.01). We demonstrate a significant difference in miR-221 expression between ADPC and AIPC. MiR-221 may contribute to NE differentiation, which may be the cause for AIPC. We also suggest that miR-221 may control the migration of AIPC cells through DVL2, working as a key regulator in advanced CaP. The role of miR-221 in other target mRNA needs to be further investigated.
Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment.
Background: Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. We aimed to investigate clinical significance of Rab25 in prostate cancer (PCa). Methods: Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were respectively performed to detect Rab25 mRNA and protein expression in PCa and adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve analysis was used to evaluate predictive diagnostic value of Rab25. Associations of Rab25 expression with various clinicopathological characteristics and biochemical recurrence-free survival of PCa patients were statistically evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the cell migration and invasion activities were evaluated by Transwell assay, following the transfection of Rab25 small interfering RNA. Results: Ras-related protein 25 mRNA and protein expression in PCa tissues were both significantly higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with 74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01). PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence-free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression analysis identified Rab25 as an independent biomarker for both overall and biochemical recurrence-free survivals of PCa patients. By exploring its activities in vitro, Rab25 downregulation was found to inhibit PCa cell proliferation, migration and invasion. Conclusions: High expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.
Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of TP53 and MDM2 polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The MDM2 40-bp I/D and TP53 16-bp I/D polymorphism was determined using polymerase chain reaction analysis. The results demonstrated that the MDM2 40-bp I/D polymorphism increased the risk of PCa in a co-dominant inheritance model [odds ratio (OR)=1.88; 95% confidence interval (CI)=1.11-3.19; P=0.023, D/D vs. I/I], while this variant marginally increased the risk of PCa in a dominant model (OR=1.69; 95% CI=1.00-2.83; P=0.051, I/D+D/D vs. I/I). No significant association was observed between the TP53 16-bp I/D polymorphism and PCa. In conclusion, the present study demonstrated that the 40-bp I/D polymorphism in the MDM2 promoter increased the risk of PCa in an Iranian population. Further investigations with diverse ethnicities and larger sample sizes are required to verify these results.
Protein consensus-based surface engineering (ProCoS) is a simple and efficient method for directed protein evolution combining computational analysis and molecular biology tools to engineer protein surfaces. ProCoS is based on the hypothesis that conserved residues originated from a common ancestor and that these residues are crucial for the function of a protein, whereas highly variable regions (situated on the surface of a protein) can be targeted for surface engineering to maximize performance. ProCoS comprises four main steps: (i) identification of conserved and highly variable regions; (ii) protein sequence design by substituting residues in the highly variable regions, and gene synthesis; (iii) in vitro DNA recombination of synthetic genes; and (iv) screening for active variants. ProCoS is a simple method for surface mutagenesis in which multiple sequence alignment is used for selection of surface residues based on a structural model. To demonstrate the technique's utility for directed evolution, the surface of a phytase enzyme from Yersinia mollaretii (Ymphytase) was subjected to ProCoS. Screening just 1050 clones from ProCoS engineering guided mutant libraries yielded an enzyme with 34 amino acid substitutions. The surface-engineered Ymphytase exhibited 3.8-fold higher pH stability (at pH 2.8 for 3 h) and retained 40% of the enzyme's specific activity (400 U/mg) compared with the wild-type Ymphytase. The pH stability might be attributed to a significantly increased (20 percentage points; from 9% to 29%) number of negatively charged amino acids on the surface of the engineered phytase.
Knowledge on protein folding has a profound impact on understanding the heterogeneity and molecular function of proteins, further facilitating drug design. Predicting the 3D structure (fold) of a protein is a key problem in molecular biology. Determination of the fold of a protein mainly relies on molecular experimental methods. With the development of next-generation sequencing techniques, the discovery of new protein sequences has been rapidly increasing. With such a great number of proteins, the use of experimental techniques to determine protein folding is extremely difficult because these techniques are time consuming and expensive. Thus, developing computational prediction methods that can automatically, rapidly, and accurately classify unknown protein sequences into specific fold categories is urgently needed. Computational recognition of protein folds has been a recent research hotspot in bioinformatics and computational biology. Many computational efforts have been made, generating a variety of computational prediction methods. In this review, we conduct a comprehensive survey of recent computational methods, especially machine learning-based methods, for protein fold recognition. This review is anticipated to assist researchers in their pursuit to systematically understand the computational recognition of protein folds.
In biological systems, the formation of molecular complexes is the currency for all cellular processes. Traditionally, functional experimentation was targeted to single molecular players in order to understand its effects in a cell or animal phenotype. In the last few years, we have been experiencing rapid progress in the development of ground-breaking molecular biology tools that affect the metabolic, structural, morphological, and (epi) genetic instructions of cells by chemical, optical (optogenetic) and mechanical inputs. Such precise dissection of cellular processes is not only essential for a better understanding of biological systems, but will also allow us to better diagnose and fix common dysfunctions. Here, we present several of these emerging and innovative techniques by providing the reader with elegant examples on how these tools have been implemented in cells, and, in some cases, organisms, to unravel molecular processes in minute detail. We also discuss their advantages and disadvantages with particular focus on their translation to multicellular organisms for in vivo spatiotemporal regulation. We envision that further developments of these tools will not only help solve the processes of life, but will give rise to novel clinical and industrial applications.
Nowadays, having knowledge about cellular attributes of proteins has an important role in pharmacy, medical science and molecular biology. These attributes are closely correlated with the function and three-dimensional structure of proteins. Knowledge of protein structural class is used by various methods for better understanding the protein functionality and folding patterns. Computational methods and intelligence systems can have an important role in performing structural classification of proteins. Most of protein sequences are saved in databanks as characters and strings and a numerical representation is essential for applying machine learning methods. In this work, a binary representation of protein sequences is introduced based on reduced amino acids alphabets according to surrounding hydrophobicity index. Many important features which are hidden in these long binary sequences can be clearly displayed through their cellular automata images. The extracted features from these images are used to build a classification model by support vector machine. Comparing to previous studies on the several benchmark datasets, the promising classification rates obtained by tenfold cross-validation imply that the current approach can help in revealing some inherent features deeply hidden in protein sequences and improve the quality of predicting protein structural class.
One of the primary goals of applied proteomics is the development of new computational methods for modeling the properties of the proteins from the primary structure. In this work, we used the concept of semi-supervised learning, which is relatively new machine learning philosophy that combines labeled and unlabeled instances simultaneously, to perform classification of protein mutants according to their physical properties. Unlike more traditional methods, it does not demand the specification of the class labels of every sample. This is particularly useful when many exemplars are available but the actual class membership is only available for only a marginal subset. In spite of its desirable properties, semi-supervised learning has been seldom applied in molecular biology. In the recent years, a novel algorithm capable of performing semi-supervised learning has been proposed. This algorithm, namely the TTOSOM, is a tree-based neural network inspired in the well-known Self Organizing Maps. In this paper, we use the TTOSOM to predict the stability of human lysozyme mutants. Since it plays a central role in the immunologic system, prediction of its structural stability is of primary importance for molecular biology. Our experimental results show that it is possible to predict the stability with accuracy above 64%, outperforming two well-known classifiers. This prediction is only based on historical data, i.e., without the necessity of expensive chemical substances and human resources.
Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.
Visualization of chemical concepts can be challenging for many students. This is arguably a critical skill for beginning students of biochemistry to develop, since new information is often presented visually in the form of textbook figures. It is recommended that visual literacy be explicitly taught in the classroom rather than assuming that students will develop this skill on their own. The activity described here is designed to assist students in their development of understanding of basic representations of protein three-dimensional structure as well as various types of ligands (small molecules, ions) through the use of the iPad application PyMOL. It has been used as a laboratory exercise but can also be used in a typical 50-minute class period with a portion of the activity assigned as homework. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
Background: Structural alignment of proteins is one of the most challenging problems in molecular biology. The tertiary structure of a protein strictly correlates with its function and computationally predicted structures are nowadays a main premise for understanding the latter. However, computationally derived 3D models often exhibit deviations from the native structure. A way to confirm a model is a comparison with other structures. The structural alignment of a pair of proteins can be defined with the use of a concept of protein descriptors. The protein descriptors are local substructures of protein molecules, which allow us to divide the original problem into a set of subproblems and, consequently, to propose a more efficient algorithmic solution. In the literature, one can find many applications of the descriptors concept that prove its usefulness for insight into protein 3D structures, but the proposed approaches are presented rather from the biological perspective than from the computational or algorithmic point of view. Efficient algorithms for identification and structural comparison of descriptors can become crucial components of methods for structural quality assessment as well as tertiary structure prediction. Results: In this paper, we propose a new combinatorial model and new polynomial-time algorithms for the structural alignment of descriptors. The model is based on the maximum-size assignment problem, which we define here and prove that it can be solved in polynomial time. We demonstrate suitability of this approach by comparison with an exact backtracking algorithm. Besides a simplification coming from the combinatorial modeling, both on the conceptual and complexity level, we gain with this approach high quality of obtained results, in terms of 3D alignment accuracy and processing efficiency. Conclusions: All the proposed algorithms were developed and integrated in a computationally efficient tool descs-standalone, which allows the user to identify and structurally compare descriptors of biological molecules, such as proteins and RNAs. Both PDB (Protein Data Bank) and mmCIF (macromolecular Crystallographic Information File) formats are supported.
Purpose The aim of the study was to investigate two single nucleotide polymorphisms (SNP) in PTK2 for associations with human muscle strength phenotypes in healthy men. Methods Measurement of maximal isometric voluntary knee extension (MVCKE) torque, net MVCKE torque and vastus lateralis (VL) specific force, using established techniques, was completed on 120 Caucasian men (age = 20.6 +/- 2.3 year; height = 1.79 +/- 0.06 m; mass = 75.0 +/- 10.0 kg; mean +/- SD). All participants provided either a blood (n = 96) or buccal cell sample, from which DNA was isolated and genotyped for the PTK2 rs7843014 A/C and rs7460 A/T SNPs using real-time polymerase chain reaction. Results Genotype frequencies for both SNPs were in Hardy-Weinberg equilibrium (X-2= 0.436). VL specific force was 8.3% higher in rs7843014 AA homozygotes than C-allele carriers (P = 0.017) and 5.4% higher in rs7460 AA homozygotes than T-allele carriers (P = 0.029). No associations between either SNP and net MVCKE torque (P = 0.094) or peak MVCKE torque (P = 0.107) were observed. Conclusions These findings identify a genetic contribution to the inter-individual variability within muscle specific force and provides the first independent replication, in a larger Caucasian cohort, of an association between these PTK2 SNPs and muscle specific force, thus extending our understanding of the influence of genetic variation on the intrinsic strength of muscle.
We hypothesized that impaired proteasomal function affects gene expression in cardiomyocytes. To identify those genes, a proteomics-based analysis of neonatal rat cardiac myocytes treated with the proteasome inhibitor MG132 in comparison to vehicle treated control cells was performed. MG132 treatment induced reproducible changes in the protein expression profile, which was analyzed by two-dimensional difference gel electrophoresis followed by tryptic peptide mass fingerprinting for spot identification by MALDI-TOF mass spectrometry. The identified protein alterations could be grouped into three major categories: (1) induction of small heat shock proteins (HSPs) with chaperonic function, such as HSP27, alpha beta-crystallin, and cardiovascular HSP, (2) altered expression of actin associated proteins, such as cofilin-1 and transgelin, and (3) induction of antioxidant proteins, such as peroxiredoxin-1, superoxide dismutase-1, and hemeoxygenase-1. Northern blotting revealed that expression was regulated at the mRNA level. Given that proteasomal activity is decreased in cardiovascular diseases, alterations in proteasome-dependent control of mRNA expression could provide a novel mechanism by which disease progression is modulated. (c) 2006 Elsevier Inc. All rights reserved.
The article describes in detail methodical procedures for isolation of small RNA molecules, their electrophoresis, northern blotting and finally detection by hybridization with radioactively labeled riboprobes. The presented protocols were successfully introduced and used in our laboratory.
Fuel cell (FC)/lithium-ion battery hybrid power system (HPS) gradually becomes a powerful energy source in the future. This paper presents a digital boost converter for FC current regulation in the HPS with a dual-battery energy storage unit (ESU). The digital boost converter regulates the FC current in order to control the FC power generation. Simulations have been conducted in PSIM environment, and the digital controller is implemented with a Microchip dsPIC33FJ06GS202 16-bit microcontroller. Experimental results show that the efficiency of power conversion can reach to 85%.
For many years, the role of interferon (IFN)-I has been characterized primarily in the context of viral infections. However, regulatory functions mediated by IFN-I have also been described against bacterial infections and in tumor immunology. Only recently, the interest in understanding the immune functions mediated by IFN-I has dramatically increased in the field of protozoan infections. In this review, we discuss the discrete role of IFN-I in the immune response against major protozoan infections: Plasmodium, Leishmania, Trypanosoma, and Toxoplasma.
Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1 beta was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1 beta with the consensus sequence of (126)-LQxxLxxxGL-(135). In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAS and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1 beta-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-alpha production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1 beta and SHFV-nsp1 beta. EAV-nspl was exceptional and did not block the host mRNA nuclear export.
Self-supported single poles are widely used for transmission of electricity in rural areas of India. Recently, in Unnao District of Uttar Pradesh, India, a large number self-supported poles was found to suffer extensive tilting during wind storms. This incident has raised safety concerns for the Government as well as the company in charge of the construction and installation of the poles. These prestressed concrete poles of about 8.5m height were embedded in the ground by 1.5m as per standard practice. From visual inspection of the failure sites and a detailed geotechnical investigation of soil from 24 nearby boreholes, it seemed that the failures caused primarily due to inadequate resistance from the soft soil of Indo-Gangetic plain, resulting bearing and overturning failures. In order to understand further, a test setup was created at the Institute of Technology Kanpur, where the full-scale poles had been brought from Unnao and were erected in a specifically prepared soil pit to match the in-situ soil condition of the Unnao case-study sites. The poles were erected on compacted silty clay soil deposit by adopting standard procedure of back-filling as used in site. The poles were then subjected to lateral loading and unloading through a specially designed frame. The load capacities of the poles have been found to be in the range of 0.95 to 1.48 times the design wind load for the chosen sites. It is noted that by increasing the footing dimension by only 20%, the capacity of the pole is improved by about 54%. Further, it is also found that by replacing a concrete footing by a compacted brick-stone aggregate grouted footing (a common practice in rural India), no significant alteration in the load capacity or force-deformation behavior is observed. A numerical study was also conducted to understand the experimentally observed behavior. It is found from this study that the analytical model considering nonlinear soil pole interaction (Case II) showed better prediction of experimental behavior than the fixed base model (Case I). Finally, a sensitivity analysis using First-Order-Second-Moment (FOSM) method indicated that cohesion influences the load capacity of the poles most significantly compared to other soil parameters such as friction angle, unit weight and shear modulus for the chosen soil type and available soil exploration data. (C) 2017 Elsevier Ltd. All rights reserved.
Worldwide increase in carbapenem resistance and transferable carbapenemases are significant challenges in treatment of Pseudomonas aeruginosa infections. In this study, investigation of carbapenemase production in carbapenem-resistant P. aeruginosa isolates recovered from clinical specimens in a tertiary hospital was aimed. A total of 84 carbapenem-resistant P. aeruginosa isolates were examined. Carbapenem inactivation method (CIM) was used for phenotypic detection of carbapenemase production. The existence of bla(KPC), bla(NDM), bla(IMP), bla(VIM), bla(OXA-48), and bla(GES) genes was investigated by polymerase chain reaction (PCR). Subtypes of the detected genes were identified by sequence analysis. Arbitrarily primed PCR (AP-PCR) was performed to evaluate the clonal relationship among the isolates. The presence of high-risk clones in carbapenemase producers was investigated by Matrix-assisted laser desorption/ionizationtime of flight mass spectrometry (MALDI-TOF MS). Three isolates (3.5%) were identified as carbapenemase producers by CIM tests, while PCR tests demonstrated three isolates carrying carbapenemase genes as well. bla(VIM) gene was found in two isolates and bla(GES) gene was found in one isolate. Sequence analysis demonstrated that the carbapenemases were VIM-1, VIM-2, and GES-5. AP-PCR yielded high clonal diversity among the isolates. According to MALDI-TOF MS analysis, none of the carbapenemase-producing strains belonged to the high-risk clones. In conclusion, the presence of VIM-1, VIM-2, and GES-5 type carbapenemases in P. aeruginosa isolates was demonstrated for the first time in our hospital, GES-5 being reported for the second time in Turkey. Our results will lead strategies for controlling the spread of carbapenemases and contribute to epidemiological data from Turkey.
Pseudomonas putida Bet001 and Delftia tsuruhatensis Bet002, isolated from palm oil mill effluent, accumulated poly(3-hydroxyalkanoates) (PHAs) when grown on aliphatic fatty acids, sugars, and glycerol. The substrates were supplied at 20: 1 C/N mole ratio. Among C-even n-alkanoic acids, myristic acid gave the highest PHA content 26 and 28 wt% in P. putida and D. tsuruhatensis, respectively. Among C-odd n-alkanoic acids, undecanoic gave the highest PHA content at 40 wt% in P. putida and 46 wt% in D. tsuruhatensis on pentadecanoic acid. Sugar and glycerol gave < 10 wt% of PHA content for both bacteria. Interestingly, D. tsuruhatensis accumulated both short- and medium-chain length PHA when supplied with n-alkanoic acids ranging from octanoic to lauric, sucrose, and glycerol with 3-hydroxybutyrate as the major monomer unit. In P. putida, the major hydroxyalkanoates unit was 3-hydroxyoctanoate and 3-hydroxydecanoate when grown on C-even acids. Conversely, 3-hydroxyheptanoate, 3-hydrxoynonanoate, and 3-hydroxyundecanoate were accumulated with C-odd acids. Weight-averaged molecular weight (M-w) was in the range of 53-81 kDa and 107-415 kDa for P. putida and D. tsuruhatensis, respectively. Calorimetric analyses indicated that both bacteria synthesized semicrystalline polymer with good thermal stability with degradation temperature (T-d) ranging from 178 to 282 degrees C. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Strains of Pseudomonas that produce antimicrobial metabolites and control soilborne plant diseases have often been isolated from soils defined as disease-suppressive, i.e., soils, in which specific plant pathogens are present, but plants show no or reduced disease symptoms. Moreover, it is assumed that pseudomonads producing antimicrobial compounds such as 2,4-diacetylphloroglucinol (DAPG) or phenazines (PHZ) contribute to the specific disease resistance of suppressive soils. However, pseudomonads producing antimicrobial metabolites are also present in soils that are conducive to disease. Currently, it is still unknown whether and to which extent the abundance of antimicrobials-producing pseudomonads is related to the general disease resistance of common agricultural soils. Moreover, virtually nothing is known about the conditions under which pseudomonads express antimicrobial genes in agricultural field soils. We present here results of the first side-by-side comparison of 10 representative Swiss agricultural soils with a cereal-oriented cropping history for (i) the resistance against two soilborne pathogens, (ii) the abundance of Pseudomonas bacteria harboring genes involved in the biosynthesis of the antimicrobials DAPG, PHZ, and pyrrolnitrin on roots of wheat, and (iii) the ability to support the expression of these genes on the roots. Our study revealed that the level of soil disease resistance strongly depends on the type of pathogen, e.g., soils that are highly resistant to Gaeumannomyces tritici often are highly susceptible to Pythium ultimum and vice versa. There was no significant correlation between the disease resistance of the soils, the abundance of Pseudomonas bacteria carrying DAPG, PHZ, and pyrrolnitrin biosynthetic genes, and the ability of the soils to support the expression of the antimicrobial genes. Correlation analyses indicated that certain soil factors such as silt, clay, and some macro-and micronutrients influence both the abundance and the expression of the antimicrobial genes. Taken together, the results of this study suggests that pseudomonads producing DAPG, PHZ, or pyrrolnitrin are present and abundant in Swiss agricultural soils and that the soils support the expression of the respective biosynthetic genes in these bacteria to various degrees. The precise role that these pseudomonads play in the general disease resistance of the investigated agricultural soils remains elusive.
Operational amplifier is an important portion of various analog and mixed signal circuits. Today use of mixed mode integrated circuits rises. Analog circuits particularly operational amplifiers in CMOS technology are difficult to design due to challenging and time consuming tasks like counting various conflicting benchmarks and a wide variety of design factors. This paper presents the use of Particle Swarm Optimization (PSO) algorithm for the optimum plan of two stage CMOS operational amplifier circuit. PSO algorithm has been used to accept required functionalities and performance specifications considering ideal sizing of two-stage op-amp. For circuit optimization C code of PSO algorithm has been integrated with Ngspice circuit simulator. The circuit is simulated using BSIM3v3 MOSFET models in TSMC 0.18 mu m and 0.35 um CMOS processes technology. The complete optimization system test setup is run on Ubuntu operating system. Results obtained by PSO algorithm are compared with earlier works.
Health care services show epidemiological changes and an increase in the number of consultations due to mental causes and violence without having the necessary capacity to respond to this increasing demand. Objective. To analyze and compare the demand for hospitalization due to psychosocial causes in a pediatric hospital during three different periods. Materials and methods. Descriptive, retrospective study. The cases were children/adolescents hospitalized for psychosocial causes at Hospital de Ninos de la Santisima Trinidad, Cordoba. The data were processed using frequency analysis and chi-square test. Results. 221 records were analyzed. The hospitalization rate was 0.73% in the year 2000, 1.44% in 2005 and 1.26% in 2010. The hospitalization rate for psychosocial causes increased from 0.06 in 2000 to 0.10 in the years 2005 and 2010. The most common reasons for admission were: suspected child abuse in 44.2% (p < 0.0001), suicidal behavior in 18.7%, suspected sexual abuse in 10.05% and substance abuse in 6.8%. The psychomotor agitation episode and psychotic episode showed a prevalence of 2.4% in 2000, while in 2010 it was of 9.5% for the psychomotor agitation episode and of 5.7% for the psychotic episode. Suicidal behavior and suspected sexual abuse were more common in women and the psychomotor agitation episode and substance abuse were more common in men. Conclusions. Hospitalizations for psychosocial causes and, particularly, mental causes in children/adolescents have increased and show a different behavior according to age and gender. Health problems related to violence were the most frequent ones.
Language provides rich social information about its speakers. For instance, adults and children make inferences about a speaker's social identity, geographic origins, and group membership based on her language and accent. Although infants prefer speakers of familiar languages (Kinzler, Dupoux, & Spelke, 2007), little is known about the developmental origins of humans' sensitivity to language as marker of social identity. We investigated whether 9-month-olds use the language a person speaks as an indicator of that person's likely social relationships. Infants were familiarized with videos of two people who spoke the same or different languages, and then viewed test videos of those two individuals affiliating or disengaging. Results suggest that infants expected two people who spoke the same language to be more likely to affiliate than two people who spoke different languages. Thus, infants view language as a meaningful social marker and use language to make inferences about third-party social relationships.
People perceive that if their memories and moral beliefs changed, they would change. We investigated why individuals respond this way. In Study 1, participants judged that identity would change more after changes to memories and widely shared moral beliefs (e.g., about murder) versus preferences and controversial moral beliefs (e.g., about abortion). The extent to which participants judged that changes would affect their relationships predicted identity change (Study 2) and mediated the relationship between type of moral belief and perceived identity change (Study 3). We discuss the role that social relationships play in judgments of identity and highlight implications for psychology and philosophy.
Background: Identifying neural profiles predictive of future psychopathology in at-risk individuals is important to efficiently direct preventive care. Alterations in reward processing may be a risk factor for depression. The current study characterized neural substrates of reward processing in children at low-and high-risk for psychopathology due to maternal depression status. Methods: Children with (n=27) and without (n=19) maternal depression (ages 5.9-9.6 years) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during fMRI acquisition. Results: Multiple dorsal prefrontal, temporal, and striatal regions showed significant Group (high-vs. lowrisk)xPerformance (hit vs. miss)xCondition (no reward vs. reward) interactions in a whole-brain analysis. All regions exhibited similar patterns, whereby the high-risk group showed blunted activation differences between trials with vs. without rewards when participants hit the target. Moreover, high-risk children showed activation differences between trials with vs. without rewards in the opposite direction, compared to the low-risk group, when they missed the target. Limitations: This study had a modest sample size, though larger than existing studies. Children with maternal depression are at elevated risk for future psychopathology, yet not all experience clinically significant symptoms; longitudinal research is necessary to fully track the pathway from risk to disorder. Conclusion: Children of depressed mothers exhibited attenuated neural activation differences and activation patterns opposite to children without depressed mothers. Our findings may provide targets for hypothesis driven preventive interventions and lead to earlier identification of individuals at risk.
Individuals with psychopathy are often characterized by emotional processing deficits, and recent research has examined the specific contexts and cognitive mechanisms that underlie these abnormalities. Some evidence suggests that abnormal features of attention are fundamental to emotional deficits in persons with psychopathy, but few studies have demonstrated the neural underpinnings responsible for such effects. Here, we use functional neuroimaging to examine attention-emotion interactions among incarcerated individuals (n = 120) evaluated for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R). Using a task designed to manipulate attention to emotional features of visual stimuli, we demonstrate effects representing implicit emotional processing, explicit emotional processing, attention-facilitated emotional processing, and vigilance for emotional content. Results confirm the importance of considering mechanisms of attention when evaluating emotional processing differences related to psychopathic traits. The affective-interpersonal features of psychopathy (PCL-R Factor 1) were associated with relatively lower emotion-dependent augmentation of activity in visual processing areas during implicit emotional processing, while antisocial-lifestyle features (PCL-R Factor 2) were associated with elevated activity in the amygdala and related salience network regions. During explicit emotional processing, psychopathic traits were associated with upregulation in the medial prefrontal cortex, insula, and superior frontal regions. Isolating the impact of explicit attention to emotional content, only Factor 1 was related to upregulation of activity in the visual processing stream, which was accompanied by increased activity in the angular gyrus. These effects highlight some important mechanisms underlying abnormal features of attention and emotional processing that accompany psychopathic traits.
Experiencing self-agency over one's own action outcomes is essential for social functioning. Recent research revealed that patients with schizophrenia do not use implicitly available information about their action-outcomes (i.e., prime-based agency inference) to arrive at self-agency experiences. Here, we examined whether this is related to symptoms and/or familial risk to develop the disease. Fifty-four patients, 54 controls, and 19 unaffected (and unrelated) siblings performed an agency inference task, in which experienced agency was measured over action outcomes that matched or mismatched outcome-primes that were presented before action performance. The Positive and Negative Syndrome Scale (PANSS) and Comprehensive Assessment of Symptoms and History (CASH) were administered to assess psychopathology. Impairments in prime-based inferences did not differ between patients with symptoms of over- and underattribution. However, patients with agency underattribution symptoms reported significantly lower overall self-agency experiences. Siblings displayed stronger prime-based agency inferences than patients, but weaker prime-based inferences than healthy controls. However, these differences were not statistically significant. Findings suggest that impairments in prime-based agency inferences may be a trait characteristic of schizophrenia. Moreover, this study may stimulate further research on the familial basis and the clinical relevance of impairments in implicit agency inferences.
Psychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for CSA and IPV. We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. Three hundred and eighty-three persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (Adjusted Odds Ratio=2.24, 95% CI, 1.04-4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.
Agreement between client and therapist is an essential part of the therapeutic alliance. While there are general challenges to the creation of agreement and shared meaning in all psychotherapies, there are specific challenges while working with persons with psychosis. These challenges include the different narratives of the client and the therapist with regard to their roles and the description of the condition or problem, as well as possible stigmatic views and theoretical bias. Here we present a metacognitive intersubjective model as a framework for the understanding and resolutions of these challenges. Copyright (c) 2016 John Wiley & Sons, Ltd.
Evidence-based treatment and manualized psychotherapy have a recent but rich history. As interest and research have progressed, defining the role of treatment manuals in resident training and clinical practice has become more important. Although there is not a universal definition of treatment manual, most clinicians and researchers agree that treatment manuals are an essential piece of evidence-based therapy, and that despite several limitations, they offer advantages in training residents in psychotherapy. Requirements for resident training in psychotherapy have changed over the years, and treatment manuals offer a simple and straightforward way to meet training requirements. In a search limited to only depression, two treatment manuals emerged with the support of research regarding both clinical practice and resident training. In looking toward the future, it will be important for clinicians to remain updated on further advances in evidence based manualized treatment as a tool for training residents in psychotherapy, including recent developments in online and smartphone based treatments.
Psychotic disorders are some of the most severe psychiatric conditions. Patients have difficulties in identifying facial expressions and appear to be highly sensitive to the presence of emotional distractors. Yet, no study has investigated whether perceptual load modulates the interference of emotional distractors. Our goal was to test whether psychotic patients were more sensitive to irrelevant emotional stimulus, even when the task demands a high amount of attentional resources. Twenty-two participants with schizophrenia or schizoaffective disorder and twenty-two healthy controls, performed a target letter discrimination task with emotional task-irrelevant stimulus (angry, happy and neutral facial expressions). Target-letters were presented among distrator-letters, which could be similar (low perceptual load) or different (high load); participants should discriminate the target-letter and ignore the facial expression. Results showed that patients were more prone to distraction by task-irrelevant stimulus, especially under high load, suggesting difficulties in attention control. Moreover, in psychotic patients, happy faces caused higher interference with the task, whereas neutral and angry faces resulted in less interference. These findings could provide innovative approaches regarding attentional deficits on social contexts in patients with schizophrenia spectrum disorders.
We have observed a quench of lasing at an exceptional point in an electronic circuit system by applying an asymmetric gain in coupled oscillators. Because of the analogy between an oscillation in a laser and an oscillation in an operational amplifier, the oscillation stops when the system hits an exceptional point. This phenomenon is also theoretically investigated.
The objectives of the present study were to identify the relationship between coping style and PTG among survivors 8 years after the Wenchuan earthquake, using data from a cross-sectional survey. 1369 participants were recruited from two different sites in the areas that were severely affected by the earthquake. Bivariate correlation analysis and multivariate linear regression analysis were used to assess PTG and identify associated factors. The results indicated that both positive and negative coping style can develop to PTG among adult survivors 8 years later after Wenchuan earthquake. Positive coping style had a higher correlation with "new possibilities" (beta = 0.19, p < 0.001), "personal strength" (beta = 030, p < 0.001) "appreciation of life" (beta = 0.11, p < 0.001) than negative coping style, while negative coping style had a higher correlation with "relating to others" (beta = 0.25, p < 0.001) than positive coping style. In addition, the study found PTSD and PTG co-exist after the earthquake, while depression was a barrier factor during the process of developing PTG. (C) 2017 Elsevier Ltd. All rights reserved.
Expression of the novel protein tyrosine phosphatase interacting protein 51 (PTPIP51) was investigated on mRNA and protein level in the liver of adult Wistar rats. The presence of PTPIP51 mRNA was detected by Northern blotting. Immunostaining showed expression of PTPIP51 protein in distinct non-parenchymal cells. These cells were identified as Kupffer cells, stellate cells and natural killer cells by detection of cell-specific antigens. Whereas most endothelial cells lining large vessels reacted positive to the PTPIP51 antibody, sinusoidal endothelium showed no detectable amount of PTPIP51. Furthermore, PTPIP51 was also found to be expressed in cells forming the biliary tree. An additional subcellular analysis of the non-parenchymal cells by means of electron microscopy showed the presence of PTPIP51 protein in the cytoplasm and in the nuclei of non-parenchymal cells. Most of the hepatocytes did not show any immuno-detectable amount of PTPIP51, yet, some revealed PTPIP51 protein either in the cytoplasm or in the nucleus.
Considerable research has examined the association between posttraumatic stress disorder (PTSD) symptoms and social support. One facet of this relationship that deserves greater attention concerns trauma survivors' negative expectations towards social support, termed negative network orientation. To expand our understanding of negative network orientation, the current study examined shame as a possible mediator in the relationship between PTSD symptoms and negative network orientation, in a sample of 202 female survivors of intimate partner violence (IPV). Additionally, a history of child abuse (CA) was evaluated as a moderator of the association between shame and negative network orientation in this model. Path analyses indicated a significant indirect effect between PTSD symptoms and negative network orientation through shame, indicative of mediation. A history of CA moderated this effect, such that women with a history of CA in addition to IPV showed a significantly stronger relationship between PTSD symptoms and negative network orientation through shame, relative to women who only had a history of IPV. These findings support the relevance of shame in understanding the association between PTSD symptoms and negative beliefs about social support and highlight the role of childhood abuse as a moderator in this process among IPV survivors. (C) 2017 Elsevier Ltd. All rights reserved.
Combat-related posttraumatic stress disorder (PTSD) is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here, we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused) using a novel group therapy [mindfulness-based exposure therapy (MBET)] in Afghanistan (OFF) or Iraq (OIF) combat veterans with PTSD. OFF/OIF combat veterans with PTSD (N = 23) were treated with MBET (N = 14) or a comparison group therapy [Present-centered group therapy (PCGT), N = 9]. PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale. Functional neuroimaging (3-1 fMRI) before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces). Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.43). Improvement in PTSD symptoms from pre- to post-treatment in both treatment groups was correlated with increased activity in rostral anterior cingulate cortex, dorsal medial prefrontal cortex (mPFC), and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left mPFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social emotional threat related to symptom reduction.
Background: Little is known about trajectories of PTSD symptoms across the peripartum period in women with trauma histories, specifically those who met lifetime PTSD diagnoses prior to pregnancy. The present study seeks to identify factors that influence PTSD symptom load across pregnancy and early postpartum, and study its impact on postpartum adaptation. Method: The current study is a secondary analysis on pregnant women with a Lifetime PTSD diagnosis (N = 319) derived from a larger community sample who were interviewed twice across pregnancy (28 and 35 weeks) and again at 6 weeks postpartum, assessing socioeconomic risks, mental health, past and ongoing trauma exposure, and adaptation to postpartum. Results: Using trajectory analysis, first we examined the natural course of PTSD symptoms based on patterns across peripartum, and found four distinct trajectory groups. Second, we explored factors (demographic, historical, and gestational) that shape the PTSD symptom trajectories, and examined the impact of trajectory membership on maternal postpartum adaptation. We found that child abuse history, demographic risk, and lifetime PTSD symptom count increased pregnancy-onset PTSD risk, whereas gestational PTSD symptom trajectory was best predicted by interim trauma and labor anxiety. Women with the greatest PTSD symptom rise during pregnancy were most likely to suffer postpartum depression and reported greatest bonding impairment with their infants at 6 weeks postpartum. Conclusions: Screening for modifiable risks (interpersonal trauma exposure and labor anxiety) and /or PTSD symptom load during pregnancy appears critical to promote maternal wellbeing. (C) 2016 Wiley Periodicals,
Background: Trauma is commonly associated with substance-related problems, yet associations between specific substances and specific posttraumatic stress disorder symptoms (PTSSs) are understudied. We hypothesized that substance-related problems are associated with PTSS severities, interpersonal traumas, and benzodiazepine prescriptions. Methods: Using a cross-sectional survey methodology in a consecutive sample of adult outpatients with trauma histories (n = 472), we used logistic regression to examine substance-related problems in general (primary, confirmatory analysis), as well as alcohol, tobacco, and illicit drug problems specifically (secondary, exploratory analyses) in relation to demographics, trauma type, PTSSs, and benzodiazepine prescriptions. Results: After adjusting for multiple testing, several factors were significantly associated with substance-related problems, particularly benzodiazepines (AOR = 2.78; 1.99 for alcohol, 2.42 for tobacco, 8.02 for illicit drugs), DSM-5 PTSD diagnosis (AOR = 1.92; 2.38 for alcohol, 2.00 for tobacco, 2.14 for illicit drugs), most PTSSs (especially negative beliefs, recklessness, and avoidance), and interpersonal traumas (e.g., assaults and child abuse). Conclusion: In this clinical sample, there were consistent and strong associations between several trauma-related variables and substance-related problems, consistent with our hypotheses. We discuss possible explanations and implications of these findings, which we hope will stimulate further research, and improve screening and treatment.
Compared with chronological age, criminologists have paid less attention to the biological sense of age typically expressed by pubertal development. Studies that have examined pubertal timing's effects on delinquency have almost exclusively been conducted in Western countries using mostly White samples. To our knowledge, no study has ever examined this issue in the Asian context. The current study is the first attempt to bridge this research gap by examining the association among menarcheal timing, the sex composition of schools, and delinquency in a representative sample of 1,108 ninth-grade girls in South Korea. The results show that significant association between early menarche and delinquency exists only in mixed-sex schools but not in all-girls schools. In addition, the significant linkage between early menarche and delinquency in mixed-sex schools is mediated by delinquent peer associations.
Mastitis is defined as the inflammation of the mammary gland. There is generally no effective treatment for mastitis in animals. Puerarin, extracted from Radix puerariae, has been proven to possess many biological activities. The present study aims to reveal the potential mechanism that is responsible for the antiinflammatory action of puerarin in Staphylococcus aureus (S. aureus)-induced mastitis in mice. Histopathological changes showed that puerarin ameliorated the inflammatory injury induced by S. aureus. Quantitative real-time polymerase chain reaction and ELISA analysis indicated that puerarin not only suppressed the production of pro-inflammatory cytokines such as TNF-, IL-1, and IL-6 but also promoted the secretion of IL-10. Toll-like receptor 2 (TLR2) is important in the immune defense against S. aureus infection. Research in molecular biology has shown that the expression of TLR2 was inhibited with administration of puerarin. Further studies were performed on NF-kB and mitogen-activated protein kinase signaling pathways using western blot. The results demonstrated that puerarin suppressed phosphorylated IkB, p65, p38, extracellular signal-regulated kinase 1and 2 (ERK), and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. All of the results suggested that puerarin may be a potential therapy for treating mastitis. Copyright (c) 2016 John Wiley & Sons, Ltd.
Background: Exercise training positively influences exercise tolerance and functional capacity of patients with idiopathic pulmonary arterial hypertension (IPAH). However, the underlying mechanisms are unclear. We hypothesized that exercise modulates the activated inflammatory state found in IPAH patients. Methods: Single cardiopulmonary exercise testing was performed in 16 IPAH patients and 10 healthy subjects. Phenotypic characterization of peripheral blood mononuclear cells and circulating cytokines were assessed before, directly after and 1 h after exercise. Results: Before exercise testing, IPAH patients showed elevated Th2 lymphocytes, regulatory T lymphocytes, IL-6, and TNF-alpha, whilst Th1/Th17 lymphocytes and IL-4 were reduced. In IPAH patients but not in healthy subject, exercise caused an immediate relative decrease of Th17 lymphocytes and a sustained reduction of IL-1-beta and IL6. The higher the decrease of IL-6 the higher was the peak oxygen consumption of IPAH patients. Conclusions: Exercise seems to be safe from an immune and inflammatory point of view in IPAH patients. Our results demonstrate that exercise does not aggravate the inflammatory state and seems to elicit an immunemodulating effect in IPAH patients.
In this paper, a new pulse width modulation (PWM) converter is proposed. This structure converts the analog input signal to a PWM waveform using only inverters/charge-pumps in combination with passive elements. Thus, the proposed PWM converter does not need any operational amplifier. The added feedback path current can be used to adjust the required duty-cycle of the PWM conversion based on the dynamic range of the input signal. The behavior of the proposed PWM converter is formulated and simulated in a 0.13 mu m CMOS technology. From the simulation results, the proposed PWM converter achieves 74dB linearity and draws only 1.0mA at 500MHz from 1.0V supply in a 0.13 mu m process.
The pumped storage power station (PSPS) is a special power source that has flexible operation modes and multiple functions. With the rapid economic development in China, the energy demand and the peak-valley load difference of the power grid are continuing to increase. Moreover, wind power, nuclear power, and other new energy sources also develop very fast. Developing the PSPS is of great importance to the power source structure adjustment, and the secure and stable operation of the power grids in China in the 21st century. This paper provides a survey of the PSPS development in China. Over the last two decades, China's PSPS has developed quickly. The PSPS installed capacity had reached 21.83 gigawatts (GW) by the end of 2014, ranking among the top in the world. 27 PSPSs have been completed and put into production, and many with the installed capacity of more than 1200 megawatts (MW) are still under construction, including Fengning PSPS. In addition, a lot of sites suitable for the PSPS construction have been planned. With regard to the challenges existing in the exploitation course, some suggestions are proposed. There is a bright future for the PSPS development in China.
Putamen volume is seen to alter in neurological and psychiatric disorders like Parkinson's disease, depression, schizophrenia, Alzheimer's disease, and in individuals treated with antipsychotics. To establish a trend in volume changes in pathologic states, studies on factors influencing normal variation in a given population become essential. This study aimed to evaluate the normal variations in putamen volume in the Indian population and correlate them with the effects of age and sex. Bilateral symmetry was also evaluated. The study included MR images of 98 individuals aged 10-87 years. Axial sections of T2-weighted spin echo sequences were used to estimate putamen volume. The putamen was delineated manually and its volume was estimated using Cavalieri's principle. Linear regression and paired t-test were used to analyze data. Bilateral putamen volume reduced with age in both sexes. This was statistically significant (P0.05). Age and sex interaction was not found to be statistically significant. Hemispherical asymmetry was not established as the difference between the right and left putamen volume did not reach statistical significance in both males and females (P>0.05). In conclusion, this study demonstrated an age related decline in the volumes of both putamen in males and females. The rate of volume reduction was not affected by sex. The study failed to establish a significant sex difference and hemispherical asymmetry in putamen volume. Clin. Anat. 30:461-466, 2017. (c) 2017 Wiley Periodicals, Inc.
Building-integrated photovoltaic (BIPV) Trombe wall system can provide heating/cooling and generate electricity simultaneously. Precedent studies on the BIPV Trombe wall system were focused on two major types, one with PV cells attached to glass (BIPVGTW) and the other with that attached to mass wall (BIPVMTW), characterized by low thermal (BIPVGTW) and electric efficiency (BIPVMTW). This study presents a PV blind-integrated Trombe wall system (BIPVBTW). Adopting developed models on the BIPVBTW, the optimum PV blind slat angles over three seasons (summer, winter and mid-term seasons) and time of day (9:00-17:00) are investigated. Comparative assessment of the three BIPV Trombe wall systems are conducted all year round under Hefei weather conditions, in terms of thermal and electrical performance. The results have illustrated that annual electricity output of BIPVBTW system is similar to that of BIPVGTW system, which is 1.2 times that of the BIPVMTW system. The BIPVGTW system is superior to the BIPVBTW/BIPVMTW systems in cooling load reduction, while using PVBTW/PVMTW heating load is decreased significantly compared to using the PVGTW. Combining electricity generation and cooling/heating load reduction, the total electricity saving of BIPVBTW system is over 45% higher compared to BIPVGTW/BIPVMTW systems. CO2 emissions reduction of the BIPVBTW system are about 1.5 times that of BIPVGTW/BIPVMTW systems. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a photovoltaic (PV) system with a maximum power point tracking (MPPT) facility. The goal of this work is to maximize power extraction from the photovoltaic generator (PVG). This goal is achieved using a sliding mode controller (SMC) that drives a boost converter connected between the PVG and the load. The system is modeled and tested under MATLAB/SIMULINK environment. In simulation, the sliding mode controller offers fast and accurate convergence to the maximum power operating point that outperforms the well-known perturbation and observation method (P&O). The sliding mode controller performance is evaluated during steady-state, against load varying and panel partial shadow (PS) disturbances. To confirm the above conclusion, a practical implementation of the maximum power point tracker based sliding mode controller on a hardware setup is performed on a dSPACE real time digital control platform. The data acquisition and the control system are conducted all around dSPACE 1104 controller board and its RTI environment. The experimental results demonstrate the validity of the proposed control scheme over a stand-alone real photovoltaic system. (C) 2016 Elsevier Ltd. All rights reserved.
The plasmacytoma variant translocation 1 gene (PVT1) is a large non-coding locus at adjacent of c-Myc, and long non-coding RNA PVT1 is now recognized as a cancerous gene co-amplified with c-Myc in various cancers. But the expression and functional role of PVT1 in colorectal cancer are still unelucidated. In addition, all the reported long non-coding RNAs so far are discovered in either cells or tissues, but no research about long non-coding RNAs detection in extracellular vesicles has been reported yet. In the present study, we firstly investigated the expression of PVT1 in colorectal cancer specimens and its correlation with the expression of c-Myc and other related genes by real-time polymerase chain reaction. Then, we isolated the extracellular vesicles from colorectal cancer cells culturing medium by differential centrifugation and detected the PVT1 expression in extracellular vesicles by using real-time polymerase chain reaction. The PVT1 targeting siRNA was transfected into SW480 and SW620 cells, and 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and flow cytometry were used to evaluate the cell proliferation and apoptosis. The results showed that the PVT1 expression in tumor tissues was higher than that in normal tissues, which was significantly correlated with the expression of c-Myc and three c-Myc regulating genes FUBP1, EZH2, and NPM1 and also correlated with the expression of two other PVT1-associated transcript factors nuclear factor-kappa B and myocyte-specific enhancer factor 2A. Here, we reported for the first time that PVT1 as a long non-coding RNA was successfully detected in extracellular vesicles excluded from SW620 and SW480 cells, and the expression level of PVT1 was higher in extracellular vesicles from the more aggressive cell SW620 than from SW480. The results also showed that by down-regulating the PVT1 expression, the c-Myc expression was suppressed, the cell proliferation was inhibited, and cell apoptosis was increased. Taken together, these findings implicated that PVT1 may be a new oncogene co-amplified with c-Myc in colorectal cancer tissues and extracellular vesicles and functionally correlated with the proliferation and apoptosis of colorectal cancer cells.
For a fully digital control of PWM converters, considerable research has been done based on the predictive current control (PCC) scheme. However, it requires a large amount of calculation in the step of experimental implementation. Besides, when compared with the classical linear control scheme, the sampling interval of the PCC scheme must be shorter to obtain the same control performance for current. Due to this, a digital signal processor with excellent performance is required. This paper proposes an improved simplified model PCC scheme for three-phase PWM converters. The main objective is to simplify the PCC scheme. Also, the proposed control scheme is able to reduce the calculation time without affecting the performance. Simulations and experiments are carried out to investigate the presented novel predictive current control scheme. The results indicate that the three-phase PWM converter has excellent static and dynamic performance with the proposed scheme. Besides, the calculation time can be obviously shortened.
Transgene silencing is a common phenomenon in higher plants and microalgae. In the present study, we analyzed transgene silencing in the macroalga Pyropia yezoensis. This is the first report of transgene silencing in macroalgae. Transgenic lines were generated by transformation with the PyGUS gene and a hygromycin resistance gene (PtAph7-1). Histochemical GUS staining detected PyGUS expression in only three out of 12 lines. Southern and northern blotting, polymerase chain reaction (PCR), and reverse transcription (RT)-PCR analyses indicated that the PyGUS gene was silenced in the other 9 lines. Interestingly, PyGUS gene silencing in transgenic line 7 was repeatedly initiated at a later stage, in the developmental process from monospore to thallus through asexual reproduction. We identified genes encoding Argonaute and Dicer-like protein, the major components of the RNA-silencing pathway, in the genome and transcripts of P. yezoensis. Interestingly, we found the DDA motif in the PIWI domain of the AGO, suggesting that translational repression may be the major gene-silencing pathway in P. yezoensis. In this study, the observation of PyGUS gene silencing and identification of RNA-silencing components indicate that the gene ( transgene) silencing machinery functions actively in the macroalga P. yezoensis. These results will be useful to study the regulation of gene expression and RNA-silencing mechanisms in Pyropia species and related macroalgae.
Obesity and diabetes are metabolic diseases and they are increasing in prevalence. The dynamics of gene expression associated with these diseases is fundamental to identifying genes involved in related biological processes. qPCR is a sensitive technique for mRNA quantification and the most commonly used method in gene-expression studies. However, the reliability of these results is directly influenced by data normalization. As reference genes are the major normalization method used, this work aims to identify reference genes for qPCR in adipose tissues of mice with type-I diabetes or obesity. We selected 12 genes that are commonly used as reference genes. The expression of these genes in the adipose tissues of mice was analyzed in the context of three different experimental protocols: 1) untreated animals; 2) high-fat-diet animals; and 3) streptozotocin-treated animals. Gene-expression stability was analyzed using four different algorithms. Our data indicate that TATA-binding protein is stably expressed across adipose tissues in control animals. This gene was also a useful reference when the brown adipose tissues of control and obese mice were analyzed. The mitochondrial ATP synthase F1 complex gene exhibits stable expression in subcutaneous and perigonadal adipose tissue from control and obese mice. Moreover, this gene is the best reference for qPCR normalization in adipose tissue from streptozotocin-treated animals. These results show that there is no perfect stable gene suited for use under all experimental conditions. In conclusion, the selection of appropriate genes is a prerequisite to ensure qPCR reliability and must be performed separately for different experimental protocols. (C) 2017 Elsevier Masson SAS. All rights reserved.
From an evidentiary point of view, the project Ross Cheit seeks to accomplish in his book, The Witch-Hunt Narrative: Politics, Psychology, and the Sexual Abuse of Children, is remarkably complex. I examine the methodology that underlies Cheit's scholarship to assess the strength of his claims. Cheit's work has a strong methodological core in which he asserts the existence of a "Witch-Hunt Narrative" (WHN), public perception that there are "hundreds" of legal cases involving innocent adults wrongly criminally pursued for child sexual abuse. He identifies three foundational cases in this WHN, McMartin, Michaels, and Fuster, along with dozens of others, which he distills from published lists. Using broadly collected archival and other data, Cheit investigates the veracity of this WHN. He concludes there is insufficient evidence to substantiate the witch-hunt claim. Methodologically, Cheit's research veers into more problematic territory when he seeks to extend his WHN claims beyond this central core and extend it to the academy, particularly the research of several prominent academics, including psychologists Stephen J. Ceci and Maggie Bruck. I examine these claims and argue Cheit has not paid sufficient attention to the methods and methodology upon which he bases his claims. I conclude by noting the complexity of evaluating evidence produced and utilized in, and across, disciplinary boundaries, including journalism, law, and the academy. Nonetheless, Cheit's scholarship raises a plethora of important questions and possibilities for future research.
Renewed attention is being paid to the quality of qualitative research in studies of development impact in the wake of intense debate over the role of randomised control trials. These debates raised the bar over quality while also provoking concerns about whose voices matter and the politics of evidence-based policymaking. This article argues that both of these issues can be addressed through Guba and Lincoln's trustworthiness criteria, and particularly the principle of authenticity which was developed to respond to demands for research to be transformative and emancipatory. Adopting these criteria in commissioned evaluations as checklist, artefacts' are a means to improve rigour and raise ethical standards.
Based on time-domain quality factor ( Q-factor) measurement principle, we have proposed an architecture which has the potential to be integrated on-chip. Thanks to the proposed original reconfigurable structure, the main measurement error from the offset of the operational trans conductance amplifier (OTA) used can be cancelled automatically during the measurement operation, leading to a high accuracy Q-factor measurement. The digital control circuit plays an important role in the automatic passage between the two configurations designed, i.e., peak detector and comparator. The main advantages of the proposed time-domain Q-factor measurement lay on the possibility of being integrated next to the Micro Electro Mechanical System (MEMS) resonator to be measured, the miniaturization of the whole measuring system as well as the enhancement of the measurement performance, and to guide the design of such architecture, a theoretical analysis linking the required accuracy and the given Q-factor to the circuit parameters have been given in this paper. The proposed circuit is designed and simulated in a 0.35 pm Complementary Metal Oxide Semiconductors (CMOS) technology. The post-layout simulation results show that the operating frequency can reach up to 200 kHz with an accuracy of 0.4%.
Objectives: The brief version of the World Health Organization's Quality of Life Instrument (WHOQOL-BREF) is widely used for evaluating the personal subjective quality of life (QOL) of patients and particular populations. However, in the absence of sufficient studies among the general population, normative data for WHOQOL-BREF remain scarce. To fill this gap, the present study explored more sociodemographic and health-related factors affecting the QOL. Study design: In total, 11,351 participants aged >= 35 years in rural areas of Liaoning Province were screened with a stratified cluster multistage sampling scheme in 2012-2013. Anthropometric measurements, laboratory examinations, and self-reported information on disease history were collected by trained personnel. Depression symptoms were assessed using the Patient Health Questionnaire-9. Methods: Stepwise multiple linear regression was used to explore the association between multiple factors and QOL. Results: Females and single/widowed subjects had lower QOL scores than males and married/cohabiting subjects, respectively. Total QOL scores and scores for each domain decreased as age increased, but a positive correlation was found between age and the environmental domain score. Participants with higher annual incomes, education levels, and activity levels had higher QOL scores. In the regression model, the coefficient for stroke was -2.17 (95% confidence interval [CI] -2.64, -1.71) for the total QOL score. For a one-level increase in depression level, the total QOL score decreased by 5.62 (95% CI -5.83 to -5.42), physical domain score decreased by 1.63 (95% CI -1.69 to -1.58), and psychological domain score decreased by 1.81 (95% CI -1.87 to -1.75). Conclusions: Socio-economic status including marital status is highly related to QOL. Regarding chronic diseases, stroke is an important factor of QOL and depressive symptoms have a strong negative relationship with QOL. (C) 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Increasing evidence suggests that human cytomegalovirus (HCMV) is associated with many human malignancies. However, its prevalence in gastric cancer (GC) and clinical association remain unknown. HCMV IgG and IgM antibodies in the sera of 80 GC patients and 80 healthy controls were detected using a microparticle enzyme immunoassay. The prevalence of HCMV UL47, UL55, UL56, and UL77 genes among 102 GC tumor tissues and adjacent normal specimens was measured by polymerase chain reaction (PCR) or nested PCR. Quantitative real-time PCR (Q-PCR) was used to determine viral load. Virus localization in neoplastic tissues was determined by immunohistochemistry. No significant difference of HCMV IgG and IgM seropositivity was found between GC patients and the healthy group. However, the overall HCMV DNA positivity rate was significantly higher in GC cancerous tissue compared with in paired normal tissue (P < 0.01). HCMV infection was mainly localized in the tumorous epithelium. Q-PCR in HCMV-positive specimens indicated that the viral copy number was notably higher in GC tissues than in adjacent normal specimens (P < 0.001). Clinical statistical analysis indicated that HCMV load in GC tumor tissue was positively associated with lymphatic metastasis (P = 0.043), the area under the receiver operating characteristic (ROC) curve was 0.6638. Our data clearly provide the prevalence of HCMV in GC patients. We conclude that HCMV infection in malignant tissues might be associated with carcinogenesis or progression of GC and possibly relates to lymphatic metastasis. (C) 2017 Elsevier Inc. All rights reserved.
The glutamate transporter 1 (GLT1) in rodents, or EAAT2 in humans, is alternatively spliced in a complex manner including the use of multiple 5' and 3' untranslated regions and several coding variants. We used quantitative RT-PCR to profile these splice variants in human and rat brain. We also used RT-PCR and Northern blotting to demonstrate that a novel isoform of GLT1b has an similar to 11 kb 3' UTR extending through intron 9, exon 10 and approximately 5 kb into the 3' untranslated region of GLT1. However, our most important finding concerns an aberrant transcript lacking exon 9, which contains a motif permitting translocation from the endoplasmic reticulum. This variant had previously been associated with amyotrophic lateral sclerosis until several groups reported high levels in normal brain tissue. In contrast, our data shows that this aberrant transcript is present at 0.1-0.2% of the major EAAT2 isoforms. (c) 2006 Elsevier Ltd. All rights reserved.
A novel carbon monoxide (CO) sensor is fabricated based on quartz crystal microbalance (QCM) using commercial piezoelectric crystal, modified with single-walled carbon nanotubes (SWCNTs) through spin-coating technique. For this purpose, a 10.00 +/- 0.03-V alternative-current (AC) potential with frequency of 4.62 +/- 0.02 MHz as an optimum surface acoustic wave (SAW) is applied to the piezoelectric crystal (SAW device). To follow the linear correlation between mass difference and frequency gradient, a frequency-to-voltage converter is adopted using an integrated circuit. Output potential is then filtered by electrical high-pass filter, followed by 10 fold samplification using an operational amplifier and finally connection to a PC through a voltmeter. According to figures of merit, fabricated sensor is linear from 35 to 280 parts per million (ppm). Detection limit is also similar to 5.3 ppm. Relative standard deviation for six replicate analyses is 3.04%. Based on 90% of maximum response (t(90)), response time is 5.0 s. Recovery time is also evaluated to similar to 30 s at 1.0 atmosphere pressure. Calibration sensitivity is measured to 0.057 mV/ppm. No significant interference is observed, when introducing at least 500 folds of various foreign species in air as diluents. Reliability of the sensor is finally evaluated via determination of the CO in two samples.
An intelligent electrical circuit for controlling the operation of quartz metal halide discharge (QMH) lamps is proposed. The lamp can be operated steadily at high-frequency by integrating the microcontroller ATmega128. With the application of pattern recognition, the control system enables the lamp to be turned on and off automatically according to the environment condition and maintain high-performance constant power. The results show that the efficiency of the driving circuit can approach 94.3%. The proposed model will provide opportunities to design reliable and cost-effective QMH lamps.
We revisit the shift technique applied to Quasi-Birth and Death (QBD) processes He et al. (2001) [13] in functional form by bringing the attention to the existence and properties of canonical factorizations. To this regard, we prove new results concerning the solutions of the quadratic matrix equations associated with the QBD. These results find applications to the solution of the Poisson equation for QBDs. (c) 2016 IMACS. Published by Elsevier B.V. All rights reserved.
Queer theories of anti-futurity are maddened and cripped by reinserting disability, trauma, and child abuse into analysis of queer time. The queer temporalities of the traumatized mind, including dissociation, amnesia, hypervigilance, and ongoing disorientation in time, are explored. Resisting the imperative of a cure, the queer time traveling of trauma is positioned as a means of queer and mad world-making, and as a commitment to justice.
Introduction: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.
Quinclorac is an effective herbicide, but its residue is known to be a major environmental pollutant. Therefore, isolating quinclorac-degrading bacteria, exploring the mechanisms of degradation and analyzing the proteins introduced by the pollutant, would have scientific value and practical importance. We used quinclorac-degrading bacteria WZ1 (an opportunistic pathogen with broad substrate characteristic) as the test strain, and used several techniques such as two-dimensional electrophoresis, gas chromatography-mass spectrometry and Northern Blotting to study the stress response of the strain upon environmental stress and the biodegradation of quinclorac. The results showed that strain WZ1 secreted some protective proteins such as Mn-SOD, Heat-shock protein and Taurine dioxygenase to deal with the stress of quinclorac: while the expression of proteins DsbA and Gmet_1484 related to bacterial pathogenesis decreased significantly when exposed to quinclorac (which could be used to indicate that bacterial pathogenicity was attenuated). At the same time, quinclorac also induced the expression of phthalate dioxygenase reductase and chlorocatechol 1, 2-dioxygenase. They are the key proteins participating in the degradation of quinclorac, which was proved by the Northern Blotting. With the information gathered, we attempted to define the degradation pathway of quinclorac. (C) 2008 Elsevier Ltd. All rights reserved.
Antoregulation of genes is often associated with quorum sensing systems where bacteria produce and secrete molecules allow the cells to communicate with one another, leading to the activation of certain genes at certain population densities Here we describe the identification of the agr as a quorum sensing system in Staphylococcus aureus and the isolation of agr autoinducers and inhibitors by northern blotting, real time RI PCR, and beta lactamase reporter cells assays
Breakthroughs in genetics and molecular biology in the 1970s and 1980s were heralded as a major technological revolution in medicine that would yield a wave of new drug discoveries. However, some forty years later the expected benefits have not materialized. I question the narrative of biotechnology as a Schumpeterian revolution by comparing it to the academic research paradigm that preceded it, clinical research in hospitals. I analyze these as distinct research paradigms that involve different epistemologies, practices, and institutional loci. I develop the claim that the complexity of biological systems means that clinical research was well adapted to medical innovation, and that the genetics/molecular biology paradigm imposed a predictive logic to search that was less effective at finding new drugs. The paper describes how drug discovery unfolds in each paradigm: in clinical research, discovery originates with observations of human subjects and proceeds through feedback-based learning, whereas in the genetics model,discovery originates with a precisely-defined molecular target; feedback from patients enters late in the process. The paper reviews the post-War institutional history that witnessed the relative decline of clinical research and the rise of genetics and molecular science in the United States bio-medical research landscape. The history provides a contextual narrative to illustrate that, in contrast to the framing of biotechnology as a Schumpeterian revolution, the adoption of biotechnology as a core drug discovery platform was propelled by institutional changes that were largely disconnected from processes of scientific or technological selection. Implications for current medical policy initiatives and translational science are discussed. (C) 2016 Published by Elsevier B.V.
Rabbit is the third most commonly used animal model in different fields of scientific research, such as reproductive biology, fertility and embryo transfer studies, and immunology. This animal species, often used in antibodies production, has minority of scientific records about the immunological status of its reproductive organs. The aim of this study was to find histological and immunological changes in rabbit female reproductive tract during different reproductive stages. The study was carried out on female rabbits, divided in three groups, according to the following stages of reproductive cycle: Estrous, ovulation and pregnancy. Histological and immunohistochemical stains for T- and B-cells were performed on tissue samples of cornu uteri and cervix. T lymphocytes were predominant in all anatomical parts of the uterus, in all stages of the cycle. The highest number of those cells was recorded at estrous, while the lowest was recorded at pregnancy. Cervix expressed more immunological activity than cornu uteri. The distribution and the number of immune positive cells in the rabbit female reproductive tract depend on its hormonal status.
Background: The recommended screening of rabies in `suspect' animal cases involves testing fresh brain tissue. The preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. The occurrence and location of histopathological changes and immunohistochemical (IHC) labelling for rabies in formalin fixed paraffin embedded (FFPE) canine brain is described in samples from 57 rabies suspect cases from Sri-Lanka. The presence of Negri bodies and immunohistochemical detection of rabies virus antigen were evaluated in the cortex, hippocampus, cerebellum and brainstem. The effect of autolysis and artefactual degeneration of the tissue was also assessed. Results: Rabies was confirmed in 53 of 57 (93%) cases by IHC. IHC labelling was statistically more abundant in the brainstem. Negri bodies were observed in 32 of 53 (60.4%) of the positive cases. Although tissue degradation had no effect on IHC diagnosis, it was associated with an inability to detect Negri bodies. In 13 cases, a confirmatory Polymerase chain reaction (PCR) testing for rabies virus RNA was undertaken by extracting RNA from fresh frozen tissue, and also attempted using FFPE samples. PCR detection using fresh frozen samples was in agreement with the IHC results. The PCR method from FFPE tissues was suitable for control material but unsuccessful in our field cases. Conclusions: Histopathological examination of the brain is essential to define the differential diagnoses of behaviour modifying conditions in rabies virus negative cases, but it is unreliable as the sole method for rabies diagnosis, particularly where artefactual change has occurred. Formalin fixation and paraffin embedding does not prevent detection of rabies virus via IHC labelling even where artefactual degeneration has occurred. This could represent a pragmatic secondary assay for rabies diagnosis in the field because formalin fixation can prevent sample degeneration. The brain stem was shown to be the site with most viral immunoreactivity; supporting recommended sampling protocols in favour of improved necropsy safety in the field. PCR testing of formalin fixed tissue may be successful in certain circumstances as an alternative test.
Rabies virus (RABV) remains one of the most important global zoonotic pathogens. RABV causes rabies, an acute encephalomyelitis associated with a high rate of mortality in humans and animals and affecting different parts of the world, particularly in Asia and Africa. Confirmation of rabies diagnosis relies on laboratory diagnosis, in which molecular techniques such as detection of viral RNA by reverse transcription polymerase chain reaction (RT-PCR) are increasingly being used. In this study, two real-time quantitative RT-PCR assays were developed for large-spectrum detection of RABV, with a focus on African isolates. The primer and probe sets were targeted highly conserved regions of the nucleoprotein (N) and polymerase (L) genes. The results indicated the absence of non-specific amplification and cross-reaction with a range of other viruses belonging to the same taxonomic family, i.e. Rhabdoviridae, as well as negative brain tissues from various host species. Analytical sensitivity ranged between 100 to 10 standard RNA copies detected per reaction for N-gene and L-gene assays, respectively. Effective detection and high sensitivity of these assays on African isolates showed that they can be successfully applied in general research and used in diagnostic process and epizootic surveillance in Africa using a double-check strategy. (C) 2017 Elsevier B.V. All rights reserved.
Overexpression of Rabl3 is associated with some malignancies. However, their relationship with hepatocellular carcinoma remains unclear. In this study, the expression of Rabl3 in hepatocellular carcinoma cell lines, and four pairs of matched hepatocellular carcinoma tissues and their adjacent normal hepatic tissues were detected by quantitative reverse transcription polymerase chain reaction and western blot. In addition, the protein expression of Rabl3 was examined in 162 cases of hepatocellular carcinoma by immunohistochemistry. Rabl3 in hepatocellular carcinoma cell lines was elevated at both messenger RNA and protein levels, and the Rabl3 protein was significantly upregulated by upto 3.3-fold in hepatocellular carcinoma compared with the paired normal hepatic tissues. Immunohistochemical analysis revealed that overexpressions of Rabl3 were 80.2% in hepatocellular carcinoma. Rabl3 is expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissue (p < 0.01). Statistical analysis suggested the upregulation of Rabl3 was significantly associated with lymph node metastasis, tumor thrombus of the portal vein, and advanced clinical stage (p < 0.05). Furthermore, we found that overexpression of Rabl3 in hepatocellular carcinoma cells could significantly enhance cell proliferation and growth ability. Conversely, silencing Rabl3 by small hairpin RNA interference caused an inhibition of cell proliferation and growth. Our studies suggest that the Rabl3 is a valuable marker of hepatocellular carcinoma progression and that the overexpression of Rabl3 plays an important role in the development and pathogenesis of hepatocellular carcinoma.
The enzyme squalene synthase (EC 2.5.1.21) catalyzes a reductive dimerization of two farnesyl diphosphate (FPP) molecules into squalene, a key precursor for the sterol and triterpene biosynthesis. A full-length cDNA encoding squalene synthase (designated as TeSqS) was isolated from Taxus cuspidata, a kind of important medicinal plants producing potent anti-cancer drug, taxol. The full-length cDNA of TcSqS was 1765 bp and contained a 1230 bp open reading frame (ORF) encoding a polypeptide of 409 amino acids. Bioinformatic analysis revealed that the deduced TcSqS protein had high similarity with other plant squalene synthases and a predicted crystal structure similar to other class I isoprenoid biosynthetic enzymes. Southern blot analysis revealed that there was one copy of TcSqS gene in the genome of T cuspidata. Semi-quantitative RT-PCR analysis and northern blotting analysis showed that TcSqS expressed constitutively in all tested tissues, with the highest expression in roots. The promoter region of TcSqS was also isolated by genomic walking and analysis showed that several cis-acting elements were present in the promoter region. The results of treatment experiments by different signaling components including methyl-jasmonate, salicylic acid and gibberellin revealed that the TeSqS expression level of treated cells had a prominent diversity to that of control, which was consistent with the prediction results of TcSqS promoter region in the PlantCAR-E database.
The current research expands upon the sparse existing literature on the nature of bias against interracial couples. Study 1 demonstrates that bias against interracial romance is correlated with disgust. Study 2 provides evidence that images of interracial couples evoke a neural disgust response among observers - as indicated by increased insula activation relative to images of same-race couples. Consistent with psychological theory indicating that disgust leads to dehumanization, Study 3 demonstrates that manipulating disgust leads to implicit dehumanization of interracial couples, Overall, the current findings provide evidence that interracial couples elicit disgust and are dehumanized relative to same-race couples. These findings are particularly concerning, given evidence of antisocial reactions (e.g., aggression, perpetration of violence) to dehumanized targets. Findings also highlight the role of meaningful social units (e.g., couples) in person perception, an important consideration for psychologists conducting social cognition research. (C) 2016 Elsevier Inc All rights reserved.
Integrated bipolar Operational Amplifier (op-amp) type A 741 was irradiated with neutrons and gamma rays. The radiation on gain factors, slew rate, and power supply current have been evaluated. The experimental results show a decrease of these parameter values after exposing to the radiation. The advantage of the increase of the voltage power supplies and the thermal annealing treatment on the damaged parameters was also explored. The relationship among different frequency response parameters is also studied leading to an analytical formula for the above degraded parameters.
We prove the vanishing viscosity limit of the Navier-Stokes-Boltzmann equations (see (1.3)) to the Euler-Boltzmann equations (see (1.9)) for a three-dimensional compressible isentropic flow in radiation hydrodynamics. It is shown that under some reasonable assumptions for the radiation coefficients, there exists a unique regular solution of Navier-Stokes-Boltzmann equations with degenerate viscosities, arbitrarily large initial data and far field vacuum, whose life span is uniformly positive in the vanishing viscosity limit. It is worth paying special attention to the fact that, via introducing two different symmetric structures and applying some techniques dealing with the complexity caused by the strong coupling between fluid and radiation field, we can also give some uniform estimates of (I, rho gamma-1/2, u) in H-3 and of del rho/rho in D-1, which provide the convergence of the regular solution of the viscous radiation flow to that of the inviscid radiation flow (see Li-Zhu [17]) in L-infinity([0, T]; H-s') space for any s' is an element of [2, 3) with a rate of epsilon(2(1-s'/3)). (C) 2017 Elsevier Inc. All rights reserved.
In order to explain the macroscopic radiative behaviour of an open-cell ceramic foam, knowledge of its solid phase distribution in space and the radiative contributions by this solid phase is required. The solid phase in an open-cell ceramic foam is arranged as a porous skeleton, which is itself composed of an interconnected network of ligament. Typically, ligaments being based on the assembly of grains more or less compacted, exhibit an anisotropic geometry with a concave cross section having a lateral size of one hundred microns. Therefore, ligaments are likely to emit, absorb and scatter thermal radiation. This framework explains why experimental investigations at this scale must be developed to extract accurate homogenized radiative properties regardless the shape and size of ligaments. To support this development, a 3D numerical investigation of the radiative intensity propagation through a real world ligament, beforehand scanned by X-Ray micro-tomography, is presented in this paper. The Radiative Transfer Equation (RTE), applied to the resulting meshed volume, is solved by combining Discrete Ordinate Method (DOM) and Streamline upwind Petrov-Garlekin (SUPG) numerical scheme. A particular attention is paid to propose an improved discretization procedure (spatial and angular) based on ordinate parallelization with the aim to reach fast convergence. Towards the end of this article, we present the effects played by the local radiative properties of three ceramic materials (silicon carbide, alumina and zirconia), which are often used for designing open-cell refractory ceramic foams. (C) 2017 Elsevier Ltd. All rights reserved.
This framing paper introduces the symposium on gender and the radical right. With the exception of a few recent studies, gender issues have received little attention in research on the European radical right. The purpose of this symposium is to address that and examine (1) whether radical right parties are still men's parties' - parties led and supported primarily by men and (2) to what extent and how women and women's concerns have been included by these parties. It argues that radical right parties have changed their appeal since their origins in the 1980s. There is now evidence of the fact that radical right parties, at least in some countries, exhibit an active political involvement of women and engage in some representation of women's concerns. This puts them in a more standardised' political position vis-a-vis other parties. Given the current lack of focus on this topic, and given the recent gendered changes in radical right parties, this symposium stresses the academic and political importance of studying gender relations in radical right politics.
Based on the action principle of continuous wave Doppler Radio fuze, the hardware-in-the-loop simulation system is designed. Will test the role of the fuze Doppler signal which the fuze generated will be collected by using precision operational amplifier OPA378, after its adjustment to the processor, the processor will collect the signal to AD conversion, and upload to the host computer, the received dopple signal waveform is displayed, to stop after the threshold accepted. Finally, the experimental results show that the system can simulate the CW Doppler airfuse fuze.
This paper presents a novel circuit design for input-output Rail-to-Rail CMOS Second Generation Current Conveyor (CCII) for low voltage and low power applications. The designed circuit is structured from a single stage Rail-to-Rail Operational Amplifier (Op-Amp) and a conventional CMOS inverter as a class AB amplifier. Therefore, it provides a high wide range for input signal and high output current driving capability operation. In this paper, a new technique for an automated design script is created to produce a constant trans-conductance (gm) for the Rail-to-Rail Op-Amp using Open Command Environment (OCEAN) script language. The proposed Rail-to-Rail Op-Amp is based on a DC level shifter technique, which is cited at the input stage. This script allows the design problem to be cast as a program. Therefore, it offers an efficient, reliable, and fast way to implement high-performance of analog integrated circuits. Moreover, the physics-based g(m)/I-D characteristic is used that is more suitable for short channel transistors in sub-micron processes. The circuit is simulated in IBM 0.13 mu CMOS technology with a single power supply 1.5-V. Virtuoso layout editor tool with caliber tools from Mentor Graphics are used to carry out the layout of the proposed circuit. The chip is fabricated by MOSIS Educational Program (MEP) and is tested to evaluate the performance of the proposed circuits. The measured and simulation results indicate a good agreement. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents a low-power rail-to-rail amplifier with a paralleled folded-cascold structure input stage and a feed forward class AB output stage.the switch in the bias circuit is switching off to hoost the driving capability when the input single is low,or else,the amplifier works on the switching on state to save power.simulations using SMIC 0.35um process cooled and cadence specre at 33V supply voltage,the amplifier performs almost 70dB dc gain,the CMRR reaches 140dB and the lowest static power consumption is just 0.6mW.this amplifier is used in the PGA of hige precision sigma-delta ADC as a buffer to meet the input sigle range of 2.5V when the gain of the PGA is 1 or 2.
A constant-gm, rail-to-rail operational amplifier circuit topology is presented in this paper. The amplifier input stage is realized using single NMOS pair at 0.13 mu m bulk-CMOS process technology. The overall gain variation is within the range of +/- 2.338% for the rail-to-rail common mode input range. The proposed design is able to reject the common mode input response with 115dB of common mode rejection ratio (CMRR). High slew rate is achieved and the simulated value is +19/-43 (V/mu s) of an unity gain buffer op-amp at 5pF of CL. The variation in overall gm and gain are also simulated at different corner temperatures. The circuit simulation is done in Tanner EDA at 1.8V of power supply which dissipates the power of 6.1mW.
Recently, determining the Ramsey numbers of loose paths and cycles in uniform hyper graphs has received considerable attention. It has been shown that the 2-color Ramsey number of a k-uniform loose cycle C-n(k), R(C-n(k), C-n(k)), is asymptotically 1/2(2k- 1)n. Here we conjecture that for any n >= m >= 3 and k >= 3, R(P-n(k), P-m(k)) = R(P-n(k), C-m(k)) = R(C-n(k), C-m(k)) + 1 = (k-1)n + left perpendicular m+1/2 right perpendicular. Recently the case k = 3 was proved by the authors. In this paper, first we show that this conjecture is true for k = 3 with a much shorter proof. Then, we show that for fixed m >= 3 and k >= 4 the conjecture is equivalent to (only) the last equality for any 2m >= n >= in >= 3. Finally we give a proof for the case m = 3. (C) 2016 Elsevier B.V. All rights reserved.
Background: Measuring the agreement between a gene expression profile and a known transcriptional regulatory network is an important step in the functional interpretation of bacterial physiological state. In this way, general design principles can be explored. One such interpretive framework is the relationship of digital control, that is, the impact of sequence-specific interactions, and analog control, i.e., the extent of the influence of chromosomal structure. Methods and Results: Here, we present time-resolved gene expression profiles of Escherichia coli's growth cycle as measured by RNA-seq. We extend methods which have been developed for discrete sets of differentially expressed genes and apply them to the wild type and two mutant time-series for which the global transcriptional regulators fis and hns were inactivated. We test our continuous methods using simulated 'expression profiles' generated from random Boolean network dynamics where we observe a clear trade-off between maximum response and level of detail included. In the real time-course expression data, we find strong interdependent changes of digital and analog control during the exponential growth phase and a dominance of analog control during the stationary phase. Conclusions: Our investigation puts forward a simple and reliable method for quantifying the match between time-resolved gene expression profiles and a transcriptional regulatory network. The method reveals a systematic compensatory interplay of digital and analog control in the genetic regulation of E. coli's growth cycle.
We aimed to compare the efficacy and tolerability of mirtazapine versus SSRIs and to assess whether "non-response at week 4" may be a clinical indicator for combining mirtazapine and SSRIs for subsequent treatment. One-hundred fifty-four outpatients with MDD were randomized to receive mirtazapine or SSRIs in step I (4 weeks). Non-responders in step I were randomly assigned to either mirtazapine or SSRIs monotherapy or their combination in step Ila while responders in step I continued the same monotherapy in step Ilb for 4 weeks. In step I, mirtazapine showed significantly faster improvement as shown by higher remission rate at week 2 with NNT = 8 compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. In step Ila, combination therapy showed a more favorable time course than SSRIs monotherapy. For subjects taking SSRIs in step I, combination therapy showed significant better improvement in the Hamilton Depression Rating (HAM-D) score both at week 6 (p = 0.006) and 8 (p = 0.013) than SSRIs monotherapy. About 80% of responders at week 4 could reach remission at week 8 and 64% of non-responders could not reach remission at week 8 for patients who continued monotherapy. When mirtazapine was added on for SSRIs non-responders at week 4, the remission rate increased by 5% and HAM-D score improved by 4 points. While for mirtazapine non responders, SSRIs add-on was not equally effective. Mirtazapine may provide a faster improvement and "non-response at week 4" may be indicator to mirtazapine add-on for patients receiving SSRIs. (C) 2017 Elsevier Ltd. All rights reserved.
Radish (Raphanus sativus L) is cultivated worldwide and is of agronomic importance. dsRNAs associated with partitiviruses were previously found in many R. sativus varieties. In this study, three large dsRNAs from radish were cloned using a modified single primer amplification technique. These three dsRNAs of lengths 3638, 3517 and 3299 bp shared conserved untranslated terminal regions, and each contained a major open reading frame putatively encoding the chrysoviral replicase, capsid protein and protease respectively. Isometric virus-like particles (VIP), approximately 45 nm in diameter, were isolated from the infected radish plants. Northern blotting indicated that these dsRNAs were encapsidated in the VLP. The virus containing these dsRNA genome segments was named Raphanus sativus chrysovirus 1 (RasCV1). Phylogenetic analysis revealed that RasCV1 is a new species of the Chrysoviridae family and forms a plant taxon with another putative plant chrysovirus, Anthurium mosaic-associated virus (AmaCV). Furthermore, no fungal mycelia were observed in radish leaf tissues stained with trypan blue. These results indicated that RasCV1 is most likely a plant chrysovirus rather than a chrysovirus in symbiotic fungi. An exhaustive BLAST analysis of RasCV1 and AmaCV revealed that chrysovirus-like viruses might widely exist in eudicot and monocot plants and that endogenization of chrysovirus segments into plant genome might have ever happened. (C) 2013 Elsevier B.V. All rights reserved.
Background: Hepatitis B virus (HBV) as an infectious disease that has nine genotypes (A-I) and a 'putative' genotype J. Objectives: The aim of this study was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate these RCCs in the HBV proteins structure. Methods: For detection of protein family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam search tool were used. Protein family accession numbers is a comprehensive and accurate collection of protein domains and families. It contains annotation of each family in the form of textual descriptions, links to other resources and literature references. Genome projects have used P famex tensively for large-scale functional annotation of genomic data; Pfam database is a large collection of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). The Pfam search tools are databases that identify Pfam of proteins. These Pfam IDs were analyzed in Sherlocc program and the location of RCCs in HBV genome and proteins were detected and reported as translated EMBL nucleotide sequence data library (TrEMBL) entries. The TrEMBL is a computer-annotated supplement of SWISS-PROT that contains all the translations of European molecular biology laboratory (EMBL) nucleotide sequence entries not yet integrated in SWISS-PROT. Furthermore, the structures of TrEMBL entries proteins were studied in the PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software (R). Results: The Pfam search tool found nine protein families in three frames. Results of Pfams studies in the Sherlocc program showed that this program has not identified RCCs in the external core antigen (PF08290) and truncated HBeAg gene (PF08290) of HBV. By contrast, the RCCs were identified in gene of hepatitis core antigen (PF00906 and the residues 224-234 and 251-255), large envelope protein S (PF00695 and the residues 53-56 and 70-84), X protein (PF00739 and the residues 10-24, 29-83, 95-99. 122-129, 139-143), DNA polymerase (viral) N-terminal domain (PF00242 and the residues 59-62, 214-217, 407-413) and protein P (Pf00336 and the residues 225-228). In HBV genome, seven RCCs were identified in the gene area of hepatitis core antigen, large envelope protein S andDNApolymerase, while protein structures of TrEMBL entries sequences found in Sherlocc program outputs were not complete. Conclusions: Based on the location of detected RCCs in the structure of HBV proteins, it was found that these RCCs may have a critical role in correct folding of HBV proteins and can be considered as drug targets. The results of this study provide new and deep perspectives about structure of HBV proteins for further researches and designing new drugs for treatment of HBV.
Amorphous TbFeCo material with perpendicular magnetic anisotropy is currently attracting more attention for potential applications in spintronic devices and logic memories. We systematically investigate magnetic, structural, thermal, optical and electrical properties of TbFeCo alloy films. It shows out-of-plane easy axis of the films turns into in-plane orientation after annealing. Significant increase in saturation magnetization in the temperature range between 400 and 450 degrees C is revealed by thermomagnetic measurements. The occurrence of crystallization and oxidation at high temperatures is confirmed by X-ray diffraction measurements. Pronounced changes in optical reflectance and sheet resistance are observed with temperature, in line with structural relaxation and change. The activation barriers for crystallization and oxidation are determined to be 1.01 eV and 0.83 eV, respectively, for FeCo-rich and Tb-rich samples. Better thermal stability against crystallization and oxidation is demonstrated in the FeCo-rich sample than the Tb-rich type. Our results provide some useful information for the alloy used in device fabrication. (C) 2017 Elsevier B.V. All rights reserved.
Arbitrary fractional order integrator can be designed by a method of constructing the rational approximation function in the form of continued product. This paper takes half order integrator as an example to exhibit the design process. The circuit is made up of level-N active operational amplifier network in which the size of N is equal to the order of rational function. Since the rational approximation function in the form of continued product consists of several first order damp elements and first derivative elements, it will greatly simplify the design process of fractional integrator. It only needs four different resistors and a series of regular capacitors. Thanks to the properties, the fractional integrator can be easily manufactured for industrial production and commercial purpose. It shows that the designed fractional integrator based on the proposed method is rational through performance simulations comparison with other methods and the test by Multisim 10.
Objective: The aim of the present work was to determine the presence of various rickettsiae and protozoan in raw milk and the assessment the potential, milk-borne route in the spread of selected zoonotic pathogens. Materials: A total of 119 raw milk samples collected randomly from 63 cows, 29 goats, and 27 sheep bred on 34 farms situated on eight communities in eastern Poland were examined by polymerase chain reaction (PCR) method for the presence of pathogenic rickettsiae (Coxiella burnetii, Anaplasma phagocytophilum, and Rickettsia spp.) and protozoan (Toxoplasma gondii). Results: The only prevalent pathogen was T. gondii, which was found in 10 samples of cow milk (15.9%), in one sample of goat milk (3.4%), and in one sample of sheep milk (3.7%). One sample of cow milk was positive for C. burnetii; however, the sequence analysis did not confirm any species of Coxiella or Coxiella-like organisms, but showed 100% homology to Psychrobacter alimentarius. None of the examined samples showed the presence of A. phagocytophilum or Rickettsia spp. Conclusions: The results of this study suggest a potential hazard of milk-borne Toxoplasma infection, mostly by consumption of raw cow milk. The milk-borne spread seems to be limited or nonsignificant in the case of C. burnetii, A. phagocytophilum, and Rickettsia spp. The false-positive sample for Coxiella spp. suggests that some care should be taken in the interpretation of the results obtained by using the PCR method.
The present work evaluates the microbiological quality of raw salad vegetables (RSV) consumed in Dhanbad city, India. A total of 480 samples of 8 different raw salad vegetables from local market were examined for overall microbial quality in terms of aerobic mesophilic, psychrotrophic counts, yeast, mould and total coliform levels. E. coli O157: H7, Listeria monocytogenes and Salmonella sp. were detected by real-time polymerase chain reaction (qPCR) subsequent to isolation. Results showed that all the samples were found positive for total coliform; however, E. coli was detected in 16.7% of the total samples. Pathogenic microorganisms such as E. coli O157: H7, L. monocytogenes and Salmonella spp. were detected in 1.3, 3.5 and 4.0%, respectively, of the total samples. However, pathogens were not detected in any of the cabbage samples. The Exiguobacterium sp. (Strain ISM SP 2014) was detected in the spinach sample while studying the bacterial contamination, reported for the first time on the surface of RSV. The 16S rRNA gene sequencing showed less than 92% similarity with sequences available in the public domain.
Xp11 translocation renal cell carcinomas (RCC) are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathologic manifestations. Only 3 RBM10TFE3 RCCs have been reported to date. Here, we added 4 cases of this rare type of tumors with clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Most tumors had similar patterns with mixed architectures as follows: acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with "pseudorosettelike" architectures, mimicking the typical morphology of t(6;11) RCC. Cytoplasmic vacuolization, nuclear groove, and psammoma bodies were observed in most cases. Immunohistochemically, all 4 cases demonstrated moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504S, RCC marker, PAX8 and vimentin, whereas negativity for TFEB, HMB45, and CK7. CKpan and Melan-A were at least focally expressed. The antibody to Ki-67 showed labeling of 3% to 8% (mean, 5%) of tumor cell nuclei. ;Of interest, several immunostainings demonstrated expression discrepancy in different histology patterns. RBM10-TFE3 fusion transcripts were identified in all cases by reverse transcription-polymerase chain reaction. By fluorescence in situ hybridization, all 4 cases showed unusual split signals with a distance <1 signal diameter (co-localized or subtle split signals) and usually had false-negative results. We also observed ultrastructures, including melanin pigment, nuclear groove, numerous glycogens, mitochondrion with areas of high electron density material, basement membrane material, and cell junctions with poor development. All 4 patients were alive with no evidence of recurrent disease. Our report adds to the known data regarding RBM10-TFE3 RCC.
RNA silencing is an innate antiviral immunity response of plants and animals. To counteract this host immune response, viruses have evolved an effective strategy to protect themselves by the expression of viral suppressors of RNA silencing (VSRs). Most potyviruses encode two VSRs, helper component-proteinase (HCPro) and viral genome-linked protein (VPg). The molecular biology of the former has been well characterized, whereas how VPg exerts its function in the suppression of RNA silencing is yet to be understood. In this study, we show that infection by Turnip mosaic virus (TuMV) causes reduced levels of suppressor of gene silencing 3 (SGS3), a key component of the RNA silencing pathway that functions in double-stranded RNA synthesis for virus-derived small interfering RNA (vsiRNA) production. We also demonstrate that among 11 TuMV-encoded viral proteins, VPg is the only one that interacts with SGS3. We furthermore present evidence that the expression of VPg alone, independent of viral infection, is sufficient to induce the degradation of SGS3 and its intimate partner RNA-dependent RNA polymerase 6 (RDR6). Moreover, we discover that the VPg-mediated degradation of SGS3 occurs via both the 20S ubiquitin-proteasome and autophagy pathways. Taken together, our data suggest a role for VPg-mediated degradation of SGS3 in suppression of silencing by VPg. IMPORTANCE Potyviruses represent the largest group of known plant viruses and cause significant losses of many agriculturally important crops in the world. In order to establish infection, potyviruses must overcome the host antiviral silencing response. A viral protein called VPg has been shown to play a role in this process, but how it works is unclear. In this paper, we found that the VPg protein of Turnip mosaic virus (TuMV), which is a potyvirus, interacts with a host protein named SGS3, a key protein in the RNA silencing pathway. Moreover, this interaction leads to the degradation of SGS3 and its interacting and functional partner RDR6, which is another essential component of the RNA silencing pathway. We also identified the cellular pathways that are recruited for the VPg-mediated degradation of SGS3. Therefore, this work reveals a possible mechanism by which VPg sabotages host antiviral RNA silencing to promote virus infection.
Introduction: The Reading the Mind in the Eyes Test (hereafter: Eyes Test) is considered an advanced task of the Theory of Mind aimed at assessing the performance of the participant in perspective-takingthat is, the ability to sense or understand other people's cognitive and emotional states. In this study, the item response theory analysis was applied to the adult version of the Eyes Test.Methods: The Italian version of the Eyes Test was administered to 200 undergraduate students of both genders (males=46%). Modified parallel analysis (MPA) was used to test unidimensionality. Marginal maximum likelihood estimation was used to fit the 1-, 2-, and 3-parameter logistic (PL) model to the data. Differential Item Functioning (DIF) due to gender was explored with five independent methods.Results: MPA provided evidence in favour of unidimensionality. The Rasch model (1-PL) was superior to the other two models in explaining participants' responses to the Eyes Test. There was no robust evidence of gender-related DIF in the Eyes Test, although some differences may exist for some items as a reflection of real differences by group.Conclusions: The study results support a one-factor model of the Eyes Test. Performance on the Eyes Test is defined by the participant's ability in perspective-taking. Researchers should cease using arbitrarily selected subscores in assessing the performance of participants to the Eyes Test. Lack of gender-related DIF favours the use of the Eyes Test in the investigation of gender differences concerning empathy and social cognition.
Infrared detectors are the core of infrared imaging systems, while readout integrated circuits are the key components of detectors. In order to grasp the performance of circuits quickly and accurately, a method of circuit modeling using Verilog-A language is proposed, which present a behavioral simulation model for the ROIC. At first, a typical capacitor trans-impedance amplifier(CTIA) ROIC unit is showed, then the two essential parts of it, operational amplifier and switch are modeled on behavioral level. The op amp model concludes these non-ideal factors, such as finite gain-bandwidth product, input and output offset, output resistance and so on. Non-deal factors that affect switches are considered in the switch behavioral model, such as rise and fall time, on-resistance and so on. At last time-domain modeling method for noise is presented, which is compared with the classical frequency domain method for difference. The analysis results shows that in the situation that noise interested bandwidth(NIBW) is more than 5MHz, the difference between the two methods leads to less than 1% if the sample rate of noise is larger 4 times of the NIBW
The economics of establishing perennial species as renewable energy feedstocks has been widely investigated as a climate change adapted diversification option for landholders, primarily using net present value (NPV) analysis. NPV does not account for key uncertainties likely to influence relevant landholder decision making. While real options analysis (ROA) is an alternative method that accounts for the uncertainty over future conditions and the large upfront irreversible investment involved in establishing perennials, there have been limited applications of ROA to evaluating land use change decision economics and even fewer applications considering climate change risks. Further, while the influence of spatially varying climate risk on biomass conversion economic has been widely evaluated using NPV methods, effects of spatial variability and climate on land use change have been scarcely assessed with ROA. In this study we applied a simulation-based ROA model to evaluate a landholder's decision to convert land from agriculture to biomass. This spatially explicit model considers price and yield risks under baseline climate and two climate change scenarios over a geographically diverse farming region. We found that underlying variability in primary productivity across the study area had a substantial effect on conversion thresholds required to trigger land use change when compared to results from NPV analysis. Areas traditionally thought of as being quite similar in average productive capacity can display large differences in response to the inclusion of production and price risks. The effects of climate change, broadly reduced returns required for land use change to biomass in low and medium rainfall zones and increased them in higher rainfall areas. Additionally, the risks posed by climate change can further exacerbate the tendency for NPV methods to underestimate true conversion thresholds. Our results show that even under severe drying and warming where crop yield variability is more affected than perennial biomass plantings, comparatively little of the study area is economically viable for conversion to biomass under $200/DM t, and it is not until prices exceed $200/DM t that significant areas become profitable for biomass plantings. We conclude that for biomass to become a valuable diversification option the synchronisation of products and services derived from biomass and the development of markets is vital. (C) 2017 Elsevier Ltd. All rights reserved.
The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a major public health problem in Latin America. This parasite has a complex population structure comprised by six or seven major evolutionary lineages (discrete typing units or DTUs) TcI-TcVI and TcBat, some of which have apparently resulted from ancient hybridization events. Because of the existence of significant biological differences between these lineages, strain characterization methods have been essential to study T. cruzi in its different vectors and hosts. However, available methods can be laborious and costly, limited in resolution or sensitivity. In this study, a new genotyping strategy by real-time PCR to identify each of the six DTUs in clinical blood samples have been developed and evaluated. Two nuclear (SL-IR and 18S rDNA) and two mitochondrial genes (COII and ND1) were selected to develop original primers. The method was evaluated with eight genomic DNA of T. cruzi populations belonging to the six DTUs, one genomic DNA of Trypanosoma rangeli, and 53 blood samples from individuals with chronic Chagas disease. The assays had an analytical sensitivity of 1-25 fg of DNA per reaction tube depending on the DTU analyzed. The selectivity of trials with 20 fg/mu L of genomic DNA identified each DTU, excluding non-targets DTUs in every test. The method was able to characterize 67.9% of the chronically infected clinical samples with high detection of TcII followed by TcI. With the proposed original genotyping methodology, each DTU was established with high sensitivity after a single real-time PCR assay. This novel protocol reduces carryover contamination, enables detection of each DTU independently and in the future, the quantification of each DTU in clinical blood samples. (C) 2017 Elsevier B.V. All rights reserved.
In preclinical studies, heregulin (HRG) expression was shown to be the most relevant predictive biomarker for response to patritumab, a fully human anti-epidermal growth factor receptor 3 monoclonal antibody. In support of a phase 2 study of erlotinib +/- patritumab in non-small cell lung cancer (NSCLC), a reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay for relative quantification of HRG expression from formalin-fixed paraffin-embedded (FFPE) NSCLC tissue samples was developed and validated and described herein. Test specimens included matched FFPE normal lung and NSCLC and frozen NSCLC tissue, and HRG-positive and HRG-negative cell lines. Formalin-fixed paraffin-embedded tissue was examined for functional performance. Heregulin distribution was also analyzed across 200 NSCLC commercial samples. Applied Biosystems TaqMan Gene Expression Assays were run on the Bio-Rad CFX96 real-time PCR platform. Heregulin RT-qPCR assay specificity, PCR efficiency, PCR linearity, and reproducibility were demonstrated. The final assay parameters included the Qiagen FFPE RNA Extraction Kit for RNA extraction from FFPE NSCLC tissue, 50 ng of RNA input, and 3 reference (housekeeping) genes (HMBS, IPO8, and EIF2B1), which had expression levels similar to HRG expression levels and were stable among FFPE NSCLC samples. Using the validated assay, unimodal HRG distribution was confirmed across 185 evaluable FFPE NSCLC commercial samples. Feasibility of an RTqPCR assay for the quantification of HRG expression in FFPE NSCLC specimens was demonstrated.
The receptor for advanced glycation end-products (RAGE) is thought to be expressed ubiquitously as various protein isoforms. Our objective was to use Northern blotting, immunoblotting, and sensitivity to N-glycanase digestion to survey RAGE isoforms expressed in cell lines and mouse tissues in order to obtain a more comprehensive view of the RAGE expressome. Pulmonary RAGE mRNA (1.4 kb) was smaller than cell-line and tissue RAGE mRNA (6 kb-10 kb). Three anti-RAGE antibodies that recognized three distinct RAGE epitopes were used for protein studies (N-16, H-300, and alpha ES). Lung expressed three predominant protein isoforms with apparent molecular masses of 45.1, 52.6, and 57.4 kDa (N-16/H-300) and four isoforms at 25.0, 46.9, 52.5, and 54.2 kDa (alpha ES). These isoforms were expressed exclusively in lung. Heart, ileum, and kidney expressed a 44.0-kDa isoform (N-16), whereas aorta and pancreas expressed a 53.3-kDa isoform (alpha ES). Each of these isoforms were absent in tissue extracts prepared from RAGE(-/-) mice. Cell lines expressed a 70.0-kDa isoform, and a subset expressed a 30.0-kDa isoform (alpha ES). Lung RAGE appeared to contain two N-linked glycans. Tissue and cell-line RAGE isoforms were completely insensitive to PNGase F digestion. Thus, numerous RAGE protein isoforms are detectable in tissues and cell lines. Canonical transmembrane and soluble RAGE appear to be expressed solely in lung (N-16/H-300). Non-pulmonary tissues and cell lines, regardless of the source tissue, both express distinct RAGE protein isoforms containing the N-terminal N-16 epitope or the aES RAGE epitope encoded by alternate exon 9, but lacking the H-300 epitope.
In the early 1980's, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors were proposed on the basis of radioligand binding assays. In order to provide further support to the existence of these receptors we performed quantitative autoradiographic mapping of the binding of several ligands for the 5-HT1 receptor labeling the subtypes 5-HT1A, 5-HT1B and 5-HT1C, and characterized pharmacologically these different receptors. The results demonstrated differential localization of the subtypes of 5-HT1 receptors indicating that they were expressed by different cell populations, probably neurons, in the brain and further supporting their reality. Shortly afterwards, the cloning of the genes coding for these 5-HT receptors, and many others, ended the dispute by demonstrating that they were different proteins. The advent of Molecular Biology provided new methodologies for the study of the chemical and molecular anatomy of 5-HT receptors in brain, by visualizing cells expressing their mRNA by in situ hybridization and showed that the family of mammalian 5-HT receptors has 14 members, a figure much larger than ever suspected at that time. This article is part of a Special Issue entitled SI:50th Anniversary Issue. (C) 2016 Elsevier B.V. All rights reserved.
Midkine (MK) is a unique growth and differentiation factor that modulates the proliferation and migration of various cells; however, little is known regarding its relationship to intestinal diseases. The aim of this study was to investigate MK expression and its role in dextran sulfate sodium (DSS)-induced colitis in rats. The expressions of MK, receptor-like protein-tyrosine phosphatase (RPTP)-beta, and proinflammatory cytokines were examined in rat colonic tissues after the development of DSS-induced colitis using Northern blotting, immunohistochemistry, and laser-capture microdissection (LCM) coupled with RT-PCR. The effects of MK on the migration of intestinal epithelial cells (IEC-6) were also evaluated in vitro using an intestinal wound repair model. MK expression was significantly increased in damaged colonic mucosa, mainly from day 3 to day 5 after the end of DSS administration, with abundant MK immunoreactive signals detected in submucosal fibroblasts. Expressions of proinflammatory cytokines were most strongly induced on day 1, which preceded the augmentation of MK expression. Results of LCM coupled with RT-PCR clearly indicated RPTP-beta expression in colonic epithelial cells. The migration assay showed that wound repair in the MK-treated groups was accelerated dose dependently. The present results showed for the first time that intestinal inflammation upregulates the MK-RPTP-beta system, which may stimulate mucosal regeneration during the process of healing of colitis. Additional investigations regarding the role of MK may contribute to the development of new options for the treatment of inflammatory bowel diseases.
The nomenclature of the major platelet receptors may appear complex, but in fact there are logical reasons why it developed in the way it did. In this short review, I describe the origins of this nomenclature, how it developed as more information became available and as relationships were established with receptors on other types of cells. Difficulties have also arisen with alternative nomenclature systems and the various equivalences with these are described and listed. There remain areas such as immunology and transfusion where the accepted nomenclature leaves something to be desired, but it is unlikely that major changes will occur.
DNA cloning is an essential tool regarding DNA recombinant technology as it allows the replication of foreign DNA fragments within a cell. pELMO was here constructed as an in-house cloning vector for rapid and low-cost PCR product propagation; it is an optimally designed vector containing the ccdB killer gene from the pDONR 221 plasmid, cloned into the pUC18 vector's multiple cloning site (Thermo Scientific). The ccdB killer gene has a cleavage site (CCC/GGG) for the SmaI restriction enzyme which is used for vector linearisation and cloning blunt-ended products. pELMO transformation efficiency was evaluated with different sized inserts and its cloning efficiency was compared to that of the pGEM-T Easy commercial vector. The highest pELMO transformation efficiency was observed for similar to 500 bp DNA fragments; pELMO vector had higher cloning efficiency for all insert sizes tested. In-house and commercial vector cloned insert reads after sequencing were similar thus highlighting that sequencing primers were designed and localised appropriately. pELMO is thus proposed as a practical alternative for in-house cloning of PCR products in molecular biology laboratories.
Horseradish peroxidase (HRP) with a variety of potential biotechnological applications is still isolated from the horseradish root as a mixture of different isoenzymes with different biochemical properties. There is an increasing demand for preparations of high amounts of pure enzyme but its recombinant production is limited because of the lack of glycosylation in Escherichia coli and different glycosylation patterns in yeasts which affects its stability parameters. The goal of this study was to increase the stability of non-glycosylated enzyme, which is produced in E. coli, toward hydrogen peroxide via mutagenesis. Asparagine 268, one of the N-glycosylation sites of the enzyme, has been mutated via saturation mutagenesis using the megaprimer method. Modification and miniaturization of previously described protocols enabled screening of a library propagated in E. coli XJb (DE3). The library of mutants was screened for stability toward hydrogen peroxide with azinobis (ethylbenzthiazoline sulfonate) as a reducing substrate. Asn268Gly mutant, the top variant from the screening, exhibited 18-fold increased stability toward hydrogen peroxide and twice improved thermal stability compared with the recombinant HRP. Moreover, the substitution led to 2.5-fold improvement in the catalytic efficiency with phenol/4-aminoantipyrine. Constructed mutant represents a stable biocatalyst, which may find use in medical diagnostics, biosensing, and bioprocesses. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 789-794, 2016
Location-aware recommender systems that use location-based ratings to produce recommendations have recently experienced a rapid development and draw significant attention from the research community. However, current work mainly focused on high-quality recommendations while underestimating privacy issues, which can lead to problems of privacy. Such problems are more prominent when service providers, who have limited computational and storage resources, leverage on cloud platforms to fit in with the tremendous number of service requirements and users. In this paper, we propose a novel framework, namely APPLET, for protecting user privacy information, including locations and recommendation results, within a cloud environment. Through this framework, all historical ratings are stored and calculated in ciphertext, allowing us to securely compute the similarities of venues through Paillier encryption, and predict the recommendation results based on Paillier, commutative, and comparable encryption. We also theoretically prove that user information is private and will not be leaked during a recommendation. Finally, empirical results over a real-world dataset demonstrate that our framework can efficiently recommend POIs with a high degree of accuracy in a privacy-preserving manner.
this paper introduces a kind of the rectifier circuit, adjustable constant current charging circuit, detecting voltage circuit, display circuit and power circuit of six parts of constant current source charger design scheme. The charger using op-amp composition adjustable constant current charge, constant current source circuit to avoid the constant voltage charging and lack of such as output voltage will vary with load, using a 555 timer consists of oscillator and general TL082 J - FET dual operational amplifier, compared with 3V voltage reference test voltage circuit to realize full automatic disconnection functions.
An echo state network (ESN)-based Q-learning method is developed for optimal energy management of an office, where the solar energy is introduced as the renewable source, and a battery is installed with a control unit. The energy consumption in the office, also considered as the energy demand, is separated into those from sockets, lights and air-conditioners. First, ESNs, well known for their excellent modelling performance for time series, are employed to model the time series of the real-time electricity rate, renewable energy and energy demand as periodic functions. Second, given the periodic models of the electricity rate, renewable energy and energy demand, an ESN-based Q-learning method with the Q-function approximated by an ESN is developed and implemented to determine the optimal charging/discharging/idle strategies for the battery in the office, so that the total cost of electricity from the grid can be reduced. Finally, numerical analysis is conducted to illustrate the performance of the developed method.
Recurrent spontaneous abortion (RSA) is an unknown aetiology common disease troubled women all over the world. Recent studies of circular RNAs (circRNAs) in gynecology and obstetrics area have sprung up. Our purpose in this study was to investigate the expression of circRNAs in chorionic villi from patients with RSA versus corresponding healthy gravidas, and to infer the potential role of these circRNAs in RSA occurrence. We selected 35 pairs of RSA patients and healthy control subjects, and analyzed the aberrant circRNA expression in three pairs of villi samples from each group using circRNA microarray. Altogether, including 335 up-regulated and 259 down-regulated circRNAs, 594 aberrant expressed circRNAs (FC >= 2.0, P <= 0.05) were found. Considering the raw content of each circRNAs, fold change differences and the restriction of the divergent primers, four down-regulated circRNAs (hsa_circRNA_104948, 104547, 101319 and 104938) and four up-regulated (hsa_circRNA_102116, 100709, 102424 and 103102) were selected as validation genes, using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Paired t-test and receiver operating characteristic (ROC) curves were also established. The result of content verification was accordant exactly with the microarray chip outcome (P <= 0.05 in all validation circRNAs). The area under the ROC curves (AUCs) of these eight circRNAs were all greater than 0.5. Further function analysis of circRNAs in RSA patients was performed by paper comparison. Taken together, aberrant villi circRNA expression in RSA played a vital role in its nosogenesis possibly via miRNA sponge function of circRNAs. Deeper analysis of the detailed mechanisms will be worthwhile. (C) 2017 Elsevier Masson SAS. All rights reserved.
Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation of anticoagulant protein C pathway. Genetic aberrations in THBD have been studied in arterial and venous thrombosis. However, genetic changes in THBD and their role in the risk assessment of recurrent venous thromboembolism (VTE) are not well understood. The aim of the present study was to identify the genetic aberrations in THBD and their association with the risk of VTE recurrence in a prospective population-based study. We sequenced the entire THBD gene, first in selected patients with VTE (n = 95) by Sanger sequencing and later validated those polymorphisms with minor allele frequency (MAF) 5% in the whole study population (n = 1465 with the follow-up period of 1998-2008) by Taqman polymerase chain reaction. In total, we identified 8 polymorphisms in THBD, and 3 polymorphisms with MAF 5% were further validated. No significant association between THBD polymorphisms and risk of VTE recurrence on univariate or multivariate Cox regression analysis was found (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.62-1.28, HR = 1.27, 95% CI = 0.88-1.85, and HR = 1.15, 95% CI = 0.80-1.66 for THBD rs1962, rs1042580, and rs3176123 polymorphisms, respectively), adjusted for family history, acquired risk factors for VTE, location of deep vein thrombosis, and risk of thrombophilia. Subanalysis of patients with unprovoked first VTE also showed no significant association of identified THBD polymorphisms with the risk of VTE recurrence. Our results show that aberrations in the THBD gene may not be useful for the assessment of VTE recurrence; however, further studies with large sample size are needed to confirm these findings.
Over time eukaryotic genomes have evolved to host genes carrying multiple exons separated by increasingly larger intronic, mostly non-protein-coding, sequences. Initially, little attention was paid to these intronic sequences, as they were considered not to contain regulatory information. However, advances in molecular biology, sequencing, and computational tools uncovered that numerous segments within these genomic elements do contribute to the regulation of gene expression. Introns are differentially removed in a cell type-specific manner to produce a range of alternatively-spliced transcripts, and many span tens to hundreds of kilobases. Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together. This process, called "recursive splicing," often involves non-canonical splicing elements positioned deep within introns, and different mechanisms for its deployment have been proposed. Still, the very existence and widespread nature of recursive splicing offers a new regulatory layer in the transcript maturation pathway, which may also have implications in human disease.
The application of fibers is more and more extensive, and the pollution caused by abandoned fibers is getting more serious, which has aroused wide attention. So it is necessary to find a way to solve the problem. In this paper, the para-aramid fiber (AF) was recycled and modified by phosphoric acid, and then was applied as environmental friendly flame retardant for thermoplastic polyurethane elastomer (TPU). The flame retardant properties of TPU were tested using cone calorimeter test (CCT) and thermogravimetric/Fourier transform infrared spectroscopy (TG-IR). The CCT test showed that AF-P had better flame retardant effect on TPU than pure AF. Remarkably, the pHRR value for the sample with 1.00 wt% content of AF-P was decreased by 48.1%; AF-P had improved the char forming progress and the residual mass was 30.6%, which was much more than pure TPU. TG test showed that AF-P could improve the thermal stability of TPU at high temperature. The TG-IR test revealed that AF-P had reduced the release of CO2 at the beginning. Based on the above results, it will make a great influence on the study of reuse of fibers and environmental friendly flame retardant of polymer. (C) 2017 Elsevier B.V. All rights reserved.
This study describes the analysis and design of an improved recycling folded cascode using a new input path and positive feedback which simultaneously increases transconductance considerably. The proposed amplifier with bias circuits and CMFB circuit was simulated with the TSMC 90 nm and HSPICE circuit simulator @ 1.2 V. According to the simulation results, the proposed circuit shows 75 dB, 357 MHz and 359 A mu W as DC gain, GBW and power dissipation respectively. This demonstrates 22 dB gain enhancement and 207 MHz GBW improvement, in comparison to recycling the folded cascode (for same capacitor load and power dissipation). Finally, corners and Monte-Carlo simulations were performed to verify the robustness of the proposed circuit versus process, temperature, supply voltage and device dimension mismatch variations.
The analysis of erythrocyte morphology is an important determinant in the diagnosis of many diseases. The development of more reliable and automated image analysis techniques for Red Blood Cells (RBCs) image remains an important goal in computational molecular biology. Due to the characteristic of RBCs image which captured by electron microscope (EM), a novel cascading red blood cells segmentation method is proposed. Firstly the feasibility of threshold segmentation has been analyzed and a method based on the number of connected component for coarse segmentation is put forward, successfully extracts the RBCs areas from the images with accuracy 97.52%. Then an marked watershed algorithm bases on random Hough circle detection and Mathematical Morphology is proposed for overlapped RBCs in original image. Compared to the widely used method, the accuracy of this method has improved obviously. The experimental results show that the proposed method is robust to different RBCs images in automatically separating RBCs, the extraction rate reached 82.17%. At the same time, the automatic counting accuracy up to 96.24%.
Recently, the low-cost effective biosensing systems based on advanced nanomaterials have received a key attention for development of novel assays for rapid and sequence-specific nucleic acid detection. The electrochemical biosensor based on reduced graphene oxide (rGO) modified disposable pencil graphite electrodes (PGEs) were developed herein for electrochemical monitoring of DNA, and also for monitoring of biointeraction occurred between anticancer drug, Daunorubicin (DNR), and DNA. First, rGO was synthesized chemically and characterized by using UV-Vis, TGA, FT-IR, Raman Spectroscopy and SEM techniques. Then, the quantity of rGO assembling onto the surface of PGE by passive adsorption was optimized. The electrochemical behavior of rGO PGEs was examined by cyclic voltammetry (CV). rGO-PGEs were then utilized for electrochemical monitoring of surface-confined interaction between DNR and DNA using differential pulse voltammetry (DPV) technique. Additionally, voltammetric results were complemented with electrochemical impedance spectroscopy (EIS) technique. Electrochemical monitoring of DNR and DNA was resulted with satisfying detection limits 0.55 mu M and 2.71 mu g/mL, respectively.
Fluorescent proteins (FPs) are well known and broadly used as bio-imaging markers in molecular biology research. Many FP genes were cloned from anthozoan species and it was suggested that multi-copies of these genes are present in their genomes. However, the full complement of FP genes in any single coral species remained unidentified. In this study, we analyzed the FP genes in two stony coral species. FP cDNA sequences from Acropora digitifera and Acropora tenuis revealed the presence of a multi-gene family with an unexpectedly large number of genes, separated into short-/middle-wavelength emission (S/MWE), middle-/long-wavelength emission (M/LWE), and chromoprotein (CP) clades. FP gene copy numbers in the genomes of four A. digitifera colonies were estimated as 16-22 in the S/MWE, 3-6 in the M/LWE, and 8-12 in the CP clades, and, in total, 35, 31, 33, and 33 FP gene copies per individual shown by quantitative PCR. To the best of our knowledge, these are the largest sets of FP genes per genome. The fluorescent light produced by recombinant protein products encoded by the newly isolated genes explained the fluorescent range of live A. digitifera, suggesting that the high copy multi-FP gene family generates coral fluorescence. The functionally diverse multi-FP gene family must have existed in the ancestor of Acropora species, as suggested by molecular phylogenetic and evolutionary analyses. The persistence of a diverse function and high copy number multi-FP gene family may indicate the biological importance of diverse fluorescence emission and light absorption in Acropora species.
The reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) technique has become one of the most widely used and reliable methods in gene expression studies. Successful application of qRT-PCR requires the accurate quantification of relative transcript levels, which strongly depends on the expression stability of the reference genes used as internal controls for data normalization. Plums (Prunus salicina Lindl.) are among the most numerous and commercial important fruit trees. In order to ensure the reliability of gene expression analyses using qRT-PCR in plum molecular biology research, 14 candidate reference genes were selected, and their relative expression levels were further measured by qRT-PCR using samples of plum peels obtained via different postharvest processes. Three statistical algorithms, geNorm, NormFinder, and BestKeeper, were employed to assess the expression stability of each candidate gene. A comprehensive evaluation was generated by the overall analysis approach, RefFinder to infer the final rankings. The results showed that CAC was the most stably expressed candidate reference gene across all experimental conditions. CAC and UNK under the room temperature treatment, CAC, ACT, and CLATH under the cold treatment, and CAC and ACT under all treatments were suitable for accurate gene expression quantification. In addition, relative gene expression patterns of the plant anthocyanin biosynthesis-related structural gene PsANS were evaluated using selected housekeeping genes as internal controls under two treatments to further confirm the usefulness of the selected reference genes. These results indicated that the selection of systematically validated reference genes for specific experimental conditions is necessary to avoid misinterpretation of qRT-PCR data and to obtain accurate and reliable gene expression results. (C) 2016 Elsevier B.V. All rights reserved.
Ethylene refrigeration system of a light olefins production plant was investigated using the conventional and advanced exergoeconomic analyses. In advanced analysis, investment and exergy destruction costs of system components are divided into endogenous/exogenous and avoidable/unavoidable parts to improve our knowledge about the refrigeration system. Results of the exergoeconomic analysis represent that the total cost of column T-1 (1217.67 $/h), compressor C-3 (864.88 $/h), compressor C-2 (250.43 $/h) and multi stream heat exchanger MSHE-1 (154.19 $/h) are larger than other components. Results of the advanced exergoeconomic analysis reveal that most of the total costs of components are endogenous and can be reduced only for column T-1 and compressor C-3. With increasing the efficiency of these two components, investment and exergy destruction costs has been decreased (1381.74 $/h). Large amounts of endogenous exergy destruction cost of components represent that the interactions between the components are not a main reason for exergy destruction. Therefore, an appropriate strategy for the enhancement of the system efficiency and profitability is to improve their performance. Based on the above results, column T-1 and compressor C-3 have the highest priority to improve the performance. Sensitivity of the analysis parameters to some important operating variables have also been investigated. (C) 2017 Elsevier Ltd. All rights reserved.
South Africa's refugee population has grown considerably over the last decade. Both food insecurity and mental illness are common in developing countries, but this relationship remains unexamined in an African refugee population. 335 adult refugees in Durban, South Africa were interviewed using a self-report of food insecurity and the Hopkins Symptom Checklist-25. The proportion of those who responded 'often true' to not having enough food and eating less was 23.1 and 54.3 %, respectively. The proportion of individuals with a significant level of anxiety and depressive symptomatology was 49.4 and 54.6 %, respectively. The adjusted logistic regression indicated that not eating enough was significantly associated with anxiety (aOR = 4.52, 95 % CI: 2.09-9.80) and depression (aOR = 4.51, 95 % CI: 2.01-10.09). Similarly, eating less was significantly associated with anxiety (aOR = 2.88, 95 % CI: 1.56-5.31) and depression (aOR = 2.88, 95 % CI: 1.54-5.39). The high prevalence of food insecurity, and its relationship to mental illness, highlight the importance of addressing basic needs among this population.
Over 50 million people have been displaced, some as a result of conflict, which exposure can lead to psychiatric sequelae. The aims of this study were to provide estimates of pre-emigration trauma, post-migration stress, and psychological sequelae of immigrants and refugees from predominantly Sub-Saharan Africa who immigrated to Sweden. We also examined the predictors of the psychiatric sequelae as well as acculturation within the host country. A total of 420 refugees and immigrants were enrolled using stratified quota sampling. A battery of questionnaires including the Harvard Trauma Questionnaire, Post-Migration Living Difficulties Scale, the Cultural Lifestyle Questionnaire; and the Hopkins Checklist were administered. Descriptive statistics, Chi square analyses, Pearson correlations, analysis of variance, and logistic and linear regression were performed to test the aims of the study. Eighty-nine percent of participants reported at least one traumatic experience prior to emigration. Forty-seven percent of refugees reported clinically significant PTSD and 20 % reported clinically significant depressive symptoms. Males reported a significantly greater number of traumatic events [F(1, 198) = 14.5, p < 0.001] and post-migration stress than females [F(1, 414) = 5.3, p = 0.02], particularly on the financial, discrimination, and healthcare subscales. Females reported a higher prevalence of depressive symptoms when compared to males [F(1, 419) = 3.9, p = 0.05]. Those with a shorter duration in Sweden reported higher rates of PTSD [F(63, 419) = 1.7, p < 0.001]. The greater number of traumatic events was found to be significantly associated with the severity of PTSD symptoms [F(34, 419) = 9.6, p < 0.001]. Using regression analysis, 82 and 83 % of the variances associated with anxiety and depression, respectively, was explained by gender, education, religion, PTSD and post-migration stress. Sixty-nine percent of the variance associated with PTSD included education, number of traumatic events, depressive symptoms and post-migration stress. Forty-seven percent of the variance for acculturation was accounted for by a model that included age, education, duration in Sweden, anxiety, depression, and post-migration stress. These predictors were also significant for employment status with the exception of depressive symptoms. Multidimensional interventions that provide treatments to improve psychiatric symptoms in combination with advocacy and support to reduce stress (e.g., financial, access to health care) are recommended. The focus of the intervention may also be modified based on the gender of the participants.
The purpose of this study was to determine the environmental impacts associated with a deep energy efficiency refurbishment using life cycle assessment. A prototypical refurbished model of an office building located in Auckland, New Zealand was used as a case study. The refurbishment included major changes to the building envelope with additional insulation, modified wall-window ratio, solar shading as well as technical replacement of the lighting and HVAC system. The study included identification of environmental hot spots of a deep energy refurbishment, and consideration of the effect of different electricity mixes in New Zealand on the total environmental impact of the refurbished building when compared to the un-refurbished existing building over different operation periods. An environmental payback period was calculated for each impact category. The results of this study indicate that deep energy refurbishment is associated with significant environmental impacts mainly due to the use of energy-intensive construction materials. However, the refurbishment yields net reductions in most impact categories if the building has a longer operational period. The environmental impacts of a building's operation are mainly associated New Zealand's electricity generated from coal. As future scenarios of New Zealand's electricity mix have a reduced share of electricity generated from coal, the environmental benefits of avoided electricity consumption are also reduced. The study concludes that measures to promote energy efficiency refurbishment in office buildings where a significant proportion of the operational energy is provided from renewable energy sources, should be carefully considered because they may not reduce overall environmental impacts. (C) 2017 Elsevier Ltd. All rights reserved.
This study aims at assessing the technical and economic benefits of refurbishing existing public housing villas in the UAE. Four representative federal public housing villas built between 1980s and 2010s were modeled and analyzed. The Integrated Environmental Solutions-Virtual Environment (IES-VE) energy modeling software was used to estimate the energy consumption and savings due to different refurbishment configurations applied to the villas. The refurbishment technical configurations were based on the UAE's Estidama green buildings sustainability assessment system. The refurbishment configurations include upgrading three elements: the wall and roof insulation as well as replacing the glazing. The annual electricity savings results indicated that the most cost-efficient refurbishment strategy is upgrading of wall insulation (savings up to 20.8 %) followed by upgrading the roof's insulation (savings up to 11.6 %) and lastly replacing the glazing (savings up to 3.2 %). When all three elements were refurbished simultaneously, savings up to 36.7 % were achieved (villa model 670). The savings translated to CO2 emission reduction of 22.6 t/year. The simple and discounted payback periods for the different configurations tested ranged between 8 and 28 and 10 and 50 years, respectively.
Although human mouth benefits from remarkable mechanical properties, it is very susceptible to traumatic damages, exposure to microbial attacks, and congenital maladies. Since the human dentition plays a crucial role in mastication, phonation and esthetics, finding promising and more efficient strategies to reestablish its functionality in the event of disruption has been important Dating back to antiquity, conventional dentistry has been offering evacuation, restoration, and replacement of the diseased dental tissue. However, due to the limited ability and short lifespan of traditional restorative solutions, scientists have taken advantage of current advancements in medicine to create better solutions for the oral health field and have coined it "regenerative dentistry." This new field takes advantage of the recent innovations in stem cell research, cellular and molecular biology, tissue engineering, and materials science etc. In this review, the recently known resources and approaches used for regeneration of dental and oral tissues were evaluated using the databases of Scopus and Web of Science. Scientists have used a wide range of biomaterials and scaffolds (artificial and natural), genes (with viral and non-viral vectors), stem cells (isolated from deciduous teeth, dental pulp, periodontal ligament, adipose tissue, salivary glands, and dental follicle) and growth factors (used for stimulating cell differentiation) in order to apply tissue engineering approaches to dentistry. Although they have been successful in preclinical and clinical partial regeneration of dental tissues, whole-tooth engineering still seems to be far-fetched, unless certain shortcomings are addressed. (C) 2016 Elsevier B.V. All rights reserved.
Plants are ideal systems to teach core biology concepts due to their unique physiological and developmental features. Advances in DNA sequencing technology and genomics have allowed scientists to generate genome sequences and transcriptomics data for numerous model plant species. This information is publicly available and presents a valuable tool to introduce undergraduate students to the fundamental concepts of gene expression in the context of modern quantitative biology and bioinformatics. Modern biology classrooms must provide authentic research experiences to allow developing core competencies such as scientific inquiry, critical interpretation of experimental results, and quantitative analyses of large dataset using computational approaches. Recent educational research has shown that undergraduate students struggle when connecting gene expression concepts to classic genetics, phenotypic analyses, and overall flow of biological information in living organisms, suggesting that novel approaches are necessary to enhance learning of gene expression and regulation. This review describes different strategies and resources available to instructors willing to incorporate authentic research experiences, genomic tools, and bioinformatics analyses when teaching transcriptional regulation and gene expression in undergraduate courses. A variety of laboratory exercises and pedagogy materials developed to teach gene expression using plants are discussed. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer. (C) 2016 Elsevier B.V. All rights reserved.
This paper makes the case that competitive third-party regulatory arrangements' draw attention to the service provision aspect of regulatory administration. Using multiple methods, the study examines service diversification and service quality differences exhibited by third-party administrators of US organic food regulations. By examining how the service emphases of third-party regulatory administrators differ by organizational form, the study documents that the inclusion of nonprofit and private third-party regulatory administrators may expand the services that are offered and performed alongside regulatory program functions. The implications of the findings for regulatory administration, and the field of public management generally, are discussed.
Under increasing penetration of distributed resources, regulators and electricity distribution utilities face greater uncertainty regarding the evolution of network uses and efficient system costs. This uncertainty can threaten revenue adequacy and challenges both cost of service/rate of return and incentive/performance-based approaches to the remuneration of distribution utilities. To address these challenges, this paper proposes a novel methodology to establish allowed utility revenues over a multi-year regulatory period. This method combines several "state of the art" regulatory tools designed to overcome information asymmetries, manage uncertainty, and align incentives for utilities to cost-effectively integrate distributed energy resources while taking advantage of opportunities to reduce system costs and improve performance. We use a reference network model to simulate a large-scale urban distribution network, demonstrate the practical application of this regulatory method, and illustrate its performance in the face of both benchmark and forecast errors.
In this paper a low power consumption regulator has been proposed for ultra high frequency (UHF) RFID tag that has a stable output voltage. The sub-blocks of the regulator are supplied with the elementary stage output of the rectifier. The proposed operational amplifier (OPA) circuit works in class-AB and it is biased by an adaptive biasing circuit. Besides, in the proposed regulator the used bandgap reference (BGR) circuit and the sampling circuit are based on CMOS technology and they have low power consumption. The output of this regulator is 0.81 V that has +/- 1.5 mV ripple. The values of LIR. PSRR and the efficiency of the regulator are about 7.5 (mV/V), 42.5 dB and 53% respectively. Considering 10K Omega load, the power consumption of the regulator has been calculated as 147 W. The operating frequency is 960 MHz and it is simulated in TSMC 0.18 mu m CMOS technology. (C) 2014 Elsevier GmbH. All rights reserved.
Recent development in network technology can realize the control of a remote plant by a digital controller. However, there is a delay caused by data transmission of control inputs and outputs. The delay degrades the control performance without taking it into consideration. In general, it is a difficult problem to identify the delay beforehand. We also assume that the plant's parameters have uncertainty. To solve the problem, we use reinforcement learning to achieve optimal digital control. First, we consider state feedback control. Next, we consider the case where the plant's outputs are observed, and apply reinforcement learning to output feedback control. Finally, we demonstrate by simulation that the proposed control method can search for the optimal gain and that it can adapt to the change of the delay.
The current research tested a model with satisfaction with relationship status and fear of being single as mediators in serial of the linkage relationship status - well-being measured in terms of life satisfaction, emotional and psychological well-being, and depression. Results from a sample of 556 Polish participants aged 20 to 35 (M = 22.64, SD = 3.34) demonstrated that the link between relationship status and well-being was fully mediated by satisfaction with relationship status and fear of being single operating as separate mediators, as well as by satisfaction with relationship status and fear of being single as mediators in serial. In addition, the indirect effect of relationship status on well-being through satisfaction with relationship status was larger than the indirect effect of relationship status on well-being through satisfaction with relationship status and fear of being single operating in serial. (C) 2017 Elsevier Ltd. All rights reserved.
Particle filtering (PF) is an eminent simulation-based state estimation technique, which is capable of handling massive data sets and diverse external factors. Here, an effective selection of the importance density plays a pivotal role in performances of PFs by not only preventing degeneracy problems at early stages of process, but also taking both the transition prior and likelihood into account when the likelihood appears in the tail of the prior. To this end, we propose a novel importance density selection scheme for PF based on the minimum relative entropy principle. Theoretical derivation of the proposed scheme is presented, and its effectiveness is evaluated against various sampling schemes that exist in the literature using synthetic experiments. Finally, the performance of the proposed minimum relative entropy-based density selection scheme is successfully demonstrated for short-term electricity demand forecasting of a company located in Miami, FL, USA. Note to Practitioners-This paper was motivated by the necessity of reducing utility costs in terms of energy consumption in large-scale enterprises. Determination of the lowest cost method of providing the required amount of electricity heavily relies on accurate load demand forecast. In addition, demand forecasting problems also exist in various fields, including supply chain management, manufacturing, and microgrid networks. This paper provides an eminent approach to estimate the posterior state (i.e., demand in forthcoming periods) given the prior states (i.e., past demand) and measurements. In this paper, we mathematically derive the method using the minimum relative entropy principle. To validate the proposed method, a series of synthetic experiments are designed, and a case study of short-term electricity demand forecasting is carried out. The results obtained from the proposed method have been benchmarked against those obtained from four other approaches that exist in the literature. In future research, we will extend the application scope of this paper to tracking in naval radar systems and state estimation in distributed power systems with renewables.
Blow-up solutions for the purely elliptic generalized Davey-Stewartson system are studied by using a relaxation numerical method. The numerical method is based on an implicit finite-difference scheme with a second-order accuracy in both time and space. The stability of the numerical method is analyzed by investigating the linear stability of plane wave solutions. To evaluate the ability of the relaxation method to detect blow-up, numerical simulations are conducted for several test problems. A particular attention is paid to the gap interval neither a global existence nor a blow-up result is established. The monotonicity properties of blow-up time on the coupling parameter are also investigated numerically. (C) 2016 Elsevier B.V. All rights reserved.
A compact add-on model is proposed to simulate the mechanism of charge trapping and release (detrapping) and its effect on the threshold voltage of MOSFET devices. The model uses implicit algebraic differential equations compatible with transient analysis in SPICE. It also shares the accuracy level of the transient analysis. A micro model approach is used, and each trap is treated by a two-state Markov process. The normalization of trap behavior can be enabled or disabled, so that the designer can compare average trap behavior to the result of repeated Monte-Carlo simulations of a circuit. In this manner, the model can compromise between device-level modeling and circuit-level modeling. Unlike models geared towards digital circuit design, the trapping and release rates need not be constant during electrical stress. The trapping and release rates are a function of time, as they depend on the circuit state-space equations. An operational amplifier is analyzed using the new model, and the proposed approach is compared with the state of the art. (C) 2016 Elsevier Ltd. All rights reserved.
Clergy members suffering from burnout face both personal and professional complications. This study assessed occupational burnout and stress coping mechanisms among ministers affiliated with the Assemblies of God, a denomination that has received little attention in previous burnout-related studies. A cross-sectional design was employed using two instruments with acceptable psychometric properties. Approximately 65 % of those surveyed were either suffering from burnout or on the verge of burnout. Statistical differences in coping mechanism use were found between those who were and were not experiencing some level of burnout. The results of this study add to the existing understanding of occupational burnout among clergy members and ways in which burnout may be alleviated.
Psychological research on the relationship between spirituality/religion and mental health has grown considerably over the past several decades and now constitutes a sizable body of scholarship. Among dimensions of S/R, positive beliefs about God have been significantly related to better mental health outcomes, and conversely negative beliefs about God are generally associated with more distress. However, prior research on this topic has relied heavily upon self-report Likert-type scales, which are vulnerable to self-report biases and measure only explicit cognitive processes. In this study, we developed and validated an implicit social cognition task, the Positive/Negative God Go/No-go Association Task (PNG-GNAT), for use in psychological research on spirituality and religion (S/R). Preliminary evidence in a large sample (N = 381) suggests that the PNG-GNAT demonstrates internal consistency, test-retest and split-half reliability, and concurrent evidence of validity. Further, our results suggest that PNG-GNAT scores represent different underlying dimensions of S/R than explicit self-report measures, and incrementally predict mental health above and beyond self-report assessment. The PNG-GNAT appears to be an effective tool for measuring implicit positive/negative beliefs about God.
The current study examined the cultural factors (i.e., religious background, religious participation, parents' views of prayer, and parents' concepts of God) that contribute to children's differentiation between the capabilities of human minds and God's mind. Protestant Christian, Roman Catholic, Muslim, and Religiously Non-Affiliated parents and their preschool-aged children were interviewed (N=272). Children of Muslim parents differentiated the most between God's mind and human minds (i.e., human minds are fallible but God's is not), and children who had greater differentiation between God's and humans' minds had parents who had the least anthropomorphic conceptions of God. Additionally, there was a unique effect of being raised in a Religiously Non-Affiliated home on the degree of children's differentiation between God's and human minds after religious context factors had been accounted for; in other words, children of Religious Non-Affiliates differentiated between humans and God the least and their differentiation was unrelated to religious context factors. These findings delineate the ways in which religious context differences influence concepts of God from the earliest formation.
The purpose of this study was to determine whether 3-HMG-Coenzyme A (HMG-CoA) reductase inhibition would attenuate the early pressure overload-induced activation of extracellular matrix genes in the left ventricle (LV) of the heart. Sprague-Dawley rats were randomized to 1 of 4 treatment groups: sham-operation+vehicle (SH-V), aortic constriction + vehicle (AC-V), AC + rosuvastatin (RSV, 2 mg/kg; AC-LO), and AC + RSV (10 mg/kg; AC-HI). Rats were injected with normal NaCl (V) or RSV once daily, beginning 1 day before surgery, and killed 1 or 3 days after surgery. Hemodynamic measurements were made in the open-chest anesthetized state. LV levels of transforming growth factor beta(1) (TGF-beta(1)), procollagen 1 (C1), and fibronectin (FN) mRNA were measured by Northern blotting. AC induced a similar to 25% increase in LV weight after 3 days that was not altered by RSV treatment. LV expression of TGF-beta(1), C1, and FN mRNA was similar to 2-fold, similar to 2.5-fold, and similar to 5-fold greater, respectively, in hearts of AC-V compared to SH-V rats 3 days post-operation, and was not significantly decreased by either dose of RSV. Inhibition of HMG-CoA reductase does not attenuate the pronounced aortic constriction-induced increases in the early expression of TGF-beta(1), C1, and FN in this model of acute pressure overload of the rat heart.
To investigate the effects of Biejia Ruangan Tablet (acurrency signiae-(1)e(3)-c"(2)e1/2-e,ec parts per thousand double dagger ae-(1), BRT)-containing serum on the expression of matrix metalloproteinase (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in cultured renal interstitial fibroblasts. Different BRT-containing sera were prepared by gastric gavages to rats with the high-dose (7 g/kg), mid-dose (3.5 g/kg), and low-dose (1.75 g/kg) BRT respectively. The expression of extracellular matrix in NRK-49F cells was induced by treatment with human transforming growth factor-beta 1 (recombined human TGF-beta 1), and BRT-containing serum. Western blotting and Northern blotting were used to measure type I and III procollagen, MMP-9, and TIMP-1. The high dose BRT-containing serum could decrease the type I and III procollagen gene expression which boosted by TGF-beta 1, at the same time cut down TIMP-1 protein and gene expression which increased by TGF-beta 1 (P < 0.05). Treatment of cells with recombined human TGF-beta 1 had no significant effect on MMP-9 expression and BRT-containing serum also had no effect on MMP-9 expression. High dose BRT has anti-fibrosis effects in NRK-49F cells, as indicated by its inhibition of type I and III procollagen and TIMP-1 expression.
The aim of this paper is to assess several pathways of a harmonised European policy framework for supporting renewable electricity (RES-E) in a 2030 horizon according to different criteria. The pathways combine two main dimensions: degrees of harmonisation and instruments and design elements. A quantitative model-based analysis with the Green-X model is provided. The results of the simulations show that there are small differences between the evaluated cases regarding effectiveness. All the policy pathways score similarly with respect to RESE deployment, i.e., with different degrees of harmonisation and whether using a feed-in tariff, a feed-in premium, a quota system with banding or a quota without banding scheme. In contrast, the policy costs clearly differ across the pathways, but the differences can mostly be attributed to the instruments rather than to the degrees of harmonisation. This is also the case with other criteria (static and dynamic efficiency and the socioeconomic and environmental benefits in terms of CO2 emissions and fossil fuels avoided). Both the degree of harmonisation and the choice of instrument influence the distribution of support costs across countries. Finally, our findings suggest that keeping strengthened national support leads to similar results to other policy pathways.
This study examines the energy use economic growth nexus by disaggregating energy use into two types of energy, renewable and non-renewable energy use. Our sample consists of eleven MENA Net Oil Importing Countries (NOICs) during the period 1980-2012. A multivariate panel framework was used to estimate the long run relationship and the panel Granger causality tests was employed to assess the causality direction among variables. The empirical results provide evidence for long-term equilibrium relationship between real Gross Domestic Product (GDP), renewable energy use, non-renewable energy use, real gross fixed capital formation and labor force. The results provide evidence also for positive and statistically significant elasticities. Moreover, the empirical findings from panel Error Correction Model confirm the existence of bidirectional causality between renewable energy use and economic growth, and between non-renewable energy use and economic growth, results that support the feedback hypothesis. Moreover, our empirical findings provide evidence for two way (bidirectional) causal association in both the short and long-run between renewable and non-renewable energy use which proves the substitutability and interdependence between these two types of energy sources. The policies implications of these results are also proposed and discussed.
This paper proposes a real options model for estimating the optimal subsidy for renewable energy power generation project by using stochastic process to describe the market price of electricity, CO2 price and investment cost. Two indicators, i.e., project value and threshold value, are used to derive the optimal subsidy. The least squares Monte Carlo simulation method is used to solve the model. The proposed model is used to empirically evaluate the optimal level of subsidy for solar photovoltaic power generation in China. The results show that carbon emission trading scheme helps reduce subsidy. Unit generating capacity, market price of electricity, CO2 price and the volatility of investment cost are negatively related with subsidy, whereas investment cost and the volatility of electricity price and CO2 price are positively related with subsidy. It is suggested that Chinese governments take some measures, e.g., promoting technological progress, establishing a nationwide carbon emission trading market, promoting the competition in renewable energy industry as well as maintaining the stability of CO2 price and electricity price, to reduce the required subsidy.
In the last decades increasing attention to environmental issues has come to the fore due to the looming issue of climate change. The growing demand for energy, coupled with the increasing greenhouse gas (GHG) emissions, have forced the study and development of energy plants that use renewable energy sources (RES), as electricity generation is one of the major contributors to anthropogenic emissions. Small hydropower plants are of particular interest as their potential is assumed to be high. The aim of this study is to provide a comprehensive assessment of the environmental impacts of small hydropower plants (SHPs) using Life Cycle Assessment (LCA) methodology. The main parameter set for our simplified LCA model was the weight of the components used to construct and operate the plant: concrete, aggregates and steel. Through LCA, air pollutant externalities were associated with the life cycle of SHPs. This was accomplished by applying the NEEDS framework. The results are given per impact type (human health, loss of biodiversity, crop yield, material damage and climate change). The spearhead of the study is that the environmental cost must be a parameter of the total investment cost, which may affect the indexes of the financial evaluation of the project.
The increase in installed capacity of renewable energy sources (RES) has a positive effect on the development of smart grids and demand side management (DSM). The reason for this is the intermittent nature of renewable energy, which is directly related to the problem of balancing the production and consumption of power within the power system. By using the DSM, the power consumption in the system comprising RES can be easier adjusted to the power production. The paper proposes an improved concept of DSM through the spatial and temporal DSM. The optimal spatial and temporal DSM aims at determining the power diagram of each individual load bus in order to achieve the optimal state in the whole system. The optimal state of the system can be quantified through the minimum daily energy losses or minimum daily operating costs. A mathematical definition of the optimal spatial and temporal DSM problem is presented as well as the algorithm for its solution. The proposed methodology has been tested by three test networks. The results confirm the overall system performance improvements that include: reduction of energy losses in the system, reduction of the operating costs and the increase of the voltage quality within the system. (C) 2017 Elsevier Ltd. All rights reserved.
The European Directive regarding the promotion of energy from renewable sources (Directive 2009/28 EC) specifies separate national targets for each member state of the EU community, in order at least 20% of EU total energy demands to be met by renewable energy sources by 2020. The analysis performed in this work highlights that grid connected photovoltaic (PV) systems bring remarkable energy benefits to the electricity supply of Greece, meeting in parallel its national targets. This is validated with data reported from the operator of Hellenic Electricity Market (LAGIE). On the other hand a mass energy production coming from PV systems without energy storage units and sufficient electricity network architectures is liable to cause severe disturbances to the Greek electricity network. This issue is acknowledged by representative data from the Hellenic Electricity Power Transmission and Distribution Network Operators (ADMIE and HEDNO). Furthermore, sustainable and innovative electricity network architectures (such as micro-grids, smart-grids and web of cells), as well as innovative intermittent Renewable Energy Sources (RES) stabilization techniques are discussed, in order to facilitate high PVs integration level. (C) 2017 Elsevier Ltd. All rights reserved.
Currently, the Algerian energy system relies almost exclusively on fossil resources, but a new paradigm is emerging in the country. The Algeria program on renewable energy and energy efficiency established the ambitious goal of deriving 40% of electricity production from renewable energy sources (RES) by 2030. This study addresses the sustainability objectives of this program using a methodology, which combines an analytic hierarchy process (AHP) and experts' feedback to evaluate different renewable energy options. The performance of different RES options was assessed against 13 sub-criteria reflecting social, environmental, economic and technical concerns. The results highlighted the importance of social and environmental criteria as the main drivers for the obtained final ranking, with three of these sub-criteria weighting 35% in the decision process. Solar power was shown to be particularly well suited for Algeria, outperforming most of the other renewable options in a large set of highly weighted criteria. Wind power ranked second, followed by biomass, geothermal and lastly by hydropower. Wind and solar power together achieved a total score of more than 0.5 out of 1. From the results, policy implications were drawn and directions for future research were suggested. (C) 2017 Elsevier Ltd. All rights reserved.
This study employed homogeneous and heterogeneous panel methods to examine the relationship between renewable and non-renewable electricity consumption and economic development in three transition economies in the Baltic region, namely, Estonia, Latvia and Lithuania, for the period of 1992-2011. The study put forward four hypotheses to examine the renewable electricity-development nexus. The findings indicated that there existed a unidirectional causality from the economic development to renewable electricity consumption. Thus, the results obtained from the statistical analyses have provided empirical evidence in support of the conservation hypothesis that postulates that economic development causes the expansion of renewable electricity consumption, but not vice versa.
Africa's population is growing at a faster pace, and the growth in megacities and rate of urbanization has been very rapid. Alongside, economic growth is expected to be very robust in the future. Altogether, these will pose serious challenges for the energy system in Africa; a condition that makes the development of renewables (RES) a necessity in the continent. Though the continent is well-endowed with RES, it is least developed and deployed, partly due to limited research and development in the sector. Particularly, the macroeconomic implications of RES have not been thoroughly studied in the continent, which leaves a big literature gap for the continent. This motivates the current study to investigate into the macroeconomic implications of RES using Ghana as the case study, a country that is Well-endowed with RES and one of the few in the continent that has integrated RES into their overall energy policy. Specifically, in this study, we examined the implications of RES concentration on electricity price uncertainty. Further, we investigated the persistent profile effect of both system-wide and individual shocks on the equilibrium relations. Finally, we decomposed the variance in electricity price into permanent and transitory components and explained what drives these trends. (C) 2017 Elsevier Ltd. All rights reserved.
Interest in power-to-gas (P2G) as an energy storage technology is increasing, since it allows to utilise the existing natural gas infrastructure as storage medium, which reduces capital investments and facilitates its deployment. P2G systems using renewable electricity can also substitute for fossil fuels used for heating and transport. In this study, both techno-economic and life cycle assessment (LCA) are applied to determine key performance indicators for P2G systems generating hydrogen or methane (synthetic natural gas SNG) as main products. The proposed scenarios assume that P2G systems participate in the Swiss wholesale electricity market and include several value-adding services in addition to the generation of low fossil-carbon gas. We find that none of the systems can compete economically with conventional gas production systems when only selling hydrogen and SNG. For P2G systems producing hydrogen, four other services such as heat and oxygen supply are needed to ensure the economic viability of a 1 MW P2H system. CO2 captured from the air adds $50/MW h(t) of extra levelised cost to SNG compared to CO2 supplied from biogas upgrading plants and it does not offer an economic case yet regardless of the number of services. As for environmental performance, only the input of "clean" renewable electricity to electrolysis result in environmental benefits for P2G compared to conventional gas production. In particular, more than 90% of the life cycle environmental burdens are dominated by the electricity supply to electrolysis for hydrogen production, and the source of CO2 in case of SNG. (C) 2017 Elsevier Ltd. All rights reserved.
The Jiuquan Satellite Launch Center (JSLC) is a relatively isolated special zone in the northwest region of China. The potential risk to the energy supply security and the pressure of national greenhouse gas emissions reduction clearly indicates the JSLC's need to lower its dependency on imported fossil fuels and electricity. This article presents a feasibility analysis on the available hybrid energy system based on the renewable energy availability and local electricity demand estimation in 2020 through HOMER model. The simulation results indicate that cost of energy (COE) of the three proposed options are 0.127, 0.033 and 0.123 $/kWh, respectively. It also shows that the proposed hybrid renewable energy systems can reduce carbon emissions by 40-70% compared to electricity from the existing power grid. A sensitivity analysis reveals that the COE has a significant positive relationship with carbon price and discount rate, whereas carbon price shows a significantly distinct impact on the COE for different options considered. The optimization results also show that a grid-connected renewable power system comprised of wind power and natural gas power plant is the most economic and environment-friendly energy supply option for JSLC. However, a hybrid RE system with a local energy storage facility can better guarantee the energy supply safety considering the special function and security needs of the JSLC. This study verified that constructing new coal fired power plants is not a suitable choice from both the cost effectiveness and kenvironmental protection perspectives. (C) 2016 Elsevier B.V. All rights reserved.
The recent makeshift in fuel choice, renewable energy sources has been considered as the most popular form of its kind because of its environment friendly approaches, less cost tariff policy and the natural fuel abundance. This inclusion in power system promotes Micro-grid system to optimize the overall distribution. FPGA, elaborated as Field Programmable Gate Array, proposes chances for enhanced performance and coveted flexibility in design for the digital control. Conversely, the erudite convolution of the Hardware Description Language (HDL) coding, a way translating to HDL, can be an undesirable hurdle for the professional system designers. The design, depicted in this letter, is an instance of system modeling for FPGA-based digital control, which necessarily has the desired ability to auto-generate the HDL codes. The architecture of this design uses the DSP Builder technology, in a MATLAB / SIMULINK platform. A three phase full-bridge gird tied inverter for wind system and a three phase full-bridge inverter for grid connected wind system are built that demonstrates the close correlation with the model. The necessary simulations, results and the experimental analysis have also been highlighted for the different control techniques such as PI, dq, and the PWM control technique.
The Pacific Small Island Developing States (SIDS) are among the most vulnerable to the impacts of climate change. Besides, they are some of the most dependent on imported petroleum products in the world, the use of renewable energy (RE) can help minimize the economic risk associated with the price volatility of fossil fuels. The region is increasingly adopting renewable energy (RE) targets and policies. Successful examples of RE deployment in the Pacific SIDS exist; however, many barriers persist and prevent the use of the region's RE resources in a larger scale. Challenges for RE deployment in islands can be grouped in six categories: i) lack of RE data, ii) need for policy and regulatory frameworks, iii) scarcity of financial opportunities, iv) lack of human resources, v) costly infrastructure, and vi) socio-cultural impediments. Based on a survey conducted among main stakeholders in the region, within the framework of the Pacific Region Capacity Building Initiative of the International Renewable Energy Agency (IRENA) carried out in cooperation with the Secretariat of the Pacific Community (SPC), this paper identifies the specific characteristics of these challenges in the context of the Pacific SIDS, provide a qualitative assessment and identifies recommendations to overcome these challenges. (C) 2017 Elsevier Ltd. All rights reserved.
Large-scale deployment of renewable energy sources (RES) plays a central role in reducing CO2 emissions from energy supply systems, but intermittency from solar and wind technologies presents integration challenges. High temperature co-electrolysis of steam and CO2 in power-to-gas (PtG) and power-to-liquid (PtL) configurations could utilize excess intermittent electricity by converting it into chemical fuels. These can then be directly consumed in other sectors, such as transportation and heating, or used as power storage. Here, we investigate the impact of carbon policy and fossil fuel prices on the economic and engineering potential of PtG and PtL systems as storage for intermittent renewable electricity and as a source of low-carbon heating and transportation energy in the Alpine region. We employ a spatially and temporally explicit optimization approach of RES, PtG, PtL and fossil technologies in the electricity, heating, and transportation sectors, using the BeWhere model. Results indicate that large-scale deployment of PtG and PtL technologies for producing chemical fuels from excess intermittent electricity is feasible, particularly when incentivized by carbon prices. Depending on carbon and fossil fuel price, 0.15-15 million tonnes/year of captured CO2 can be used in the synthesis of the chemical fuels, displacing up to 11% of current fossil fuel use in transportation. By providing a physical link between the electricity, transportation, and heating sectors, PtG and PtL technologies can enable greater integration of RES into the energy supply chain globally. (C) 2017 Elsevier Ltd. All rights reserved.
Microgrids assisted by renewable energy resources are complex man made systems of various interconnected components. A number of real life scenarios relating to resource management in microgrids are modeled as multi-objective optimization formulations where multiple objectives may or may not conflict with each other. While considering the type of application, input and output of the problem, the nature of optimization problem changes. To address various types of optimization problems relating to microgid design, planning and operation, there exist a number of optimization solution types. We investigate the existing literature to classify different optimization objectives with respect to designing, planning and operation of microgrids. Some mathematical formulations for commonly used objectives relating to resource management in microgrids have been tabulated. We also classified the optimization types being used to address various optimization problems relating to resource management in microgrids. Various types of solution approaches along with the relevant simulation tools are also presented. We also reviewed the multicriteria optimization for different application areas of smart grid. The article can serve as a foundation for further research in the area of multicriteria decision making relating to resource management in micrgorids.
Photovoltaic (PV) cell plays crucial role to utilize the solar energy. The regional differences in the PV industry have created unbalanced flows of PV cells. This paper examined patterns of the PV cells international trade from spatial and temporal perspectives. Data sources are regional monetary importexport tables and the world renewable energy statistics in 1996-2015. Based on the Haggett's cognitive model of spatial structure, the patterns and evolution characteristics are identified with an aid of ArcGIS. This study revealed most PV cells exporters are distributed in East Asia and Southeast Asia intensively whereas relatively balanced exports are presented in Europe and North American in recent years. Most PV cells are flowing from east to west while the pattern of PV cells international trade has transformed from single-pole to multi-pole. Meanwhile, the international trade intensity of PV cells grew steadily at the global scale, and evolution features of PV cells trades varied from region to region. Economics conditions, incentive policy and producers' demand are three critical factors. These findings provide a useful reference for identifying the intensity, orientation, main connections and development trend of traders. Moreover, the PV industrial practitioners can benefit from this research to develop corresponding international business strategies. (C) 2017 Elsevier Ltd. All rights reserved.
Salinity gradient solar ponds act as an integrated thermal solar energy collector and storage system. The temperature difference between the upper convective zone and the lower convective zone of a salinity gradient solar pond can be in the range of 40-60A degrees C. The temperature at the bottom of the pond can reach up to 90A degrees C. Low-grade heat (< 100A degrees C) from solar ponds is currently converted into electricity by organic Rankine cycle engines. Thermoelectric generators can operate at very low temperature differences and can be a good candidate to replace organic Rankine cycle engines for power generation from salinity gradient solar ponds. The temperature difference in a solar pond can be used to power thermoelectric generators for electricity production. This paper presents an experimental investigation of a thermoelectric generators heat exchanger system designed to be powered by the hot water from the lower convective zone of a solar pond, and cold water from the upper convective zone of a solar pond. The results obtained have indicated significant prospects of such a system to generate power from low-grade heat for remote area power supply systems.
Flexibility requirements in prospective energy systems will increase to balance intermittent electricity generation from renewable energies. One option to tackle this problem is electricity storage. Its demand quantification often relies on optimization models for thermal and renewable dispatch and capacity expansion. Within these tools, power plant modeling is typically based on simplified linear programming merit order dispatch (LP) or mixed-integer unit-commitment with economic dispatch (MILP). While the latter is able to capture techno-economic characteristics to a large extent (e.g. ramping or start-up costs) and allows on/off decision of generator units, LP is a simplified method, but superior in computational effort. We present an assessment of how storage expansion is affected by the method of power plant modeling and apply a cost minimizing optimization model, comparing LP with MILP. Moreover, we evaluate the influence of wind and photovoltaic generation shares and vary the granularity of the power plant mix within MILP. The results show that LP underestimates storage demand, as it neglects technical restrictions which affect operating costs, leading to an unrealistically flexible thermal power plant dispatch. Contrarily, storage expansion is higher in MILP. The deviation between both approaches however becomes less pronounced if the share of renewable generation increases. (C) 2016 Elsevier Ltd. All rights reserved.
Following the dominant firm-competitive fringe model, this paper analyses the response of Japan's nonrenewable electricity utilities to the renewable portfolio standards (RPS) and feed-in tariff (FIT) scheme. The output of electricity from renewable energy sources (RES-E) is primarily correlated with the magnitude of the RPS requirement and the fixed tariff. Nonrenewable firms suffer a reduction in revenue due to increased RES-E production under both schemes. The RPS requirement has direct impact on the renewable energy certificate (NEC) price. If the incumbent nonrenewable electricity utilities gain market power in both electricity and NEC markets, they can suppress the RPS quota to preserve their vested benefits. In the FIT scheme, the above-market RES-E generation cost is passed on to consumers via a surcharge. Since grid-connected RES-E accelerated rapidly under FIT, nonrenewable electricity utilities would face a substantial increase in costs to maintain network reliability due to the intermittent and variable nature of RES-E technologies. The Japanese government should therefore take measures to ensure variable renewable power occupies a higher share of the electricity system, and to do so in a cost-effective manner. (C) 2017 Elsevier Ltd. All rights reserved.
Wind energy has seen a tremendous growth for electricity generation worldwide and reached 456 GW by the end of June 2016. According to the World Wind Energy Association, global wind power will reach 500 GW by the end of 2016. Africa is a continent that possesses huge under-utilized wind potentials. Some African countries, e.g., Morocco, Egypt, Tunisia and South Africa, have already adopted wind as an alternative power generation source in their energy mix. Among these countries, South Africa has invested heavily in wind energy with operational wind farms supplying up to 26,000 GWh annually to the national grid. However, two African countries, i.e., Cameroon and Nigeria, have vast potentials, but currently are lagging behind in wind energy development. For Nigeria, there is slow implementation of renewable energy policy, with no visible operational wind farms; while Cameroon does not have any policy plan for wind power. These issues are severely hindering both direct foreign and local investments into the electricity sector. Cameroon and Nigeria have huge wind energy potentials with similar climatic conditions and can benefit greatly from the huge success recorded in South Africa in terms of policy implementation, research, development and technical considerations. Therefore, this paper reviews the wind energy potentials, policies and future renewable energy road-maps in Cameroon and Nigeria and identifies their strength and weakness, as well as providing necessary actions for future improvement that South Africa has already adopted.
Utilization of wind turbines to produce energy has been increasing in recent years, due to technology advancement, cost stability and environmental issues. In this paper, the wind resource and economic feasibility have been studied to avoid investment risk in cites of Zabol, Zahak, Zahedan and Mirjaveh in Sistan and Balouchestan province of Iran. The Weibull distribution function has been applied to estimate the wind power and energy density, using meteorological data. Determination of coefficient, root mean square error, mean bias error and mean bias absolute error are also calculated to ensure the accuracy of the statistical analysis of fitted distribution. Windographer software has been employed to investigate the prevailing wind direction. The estimated annual energy densities are 2495.36, 2355.69, 126524 and 1214.01 kWh/m(2)/year, and the annual mean power densities are 284.97, 269.02, 144.49 and 138.64 W/m(2). It is found that Zabol and Zahedan are suitable for large scale power generation. The results indicate that using DW61-900 kW wind turbines are highly beneficial for Zabol and Zahak, while for Zahedan, DW52/54-250 kW wind turbine is more appropriate for generating electricity. However, Mirjaveh is suitable for off-grid applications. It should be noted that in this analysis, monetary units are presented in 2016 U.S. dollar. (C) 2017 Elsevier Ltd. All rights reserved.
While several studies have examined the effect of renewable portfolio standard laws on renewable generation in states, previous literature has not assessed the potential for spatial dependence in these policies. Using recent spatial panel methods, this paper estimates a number of econometric models to examine the impact of RPS policies when spatial autocorrelation is taken into account. Consistent with previous literature, we find that RPS laws do not have a significant impact on renewable generation within a state. However, we find evidence that state RPS laws have a significant positive impact on the share of renewable generation in the NERC region as a whole. These findings provide evidence that electricity markets are efficiently finding the lowest-cost locations to serve renewable load in states with more stringent RPS laws. In addition, our results suggest that RPS laws may be more effective tools for environmental policy than for economic development.
Arctic charr Salvelinus alpinus L. is an important species in Icelandic aquaculture and the most common wild salmonid in Iceland. A study on the course of infection with the bacterium Renibacterium salmoninarum was conducted using 3 different challenge methods in brackish and fresh water. Bacterial isolation, ELISA and PCR tests were used for detection of the bacterium in multiple organ samples. In an experiment, run for 34 wk in brackish water, infection was established by intraperitoneal injection with 5 x 10(6) colony forming units (CFU) fish(-1). There were external and internal symptoms of bacterial kidney disease (BKD) and mortalities between 6 and 13 wk after injection. A cohabitation trial was run simultaneously and infection was well established after 4 wk, as demonstrated by the detection methods applied. Symptoms of BKD were not seen and all but 1 cohabitant survived. In a separate experiment, infection was established by pumping a fixed amount of water from a tank with fingerlings infected by intraperitoneal injection into tanks with naive fish, in fresh or brackish water, for 6 wk. Fish in the inflow tanks were reared for an additional 3 wk. There were neither macroscopic symptoms nor mortalities. ELISA and PCR tests showed that infection started to take hold after 3 wk. The challenge trials demonstrated that Arctic charr is susceptible to R. salmoninarum. Cohabitation and inflow of water from tanks with infected fish provide useful models for further studies on R. salmoninarum infection acquired in a natural way in Arctic charr.
Background: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. Results: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization. This method, referred to as the Repertoire Dissimilarity Index (RDI), uses a bootstrapped subsampling approach to account for variance in sequencing depth, and, coupled with a data simulation approach, allows for direct quantification of the average variation between repertoires. We use the RDI method to recapitulate known differences in the formation of the CD4(+) and CD8(+) T cell repertoires, and further show that antigen-driven activation of naive CD8(+) T cells is more selective than in the CD4(+) repertoire, resulting in a more specialized CD8(+) memory repertoire. Conclusions: We prove that the RDI method is an accurate and versatile method for comparisons of immune repertoires. The RDI method has been implemented as an R package, and is available for download through Bitbucket.
Reproductive interference is known to occur in the morphologically similar species Neoseiulus womersleyi and Neoseiulus longispinosus: crosses between N. longispinosus females and N. womersleyi males produce (a few) female offspring, reciprocal crosses produce only male offspring. Details of the interspecific reproduction process remain largely unknown. In this article, we investigated intraspecific and interspecific crosses, spermathecal vesicles and spermatophores in females, and molecular identification of F-1 hybrids based on the internal transcribed spacer (ITS) region of nuclear ribosomal RNA (rRNA). The copulation times of interspecific crosses were similar to those of intraspecific crosses, yet interspecific crosses between N. womersleyi females and N. longispinosus males exhibited extremely low fecundity with no female offspring. On the other hand, 1 out of 35 reciprocal crosses produced viable, but sterile female offspring (F-1). Intraspecific crosses of N. womersleyi and N. longispinosus showed female-biased offspring sex ratios. Most N. womersleyi females (12 out of 15 females tested) that mated with N. longispinosus males had inflated vesicle(s) and were inseminated. Of the crosses between N. longispinosus females and N. womersleyi males, 14 pairs had neither inflated spermathecal vesicles nor were inseminated, and in only one pair, vesicles were inflated and insemination occurred that enabled the production of female offspring. Polymerase chain reaction products of the ITS region of rRNA gene digested with ClaI exhibited two fragments (361 and 278 bp) for the N. womersleyi and only a single fragment (642 bp) for the N. longispinosus, whereas three fragments for the F-1 hybrids (642, 361, and 278 bp), confirming the identification. Our results confirmed the asymmetric reproductive interference between N. womersleyi and N. longispinosus and demonstrated that the F-1 female offspring produced were (sterile) hybrids.
The past two decades of growth in renewable energy sources of electricity (RES-E) have been largely driven by out-of-market support policies. These schemes were designed to drive deployment on the basis of specific subsidies sustained in time to allow for the larger costs as well as to limit investor risk. While these policies have proven to be effective, the way they have been designed to date has led to costly market distortions that are becoming more difficult to ignore as penetrations reach unpreceded levels. In the context of this growing concern, we provide a critical analysis of the design elements of RES-E support schemes, focusing on how they affect this trade-off between promoting and efficiently integrating RES-E. The emphasis is on the structure of the incentive payment, which in the end turns to be the cornerstone for an efficient integration. We conclude that, while needed, a well-designed and further developed capacity-based support mechanism complemented with ex-post compensations defined for reference benchmark plants, such as the mechanism currently implemented in Spain, is an alternative with good properties if the major goal is truly market integration. The approach is robust to future developments in technology cost, performance and market penetration of RES-E.
Background: Though many countries, including China, are moving towards malaria elimination, malaria remains a major global health threat. Due to the spread of antimalarial drug resistance and the need for innovative medical products during the elimination phase, further research and development (R&D) of innovative tools in both epidemic and elimination areas is needed. This study aims to identify the trends and gaps in malaria R&D in China, and aims to offer suggestions on how China can be more effectively involved in global malaria R&D. Methods: Quantitative analysis was carried out by collecting data on Chinese malaria-related research programmes between 1985 and 2014, invention patents in China from 1985 to 2014, and articles published by Chinese researchers in PubMed and Chinese databases from 2005 to 2014. All data were screened and extracted for numerical analysis and were categorized into basic sciences, drug/drug resistance, immunology/vaccines, or diagnostics/detection for chronological and subgroup comparisons. Results: The number of malaria R&D activities have shown a trend of increase during the past 30 years, however these activities have fluctuated within the past few years. During the past 10 years, R&D on drug/drug resistance accounted for the highest percentages of research programmes (32.4%), articles ( 55.0% in PubMed and 50.6% in Chinese databases) and patents (45.5%). However, these R&D activities were mainly related to artemisinin. R&D on immunology/vaccines has been a continuous interest for China's public entities, but the focus remains on basic science. R&D in the area of high-efficiency diagnostics has been rarely seen or reported in China. Conclusions: China has long been devoted to malaria R&D in multiple areas, including drugs, drug resistance, immunology and vaccines. R&D on diagnostics has received significantly less attention, however, it should also be an area where China can make a contribution. More focus on malaria R&D is needed, especially in the area of diagnostics, if China would like to contribute in a more significant way to global malaria control and elimination.
Funding bodies have tended to encourage collaborative research because it is generally more highly cited than sole author research. But higher mean citation for collaborative articles does not imply collaborative researchers are in general more research productive. This article assesses the extent to which research productivity varies with the number of collaborative partners for long term researchers within three Web of Science subject areas: Information Science & Library Science, Communication and Medical Informatics. When using the whole number counting system, researchers who worked in groups of 2 or 3 were generally the most productive, in terms of producing the most papers and citations. However, when using fractional counting, researchers who worked in groups of 1 or 2 were generally the most productive. The findings need to be interpreted cautiously, however, because authors that produce few academic articles within a field may publish in other fields or leave academia and contribute to society in other ways.
Child protection continues to be a pressing social problem. Robust and relevant research is essential in order to ensure that the scale and nature of child maltreatment are understood and that preventative and protective measures are effective. This paper reports selected results from a mapping review of research conducted in the UK and published between January 2010 and December 2014. The purpose of the review was twofold: to develop a typology of child protection research; and to use this typology to describe the features and patterns of empirical research undertaken recently in the UK in order to inform a future research agenda. The paper reports the maltreatment types, substantive topics and research designs used within empirical research published in academic journals. It identifies a number of challenges for the field including the need for conceptual clarity regarding types of abuse, greater methodological diversity and a shift of focus from response to prevention of child maltreatment. The importance of a national strategic agenda is also emphasised. Copyright (C) 2016 John Wiley & Sons, Ltd.
Smart-metering allows electricity utilities to provide consumers with better information on their energy usage and to apply time-of-use pricing. These measures have been shown to reduce electricity consumption and induce time-shifting of demand. Less is known about how they affect residential energy efficiency investment behaviour. We use data from a randomised-controlled trial on a sample of almost 2500 Irish consumers, conducted over a 12-month period to investigate the effect of smart-metering and residential feedback on household investment behaviour. The results show that exposure to time-of-use pricing and information stimuli, while reducing overall and peak usage, can also have the unintended effect of reducing investment in energy efficiency measures within the home. Our findings indicate that households exposed to treatment were less likely to adopt any energy saving measure (23-28 % on average), and those households adopted less energy saving features than those in the control group (15-21 % on average). This result highlights the potential for behavioural interventions to have unintended consequences on behaviours other than those specifically targeted. Furthermore, it underlines the importance of examining a wider range of outcomes and allowing longer time-scales when evaluating this type of experiment.
Background: Adverse childhood experiences (ACEs) including child abuse and household problems (e.g. domestic violence) increase risks of poor health and mental well-being in adulthood. Factors such as having access to a trusted adult as a child may impart resilience against developing such negative outcomes. How much childhood adversity is mitigated by such resilience is poorly quantified. Here we test if access to a trusted adult in childhood is associated with reduced impacts of ACEs on adoption of health-harming behaviours and lower mental well-being in adults. Methods: Cross-sectional, face-to-face household surveys (aged 18-69 years, February-September 2015) examining ACEs suffered, always available adult (AAA) support from someone you trust in childhood and current diet, smoking, alcohol consumption and mental well-being were undertaken in four UK regions. Sampling used stratified random probability methods (n = 7,047). Analyses used chi squared, binary and multinomial logistic regression. Results: Adult prevalence of poor diet, daily smoking and heavier alcohol consumption increased with ACE count and decreased with AAA support in childhood. Prevalence of having any two such behaviours increased from 1.8% (0 ACEs, AAA support, most affluent quintile of residence) to 21.5% (>= 4 ACEs, lacking AAA support, most deprived quintile). However, the increase was reduced to 7.1% with AAA support (>= 4 ACEs, most deprived quintile). Lower mental well-being was 3.27 (95% Cls, 2.16-4.96) times more likely with >= 4 ACEs and AAA support from someone you trust in childhood (vs. 0 ACE, with AAA support) increasing to 8.32 (95% Cls, 6.53-10.61) times more likely with = 4 ACEs but without AAA support in childhood. Multiple health-harming behaviours combined with lower mental well-being rose dramatically with ACE count and lack of AAA support in childhood (adjusted odds ratio 32.01, 95% Cls 18.31-55. 98, >= 4 ACEs, without AAA support vs. 0 ACEs, with AAA support). Conclusions: Adverse childhood experiences negatively impact mental and physical health across the life-course. Such impacts may be substantively mitigated by always having support from an adult you trust in childhood. Developing resilience in children as well as reducing childhood adversity are critical if low mental well-being, health-harming behaviours and their combined contribution to non-communicable disease are to be reduced.
Relationships between the corticotropin-releasing hormone receptor 1 (CRHR1) [rs878886] and serotonin transporter promoter polymorphism (5-HTTLPR), with resilience and satisfaction with life were examined in 172 adolescents; 70 refugee adolescents living in the Netherlands and 102 non-refugee (Dutch) adolescents. Genetic variation in the CRHR1 was related with self-reported resilience and satisfaction with life, while the 5-HTTLPR polymorphism was not. These findings did not depend on being a refugee or a non-refugee (Dutch) adolescent and did hold after accounting for age, number of exposures to potentially traumatic events and gender. This implies that adolescents who are G-allele carriers of CRHR1 (rs878886) might be more susceptible to mental health problems following trauma, further suggesting innate differences in CRHR1 as a factor in resilience. (C) 2017 Elsevier Ltd. All rights reserved.
Child abuse is associated with a number of negative psychosocial outcomes, including mental health problems, substance abuse, and interpersonal violence. Yet some children thrive or "adapt well" despite experiencing abuse; researchers are increasingly interested in the protective factors and mechanisms that may prevent negative outcomes. The purpose of this study was to explore the role of resiliency characteristics in the relationship between childhood abuse and the negative outcomes of depression, posttraumatic stress disorder (PTSD), substance abuse, and revictimization in adolescent girls involved in child welfare. Participants were 237 adolescent girls ages 12-19 years (M = 14.9, SD = 1.6), and who were youths of color (75%) and white (25%). Data were collected through surveys assessing histories of physical, sexual, and emotional child abuse; symptoms of post traumatic stress and depression; lifetime substance use; and experiences of physical, verbal, and relational revictimization in the last three months. All forms of childhood abuse were significantly associated with symptoms of depression and PTSD as well as revictimization and substance use. Higher levels of resiliency were associated with fewer depression and PTSD symptoms and experiencing less revictimization. Resiliency significantly moderated the relationship between sexual abuse and depression, PTSD, and revictimization. Resiliency also moderated the relationship between emotional abuse and depression. No significant interactions emerged in the relationship between physical abuse and any of the mental health and behavioral problems. This study suggests that resiliency may serve as a protective factor in the relationship between abuse (sexual and emotional) and depression, PTSD, and revictimization during adolescence. (C) 2016 Elsevier Ltd. All rights reserved.
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor. The number of reported mutations is extremely variable, depending on the steroid receptor, ranging from 3 for the estrogen receptor to more than 500 for the androgen receptor. Loss of function of others factors implicated on the steroid hormone signaling pathway, such as molecular chaperones or coactivators, might also be involved in the pathogenesis of steroid resistance. Therapy is essentially symptomatic, there is currently no pharmacological strategy enabling restoration of the impaired hormone signaling pathway. Identification of steroid resistance syndrome and their characterization should allow a better understanding of underlying molecular defects, opening new avenues for the development of novel alternative options for the disease management. (C) 2016 Published by Elsevier Masson SAS. All rights reserved.
The pleiotropic drug resistance 5 gene (pdr5) encodes a multidrug membrane transporter and plays a very important role in the efflux of a broad range of chemicals in yeast cells. To study the possible function of pdr5 in insect cells, two stably pdr5-transformed lepidopteran insect cell lines, Sf21 and CF-203, were developed. Transcripts of pdr5 were detected in these two lines using Northern blotting and RT-PCR analysis. When cells were treated with the protein synthesis inhibitor diacetoxyscirpenol, the transformed Sf21. and CF-203 cell lines showed increased tolerance to this chemical. However, unlike in yeast cells, ecdysone agonist RH5992 could not be excluded by PDR5, probably because of low expression levels or imperfect incorporation of the recombinant protein in these transformed cell lines.
Objective: Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human. Methods and results: Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytcs/ macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10-100 ng/mL for 4 similar to 24 b). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3-2.5 (p < 0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p < 0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration. Conclusions: Resistin secreted from macrophages may contribute to atberogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
One of the most efficient ways to connect a resistive sensor array is using columns and rows in a 2-D structure. The main problem in this implementation is crosstalk appearing due to non-idealities in the readout circuits. Crosstalk causes measurement errors which restrict the usable range in array size or resistive sensors values. This paper analyses the way in which these factors affect accuracy, setting out a new approach to eliminate or reduce their influence based on just an additional operational amplifier and some calibration resistors without a significant increase in readout time. The first method involves introducing an additional column in order to eliminate the combined effect of the output resistance buffers for row selection, offset voltages and bias current of the operational amplifier. In the second method, a row of resistors is added in order to reduce the effect of finite gains. Theoretical analysis has been performed and validated by simulation. Results show that an improvement in accuracy compared with other proposals in the literature is possible.
By sharing rows and columns, the 2-D networked resistive sensor arrays simplified the interconnect complexity but suffered from the crosstalk problem among its elements. The crosstalk was mainly affected by the multiplexers' resistor, adjacent column elements, adjacent row elements, and array size. First, we designed an improved isolated drive feedback circuit (IIDFC) using one operational amplifier to reduce the crosstalk caused by the adjacent column elements in the 2-D networked resistive sensor array. Then, a mathematical equivalent resistance expression of the element being tested (EBT) for this circuit was analytically derived. Then, the IIDFC and its equivalent resistance expression of the EBT were evaluated by the simulations. The simulation results show that the IIDFC can greatly reduce the crosstalk error caused by the adjacent column elements in the 2-D networked resistive sensor array with the row-column fashion and its resistance expression of the EBT can be used as a general formula to evaluate the performance of the IIDFC.
Previous studies for measuring the high direct voltage focused on the resistive voltage divider or the hall voltage sensor. The cost of the hall voltage sensor is expensive and additional shielding method must be taken into account when using the voltage divider. In this paper, resistive voltage divider, integrated operational amplifiers and photocouplers are used cooperatively to design the 1kV DC voltage measurement circuit. Two photocouplers are used together with each current transfer ratio (CTR) balance each other out to reduce the influences on the high input direct voltage and the low output direct voltage ratio. The experimental results, with carefully setting the offset and gain calibration values, show that measurement circuit can get a good measurement accuracy with low cost for solar energy system.
This study presents the design and performance evaluation of the digital control adapted to an LLC series resonant dc-to-dc converter operating with wide input and load variations. The proposed control design correctly incorporates the wide-varying power stage dynamics and variable small-signal gain of a digitally controlled oscillator, thereby offering satisfactory converter performance for all the operational conditions. The proposed digital controller adopts the push-pull mode control scheme, which executes the control action two times in one switching period, to minimise the time delay and enhance the performance. Using a 150 W experimental converter, the performance of the proposed push-pull mode digital control is demonstrated in comparison with that of the conventional complementary mode digital control, which performs the control action only once in one switching period.
LC parallel resonance circuit, the equivalent impedance is purely resistive and the value of the maximum, by using this feature, the resonant circuit in the integrated operational amplifier feedback resistor position, can be at the resonant frequency to achieve specific signal of a frequency selection amplifying. This design is mainly by the attenuation frequency selection network, a frequency selection amplifying module and automatic gain control module, the two integrated operational amplifier and frequency selection network combination, to achieve stable resonant amplification, amplification of up to 81dB, resonant frequency of 15MHz; by using 3.6V single power supply, the power consumption is only 320mW, observed in the spectrum analyzer waveform of high Q value, the smaller rectangle coefficient, frequency offset in 100KHz, 3dB bandwidth in the 300KHz, the whole system has stable output, no excitation signal output.
The main goal of radiotherapy is to destroy the tumor while minimizing harm to nearby healthy tissue. Advances in the digital control have enabled planning and performing accurate treatments. However, todays technology is unable to compensate respiration induced motion, and therefore, ensure sufficient precision. One of the tasks in compensating respiratory motion is predicting position of the functional target ( tumor) from an external marker during fraction. Performance of techniques, such as Pearson correlation, Gaussian filters, Fourries transformation, cross correlation, linear interpolation and partial-least squares, still leave plenty space for the improvement. We reports results of work in progress, i.e. experiments of applying different types of regressions to predict motion of functional target from different external markers. Results seem to be promising in most of the cases.
We explore the integration of societal issues in undergraduate training within the life sciences. Skills in thinking about science, scientific knowledge production and the place of science in society are crucial in the context of the idea of responsible research and innovation. This idea became institutionalized and it is currently well-present in the scientific agenda. Developing abilities in this regard seems particularly relevant to training in the life sciences, as new developments in this area somehow evoke the involvement of all of us citizens, our engagement to debate and take part in processes of change. The present analysis draws from the implementation of a curricular unit focused on science-society dialogue, an optional course included in the Biochemistry Degree study plan offered at the University of Porto. This curricular unit was designed to be mostly an exploratory activity for the students, enabling them to undertake in-depth study in areas/topics of their specific interest. Mapping topics from students' final papers provided a means of analysis and became a useful tool in the exploratory collaborative construction of the course. We discuss both the relevance and the opportunity of thinking and questioning the science-society dialogue. As part of undergraduate training, this pedagogical practice was deemed successful. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):46-52, 2017.
Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting-state functional connectivity between data-driven networks, or components (referred to as, inter-component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter-component connectivity at rest using a group-matched schizophrenia and control sample. We then assessed whether inter-component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity-symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter-component connectivity, a medial-fronto-temporal metric and an orbito-fronto-temporal metric were related to cognitive empathy. Moreover, the medial-fronto-temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. (C) 2016 Wiley Periodicals, Inc.
Background: The polyphenol resveratrol (RSV) is found in the skin of red grapes and has been reported to exhibit anticancer properties. The antitumor effects of RSV in the gastrointestinal tract have gained considerable interest due to the high exposure of this tissue to this dietary compound. One of the hallmarks of cancer cells is their particular metabolism mainly relying on glycolysis for ATP production rather than mitochondrial oxidative phosphorylation. Although RSV has been described to act as a calorie-restriction mimetic, modulating energy metabolism in normal tissues, little efforts have been done to study the effects of this polyphenol in the metabolism of cancer cells. Taking this into account, the aim of this study was to explore metabolic effects of this poly phenol in colon cancer. Methods: Oxygen consumption, ATP levels, Western blotting and other molecular biology techniques were carried out to characterize the metabolic signature of RSV in SW620 colon cancer cells. Results: Paradoxically, the cytotoxic effects of RSV were associated with an increase in oxygen consumption supported by mitochondrial biogenesis and increased fatty acid oxidation. This partial reversion of the Warburg effect was followed by hyperpolarization of mitochondria] membrane and ROS production, leading to an increased apoptosis. Conclusions: Our results propose that the anticancer mechanisms of RSV could reside in targeting cancer cell metabolism, promoting mitochondrial electron transport chain overload and, ultimately, increasing ROS production. General significance: These results shed new light into the anticancer mechanism of RSV supporting the ability of this compound in potentiating the effects of chemotherapy. (C) 2016 Elsevier B.V. All rights reserved.
In order to identify candidate cation channels important for retinal physiology, 28 TRP channel genes were surveyed for expression in the mouse retina. Transcripts for all TRP channels were detected by RT-PCR and sequencing. Northern blotting revealed that mRNAs for 12 TRP channel genes are enriched in the retina. The strongest signals were observed for TRPC1, TRPC3, TRPM1, TRPM3, and TRPML1, and clear signals were obtained for TRPC4, TRPM7, TRPP2, TRPV2, and TRPV4. In situ hybridization and immunofluorescence revealed widespread expression throughout multiple retinal layers for TRPC1, TRPC3, TRPC4, TRPML1, PKD1, and TRPP2. Striking localization of enhanced mRNA expression was observed for TRPC1 in the photoreceptor inner segment layer, for TRPM1 in the inner nuclear layer (INL), for TRPM3 in the INL, and for TRPML1 in the outer plexiform and nuclear layers. Strong immunofluorescence signal in cone outer segments was observed for TRPM7 and TRPP2. TRPC5 immunostaining was largely confined to INL cells immediately adjacent to the inner plexiform layer. TRPV2 antibodies stained photoreceptor axons in the outer plexiform layer. Expression of TRPM1 splice variants was strong in the ciliary body, whereas TRPM3 was strongly expressed in the retinal pigmented epithelium. (C) 2011 Elsevier Ltd. All rights reserved.
Background: Fractures are a frequent reason for emergency department visits and evaluation for abusive head trauma is an associated concern in infants. Recent guidelines have suggested that retinal examination may not be necessary in the absence of intracranial injury, but there is a lack of empirical evidence in infants < 1 year of age. Objective: Our aim was to evaluate the prevalence of retinal hemorrhages in infants with isolated long bone fractures. Methods: Retrospective chart review of infants < 1 year of age who presented to an urban, tertiary care pediatric hospital between January 2004 and April 2014 with the diagnosis of an acute long bone fracture or retinal hemorrhages. Patients were excluded for head injury, altered mental status, injury mechanism of motor vehicle accident, multiple fractures or injuries outside the fracture area. Patients were identified through trauma registry data and International Classification of Diseases codes. Results: One hundred and forty-six patients had isolated long bone fractures, of which 68 patients did not undergo a retinal examination and 78 patients had dilated eye examinations, with no patients identified as having retinal hemorrhages. There were 46 patients identified with retinal hemorrhages concerning for abuse. No patients with retinal hemorrhages had isolated long bone fractures. Conclusions: In infants < 1 year of age presenting with isolated long bone fractures, a dilated eye examination to evaluate for retinal hemorrhages is not likely to yield additional information. Our results support recent studies that a subset of children and infants may not require dilated eye examinations in the evaluation of possible abuse. (C) 2016 Elsevier Inc. All rights reserved.
A system is described for determination of discrete pulse train characteristics of multi spot laser delivery systems for retinal photocoagulation. While photodiodes provide an ideal detection mechanism, measurement artifacts can potentially be introduced by the spatial pattern of the delivered beam relative to a discrete photodiode element. This problem was overcome by use of an integrating sphere to produce a uniform light field at the site of the photodiode detector. A basic current driven photodiode detection circuit incorporating an operational amplifier was used to generate a signal captured by a commercially available USB interface device at a rate of 10 kHz. Studies were undertaken of a Topcon Pascal Streamline laser system with output at a wavelength of 577 nm (yellow). This laser features the proprietary feature of 'Endpoint Management'(TM) where pulses can be delivered as 100% of set energy levels with visible reaction on the retina and also at a reduced energy level to create potentially non visible but clinically effective lesions. Using the pulse train measurement device it was identified that the 'Endpoint Management'(TM) delivery mode of pulses of lower energy was achieved by reducing the pulse duration of pulses for non-visible effect pulses while maintaining consistent beam power levels within the delivered pulse profile. The effect of eye geometry in determining safety and effectiveness of multi spot laser delivery for retinal photocoagulation is discussed. (C) 2015 IPEM. Published by Elsevier Ltd. All rights reserved.
To investigate whether activation of the liver X receptors (LXRs) inhibits amyloid beta(1-40) (A beta(1-40)) induced inflammatory and senescent responses in human retinal pigment epithelial (RPE) cells. Confluent cultures of human primary RPE and ARPE-19 cells pretreated with 5 mu Ie of TO901317 (TO90), a synthetic agonist of LXR, or vehicle were incubated with 1 mu Ie of A beta(1-40) or A beta(40-1). The optimum concentrations of A beta(1-40) and TO90 were determined by cell viability assay. Pro-inflammatory cytokines IL-6, IL-8, MCP-1 were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Expression and localization of an aging protein p16INK4a (p16) were analyzed by western blotting and immunofluorescence. Expressions of LXRs and one of their target genes ATP-binding cassette transporter A1 (ABCA1) were examined by real-time PCR and western blotting. Phosphorylated transcription inhibition factor-kappa B-alpha (p-I kappa B-alpha) was assessed by western blotting. A negative linear relationship between the A beta(1-40) concentration and the cell viability was evident, indicating A beta(1-40) decreased ARPE-19 cell viability in a dose-dependent manner. A beta(1-40) enhanced the expression of IL-6, IL-8, MCP-1 as well as p16 in both RPE cell lines at both mRNA and protein levels, whereas TO90 counteracted the detrimental effects. TO90 upregulated the expression of LXR alpha and its target gene ABCA1, but it did not affect the expression of LXR beta. Meanwhile, TO90 inhibited the phosphorylation of I kappa B-alpha mediated by A beta(1-40) stimulation. Activation of the LXR alpha-ABCA1 axis may alleviate A beta(1-40) induced inflammatory and senescent responses in RPE cells. The beneficial effect appears associated with the inhibition of the NF-kappa B signaling pathway.
Background:High-mobility group proteins A (HMGA) are more abundant in rapidly dividing and transformed cells. These are a group of proteins regulating tumorigenesis and tumor invasion. Increased expression of HMGA1 and HMGA2 has been reported in various benign and malignant tumors. The aim of the present study was to analyze expression of HMGA1 and HMGA2 proteins in retinoblastoma.Methods:Protein expression of HMGA1 and HMGA2 in 80 formalin-fixed retinoblastoma tissues was performed by immunohistochemistry, and their mRNA expressions were analyzed on 40 fresh primary enucleated retinoblastoma samples by semiquantitative reverse transcription polymerase chain reaction. Results were then correlated with clinicopathologic parameters.Results:Immunohistochemical analysis of HMGA1 and HMGA2 was seen in 56.25% and 58.75% of retinoblastoma cases, respectively. mRNA expressions of HMGA1 and HMGA2 was found to be 57.55% and 62.5%, respectively. The mRNA results correlated well with immunostaining results. Expression of both HMGA1 and HMGA2 was significantly associated with choroidal invasion and poor tumor differentiation.Conclusions:HMGA1 and HMGA2 proteins may contribute to tumorigenesis of Rb. Expression of HMGA1 and HMGA2 predicts poor prognosis and could serve as a therapeutic target in the management of RB. Further experiments are needed to determine the role of these proteins as therapeutic targets in tumorigenesis.
Objective Several studies have reported that retinoic acid (RA) might be used to treat malignancies. The effects of RA are mediated by the RA receptor (RAR), and RAR/RAR especially acts as a tumor suppressor. However, little is known about its role in human endometrial cancer. Materials and Methods In this study, we examined the effects of all-trans RA (ATRA) on progression of human endometrial cancer cell line, RL95-2 and Hec1A. We then examined the expression of RAR and RAR in 50 endometrial cancer tissues by using immunohistochemistry. Results We found inhibitory effects of ATRA on cell proliferation, apoptosis, and migration in RL95-2 cells, but not in Hec1A cells. RAR or RAR knockdown individually could not cancel out the inhibition of cell proliferation by ATRA in RL95-2 cells, but simultaneous knockdown of RAR and RAR could block its effect on proliferation. RAR and RAR knockdown dose dependently reduced the inhibition of migration by ATRA, but the effect was more pronounced with RAR knockdown than with RAR knockdown. We confirmed that RAR gene was directly regulated by ATRA in microarray and real-time reverse transcription polymerase chain reaction. Furthermore, the RAR agonist (BMS453) significantly suppressed proliferation of RL95-2 cells. In immunohistochemical analysis, RAR expression was positively correlated with tumor grade, and RAR showed the opposite tendency in endometrial cancer. Conclusions Retinoic acid might have multiple antitumor effects, and RAR may be a potent therapeutic target in RA treatment for endometrial cancers.
Purpose To describe factors associated with RTW in patients 2-5 years after stroke. Methods Cross sectional study, including patients 2-5 years after hospitalization for a first-ever stroke, who were < 65 years and had been gainfully employed before stroke. Patients completed a set of questionnaires on working status and educational level, physical functioning (Frenchay Activities Index, FAI), mental functioning (Hospital Anxiety and Depression Scale, HADS), Coping Orientations to Problems Experienced, (COPE easy) and quality of life (Short-Form(SF)-36 and EQ(Euroqol)-5D). Caregivers completed the Caregiver Strain Index (CSI). Baseline stroke characteristics were gathered retrospectively. Baseline characteristics and current health status were compared between patients who did and did not RTW by means of logistic regression analysis with odds ratios (OR) and 95 % confidence intervals (CI), adjusted for age and gender. Results Forty-six patients were included, mean age of 47.7 years (SD 9.7), mean time since stroke of 36 months (SD 11.4); 18 (39 %) had RTW. After adjusting for age and gender a shorter length of hospitalization was associated with RTW (OR 0.87; CI 0.77-0.99). Of the current health status, a lower HADS depression score (0.76; 0.63-0.92), a less avoidant coping style (1.99; 0.80-5.00), better scores on the FAI (1.13; 1.03-1.25), the mental component summary score of the SF36 (1.07; 1.01-1.13), the EQ5D (349; 3.33-36687) and the CSI (0.68; 0.50-0.92) were associated with the chance of RTW. Conclusions A minority of working patients RTW after stroke; a shorter duration of the initial hospitalization was associated with a favorable work outcome. The significant association between work status and activities, mental aspects and quality of life underlines the need to develop effective interventions supporting RTW.
Dynamic pricing for network revenue management has received considerable attention in research and practice. Based on data obtained from a major hotel, we use a large-scale numerical study to compare the performance of several heuristic approaches proposed in the literature. The heuristic approaches we consider include deterministic linear programming with resolving and three variants of dynamic programming decomposition. Dynamic programming decomposition is considered one of the strongest heuristics and is the method chosen in some recent commercial implementations, and remains a topic of research in the recent academic literature. In addition to a plain-vanilla implementation of dynamic programming decomposition, we consider two variants proposed in recent literature. For the base scenario generated from the real data, we show that the method based on Zhang (2011) [An improved dynamic programming decomposition approach for network revenue management. Manufacturing Service Oper. Management 13(1): 35-52.] leads to a small but significant lift in revenue compared with all other approaches. We generate many alternative problem scenarios by varying capacity-demand ratio and network structure and show that the performance of the different heuristics can be strongly influenced by both. Overall, our paper shows the promise of some recent proposals in the academic literature but also offers a cautionary tale on the choice of heuristic methods for practical network pricing problems.
This paper proposes a hardware optimized low power three stage compensated operational amplifier with a capability of driving a wide range of capacitive loads ranging from 200pF to 5nF. The amplifier is compensated by implementing Embedded Capacitance Multiplier (CM) Compensation on the outer Miller capacitor of traditional Reverse Nested Miller Compensation (RNMC) with a feed forward stage. This provides a unity gain bandwidth (UGB) greater than 1MHz and phase margin greater than 60 degrees for the range of loads mentioned above. The circuit has a 100uW of DC power dissipation for a 2V supply. The proposed technique uses two compensation capacitances of 1pf and 500fF only. The design achieves a unity gain bandwidth of 9.227MHz at 500pF capacitive load. The simulation is carried for 180nm CMOS technology in Cadence Virtuoso environment.
Containing high salinity and biotoxic organic compounds, reverse osmosis (RO) concentrate from municipal wastewater treatment plants has high environmental risks. The aim of this study was to investigate the feasibility of RO concentrate treatment using the microbial electrolysis desalination and chemical production cell (MEDCC). RO concentrate Was put into the desalination chamber. Both acid production and cathode chambers contained with 1 g/L NaCl. Within 18 h operation, the maximum desalination rate of 86 +/- 7% and no significant COD removal in the RO concentrate were achieved in the MEDCC, although the humic-like and fulvic acid-like organic compoundscould transfer from the desalination chamber into the acid-production chamber. The minimum and maximum pH in the acid-production and cathode chambers reached 1.08 +/- 0.06 and 12.2 +/- 0.10, respectively. The average total energy consumption was 6.51 +/- 0.17-9.81 +/- 0.23 kWh/m(3), among which 37%-61% was provided by the bioenergy from substrate utilization. The acid and alkali recovery, COD rejection in the treated RO concentrate and low electricity consumption in the MEDCC indicate that MEDCC may be a novel method for RO concentrate treatment in practical applications. (C) 2017 Elsevier B.V. All rights reserved.
Background: To date, research about revictimization has mainly focused on sexual revictimization, revealing that childhood sexual abuse increases the risk of exposure to sexual violence in adulthood. Co-occurring physical abuse during childhood similarly increases the risk of sexual revictimization. However, there is a research gap concerning physical revictimization and the specific effect of different forms of child abuse (sexual, physical, and emotional) on being revictimized. Objective: The present study aims at investigating the specific relationship between different subtypes of childhood abuse and different forms of exposure to violence in adulthood. Method: In all, 142 female participants (aged 19-66 years) completed online questionnaires capturing their sexual, physical, and emotional abuse histories during child and adulthood, as well as current symptoms of posttraumatic stress disorder (PTSD) and depression. Results: Linear regression analysis revealed that sexual and physical childhood abuse are specific predictors of sexual victimization in adulthood (standardized beta coefficient = .49*** and .20*, respectively). Physical and emotional maltreatment, on the other hand, are specifically associated with physical victimization in adulthood (standardized beta coefficient = .67*** and .20**, respectively). Conclusion: On the basis of the present findings, we can assume that particular subtypes of childhood abuse are associated with an increased risk of experiencing specific forms of violence as adults. This result has important clinical implications in particular with respect to the development of effective treatment and prevention programs for survivors of childhood abuse.
The system is made by the connection of broadband amplifier OPA847, current-feedback operational amplifier OPA695, attenuation network, filter circuit and MCU gain control module. In the first stage, the system can achieve 2 times fixed-gain by OPA847. Then, in the intermediate stage, it is made by the connection of two OPA847 to achieve 5 times gain. in the latter part, the system achieves 21 similar to 100V//V gain variation by OPA695 and T attenuation network. In the last stage, the system achieves the gain reduction by the high-pass filter network, AT89C52 is used to control the gain adjustment of this system, as well as the real-time display of the present output voltage gain. The range of the gain is 12dB similar to 40dB, changed by 4dB step-by-step. After testing, the whole system has stable performance and good control.
Objective To perform a population-based study in rheumatoid arthritis (RA) patients, in order to evaluate the efficacy and safety of pharmacologic treatments. Methods 1087 patients with RA were enrolled; inclusion criteria were: newly diagnosed RA, already diagnosed RA with high disease activity (HDA) (DAS28 >= 4.2) starting biologic DMARDs (bDMARDs), already diagnosed RA with HDA continuing with conventional DMARDs (cDMARDs). The following data were collected: demographics, clinical and laboratory features, imaging and prescribed drugs. All parameters except immunology and imaging (performed yearly) were repeated at each follow-up evaluations (after 3, 6 and 12 months, and thereafter every 12 months). In order to evaluate clinical response, the EULAR response criteria were used as the gold standard. Results 414 (38.1%) newly diagnosed patients with RA, 477 (43.9%) RA patients who started bDMARDs and 196 (18.0%) RA patients who continued with cDMARDs were enrolled from April 2012 to March 2015 at 12 Rheumatology Centres in the Emilia Romagna Region. Statistical analyses showed a relative risk ratio (RRR) for moderate response of 1.65 in RA patients who started bDMARDs (p=0.16) and 2.49 for newly diagnosed RA (p=0.01). Sex, age and Health Assessment Questionnaire were not statistically significant. A RRR of 2.00 has been confirmed for RA patients who started bDMARDs (p<0.0005) for a good response as well as 2.20 for newly diagnosed RA (p<0.0005). An increase in adverse events among bDMARDs was found, but when looking at infections or neoplasia, no differences were highlighted between RA which started bDMARDs and RA who continued with cDMARDs. Conclusion Our results are in line with already published papers from British and Swedish Registries: a greater likelihood to have a good response is demonstrated for not longstanding RA starting cDMARDs or RA with HDA when a bDMARD is started. Also a good safety profile is demonstrated.
Objectives: To prospectively evaluate the immunogenicity of a 13-valent conjugated pneumococcal vaccine (PCV13) in rheumatoid arthritis (RA) patients undergoing etanercept therapy. Methods: Twenty-two RA patients treated with etanercept (ETA) in combination with methotrexate (MTX) (n=15) or monotherapy (n=7) for at least one year were included. Altogether 24 osteoarthritis patients not receiving biological or MTX therapy, treating only NSAIDs or analgesics served as controls. All subjects were vaccinated with a single dose (0.5 ml) of the PCV13. Pneumococcal antibody levels at baseline, 4 and 8 weeks were assessed by a VaccZyme (TM) Anti-PCP IgG Enzyme Immunoassay Kit. Based on recommendations of the American Academy of Allergy, Asthma & Immunology, an at least two-fold increase in antibody level, as the protective antibody response (pAR) was an indicator of responsiveness (i.e., ratio of postvaccination and prevaccination antibody levels). The antibody levels and their ratios were analysed in a variety of different ways, vaccine safety parameters (fever, infections, changes in regular antirheumatic treatments) were assessed at baseline, 4 and 8 weeks after vaccination. Results: Four weeks after vaccination, the anti-pneumococcal antibody levels significantly increased in both groups. At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline. Compared with postvaccination levels at 4 and 8 weeks between two groups, the mean protective antibody levels were higher in control group (1st month P=0.016; 2nd month: P=0.039). Possible predictors of pAR were analysed by logistic regression model. In RA, increases of antibody levels at week 8 compared to baseline exerted a negative correlation with age, (Spearman's R=-0,431; P=0.045). There were no clinically significant side effects or reaction after administration of vaccine observed in any of these patients after the 2-month follow-up period, all patients medical condition were stable. Conclusions: In RA patients treated with ETA, vaccination with PCV13 is effective and safe, resulting in pAR one and two months after vaccination. Higher age at vaccination was identified as predictors of impaired pAR. The efficacy of vaccination may be more pronounced in younger RA patients. The vaccine is safe in RA patients on ETA. (C) 2016 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Shikonin, a major effective component in the Chinese herbal medicine Lithospermum erythrorhizon Sieb., exhibits an anti-inflammatory property towards rheumatoid arthritis (RA), but the potential mechanism is unclear. Our aim was to investigate the mechanism of shikonin on the lipopolysaccharide (LPS)-induced fibroblast-like synoviocyte (LiFLS) inflammation model. Fibroblast-like synoviocytes (FLSs) were treated with 200 mu g/ml of LPS for 24 h to establish the RA-like model, LiFLS. FLSs were pretreated with shikonin (0.1-1 mu M) for 30 min in the treatment groups. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect mRNA and protein levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha. Signal proteins involved in IL-10 production were analyzed by Western blotting. Shikonin significantly reversed the inhibitory effects of LPS on IL-10 expression in FLSs by inactivating the PKC-NF-kappa B pathway. In addition, shikonin inhibited LPS-induced TNF-alpha expression in FLSs, and this effect was markedly diminished by IL-10-neutralizing antibody. The IL-10-mediated suppression of TNF-alpha transcription was demonstrated by no response to the protein synthesis inhibitor cyclohexamide and no mRNA decay. Shikonin inhibits LPS-induced TNF-alpha production in FLSs through suppressing the PKC-NF-kappa B-dependent decrease in IL-10, and this study also highlights the potential application of shikonin in the treatment of RA.
Background: Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). Method: RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls. Results: There were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples. Conclusion: Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.
The Arthritis Self-Efficacy Scale-8 (ASES-8) is a valid tool to measure patients' arthritis-specific self-efficacy. However, evidence about reliability and validity of the ASES-8 in Chinese arthritis patients is lacking. This study aimed to culturally adapt and test the psychometric properties of the Chinese version of the ASES-8. Chinese ASES-8 was translated from original English version using translation and back-translation procedures. Validation survey was then conducted in a university-affiliated hospital by a set of questionnaires comprised Chinese ASES-8, pain-VAS, The Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), and Short Form 36-Item Health Survey (SF-36) physical functioning subscale. A convenience sample of 134 patients with rheumatoid arthritis was recruited from the department of rheumatology. Validity was assessed by Pearson's correlation analysis and exploratory factor analysis. Reliability was assessed using the intra-class correlation coefficient (ICC) and Cronbach's alpha. Exploratory factor analysis extracted one dimension that explained of the 71.35% variation. Significant negative correlations were found between the ASES-8 and pain-VAS, HADS-D, HADS-A scores (r -0.487 to -0.656, p < 0.01), while positive correlations were found between the ASES-8 and SF-36 PH (r = 0.561, p < 0.01), FACIT-F (r = 0.660, p < 0.01). Excellent test-retest reliability (ICC = 0.98) and internal consistency (Cronbach's alpha = 0.942) were demonstrated. The Chinese version of the ASES-8 had statistically acceptable levels of reliability and validity for assessing self-efficacy in patients with rheumatoid arthritis. This disease-specific scale is particularly valuable for use among patients with rheumatoid arthritis from the Chinese population.
Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed. Genetic changes and corresponding mechanisms caused by overexpressing Dvl2 in RA-FLSs were assessed. Dvl2 was found to be overexpressed in RA synovial tissue and RA-FLSs. Overexpression of Dvl2 increased apoptosis and inhibited inflammatory cytokine secretion by RA-FLSs in vivo and in vitro, and Dvl2 inhibited expression of antiapoptotic and inflammatory genes. One possible mechanism is that Dvl2 decreases the nuclear translocation of P65 and inhibits its ability to bind to the promoters of NF-kappa B target genes. Our findings reveal an underappreciated role of Dvl2 in regulating inflammation and RA-FLS apoptosis and provide insight into crosstalk between the Wnt and nuclear factor-kappa B (NF-kappa B) pathways.
As the prevalence and socioeconomic burden of allergic rhinitis is steadily increasing every year, it is essential that clinical practitioners diagnose and manage allergic rhinitis in an evidence-based manner. Therefore, the Korean Academy of Asthma, Allergy and Clinical Immunology developed new clinical guidelines for Korean patients and practitioners. We first performed a questionnaire survey to address the core questions, about which clinical practitioners are the most curious. A large group of physicians (allergists), pediatricians, and otorhinolaryngologists developed answers for those questions by performing a systematic literature review and determining the appropriate levels of recommendation. In this article, we propose 11 answers for core questions regarding the diagnosis and differential diagnosis of allergic rhinitis.
The social and economic burden of allergic rhinitis (AR) is increasing, with significant effects on the quality of life of patients suffering from AR. Therefore, physicians require evidence-based guidelines regarding the diagnosis, differential diagnosis and proper management management of patients with AR. The Korean Academy of Asthma, Allergy and Clinical Immunology developed new clinical guidelines for the appropriate management of AR, especially in Korean patients. For the core questions (i.e. questions that most practitioners were curious about), several experts in the field of allergology, pediatrics, and otorhinolaryngology developed a set of practical guidelines based on a systematic review of the literature. Furthermore, we determined the level of evidence associated with the recommendations for each answer. In this article, we suggest 15 answers for core questions about the medical treatment of AR.
Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 +/- 1.6 mu M. nzyme-linked immunosorbent assay and fluorescence quantitative polymeraSe chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor oc-, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor kappa B (NF-kappa B) activation by suppressing IxBa phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-KB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced" inflammation via the suppression of ROS-sensitive inflammatory signaling.
The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation. The effect of RHOG knockdown on DOCK1, VAV, and RAC1 expression was evaluated in the human ovarian cells (SKOV3), theca cells, and granulosa cells from SD rats with the help of flow cytometry. Oocyte at secondary follicles along with stromal cells showed optimal expression of RHOG. Immunoblotting of RHOG revealed its maximum expression at diestrus and proestrus, which was downregulated at estrus stage. Mild immunostaining of RHOG was also present in the theca and granulosa cells of the secondary and antral follicles. Polycystic ovary exhibited weak immunostaining for RHOG and that was corroborated by immunoblotting-based investigations. RHOG effectors DOCK1 and ELMO1 were found reduced in the ovary in PCOS condition/DHEA. RHOG silencing reduced the expression of DOCK1 and RAC1 in the theca and granulosa cells from SD rat antral follicles and that was mirrored in the human ovarian cells. Collectively, RHOG can mediate signaling through downstream effectors DOCK1 and RAC1 during ovarian follicular development (theca and granulosa cells and oocyte), but DHEA downregulated them in the PCOS ovary.
This study investigated the structural, biomechanical and fractographic features of rib fractures in a piglet model, to test the hypothesis that fist impact, apart from thoracic squeezing, may result in lateral costal fractures as observed in abused infants. A mechanical fist with an accelerometer was constructed and fixed to a custom jig. Twenty stillborn piglets in the supine position were impacted on the thoracic cage. The resultant force versus time curves from the accelerometer data showed a number of steps indicative of rib fracture. The correlation between impact force and number of fractures was statistically significant (Pearson's r=0.528). Of the fractures visualized, 15 completely pierced the parietal pleura of the thoracic wall, and 5 had butterfly fracture patterning. Scanning electron microscopy showed complete bone fractures, at the zone of impact, were normal to the axis of the ribs. Incomplete vertical fractures, with bifurcation, occurred on the periphery of the contact zone. This work suggests the mechanism of rib failure during a fist impact is typical of the transverse fracture pattern in the anterolateral region associated with cases of non-accidental rib injury. The impact events investigated have a velocity of similar to 2-3 m/s, approximately 2 x 10(4) times faster than previous quasi-static axial and bending tests. While squeezing the infantile may induce buckle fractures in the anterior as well as posterior region of the highly flexible bones, a fist punch impact event may result in anterolateral transverse fractures. Hence, these findings suggest that the presence of anterolateral rib fractures may result from impact rather than manual compression. (C) 2016 Elsevier Ltd. All rights reserved.
Sinorhizobium meliloti harbours genes encoding orthologs of ribonuclease (RNase) E and RNase J, the principle endoribonucleases in Escherichia coli and Bacillus subtilis, respectively. To analyse the role of RNase J in S. meliloti, RNA from a mutant with miniTn5-insertion in the RNase J-encoding gene was compared to the wild-type and a difference in the length of the 5.8S-like ribosomal RNA (rRNA) was observed. Complementation of the mutant, Northern blotting and primer extension revealed that RNase J is necessary for the 5'-end maturation of 16S rRNA and of the two 23S rRNA fragments, but not of 5S rRNA. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Plant microRNAs (miRNAs) play important roles as modulators of gene expression at the post-transcriptional level. Previous studies have shown that high-throughput sequencing is a powerful tool for the identification of miRNAs, and it is believed that many more miRNAs remain to be discovered. Here, we found 23 novel conserved miRNAs from three rice cultivars by high-throughput sequencing and further identified these through subsequent cloning and quantitative real-time polymerase chain reaction (qPCR). Eight of these novel miRNAs were detected with significant signals in the three rice cultivars by northern blotting assays. The quantitative analysis of their expression profiles showed that most of these miRNAs were perfectly or imperfectly negatively correlated with their target genes, which suggests that these miRNAs may play important roles during rice development. This is the first genome-wide investigation of miRNAs from different rice cultivars, and the data obtained expand the known rice miRNA inventory and provide further information about the regulatory roles played by miRNAs in rice development. (C) 2014 Elsevier B.V. All rights reserved.
Rice stripe virus (RSV) often causes severe rice yield loss in temperate regions of East Asia. Although the correlation of small interfering RNAs (siRNAs) with transgenic virus resistance of plants using RNA interference (RNAi) is known for decades, no systematical research has been done on the profiling of siRNAs from a genomic scale. Our research is aiming to systematically study the RNAi impact in RSV-resistant transgenic rice, which was generated by introducing an inverted repeat construct that targets RSV nucleocapsid protein (NCP) gene. In this paper, three independent RSV-resistant transgenic rice lines were generated, their stable integration of the T-DNA fragment and the expression of siRNAs were confirmed by Southern blotting and Northern blotting analyses, and the majority of siRNAs were in lengths of 21, 22, and 24 nucleotides (nt), which have validated a connection between the presence of the RSV NCP homologous siRNAs and the RSV resistance in those transgenic rice lines. In one of these transgenic lines (T4-B1), the T-DNA fragment was found to have been inserted at chromosome 1 of the rice genome, substituting the rice genome fragment from 32 158 773 to 32 158 787 nt. Bioinformatics analysis of small RNA-Seq data on the T4-B1 line also confirmed the large population of NCP-derived siRNAs in transgenic plants, and the RSV-infected library (T4-B1-V) possessed more siRNAs than its mock inoculated libraries (T4-B1-VF), these results indicating the inverted repeat construct and RSV could introduce abundance of siRNAs in transgenic rice. Moreover, a varied expression level of specific siRNAs was found among different segments of the NCP gene template, about 47% of NCP-derived siRNAs reads aligned with the fragment from 594 to 832 nt (239 nt in length) in NCP gene (969 nt in length) in the T4-B1-V, indicating a potential usage of hotspot regions for RNAi silencing in future research. In conclusion, as the first study to address the siRNA profile in RSV-resistant transgenic plant using next generation sequencing (NGS) technique, we confirmed that the massive abundance of siRNA derived from the inverted repeat of NCP is the major reason for RSV-resistance.
Metaphyseal changes in rickets and child abuse-related fractures may be difficult to distinguish; therefore, it is important to follow a standardized procedure in order to detect mineralization defects of the skeleton and differentiate them from healing fractures. We present a typical post-mortem case of rickets in a 3.5-year-old boy where different diagnostic tools were applied to confirm this condition. At autopsy a rachitic rosary was seen. Vitamin D insufficiency found in laboratory analyses, metaphyseal fraying in radiography and an accumulation of non-mineralized bone (osteoid) in undecalcified histological preparations led to the correct diagnosis. This case shows that the appropriate methodology to use undecalcified bone preparations is of paramount importance to detect mineralization defects. Moreover, as in this case which involved a combination of rickets and child abuse, the situation is often more complex where neglect and abuse may lead to vitamin D insufficiency.
Background: Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary. Methods: Immunohistochemistry staining, western blot analysis, and quantitative reverse transcription polymerase chain reaction were used to determine the mRNA and protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer stem-like cells were obtained from gastric cancer tumor and cell lines by tumorsphere culture. The adeno-associated virus system was used to upregulate RNF43 expression in cancer cells. Functional experiments including tumorsphere formation, chemotherapy resistance, surface marker detection, and tumor xenograft assay were performed to measure stem-like properties in gastric cancer stem-like cells after RNF43 overexpression. Results: RNF43 loss was significantly associated with TNM stage, distant metastasis, and Lauren classification, and predicted worse prognosis in gastric cancer patients. RNF43 expression was even lower in tumorspheres derived from tumor tissues or cell lines compared with adherent cancer cells and normal gastric cells. Overexpression of RNF43 in gastric cancer cells impaired their stem-like properties, including sphere formation ability, chemoresistance in vitro, and tumorigenicity in vivo. Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing cells, while Wnt pathway activators could reverse the trend to some extent. Conclusions: Our findings indicated that RNF43 might not only participate in gastric cancer progression, but also attenuate the stemness of gastric cancer stem-like cells through the Wnt/beta-catenin pathway.
The present study examines prevalence and correlates of exchanging sex for drugs, money, food shelter, or other favors (sex exchange) among a nationally representative sample of youth and young adults. Adolescents and young adults (n=11,620, 53% female, 47% male) from the National Longitudinal Study of Adolescent Health were used for the current sample. Participants completed in-home interviews at both waves. Results revealed that sex exchange was reported by 4.9% (n=569) of the population in wave 2 or wave 3, and 4.6% (n=26) of those who exchanged sex did so at both waves. More males reported exchanging sex than females (n=332 versus n=237). Respondents who reported child sexual abuse were more likely to exchange sex (95% CI 2.51-4.28, p<.05) than respondents who reported any other form of child abuse. Both males and females who engaged in sex exchange were at greater risk for sexually transmitted infections; however, the odds of ever exchanging sex were highest among males who ever had gonorrhea (OR=6.2; 95% CI 3.75-10.3). Although sex exchange has been studied extensively among homeless and runaway youth, the current study reveals sex exchange also occurs in the general population.
BACKGROUND: Reactions to rituximab occur frequently, with up to 77% of patients developing a reaction during initial exposure. The safety of rechallenging patients after a reaction is not clear and standard guidelines are lacking. OBJECTIVE: To better understand clinical decision making surrounding rituximab reactions and subsequent rechallenge. METHODS: We performed a 5-year retrospective review of all rituximab reactions at a large academic outpatient infusion center. Patients' demographic characteristics, clinical symptoms, and management of reactions were reviewed. Reaction severity was classified using standard criteria. RESULTS: Between June 2006 and January 2011, 67 patients (mean age, 58 +/- 13 years, 54% men) with at least 1 rituximab reaction were identified. Most reactions occurred during the first exposure to rituximab (63%). Most reactions (n = 59 [88%]) were grade 1 or 2. Fifty-one patients (n = 51 [88%]) were rechallenged with rituximab on the same day as the initial reaction. Most patients with a grade 1 reaction tolerated rechallenge. Conversely, all 4 patients with a grade 3 reaction had a reaction during rechallenge. The outcome of same-day rechallenge after an initial grade 2 reaction was varied; most patients (26 of 31 [84%]) tolerated same-day challenge, but 5 patients had a reaction (all grade 1-2 severity). CONCLUSIONS: Consistent with previous data, our observations suggest that patients who experience grade 1 reactions to rituximab can be safely rechallenged the same day. A grade 3 or 4 reaction should prompt referral to an allergy specialist for risk assessment before additional rituximab administration. Further research is needed to understand the optimal management of patients with grade 2 reactions. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background: Rituximab (RTX) is increasingly used in the treatment of neuromyelitis optica spectrum disorder (NMO-SD). Administration regimen is not consensual as there is no reliable biomarker of RTX efficacy. In most cases, after induction, RTX is administered systematically every 6 months. Objective: To assess efficacy and safety of a maintenance regimen based on CD19 + CD27 + memory B-cell (mBc) detection. Methods: We conducted a study in two French centers, including patients with NMO-SD who received an induction therapy with RTX. We compared the number of administered infusions, relapses and EDSS depending on two maintenance schemes (S1: administration of 1 g RTX infusion every 6 months or S2: a scheme based on regular mBc detection. 1 g RTX was administered if mBc was >0.05%) Results: 40 patients were included (mean age: 40.2 years, F/M sex ratio: 5/1). Aquaporin-4 antibodies were positive in 75% patients. Under S1 regimen, all patients received 2 infusions per year, whereas under S2, they received 1.62 infusion per year. The mean interval between infusions under S2 was 7.4 months, without decrease of clinical efficacy. Conclusion: In our study, mBc-based administration of RTX allowed personalizing treatment administration and in several cases to lower the cumulative dose without loss of efficacy. (C) 2017 Elsevier B.V. All rights reserved.
Aims: Immunoglobulin superfamily (IgSF) proteins play a critical role in development of the nervous system. Here, a new member of IgSF gene family was cloned from rat brain, which was subsequently identified as rat homolog of Drosophila Kirre. This new molecule was named as rat Kirre (rKirre). We aimed to reveal the developmental expression of rKirre, both at mRNA and protein levels, in the central nervous system. The deduced amino acid sequence of rKirre showed a putative PDZ binding motif at the C-terminus, which provided a rationale for analyzing the co-localization of rKirre and post-synaptic density protein 95 (PSD-95) in cultured rat cortical neurons. Main methods: cDNA library screening was used in the isolation of cDNA. Northern blotting and Western blotting were used to reveal the levels of rKirre expression. In situ hybridization and immuno-fluorescent staining were used to determine the localization of rKirre. Key findings: The rKirre gene was found to be highly expressed in the cerebrum, hippocampus, cerebellum, brain stem and spinal cord of adult rats. In parallel, the protein level of rKirre was also increased in a developing cerebral cortex. In cultured rat cortical neurons, the amount of rKirre was significantly increased during neuronal differentiation. Immuno-cytofluorescent staining indicated that rKirre was present along the neurites of cortical neurons, and was co-localized with PSD-95. Significance: These results suggested that rKirre might play an essential role in neuronal differentiation and development in the central nervous system. (c) 2011 Elsevier Inc. All rights reserved.
The exoribonuclease polynucleotide phosphorylase (PNPase, encoded by pnp) is a major player in bacterial RNA decay. In Escherichia coli, PNPase expression is post-transcriptionally regulated at the level of mRNA stability. The primary transcript is very efficiently processed by the endonuclease RNase III at a specific site and the processed pnp mRNA is rapidly degraded in a PNPase-dependent manner. While investigating the PNPase autoregulation mechanism we found, by UV-cross-linking experiments, that the ribosomal protein S1 in crude extracts binds to the pnp-mRNA leader region. We assayed the potential role of S1 protein in pnp gene regulation by modulating S1 expression from depletion to overexpression. We found that S1 depletion led to a sharp decrease of the amount of pnp and other tested mRNAs, as detected by Northern blotting, whereas S1 overexpression caused a strong stabilization of pnp and the other transcripts. Surprisingly, mRNA stabilization depended on PNPase, as it was not observed in a pnp deletion strain. PNPase-dependent stabilization, however, was not detected by chemical decay assay of bulk mRNA. Overall, our data suggest that PNPase exonucleolytic activity may be modulated by the translation potential of the target mRNAs and that, upon ribosomal protein S1 overexpression, PNPase protects from degradation a set of full-length mRNAs. It thus appears that a single mRNA species may be differentially targeted to either decay or PNPase-dependent stabilization, thus preventing its depletion in conditions of fast turnover.
An increase in the unspliced cox2 transcript and accompanying decrease in the frequency of RNA editing near the exon/intron junction (intron binding site 1, IBS1) have been reported in cold-treated wheat. Here, an attempt was made to clarify whether a similar phenomenon occurs in rice. Levels of unspliced cox2 transcript increased and its editing at the IBS was abolished after cold treatment. The accumulation of COXII protein remained unaffected. The accumulation of intron-containing transcripts of another eight mitochondrial genes, 23 introns in total, was analyzed by Northern blotting and semi-quantitative RT-PCR. An increase in 14 of the 23 intron-adjoining cDNA after cold treatment was observed. Six RNA editing sites in the IBS of four genes were tested as to their status by sequencing cDNA. One of these sites in the nad7 transcript showed a close association with splicing, with editing and splicing occurring simultaneously, irrespective of cold treatment. Two other sites in the intron-containing cox2 and rps3 transcripts were sensitive to cold, where editing frequency began to decrease 1 day after cold treatment, and finally exhibited a tight association with splicing 14 days later. The other sites were efficiently edited. The intron-spliced transcripts were fully edited at all six sites.
Aim: To study the effect of pSilencer 1.0-U6-siRNA-stat3 on the growth of human laryngeal tumors in nude mice. Methods: Hep2 cells were transplanted into nude mice, then at the time of tumor formation, growth rates were observed. After the tumor formed, pSilencer 1.0-U6-siRNA-stat3 was injected. Tumor volumes were calculated, and growth curves were plotted. Representative histological sections were taken from mice bearing transplantation tumors in both treated and control groups, and stat3, pTyr- stat3, Bcl-2, cyclin D1, and survivin expression were detected by Western blotting. survivin mRNA levels were detected by Northern blotting, hematoxylin and eosin staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay to confirm the apoptosis of tumors. Results: In nude mice, pSilencer 1.0-U6-siRNA-stat3 significantly suppressed the growth of tumors compared with controls (P < 0.01). In suppressed stat3 expression, and downregulated BcL2, cyclin D1, and survivin expression within the tumor. This significantly induced apoptosis of the tumors. Conclusion: pSilencer 1.0-U6-siRNA-stat3 was able to inhibit the growth of transplanted human laryngeal tumors in nude mice and induce apoptosis.
AIM: To inhibit the expression of vascular endothelial growth factor (VEGF) in colon cancer cell line by RNA interference (RNAi). METHODS: Followed the service of E-RNAi, we designed and constructed two kinds of shRNA expression vectors aiming at the VEGF gene, then transfected them into colon cancer HT29 cells by lipofectamine (TM) 2000. The level of VEGF mRNA was investigated by RT-PCR and Northern blotting. The protein expression of VEGF was observed by immunofluoresence staining and Western blotting. RESULTS: We got two kinds of VEGF specific shRNA expression vectors which could efficiently inhibit the expression of VEGF in HT29 cells. RT-PCR, Northern blotting, immunofluoresence staining and Western blotting showed that inhibition rate for VEGF expression was up to 42%, 89%, 73% and 82%, respectively. CONCLUSION: The expression of VEGF can be inhibited by RNA interference in HT29 cells.
We prepared total RNA from the Gram-positive soil bacterium Bacillus subtilis by different RNA extraction procedures to compare their suitability for Northern blot detection of tiny RNAs (similar to 14-mers) or RNAs of intermediate size (100-200 nt) in terms of signal quality, intensity, and reproducibility. Our analysis included two hot phenol methods and two TRIzol extraction procedures. We found that signal intensity/detection sensitivity makes the key difference. Total RNAs prepared by the hot phenol method comprise the length spectrum from tRNAs to large ribosomal RNAs. Larger RNAs are less abundant in TRIzol preparations which instead enrich for RNAs of tRNA size and smaller. Thus, hot phenol methods are the choice for the detection of intermediate-sized and longer RNAs, whereas TRIzol extraction procedures are more suited for the detection of tiny RNAs.
RNA silencing and suppression of silencing are host and virus interactions for defense and counter-defense. Here, we explored the function effect of HC-Pro encoded by Sugarcane mosaic virus (SCMV) on the suppression of RNA silencing. siRNA northern blotting assay indicated that the replication of SCMV was regulated by host RNA silencing machinery. Co-expression assay demonstrated that the HC-Pro encoded by SCMV suppressed the RNA silencing induced by sense RNA and dsRNA. Transitive RNA silencing assay showed that HC-Pro down-regulated the accumulation of 3' secondary siRNA, but not 5' secondary and primary siRNA. Meanwhile, the 2b gene of Tomato aspermy cucumovirus (Tav) evidently down-regulated the accumulation of 5' secondary siRNA. Importantly, we found that HC-Pro and Tav2b down-regulated the accumulation of RDR6 mRNA. Thus, HC-Pro, an RNA silencing suppressor encoded by SCMV, regulates the accumulation of different siRNAs and has more than one target in the RNA silencing pathway. (c) 2008 Elsevier Inc. All rights reserved.
In eukaryotes, RNA silencing encompasses a range of biochemical processes mediated by similar to 20-25 nt small RNAs (smRNAs). This chapter describes northern blot hybridization techniques optimized for detection of such smRNAs, whether extracted from plant or animal tissues. The basic protocol is described, and control blots illustrate the detection specificity and sensitivity of this method using DNA oligonucleotide probes. Known endogenous smRNAs are analyzed in samples prepared from several model plant species, including Arabidopsis thaliana, Nicotiana benthamiana, Oryza sativa, Zea mays, and Physcomitrella patens, as well as the animals Drosophila melanogaster and Miss musculus. Finally, the usefulness of northern blotting in dissecting smRNA biogenesis is shown for the particular case of DNA virus infection.
We describe a method to facilitate electrophoretic separation of high-molecular-weight RNA species, such as ribosomal RNAs and their precursors, on agarose-formaldehyde gels. Two alternative "pK-matched" buffer systems were substituted for the traditionally used Mops-based conductive medium. The key advantages include shortened run times, a 5-fold reduction in formaldehyde concentration, a significantly improved resolution of long RNAs, and consistency in separation. The new procedure has a streamlined work flow that helps to minimize errors and is broadly applicable to agarose gel electrophoresis of RNA samples and their subsequent analysis by Northern blotting. (c) 2013 Elsevier Inc. All rights reserved.
Quantification of gene expression provides valuable information regarding the response of cells or tissue to stimuli and often is accomplished by monitoring the level of messenger RNA (mRNA) being transcribed for a particular protein. Although numerous methods are commonly used to monitor gene expression, including Northern blotting, real-time polymerase chain reaction, and RNase protection assay, each method has its own drawbacks and limitations. Capillary electrophoresis with laser-induced fluorescence (CE-LIF) can reduce protocol time, eliminate the need for radioactivity, and provide superior sensitivity and dynamic range for quantification of RNA. In addition, CE-LIF can be used to directly determine the amount of an RNA species present, something that is difficult and not normally accomplished using current methods. Gene expression is detected using a fluorescently labeled riboprobe specific for a given RNA species. This direct approach was validated by analyzing levels of 28S RNA and also used to determine the amount of discoidin domain receptor 2 mRNA in cardiac tissue. (c) 2006 Elsevier Inc. All rights reserved.
Dnop5 is a member of the conserved nop5/sik1 gene family, which encode components of small nucleolar ribonucleoprotein( snoRNP) complexes. To study the function of DNop5, we generated the polyclonal antibody and determined its expression pattern. It is highly expressed in different periods of the Drosophila development. We used heritable RNA interference (RNAi) in combination with the yeast GAL4/UAS binary system to knock down the DNop5 protein. It resulted in lethality and dramatic somatic anomalies in RNAi mutant fly, in which the DNop5 protein is reduced efficiently. Northern blotting showed that the processing of 18S rRNA was disrupted in DNop5 knock down fly, but 28S rRNA is normal. These results suggest that DNop5 is essential for the Drosophila growth and function in the execution of early pre-rRNA processing steps that lead to formation of 18S rRNA.
The tombusvirus P19 VSR (viral suppressor of RNA interference) binds siRNAs with high affinity, whereas the Flockhouse Virus (FHV) B2 VSR binds both long double-stranded RNA (dsRNA) and small interfering RNAs (siRNAs). Both VSRs are small proteins and function in plant and animal cells. Fusing a Nuclear Localization Signal (NLS) to the N-terminus shifts the localization of the VSR from cytoplasmic to nuclear, allowing researchers to specifically probe the subcellular distribution of siRNAs, and to investigate the function of nuclear and cytoplasmic siRNAs. This chapter provides a detailed protocol for the immunoprecipitation of siRNAs bound to epitope-tagged VSR and subsequent analysis by 3'-end-labeling using cytidine-3',5'-bis phosphate ([5'-P-32]pCp) and northern blotting.
Background: The gutless marine worm Olavius algarvensis has a completely reduced digestive and excretory system, and lives in an obligate nutritional symbiosis with bacterial symbionts. While considerable knowledge has been gained of the symbionts, the host has remained largely unstudied. Here, we generated transcriptomes and proteomes of O. algarvensis to better understand how this annelid worm gains nutrition from its symbionts, how it adapted physiologically to a symbiotic lifestyle, and how its innate immune system recognizes and responds to its symbiotic microbiota. Results: Key adaptations to the symbiosis include (i) the expression of gut-specific digestive enzymes despite the absence of a gut, most likely for the digestion of symbionts in the host's epidermal cells; (ii) a modified hemoglobin that may bind hydrogen sulfide produced by two of the worm's symbionts; and (iii) the expression of a very abundant protein for oxygen storage, hemerythrin, that could provide oxygen to the symbionts and the host under anoxic conditions. Additionally, we identified a large repertoire of proteins involved in interactions between the worm's innate immune system and its symbiotic microbiota, such as peptidoglycan recognition proteins, lectins, fibrinogen-related proteins, Toll and scavenger receptors, and antimicrobial proteins. Conclusions: We show how this worm, over the course of evolutionary time, has modified widely-used proteins and changed their expression patterns in adaptation to its symbiotic lifestyle and describe expressed components of the innate immune system in a marine oligochaete. Our results provide further support for the recent realization that animals have evolved within the context of their associations with microbes and that their adaptive responses to symbiotic microbiota have led to biological innovations.
The brain plays a central role in organismal aging but is itself most sensitive to aging-related functional impairments and pathologies. Insights into processes underlying brain aging are the basis to positively impact brain health. Using high-throughput RNA sequencing and quantitative polymerase chain reaction (PCR), we monitored cerebral gene expression in mice throughout their whole lifespan (2, 9, 15, 24, and 30 months). Differentially expressed genes were clustered in 6 characteristic temporal expression profiles, 3 of which revealed a distinct change between 24 and 30 months, the period when most mice die. Functional annotation of these genes indicated a participation in protection against cancer and oxidative stress. Specifically, the most enriched pathways for the differentially expressed genes with higher expression at 30 versus 24 months were found to be glutathione metabolism and chemokine signaling pathway, whereas those lower expressed were enriched in focal adhesion and pathways in cancer. We therefore conclude that brains of very old mice are protected from certain aspects of aging, in particular cancer, which might have an impact on organismal health and lifespan. (C) 2017 Elsevier Inc. All rights reserved.
Background: Contamination is a well-known but often neglected problem in molecular biology. Here, we investigated the prevalence of cross-contamination among 446 samples from 116 distinct species of animals, which were processed in the same laboratory and subjected to subcontracted transcriptome sequencing. Results: Using cytochrome oxidase 1 as a barcode, we identified a minimum of 782 events of between-species contamination, with approximately 80% of our samples being affected. An analysis of laboratory metadata revealed a strong effect of the sequencing center: nearly all the detected events of between-species contamination involved species that were sent the same day to the same company. We introduce new methods to address the amount of within-species, between-individual contamination, and to correct for this problem when calling genotypes from base read counts. Conclusions: We report evidence for pervasive within-species contamination in this data set, and show that classical population genomic statistics, such as synonymous diversity, the ratio of non-synonymous to synonymous diversity, inbreeding coefficient FIT, and Tajima's D, are sensitive to this problem to various extents. Control analyses suggest that our published results are probably robust to the problem of contamination. Recommendations on how to prevent or avoid contamination in large-scale population genomics/molecular ecology are provided based on this analysis.
Deep-sequencing of bacterial transcriptomes using RNA-Seq technology has made it possible to identify small non-coding RNAs, RNA molecules which regulate gene expression in response to changing environments, on a genome-wide scale in an ever-increasing range of prokaryotes. However, a simple and reliable automated method for identifying sRNA candidates in these large datasets is lacking. Here, after generating a transcriptome from an exponential phase culture of Mycobacterium tuberculosis H37Rv, we developed and validated an automated method for the genome-wide identification of sRNA candidate-containing regions within RNA-Seq datasets based on the analysis of the characteristics of reads coverage maps. We identified 192 novel candidate sRNA-encoding regions in intergenic regions and 664 RNA transcripts transcribed from regions antisense (as) to open reading frames (ORF), which bear the characteristics of asRNAs, and validated 28 of these novel sRNA-encoding regions by northern blotting. Our work has not only provided a simple automated method for genome-wide identification of candidate sRNA-encoding regions in RNA-Seq data, but has also uncovered many novel candidate sRNA-encoding regions in M. tuberculosis, reinforcing the view that the control of gene expression in bacteria is more complex than previously anticipated.
Background: The phenomenon of immune priming, i.e. enhanced protection following a secondary exposure to a pathogen, has now been demonstrated in a wide range of invertebrate species. Despite accumulating phenotypic evidence, knowledge of its mechanistic underpinnings is currently very limited. Here we used the system of the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus thuringiensis (Bt) to further our molecular understanding of the oral immune priming phenomenon. We addressed how ingestion of bacterial cues (derived from spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects gene expression upon later challenge exposure, using a whole-transcriptome sequencing approach. Results: Whereas gene expression of individuals primed with the orally non-pathogenic strain showed minor changes to controls, we found that priming with the pathogenic strain induced regulation of a large set of distinct genes, many of which are known immune candidates. Intriguingly, the immune repertoire activated upon priming and subsequent challenge qualitatively differed from the one mounted upon infection with Bt without previous priming. Moreover, a large subset of priming-specific genes showed an inverse regulation compared to their regulation upon challenge only. Conclusions: Our data demonstrate that gene expression upon infection is strongly affected by previous immune priming. We hypothesise that this shift in gene expression indicates activation of a more targeted and efficient response towards a previously encountered pathogen, in anticipation of potential secondary encounter.
The potato (Solanum tuberosum L.) mitochondrial cox3/sdh4/pseudo-cox2 gene cluster has previously been identified by heterologous hybridization using a Marchantia polymorpha sdh4 probe. In our present study we used Southern blotting using sdh4 and cox2 probes to show that the sdh4 and cox2 genes are clustered in the mitochondria of potato, soybean and pea. Northern blotting revealed cotranscription of sdh4 and cox2 in potato but not in cauliflower, indicating that these genes are not clustered in cauliflower. A putative recombination point was detected downstream of the cox2 pseudogene (pseudo-cox2) in potato mitochondrial DNA (mtDNA). This sequence corresponds to a 32 bp sequence which appears to be well-conserved and is adjacent to the terminals of some mitochondrial genes in Citrullus lanatus, Beta vulgaris and Arabidopsis thaliana and is probably involved in the genic rearrangements. It is possible the potato mtDNA pseudo-cox2 gene was generated by recombination during evolution in the same way as that of several other mitochondrial genes and remains as an inactive partial copy of the functional cox2 which was also detected in potato mtDNA.
With the increase in device variability, the performance uncertainty poses a daunting challenge to analog/mixed-signal circuit design. This situation requires a robust design approach to add large margins to the circuit and system-level specification to ensure correct operation and the overall yield. In this paper, we propose a new robust design approach by using norm metrics to quantify the robustness for both design parameters and performance uncertainty. In addition, we adopt a surrogating procedure to achieve robustness in design space and to reduce uncertainty in performance space. The end result of the proposed method is a Pareto-surface that provides the designer with trade-offs between design robustness and performance uncertainty. One advantage of this new approach is the ability to take into account the strong nonlinear relationship between performance and design parameters. Considering a set of highly nonlinear circuit performances, we demonstrate the effectiveness of this robust design framework on a fully CMOS operational amplifier circuit. (C) 2015 Elsevier B.V. All rights reserved.
This paper deals with the problem of robust stability analysis of grid-connected converters with LCL filters controlled through a digital signal processor and subject to uncertain grid inductance. To model the uncertain continuous-time plant and the digital control gain, a discretization procedure, described in terms of a Taylor series expansion, is employed to determine an accurate discrete-timemodel. Then, a linear matrix inequality-based condition is proposed to assess the robust stability of the polynomial discrete-time augmented system that includes the filter state variables, the states of resonant controllers and the delay from the digital control implementation. By means of a parameterdependent Lyapunov function, the proposed strategy has as main advantage to provide theoretical certification of stability of the uncertain continuous-time closed-loop system, circumventing the main disadvantages of previous approaches that employ approximate discretized models, neglecting the errors. Numerical simulations illustrate the benefits of the discretization technique and experimental results validate the proposed approach.
Fresh (frozen/thawed) muscle samples from four 2-12-year-old roe deer (Capreolus capreolus) from the Sondrio province in north-eastern Italy were examined under a dissecting microscope, and about 180 sarcocysts were isolated and identified to morphological type in wet mounts by light microscopy (LM). Seventy-seven of these sarcocysts were subsequently examined by molecular methods, comprising polymerase chain reaction (PCR) amplification and sequencing of the partial cytochrome c oxidase subunit I gene (cox1) of all isolates, as well as PCR amplification, cloning and sequencing of the complete18S ribosomal RNA (rRNA) gene of two isolates of each species found. By LM, three major sarcocyst types were recognised: spindle-shaped sarcocysts, 0.5-3 mm long, either with no clearly recognisable protrusions (thin-walled) or with finger-like protrusions (thick-walled); and slender, thread-like sarcocysts, 2-3 mm long, with hair-like protrusions. Sequencing of cox1 revealed that the sarcocysts belonged to four different species. Those with no visible protrusions either belonged to Sarcocystis gracilis (n = 24) or to a Sarcocystis taeniata-like species (n = 19), whereas those with finger- and hair-like protrusions belonged to Sarcocystis silva (n = 27) and Sarcocystis capreolicanis (n = 7), respectively. The 19 cox1 sequences of the S. taeniata-like species, comprising five haplotypes, differed from each other at 0-16 of 1038 nucleotide positions (98.5-100% identity). They differed from 25 previous cox1 sequences of S. taeniata from moose and sika deer (with 98.0-100% intraspecific identity), at 33-43 nucleotide positions (95.9-96.8% interspecific identity), and there were 20 fixed nucleotide differences between the two populations. In the phylogenetic analysis based on cox1 sequences, the two populations formed two separate monophyletic clusters. The S. taeniata-like species in roe deer was therefore considered to represent a separate species, which was named Sarcocystis linearis n. sp. At the 18S rRNA gene, however, the two species could not be clearly separated from each other. Thus, there was considerable intraspecific sequence variation in the 18S rRNA gene of S. linearis (98.1-99.9% identity between 24 sequences), which was similar both in magnitude and nature to the variation previously found in this gene of S. taeniata. The new 18S rRNA gene sequences of S. linearis shared an identity of 97.9-99.6% with those of S. taeniata (overlap between intra- and interspecific identity), and in the phylogenetic tree, sequences of the two species were interspersed. By scanning electron microscopy (SEM), the sarcocysts of S. linearis were found to possess regularly spaced, thin and narrow ribbon-like cyst wall protrusions (about 2.8-3.2 mu m long, 0.3-0.4 mu m wide and about 0.02-0.03 mu m thick), terminating in a plate-like structure of the same thickness but with an elliptic outline (about 0.3-0.4 mu m wide and 0.7-0.9 mu m long). The terminal plates were connected in the middle with the band-like portion of the protrusions like the board of a seesaw (tilting board). The terminal plates of adjacent protrusions were neatly arranged in a hexagonal pattern resembling tiles on a roof. Together, they formed an outer roof-like layer facing the surrounding cytoplasm of the host cell and completely covering the band-like proximal portion of the protrusions, which overlapped and were stacked in three to four layers close to the cyst surface. The sarcocyst morphology of S. linearis was consistent with that of an unnamed Sarcocystis sp. in roe deer previously found by transmission electron microscopy in several countries, including Italy. A few sarcocysts of S. gracilis and S. silva were also examined by SEM, confirming the presence of regularly distributed, short knob-like protrusions in S. gracilis (as seen in previous SEM studies) and revealing tightly packed, erect 6-7-mu m-long villus-like protrusions having regularly distributed round depressions on their surface in S. silva. The sequencing of cox1 of 7, 24 and 27 new isolates of S. capreolicanis, S. gracilis and S. silva, respectively, recovered 7, 11 and 10 new haplotypes from each of the three species and expanded our knowledge on the intraspecific sequence variation at this marker. Similarly, the study revealed a more extensive intragenomic sequence variation at the 18S rRNA gene of S. capreolicanis and S. silva than known from previous studies and confirmed a near absence of such variation in the 18S rRNA gene of S. gracilis.
In this paper a new method to increase the bandwidth of Rogowski current sensors is presented. Instead of using a termination resistor, in the proposed method a simple circuit based on transimpedance amplifier is used to suppress the parasitic capacitance of the coil. Using the lumped model of Rogowski coil, bandwidth, gain, and noise of the proposed current sensor is analyzed. The analyses are validated by both simulation and measurement results. Measurement of the proposed circuit demonstrates that without having any special coil design, a bandwidth close to 12 MHz can be achieved, using a simple circuit with off-the-shelf electronic components. (C) 2017 Elsevier B.V. All rights reserved.
The main tendency of rolling mills drives modernization is outdated analog control systems replacement with new digital ones. At the same time, a power section of the drive remains the same. This gives an opportunity to develop and implement adaptive digital control system for such plants in order to take into consideration their high nonlinearity. Having considered different types of such systems, the ones which does not change the well-accepted PID control algorithm, but tune its parameters KP, KI, KD are believed to have the highest chances to be applied into industry. The main aim of this research is to develop and apply a neural tuner to adjust armature current PI-controller parameters of a two-high reversing rolling mill drive online. The neural tuner consists of 1) a neural network calculating KP and KI values and trained online with the help of backpropagation method and 2) a rule base, which conditions is used to estimate transient quality, whereas consequences are values of a learning rate of the network output layer neurons. Modeling experiments are conducted with a model of the plant under consideration. They are used to check the ability of the tuner to: 1) adjust the PI-controller parameters back to optimal values; 2) cope with an armature winding parameters drift. Such experiments are conducted both for the systems with the neural tuner and a conventional PI-controller. As far as the second type of experiments is concerned, the system with the neural tuner is able to achieve 2% energy consumption decrease comparing to a conventional PI-controller based control system.
This study elucidated the potential antidepressant-like effect of prolonged RoprenA (R) administration (8.6 mg/kg, orally, once daily for 28 days) using a beta-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of beta-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5 mg/kg, subcutaneous, once daily, 28 days) supplementation. RoprenA (R) was administered to the GDX rats and GDX rats treated with TP. Depression-like behavior was assessed in the forced swimming test, and the spontaneous locomotor activity was assessed using the open-field test. The corticosterone and testosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with RoprenA (R) significantly decreased the immobility time of GDX rats with beta-amyloid (25-35) in the forced swimming test. Coadministration of RoprenA (R) with TP exerted a markedly synergistic antidepressant-like effect in the GDX rats with beta-amyloid (25-35 on the same model of depression-like behavior testing. RoprenA (R) administered alone or together with TP significantly enhanced crossing, frequency of rearing, and grooming of the GDX rats with beta-amyloid (25-35) in the open-field test. Moreover, RoprenA (R) administered alone or together with TP significantly decreased the elevated corticosterone levels in the blood serum of GDX rats with beta-amyloid (25-35) following the forced swimming test. These results indicate that RoprenA (R) has a marked antidepressant-like effect in the experimental model of Alzheimer's disease in male rats with altered levels of androgens.
Rosacea is a chronic cutaneous inflammatory disease that affects the facial skin. Clinically, rosacea can be categorized into papulopustular, erythematotelangiectatic, ocular, and phymatous rosacea. However, the phenotypic presentations of rosacea are more heterogeneous. Although the pathophysiology of rosacea remains to be elucidated, immunologic alterations and neurovascular dysregulation are thought to have important roles in initiating and strengthening the clinical manifestations of rosacea. In this article, we present the possible molecular mechanisms of rosacea based on recent laboratory and clinical studies. We describe the genetic predisposition for rosacea along with its associated diseases, triggering factors, and suggested management options in detail based on the underlying molecular biology. Understanding the molecular pathomechanisms of rosacea will likely aid toward better comprehending its complex pathogenesis.
This paper presents the development of a wireless flow transmitter using rotameter and operational amplifier based signal conditioning circuit. The rotameter is a linear gravity based flow measuring device. It consists of a display unit which directly displays the flow rate. For industrial applications a new circuitry is required to transmit the measured flow rate to the control unit at remote areas. A ferromagnetic wire attached to the float of rotameter acts as a core of an inductance pickup coil constitutes the flow sensor. The self-inductance of the coil changes according to the change in flow rate. An operational amplifier based circuit is used for the measurement of self-inductance. The voltage corresponding to the flow rate is finally converted into 4-20 mA current. A wireless readout is provided using a microcontroller unit and a Bluetooth module. The results show a linear relation between the variation of self-inductance of a pickup coil as well as transmitter output with respect to flow rate. The theoretical equations and the simulation results are added in this paper.
Background: Rotaviruses are the major cause of diarrhea among the infants and young children all over the world causing over 500,000 deaths and 2.4 million hospitalizations each year. In Nepal Rotavirus infection positivity rates ranges from 17.0 to 39.0% among children less than 5 years. However, little is known about the molecular genotypes of Rotavirus prevailing. The objective of this study was to estimate the burden of Rotavirus gastroenteritis and determine the genotypes of Rotavirus among children less than 5 years. Methods: The cross sectional study was conducted from January to November 2014 among children less than 5 years old visiting Kanti Children's Hospital and Tribhuvan University Teaching Hospital. Rotavirus antigen detection was performed by Enzyme Linked Immunosorbent Assay (ELISA) using ProSpecT Rotavirus Microplate Assay. Among the Rotavirus antigen positive samples, 59 samples were used for Rotavirus RNA extraction. Multiplex PCR was performed to identify G type comprising G1-G4, G8-G10 and G12 and P type comprising P[4], P[6], P[8], P[9], P[10], and P[11]. Results: A total of 717 diarrheal stool samples were collected from patients ranging from 10 days to 59 months of age. Rotavirus antigen positive was found among (N = 164) 22.9% of patients. The highest number of the diarrhea was seen in January. Molecular analysis of Rotavirus genotypes revealed that the predominant G-Type was G12 (36%) followed by G9 (31%), G1 (21%), G2 (8.6%). The predominant P- type was P6 (32.8%) followed by P8 (31%), P10 (14.8%), P4 (14.8%). A total of seven G/P type combinations were identified the most common being G12P [6] (35.8%), G1P [8] (15.1%), G9P [8] (15. 1%). Conclusion: Rotavirus diarrhea is, mostly affecting children from 7 to 24 months in Nepal, mostly occurring in winter. The circulating genotypes in the country are found to be primarily unusual genotypes and predominance of G12P[6]. It is recommended to conduct genotyping of Rotavirus on large samples before starting vaccination in the country.
Of 2,754 stool specimens collected from children with acute gastroenteritis during 2013-2014 in Sukhothai and Phetchaboon provinces, Thailand, 666 (24.2%) were positive for rotavirus A (RVA) in polyacrylamide gel electrophoresis (PAGE). The G and P types of all RVA-positive specimens were determined by semi-nested RT-PCR. G1P[8] (56.5%) was most prevalent, followed by G2P[4] (22.1%). Unusual G8P[8] human RVAs (HuRVAs) were detected at a high frequency (20.0%). Interestingly, 171 of the 376 G1P[8] HuRVAs and all of the 133 G8P[8] HuRVAs showed a short RNA pattern in PAGE. Thus, it was shown that the properties of HuRVAs have been markedly unusual in recent years in Thailand. (C) 2016 Wiley Periodicals, Inc.
Group A rotaviruses (RVAs) are the primary cause of acute gastroenteritis (AGE) in young children worldwide. Several commercial tests including latex agglutination, enzyme-linked assays (ELISA) and immunochromatographic tests (ICT) have been developed for the diagnosis of RVA infection. In the present study, the performance of two commercially available one-step chromatographic immunoassays, CerTest Rotavirus + Adenovirus (Biotec S.L, Zaragoza, Spain) and Vikia Rota-Adeno (bioMerieux SA, Lyon, France) were retrospectively evaluated using Real-time PCR as reference test. Re-testing by Real-time PCR of 2096 stool samples of children hospitalized with AGE previously screened by ICTs (1467 by CerTest and 629 by Vikia) allowed to calculate higher sensitivity for Vikia (94% vs 85% of CerTest) and higher specificity for CerTest (93% vs 89% of Vikia). Accordingly, higher Positive Predictive Values (87% vs 78%) and Positive Likelihood Ratios (12.32 vs 8.8) were found for CerTest and lower Negative Predictive Values (91% vs 97%) and Negative Likelihood Ratios (0.16 vs 0.06) for Vikia. However, both CerTest and Vikia showed a substantial agreement (K = 0.79) with the Real-time PCR. A correlation between false negative results by ICTs and high Cycle Threshold values of Real-time PCR, indicative of low viral load, was observed. False positive results by the two ICT assays were not related to Norovirus, Adenovirus or Astrovirus infections, therefore the risk of cross-reactions was excluded. Both CerTest and VIKIA were able to detect the wide range of RVA genotypes circulating over the study period (including G1P[8], G2P[4], G3, G4, G9 and G12P[8]). The results of the present study showed a satisfactory efficacy of the two diagnostic tests analyzed. (C) 2017 Elsevier B.V. All rights reserved.
Rotavirus A (RVA) causes acute diarrhea in children as well as animals. As part of a crosssectional study of children less than 5 years of age hospitalized for acute diarrhea in Vietnam during a 15-month period (2007-2008), 322 (43.5%) of 741 fecal specimens contained RVA with 92% either G1P[8] or G3P[8]. This study was undertaken to further characterize strains that remained untypeable to complete the G and P genotypes of the 322 rotavirus-positive specimens. While 307 (95.3%) strains possessed the common human RVA genotypes: G1P[8] (45.0%), G2P[4] (2.8%), G3P[8] (46.9%), and G9P[8] (0.6%), sequencing of initially untypeable specimens revealed the presence of two unusual strains designated NT0073 and NT0082 possessing G9P[19] and G10P[14], respectively. The genotype constellation of NT0073 (G9-P[19]-I5-R1-C1-M1-A8-N1-T7-E1-H1) and the phylogenetic trees suggested its origin as a porcine RVA strain causing diarrhea in a 24-month-old girl whereas the genotype constellation of NT0082 (G10-P[14]-I2-R2-C2-M2-A3N2- T6-E2-H3) and the phylogenetic trees suggested its origin as an RVA strain of artiodactyl origin (such as cattle, sheep and goats) causing diarrhea in a 13-month-old boy. This study showed that RVA strains of animal host origin were not necessarily attenuated in humans. A hypothesis may be postulated that P[19] and P[14] VP4 spike proteins helped the virus to replicate in the human intestine but that efficient onward human-to-human spread after crossing the host species barrier may require the virus to obtain some additional features as there was no evidence of widespread transmission with the limited sampling performed over the study period. (C) 2016 Wiley Periodicals, Inc.
Rousseau's project in his Social Contract was to construct a conception of human subjectivity and political institutions that would transcend what he saw to be the limits of liberal political theory of his time. I take this as a starting point to put forward an interpretation of his theory of the general will as a kind of social cognition that is able to preserve individual autonomy and freedom alongside concerns with the collective welfare of the community. But whereas many have seen Rousseau's ideas as a prelude to communitarianism or authoritarianism, we should instead see his project as articulating an alternative model of moral-cognitivist reasoning. In order to provide a framework for this interpretation, I propose reading his conception of the general will through the theory of collective intentionality and social ontology. I end with a consideration of how this interpretation of the general will can provide a more satisfying understanding of political and practical rationality contemporary debates over republicanism and liberalism.
We have cloned a novel transcriptional repressor protein, termed simiRP58, which has high homology to RP58. Both simiRP58 and RP58 belong to the POZ domain and Kruppel Zn finger (POK) family of proteins. Using the luciferase assay system, we found that simiRP58 also has transcriptional repressor activity like RP58. Northern blotting and quantitative RT-PCR showed that simiRP58 was expressed in testes at the highest level. In situ hybridization of testes showed that simiRP58 is expressed by spermatocytes in only a portion of the seminiferous tubules. In contrast, expression of RP58 by spermatocytes was ubiquitous in all seminiferous, tubules. Using COS-7 cells, we observed that simiRP58 was localized in the cytoplasm, which is in contrast to RP58 that was localized in the nucleus. Interestingly, co-transfection with simiRP58 and RP58 induced changes in the localization patterns of both proteins. (c) 2008 Elsevier Inc. All rights reserved.
Background: Cervical cancer is a common gynecologic malignant tumor and has a great impact on women's health. Human papillomavirus (HPV) is implicated in cervical cancer and precancerous lesions and the two are possibly two stages of disease progression. With the technological development of molecular biology and epidemiology, detection and treatment of HPV has become an important means to prevent cervical cancer. Methods: Here we present a novel, rapid, sensitive and specific isothermal method of recombinase polymerase amplification (RPA), which is established to detect the two most common high-risk human papillomavirus type 16 and type 18 DNA. In this study, we evaluate the efficacy of the RPA assay, incubating clinical specimens of HPV16 and HPV18 using plasmids standard. It operates at constant low temperature without the thermal instrumentation for incubation. The products can be detected via agarose gel electrophoresis assay, reverse dot blot assay, and quantitative real-time assay with SYBR Green I. We assess the diagnostic performance of the RPA assay for detecting of HPV16 and HPV18 in 335 clinical samples from patients suspected of cervical cancer. Results: The results revealed no cross-reaction with other HPV genotypes and the RPA assay achieve a sensitivity of 10(0) copies. Compared with TaqMan qPCR, the RPA technique achieves exponential amplification with no need for pretreatment of sample DNA at 37 degrees C for 20 minutes, which reveals more satisfactory performance. The agreement between the RPA and qPCR assays was 97.6% (kappa = 0.89) for HPV16 positivity and 98.5% (kappa = 0.81) for HPV18 positivity, indicating very good correlation between both tests. Conclusions: Importantly, the RPA assay was demonstrated to be a useful and powerful method for detection of HPV virus, which therefore may serve as a valuable tool for rapid diagnosis of HPV infection in both commercial and clinical applications.
Rice stripe virus (RSV) is an insect-borne tenuivirus of economical significance. It is endemic to the rice growing regions of East Asia and exhibits more genetic diversity in Yunnan Province of China. To gain more insights into the molecular epidemiology and evolution of RSV, recombination analyses were conducted and potential events were detected in each of the four RNA segments of RSV. Bayesian coalescent method was then applied to the time-stamped coding sequences of the CP gene. The nucleotide substitution rate and the divergence time were estimated. Age calculations suggested that the first diversification event of the RSV isolates analyzed might take place in the early 20th century, and RSV has existed in Yunnan long before notice. Surveys of codon usage variation showed that the RSV genes had influences other than mutational bias. In codon choice, RSV conformed to neither vector small brown planthopper nor host rice, although the former exerted a more dominant influence on shaping codon usage pattern of RSV. In addition, CpG dinucleotide deficiency was observed in RSV. (C) 2017 Elsevier Inc. All rights reserved.
This paper addresses the impact of electrode contaminations on the interfacial energy level alignment, the molecular conformation, orientation and surface morphology deposited organic film at organic semiconductor/noble metal interfaces by varying of film thickness from sub-monolayer to multilayer, which currently draws significant attention with regard to its application in organic electronics. The UHV clean Ag and unclean Ag were employed as substrate whereas rubrene was used as an organic semiconducting material. The photoelectron spectroscopy (XPS and UPS) was engaged to investigate the evolution of interfacial energetics; polarization dependent near edge x-ray absorption fine structure spectroscopy (NEXAFS) was employed to understand the molecular conformation as well as orientation whereas atomic force microscopy (AFM) was used to investigate the surface morphologies of the films. The adventitious contamination layer was acted as a spacer layer between clean Ag substrate surface and rubrene molecular layer. As a consequence, hole injection barrier height, interface dipole as well as molecular-conformation, molecular-orientation and surface morphology of rubrene thin films were found to depend on the cleanliness of Ag substrate. The results have important inferences about the understanding of the impact of substrate contamination on the energy level alignment, the molecular conformation as well as orientation and surface morphology of deposited rubrene thin film at rubrene/Ag interfaces and are beneficial for the improvement of the device performance. (C) 2017 Elsevier B.V. All rights reserved.
Studies proved that addition of nitrate in rumen could lead to reduction of methane emission. The mechanism of this function was involved in the competition effect of nitrate on hydrogen consumption and the inhibitory effect of generated nitrite on methanogen proliferation. The present study investigated an alternative mechanism that denitrifying anaerobic methane oxidizing (DAMO) bacteria, DAMO archaea and anammox bacteria may co-exist in rumen, therefore, more methane can be oxidized when addition of nitrate. Ruminal batch culture model was used to test the effects of addition of 5 mM NaNO3, 4 mM NH4Cl, or both into the culture substrate on methane production, fermentation patterns, and population of methanogens, NC10 and anaerobic methanotrophic-2d (ANME-2d). Our results showed that NC10 in the ruminal culture was detected by polymerase chain reaction (PCR) when using NC10 special primer sets, and addition of nitrate reduced methane production and the relative proportions of methanogen, whereas increased the relative proportion of NC10. A combined addition of ammonia salt and nitrate did not show further inhibitory effect on methane production but accelerated nitrate removal. We did not detect DAMO archaea in ruminal culture by real-time PCR when using ANME-2d special primer sets. The present study may encourage researchers to pay more attention to methane oxidation performed by anaerobic methanotroph when studying the strategies of inhibiting ruminal methane emission.
Children with developmental dyspraxia (DD) express impairments in the acquisition of various motor skills and in the development of their social cognition abilities. Although the neural bases of this condition are not fully understood, they are thought to involve frontal cortical areas, subcortical structures, and the cerebellum. Although cerebellar dysfunction is typically difficult to assess and quantify using traditional neurophysiological methods, oculomotor analysis may provide insight into specific cerebellar patterns. The aim of the present study was to investigate, in dyspraxic and typically developing subjects, various oculomotor saccade tasks specifically designed to reveal frontal and cerebellar dysfunction. In addition to evidence supporting prefrontal dysfunction, our results revealed increased variability of saccade accuracy consistent with cerebellar impairments. Furthermore, we found that dyspraxic patients showed decreased velocities of non-visually guided saccades. A closer analysis revealed significant differences in saccade velocity profiles with slightly decreased maximum saccade velocities but markedly prolonged deceleration phases. We show that this pattern was not related to a decreased state of alertness but was suggestive of cerebellar dysfunction. However, the clear predominance of this pattern in non-visually guided saccades warrants alternative hypotheses. In light of previous experimental and anatomical studies, we propose that this unusual pattern may be a consequence of impaired connections between frontal areas and cerebellar oculomotor structures.
Saccharomyces cerevisiae is frequently used as a bioreactor for conversion of exogenously acquired metabolites into value-added products, but has not been utilized for bioconversion of low-cost lipids such as triacylglycerols (TAGs) because the cells are typically unable to acquire these lipid substrates from the growth media. To help circumvent this limitation, the Yarrowia lipolytica lipase 2 (LIP2) gene was cloned into S. cerevisiae expression vectors and used to generate S. cerevisiae strains that secrete active Lip2 lipase (Lip2p) enzyme into the growth media. Specifically, LIP2 expression was driven by the S. cerevisiae PEX11 promoter, which maintains basal transgene expression levels in the presence of sugars in the culture medium but is rapidly upregulated by fatty acids. Northern blotting, lipase enzyme activity assays, and gas chromatographic measurements of cellular fatty acid composition after lipid feeding all confirmed that cells transformed with the PEX11 promoter-LIP2 construct were responsive to lipids in the media, i.e., cells expressing LIP2 responded rapidly to either free fatty acids or TAGs and accumulated high levels of the corresponding fatty acids in intracellular lipids. These data provided evidence of the creation of a self-regulating positive control feedback loop that allows the cells to upregulate Lip2p production only when lipids are present in the media. Regulated, autonomous production of extracellular lipase activity is a necessary step towards the generation of yeast strains that can serve as biocatalysts for conversion of low-value lipids to value-added TAGs and other novel lipid products.
Background: Sugarcane (Saccharum spp.) is the main raw material for sugar and ethanol production. Among the abiotic stress, drought is the main one that negatively impact sugarcane yield. Although gene expression analysis through quantitative PCR (qPCR) has increased our knowledge about biological processes related to drought, gene network that mediates sugarcane responses to water deficit remains elusive. In such scenario, validation of reference gene is a major requirement for successful analyzes involving qPCR. Results: In this study, candidate genes were tested for their suitable as reference genes for qPCR analyses in two sugarcane cultivars with varying drought tolerance. Eight candidate reference genes were evaluated in leaves sampled in plants subjected to water deficit in both field and greenhouse conditions. In addition, five genes were evaluated in shoot roots of plants subjected to water deficit by adding PEG8000 to the nutrient solution. NormFinder and RefFinder algorithms were used to identify the most stable gene(s) among genotypes and under different experimental conditions. Both algorithms revealed that in leaf samples, UBQ1 and GAPDH genes were more suitable as reference genes, whereas GAPDH was the best reference one in shoot roots. Conclusion: Reference genes suitable for sugarcane under water deficit were identified, which would lead to a more accurate and reliable analysis of qPCR. Thus, results obtained in this study may guide future research on gene expression in sugarcane under varying water conditions.
Managing the aging of digital control systems ensures that nuclear power plant systems are in adequate safety margins during their life cycles. Software is a core component in the execution of control logic and differs between digital and analog control systems. The hardware aging management for the digital control system is similar to that for the analog system, which has matured over decades of study. However, software aging management is still in the exploratory stage. Software aging evaluation is critical given the higher reliability and safety requirements of nuclear power plants. To ensure effective inputs for reliability assessment, this paper provides the required software aging information during the life cycle. Moreover, the software aging management scheme for safety digital control system is proposed on the basis of collected aging information.
The migration towards digital control systems creates new security threats that can endanger the safety of industrial infrastructures. Addressing the convergence of safety and security concerns in this context, we provide a comprehensive survey of existing approaches to industrial facility design and risk assessment that consider both safety and security. We also provide a comparative analysis of the different approaches identified in the literature. (C) 2015 Elsevier Ltd. All rights reserved.
Though there are many computational models proposed for saliency detection, few of them take object boundary information into account. This paper presents a hierarchical saliency detection model incorporating probabilistic object boundaries, which is based on the observation that salient objects are generally surrounded by explicit boundaries and show contrast with their surroundings. We perform adaptive thresholding operation on ultrametric contour map, which leads to hierarchical image segmentations, and compute the saliency map for each layer based on the proposed robust center bias, border bias, color dissimilarity and spatial coherence measures. After a linear weighted combination of multi-layer saliency maps, and Bayesian enhancement procedure, the final saliency map is obtained. Extensive experimental results on three challenging benchmark datasets demonstrate that the proposed model outperforms eight state-of-the-art saliency detection models.
Salivary diagnostics has great potential to be used in the early detection and prevention of many cancerous diseases. If implemented with rigour and efficiency, it can result in improving patient survival times and achieving earlier diagnosis of disease. Recently, extraordinary efforts have been taken to develop non-invasive technologies that can be applied without complicated and expensive procedures. Saliva is a biofluid that has demonstrated excellent properties and can be used as a diagnostic fluid, since many of the biomarkers suggested for cancers can also be found in whole saliva, apart from blood or other body fluids. The currently accepted gold standard methods for biomarker development include chromatography, mass spectometry, gel electrophoresis, microarrays and polymerase chain reaction-based quantification. However, salivary diagnostics is a flourishing field with the rapid development of novel technologies associated with point-of-care diagnostics, RNA sequencing, electrochemical detection and liquid biopsy. Those technologies will help introduce population-based screening programs, thus enabling early detection, prognosis assessment and disease monitoring. The purpose of this review is to give a comprehensive update on the emerging diagnostic technologies and tools for the early detection of cancerous diseases based on saliva.
Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma. Successful treatment with anti-androgen therapy in other androgen receptor-positive malignancies such as prostate and breast cancer has inspired researchers to investigate this treatment in salivary gland cancer as well. In this review, we describe the prevalence, biology, and therapeutic implications of androgen receptor signaling in salivary gland cancer.
Background: Salmonella enterica serovar Typhi, as causative agent of typhoid fever, is one of the most important endemic pathogens. Non-typhoidal Salmonella serovars, including Typhimurium, Infantis, and Enteritidis are amongst the most prevalent serotypes worldwide and in developing areas such as Iran. The aim of this study was to apply a uniplex PCR for rapid detection of Salmonella spp., and a multiplex PCR for the simultaneous detection of the four most common Salmonella serovars in Iran. Methods: Current research was done in 2010 at Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. For detection of Salmonella spp a pair of primers was used to replicate a chromosomal sequence. Four other sets of primers were also designed to amplify the target genes of four Salmonella species including S. typhi, and three non-typhoidal Salmonella spp (S. enteritidis, S. infantis, and S. typhimurium). The assay specificity was investigated by testing 15 different Salmonella serovars and 8 other additional non-Salmonella species. Results: The Salmonella genus-specific PCR yielded the expected DNA band of 404 bp in all Salmonella spp., strains tested. The uniplex and multiplex PCR assays produced also the expected fragments of 489 bp, 304 bp, 224 bp, and 104 bp for serovars Typhi, Enteritidis, Typhimurium, and Infantis, respectively. Each species-specific primer pair set did not show any cross-reactivity when tested on other Salmonella serovars or other non- but related- Salmonella strains. Conclusion: Both uniplex and multiplex PCR protocols had a good specificity. They can provide an important tool for the rapid and simultaneous detection and differentiation of the four most prevalent Salmonella serovars in Iran.
Salmonella is a major food-borne pathogen in humans and a cause of local or systemic disease in animals. Therefore, rapid and reliable methods to detect these poultry-associated Salmonella serotypes are necessary for efficient control of Salmonella in poultry. The present study aimed to develop a real-time multiplex PCR (MqPCR) method to simultaneously detect and/or differentiate Salmonella sp. and poultry-associated serotypes, including Salmonella Enteritidis, Salmonella Typhimurium, Salmonella Pullorum, and Salmonella Gallinarum. A MqPCR method was designed using four specific primer pairs and probes for the detection of Salmonella sp., including S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Gallinarum. Additionally, a novel TaqMan-based MqPCR method combined with propidium monoazide (PMA) treatment was developed for the simultaneous quantification of viable cells of Salmonella sp. and these four Salmonella serotypes in rinse water of chicken carcasses. The MqPCR assay specifically detected Salmonella sp., S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Gallinarum, showing 100% sensitivity and 100% specificity. This optimized PMA-MqPCR assay could detect live Salmonella (10(0)-10(6) CFU/reaction) without enrichment in live/dead cell mixtures from spiked rinse water of chicken carcasses. The procedure for detecting live Salmonella required less than 2 h to complete. This PMA TaqMan-based MqPCR technique facilitates accurate and rapid monitoring of contamination with viable Salmonella. Also, the assay enables simultaneous identification of S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Gallinarum in rinse water of chicken carcasses. The assay developed in this study will be useful in diagnostic laboratories for improving Salmonella control in poultry and poultry products.
Introduction: Invasive non-typhoidal Salmonella (iNTS) infections cause a high burden of lethal sepsis in young children and HIV patients, often associated with malaria, anaemia, malnutrition and sickle-cell disease. Vaccines against iNTS are urgently needed but none are licensed yet. Areas covered: This review illustrates how immunology, epidemiology and within-host pathogen behaviour affect invasive Salmonella infections and highlights how this knowledge can assist the improvement and choice of vaccines. Expert Commentary: Control of iNTS disease requires approaches that reduce transmission and improve diagnosis and treatment. These are often difficult to implement due to the fragile ecology and economies in endemic countries. Vaccines will be key tools in the fight against iNTS disease. To optimise vaccine design, we need to better define protective antigens and mechanisms of resistance to disease in susceptible populations even in those individuals where innate immunity may be impaired by widespread comorbidities.
Food of non-animal origin is a major component of the human diet and has been considered to pose a low risk from the point of view of bacteriological safety. However, an increase in the number of outbreaks of illness caused by such pathogens and linked to the consumption of fresh fruit and vegetables have been reported from around the world recently. Salmonella spp., STEC (Shiga toxin producing Escherichia coli) and Listeria monocytogenes are among the most frequently identified agents. Additionally, the transmission of antibiotic resistant strains including also the methicillin resistant S. aureus (MRSA) to humans via the food chain is one of the greatest public health problems being confronted today. Therefore, we focused on the bacterial safety of fruit, vegetables and sprouts on sale in the Czech Republic. One strain (0.3%) of Salmonella Enteritidis phage type PT8, one strain (0.3%) of MRSA and 17 strains (5.0%) of L. monocytogenes were isolated from a total of 339 collected samples. The most problematic commodities were frozen fruit and vegetables (packed and unpacked) and fresh-cut vegetables. Our findings indicate deficiencies in hygiene practices during harvesting, processing and distribution of these commodities. Although sprouts and berries are the most likely to be contaminated by human pathogens, only two samples were positive for the presence of L monocytogenes. (C) 2016 Elsevier Ltd. All rights reserved.
The oceanic N-2-fixing cyanobacterium Trichodesmium spp. form extensive surface blooms and contribute significantly to marine carbon and nitrogen cycles in the oligotrophic subtropical and tropical oceans. Trichodesmium grows in salinities from 27 to 43 parts per thousand (ppt), yet its salt acclimation strategy remains enigmatic because the genome of Trichodesmium erythraeum strain IMS101 lacks all genes for the biosynthesis of any known compatible solute. Using NMR and liquid chromatography coupled to mass spectroscopy, we identified the main compatible solute in T. erythraeum strain IMS101 as the quaternary ammonium compound N,N,N-trimethyl homoserine (or homoserine betaine) and elucidated its biosynthetic pathway. The identification of this compatible solute explains how Trichodesmium spp. can thrive in the marine system at varying salinities and provides further insight into the diversity of microbial salt acclimation.
The suadea salsa full-length S-adenosylmethionine synthetase (SsSAMS2) was introduced into tobacco (Nicotiana tabacum L.) by Agrobacterium tumefaciens-mediated transformation. The gene transformation and expression in tobacco were confirmed by PCR, RT-PCR and Northern blotting analysis. Several transgenic lines (ST lines) overexpressing SsSAMS2 gene under the control of cauliflower mosaic virus 35S promoter showed more seeds number and weight, and accumulated higher free total polyamines (PAs) than wild-type plants (WT lines) and transformants with blank vector (BT lines). Salt stress-induced damage was attenuated in these transgenic plants, in the symptom of maintaining higher photosynthetic rate and biomass. These results that the transgenic plants overexpressing suadea salsa SAMS2 are more tolerant to salt stress than wild-type plants suggest that PAs may play an important role in contributing salt tolerance to plants.
To understand the molecular and cellular mechanisms underlying the salt response and to isolate differentially expressed genes, we constructed a forward subtractive cDNA library from Salsola ferganica treated with 600 mM NaCl for different lengths of time (0, 4, 8, 12, 16, 24, 36 h) using the suppression subtractive hybridization (SSH) technique. This SSH library contained approximately 2,200 positive clones, with the insert size ranging from 250 to 700 bp. Eighty clones were selected for further study based on results from reverse Northern blotting and sequencing and, these cDNAs are the first reported expressed sequence tags (ESTs) of Salsola ferganica listed in GenBank. Among these 80 differentially expressed genes, 32 are genes with known function that display a high homology (between 68 and 100% identity) to known sequences, 47 have an unknown function, showing no homology with known sequences, and one is a novel gene that does not match any previously reported genes. Five cDNA fragments, sf3d8, sf6d8, sf4a8, sf8d6, and sf6c7, were randomly chosen from the 80 differentially expressed genes for reverse transcription-PCR analysis. The expression of sf8d6 was entirely induced by salt stress and that of sf3d8, sf6d8, sf4a8, and sf6c7 was increased from a relatively lower level. The isolated ESTs reported here may enable us to find new genes involved in salt tolerance in Salsola ferganica.
Salvador Dali's relationship with science is one of the most important aspects of his artistic production, spanning disciplines such as physics, mathematics and biology. Considering his interest in the different sciences, the aim of this paper is to explore the special relationship between the painter and molecular biology, establishing a catalogue of works permitting the identification of its importance within Dali's career. We will try to demonstrate that the so-called "DNA period" encompasses a broader chronology than the one traditionally proposed, extending it from 1957 until the 1980s. That would place Dali as the pioneer in the incorporation of molecular biology into art history.
This paper presents the design of sampled analog wavelet processor architecture for cochlear implant application using discrete Haar wavelet transform. Basic element of sampled analog wavelet processor architecture is operational amplifier based switched capacitor integrator circuit. This architecture distributes input signal frequencies into different predefined frequency band and based on cochlear sensitivity region for different frequencies by using arbitrary tree structure. The presented architecture is beneficial in terms of processing time of input signal, area and complexity by avoiding quantization and encoding process part of data converter circuits. Simulation results for this architecture is carried out with CMOS 90 nm technology.
This article investigates the sampled-data disturbance rejection control problem for a class of non-integral-chain systems with mismatched uncertainties. Aiming to reject the adverse effects caused by general mismatched uncertainties via digital control strategy, a new generalized discrete-time extended state observer is first proposed to estimate the lumped disturbances in the sampling point. A disturbance rejection control law is then constructed in a sampled-data form, which will lead to easier implementation in practices. By carefully selecting the control gains and a sampling period sufficiently small to restrain the state growth under a zero-order-holder input, the bounded-input bounded-output stability of the hybrid closed-loop system and the disturbance rejection ability are delicately proved even the controller is dormant within two neighbor sampling points. Numerical simulation results demonstrate the feasibility and efficacy of the proposed method.
With the development of digital control technology, sampled-data control shows its prominent superiority for most practical industries. In the framework of sampled-data control, this paper studies the stabilization problem for a class of switched linear neutral systems meanwhile taking into account asynchronous switching. By utilizing the relationship between the sampling period and the dwell time of switched neutral systems, a bond between the sampling period and the average dwell time is revealed to form a switching condition, under which and certain control gains conditions exponential stability of the closed-loop systems is guaranteed. A simple example is given to demonstrate the effectiveness of the proposed method. (C) 2016 Elsevier Ltd. All rights reserved.
This paper is concerned with the sampling-interval-dependent stability of linear sampled-data systems with non-uniform sampling. A new Lyapunov-like functional is constructed to derive sampling-interval-dependent stability results. The Lyapunov-like functional has three features. First, it depends on time explicitly. Second, it may be discontinuous at the sampling instants. Third, it is not required to be positive definite between sampling instants. Moreover, the new Lyapunov-like functional can make use of the information fully of the sampled-data system, including that of both ends of the sampling interval. By making a new proposition for the Lyapunov-like functional, a sampling-interval-dependent stability criterion with reduced conservatism is derived. The new sampling-interval-dependent stability criterion is further extended to linear sampled-data systems with polytopic uncertainties. Finally, examples are given to illustrate the reduced conservatism of the stability criteria.
Here, we report a method for time-resolved, longitudinal extraction and quantitative measurement of intracellular proteins and mRNA from a variety of cell types. Cytosolic contents were repeatedly sampled from the same cell or population of cells for more than 5 d through a cell-culture substrate, incorporating hollow 150-nm-diameter nanostraws (NS) within a defined sampling region. Once extracted, the cellular contents were analyzed with conventional methods, including fluorescence, enzymatic assays (ELISA), and quantitative real-time PCR. This process was nondestructive with >95% cell viability after sampling, enabling long-term analysis. It is important to note that the measured quantities from the cell extract were found to constitute a statistically significant representation of the actual contents within the cells. Of 48 mRNA sequences analyzed from a population of cardiomyocytes derived from human induced pluripotent stemcells (hiPSC-CMs), 41 were accurately quantified. The NS platform samples from a select subpopulation of cells within a larger culture, allowing native cell-to-cell contact and communication even during vigorous activity such as cardiomyocyte beating. This platform was applied both to cell lines and to primary cells, including CHO cells, hiPSC-CMs, and human astrocytes derived in 3D cortical spheroids. By tracking the same cell or group of cells over time, this method offers an avenue to understand dynamic cell behavior, including processes such as induced pluripotency and differentiation.
Antiretroviral therapy (ART) can be compromised by selection of drug resistance strains, which can be promoted by lack of adherence during therapy and drug tolerance, and some of these drug-resistant strains can persist for years as minority populations. The K103N drug resistance mutation is selected by the use of non-nucleotide reverse transcriptase inhibitors, including nevirapine or efavirenz (EFV), used in low-income countries. Here we describe the use of a less expensive qualitative point mutation polymerase chain reaction (PMqPCR(K103N)) targeting K103N mutation. To validate the use of this methodology, we tested previously sequenced samples from patients treated with highly active ART with viral loads above 2,000 copies/ml and compared the results of our assay with Illumina deep sequencing. Due to its low cost and high specificity, this test is particularly suitable for low-income countries to screen for pretreatment resistance in patients either initiating ART or failing first-line regimens containing EFV.
Background: During the last few years, investigators have debated the role that infectious agents may have in sarcoidosis pathogenesis. With the emergence of new molecular biology techniques, several studies have been conducted; therefore, we performed a meta-analysis in order to better explain this possible association. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the Cochrane collaboration guidelines. Four different databases (Medline, Scopus, Web of Science, and Cochrane Collaboration) were searched for all original articles published from 1980 to 2015. The present meta-analysis included case-control studies that reported the presence of microorganisms in samples of patients with sarcoidosis using culture methods or molecular biology techniques. We used a random effects or a fixed-effect model to calculate the odds ratio (OR) and 95% confidence intervals (CI). Sensitivity and subgroup analyses were performed in order to explore the heterogeneity among studies. Results: Fifty-eight studies qualified for the purpose of this analysis. The present meta-analysis, the first, to our knowledge, in evaluation of all infectious agents proposed to be associated with sarcoidosis and involving more than 6000 patients in several countries, suggests an etiological link between Propionibacterium acnes and sarcoidosis, with an OR of 18.80 (95% CI 12.62, 28.01). We also found a significant association between sarcoidosis and mycobacteria, with an OR of 6.8 (95% CI 3.73, 12.39). Borrelia (OR 4.82; 95% CI 0.98, 23.81), HHV-8 (OR 1.47; 95% CI 0.02, 110.06) as well as Rickettsia helvetica, Chlamydia pneumoniae, Epstein-barr virus and Retrovirus, although suggested by previous investigations, were not associated with sarcoidosis. Conclusion: This meta-analysis suggests that some infectious agents can be associated with sarcoidosis. What seems clear is that more than one infectious agent might be implicated in the pathogenesis of sarcoidosis; probably the patient's geographical location might dictate which microorganisms are more involved. Future investigations and more clinical trials are need to bring these evidences to a more global level.
Mesenchymal neoplasms of the thymus and mediastinum account for only 2 % of neoplasms of the mediastinum and are therefore very rare. With very few exceptions the histology, immunohistochemistry and (based on current knowledge) molecular biology of mediastinal soft tissue tumors are not different from their counterparts in other organs. Characteristic features are more concerned with clinical epidemiological and therapeutic aspects as well as the multitude of possible differential diagnoses. With the exception of organ-specific tumors, such as gastrointestinal stromal tumors (GIST), virtually all entities encountered in peripheral soft tissues can also arise in the mediastinum. Primary mediastinal soft tissue sarcomas (STS) must be distinguished from secondary radiation-induced STS after irradiation, e. g. for breast cancer and Hodgkin's lymphoma and from STS arising as somatic type malignancies in mediastinal germ cell tumors.
Herein, two classic animal behavior despair tests-the forced swim test and tail suspension test were used to evaluate the antidepressant-like activity of saringosterol from Sargassum fusiforme in mice. Saringosterol was found to significantly shorten immobility time in the forced swim test and tail suspension test at doses of 10, 20, and 30 mg/kg in mice. The measurement of locomotor activity indicated that saringosterol had no central nervous system-stimulating effects. In addition, it was found that the saringosterol significantly increased noradrenaline, serotonin (5-HT), and the metabolite 5-hydroxyindoleacetic acid in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters.
The environmental impact of major oil spills on marine microorganisms has yet to be thoroughly investigated using molecular biology techniques. The Deepwater Horizon (DWH) drilling rig explosion of 2010 affected an approximately 176,000 km(2) surface area of the Gulf of Mexico (GOM) when an estimated 210 million gallons of oil from the Macondo Prospect spilled into the environment. Pelagic Sargassum, a complex of two surface drifting species (Sargassum natans and Sargassum fluitans) of marine brown macroalgae and a critically important habitat in the GOM ecosystem, was suffused by Macondo Prospect 252 oil released during the DWH event. Using 16S rRNA PCR and Roche 454 pyrosequencing, the effect of the oil on the bacterial population associated with pelagic Sargassum and contiguous waters was examined by comparing sequence data generated from samples collected from oiled and non-oiled locations in the northern GOM. Sequence data showed similar microbial composition in Sargassum regardless of exposure to oil primarily dominated by five phyla; Proteobacteria, Bacteroidetes, Actinobacteria, Verrucomicrobia, and unclassified bacteria. The microbial composition in water samples was significantly less diverse than for Sargassum and consisted primarily of Proteobacteria, Firmicutes, and Bacteroidetes. Due to the evenly distributed abundance of microbial species on oiled and non-oiled pelagic Sargassum, study findings indicate that DWH spilled oil had minimal effect on the composition and diversity of the microbial community associated with Sargassum and contiguous waters. However, higher abundances of Sulfitobacter and one species of Psychrobacter were found in oiled water samples when compared to non-oiled water samples indicating some effect of DHW oil in the microbial composition of seawater. Though there are a number of marine studies using molecular biology approaches, this is the first molecular examination of the impact of the DWH oil spill on bacterial communities associated with pelagic Sargassum and contiguous waters from the GOM.
Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections. (C) 2016 Elsevier B.V. All rights reserved.
There remain more questions than answers regarding the manifestation of certain diseases, such as Ebola, in some otherwise healthy individuals but not in others. Sasang medicine offers a possible clue to solving this mystery by introducing a constitutionally based, intrinsic approach to determining disease susceptibility. The Sasang constitution is identified by a detailed examination of inherent physiological and psychological traits that are likely, but not yet, to be associated with specific genetic patterns. Hence, it is anticipated that after further examination, the Sasang model will contribute to the advancement of medical research and treatment by establishing genetically traceable psychological and physiological traits that contribute to, or offer protection against, various diseases. To progress along this journey, additional research involving Sasang-based organ-associated emotions and inherent emotional/physiological inclinations is warranted. This study presents an argument in favor of additionally examining constitutionally specific disease components related to viral epidemiology.
The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro-and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.
Nucleoside diphosphate kinase (NDPK) is a key metabolic enzyme that catalyzes the synthesis of non-adenine nucleoside triphosphate (NTP) by transferring the terminal phosphate between nucleoside diphosphate (NDP) and NTP. NDPK regulates a variety of eukaryotic cellular activities including cell proliferation, development, and differentiation. The ndpk cDNA was cloned from the hemocytes of the scallop Chlamys farreri and designated Cf-ndpk. The full-length sequence of Cf-ndpk consists of 715 bp encoding a polypeptide of 153 amino acids with a calculated molecular mass of 16927.52 daltons and pI of 7.64. The mRNA expression and distribution of Cf-ndpk in both bacterially challenged and unchallenged scallops were studied by Northern blotting and in situ hybridization. The results showed that Cf-ndpk transcripts were present in hemocytes, gill, adductor muscle, mantle, digestive gland, foot, and gonad, and the expression level increased in hemocytes after bacterial challenge. Recombinant Cf-NDPK expressed in Escherichia coli could transfer the terminal phosphate between UDP and ATP. The Cf-NDPK protein was present in all tested tissues including foot, adductor muscle, digestive gland, gonad, mantle, gill, and hemolymph. It was up-regulated in hemolymph after bacterial challenge. Taken together, these results suggest that NDPK may play roles in the innate immune response of scallop.
Aberrant expression of scavenger receptor class B type 1 has been reported in several human cancers. Nevertheless, the roles of scavenger receptor class B type 1 in clear cell renal cell carcinoma remain unclear. The aim of this study was to evaluate the diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma. The messenger RNA level of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues was detected by quantitative reverse transcription polymerase chain reaction, while protein level was determined by western blot and immunohistochemistry. The lipid content between clear cell renal cell carcinoma tissues and normal kidney tissues was differentiated by Oil Red O and hematoxylin-eosin staining. The diagnostic value of scavenger receptor class B type 1 was determined by receiver operating characteristic curve. The prognostic significance of scavenger receptor class B type 1 was assessed by Kaplan-Meier analysis and Cox regression analysis. Our results showed that the expression of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues at both messenger RNA and protein level was much higher than that in normal kidney tissues. Receiver operating characteristic curve analysis exhibited a significant value of area under the curve (0.8486, 95% confidence interval: 0.7926-0.9045) with strong sensitivity (0.75, 95% confidence interval: 0.6535-0.8312) and specificity (0.90, 95% confidence interval: 0.8238-0.9510). Kaplan-Meier analysis revealed that patients with higher scavenger receptor class B type 1 expression had shorter progression-free survival time. Cox analysis indicated that scavenger receptor class B type 1 was an independent prognostic biomarker. In conclusion, our findings implied that scavenger receptor class B type 1 might serve as a diagnostic and independent prognostic biomarker in clear cell renal cell carcinoma.
Methicillin-resistant Staphylococcus aureus (MRSA) as a major cause of infection in health care, hospital and community settings is a global health concern. The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of circulating molecular types of MRSA in a burn hospital in Tehran, the capital of Iran. During a 10-month study period, 106 Staphylococcus aureus isolates were assessed. Isolates were subjected to susceptibility testing using the disk diffusion method and Polymerase Chain Reaction (PCR) for detection of mecA, fern and nuc genes. The presence of PVL and tst encoding genes were determined by PCR method. All the MRSA isolates were genotyped by multilocus sequence typing (MLST), spa typing, SCCmec typing and agr typing. The presence of mecA gene was confirmed in all the Staphylococcus aureus isolates. Antimicrobial susceptibility testing revealed a high resistance rate (90.6%) to ampicillin, tetracycline, and erythromycin. The rates of resistance to remaining antibiotics tested varied between 18.9% and 84.9%. The high-level of resistance to mupirocin was confirmed in 19.8% of MRSA strains isolated from burn patients. Multi-drug resistance was observed in 90.6% of isolates. Sixteen of the 106 MRSA isolates (15.1%) harbored PVL-encoding genes. The majority of our MRSA strains carried SCCmec III (71.7%). ST239-SCCmec III/t037 (34%) was the most common genotype followed by ST239-SCCmec III/t030 (24.5%), ST15-SCCmec IV/t084 (15.1%), ST22-SCCmec IV/t790 (13.2%), and ST239-SCCmec III/t631 (13.2%). Mupirocin resistant MRSA isolates belonged to ST15-SCCmec IV/t084 (40%), ST22-SCCmec IV/t790 (23.3%), ST239-SCCmec III/t631 (20%), and ST239-SCCmec III/t030 (16.7%) clones. The results showed that genetically diverse strains of MRSA are circulating in our burn hospitals with relatively high prevalence of ST239-SCCmec III/t037 clone. The findings support the need for regular surveillance of MRSA to determine the distribution of existing MRSA clones and to detect the emergence of new MRSA clones. (C) 2017 Elsevier Ltd. All rights reserved.
Outdoor industrial-scale microalgae cultivation is limited by several factors, among which a low efficiency of overall light energy conversion plays a key role, mainly due to photosaturation and photo inhibition under high irradiations. This work aims at improving the overall photoconversion efficiency in a microalgal production photobioreactor (PBRs), by exploiting an advanced photovoltaic (PV) technology. A semi-transparent dye sensitized solar cells module (DSC) is placed on the irradiated surface, thus absorbing part of the incident light to produce electricity, while transmitted photons are used by algal cells for photosynthesis. Experiments are carried out in a continuous laboratory scale flat-panel PBR, at different constant light intensities and under a day-night irradiation regime, to ascertain the performances of this combined PV-PBR system in terms of biomass productivity and overall photoconversion efficiency, compared to traditional transparent PBRs. The results obtained show that the configuration proposed, combining biomass production with innovative photovoltaics technology, could be a valuable way to improve light energy utilization and efficiency in microalgal production. (C) 2017 Elsevier Ltd. All rights reserved.
Thioredoxin peroxidases (TPxs) play an important role in maintaining redox homeostasis and in protecting organisms from the accumulation of toxic reactive oxygen species (ROS). In this study, we isolated the thioredoxin peroxidase-3 gene of Schistosoma japonicum, SjTPx-3. The open reading frame (ORF) of SjTPx-3 was 663 bp encoding 220 amino acids with a molecular weight of 24.99 kDa and an isoelectric point of 6.20. Quantitative real-time reverse transcription-polymerase chain reaction indicated that SjTPx-3 was expressed in all different stages of the parasites, with highest expression in 35-day-old worms. The ORF of SjTPx-3 was subcloned into pET-32a (+) vectors and expressed in Escherichia coli. Recombinant SjTPx-3 (rSjTPx-3) was expressed as a soluble protein with good antigenicity, as demonstrated by western blotting. Immunohistochemical analysis revealed that SjTPx-3 was mainly localized on the tegument of the parasites. Mice vaccinated with rSjTPx-3 had a 37.02% (P < 0.05) reduction in worm burden and 56.52% (P < 0.05) reduction in liver egg production compared with control, unvaccinated mice. Enzyme-linked immunosorbent assay analysis demonstrated that rSjTPx-3 could induce high levels of anti-rSjTPx-3-specific IgG, IgG1, and IgG2a antibodies. Characteristic Th1 and Th2 immune response cytokines were detected by flow cytometry and were increased by rSjTPx-3. Taken together, these results suggest that SjTPx-3 is an antioxidant enzyme responsible for protecting S. japonicum from oxidative stress. rSjTPx-3 may represent a potential vaccine candidate and/or new drug target for patients with schistosomiasis.
Introduction: Schistosomiasis is a neglected tropical disease affecting hundreds of millions of people worldwide. Recent advances in the field of proteomics and the development of new and highly sensitive mass spectrometers and quantitative techniques have provided new tools for advancing the molecular biology, cell biology, diagnosis and vaccine development for public health threats such as schistosomiasis.Areas covered: In this review we describe the latest advances in research that utilizes proteomics-based tools to address some of the key challenges to developing effective interventions against schistosomiasis. We also provide information about the potential of extracellular vesicles to advance the fight against this devastating disease.Expert commentary: Different proteins are already being tested as vaccines against schistosomiasis with promising results. The re-analysis of the Schistosoma spp. proteomes using new and more sensitive mass spectrometers as well as better separation approaches will help identify more vaccine targets in a rational and informed manner. In addition, the recent development of new proteome microarrays will facilitate characterisation of novel markers of infection as well as new vaccine and diagnostic candidate antigens.
Currently in China, the schistosomiasis control program has shifted its focus from transmission control to the elimination of the disease. Effective forecast and surveillance systems of schistiosomiasis are of great importance for issuing timely and early warnings on risk of infection, and therefore implementing preventive measures to avoid infection. There is great demand in more sensitive and specific methods to improve the surveillance system for early detection of S. japonicum infection in sentinel mice. In this study, we reported a sensitive nested-PCR assay targeting a 303-bp fragment from highly repetitive retrotransposon SjCHGCSI9 to detect the S. japonicum DNA in sera of experimental mice. Meanwhile, detection efficacy of the nested-PCR was compared with two conventional methods for field monitoring schistosomiasis such as ELISA and IHA. The nested-PCR assay could detect the specific DNA at 3-day post infection in sera of mice with 5 cercariae infection, while for ELISA and IHA, both show negative results even after 2 weeks post-infection in mice with 20 cercariae infection. Our results demonstrated the DNA based assay was more sensitive to make early diagnosis of S. japonicum infection in sentinel mice models, which will improve the early-warning ability of schistosomiasis surveillance system. (C) 2016 Published by Elsevier Inc.
Attachment has recently been proposed as a key developmental construct in psychosis, in particular with respect to interpersonal functioning and social cognition. The current study examined the latent structure of the self-report Psychosis Attachment Measure (PAM) and its relationship to lower-level perceptual and higher-order inferential social cognitive processes. The PAM was administered to 138 psychiatrically stable outpatients with schizophrenia alongside a battery of symptom, social cognitive, and functional measures. PAM responses were analyzed using latent variable measurement models, which did not yield evidence of the coherent two-dimensional structure predicted by previous literature. A unidimensional subscale comprising 6 of the 16 original PAM items possessed the strongest psychometric properties. This subscale was generally uncorrelated with social cognitive measures and showed weak correlations with some symptoms measures and with community functioning. These results suggest that either the PAM may not measure attachment in psychosis or it may measure only attachment anxiety but demonstrate little construct validity in this population. These results tell a cautionary tale regarding making theoretical inferences on the basis of measures without coherent latent structure. Attachment measures with stronger psychometric properties will help clarify putative relationships between attachment and social cognitive processes in psychosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
This research explored the relationship between executive functions (working memory and reasoning subtests of the Wechsler Adult Intelligence Scale, Trail Making and Stroop tests, fluency and planning tasks, and Wisconsin Card Sorting Test) and emotional intelligence measured by the Mayer-Salovey-Caruso Emotional Intelligence Test in patients with schizophrenia or borderline personality disorder compared to a control group. As expected, both clinical groups performed worse than the control group in executive functions and emotional intelligence, although the impairment was greater in the borderline personality disorder group. Executive functions significantly correlated with social functioning. Results are discussed in relation to the brain circuits that mediate executive functions and emotional intelligence and the findings obtained with other models of social cognition. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
For at least a century, a debate has continued as to whether cancer risk is reduced in schizophrenia. Genetic studies have also suggested the 2 conditions may share protein transcriptional pathways. The author predicted that if the pathophysiology of schizophrenia confers protection from cancer, then the immunology of schizophrenia should reflect a state of tumor suppression, ie, the opposite of tumor escape. To examine this possibility, the author performed a literature search for measurements of cytokines in drug-na < ve first episode subjects with schizophrenia for comparison with cytokine expression in tumor escape vs tumor suppression. The comparison showed that instead of either tumor suppression or escape, schizophrenia appears to be in a state of tumor equilibrium. Based on this finding, the author hypothesized that the clinical presentation of schizophrenia may involve cell transformation similar to an early stage of cancer initiation or an attenuated tumorigenesis. While this condition could reflect the presence of an actual tumor such as an ovarian teratoma causing anti-NMDA receptor encephalitis, it would only explain a small percentage of cases. To find a more likely tumor model, the author then compared the cytokine profile of schizophrenia to individual cancers and found the best match was melanoma. To demonstrate the viability of the theory, the author compared the hallmarks, emerging hallmarks, and enabling characteristics of melanoma to schizophrenia and found that many findings in schizophrenia are understood if schizophrenia is a condition of attenuated tumorigenesis.
There has been a growing link between a history of cannabis use and neurocognitive performance in patients with schizophrenia. Fewer neurocognitive deficits may be a marker of the superior social cognition needed to obtain illicit substances, or cannabis use may indicate a distinct path to schizophrenia with less neurocognitive vulnerability. This study sought to determine whether the relationship of cannabis use and executive function exists independently of social cognition. Eighty-seven patients with schizophrenia were administered measures of social cognition and executive function. Social cognition was assessed using the Bell-Lysaker Emotion Recognition Test to measure affect recognition, and the Eyes and Hinting Tests to measure theory of mind. Executive function was assessed by the Mental Flexibility component of the Delis-Kaplan Executive Functioning Scale. The relations between the variables were examined with structural equation modeling. Cannabis use positively related to executive function, negatively related to affect recognition, and had no relationship with theory of mind. There were no indirect effects of other illicit substances on amount of regular cannabis use. Alcohol use was related to worse affect recognition. The relationship between cannabis use and better executive function was supported and was not explained by superior social cognition
Objective: Few studies have evaluated the effects of visual remediation strategies in schizophrenia despite abundant evidence of visual-processing alterations in this condition. We report preliminary, case-study-based evidence regarding the effects of visual remediation in this population. Method: We describe implementation of a visual-perceptual training program called ULTIMEYES (UE) and initial results through 3 brief case studies of individuals with schizophrenia. UE targets broad-based visual function, including low-level processes (e.g., acuity, contrast sensitivity) as well as higher level visual functions. Three inpatients, recruited from a research unit, participated in at least 38 sessions 3 to 4 times per week for approximately 25 min per session. Contrast sensitivity (a trained task), as well as acuity and perceptual organization (untrained tasks), were assessed before and after the intervention. Levels of progression through the task are also reported. Results: UE was well tolerated by the participants and led to improvements in contrast sensitivity, as well as more generalized gains in visual acuity in all 3 participants and perceptual organization in 2 participants. Symptom profiles were somewhat different for each participant, but all were symptomatic during the intervention. Despite this, they were able to focus on and benefit from training. The adaptive nature of the training was well suited to the slower progression of 2 participants. Conclusions and Implications for Practice: These case studies set the stage for further research, such as larger, randomized controlled trials of the intervention that include additional assessments of perceptual function and measures of cognition, social cognition, and functional outcomes.
Whenmaking decisions in everyday life, we often have to choose between uncertain outcomes. Economic studies have demonstrated that healthy people tend to prefer options with known probabilities (risk) than those with unknown probabilities (ambiguity), which is referred to as "ambiguity aversion." However, it remains unclear how patients with schizophrenia behave under ambiguity, despite growing evidence of their altered decision-making under uncertainty. In this study, combining economic tools and functional magnetic resonance imaging (fMRI), we assessed the attitudes toward risk/ambiguity and investigated the neural correlates during decision-making under risk/ambiguity in schizophrenia. Although no significant difference in attitudes under risk was observed, patients with schizophrenia chose ambiguity significantly more often than the healthy controls. Attitudes under risk and ambiguity did not correlate across patients with schizophrenia. Furthermore, unlike in the healthy controls, activation of the left lateral orbitofrontal cortex was not increased during decision-making under ambiguity compared to under risk in schizophrenia. These results suggest that ambiguity aversion, a well-established subjective bias, is attenuated in patients with schizophrenia, highlighting the need to distinguish between risk and ambiguity when assessing decision-making under these situations. Our findings, comprising important clinical implications, contribute to improved understanding of the mechanisms underlying altered decision-making in patients with schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Twenty years have passed since the dysconnection hypothesis was first proposed (Friston and Frith, 1995; Weinberger, 1993). In that time, neuroscience has witnessed tremendous advances: we now live in a world of non-invasive neuroanatomy, computational neuroimaging and the Bayesian brain. The genomics era has come and gone. Connectomics and large-scale neuroinformatics initiatives are emerging everywhere. So where is the dysconnection hypothesis now? This article considers how the notion of schizophrenia as a dysconnection syndrome has developed - and how it has been enriched by recent advances in clinical neuroscience. In particular, we examine the dysconnection hypothesis in the context of (i) theoretical neurobiology and computational psychiatry; (ii) the empirical insights afforded by neuroimaging and associated connectomics - and (iii) how bottom-up (molecular biology and genetics) and top-down (systems biology) perspectives are converging on the mechanisms and nature of dysconnections in schizophrenia. (C) 2016 The Authors. Published by Elsevier B.V.
Objective: To investigate whether risperidone improves social cognitive impairments and executive dysfunction in people with schizophrenia. Methods: Fifty-six patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for schizophrenia were allocated to a risperidone treatment group (RTG, n= 28) and a typical antipsychotic treatment group (TATG, n= 28). Twenty-eight healthy volunteers were recruited as the normal control group (NCG). The Positive and Negative Syndrome Scale, Interpersonal Perception Task-15 (IPT-15), and Wisconsin Card Sorting Test (WCST) were rated at baseline and after 4 and 12 weeks of treatment with risperidone or typical antipsychotics. Results: Risperidone and typical antipsychotics decreased Positive and Negative Syndrome Scale scores for total psychopathology and positive and negative symptoms. At baseline, in the IPT-15, total scores and five factor scores, as well as the number of categories completed and the percentage of conceptual level responses, were significantly lower in the RTG and TATG than in the NCG, whereas total response errors, perseverative errors, and failure to maintain set were significantly higher in the patient groups than in the NCG. Repeated measures analysis of variance revealed a significant main effect of time period (baseline, 4 weeks, and 12 weeks) for IPT-15 scores and WCST performances, and significant interactions for time period x group (RTG and TATG). Multivariate analysis of variance showed no significant differences between the RTG and TATG on IPT-15 scores at 4 weeks, but there were significant differences between these two groups at 12 weeks. Significant differences were also found between the RTG and TATG on WCST performances at 4 and 12 weeks. Conclusion: Individuals with schizophrenia have impairments in social cognitive and executive function, which might be improved by risperidone.
Introduction: The accurate discrimination of another person's eyegaze direction is vital as it provides a cue to the gazer's focus of attention, which in turn supports joint attention. Patients with schizophrenia have shown a "direct gaze bias" when judging gaze direction. However, current tasks do not dissociate an early perceptual bias from high-level top-down effects. We investigated early stages of gaze processing in schizophrenia by measuring perceptual sensitivity to fine deviations in gaze direction (i.e., the cone of direct gaze: CoDG) and ability to reflexively orient to locations cued by the same deviations. Methods: Twenty-four patients and 26 controls completed a CoDG discrimination task that used realistic direct-face images with six fine degrees of deviation (i.e., 3, 6 or 9 pixels to the left and right) and direct gaze, and a gaze cueing task that assessed reflexive orienting to the same fine-grained deviations. Results: Our data showed patients exhibited no impairment in gaze discrimination, nor did we observe a reduced orienting response. Conclusions: These results suggest that while patients may suffer deficits associated with interpreting another person's gaze, the earliest processes concerned with detecting averted gaze and reflexively orienting to the gazed-at location are intact.
Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task. In a second cohort (n = 21 schizophrenia/schizoaffective patients, n = 13 healthy controls), event-related potential and event-related time-frequency measures of auditory dysfunction were assessed during administration of the NMDAR agonist D-serine. Mismatch negativity was used as a functional read-out of auditory-level function. Clinical trials registration numbers were NCT01474395/NCT02156908. Schizophrenia/schizoaffective patients showed significantly reduced auditory plasticity versus healthy controls (P = 0.001) that correlated with measures of cognitive, occupational and social dysfunction. In event-related potential/time-frequency analyses, patients showed highly significant reductions in sensory N1 that reflected underlying impairments in theta responses (P < 0.001), along with reduced theta and beta-power modulation during retention and motor-preparation intervals. Repeated administration of D-serine led to intercorrelated improvements in (i) auditory plasticity (P = 0.001); (ii) theta-frequency response (P < 0.05); and (iii) mismatch negativity generation to trained versus untrained tones (P = 0.02). Schizophrenia/schizoaffective patients show highly significant deficits in auditory plasticity that contribute to cognitive, occupational and social dysfunction. D-serine studies suggest first that NMDAR dysfunction may contribute to underlying cortical plasticity deficits and, second, that repeated NMDAR agonist administration may enhance cortical plasticity in schizophrenia.
Patients with severe mental illnesses manifest substantial deficits in self-assessment of the abilities that impact everyday functioning. This study compares patients with schizophrenia to healthy individuals on their social cognitive performance, their assessment of that performance, and the convergence between performance and indicators of effort in solving tasks. Patients with schizophrenia (n = 57) and healthy controls (HC; n = 47) completed the Bell-Lysaker Emotion Recognition Test (BLERT), a psychometrically sound assessment of emotion recognition. Participants rated their confidence in the accuracy of their responses after each item. Participants were instructed to respond as rapidly as possible without sacrificing accuracy; the time to complete each item was recorded. Patients with schizophrenia performed less accurately on the BLERT than HC. Both patients and HC were more confident on items that they correctly answered than for items with errors, with patients being less confident overall; there was no significant interaction for confidence between group and accuracy. HC demonstrated a more substantial adjustment of response time to task difficulty by taking considerably longer to solve items that they got wrong, whereas patients showed only a minimal adjustment. These results expand knowledge about both self-assessment of social cognitive performance and the ability to appraise difficulty and adjust effort to social cognitive task demands in patients with schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
While attributional style is regarded as a core domain of social cognition, questions persist about the psychometric characteristics of measures used to assess it. One widely used assessment of attributional style is the Ambiguous Intentions Hostility Questionnaire (AIHQ). Two limitations of the AIHQ include (1) a possible restricted range resulting from too few and too homogenous item scenarios, and (2) use of rater scores that are cumbersome and time-consuming to score and have unknown incremental validity. The present study evaluated the psychometric properties of the AIHQ while concurrently testing changes aiming to improve the scale, in particular expansion of the number of self-report items and removal of the rater-scored items. One hundred sixty individuals diagnosed with schizophrenia and 58 healthy controls completed the full AIHQ along with measures of symptoms, functioning, and verbal intelligence. The AIHQ particularly the self-reported blame score demonstrated adequate internal consistency, test-retest reliability, and distinguished patients from controls. It also was significantly related to clinically-rated hostility and suspiciousness symptoms, and correlated with functional capacity even after controlling for verbal intelligence. Incremental validity analyses suggested that a higher number of self-report items strengthens relationships to outcomes in a manner that justifies this expansion, while rater-scored items had mixed results in providing additional information beyond self-report in the AIHQ. (C) 2017 Published by Elsevier Ltd.
Introduction: Relationship perception focuses on social interactions, is reduced in schizophrenia and is related to daily functioning. It can be assessed with the Relationships Across Domains (RAD) test, built on Relational Models Theory which states that people use four relational models to interpret social interaction. RAD is time consuming, low on tolerability and only used in English-speaking countries. We evaluated the psychometric properties of a translated, abbreviated Norwegian version.Methods: Sixty-two schizophrenia participants and 56 healthy controls underwent assessments of social and non-social cognition. The schizophrenia group completed functional and clinical measures. RAD's internal consistency was investigated with Cronbach's alphas, group differences with logistic regressions and associations between study variables with Pearson's correlations.Results: RAD was reduced from 25 (Cronbach's alpha=.809) to 12 vignettes (Cronbach's alpha=.815). Schizophrenia participants had significant impairments, with larger effect sizes for the full version. Associations of RAD with study variables were similar for the two versions: smaller for clinical measures and larger for functional and cognitive measures. Results were comparable to results for the English version.Conclusions: The length of the Norwegian RAD was reduced while retaining its psychometric properties, which were similar to the English version. This suggests the test's cross-cultural utility.
Context: Patients with schizophrenia display abnormalities in pitch discrimination of non-verbal tones as revealed by the Tone-Matching Task (TMT). It may lead to deficits in higher-order cognitive functions and clinical symptoms. Objectives: We conducted a systematic review and meta-analysis pooling data about TMT score differences between patients with schizophrenia and healthy controls, to evaluate the deficit's effect size, and to develop reliable knowledge about pitch processing impairment and its pejorative impact. Method: Relevant publications were identified by a systematic search of PubMed and EMBASE databases. Then, we excluded non-relevant studies for the meta-analysis. Effect size for percent of correct responses to the TMT was expressed as standardized mean difference (SMD). Results: Eighteen of 167 identified studies met eligibility criteria for review, of which 10 were included in the meta-analysis. Our meta-analysis showed that the effect size for the percent of correct response to the TMT between patients (N=371) and controls (N=342) was large: SMD=1.17 [95% CI: 0.926-1.418] (z-value=9.338 and p-value = 0.001). Meta-analysis showed moderate heterogeneity between studies (Q(9)=17.22, p=0.04, I-2=47.74%). The relationship between tone-matching impairment and clinical symptoms of schizophrenia remains heterogeneous across studies. Some authors observed significant correlations between tone-matching performance and a number of higher-order cognitive abilities. Conclusion: This review and meta-analysis highlights a large significant disturbance in tone-matching ability in patients as compared with controls. The study of basic auditory processing opens promising perspectives for pathophysiological modelling of the disorder and therapeutic issues. (C) 2016 Elsevier B. V. All rights reserved.
A significant correlation exists between violence and schizophrenia (SCZ). Recent studies matched sonic cognitive deficits like strong risk factors for violence with interesting applications in terms of treatment. Our objective was to conduct a systematic review of the effectiveness of cognitive remediation (CR) and social cognitive training (SCT) in the management of violent and aggressive behaviors in SCZ. Methods: The electronic databases Pubmed, Web of Science, Cochrane Library and ScienceDirect were searched in, using combinations of terms relating to SCZ, CR and violence. Studies were selected and data were extracted using a PRISMA statement. Inclusion criteria were adults with SCZ and a documented collection of disruptive and violent behaviors, for whom researchers had used a CR or SCT program. Results: Eleven studies were identified, two related to non-specific CR intervention and nine to codified CR or SCT programs. Results showed that these programs had a positive impact on the control and reduction of global aggressive attitudes and physical assaults. Therapeutic targets were social cognition and executive functions through the improvement of interpersonal relationships and impulsivity feature respectively. Effectiveness was proved at various stages of the illness, in different types of patients and units, with effects persisting for up to 12 months after interruption of CR. Conclusions are limited by some methodological restrictions. Conclusion: Although current evidences need to be completed with further randomized studies, CR and SCI. appear to be promising approaches in the management of violence in SCZ.
Do social cognition and epistemological understanding promote elementary school children's experimentation skills? To investigate this question, 402 children (ages 8, 9, and 10) in 2nd, 3rd, and 4th grades were assessed for their experimentation skills, social cognition (advanced theory of mind [AToM]), epistemological understanding (understanding the nature of science), and general information- processing skills (inhibition, intelligence, and language abilities) in a whole- class testing procedure. A multiple indicators multiple causes model revealed a significant influence of social cognition (AToM) on epistemological understanding, and a McNemar test suggested that children's development of AToM is an important precursor for the emergence of an advanced, mature epistemological understanding. Children's epistemological understanding, in turn, predicted their experimentation skills. Importantly, this relation was independent of the common influences of general information processing. Significant relations between experimentation skills and inhibition, and between epistemological understanding, intelligence, and language abilities emerged, suggesting that general information processing contributes to the conceptual development that is involved in scientific thinking. The model of scientific thinking that was tested in this study (social cognition and epistemological understanding promote experimentation skills) fitted the data significantly better than 2 alternative models, which assumed nonspecific, equally strong relations between all constructs under investigation. Our results support the conclusion that social cognition plays a foundational role in the emergence of children's epistemological understanding, which in turn is closely related to the development of experimentation skills. Our findings have significant implications for the teaching of scientific thinking in elementary school and they stress the importance of children's epistemological understanding in scientific- thinking processes.
In the field of power electronics and instrumentation, SCR is a power electronics device used and the analog gate trigger circuit of SCR is often designed to trigger the SCR. There is nonlinear relationship between the conduction angle of the SCR and the input signal of the analog gate trigger circuit. The nonlinear can introduce the errors into the control system and the nonlinear compensation is difficult to do. The paper takes the double base diode as an example and designs a analog circuit which is used to trigger the SCR and there is the linear relationship between the conduction angle of the SCR and the input signal of the analog circuit. The circuit's practice reveal that it is reliable and practical method of triggering the SCR.
Dalian sea cucumber, Yantai sea cucumber, and Weihai sea cucumber, which belong to Apostichopus japonicus, are protected as geographical indications in China based on their high nutritional values and medical propertys. The 26 samples, including Dalian sea cucumbers (9 samples) in Liaoning province, Yantai sea cucumbers (9 samples), and Weihai sea cucumbers (8 samples) in Shandong province, were individually collected from the designated geographical sea areas and the genetic relationships and DNA polymorphisms were evaluated by random amplified polymorphic DNA technology and gene segments sequencing. The RAPD dendrogram showed that the genetic diversity of the three types of sea cucumbers was rich. The neighbor-joining tree shows that the genetic relationship of the samples from the adjacent sea areas is closer. It demonstrates that the gene characteristics of sea cucumbers from different sea areas were obvious and the genetic diversity analysis by RAPD-PCR can be used as a rapid method for geographical discrimination.
Seafood fraud - often involving substitution of one species by another - has attracted much attention as it is prevalent worldwide. Whilst DNA analysis has helped to combat this type of fraud some of the methods currently in use are time-consuming and require sophisticated equipment or highly-trained personnel. This work describes the development of a new, real-time PCR TaqMan assay for the detection of ling (Molva molva) in seafood products. For this purpose, specific primers and a minor groove binding (MGB) TaqMan probe were designed to amplify the 81 bp region on the cyt b gene. Efficiency, specificity and cross-reactivity assays showed statistically significant differences between the average Ct value obtained for Molva molva DNA (19.45 +/- 0.65) and the average Ct for non-target species DNA (38.3 +/- 2.8), even with closely related species such as Molva dypterygia (34.9 +/- 0.09). The proposed methodology has been validated with 31 commercial samples. (C) 2017 Elsevier Ltd. All rights reserved.
Offshore cultivation of seaweed provides an innovative feedstock for biobased products supporting blue growth in northern Europe. This paper analyzes two alternative exploitation pathways: energy and protein production. The first pathway is based on anaerobic digestion of seaweed which is converted into biogas, for production of electricity and heat, and digestate, used as fertilizer; the second pathway uses seaweed hydrolysate as a substrate for cultivation of heterotrophic microalgae. As a result the seaweed sugars are consumed while new proteins are produced enhancing the total output. We performed a comparative Life Cycle Assessment of five scenarios identifying the critical features affecting resource efficiency and environmental performance of the systems with the aim of providing decision support for the design of future industrial scale production processes. The results show that all scenarios provide environmental benefits in terms of mitigation of climate change, with biogas production from dried Laminaria digitata being the most favorable scenario, quantified as -18.7*10(2) kg CO2 eq./ha. This scenario presents also the lowest consumption of total cumulative energy demand, 1.7*10(4) MJ/ha, and even resulting in a net reduction of the fossil energy fraction, -1.9*10(4) MJ/ha compared to a situation without seaweed cultivation. All scenarios provide mitigation of marine eutrophication thanks to bioextraction of nitrogen and phosphorus during seaweed growth. The material consumption for seeded lines has 2-20 times higher impact on human toxicity (cancer) than the reduction achieved by energy and protein substitution. However, minor changes in cultivation design, i.e. use of stones instead of iron as ballast to weight the seeded lines, dramatically reduces human toxicity (cancer). Externalities from the use of digestate as fertilizer affect human toxicity (non-cancer) due to transfer of arsenic from aquatic environment to agricultural soil. However concentration of heavy metals in digestate does not exceed the limit established by Danish regulation. The assessment identifies seaweed productivity as the key parameter to further improve the performance of the production systems which are a promising service provider of environmental restoration and climate change mitigation. (C) 2017 Elsevier Ltd. All rights reserved.
Aims: Self-reported information from questionnaires is frequently used in clinical epidemiological studies, but few provide information on the reproducibility of instruments applied in secondary coronary prevention studies. This study aims to assess the test-retest reproducibility of the questionnaire applied in the cross-sectional NORwegian CORonary (NOR-COR) Prevention Study. Methods: In the NOR-COR study 1127 coronary heart disease (CHD) patients completed a self-report questionnaire consisting of 249 questions, of which there are both validated instruments and de novo questions. Test-retest reliability of the instrument was estimated after four weeks in 99 consecutive coronary patients. Intraclass Correlation Coefficient (ICC) and Kappa () were calculated. Results: The mean interval between test and retest was 33 (+/- 6.4) days. Reproducibility values for questions in the first part of the questionnaire did not differ from those in the latter. A good to very good reproducibility was found for lifestyle factors (smoking: = 1.0; exercise: ICC = 0.90), medical factors (drug adherence: ICC = 0.74; sleep apnoea: ICC = 0.87), and psychosocial factors (anxiety and depression: ICC = 0.95; quality of life 12-Item Short-Form Health Survey (SF12): ICC = 0.89), as well as for the majority of de-novo-created variables covering the patient's perceptions, motivation, needs, and preferences. Conclusions: The present questionnaire demonstrates a highly acceptable reproducibility for all key items and instruments. It thus emerges as a valuable tool for evaluating patient factors associated with coronary risk factor control in CHD patients.
We investigated the implicit attitudes of Chinese youth towards the second-generation rich, and the relationship of these with their explicit attitudes. Participants were 119 undergraduate students ( 58 men and 61 women). Using the Semantic Differential Measure and the Feeling Thermometer Scale, we examined the participants' explicit attitudes, and we used the Implicit Association Test to assess their implicit attitudes toward the second-generation rich. Results showed that the participants did not show a negative implicit attitude towards the second-generation rich. However, the participants exhibited a negative explicit attitude toward the second-generation rich. These results are consistent with previous research. This suggests that the second-generation rich can take advantage of these findings and project a more positive image of themselves to other people in China.
Sediment microbial fuel cells (SMFCs) are expected to be used as a renewable power source for remote environmental monitoring; therefore, evaluation of their long-term power performance is critical for their usability. In' this paper, we present novel data needed to understand the long-term performance of SMFCs. We used 3-D Microemulsion (3DMe)(TM) doped anodes, which slowly release lactate and its fermented products. During our tests, anode-limited SMFCs with and without 3DMe-doped anodes were operated for more than 18 months with a load simulating a sensor operation. We found that dclping an anode with an electron donor reduced startup time and increased maximum power (55 +/- 2 mu W compared to 46 +/- 2 mu W) in the control systems. We found that the long-term steady power performance is approximately 33% of the maximum power (similar to 18 LW). Finally, our small-sized SMFCs generated higher power densities than those in the literature (28 mW/m(2) versus 4 mW/m2). Using electron donor doped anodes can be practical when a short startup time and initial high power are needed. However, if long-term power is critical, the addition of an electron donor does not provide a practical advantage. In addition, in long-term operation enrichment of the anode surface with electrochemically active bacteria does not provide any advantage. (C) 2016 Elsevier Ltd. All rights reserved.
Recent advances in sediment source tracing or fingerprinting procedures have focussed primarily on the use of novel sediment properties that are either easier to measure or provide improved source discrimination, or on improved procedures for representing and estimating the uncertainty associated with the final source apportionment results. Spatial variability of source properties has long been recognised as a potential problem for the approach, but there have been few attempts to explore the nature and magnitude of such variability and its wider implications for source fingerprinting investigations. This contribution addresses this issue with particular reference to surficial sediment sources. It reports the results of an investigation aimed at documenting the magnitude and nature of the spatial variability of the geochemical properties of surface soils within a single 7 ha cultivated field and exploring the implications of the findings for sediment source fingerprinting procedures. Samples of surface soil were collected from 52 points located within the field. Particular attention is directed to the extent of the spatial variability of 53 geochemical properties of the surface soil which could potentially be used as fingerprints, the importance of the influence of soil redistribution rate on the properties of the surface soil, provision of guidelines for selecting sampling points and the degree of correlation between different soil properties and its implications for the numerical procedures employed in sediment source fingerprinting studies. A novel aspect of the study is that caesium-137 (Cs-137) measurements were used to provide information on the magnitude and spatial pattern of the soil redistribution rate within the field, so that the influence of soil redistribution rate in causing systematic spatial variability of fingerprint properties could be further explored. (C) 2016 Elsevier Ltd. All rights reserved.
Many studies deal with the impact of prevention campaigns. Whatever the method used, most of them postulate that people take the campaign into consideration as soon as they are exposed to it. The cognitive dissonance theory (Festinger, 1957, 1964) postulates the principle of selective exposure. People tend to both expose themselves to consistent information to strengthen their attitude and behavior and avoid inconsistent one. Avoiding inconsistent information prevents them from threatening position which could modify their attitude. The goal of this research consists in verifying a selective exposure effect concerning smoking prevention using a measure of implicit attitude. This research was conducted in a professional training institute. Participants were recruited on the pretext of a consultation as part of a training design on addictions. They were either employees or trainees from the institute. Forty-four smokers and 80 non-smokers took part in the experiment. They had to precise which prevention thematic (among six addictions) would interest them in order to construct a new training/formation program dealing with dangers of addiction the harmful effects of tobacco, alcohol, drugs etc. People were asked what kind of topic would interest them most. Then, their attitudes and behavior toward smoking were evaluated. To evaluate smoking attitudes, we used both an explicit (Attitude Toward Smoking Scale [ATS]; Etter et al., 2000) and an implicit measure (Single Category Implicit Association Test Personalized [SC-IAT-P]; Bardin et al., 2014). Smoking habits were also recorded. Results revealed that smokers have an implicit attitude less negative than non-smokers. Implicit attitude of smokers also predicts selective exposure. The more their attitude is positive, the less people would like to expose themselves to smoking prevention information. At last, smokers who have already considered quitting are more inclined to expose to such information than other smokers. These results support the hypothesis of an effect on attitudes explicit and implicit in the expression of needs in the context of smoking prevention training design. (C) 2015 Societe Francaise de Psychologie. Published by Elsevier Masson SAS. All rights reserved.
This paper presents an experimental investigation on specimens manufactured by Selective Laser Sintering (SLS), with the purposes of giving designers advice when designing 3D printed parts, and laying the basis for a step forward in the field of fracture mechanics of 3D complex parts. The aim is to investigate the effect of building direction in Polyamide (PA) 3D printed samples and to assess whether a crack can be initiated directly from the sintering process for fracture mechanics study purposes. Six different configurations of Mode I Compact Tension (CT) specimens were manufactured and tested; the experiments were monitored by Digital Image Correlation (DIC) and fractured surfaces were analyzed using microscopy. Results showed that samples with better mechanical performance are those in which all the layers contain a portion of the crack. On the other hand, those with layers parallel to the crack plan offer a preferential pathway for the crack to propagate. DIC and fractography investigations showed that, under certain conditions, small-radius geometries, or too-close surfaces may bond together depending on printer resolution. Experiments also showed that SLS is capable of printing specimens with internal cracks that can be used to study fracture mechanics of complex parts or parts with internal cracks. (C) 2016 Elsevier Ltd. All rights reserved.
By grounding the self in the body, experimental psychology has taken the body as the starting point for a science of the self. One fundamental dimension of the bodily self is the sense of body ownership that refers to the special perceptual status of one's own body, the feeling that "my body" belongs to me. The primary aim of this review article is to highlight recent advances in the study of body ownership and our understanding of the underlying neurocognitive processes in three ways. I first consider how the sense of body ownership has been investigated and elucidated in the context of multisensory integration. Beyond exteroception, recent studies have considered how this exteroceptively driven sense of body ownership can be linked to the other side of embodiment, that of the unobservable, yet felt, interoceptive body, suggesting that these two sides of embodiment interact to provide a unifying bodily self. Lastly, the multisensorial understanding of the self has been shown to have implications for our understanding of social relationships, especially in the context of self-other boundaries. Taken together, these three research strands motivate a unified model of the self inspired by current predictive coding models.
The mental representation of the self is a complex construct, comprising both conceptual information and perceptual information regarding the body. Evidence suggests that both the conceptual self-representation and the bodily selfrepresentation are malleable, and that these different aspects of the self are linked. Changes in bodily self-representation appear to affect how the self is conceptualized, but it is unclear whether the opposite relationship is also true: Do changes to the conceptual self-representation affect how the physical self is perceived? First, we adopted a perceptual matching paradigm to establish an association between the self and an unfamiliar face (Experiment 1). Robust attentional and perceptual biases in the processing of this newly self-associated object suggested that the conceptual self-representation was extended to include it. Next, we measured whether the bodily self-representation had correspondingly changed to incorporate the new face (Experiment 2). Participants rated morphs between their own and the newly-associated according to how similar they were to the self, before and after performing the perceptual matching task. Changes to the conceptual self did not have an effect on the bodily self-representation. These results suggest that modulatory links between aspects of the mental self-representation, when focused on the nonsocial self, are unidirectional and flow in a bottom-up manner.
Autoimmune diseases occur when the immune system incorrectly recognizes self-molecules as foreign; in the case of multiple sclerosis (MS), myelin is attacked. Intriguingly, new studies reveal toll-like receptors (TLRs), pathways usually involved in generating immune responses against pathogens, play a significant role in driving autoimmune disease in both humans and animal models. We reasoned polyplexes formed from myelin self-antigen and regulatory TLR antagonists might limit TLR signaling during differentiation of myelin-specific T cells, inducing tolerance by biasing T cells away from inflammatory phenotypes. Complexes were formed by modifying myelin peptide with cationic amino acids to create peptides able to condense the anionic nucleic-acid based TLR antagonist. These immunological polyplexes eliminate synthetic polymers commonly used to condense polyplexes and do not rely on gene expression; however, the complexes mimic key features of traditional polyplexes such as tunable loading and co-delivery. Using these materials and classic polyplex analysis techniques, we demonstrate condensation of both immune signals, protection from enzymatic degradation, and tunable physicochemical properties. We show polyplexes reduce TLR signaling, and in primary dendritic cell and T cell co-culture, reduce myelin-driven inflammation. During mouse models of MS, these tolerogenic polyplexes improve the progression, severity, and incidence of disease. (C) 2016 The Authors. Published by Elsevier Ltd.
Self-awareness is often impaired after acquired brain injury (ABI) and this hampers rehabilitation, in general: unrealistic reports by patients about their functioning and poor motivation and compliance with treatment. We evaluated a self-awareness treatment that was part of a treatment protocol on executive dysfunction (Spikman, Boelen, Lamberts, Brouwer, & Fasotti, 2010). A total of 63 patients were included, aged 17-70, suffering non-progressive ABI, and minimum time post-onset of 3 months. Self-awareness was measured by comparing the patient's Dysexecutive Questionnaire (Wilson, Alderman, Burgess, Emslie, & Evans, 1996) score with that of an independent other. As emotion recognition is associated with self-awareness and influences the effect of rehabilitation treatment, we assessed this function using the Facial Expressions of Emotion-Stimuli and Tests (Young, Perrett, Calder, Sprengelmeyer, & Ekman, 2002). Results showed that patients in the experimental treatment group (n = 29) had better self-awareness after training than control patients (n = 34). Moreover, our results confirmed that the level of self-awareness before treatment was related to emotion recognition. Hence, self-awareness can improve after neuropsychological treatment fostering self-monitoring. Since neuropsychological treatment involves social learning, impairments in social cognition should be taken into account before starting and during treatment.
This article presents a rail-to-rail CMOS operational amplifier of constant gm. It offers simple topology and low power consumption. It uses a simplified shift level circuit at the input, a self-biased folded cascode as the intermediate stage and a class AB, or push-pull output stage to provide large gain. The amplifier, implemented in IBM 130nm CMOS technology, works on a 1.5V power supply voltage and consumes just 215 mu W, and offers a 125dB gain. A comparison to other work in the literature reveal a large gain, low power, rail-to-rail amplifier suitable to many applications.
In this article, an on-chip self-calibrated 8-bit R-2R digital-to-analog converter (DAC) based on digitally compensated input offset of the operational amplifier (OPAMP) is presented. To improve the overall DAC performance, a digital offset cancellation method was used to compensate deviations in the input offset voltage of the OPAMP caused by process variations. The whole DAC as well as offset compensation circuitry were designed in a standard 90 nm CMOS process. The achieved results show that after the self-calibration process, the improvement of 48% in the value of DAC offset error is achieved.
Growing evidence suggests that positive mental health or wellbeing protects against psychopathology. How and why those who flourish derive these resilient outcomes is, however, unknown. This exploratory study investigated if self-compassion, as it continuously provides a friendly, accepting and situational context for negative experiences, functions as a resilience mechanism and adaptive emotion regulation strategy that protects against psychopathology for those with high levels of positive mental health. Participants from the general population (n = 349) provided measures at one time-point on positive mental health (MHC-SF), self-compassion (SCS-SF), psychopathology (HADS) and negative affect (mDES). Self-compassion significantly mediated the negative relationship between positive mental health and psychopathology. Furthermore, higher levels of self-compassion attenuated the relationship between state negative affect and psychopathology. Findings suggest that especially individuals with high levels of positive mental health possess self-compassion skills that promote resilience against psychopathology. These might function as an adaptive emotion regulation strategy and protect against the activation of schema related to psychopathology following state negative affective experiences. Enhancing self-compassion is a promising positive intervention for clinical practice. It will not only impact psychopathology through reducing factors like rumination and self-criticism, but also improve positive mental health by enhancing factors such as kindness and positive emotions. This may reduce the future risk of psychopathology.
The formation of a coherent and unified self-concept represents a key developmental stage during adolescence. Imaging studies on self-referential processing in adolescents are rare, and it is not clear whether neural structures involved in self-reflection are also involved in reflections of familiar others. In the current study, 41 adolescents were asked to make judgments about trait adjectives during functional magnetic resonance imaging (fMRI): they had to indicate whether the word describes themselves, their friends, their teachers or politicians. Findings indicate a greater overlap in neural networks for responses to self- and friend-related judgments compared to teachers and politicians. In particular, classic self-reference structures such as the ventromedial prefrontal cortex and medial posterior parietal cortex also exhibited higher activation to judgments about friends. In contrast, brain responses towards judgments of teachers (familiar others) compared to politicians (unfamiliar others) did not significantly differ. Results support behavioral findings of a greater relevance of friends for the development of a self-concept during adolescence and indicate underlying functional brain processes. Hum Brain Mapp 38:987-996, 2017. (c) 2016 Wiley Periodicals, Inc.
Maladaptive self-criticism has been associated with diminished goal-progress. The present study examined the impact of failure and success experiences on performance on working memory measures, in order to gauge goal-directed performance. Participants with varying levels of self-criticism completed a baseline working memory task, a randomly assigned success or failure feedback manipulation on a separate task, followed by a second working memory measure. Results demonstrated varying feedback-dependent test-retest performance across levels of self-criticism. While low self-critics did not differ in test-retest scores across feedback conditions, failure resulted in a decrease of performance in moderate self-critics, and an increased performance in high self-critics. Conversely, after success, moderate self-critics displayed an increase, while high self-critics displayed a decrease in performance at retest. Findings shed light on varying perceptions and responses to failure versus success across levels of self-criticism, which has important implications for factors that impact motivation and goal-directed performance. (C) 2017 Elsevier Ltd. All rights reserved.
Experimental self-driving cars are being tested on public roads, and will at some point be commercially sold or made otherwise available to the public. A self-driving car and its digital control systems take over control tasks previously performed by the human driver. This places high demands on this control system which has to perform the highly complex task of driving the car through traffic. When this system does not perform its task adequately and damage ensues the failure of the control system may be used as a stepping stone to claim liability of the manufacturer of the car or the control system. Uncertainties about the application of (product) liability law may slow down the uptake of self-driving cars more than is warranted on the basis of technical progress. This article examines how the decision about the timing of a market introduction can be approached and how possible chilling effects of liability law can be redressed with an adequate system of obligatory insurance. (C) 2015 Maurice Schellekens. Published by Elsevier Ltd. All rights reserved.
Orth, Trzesniewski, and Robins (2010) concluded that the nationally representative Americans' Changing Lives (ACL) cohort-sequential study demonstrated moderate to large age differences in self-esteem, and no birth cohort (generational) differences in the age trajectory. In a reanalysis of these data using 2 different statistical techniques, we find significant increases in self-esteem that could be attributed to birth cohort or time period. First, hierarchical linear modeling analyses with birth cohort as a continuous variable (vs. the multiple group formulation used by Orth et al.) find that birth cohort has a measurable influence on self-esteem through its interaction with age. Participants born in later years (e.g., 1960) were higher in self-esteem and were more likely to increase in self-esteem as they aged than participants born in earlier years (e.g., 1920). However, the estimated age trajectory up to age 60 is similar in Orth et al.'s results and in the results from our analyses including cohort. Second, comparing ACL respondents of the same age in 1986 versus 2002 (a time-lag design) yields significant birth cohort differences in self-esteem, with 2002 participants of the same age higher in self-esteem than those in 1986. Combined with some previous studies finding significant increases in self-esteem and positive self-views over time, these results suggest that cultural change in the form of cohort and time period cannot be ignored as influences in cross-sectional and longitudinal studies.
Precise cell positioning is indispensable in the fields of biophysics and cellular biology. Acoustic microbeam produced by a highly focused ultrasound transducer has recently been investigated for a particle or cell manipulation. By virtue of the relatively good piezoelectric property, Sc doped AIN film was introduced for a highly focused ultrasound transducer application. Using a sputtering approach, a self focused AIScN film based device has been designed, fabricated, and characterized at a frequency of' similar to 230 MHz. It had a narrow lateral beam width (similar to 8.2 mu m). The AIScN ultrasound transducer was not only shown to be capable of remote controlling a single 10 mu m polystyrene microsphere in distilled water, but also demonstrated to possess the capability to manipulate without contact individual 10 mu m epidermoid carcinoma cell in two dimensions within a range of hundreds of micrometers in phosphate buffered saline. Most importantly, the cell manipulation was realized in continuous mode and no switch-on and -off operation was needed. These results suggest that self-focused AIScN film ultrasound transducer is a promising candidate for biomedical and molecular biology applications.
The dominant view of self-help is that it is a remedy exercised by individuals as an alternative to seeking state-sanctioned aid. In other words, self-help consists in 'legally permissible conduct that individuals undertake absent the compulsion of law and without the assistance of a government official in efforts to prevent or remedy a legal wrong.' Indeed, self-help is often vaunted as an efficient, or at least potentially efficient, alternative to the slower, costlier, and more cumbersome civil justice system. In our world of increasingly exorbitant legal costs, in which few have meaningful access to the civil justice system, remedies that can be initiated and executed without prohibitive expense merit scholarly attention. Notwithstanding this potential promise, the legal scholarship on self-help is meagre, and, moreover, just what behaviour counts as self-help is left unclear. Self-help, as it is currently understood, risks becoming a meaningless term, a cipher through which almost any behaviour initiated by an individual in furtherance of her legal rights can count as selfhelp. This article defends a narrower conception of self-help than that recommended by the dominant view. In so doing, it clarifies some of our misgivings about, and checks some of our hopes for, self-help. Self-help, properly understood, is not an alternative to the civil justice system. It is a privilege to act vis-a-vis another in a certain way when certain circumstances exist, and its exercise is always defeasible to a final determination by a court. Self-help, in other words, is not equivalent to taking the law into one's own hands, as some have implied. This conclusion should comfort those who might worry about the extra-legal nature of self-help and who ask with some trepidation how the unilateral action of one individual can determine the scope and existence of the rights of another. Based on this article's understanding of self-help, it simply cannot. This conclusion, however, might disappoint those who hope that self-help can be a part of the solution to our current access-to-justice crisis. If it is not a true alternative to the civil justice system, then the specter of costly, inefficient litigation and adjudication remains.
The phenomenon of taking and sharing selfies has become widespread in everyday life. However, previous studies on the selfie have not dealt with the effect of the experience of a selfie. Therefore, we examined the effect of the selfie on people who took and shared their selfies. Based on the social comparison theory, we focused on two psychological factors: social sensitivity and self-esteem. In the experiment, we manipulated the context of experiencing selfieS. The participants were asked to take a picture of a self-portrait or a cup, using their own smartphone. Then, they were instructed to either post it on social media or save it on their smartphone. The participants' social sensitivity was assessed by measuring their reaction time (RT) to a social probe, and self-esteem was evaluated by measuring the size of their signatures. We found that participants' RT to a social probe decreased and the size of their signature decreased, after they took and shared their selfie. These results suggest that taking and sharing selfies could result in greater social sensitivity and lower self-esteem of selfie takers. (C) 2017 Elsevier Ltd. All rights reserved.
This paper addresses the self-interference (SI) cancellation in a full-duplex radio transceiver. In particular, we focus on shared-antenna based full-duplex transceivers where the self-interference coupling channel is always frequency-selective and can also be strongly time-varying depending on the antenna matching characteristics and reflections from the surroundings. A novel digitally-controlled RF self-interference canceller structure is described, being able to process the signals in a frequency-selective manner as well as track adaptively the time-varying SI features, stemming from the fast digital control loop. A complete demonstrator board is developed, reported and measured, incorporating both the RF processing and the digital control processing. Comprehensive RF measurements are then also carried out and reported at 2.4GHz ISM band, evidencing more than 40dBs of active RF cancellation gain up to 80MHz instantaneous waveform bandwidths. Furthermore, real-time self-adaptive tracking features are successfully demonstrated.
Self-other discrimination is a crucial mechanism for social cognition. Neuroimaging and neurostimulation research has pointed to the involvement of the right temporoparietal region in a variety of self-other discrimination tasks. Although repetitive transcranial magnetic stimulation over the right temporoparietal area has been shown to disrupt self-other discrimination in face-recognition tasks, no research has investigated the effect of increasing the cortical excitability in this region on self-other face discrimination. Here we used transcranial direct current stimulation (tDCS) to investigate changes in self-other discrimination with a video-morphing task in which the participant's face morphed into, or out of, a familiar other's face. The task was performed before and after 20 min of tDCS targeting the right temporoparietal area (anodal, cathodal, or sham stimulation). Differences in task performance following stimulation were taken to indicate a change in self-other discrimination. Following anodal stimulation only, we observed a significant increase in the amount of self-face needed to distinguish between self and other. The findings are discussed in relation to the control of self and other representations and to domain-general theories of social cognition.
Vibration exists everywhere especially in the public railway operation system. The vibration acceleration is the key factor to monitor and evaluate the structure health of the railway equipment. In this paper, a kind of self-powered triboelectric nano vibration accelerometer (TEVA) is presented. A low frequency spring mass vibration model is built to calculate the vibration sensitive performance and the electric output of the TEVA. The prototype of the TEVA is demonstrated and characterized through the railway vibration simulation platform. It has been testified that TEVA can successfully harvest the low frequency vibration energy and convert it to electrical power to achieve the self-powered vibration acceleration monitoring system. The output current and voltage of TEVA are also sensitive to the vibration acceleration from 1.07 m/s(2) to 1.25 m/s(2) linearly. Hence it can be used as a self-powered nano vibration accelerator for the fault diagnosis. In addition, the generated electricity is used for charging the lithium battery (from 1.5V to 3.1 V) which supplies power to the ZigBee module. The experiment shows that the charged battery through TEVA can support the wireless communication between ZigBee modules, with temperature and humidity sensors embedded on it. The temperature and humidity on the train are 22 degrees C and 35% RH respectively. Therefore, the vibration energy can be harvested and stored for the power supply of wireless sensor network nodes in the near future.
Wearable healthcare devices with monitoring, treating and protecting applications can provide reliable and newfangled interactive service for people. Herein, a bi-functional smart face mask based on electrospun polyetherimide (PEI) electret nonwoven is developed. By virtue of the surplus charges maintained steadily in the PEI nonwoven, the smart face mask possesses bi-functions of removing the particulate matter and generating electricity. Moreover, the unique applications for dynamically monitoring the particulate matter removal ability and human's respiratory rates are demonstrated. Besides offering an unique air filter, this study will promisingly promote the progress of self-powered wearable electronics.
Rolling circle amplification (RCA) is an isothermal amplification technique with high efficiency and perfect accuracy for nucleic acids detection. However, RCA technique suffers the limitation to detect short DNA or RNA molecules. For long nucleic acid molecules, enzymatic restriction as well as heat denaturation process is usually required, which makes the amplification not effective and strictly isothermal. In this article, a simple and efficient one-pot self-primed isothermal amplification (SIA) was developed for detection of genomic DNA directly based on the combination of nicking endonuclease assisted strand displacement amplification (SDA) and exponential RCA. In virtue of numerous nicking sites on the genome, a pre-amplification of the whole genome was performed through SDA with the specific cleaving of nicking endonuclease. Meanwhile, the single strand DNA with HPV target sequence generated from SDA could hybrid with the circle probe as a primer and trigger the exponential RCA as a result of the existence of nicking endonuclease. As the reaction temperature and enzyme were the same, the amplification could be operated in one pot. The reaction solution after amplification was added on the electrode for hybridization with the sulfydryl probe to achieve the electrochemical signal. Based on the isothermal amplification, genotyping of HPV 11, 16, 18 and the detection of HPV 18 in Hela cell line were attempted with satisfied results. This approach should be a promising tool for pathogene detection in clinical diagnostics and research.
A self-sustaining sensor platform is a core component for Internet-of-Things and smart-grid systems. However, monitoring, processing, and displaying the minute changes of a targeted-environmental element in a real-time fashion without external power sources is challenging because of a practical difficulty of doing energy harvesting and analysis of dynamics at the same time. Here, we present a self-sustaining water-motion-sensing (SS-WMS) platform to monitor and display the time-varying dynamics of water-motion, i.e., frequency and amplitude, using only the energy harvested from the water-motion itself. A water-contact triboelectric nanogenerator (WC-TENG) produces electrical energy, correlated with the repetitive squeezing and releasing of a water droplet. The SS-WMS integrated circuit (IC) harvests the energy and simultaneously analyzes the dynamics of water-motion, which is converted into binary codes to be displayed through LEDs powered by the gathered energy. The proposed platform would contribute to advanced sensing functions of a self-sustaining system for various targeted-ambient elements.
One of teenagers' key developmental tasks is to engage in new and meaningful relationships with peers and adults outside the family context. Attachment-derived expectations about the self and others in terms of internal attachment working models have the potential to shape such social reorientation processes critically and thereby influence adolescents' social-emotional development and social integration. Because the neural underpinnings of this developmental task remain largely unknown, we sought to investigate them by functional magnetic resonance imaging. We asked n = 44 adolescents (ages 12.01-18.84 years) to evaluate positive and negative adjectives regarding either themselves or a close other during an adapted version of the well-established self-other trait-evaluation task. As measures of attachment, we obtained scores reflecting participants' positive versus negative attachment-derived self- and other-models by means of the Relationship Questionnaire. We controlled for possible confounding factors by also obtaining scores reflecting internalizing/externalizing problems, schizotypy, and borderline symptomatology. Our results revealed that participants with a more negative attachment-derived self-model showed increased brain activity during positive and negative adjective evaluation regarding the self, but decreased brain activity during negative adjective evaluation regarding a close other, in bilateral amygdala/parahippocampus, bilateral anterior temporal pole/anterior superior temporal gyrus, and left dorsolateral prefrontal cortex. These findings suggest that a low positivity of the self-concept characteristic for the attachment anxiety dimension may influence neural information processing, but in opposite directions when it comes to self- versus (close) other-representations. We discuss our results in the framework of attachment theory and regarding their implications especially for adolescent social-emotional development and social integration.
Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD. Task-related fMRI have also demonstrated the relative preservation of frontal and parietal regions alongside preserved memory performance. In addition, recent longitudinal studies have demonstrated that, with disease progression, atrophy encroaches into the contralateral temporal pole and medial prefrontal cortices, which reflects emerging changes in behaviour and social cognition. Notably, unlike other frontotemporal dementia subtypes, recent research has demonstrated strong clinicopathological concordance in SD, with TDP43 type C as the most common pathological subtype. Moreover, an underlying genetic cause appears to be relatively rare in SD, with the majority of cases having a sporadic form of the disease. The relatively clear diagnosis, clinical course, and pathological homogeneity of SD make this syndrome a promising target for novel disease-modifying interventions. The development of neuroimaging markers of disease progression at the individual level is an important area of research for future studies to address, in order to assist with this endeavour.
Aiming at the difficult problem of high precision frequency stabilization of semiconductor laser diode, the laser frequency control is realized through the design of the semiconductor drive system. Above all, the relationship between the emission frequency and the temperature of LD is derived theoretically. Then the temperature corresponding to the stable frequency is obtained. According to the desired temperature stability of LD, temperature control system is designed, which is composed of a temperature setting circuit, temperature gathering circuit, the temperature display circuit, analog PID control circuit and a semiconductor refrigerator control circuit module. By sampling technology, voltage of platinum resistance is acquired, and the converted temperature is display on liquid crystal display. PID analog control circuit controls speed stability and precision of temperature control. The constant current source circuit is designed to provide the reference voltage by a voltage stabilizing chip, which is buffered by an operational amplifier. It is connected with the MOSFET to drive the semiconductor laser to provide stable current for the semiconductor laser. PCB circuit board was finished and the experimental was justified. The experimental results show that: the design of the temperature control system could achieve the goal of temperature monitoring. Meanwhile, temperature can be stabilized at 40 degrees C +/- 0.1 degrees C. The output voltage of the constant current source is 2 V. The current is 35 mA.
We introduce a self-consistent approach for the description of the nonlinear light propagation in InAs/InGaAs quantum-dot semiconductor optical amplifiers and, using it, numerically analyze the four-wave mixing conversion efficiency in such amplifiers. This approach is based on a delay-differential equation for the optical field propagating through the amplifier and additional equations describing the microscopically calculated charge-carrier dynamics in the quantum-dot states and the surrounding quantum well reservoir. Here, we draw our attention to the studies of the hierarchy of the nonlinear effects involved in the four-wave-mixing processes We observe that the spectral hole burning is the most important effect to drive the four-wave mixing The charge-carrier density pulsation appearing together with the spectral hole burning constitutes the second most important effect, while the charge-carrier heating turned out to be negligible. Furthermore, we found that the four-wave mixing conversion efficiency can be effectively increased when higher device pump current or higher device temperature is used, provided that the frequencies of the injected light sources are adjusted to the temperature-dependent gain maximum.
Background: Senecavirus A (SVA), a member of the family Picornaviridae, genus Senecavirus, is a recently identified single-stranded RNA virus closely related to members of the Cardiovirus genus. SVA was originally identified as a cell culture contaminant and was not associated with disease until 2007 when it was first observed in pigs with Idiopathic Vesicular Disease (IVD). Vesicular disease is sporadically observed in swine, is not debilitating, but is significant due to its resemblance to foreign animal diseases, such as foot-and-mouth disease (FMD), whose presence would be economically devastating to the United States. IVD disrupts swine production until foreign animal diseases can be ruled out. Identification and characterization of SVA as a cause of IVD will help to quickly rule out infection by foreign animal diseases. Methods: We have developed and characterized an indirect ELISA assay to specifically identify serum antibodies to SVA. Viral protein 1, 2 and 3 (VP1, VP2, VP3) were expressed, isolated, and purified from E. coli and used to coat plates for an indirect ELISA. Sera from pigs with and without IVD symptoms as well as a time course following animals from an infected farm, were analyzed to determine the antibody responses to VP1, VP2, and VP3. Results: Antibody responses to VP2 were higher than VP1 and VP3 and showed high affinity binding on an avidity ELISA. ROC analysis of the SVA VP2 ELISA showed a sensitivity of 94.2% and a specificity of 89.7%. Compared to IFA, the quantitative ELISA showed an 89% agreement in negative samples and positive samples from 4-60 days after appearance of clinical signs. Immune sera positive for FMDV, encephalomyocarditis virus, and porcine epidemic diarrhea virus antibodies did not cross-react. Conclusions: A simple ELISA based on detection of antibodies to SVA VP2 will help to differentially diagnose IVD due to SVA and rule out the presence of economically devastating foreign animal diseases.
For older populations, improved ready-made meal packaging may potentially contribute to adequate nutritional intakes, and in turn facilitate maintenance of independent living. Consequently, a deeper understanding of the features of ready-made meal packages important for older people is a step towards this goal. Features of ready-made meal packaging appreciated by 'current' (aged 65 >= years) and 'future' (aged 55-64 years) seniors were studied as an internet survey in Finland (n = 764) and in the Netherlands (n = 457). Only minor significant differences were found between these two senior groups. The four packaging features most valued by both the Finnish and Dutch consumers were: easy readability, easy disposability and recyclability, visibility of the contents, and easy opening. These features were basically the same regardless of age group, gender or country. Older people did not show interest either in multi packages or in eating meals directly from the package. Future senior men frequently using ready-made meals were identified as a promising target segment for the development and marketing of novel readymade meals. More generally, special attention should be paid in package design to age-relevant features, such as easy opening and easy-to-read information, and the impact of culture-specific translation of the features into packaging design. (C) 2016 Elsevier Ltd. All rights reserved.
Background. The experience of 'sensed presence' a feeling or sense that another entity, individual or being is present despite no clear sensory or perceptual evidence is known to occur in the general population, appears more frequently in religious or spiritual contexts, and seems to be prominent in certain psychiatric or neurological conditions and may reflect specific functions of social cognition or body-image representation systems in the brain. Previous research has relied on ad-hoc measures of the experience and no specific psychometric scale to measure the experience exists to date. Methods. Based on phenomenological description in the literature, we created the 16-item Sensed Presence Questionnaire (SenPQ). We recruited participants from (i) a general population sample, and; (ii) a sample including specific selection for religious affiliation to complete the SenPQ and additional measures of well-being, schizotypy, social anxiety, social imagery, and spiritual experience. We completed an analysis to test internal reliability, the ability of the SenPQ to distinguish between religious.and non-religious participants,. and.whether. the SenPQ was specifically related to positive schizotypical experiences and social imagery. A factor analysis was also conducted.. examine underlying latent variables. Results, The SenPQ was found to be reliable and valid, with religious participants significantly endorsing.more items than non-religious participants, and the scale showing a selective relationship with construct relevant measures. Principal components analysis indicates two potential underlying factors interpreted as reflecting 'benign' and 'malign' ensed presence experiences. Discussion. The SenPQ appears to be a reliable and valid measure of sensed presence experience although further validation in neurological and psychiatric conditions is warranted.
The rising level of electromagnetic pollution recorded in recent years represents a serious threat to the reliability of electronic devices and systems, which our life is plenty of. Besides corrupting nominal signals, electromagnetic interference ( EMI) collected by interconnects can drive active nonlinear devices, which integrated circuits are made of, out of their nominal operating region and this usually results in distortion of the signals. The most harmful effect of such a process is the generation of the baseband intermodulation products, i. e., demodulated EMI that can be distinguished from nominal signals unlikely. This point is addressed in the first part of this paper where the expression of the offset induced by the radio frequency interference in MOS differential pair is derived then used to show the effect of EMI in feedback operational amplifiers. Some techniques to obtain higher immunity levels are also presented. The second part of this paper focuses on low-offset low-noise amplifiers of common use in sensor signal conditioning circuits that usually show high susceptibility to EMI. Aiming to address this issue, a new technique based on the dynamic cancelation of EMI-induced errors is presented, and evidences of its effectiveness are provided showing simulation and measurement results.
The zero-potential scanning circuit is widely used as read-out circuit for resistive sensor arrays because it removes a well known problem: crosstalk current. The zero-potential scanning circuit can be divided into two groups based on type of row drivers. One type is a row driver using digital buffers. It can be easily implemented because of its simple structure, but we found that it can cause a large read-out error which originates from on-resistance of the digital buffers used in the row driver. The other type is a row driver composed of operational amplifiers. It, very accurately, reads the sensor resistance, but it uses a large number of operational amplifiers to drive rows of the sensor array; therefore, it severely increases the power consumption, cost, and system complexity. To resolve the inaccuracy or high complexity problems founded in those previous circuits, we propose a new row driver which uses only one operational amplifier to drive all rows of a sensor array with high accuracy. The measurement results with the proposed circuit to drive a 4 x 4 resistor array show that the maximum error is only 0.1% which is remarkably reduced from 30.7% of the previous counterpart.
Depression of heart-rate variability (HRV) in conditions of systemic inflammation has been shown in both patients and experimental animal models and HRV has been suggested as an early indicator of sepsis. The sensitivity of HRV-derived parameters to the severity of sepsis, however, remains unclear. In this study we modified the clinically relevant porcine model of peritonitis-induced sepsis in order to avoid the development of organ failure and to test the sensitivity of HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated and instrumented domestic pigs of both sexes, sepsis was induced by fecal peritonitis. The dose of feces was adjusted and antibiotic therapy was administered to avoid multiorgan failure. Experimental subjects were screened for 40h from the induction of sepsis. In all septic animals, sepsis with hyperdynamic circulation and increased plasma levels of inflammatory mediators developed within 12h from the induction of peritonitis. The sepsis did not progress to multiorgan failure and there was no spontaneous death during the experiment despite a modest requirement for vasopressor therapy in most animals (9/11). A pronounced reduction of HRV and elevation of heart rate developed quickly (within 5h, time constant of 1.970.80h for HRV parameter TINN) upon the induction of sepsis and were maintained throughout the experiment. The frequency domain analysis revealed a decrease in the high-frequency component. The reduction of HRV parameters and elevation of heart rate preceded sepsis-associated hemodynamic changes by several hours (time constant of 11.28 +/- 2.07h for systemic vascular resistance decline). A pronounced and fast reduction of HRV occurred in the setting of a moderate experimental porcine sepsis without organ failure. Inhibition of parasympathetic cardiac signaling probably represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV to systemic inflammation may allow early detection of a moderate sepsis without organ failure. Impact statement A pronounced and fast reduction of heart-rate variability occurred in the setting of a moderate experimental porcine sepsis without organ failure. Dominant reduction of heart-rate variability was found in the high-frequency band indicating inhibition of parasympathetic cardiac signaling as the main mechanism of heart-rate variability reduction. The sensitivity of heart-rate variability to systemic inflammation may contribute to an early detection of moderate sepsis without organ failure.
Acute septic arthritis is a condition with the potential for joint destruction, physeal damage, and osteonecrosis, which warrants urgent identification and treatment. The organism most frequently responsible is Staphylococcus aureus; however, our understanding of pathogens continues to evolve as detection methods continue to improve. MRI has improved our ability to detect concurrent infections and is a useful clinical tool where available. The treatment course involves intravenous antibiotics followed by transition to oral antibiotics when clinically appropriate. The recommended surgical treatment of septic arthritis is open arthrotomy with decompression of the joint, irrigation, and debridement and treatment of concurrent infections.
What actually happens inside genetic databases, how do they work upon data and who does this work? While they have become central tools for doing science, not much is known about the work that goes on inside these vital infrastructures. Ethnographic explorations of two of the world's largest nucleotide sequence databases, GenBank and the European Molecular Biology Laboratory's EMBL-Bank, reveal manifold goings-on. Like most infrastructural work, it is modest and invisible routines that build and maintain the vast interconnected suite of bioinformational resources. Data curators construct organisms out of sulphuric sludge, dataflow engineers as self-styled genetic information plumbers keep the data deluge flowing, and a data submissions support assistant manages to make room for care amidst this deluge. Taken together, these data labours render tangible the modest and processual aspects of data infrastructure while also revealing the databases to be situated and lively spaces of convergence. Inventively analysing data labours paves surprising ways for encountering and making sense of databases, data and the work they do. Here, practices of natural history, like specimen-making and curation, are continued by other means while the assembly of sludge sheds light on the absences and deletions which mystify infrastructural maintenance work.
A prototype bio-catalyzed electrogenic system integrated with a biological treatment process (SBR-BET) was evaluated to study specific function of anoxic condition on the electrogenic activity. A multiphasic approach was employed, where the influence of DO on bio-electrogenic activity was optimized initially, later optimal anode to cathode inter-electrode distance was enumerated. Amongst the four electrode distances evaluated, 2 cm showed higher power output. Bioelectrokinetics analysis was used to validate the system performance with the experimental variation studied. The redox behavior showed an increase in cathodic catalytic activity with an increase in the inter-electrode distance. Spatiometabolic distribution depicted the microbial stratification on the anode. Electrochemically active bacteria present on the anode surface (inner and outer layers of biofilms) showed relatively uniform diversity compared with the suspension culture. (C) 2017 Elsevier B.V. All rights reserved.
Sericins are glue proteins of Bombyx mori silk fibers. They are produced in the middle silk gland (MSG) cells, stored in the lumen, and pushed out from the spinneret surrounding the fibroin fibers. The Ser2 gene was partly cloned from the anterior region of the MSG more than 20 years ago and is regarded as a sericin-encoding gene: however, Ser2 proteins do not appear to be major components of cocoon proteins. We used northern blotting to analyze the expression of three sericin genes-Ser1, Ser2, and Ser3-in the MSG of third to fifth instar larvae and measured the corresponding cDNA levels by competitive PCR. The results revealed that Ser2 gene expression dominated until the middle period of the fifth instar, while the expression of the other genes was mainly observed after the middle fifth instar. Protein analysis demonstrated that the two Ser2 proteins produced by alternative splicing were major coating proteins of larval silk threads spun during the growing stages. The molecular components of larval silk sericin were completely different from those of cocoon sericin, and the difference may be related to the functions of the two kinds of silk fibers. (c) 2010 Elsevier Ltd. All rights reserved.
In this paper, we present a novel method based on a single-phase active power filter (APF) for series arc faults detection in an AC electrical installation. The APF's reference current is used as the starting point for our method tested on a large variety of loads: resistors, vacuum cleaner, rotary drill, dimmer and AC-DC power supplies. Firstly, the proposed method is validated at the simulation level using the Matlab software and then experimentally using the Hardware-In-the-Loop (HIL) approach with an FPGA Altera Stratix III prototyping board. The results obtained in this work show that series arc faults can be successfully detected with an APF, only by updating its digital control with the arc fault detection functionality, instead of designing from the very beginning an arc-fault detection specific device. (C) 2016 Elsevier B.V. All rights reserved.
Bacteriophages are the source of many valuable tools for molecular biology and genetic manipulation. In Streptomyces, most DNA cloning vectors are based on serine integrase site-specific DNA recombination systems derived from phage. Because of their efficiency and simplicity, serine integrases are also used for diverse synthetic biology applications. Here, we present the genome of a new Streptomyces phage, phi Joe, and investigate the conditions for integration and excision of the phi Joe genome. phi Joe belongs to the largest Streptomyces phage cluster (R4-like) and encodes a serine integrase. The attB site from Streptomyces venezuelae was used efficiently by an integrating plasmid, pCMF92, constructed using the phi Joe int-attP locus. The attB site for phi Joe integrase was occupied in several Streptomyces genomes, including that of S. coelicolor, by a mobile element that varies in gene content and size between host species. Serine integrases require a phage-encoded recombination directionality factor (RDF) to activate the excision reaction. The phi Joe RDF was identified, and its function was confirmed in vivo. Both the integrase and RDF were active in in vitro recombination assays. The phi Joe site-specific recombination system is likely to be an important addition to the synthetic biology and genome engineering toolbox. IMPORTANCE Streptomyces spp. are prolific producers of secondary metabolites, including many clinically useful antibiotics. Bacteriophage-derived integrases are important tools for genetic engineering, as they enable integration of heterologous DNA into the Streptomyces chromosome with ease and high efficiency. Recently, researchers have been applying phage integrases for a variety of applications in synthetic biology, including rapid assembly of novel combinations of genes, biosensors, and biocomputing. An important requirement for optimal experimental design and predictability when using integrases, however, is the need for multiple enzymes with different specificities for their integration sites. In order to provide a broad platform of integrases, we identified and validated the integrase from a newly isolated Streptomyces phage, phi Joe. phi Joe integrase is active in vitro and in vivo. The specific recognition site for integration is present in a wide range of different actinobacteria, including Streptomyces venezuelae, an emerging model bacterium in Streptomyces research.
This study adopted a social-ecological perspective to exploring perpetration of serious physical violence against others among Arab-Palestinian adolescents. A total of 3178 adolescents (aged 13-18) completed anonymous, structured, self-report questionnaire, which included selected items from several instruments that measured variables relating to the constructs examined in the study. We explored the association of individual characteristics (age, gender, normative beliefs about violence, and perceived ethnic discrimination), familial characteristics (parent-adolescent communication and socioeconomic status), and contextual characteristics (exposure to community violence in the neighborhood) with perpetration of serious physical violence against others. A moderation-mediation model was tested, and 28.4% of the adolescents reported that they had perpetrated serious physical violence against others at least once during the month preceding the study. The findings also show that exposure of youth to violence in their neighborhood correlated significantly and positively with their perpetration of serious physical violence against others. A similar trend was revealed with respect to personal perceptions of ethnic discrimination. These correlations were mediated by the adolescents' normative beliefs about violence. Furthermore, the correlation of direct exposure to violence in the neighborhood and normative beliefs about violence with perpetration of serious physical violence against others was stronger among adolescents who have poor communication with their parents than among those who have strong parental communication. (C) 2016 Elsevier Ltd. All rights reserved.
Background. Invasive meningococcal disease (IMD) incidence increased in Quebec, starting in 2003, and was caused by a serogroup B sequence type 269 clone. The Saguenay-Lac-Saint-Jean (SLSJ) region was particularly affected with a rate of 3.4 per 100 000 person-years in 2006-2013. In May 2014, an immunization campaign was launched in SLSJ, using the 4-component protein-based meningococcal vaccine (MenB-4C). We aimed to evaluate the impact of the campaign 2 years after its initiation. Methods. Immunization registry data and serogroup B invasive meningococcal disease (B-IMD) cases notified to public health authorities and confirmed by culture or polymerase chain reaction from July 1996 to December 2016 were analyzed, including a multivariate Poisson regression model of incidence rates. Results. By the end of the campaign, 82% of the 59 000 targeted SLSJ residents between 2 months and 20 years of age had been immunized. Following the initiation of the campaign, no B-IMD case occurred among vaccinees, whereas 2 cases were reported among unvaccinated adult SLSJ residents, and a third case in an unvaccinated child who had stayed in the region during the week prior to disease onset, in 2015. B-IMD incidence decreased in all other regions in the years 2015-2016 but sporadic cases continued to occur. A multivariate analysis showed a significant effect of the campaign in the SLSJ region (relative B-IMD risk: 0.22; P =.04). Conclusions. Results suggest a high level of protection provided by MenB-4C following mass vaccination at regional level. This, along with reassuring safety data, supports the current recommendations for MenB-4C use for controlling outbreaks caused by clones covered by the vaccine.
This study aims to determine the prevalence of human immunodeficiency virus (HIV) infections and hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among blood donors at the Blood Donor Center, Mohammed V Military Teaching Hospital between 2010 and 2012. We conducted a retrospective study among military blood donors aged 18-50 years, with a male predominance (95%). Pre-donation interview is the first selection barrier for individuals at risk. Biological screening was performed by liquid enzyme immunoassay technique using antibodies and/or antigen. Fourth generation combined HCV and HIV antigen/antibody ELISA (enzyme-linked immunosorbent assay) test was used. The Blood Donor Center and the laboratory of virology used the same technique performed in duplicate to confirm results. Out of 25661 tested samples, the prevalence rate of HBV infections was 3.97 % (n = 102), the prevalence rate of HCV infections was 2.45 % (n = 63) and the prevalence rate of HIV infections was 0.15 % (n = 4). A single case with HBV and HCV virus co-infection (0.039 %) was registered, no association between HIV-HBV, HIV-HCV or HBV, HCV and HIV infections was recorded. The low seroprevalence rates of viral markers recorded in our study show improvement in preventive measures for donor selection and screening tests. The registered prevalence encourages the use of combined reagent, which is the only alternative to molecular biology in developing countries.
Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) converts intracellular free cholesterol into cholesterol ester for storage in lipid droplets and plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions. Serotonin (5-HT), a potent vasoconstrictor that is released from activated platelets, increases uptake of oxidized low-density lipoprotein (LDL) by macrophages, leading to foam cell formation, and contributes to the development of atherosclerotic plaque. However, it is not yet known whether 5-HT affects ACAT-1 expression in human monocyte-macrophages as the molecular mechanism of enhanced foam cell formation by 5-HT remains unclear. We examined the effects of 5-HT on ACAT-1 expression during differentiation of cultured human monocytes into macrophages. Expression of ACAT-1 protein but not 5-HT(2A) receptor increased in a time-dependent manner. 5-HT increased ACAT activity in a concentration-dependent manner after 7 days in primary monocyte Culture. Immunoblotting analysis showed that 5-HT at 10 mu M increased ACAT-1 protein expression level by two-fold, and this effect was abolished completely by a 5-HT(2A) receptor antagonist (sarpogrelate), its major metabolite (M-1), a G protein inactivator (GDP-beta-S), a protein kinase C (PKC) inhibitor (rottlerin), a Src family inhibitor (PP2). or a mitogen-activated protein kinase (MAPK) kinase inhibitor (PD98059). Northern blotting analysis indicated that among the four ACAT-1 mRNA transcripts (2.8-, 3.6-, 4.3-, and 7.0-kb), the levels of the 2.8- and 3.6-kb transcripts were selectively up-regulated by similar to 1.7-fold by 5-HT (10 mu M). The results of the present Study suggested that 5-HT may play a crucial role in macrophage-derived foam cell formation by up-regulating ACAT-1 expression via the 5-HT(2A) receptor/G protein/c-Src/PKC/MAPK pathway, contributing to the progression of atherosclerotic plaque. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
We previously demonstrated that serotonin (5-HT) and 5-HT2A receptor (5-HT2AR) levels in platelets were up- or down-regulated after myocardial infarction (MI) associated with depression. In this study, we further evaluated the effects of pretreatment with ginseng fruit saponins (GFS) on the expression of 5-HT and 5-HT2AR in MI with or without depression. Eighty Sprague-Dawley (SD) rats were treated with saline and GFS (n=40 per group). The animals were then randomly divided into four subgroups: sham, MI, depression, and MI + depression (n=10 per subgroup). Protein levels of 5-HT and 5-HT2AR in the serum, platelets and brain tissues were determined with ELISA. The results demonstrated that serum 5-HT levels was significantly increased by GFS pretreatment in all subgroups (except the sham subgroup) when compared with saline-treated counterparts (p<0.01). In platelets, GFS pretreatment significantly increased 5-HT levels in all subgroups when compared with their respective saline-treated counterparts (p<0.01). Brain 5-HT levels also declined with GFS pretreatment in the MI-only and depression-only subgroups (p<0.05 vs. saline pretreatment). With respect to 5-HT2AR levels, platelet 5-HT2AR was decreased in GFS pretreated MI, depression and MI + depression subgroups (p<0.01 vs. saline pretreatment). Similarly, brain 5-HT2AR levels decreased in all four subgroups pretreated with GFS (p<0.01 vs. saline pretreatment). We conclude that GFS plays a clear role in modulating 5-HT and 5-HT2AR expressions after MI and depression. Although the effects of GFS on brain 5-HT remain to be elucidated, its therapeutic potential for comorbidities of acute cardiovascular events and depression appears to hold much promise.
Objectives: To compare the results of systemic antitubercular therapy (ATT) and immunomodulatory therapy (IMT) in patients with serpiginous choroiditis (SC) or multifocal serpiginoid choroiditis (MSC). Materials and Methods: The clinical records of 28 patients with SC and MSC were reviewed. Patients were divided into 2 groups according to the treatment applied. Group 1 included 12 patients with MSC and 5 with SC treated with ATT and corticosteroid (CS); group 2 included 9 patients with MSC and 2 with SC treated with conventional IMT, interferon alpha-2a, and/or CS monotherapy. Results: In group 1, clinical remission was achieved in 12/12 MSC and 3/5 SC (total 15/17) patients with administration of ATT for 1 year. Two patients (1 SC, 1 MSC) had reactivation 2 and 7 months after cessation of ATT. Two patients with recurrence after completion of ATT and 2 patients resistant to ATT received IMT +/- CS therapy. In group 2, clinical remission was achieved in 7/9 MSC and 2/2 SC (total 9/11) patients after 1 year of treatment. Recurrent inflammation was observed in 2 MSC patients 2 and 112 months after initiation of therapy, but responded well to local/systemic CS or IMT modification, and clinical remission was achieved in 7.8 +/- 4.3 months. Cumulative dose of CS was higher in group 2 (p= 0.057). Nine of 12 MSC patients treated with ATT and 4/9 MSC patients treated with IMT achieved remission (p= 0.203). One of 5 SC patients treated with ATT and 2/2 SC patients treated with IMT achieved remission (p= 0.142). Conclusion: Although a statistically significant result could not be achieved in this small case series, our results suggest that ATT may be an appropriate first choice in the treatment of MSC associated with latent tuberculosis, and may be administered in patients with SC who are unresponsive to IMT.
To render future SFR more robust and safe, certain BDBE have been considered in the recent years. A Core Disruptive Accident leading to a whole core meltdown scenario has gained the interest of researchers. Various design concepts and safety measures have been suggested and incorporated in design to address such a low probability scenario. A core catcher concept, in particular, has proved to be inevitable as an in vessel core retention device in SFR for safe retention of core debris arising out after the severe accident. This study aims to analyse the cooling capability of the innovative design concept of core catcher to remove decay heat of degraded core after the accident. First, the capability of single collection tray is established and then the study is extended to two and three collection trays with different design concepts. Transient forms of governing equations of mass, momentum and energy conservations along with k-epsilon turbulence model are solved by finite volume based CFD solver. Boussinesq approximation is invoked to model buoyancy in sodium. The study shows that a single collection tray is capable of removing up to 20 MW decay heat load in a typical 500 MWe pool type SFR. Further, studies are carried out to improve the natural circulation of sodium around the source, in the lower plenum and to distribute core debris of the whole core to multiple collection trays. It is found that the double and triple collection trays can accommodate decay loads up to 29 MW. Provision of openings in the collection trays has proved to be effective in improving the heat transfer and sodium flow as well as in distributing the core debris to the successive plates. Detailed analysis of isotherms and velocity field in the multiple collection trays with openings reveals improved natural circulation in and around the collection trays in the lower plenum. A three tray core catcher device with multiple openings can accommodate the decay heat of whole core meltdown, without exceeding the safe temperature limits of structural material. Special attention has been paid to the space constraint in the lower plenum while incorporating the three tray core catcher device. (C) 2017 Elsevier Ltd. All rights reserved.
Cytokine antagonists are monoclonal antibodies that offer new treatment options for refractory asthma but will also increase complexity because they are effective only for patients with certain asthma subtypes that remain to be more clearly defined. The clinical and inflammatory heterogeneity within refractory asthma makes it difficult to manage the disease and to determine which, if any, biologic therapy is suitable for a specific patient. The purpose of this article is to provide a data-driven discussion to clarify the use of biologic therapies in patients with refractory asthma. We first discuss the epidemiology and pathophysiology of refractory asthma. We then interpret current evidence for biomarkers of eosinophilic or type 2-high asthma so that clinicians can determine potential treatments for patients based on knowledge of their effectiveness in specific asthma phenotypes. We then assess clinical data on the efficacy, safety, and mechanisms of action of approved and pipeline biologic therapies. We conclude by discussing the potential of phenotyping or endotyping refractory asthma and how biologic therapies can play a role in treating patients with refractory asthma. (C) 2017 American Academy of Allergy, Asthma & Immunology
Insulin-like growth factor (IGF)-1 functions as a neuroprotective hormone and may protect against cognitive impairment, which may occur as a result of sevoflurane exposure. The aim of the present study was to assess the effect of sevoflurane on the production of IGF-1 and investigate the molecular mechanisms underlying this regulation. The BRL rat hepatocyte cell line and adult mice were exposed to 1 or 2 minimal alveolar concentrations sevoflurane for 4 or 8 h. IGF-1 and microRNA-98 levels were quantified using an enzyme-linked immunosorbent assay, western blotting and reverse transcription-quantitative polymerase chain reaction analyses. The importance of microRNA-98 in the regulation of IGF-1 by sevoflurane was investigated using a microRNA-98 inhibitor. Sevoflurane treatment reduced IGF-1 levels and simultaneously upregulated microRNA-98 expression levelsin rat hepatocytes and adult mice. Inhibition of microRNA-98 attenuated this effect. Therefore, sevoflurane may reduce the synthesis of IGF-1 by upregulating microRNA-98 expression.
Concrete corrosion is one of the most significant problems affecting valuable sewer infrastructure on a global scale. This problem occurs in the aerobic zone of the sewer, where a layer of surface corrosion develops on the exposed concrete and the surface pH is typically lowered from around 11-10 (pristine concrete) to pH 2-4. Acidophilic microorganisms become established as biofilms within the concrete corrosion layer and enhance the loss of concrete mass. Until recently, the acidophilic community was considered to comprise relatively few species of microorganisms, however, the biodiversity of the corrosion community is now recognized as being extensive and varying from different sewer environmental conditions. The diversity of acidophiles in the corrosion communities includes chemolithoautotrophs, chemolithoheterotrophs, and chemoorganoheterotrophs. The activity of these microorganisms is strongly affected by H2S levels in the sewer gas phase, although CO2, organic matter, and iron in the corrosion layer influence this acidic ecosystem. This paper briefly presents the conditions within the sewer that lead to the development of concrete corrosion in that environment. The review focuses on the acidophilic microorganisms detected in sewer corrosion environments, and then summarizes their proposed functions and physiology, especially in relation to the corrosion process. To our knowledge, this is the first review of acidophilic corrosion microbial communities, in which, the ecology and the environmental conditions (when available) are considered. Ecological studies of sewer corrosion are limited, however, where possible, we summarize the important metabolic functions of the different acidophilic species detected in sewer concrete corrosion layers. It is evident that microbial functions in the acidic sewer corrosion environment can be linked to those occurring in the analogous acidic environments of acid mine drainage and bioleaching.
Sewing needles are rare causes of penetrating cardiac injury. Suicidal attempt, accidental penetration, domestic violence, and child abuse are likely causes for such injury.(1) Owing to their sharp nature, needles can rapidly migrate through the tissues. Fatalities are due to cardiac tamponade, infection, peripheral embolism, and valve dysfunction.
1. The quail is a potentially important avian model for molecular studies; a major drawback is the inability to sex visually before 3 weeks of age. Molecular sexing is therefore an absolute requirement when animals are sampled before that age.2. A low-cost method using common laboratory equipment based on Allele-Specific Multiplex-Polymerase Chain Reaction was developed to undertake reliable molecular identification of the sex of Coturnix japonica directly at hatching.3. This simple method works with down feathers collected from behind the neck of the newly hatched quail and includes internal controls during the PCR to limit risks of error. Males and females can be discriminated on the basis of the presence of one or two amplicons, respectively.
We conducted an exploratory review of the current literature on child sexual abuse disclosure in everyday contexts. The aim of this study was to provide an overview of relevant publications on the process of child sexual abuse disclosure, in order to generate new directions for future research and clinical practice. The findings of the exploratory review show that disclosure is a relational process, which is renegotiated by each interaction and evolves over an extended period of time. The characteristics and reactions of the interaction partner appear to be as critical to this process as the behavior and words of children themselves. Methodological limitations of the review and the publications are discussed, as well as directions for future research and implications for practice.
The articles and comments in this issue bear out the enduring impact of The Witchhunt Narrative. There is not sufficient space to acknowledge or respond to most of this feedback. This response corrects an error that was identified by one commenter and it responds to questions raised by another commenter about my analysis of the "Concerned Scientists" brief. This response also documents how Wood, Nathan, and others have misapplied the term ritual abuse, misstated the facts of many cases, and promoted "mythical numbers" that significantly exaggerate the number of false convictions. These critics are wrong about the only three cases they discuss in detail. The McMartin Preschool case began with credible evidence of child sexual abuse that continues to be distorted by critics. The Keller case began with even stronger medical evidence that is not diminished by the dubious and incomplete "retraction" of the Emeregency Room doctor. The Fuster case involved overwhelming evidence of abuse, medical and testimonial, that continues to be distored or overlooked by critics. Those who promote the witchhunt narrative rely on selective use of evidence to reach an apparently predetermined result. That is politics and advocacy, not scholarship. This dismissive approach to children's testimony has caused documented harm to children.
This article provides an overview of The Witch-Hunt Narrative, focusing on the challenges of gathering information from young children, such as those involved in sexual abuse allegations in day care. The article summarizes the research methodology of The Witch-Hunt Narrative, which involves a series of case studies. The article articulates Cheit's hypothesis, which is that the witch-hunt narrative originated in two key publications, a series of articles by two journalists, Tom Charlier and Shirley Dowling, and the book, Satan's Silence: Ritual Abuse and the Making of a Modern-Day Witch-Hunt, by Debbie Nathan and Michael Snedeker, and notes his disputes with the evidence from these two publications. Cheit deals in depth with three hotly contested day care center cases: the McMartin Pre-School case in Manhattan Beach, California, the Wee Care Day Nursery case in Maplewood, New Jersey, and the Country Walk Babysitting Service case in Dade County, Florida. The article summarizes Cheit's research and conclusions related to these three cases and also notes how forensic interview practices used in these cases would not be supported today. The article concludes with noting that despite the impressive progress in forensic interviewing of children when sexual abuse is alleged, methods for gathering information from young children remain inadequate. Moreover, there are no easy answers to the reasons for the rise and fall of allegations of sexual abuse in day care and of allegations of ritual abuse.
Allegations of sexual abuse made against the former BBC entertainer, Jimmy Savile by former pupils of a girls' residential school attracted worldwide publicity when they were reported in a TV programme in 2012. The Savile case has had major political and cultural reverberations, with the establishment of official inquiries across the countries of the UK to investigate claims of historical abuse. Responses reinforce what has become a default position in respect of allegations of historical abuse-that we should believe those telling such stories. This article presents a case study, which introduces some caution in that regard. Accounts of the past are constructed in particular social and cultural contexts and cannot be regarded as necessarily reflecting any wider, objective reality. Moreover, unquestioning 'belief', while it may be posited as giving voice to former care home residents, may mask another politics of voice, within which these views are appropriated by more powerful cultural elites. This situation has implications for those who claim abuse, those accused of such abuse and for natural and social justice. The article begins to address some of the ethical issues raised when professionals encounter stories of historical abuse.
Sexual abuse of children and adolescents places these victims at risk of contracting sexually transmitted infections (STIs) and represents an important public health issue. The timely diagnosis and management of STIs can prevent negative long-term health effects and have important forensic implications. The emergency department is a common setting for patients to initially present with reported sexual abuse, and it is important for emergency care providers to have an understanding of the recommended approach to STI screening and management of these patients.
As a result of his assignment to the Federal Bureau of Investigation (FBI) Behavioral Science Unit, the author consulted on and has firsthand knowledge of most of the cases discussed in Cheit's book. He came to believe that there is a middle ground. Some of what victims allege may be true and accurate, some may be misperceived or distorted, some may be symbolic, and some may be contaminated or false. The problem and challenge, however, is to determine which is which. He basically agrees with much of what Cheit sets forth about seeds of truth in many allegations. He has concerns about some confusing and inconsistent definitions. What was and is referred to by many as the backlash can be confused with what Cheit refers to in his book as the witch-hunt narrative. Many professionals, including possibly Cheit, do not seem fully aware of the wide diversity of ways in which children are sexually victimized. The author believes that any delayed reporting and minimization of recent cases involving the Catholic priests and Penn Sate have more to do with inaccurate stereotypes perpetuated by child abuse idealists than some witch-hunt narrative. From a law enforcement perspective, more benefit would have come had Cheit's extensive research focused more on documenting how allegations became so bizarre and inaccurate and less on the alleged far-ranging harm caused by the witch-hunt narrative. In the author's opinion, it is that process and not the witch-hunt narrative that caused most of the long-term damage discussed.
Childhood sexual abuse (CSA) is highly prevalent and associated with a wide variety of negative mental and physical health outcomes. School-based CSA education and prevention programs have shown promise, but it is unclear to what extent community-level characteristics are related to their effectiveness. The present cluster randomized controlled trial evaluated community-level moderators of the Safe@Lastprogramcomparedtoawaitlistcontrolcondition.(*) Knowledge gains from pre- to post-intervention were assessed in 5 domains: safe versus unsafe people: safe choices; problem-solving; clear disclosure; and assertiveness. Participants were 1177 students (46% White, 26% African American, 15% Hispanic, 4% Asian American, 6% Other) in grades 1 through 6 from 14 public schools in Tennessee. Multilevel models accounting for the nesting of children within schools revealed large effect sizes for the intervention versus control across all knowledge domains (d's ranged from 1.56 to 2.13). The effectiveness of the program was moderated by mean per capita income and rates of substantiated cases of child abuse and neglect in the community. Intervention effects were stronger for youth living in lower as compared to higher income counties, and for youth attending schools in counties with lower as compared to higher abuse/neglect rates. Child characteristics (sex, race) did not moderate intervention effects. This research identified two community-level factors that predicted the effectiveness of a CSA education and prevention program designed to improve children's knowledge of personal safety skills. School-based CSA prevention programs may require modification for communities with higher rates of child abuse and neglect. (C) 2016 Elsevier Ltd. All rights reserved.
We provide a brief response to a commentary submitted by Rosky in which he questions the rationale and methodological merits of our original study about full-disclosure polygraph outcome differences between juvenile and adult sex offenders. At the heart of Rosky's substantive concerns is the premise that only research tying polygraphy outcomes to actual recidivism is useful or worthwhile. He also questions the overall utility and validity of polygraphy. We acknowledge and challenge these two points. Furthermore, many of the methodological concerns expressed by Rosky represent either a misunderstanding of our research question, study design, and sample, or a disregard for the explicit declarations we made with respect to our study limitations. Overall, it appears Rosky has accused us of not answering well a question we were not trying to ask. Our response addresses the key substantive and methodological concerns extended by Rosky and clarifies the actual aims and scope of our original study. We also argue that a calm, rational, and scientific discussion is the best approach to understanding how to improve clinical methods used in sex offender treatment.
The sexual assault of a child has a profound impact on not just the child, but those closest to them. This research examined the ways that women react and cope with the sexual assault of their child within the framework of their role as mothers, or how they are able to "do mother" in the aftermath of the assault. A total of 21 mothers who had a child sexually assaulted were interviewed across the state of Illinois. The experiences of these women are presented and discussed within the feminist literature regarding the societal role of mother.
Intimate partner violence and sexual assault of college students has garnered increased attention and publicity. Current studies have focused primarily on general campus populations with little to no attention to students with disabilities. While studies suggest the rate of abuse of individuals with disabilities is similar or higher compared to the general population, there remains a lack of focus on this issue. Individuals with disabilities are at particularly high risk for abuse, both through typical forms of violence (physical, sexual, emotional, and economic) and those that target one's disability. In an effort highlight and explore this issue further, an exploratory study was conducted to learn the rates of abuse among university students who have identified as having a disability. This is a cross-sectional survey of 101 students of students with disabilities from a large northeastern public university. Experiences of abuse were measured through the use of the Abuse Assessment Screen- Disability (AAS-D) scale. Students were asked about experiences of physical, sexual, psychological, and disability related abuse within the last year and help seeking behaviors when an incident of abuse occurred. We found that 22 % of participants reported some form of abuse over the last and nearly 62% (n= 63) had experienced some form of physical or sexual abuse before the age of 17. Those who were abused in the past year, 40% reported little or no knowledge of abuse-related resources and only 27% reported the incident. Authors discuss implications results have for programs and policies on campus for individuals with disabilities.
Although early sexual initiation has been linked to negative outcomes, it is unknown whether these effects are causal. In this study, we use propensity score methods to estimate the causal effect of early sexual initiation on young adult sexual risk behaviors and health outcomes using data from the National Longitudinal Study of Adolescent to Adult Health. We found that early sexual initiation predicted having two or more partners (for both males and females) and having a sexually transmitted infection in the past year (females only) but did not predict depressive symptoms in the past week (for either gender). These results underscore the importance of continued programmatic efforts to delay age of sexual initiation, particularly for females.
Research examining children with sexual behavior problems (SBP) almost exclusively relies on caregiver reports. The current study, involving a sample of 1112 children drawn from a prospective study, utilizes child self-reports and teacher reports, as well caregiver-reports. First, analyses examined children displaying any SBP; a second set of analyses specifically examined children displaying interpersonal forms of SBP. Caregivers reported greater internalizing, externalizing, and social problems for children with general SBP and/or interpersonal SBP when compared to children without SBP. Caregiver concerns were rarely corroborated by teacher and child reports. Protective services records indicated that SBP was linked to childhood sexual abuse, but sexual abuse occurred in the minority of these cases. Physical abuse was more common among children with interpersonal forms of SBP. The data in the current study suggest the need for multiple reporters when assessing children presenting with SBP and that conventional views of these children may be misleading.
Fresh injuries of the anal region concerning infants should always lead to the suspicion of sexual abuse (rape as described in A 176 of the German Penal Code). A differentiation must be made between findings indicative of acute and chronic anal sexual abuse. In clinical forensic medicine such injuries due to acute anal penetration must be documented and an expert opinion must be made. In individual cases a differential diagnosis with respect to an alleged accidental event or to pre-existing diseases must be taken into consideration. To demonstrate the relevant findings and the difficulties arising in the assessment, four cases are presented.
Adolescent sexual development is not the same across the board, and can be seen as both normative as well as risky behavior, depending on factors such as age of onset and number of partners. This longitudinal study identified developmental trajectories of annual number of sexual partners from adolescence to emerging adulthood and their antecedents. From the ages of 16-22, 332 participants (60.8 % females) annually reported their number of sexual partners. Measures of adolescent and family characteristics taken at ages 13-15 were used as predictors. Group-based modeling identified four trajectory groups: the abstainers group (9.1 %), low-increasing group (30.6 %), medium-increasing group (53.0 %), and multiple-partners group (7.3 %). Multinomial logistical regressions indicated that better social competence increased chances of belonging to the multiple-partners group as compared to the abstainers and low-increasing groups, and more substance use predicted membership in the multiple-partners group as compared to the abstainers group. Moreover, females were overrepresented in the low-increasing and medium-increasing groups. These results imply a greater diversity in sexual development than proposed in the literature and highlight the importance of identifying the strengths and competencies associated with healthy sexual development along with the early risk factors.
During the course of sexual development, many people experience dissonance between dimensions of sexual orientation, including attraction, behavior, and identity. This study assesses the relationship between sexual orientation discordance and mental health. Data were obtained from the National Longitudinal Study of Adolescent to Adult Health (n = 8,915; female = 54.62 %; non-Hispanic black = 18.83 %, Hispanic = 14.91 %, other race (non-white) = 10.79 %). Multivariable linear regression evaluated the correlation between sexual orientation discordance and perceived stress and depressive symptomatology. Models were stratified by sex and sexual identity. Among self-identified heterosexual females and mostly heterosexual males, sexual orientation discordance predicted significantly increased depressive symptomatology. No other subpopulation demonstrated a significant correlation between sexual orientation discordance and depressive symptomatology or perceived stress. The association between sexual orientation discordance and depressive symptomatology suggests a link between sexuality, self-concept, and mental health.
Sezary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-gamma was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-gamma. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists.
Growing electricity demand from a range of sources and the changes of the power grid structures open the possibility of more frequent and much higher fault current. Traditional solutions to the fault are difficult to satisfy the requirement of the new power grid due to many factors, such as high cost, additional impact to power grid in normal loading condition, which leads to the research for an efficient alternative solution of interest to both academia and industry: Superconducting fault current limiter (SFCL).In this paper, two types of low-inductance solenoidal coils, the braid type and the nonintersecting type, are built with 2G high-temperature superconductors. The current limiting performance, the recovery characteristics, and the ac losses of both types of coils are tested and compared in detail. Experimental results show that both types of coils can effectively limit fault current and recover in several seconds. Furthermore, comparison between the ac losses of both types of SFCLs shows that the ac loss of the braid type coil is lower than that of the single tape by about an order of magnitude in low-current regions.
A new voltage-mode bandpass shadow filter is presented. The filter is built around the current-feedback operational-amplifier. The parameters of the filter can be controlled by adjusting the gains of external amplifiers built around the current-feedback operational-amplifier. Contrary to the conjecture based on the current-mode shadow filter realization where a summing junction must be used, no summing amplifiers are used in this voltage-mode realization. Experimental results obtained using the AD844 current-feedback operational-amplifier are presented. The results obtained confirm the functionality of the proposed circuit.
Shaking and smothering in response to infant crying are life-threatening child abuse. Parental childhood abuse history is known to be one of the most robust risk factors for abusing their offspring. In addition to childhood abuse history, other adverse childhood exposures (ACEs) need to be considered due to co-occurrence. However, few studies have investigated the impact of ACEs on caregivers shaking and smothering their infant. This study aims to investigate the association of ACEs with shaking and smothering among caregivers of infants in Japan. A questionnaire was administered to caregivers participating in a four-month health checkup between September 2013 and August 2014 in Chiba City, Japan, to assess their ACEs (parental death, parental divorce, mentally ill parents, witness of intimate partner violence, physical abuse, neglect, psychological abuse and economic hardship), and shaking and smothering toward their infants (N = 4297). Logistic regression analysis was used to examine the cumulative and individual impacts of ACEs on shaking and smothering. Analyses were conducted in 2015. A total of 28.3% reported having experienced at least one ACE during their childhood. We found that only witness of IPV had a significant association with shaking of infant (OR=1.93, 95% CI: 1.03-3.61). The total number of ACEs was not associated with either shaking or smothering. Our findings suggest that shaking and smothering in response to crying can occur regardless of ACEs. Population-based strategies that target all caregivers to prevent shaking and smothering of infants are needed. (C) 2016 Elsevier Ltd. All rights reserved.
Coal is the top fuel for power generation in both China and the United States. Its replacement is one critical method to mitigate the serious environmental impacts. Natural gas is associated with much less air pollution and is one of the most important alternative fuels. In the United State shale gas - one key type of unconventional natural gas - has become a disruptive energy resource during the past years. China has the world's largest resource of shale gas, and it is keen to develop them to alleviate unacceptable air pollution and to ensure energy security. However, one big obstacle standing between the ambition and the reality is the potentially serious environmental impacts caused by shale gas development. We construct an analytical framework, focusing on the coverage and implementability of monitoring, reporting and verification (MRV) systems, to qualitatively evaluate the probability of detecting noncompliance for enhancing compliance - in China and the United States on three prominent environmental impacts, including water contamination, water consumption and methane leakage. China should improve significantly on the implementability dimension and pay urgent attention to currently weak MRV systems on water contamination. The United States needs to extend the MRV coverage of ground water consumption. Only when the environmental impacts in shale gas development were effectively controlled, the fuel switching to replace coal could bring significant environmental gains. (C) 2015 Elsevier B.V. All rights reserved.
This paper presents the design and experimental evaluation of discrete time sliding mode controller using multirate output feedback to minimize structural vibration of a cantilever beam using shape memory alloy wires as control actuators and piezoceramics as sensor and disturbance actuator. Linear dynamic models of the smart cantilever beam are obtained using online recursive least square parameter estimation. A digital control system that consists of Simulink (TM) modeling software and dSPACE DS1104 controller board is used for identification and control. The effectiveness of the controller is shown through simulation and experimentation by exciting the structure at resonance.
Information sharing is an integral part of human interaction that serves to build social relationships and affects attitudes and behaviors in individuals and large groups. We present a unifying neurocognitive framework of mechanisms underlying information sharing at scale (virality). We argue that expectations regarding self-related and social consequences of sharing (e.g., in the form of potential for self-enhancement or social approval) are integrated into a domain-general value signal that encodes the value of sharing a piece of information. This value signal translates into population-level virality. In two studies (n = 41 and 39 participants), we tested these hypotheses using functional neuroimaging. Neural activity in response to 80 New York Times articles was observed in theory-driven regions of interest associated with value, self, and social cognitions. This activity then was linked to objectively logged population-level data encompassing n = 117,611 internet shares of the articles. In both studies, activity in neural regions associated with self-related and social cognition was indirectly related to population-level sharing through increased neural activation in the brain's value system. Neural activity further predicted population-level outcomes over and above the variance explained by article characteristics and commonly used self-report measures of sharing intentions. This parsimonious framework may help advance theory, improve predictive models, and inform new approaches to effective intervention. More broadly, these data shed light on the core functions of sharing-to express ourselves in positive ways and to strengthen our social bonds.
The animal selection with favourable phenotypes of the past has been, currently, replaced by the genotype selection on quantitative traits, assisted by the expanding molecular techniques in the context of livestock improvement. In this study, the c. 112T>C polymorphism in exon II of beta-lactoglobulin (beta-LG) gene was investigated in Karagouniko and Chios sheep breeds by using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), and possible associations with milk traits were examined. In total, 125 blood DNA samples were isolated for PCR-RFLP analysis and the respective 217 milk samples' composition profile was obtained. The goodness of fit test to Hardy-Weinberg equilibrium (HWE) for beta-LG genotypes was estimated and associations found between beta-LG genotypes and raw milk composition. Two alleles and three genotypes were observed (AA, AB and BB) in both breeds, and Chios breed significantly deviated (P <= 0.05) from Hardy-Weinberg equilibrium (HWE). Conclusively, linear mixed model analysis on samples, from both breeds collectively, showed significant effects of beta-LG genotype on lactose percentage and somatic cell count (SCC), lactation stage on daily milk yield and protein, while the breed effect was significant only on daily milk yield.
Gene expression is regulated at several levels in plants, and one of the most recently discovered regulatory layers involve short RNAs. Short RNAs are produced through several pathways and target either mRNAs or genomic DNA. Different classes of short RNAs have slightly different sizes and detection of their accumulation is an important step in validating and studying non-coding short RNAs. Northern blotting is routinely used to detect short RNAs because it gives information about both the amount and size of the analysed short RNAs. Choice of the right RNA extraction protocol is crucial when short RNAs are being studied, because several routinely used commercial RNA extraction kits do not yield any short RNAs. This chapter describes optimised RNA extraction methods, which give good yields of short RNAs, and separation, transfer and hybridisation protocols to study the accumulation of short RNAs.
Small RNAs (sRNAs) play fundamental roles in modifying the transcriptomes and proteomes of organisms. sRNAs can be classified according to their origin and way faction into classes such as microRNAs, transacting siRNAs, heterochromatin siRNAs, Piwi-interacting RNAs, and natural antisense siRNAs, although microRNAs are the most conserved and studied class. The expression pattern of a sRNA can be indicative of its biological function. Northern blotting is one of the most widely used methods to identify, validate, and study the expression profile of sRNAs because it is a quantitative, relatively inexpensive technique that is readily available for most laboratories. This chapter describes a protocol for sRNA Northern blot analysis, which includes RNA extraction, polyacrylamide gel electrophoresis, hybridisation, or the detection of sRNA using oligonucleotide probes.
Wind speed forecasting plays a pivotal role in power dispatching and normal operations of power grids. However, it is both a difficult and challenging problem to achieve high-precision forecasting for the wind speed because the original sequence includes many nonlinear stochastic signals. The current conventional forecasting methods are more suitable for capturing linear trends, and artificial neural networks easily fall into a local optimum. This paper proposes a model that combines a denoising method with a dynamic fuzzy neural network to address the problems above. Singular spectrum analysis optimized by brain storm optimization is applied to preprocess the original wind speed data to obtain a smoother sequence, and a generalized dynamic fuzzy neural network is utilized to perform the forecasting. With a smaller and simpler structure of the neural network, the model can effectively achieve a rapid learning rate and accurate forecasting. Three experimental results, which cover 10-min, 30-min and 60-min interval wind speed time series data, demonstrate that the model can both satisfactorily approximates the actual value and be used as an effective and simple tool for the planning of smart grids. (C) 2017 Elsevier B.V. All rights reserved.
Background and Objective: Oral epithelial cells help to prevent against bacterial infection in the oral cavity by producing antimicrobial peptides (AMPs). A broad-spectrum AMP, calprotectin (a complex of S100A8 and S100A9 proteins), is expressed by oral epithelial cells and is up-regulated by interleukin-1 alpha (IL-1 alpha). Shosaikoto (SST) is a traditional Japanese herbal medicine that has immunomodulatory effects and is reported to enhance the levels of IL-1 alpha in epithelial cells. The purpose of this study was to investigate the effect of SST on the expression of calprotectin and other AMPs through the regulation of IL-1 alpha in oral epithelial cells. Material and Methods: Human oral epithelial cells (TR146) were cultured with SST (at concentrations ranging from 10 to 250 mu g/mL) in the presence or absence of anti-IL-1 alpha or IL-1 receptor antagonist. The expression of S100A8- and S100A9-specific mRNAs was examined by northern blotting. Calprotectin expression and IL-1 alpha secretion were investigated by immunofluorescent staining or ELISA. The expression of other AMPs and IL-1 alpha was analyzed by RT-PCR and by quantitative real-time PCR. Results: Shosaikoto (25 mu g/mL) significantly increased the expression of S100A8- and S100A9-specific mRNAs and calprotectin protein. Shosaikoto increased S100A7 expression, but had no effect on the expression of other AMPs. The expression of IL-1 alpha-specific mRNA and its protein were slightly increased by SST. A neutralizing antibody against IL-1 alpha or IL-1 receptor antagonist inhibited SST up-regulated S100A8/S100A9 mRNA expression. Conclusion: These results suggest that SST increases the expression of calprotectin and S100A7 in oral epithelial cells. In response to SST, up-regulation of calprotectin may be partially induced via IL-1 alpha.
In this work, we demonstrate the technology of wafer-scale transistor-level heterogeneous integration of GaAs pseudomorphic high electron mobility transistors (pHEMTs) and Si complementary metal-oxide semiconductor (CMOS) on the same Silicon substrate. GaAs pHEMTs are vertical stacked at the top of the Si CMOS wafer using a wafer bonding technique, and the best alignment accuracy of 5 mu m is obtained. As a circuit example, a wide band GaAs digital controlled switch is fabricated, which features the technologies of a digital control circuit in Si CMOS and a switch circuit in GaAs pHEMT, 15% smaller than the area of normal GaAs and Si CMOS circuits.
This paper presents benefits of using 650 V SiC cascodes to realize a 1.5 kW single phase, continuous conduction mode (CCM) totem-pole, bridgeless power factor correction (PFC) AC/DC converter switching at 100 kHz. By exploiting the excellent switching and conduction performance of SiC cascodes, the compatibility with a 12 V gate drive and synchronous rectification of the full-bridge, a very high peak efficiency of 98.6% is achieved for this AC/DC converter at high line (230 V) AC input with 400 V DC output. With correct digital control of the full-bridge gate signals the inductor current spike at zero-crossing is significantly reduced and a total harmonic distortion (THD) of 1.83% is achieved at high line near full load.
Obesity has been linked to cardiovascular disease, hypertension, diabetes and the metabolic syndrome, with elevated markers of systemic inflammation. Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane adhesion molecule involved in leukocyte migration to sites of inflammation. In human obesity, elevated expression of the soluble form of ICAM-1 (sICAM-1) is positively correlated with abdominal fat deposition. Increases in adiposity have also been correlated with macrophage infiltration into adipose tissue. Here we investigate adipose tissue production and transcriptional regulation of ICAM-1 in a mouse model of dietary obesity. After feeding mice a high-fat diet, ICAM-1 expression in serum and adipose tissue was analyzed by ELISA, Northern blotting, real-time quantitative PCR, and flow cytometry. After 6 mo on the high-fat diet, sICAM-1 levels significantly correlated with body weight and abdominal fat mass. ICAM-1 mRNA was expressed in adipose tissue of mice, with significantly higher levels in males than females. After only 3 wk, there were adipose tissue-specific increases in mRNAs for ICAM-1, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in male mice. Analysis of the stromal-vascular fraction of male adipose tissue revealed CD11b-negative cells with increased surface ICAM-1 and CD34. We also found two populations of F4/80+, CD11b+, ICAM-1+ cells, one of which also expressed CD14 and CD11c and was increased in response to a high-fat diet. These results indicate that within 3 wk on a high-fat diet, male mice exhibited significant increases in pro-inflammatory factors and immune cell infiltration in adipose tissue that may represent links between obesity and its associated inflammatory complications.
Thermistor is most widely used sensor in the temperature measurement due to its high sensitivity and fast response. The non-linearity of the thermistor gives rise to several difficulties for on-chip interface, direct digital readout, wireless transmission and so on. Hence, an effective lineariser is needed to overcome the difficulties. In this study, an artificial neural network-based lineariser has been developed for the thermistor connected in operational amplifier circuit. Operational amplifier-based thermistor signal conditioning circuit exhibits a stable temperature-voltage relation over a range of 0-100 degrees C with low linearity. A multilayer perceptron feed-forward neural network is used for non-linearity compensation of thermistor circuit to further improve the linearity. A linearity of +/- 0.3% is achieved over 0-100 degrees C with high temperature stability. A notable feature of the proposed method is the non-linearity error remains low over the entire dynamic range of the thermistor. The efficacy of the method is established through simulation studies and its practicality demonstrated with experimental results obtained on a prototype unit built and tested.
PURPOSE. To investigate the role of the serine/threonine kinase SIK2, a member of the saltinducible kinase (SIK) family, in insulin-dependent cell survival and hyperglycemia-induced cell death in Muller glia. METHODS. Expression studies were performed by RT-PCR, immunostaining, Northern blotting, and immunoblotting. Insulin-dependent changes in SIK2 activity were investigated by in vitro kinase assays in MIO-M1 Muller cell line. Akt activation was studied by immunoblotting and cell death by TUNEL assay. The potential role of SIK2 in insulin signaling was explored by overexpression and sh-RNA knock-down approaches. Effects of hyperglycemia were studied in vitro and in vivo in streptozotocin-injected rats. RESULTS. SIK2 expression was detected throughout adult retina, except for the outer nuclear layer. Insulin stimulation of MIO-M1 cells resulted in a rapid 2-fold increase of SIK2 activity, increased insulin receptor substrate 1 (IRS1)-SIK2 interaction, and reduced cell death. pAkt levels following insulin treatment were modulated by SIK2 activity. Under hyperglycemia, increased SIK2 activity/expression was concomitant to decreased Akt activation and enhanced apoptosis; whereas knockdown of SIK2 under normo-and hyperglycemic conditions resulted in a rapid increase in pAkt levels and blunted cell death. SIK2 overexpression under normoglycemia had an opposite effect. SIK2 activity increased significantly within 2 weeks of induction of hyperglycemia in the rat retina. CONCLUSIONS. Results indicate that SIK2 functions as a negative modulator of the insulindependent survival pathway and contributes to hyperglycemia-induced cell death of Muller glia in vitro. Although still hypothetical at this point, our study suggests that SIK2 could serve a similar role during the development of diabetic retinopathy in vivo and that it represents a potential target to control disease progression.
This paper reports on the design and implementation of an integrated operational amplifier in bipolar SiC, and elaborates on its operation in positive-feedback configuration. The opamp is studied in different feedback setups: closed-loop compensated amplifier, comparator with hysteresis (Schmitt trigger), and as a relaxation oscillator. Measurement results suggest a stable closed-loop opamp with similar to 40 dB gain, a Schmitt trigger with constant threshold levels over a wide temperature range, and a relaxation oscillator tested up to 540 kHz. All the setups were tested from 25 degrees C up to 500 degrees C. (C) 2015 Elsevier Ltd. All rights reserved.
In this letter, silicon carbide MOSFET-based integrated circuits have been designed, fabricated, and successfully tested from -193 degrees C (80 K) to 500 degrees C. Silicon carbide single MOSFETs remained fully operational over a 700-degrees C wide temperature range and exhibited stable I-V characteristics. The circuits that include operational amplifier (op-amp), 27-stage ring oscillator, and buffer were tested and shown to be functional up to 500 degrees C with relatively small performance variation between 300 degrees C and 500 degrees C. High-temperature evaluation of these circuits confirmed stable operation and survivability of both the ring oscillator and op-amp for more than 100 h at 500 degrees C.
Research in the field of electronics of 1D group-IV semiconductor structures has attracted increasing attention over the past 15 years. The exceptional combination of the unique 1D electronic transport properties with the mature material know-how of highly integrated silicon and germanium technology holds the promise of enhancing state-of-the-art electronics. In addition of providing conduction channels that can bring conventional field effect transistors to the uttermost scaling limits, the physics of 1D group IV nanowires endows new device principles. Such unconventional silicon and germanium nanowire devices are contenders for beyond complementary metal oxide semiconductor (CMOS) computing by virtue of their distinct switching behavior and higher expressive value. This review conveys to the reader a systematic recapitulation and analysis of the physics of silicon and germanium nanowires and the most relevant CMOS and CMOS-like devices built from silicon and germanium nanowires, including inversion mode, junctionless, steep-slope, quantum well and reconfigurable transistors.
With the fast development of high voltage DC (HVDC) cable, cable insulation under DC conditions has got more attention. In this paper, tests were conducted to study the electrical tree initiation in silicone rubber (SIR) under DC and polarity reversal voltages. It is found that electrical tree initiation has significant polarity effects under both DC and polarity reversal voltages. There are only single-branch-like trees and branch-like trees under DC and polarity reversal voltages. As for pre-stressing effects under polarity reversal, the pre-stressing voltage has positive effects to electrical tree initiation, while the pre-stressing time has little influence. Space charge distribution of SIR under high electric field was studied with flat plate pulsed electro-acoustic (PEA) system, and their characteristics were discussed to explain this phenomenon. Moreover, different treeing breakdown phenomenon is found under polarity reversal voltage which differs from that under DC voltage. The existence of fast charges and slow charges gives reasonable explanation to it. Special attention should be paid to the transient situation like polarity reversal which would result in irreversible effects more easily, and affect true length of life for HVDC cables. (C) 2017 Elsevier B.V. All rights reserved.
Silver carp is one of the most important planktivorous fish in Chinese aquaculture and plays a significant role controlling cyanobacterial blooms. A balanced gut microbiota is crucial for growth and health of the host because of its important roles in immune defense, digestion of complex carbohydrates, and production of enterocytes. In our study, the dominant bacterial and cellulolytic bacterial (Clostridium I, Clostridium III, Clostridium XIVab, and Fibrobacter) communities in the contents and mucus of the silver carp gut (foregut, midgut, and hindgut) were analyzed by denaturing gradient gel electrophoresis and quantitative polymerase chain reaction (qPCR) analyses. The results revealed that the dominant and cellulolytic bacterial communities were significantly different among gut regions as well as in contents and mucus. Bacterial diversity and richness in contents and mucus increased along the gut and were higher in contents than those in local mucus. A sequence analysis of gut samples exhibited the conservative phylotypes of Proteobacteria, Actinobacteria, and Firmicutes. The gut of silver carp harbored an abundance of cellulolytic bacteria, particularly Clostridium XIV ab. The foregut segment had the highest proportions of the four cellulolytic bacteria, followed by the midgut and hindgut. However, the proportions of cellulolytic species in the silver carp gut was much lower than those in the terrestrial vertebrate gastrointestinal tract. We conclude that gut bacteria could help silver carp obtain energy from cyanobacteria, which may be why silver carp can maintain high growth rates during cyanobacterial blooms.
The immunomodulatory effects of dietary p-glucan were evaluated in silver catfish. p-glucan was added to the diet (0.01%, and 0.1%) and fed to the fish for 21 days, to evaluate effects on blood and some innate immune parameter, or fed for 42 days, to evaluate growth rate and resistance to challenge with pathogenic Aeromonas hydrophila. We found that adding p-glucan to the diet had no effect on fish growth and no effect on blood cells, or serum bacterial agglutination and serum myeloperoxidase activity. However, fish that received p-glucan in the diet had the natural hemolytic activity of complement significantly higher compared to control fish. Furthermore, fish fed with p-glucan and challenged with A. hydrophila had fewer bacteria in blood and presented a significantly higher survival rate compared to control fish. Thus, we concluded that p-glucan might be explored as feed additive aiming to improve silver catfish innate immunity and resistance to specific pathogen.
Appropriately defining and efficiently calculating similarities from large data sets are often essential in data mining, both for gaining understanding of data and generating processes and for building tractable representations. Given a set of objects and their correlations, we here rely on the premise that each object is characterized by its context, i.e., its correlations to the other objects. The similarity between two objects can then be expressed in terms of the similarity between their contexts. In this way, similarity pertains to the general notion that objects are similar if they are exchangeable in the data. We propose a scalable approach for calculating all relevant similarities among objects by relating them in a correlation graph that is transformed to a similarity graph. These graphs can express rich structural properties among objects. Specifically, we show that concepts-abstractions of objects-are constituted by groups of similar objects that can be discovered by clustering the objects in the similarity graph. These principles and methods are applicable in a wide range of fields and will be demonstrated here in three domains: computational linguistics, music, and molecular biology, where the numbers of objects and correlations range from small to very large.
During orthodontic tooth movement, the periodontal ligament (PDL) is exposed to continuous mechanical strain. However, many researchers have applied cyclic tensile strain, not continuous tensile strain, to PDL cells in vitro because there has been no adequate device to apply continuous tensile strain to cultured cells. In this study, we contrived a novel device designed to apply continuous tensile strain to cells in culture. The continuous tensile strain was applied to human immortalized periodontal ligament cell line (HPL cells) and the cytoskeletal structures of HPL cells were examined by immunohistochemistry. The expression of both inflammatory and osteogenic markers was also examined by real-time reverse transcription polymerase chain reaction. The osteogenic protein, Osteopontin (OPN), was also detected by western blot analysis. The actin filaments of HPL cells showed uniform arrangement under continuous tensile strain. The continuous tensile strain increased the expression of inflammatory genes such as IL-1 beta, IL-6, COX-2 and TNF-alpha, and osteogenic genes such as RUNX2 and OPN in HPL cells. It also elevated the expression of OPN protein in HPL cells. These results suggest that our new simple device is useful for exploring the responses to continuous tensile strain applied to the cells.
Recent embodied theories of meaning known as 'simulation semantics' posit that language comprehension engages, or even amounts to, mental simulation. What is meant here by 'language comprehension', however, deviates from the perspectives on interpersonal communication adhered to by researchers in social psychology and interactional linguistics. In this paper, we outline four alternative perspectives on comprehension in spoken interaction, each of which highlights factors that have remained largely outside the current purview of simulation theories. These include perspectives on language comprehension in terms of (i) striving for inter-subjective conformity; (ii) recognition of communicative intentions; (iii) prediction and anticipation in a dynamic environment; and (iv) integration of multimodal cues. By contrasting these views with simulation theories of comprehension, we outline a number of fundamental differences in terms of the kind of process comprehension is assumed to be (passive and event-like versus active and continuous), as well as the kind of stimulus that language is assumed to be (comprising unimodal units versus being multimodal and distributed across conversational turns). Finally, we discuss potential points of connection between simulation semantics and research on spoken interaction, and touch on some methodological implications of an interactive and multimodal reappraisal of simulation semantics.
A simultaneous bidirectional transceiver over a single wire has been developed in a 65 nm CMOS technology for a command and control bus. The echo signals of the simultaneous bidirectional link are cancelled by controlling the decision level of receiver comparators without power-hungry operational amplifier (op-amp) based circuits. With the clock information embedded in the rising edges of the signals sent from the source side to the sink side, the data is recovered by an open-loop digital circuit with 20 times blind oversampling. The data rate of the simultaneous bidirectional transceiver in each direction is 75 Mbps and therefore the overall signaling bandwidth is 150 Mbps. The measured energy efficiency of the transceiver is 56.7 pJ/b and the bit-error-rate (BER) is less than 10(-12) with 2(7)-1 pseudo-random binary sequence (PRBS) pattern for both signaling directions.
The guiding mechanism based on flexure hinges (FHs) is widely used in micro/nano-manufacturing technology. Both the stiffness and the frequency of FHs play significant roles in their dynamic performance, so the design task of such a structure is to find the optimal topology and corresponding size of FHs under stiffness and frequency constraints. However, the existing optimization methods pay more attention to the stiffness than to the frequency constraint owing to difficulties in dynamic topology optimization. In this article, with the symmetrical layout assumption of FHs and the analytical equivalent stiffness and mass expression of a single FH, the simultaneous topology and size optimization problem is converted to an analytical optimization formula with both discrete and continuous variables. Finally, the tension stiffening effect is used to compensate for manufacturing errors. A design case is used to illustrate the efficiency of the proposed method.
Child maltreatment remains a significant problem in the United States. Single mothers are at elevated risk for maltreatment due to financial limitations and lower levels of available supports. The current study investigates whether neigborhood social cohesion and informal social control were associated with child maltreatment in a sample of single mothers, and further examines the direct and indirect pathways through which these associations occur. The current study uses an analytic sample of 1,158 mothers who participated in the third and fourth wave Fragile Families and Child Wellbeing (FFCW) study to estimate the direct associations between social cohesion, informal social control, and child maltreatment, as well as two potential mediators, maternal depression and parenting stress. Descriptive statistics reveal that participants were economically disadvantaged, approximately 57% possessed at least a high school diploma or GED, and the majority of participants were African American, Non-Hispanic (64.7%), followed by Hispanic (19.9%) and White, non-Hispanic (12.8%). The structural equation models did not show significant associations between informal social control and either physical abuse or neglect. Social cohesion, on the other hand, was indirectly related to physical abuse and neglect. Maternal depression mediated the relationship between social cohesion and maltreatment. While parenting stress did not explain the relationship between social cohesion and child maltreatment, parenting stress was individually associated with both physical abuse and neglect. The findings suggest that maternal depression may be an important pathway through which social cohesion is affects child abuse and neglect for single, non-cohabitating mothers. (C) 2016 Elsevier Ltd. All rights reserved.
This study proposes a simple control scheme for using single-stage flyback (SSF) converters in lighting source applications for LEDs. Among the advantages of the average current mode is an I/O current ripple that is only one-half of the critical conduction mode (CRM). This condition helps extend the output capacitor lifetime while lowering the input EMI capacitance input EMI capacitance. The SSF converter proposed in this study operates in continuous conduction mode (CCM). In addition, two sample-and-hold (S/H) circuits are placed at the output voltage loop and feed-forward path, respectively. Since these S/H circuits access the average output current and average feed-forward voltage, the LED driver is unaffected by the 120-Hz ripple noise, the total harmonic distortion (THD) is reduced, and the transient response of the output current is improved. Finally, the operation principles and design considerations of the studied LED driver are analyzed and discussed. A laboratory prototype is also designed and tested to verify the feasibility. Copyright (C) 2014 John Wiley & Sons, Ltd.
Oxygen vacancies play an important role in many photocatalytic reaction, and have attracted enormous attention from the scientists and engineers. The surface or bulk oxygen vacancies have a different function in the photo-reaction process. Herein, three different TiO2 nanoparticles possessing surface oxygen vacancies (SO) and/or bulk single-electron-trapped oxygen vacancy (SETOV) were fabricated by dehydration or reduction of different titania precursors. The three kinds of TiO2 nanoparticles were characterized systematically by XRD, TEM, Raman, XPS, ESR, TG, UV-vis DRS, and PL techniques. The photocatalytic reduction results of CO2 indicated that both the bulk SETOVs and surface oxygen vacancies contributed to the enhancement of the light absorption, while the surface vacancies facilitated to the separation of the photo-generated charge carriers, and on the contrast, the bulk SETOVs acted as the recombination center. The co-existence of the surface and bulk oxygen vacancies exhibited a synergistic effect to improve the photoreduction efficiency of CO2 to CH4. Through adjusting the ratio of the surface and bulk oxygen vacancies and analyzing the positron lifetime and relative intensity by positron annihilation, the photoreduction efficiency of CO2 improved with the increase of the ratio of surface oxygen vacancies to bulk SETOVs. (C) 2017 Elsevier B.V. All rights reserved.
The schematic method for increasing of radiation hardness of bipolar operational amplifiers for ASET effects is presented. The method is based on the use of improved current mirror and modified input stage circuit.
The pricing of options in the fast mean-reverting stochastic volatility model using the singular perturbation method has received a considerable amount of attention in the last two decades. However, it is not to easy to estimate the accuracy of the approximation if the payoff function is not smooth or bounded, as is the case for European call options. In this article, we introduce a new novel approach for pricing options in the fast mean-reverting stochastic volatility model. Combinations of Fourier analysis and singular perturbation methods enable us to estimate the accuracy easily. We also show that this method allows us to derive the price of European and Bermudan options in the fast mean-reverting stochastic volatility environment with jumps. (C) 2017 Elsevier B.V. All rights reserved.
Singular value decomposition (SVD), as an effective signal denoising tool, has been attracting considerable attention in recent years. The basic idea behind SVD denoising is to preserve the singular components (SCs) with significant singular values. However, it is shown that the singular values mainly reflect the energy of decomposed SCs, therefore traditional SVD denoising approaches are essentially energy-based, which tend to highlight the high-energy regular components in the measured signal, while ignoring the weak feature caused by early fault. To overcome this issue, a reweighted singular value decomposition (RSVD) strategy is proposed for signal denoising and weak feature enhancement. In this work, a novel information index called periodic modulation intensity is introduced to quantify the diagnostic information in a mechanical signal. With this index, the decomposed SCs can be evaluated and sorted according to their information levels, rather than energy. Based on that, a truncated linear weighting function is proposed to control the contribution of each SC in the reconstruction of the denoised signal, In this way, some weak but informative SCs could be highlighted effectively. The advantages of RSVD over traditional approaches are demonstrated by both simulated signals and real vibration acoustic data from a two-stage gearbox as well as train bearings. The results demonstrate that the proposed method can successfully extract the weak fault feature even in the presence of heavy noise and ambient interferences. (C) 2017 Elsevier Ltd. All rights reserved.
This paper shows that a Wien-bridge oscillator is not always a sinusoidal oscillator. Depending on the differential input voltage of the operational amplifier used, the output of the Wien-bridge oscillator can move from a nearly sinusoidal wave to a nearly square wave. This depends largely on the values of the passive components used. Experimental results that confirms the presented theory are included. These results confirm the previously made observations that sinusoidal oscillators and multivibrators are not separate classes of circuits as the same circuit can provide the two modes of operation depending on the values of the passive components used.
Silicon Photo-Multipliers (SiPM) are regarded as novel photo-detectors to replace conventional Photo Multiplier Tubes (PMTS). However, the breakdown voltage dependence on the ambient temperature results in a gain variation of similar to 3%/degrees C. This severely limits the application of this device in experiments with wide range of operating temperature, especially in space missions. An experimental setup was established to investigate the temperature and bias voltage dependence of gain for the Multi-Pixel Photon Counter (MPPC). The gain and breakdown voltage dependence on operating temperature of an MPPC can be approximated by a linear function, which is similar to the behavior of a zener diode. The measured temperature coefficient of the breakdown voltage is (59.4 0.4 mV)/degrees C. According to this fact, an analog power supply based on two zener diodes and an operational amplifier was designed with a positive temperature coefficient. The measured temperature dependence for the designed power supply is between 63.65-64.61 mV/degrees C at different output voltages. The designed power supply can bias the MPPC at an over-voltage with a temperature variation of similar to 5 mV/degrees C. The gain variation of the MPPC biased at over-voltage of 2 V was reduced from 2.8%/degrees C to 0.3%/degrees C when biased the MPPC with the designed power supply for gain control. Detailed design and performance of the analog power supply in the temperature range from similar to 42.7 degrees C to 20.9 degrees C will be discussed in this paper.
RNA interference strategies offer an alternative to small molecular drug targeting. Small interfering RNA (siRNA) constitutes a class of molecules that allows the effective and specific inhibition of the biosynthesis of any protein. Indeed, siRNA have emerged as a major tool in molecular biology techniques and an important approach to identify suitable therapy targets in cancer. However, siRNA therapy approaches in vivo are scarce. Two major problems hinder siRNA as a therapeutic tool: (1) delivery through the bloodstream leads to degradation or rapid renal clearance (stabilization) and (2) specific uptake by the desired cell type (specificity). This review summarizes the ongoing attempts to use RNAi against disease-causing factors. We compare methods to stabilize siRNA in different conjugates and that decorate these complexes with targeting molecules such as antibodies, single-chain Fv or Fab fragments, to enable specific uptake of the carriers by the respective cells. We propose the development of antibody-coupled siRNA complexes, which have shown to allow stabilization as well as targeted uptake of siRNA to cancer cells.
The emergence of small RNAs as key and potent regulators of gene expression has prompted the need for robust detection and assay protocols to be developed for investigating their generation and tissue distribution. The physicochemical nature of these RNAs allows traditional assay methods to be employed; however, due to the relatively small size of endo-siRNAs, key changes to these protocols are required. Here, we present a method for the nonradioactive detection of endo-siRNAs in mouse tissue and microinjected Xenopus oocytes. The method comprises steps for RNA extraction, PAGE, and low-stringency northern blotting using DIG-labelled RNA probes. Moreover, it includes a strategy to design and generate cheap hybridization probes with greatly increased sensitivity. These methods may be used as a simple and robust protocol for nonradioactive detection of small RNAs or be combined with other strategies to potentially enhance signal intensity.
Some of the main concerns with in vivo application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol ( PEG) with variable chain length affects siRNA pharmacokinetics and biodistribution. The PEG chains were conjugated to chemically stabilized siRNA at the 5 ' terminal end of the passenger strand using click chemistry. The siRNA conjugate remained functionally active and showed significantly prolonged circulation in the blood stream after intravenous injection. siRNA conjugated with 20kDa PEG (PEG20k-siRNA) was most persistent, approximately 50% PEG20k-siRNA remained Ih post-injection, while the uncoupled siRNA was rapidly removed >90% at 15min. In vivo fluorescent imaging of the living animal showed increased concentration of siRNA in peripheral tissue and delayed urine excretion when coupled to PEG 20k. Biodistribution studies by northern blotting revealed equal distribution of conjugated siRNA in liver, kidney, spleen and lung without significant degradation 24 h post-injection. Our study demonstrates that PEG conjugated siRNA can be applied as a delivery system to improve siRNA bioavailability in vivo and may potentially increase the efficiency of siRNA in therapeutic applications.
As a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, demalonylase, and desuccinylase, sirtuin 5 (SIRT5) in host cells has been reportedly observed in the mitochondria, in the cytosol/cytoplasm or in the nucleus. Various functional roles of SIRT5 have also been described in cellular metabolism, energy production, detoxification, oxidative stress, and apoptosis, but some of the reported results are seemingly inconsistent or even contradictory to one another. Using immunocytochemistry, molecular biology, gene transfection, and flow cytometry, we investigated the expression, subcellular distribution, and possible functional roles of SIRT5 in regulating apoptosis and oxidative stress of cultured SH-EP neuroblastoma cells. Both endogenous and transfected exogenous SIRT5 were observed in mitochondria of host SH-EP cells. Overexpression of SIRT5 markedly protected SH-EP cells from apoptosis induced by staurosporine or by incubation in Hank's balanced salt solution. SIRT5 also lowered the level of oxidative stress and countered the toxicity of hydrogen peroxide to SH-EP cells. It was suggested that the anti-apoptotic role of SIRT5 was mediated, at least in part, by its anti-oxidative effect in SH-EP neuroblastoma cells although the involved molecular mechanisms remain to be elucidated in details.
We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjogren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4(fl/fl,CD4-Cre); Smad4 tKO) NOD mice had accelerated development of SS compared with wildtype (Smad4(+/+,CD4-Cre); WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age. Activated/memory T cells and cytokine (IFN-Y, IL-17)- producing T cells were increased in Smad4 tKO NOD mice, however the proportion and function of regulatory T (Treg) cells were not different between Smad4 tKO and WT NOD mice. Effector T (Teff) cells from Smad4 tKO NOD mice were less sensitive than WT Teff cells to suppression by Treg cells. Th17 differentiation capability of Teff cells was similar between Smad4 tKO and WT NOD mice, but IL-17 expression was increased under inducible Treg skewing conditions in T cells from Smad4 tKO NOD mice. Our results demonstrate that disruption of the Smad4 pathway in T cells of NOD mice increases Teff cell activation resulting in upregulation of Th17 cells, indicating that Smad4 in T cells has a protective role in the development of SS in NOD mice.
Aims: Evidence suggests ongoing practice variability in the quality of skeletal survey examinations for non-accidental injury. The purpose of the study was to investigate the effects on examination quality following the implementation of imaging checklists. Method: A retrospective evaluation of skeletal survey examinations was carried out on studies performed between January 2007 and November 2014 at a large District General Hospital Trust. Longitudinal assessment was undertaken over three periods, before and following the introduction of two versions of imaging checklists, following modifications. Examinations were assessed and scored using three measures for completeness and quality employing a modified established scoring system against a professional body national standards document. Results: A total of 121 examinations met the inclusion criteria, all quality assessment measures showed improvements between each period. Examination completeness increased from median of 13 projections, to 20 throughout the three periods. Mann Whitney u Tests showed significant differences between each period. The mean combined anatomy score reduced from 3.11 to 1.10 throughout the three periods. Independent t Tests and Mann Whitney u Tests showed a significant decrease throughout the study period. Total percentage examination quality increased from median 44-83% throughout the three periods. Independent t Tests also showed significant differences between each period. Conclusion: The use of imaging checklists to improve quality and to support the optimal acquisition of the non-accidental injury skeletal survey shows encouraging results. However, further work is needed to optimise content and the use of checklists in practice. (C) 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.
The prevalence of skull fractures after mild head trauma is 2 % in children of all ages and 11 % in children younger than 2 years. The current standard management for a child diagnosed with an isolated skull fracture (ISF), in our institute, is hospitalization for a 24-h observation period. Based on data from the literature, less than 1 % of all minor head injuries require neurosurgical intervention. The main objective of this study was to evaluate the risk of neurological deterioration of ISF cases, in order to assess the need for hospitalization. We reviewed the medical charts of 222 children who were hospitalized from 2006 to 2012 with ISF and Glascow Coma Scale-15 at the time of arrival. We collected data regarding demographic characteristics, mechanism of injury, fracture location, clinical symptoms and signs, need for hospitalization, and need for repeated imaging. Data was collected at three time points: at presentation to the emergency room, during hospitalization, and 1 month after admission, when the patients' parents were asked about the course of the month following discharge. None of the 222 children included in the study needed neurosurgical intervention. All were asymptomatic 1 month after the injury. Two children underwent repeated head CT due to persistence or worsening of symptoms; these CT scans did not reveal any new findings and did not lead to any intervention whatsoever. Children arriving at the emergency room with a minor head injury and isolated skull fracture on imaging studies may be considered for discharge after a short period of observation. Discharge should be considered in these cases provided the child has a reliable social environment and responsible caregivers who are able to return to the hospital if necessary. Hospital admission should be reserved for children with neurologic deficits, persistent symptoms, suspected child abuse, or when the parent is unreliable or is unable to return to the hospital if necessary. Reducing unnecessary hospitalizations can prevent emotional stress, in addition to saving costs for the child's family and the health care system.
Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens and by chronic inflammation. Although the etiology of SLE remains unclear, the influence of environment factors, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, is generally considered as main players in the pathogenesis of SLE. We studied DNA methyltransferases' (DNMTs) type 1, 3A and 3B transcript levels in peripheral blood mononuclear cells from patients diagnosed with systemic lupus erythematosus and from the healthy control subjects. Furthermore, the association of DNMT1, DNMT3A, and DNMT3B mRNA levels with gender, age, and major clinical manifestations was analyzed. Peripheral blood mononuclear cells (PBMCs) were isolated from 32 SLE patients and 40 healthy controls. Reverse transcription and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine DNMT1, DNMT3A, and DNMT3B mRNA expression levels. Significantly lower DNMT1 (p = 0.015543) and DNMT3A (p = 0.003652) transcript levels in SLE patients were observed compared with healthy controls. Nevertheless, the DNMT3B mRNA expression levels were markedly lower compared with DNMT1 and DNMT3A, both in PBMCs from affected patients and those from control subjects. Furthermore, the DNMT1 transcript levels were positively correlated with SLE disease activity index (SLEDAI) (r (s) = 0.4087, p = 0.020224), while the DNMT3A transcript levels were negatively correlated with patients age (r (s) = -0.3765, p = 0.03369). Our analyses confirmed the importance of epigenetic alterations in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, such as phototosensitivity and arthritis, might be associated with the dysregulation of DNA methyltransferases' mRNA expression levels.
Aberrant T cell immune responses appear central to the development of systemic lupus erythematosus (SLE). We previously reported that Gaq, the alpha subunit of Gq, regulates T and B cell immune responses, promoting autoimmunity. To address whether Gaq contributes to the pathogenesis of SLE, Gaq mRNA expression was studied using real time-PCR in PBMCs and T cells from SLE patients as well as age- and sex-matched healthy controls. Our results showed that Gaq mRNA expression was decreased in PBMCs and T cells from SLE patients compared to healthy individuals. Correlation analyses showed that Gaq expression in T cells from SLE patients was associated with disease severity (as per SLE Disease Activity Index), the presence of lupus nephritis, and expression of Th1, Th2 and Th17 cytokines. In keeping with clinical results, T-helper cell subsets (Th1, Th2 and Th17) were over-represented in Gaq knockout mice. In addition, Gaq expression in SLE T cells was negatively correlated with the expression of Bcl-2, an anti-apoptotic gene, and positively correlated with the expression of Bax, a pro-apoptotic gene. These data suggest that reduced Gaq levels in T cells may promote enhanced and prolonged T cell activation, contributing to the clinical manifestations of SLE.
The symptoms of sleep apnea, such as sleep fragmentation and oxygen desaturation, might be risk factors for subsequent mood disorder (MD), but associations between sleep apnea and MD remain unclear. This nationwide population-based study thus aimed to identify the risk of MD in patients with vs. without sleep apnea. This cohort study used data from the National Health Insurance database. In total, 5415 patients diagnosed with sleep apnea between 2000 and 2010 were evaluated, and 27,075 matched non-sleep apnea enrollees were included as a comparison cohort. All subjects were followed until 2011. The Cox proportional hazard ratio (HR) was used to investigate the relationship between MD and sleep apnea while controlling covariates and comorbidities of sleep apnea. Of 5415, 154 patients with sleep apnea (2.84 %) were diagnosed with MD during the follow-up period in comparison with 306 of 27,075 individuals (1.13 %) without antecedent sleep apnea. After adjusting for the selected factors and comorbidities, we found that patients with sleep apnea were from 1.82- to 2.07-fold greater risk of MD than the comparisons. Of the three subcategories of MD (major depressive disorder, bipolar disorder, and unspecified MD), sleep apnea had the highest predisposing risk with respect to major depressive disorder (adjusted HR from 1.82 to 2.07) and bipolar disorder (adjusted HR from 2.15 to 3.24). There is a greater likelihood of MD manifesting in patients with a history of sleep apnea. Health professionals are thus advised to carefully monitor the psychological impacts of sleep apnea.
This study aimed to determine the prevalence of clinical depression as defined by ICD-10 criteria in all patients with obstructive sleep apnea (OSA) referred to a sleep center. Prospective general and sleep evaluations were conducted in 447 consecutive patients referred to our sleep center during the first quarter of 2008. Inclusion criteria were Apnea Hypopnea Index (AHI) >9, completion of the Beck Depression Inventory (BDI-II) with a score >= 14 and World Health Organization WHO-5 Well-Being Index (WHO-5)9. Out of these, 85 met the combined screening criterion BDI II >= 14 and WHO-5 <= 13. Eighty-one patients underwent a psychiatric examination by psychiatric sleep specialists. In 21.5 % of the sample, clinical depression was diagnosed. Other complaints existed in 12 % (n = 10); 7 % (n = 6) of patients had a different psychiatric diagnosis. The prevalence of clinical depression according to ICD-10 criteria in a selected clinical sample (referred to the sleep center) was 21.5 %. Mood scales tend to overestimate complaints as compared to psychiatric consultation. Interdisciplinary cooperation is recommended for both OSA patients with symptoms of depression and depressed patients with treatment resistance.
Sleep problems can boost inflammation and may jeopardize interpersonal functioning, risks that may be magnified in couples. This observational study examined the effects of self-reported recent sleep duration on couples' inflammation, inflammatory responses to a problem discussion, interpersonal behavior, and use of emotion regulation strategies (emotion expression, cognitive reappraisal) during conflict. People who slept less had higher stimulated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production after the marital problem discussion than those who slept more. However, using emotion expression and cognitive reappraisal strategies during conflict protected couples who slept less from inflammatory reactivity. Specifically, people's short sleep did not relate to inflammatory increases when they expressed their own feelings more or when their partner reappraised or expressed their emotions more. When both partners slept less, couples interacted in a more hostile way than when at least one partner slept more. These data point to the combination of short sleep and marital conflict as a novel path to heightened inflammation, a risk that partners' emotion regulation strategies may counteract. The study also highlights the role of short sleep in more negative or punishing marital behavior. (C) 2017 Elsevier Ltd. All rights reserved.
BACKGROUND Adenoid hypertrophy is one of the main causes of upper airway obstruction and Obstructive Sleep Apnoea (OSA) in children. Studies have shown that administration of mometasone furoate aqueous nasal spray significantly improved oxygen saturation in children with sleep-disordered breathing. The aim of this study is to evaluate the effect of mometasone furoate aqueous nasal spray on oxygen saturation measured through nocturnal pulse oximetry and quality of life in children with sleep-disordered breathing due to adenoid hypertrophy. MATERIALS AND METHODS Eighty children suspected of having sleep-disordered breathing due to adenoid hypertrophy, whose parents were not willing for surgery (Adenoidectomy) were enrolled in a non-controlled clinical trial. Quality of life questionnaire was distributed pre-and post-interventional and the symptoms were scored depending on its frequency of occurrence. Pre-and post-intervention x-ray nasopharynx taken. Pre-and post-intervention nocturnal oxygen saturation monitoring was done and Oxygen Desaturation Index (ODI) as well as desaturation events were recorded. Data was analysed using paired student t-test and Wilcoxon's Signed Rank Tests. RESULTS Out of the 80 study population, 43 were males (53.8 %) and 37 were females (46.2%). Age distribution of the population ranged from 3 to 10 years with a mean age of 6.2 years. The study showed a strong positive correlation between grade of adenoid size and ODI (r -0.790; p < 0.001). All the pulse oximetric parameters improved significantly after drug administration (p < 0.001). There was a significant improvement in the quality of life of these children after the treatment. CONCLUSION The study revealed mometasone furoate aqueous nasal spray therapy leads to significant reduction in adenoid size and gives symptomatic relief for children with sleep disordered breathing. It can be recommended as the prime medical treatment modality for children with sleep disordered breathing, as it substantially reduced the morbidity and health care utilisation by these children.
Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:34-40)
We take on the challenge posed by Horton and Kraftl [2006. What Else? Some More Ways of Thinking and Doing Children's Geographies'. Children's Geographies 4 (1): 69-95, 71.] that research be slowed down' through methodological and theoretical routes to acknowledge seemingly trivial details in children's lives. Based on an ethnographic study in an Australian preschool focusing on children's place-making in a globalizing world, this paper discusses one event in the home corner to exemplify what we understand as and how we enact methodological slowness. The event is revisited by recognizing the role of the unexpected, the troubling and paying attention to data that overspills the research engagement in conducting ideally preset qualitative research'. Research engagements not only reflect but also produce children's lives. Researching the global' is doing the global' as the frames, practices and traditions of research itself are part and parcel of the so-called answers we produce. As result, a more nuanced and complex understanding of how the global' is made and circulated by children surfaces.
Background: The small brown planthopper (SBPH) is an important pest of cereal crops and acts as a transmission vector for multiple RNA viruses. Rapid diagnosis of virus in the vector is crucial for efficient forecast and control of viral disease. Reverse transcription polymerase chain reaction (RT-PCR) is a rapid, sensitive and reliable method for virus detection. The traditional RT-PCR contains a RNA isolation step and is widely used for virus detection in insect. However, using the traditional RT-PCR for detecting RNA virus in individual SBPHs becomes challenging because of the expensive reagents and laborious procedure associated with RNA isolation when processing a large number of samples. Results: We established a simplified RT-PCR method without RNA isolation for RNA virus detection in a single SBPH. This method is achieved by grinding a single SBPH in sterile water and using the crude extract directly as the template for RT-PCR. The crude extract containing the virus RNA can be prepared in approximately two minutes. Rice stripe virus (RSV), rice black streaked dwarf virus (RBSDV) and Himetobi P virus (HiPV) were successfully detected using this simplified method. The detection results were validated by sequencing and dot immunobinding assay, indicating that this simplified method is reliable for detecting different viruses in insects. The evaluation of the sensitivity of this method showed that both RSV and HiPV can be detected when the cDNA from the crude extract was diluted up to 103 fold. Compared to the traditional RT-PCR with RNA isolation, the simplified RT-PCR method greatly reduces the sample processing time, decreases the detection cost, and improves the efficiency by avoiding RNA isolation. Conclusions: A simplified RT-PCR method is developed for rapid detection of RNA virus in a single SBPH without the laborious RNA isolation step. It offers a convenient alternative to the traditional RT-PCR method.
Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.
Nuclear Power Plants (NPPs) have been historically deployed to cover the base-load of the electricity demand. Nowadays some NPPs might perform daily load cycling operation (i.e. load following) between 50% and 100% of their rated power. With respect to the insertion of control rods or comparable action to reduce the nuclear power generation, a more efficient alternative might be the "Load Following by Cogeneration", i.e. diverting the excess of power, respect to the electricity demand, to an auxiliary system. A suitable cogeneration system needs: 1. To have a demand of electricity and/or heat in the region of 500 MWe-1.5 GWt; 2. To meet a significant market demand; 3. To have access to adequate input to process; 4. To be flexible: cogeneration might operate at full load during the night when the request of electricity is low, and be turned off during the daytime. From the economic standpoint, it is essential that the investment in the auxiliary system is profitable. This paper provides a techno-economic assessment of systems potentially suitable for coupling with a NPP for load following. The results show that district heating, desalination and hydrogen might be technically and economically feasible. (C) 2016 Elsevier Ltd. All rights reserved.
Background: Small non-coding RNAs are essential regulators of gene expression at the transcriptional and posttranscriptional levels. High-throughput sequencing has revealed thousands of predicted small RNAs; however, only a few of these have been well characterized. Northern blotting is the most convincing method for small RNA validation. Findings: In this study, we improved the Northern blot method by using biotin-labeled probes. miRNAs and siRNAs derived from both Arabidopsis thaliana and Oryza sativa were investigated. The results suggest that this improved method is sensitive and efficient, with approximately 5 mu g of total RNA being sufficient for detection. Furthermore, long-term storage of probes labeled in this manner is more convenient, less contaminative and degradative compared with traditional probes. Conclusions: This protocol is an alternative strategy for small RNA detection and represents an efficient means of researching small RNAs.
Purification of RNA fragments from a complex mixture is a very common technique, and requires consideration of the time, cost, purity and yield of the purified RNA fragments. This study describes the fastest method of purifying small RNA with the lowest cost possible, without compromizing the yield and purity. The technique describes the purification of small RNA from polyacrylamide gel, resulting in a good yield of small RNA with minimum experimental steps in avoiding degradation of the RNA, obviating the use of ethidium bromide and phenol-chloroform extraction, as well as siliconized glass wools to remove the polyacrylamide gel particles. The purified small RNA is suitable for a wide variety of applications such as ligation, end labelling with radio isotope, RT-PCR (Reverse Transcriptase-PCR), Northern blotting, experimental RNomics study and also Systematic Evolution of Ligands by Exponential Enrichment (SELEX).
Many small RNAs have been cloned from animal gonads, for example, endogenous small interfering RNAs (endo-siRNAs) were found in oocytes and piwi-interacting RNAs (piRNAs) were found in testis. Gallus gallus (chicken) is an important model organism, but few small RNAs have been identified from its gonads. In this study, we isolated and cloned 156 small RNAs from adult chicken testes. Since there is a reasonably even distribution from 22 to 33 nt, these small RNAs are slightly longer than miRNAs and endo-siRNAs. Genome mapping indicated that these small RNAs were derived from intergenic regions, exons, introns, and repetitive elements including chicken repeat 1, long terminal repeats, and simple repeats. Since they are similar with piRNAs, we named them piRNA-like RNAs (pil-RNAs). Northern blotting of 16 selected sequences showed that nine are specifically expressed in the adult testis. The vast majority of these pil-RNAs are poorly conserved between species, suggesting that they are unique to the adult chicken testis. Further analysis of the cloned pil-RNAs will improve our understanding of the function of small RNAs in animal gonad development.
Small RNAs (20-24 nucleotides long and nonprotein coding) have been increasingly investigated. They are responsible for phenomena described as RNA interference (RNAi), cosuppression, gene silencing, or quelling. Major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biosynthesis. MiRNAs control the expression of cognate target genes by binding to reverse complementary sequences, resulting in cleavage or translational inhibition of the target RNA. SiRNAs have similar structure, function, and biogenesis as miRNAs; siRNAs derive from long double-stranded RNA of transgenes, endogenous repeat sequences, or transposons. Understanding these fundamental processes requires the sensitive and specific detection of small RNA species. In this report, we present a simple Northern blot protocol for small RNAs in transgenic plants.
The objective of this work was to comparatively study the tissue tropism and the associated pathology of 2 autochthonous small ruminant lentivirus (SRLV) field strains using an experimental infection in sheep through the bone marrow. Fifteen male, SRLV-free lambs of the Rasa Aragonesa breed were inoculated with strain 697 (nervous tissue origin, animals A1-A6), with strain 496 (articular origin, animals B1-B6), or with uninfected culture medium (C1-C3). Clinical, serologic, and polymerase chain reaction (PCR) evaluations were performed periodically. Two lambs from each infected group and a control animal were euthanized at 134, 273, and 319 days postinfection. Tissues were analyzed by gross and histopathologic evaluation; immunohistochemistry for CD3, CD4, CD8, CD68, and FoxP3 cell markers; lung morphometric evaluation; and tissue proviral quantification by PCR. All infected animals became positive either by enzyme-linked immunosorbent assay and/or PCR, with group B lambs showing the highest serologic values and more consistently positive PCR reactions. Group A lambs showed representative lung lesions but only mild histopathologic changes in the central nervous system (CNS) or in carpal joints. Contrarily, group B lambs demonstrated intense carpal arthritis and interstitial pneumonia but an absence of lesions in the CNS. Proviral copies in tissues were detected only in group B lambs. Experimental infection with these SRLV strains indicates that strain 496 is more virulent than strain 697 and more prone to induce arthritis, whereas strain 697 is more likely to reproduce encephalitis in Rasa Aragonesa lambs. Host factors as well as viral factors are responsible for the final clinicopathologic picture during SRLV infections.
The increasing population living in cities is leading to higher resource utilization, which strains the cities' ability to focus on sustainability. Adoption of different technologies can transform cities into "smart cities" that utilize energy in a more efficiently. This paper presents results from a technology assessment tool developed together with six mid-sized European cities. The main areas of focus have been evaluated based on the cities' priorities: transportation (both public and private) and consumers' perspectives on the use of smart electricity meters. The use of electric vehicles in Sweden, and a techno-economic evaluation of biogas-derived biomethane and electricity use in public transportation have been analyzed. The main conclusions show an overall higher efficiency for biogas-derived electricity use in electric buses; a need for higher consumer engagement through more detailed information provision for both increasing EV market penetration and electricity savings; and a need to establish detailed technology assessments for successful technology adoption in cities. (C) 2016 Elsevier Ltd. All rights reserved.
With the advancement in technologies, the power requirement around the globe is tremendously increasing, putting extra loads on grids. The existing grids cannot bear that load and also do not provide the interface with Distributed Renewable Energy Sources (DRES). Building new lines and substations alone do not serve the purpose of overcoming energy shortfall. Thus a major transformation in electricity infrastructure is need of the hour to meet the ever growing demands of electricity. Converting current power management system to a smart autonomic system is pertinent to achieve an increasing amount of renewable energy generation. This paper presents a comprehensive review of advances in control of smart grids. Various robust and adaptive strategies are spotlighted with a detailed description of control of overloads and power smart grids. Also, power generation, storage and management techniques and development of operational schedule of sources and loads are elaborated. Recently reported systems and Information and Communication Technologies (ICT) techniques in smart grid are highlighted. Renewable energy has potential to eliminate the current electricity crisis in Pakistan's energy sector. The solar, wind, hydro and biogas/biomass are the alternative energy resources found abundantly in the country, which have tremendous potential to offer environment-friendly energy solutions. This in-depth study reveals that a lot of opportunities and potential of smart grid technology exist in developing countries like Pakistan that need to be exploited so as to cope with energy crisis.
A Non-Technical Loss (NTL) fraud occurs when a fraudster tampers with a smart meter so that the meter registers less electricity consumption than the actual consumed amount, and therefore the utility becomes the victim who suffers the corresponding economic loss. In the literature, many detection schemes have been proposed to detect NTL frauds. However, some NTL frauds are far more complicated than what the existing schemes expect. We recently discovered a new potential type of frauds, a variant of NTL frauds, called Colluded Non-Technical Loss (CNTL) frauds in the Smart Grid. In a CNTL fraud, multiple fraudsters can co-exist or collaborate to commit the fraud. Existing detection schemes cannot detect CNTL frauds since these methods do not consider the co-existing or collaborating fraudsters, and therefore cannot distinguish one from many fraudsters. In this paper, we propose a CNTL fraud detector to detect CNTL frauds. The proposed method can quickly detect a tampered meter based on recursive least squares. After identifying the tampered meter, the proposed scheme can detect different fraudsters using mathematical models. Our experiments show that our method is effective in detecting CNTL frauds. (C) 2016 Elsevier B.V. All rights reserved.
Traditional power grid and its demand-side management (DSM) techniques are centralized and mainly focus on industrial consumers. The ignorance of residential and commercial sectors in DSM activities degrades the overall performance of a conventional grid. Therefore, the concept of DSM and demand response (DR) via residential sector makes the smart grid (SG) superior over the traditional grid. In this context, this paper proposes an optimized home energy management system (OHEMS) that not only facilitates the integration of renewable energy source (RES) and energy storage system (ESS) but also incorporates the residential sector into DSM activities. The proposed OHEMS minimizes the electricity bill by scheduling the household appliances and ESS in response to the dynamic pricing of electricity market. First, the constrained optimization problem is mathematically formulated by using multiple knapsack problems, and then solved by using the heuristic algorithms; genetic algorithm (GA), binary particle swarm optimization (BPSO), wind driven optimization (WDO), bacterial foraging optimization (BFO) and hybrid GA-PSO (HGPO) algorithms. The performance of the proposed scheme and heuristic algorithms is evaluated via MATLAB simulations. Results illustrate that the integration of RES and ESS reduces the electricity bill and peak-to-average ratio (PAR) by 19.94% and 21.55% respectively. Moreover, the HGPO algorithm based home energy management system outperforms the other heuristic algorithms, and further reduces the bill by 25.12% and PAR by 24.88%.
In a typical smart grid, a large number of smart meters are deployed at energy consumers' premises, which can report real-time usage data to the control center of the energy producer. Although such a communication model can help to improve the efficiency and reliability of electricity delivery, which is crucial to our society, it also leads to several security issues: (1) attackers may violate the privacy of energy consumers, and (2) attackers may tamper with the transmitted data for their own benefits or purposes. To deal with these security issues, many researchers have proposed different schemes for privacy preservation or abnormal data detection. However, existing studies usually address them separately. In this paper, we jointly resolve these two major security issues in the smart grid. Specifically, we propose a privacy-aware data dissemination scheme for smart grid with abnormal data traceability (PDDS), based on bilinear group theory and non-interactive zero-knowledge proof. In our scheme, we design a novel link function that can verify whether there are different signatures that are signed by the same consumer, which effectively reduces the time and communication overhead for tracing. To evaluate the correctness and performance of the proposed scheme, we first develop a solid security analysis, which shows that the proposed scheme can efficiently preserve identity confidentiality and data integrity. We then conduct extensive simulation experiments, which further demonstrate that our scheme can significantly reduce communication costs. (C) 2016 Elsevier B.V. All rights reserved.
With smart grid, the power supply will shift from the 1: N tree structure with centralized power plants to the M:N structure with various kinds of distributed energy resources based on renewable energy, batteries, and so on. Deregulation of the electricity market will yield a truly competitive market, where anyone can become a power seller or buyer, which will necessitate a real-time multiseller-multibuyer power trading system. However, it is difficult to realize such a system without centralized control, because of the additional trade complexity created by a large number of sellers, including ordinary homes. In this paper, the authors propose a novel distributed power cooperation algorithm that maximizes each home's welfare based on local information. The proposed algorithm enables each home to calculate the same electricity market price from only local household information, to trade, and to maximize all members' satisfaction in smart grid by balancing consumption against supply. The authors formulate a distributed optimization problem and logically prove that the authors' algorithm can obtain the same optimal user welfare as the global optimal approach but within a much shorter time. (C) 2016 American Society of Civil Engineers.
Efficient power management in smart grids requires obtaining power consumption data from each resident. However, data concerning user's electricity consumption might reveal sensitive information, such as living habits and lifestyles. In order to solve this problem, this paper proposes a privacy-preserving cube-data aggregation scheme for electricity consumption. In our scheme, a data item is described as a multi-dimensional data structure (l-dimensional), and users form and live in multiple residential areas (m areas, and at most n users in each area). Based on Horner's Rule, for each user, we construct a user-level polynomial to store dimensional values in a single data space by using the first Horner parameter. After embedding the second Horner parameter into the polynomial, the polynomial is hidden by using Paillier cryptosystem. By aggregating data from m areas, we hide the area-level polynomial into the final output. Moreover, we propose a batch verification scheme in multi-dimensional data to reduce authentication cost. Finally, our analysis shows that the proposed scheme is efficient in terms of computation and communication costs, suitable for massive user groups, and supports the flexible and rapid growth of residential scales in smart grids.
A smart community is a distributed system consisting of a set of smart homes which utilize the smart home scheduling techniques to enable customers to automatically schedule their energy loads targeting various purposes such as electricity bill reduction. Smart home scheduling is usually implemented in a decentralized fashion inside a smart community, where customers compete for the community level renewable energy due to their relatively low prices. Typically there exists an aggregator as a community wide electricity policy maker aiming to minimize the total electricity bill among all customers. This paper develops a new renewable energy aware pricing scheme to achieve this target. We establish the proof that under certain assumptions the optimal solution of decentralized smart home scheduling is equivalent to that of the centralized technique, reaching the theoretical lower bound of the community wide total electricity bill. In addition, an advanced cross entropy optimization technique is proposed to compute the pricing scheme of renewable energy, which is then integrated in smart home scheduling. The simulation results demonstrate that our pricing scheme facilitates the reduction of both the community wide electricity bill and individual electricity bills compared to the uniform pricing. In particular, the community wide electricity bill can be reduced to only 0.06 percent above the theoretic lower bound.
Behind the roll-out of smart metering technologies lies a belief that personalised, fact-based information enhances energy awareness and allows consumers to modify their behaviour. Amongst others, practice theoretical accounts have shown that this belief stems from a linear, individualistic and unrealistic interpretation of behaviour change. However, in emphasising how energy use is grounded in socio-material realities of everyday life, practice-based studies have not fully considered the role and potential of information in reconfiguring domestic practices. This article takes a smart grid pilot project in the Netherlands as a case to analyse the interrelatedness of policy interventions, information flows and domestic practices. We argue that the effects of policy interventions on domestic practices can be better understood when seen as part of a configuration of heterogeneous practices. This helps in understanding when and how information is accomplished and put-to-work, and in identifying what can be done to improve smart grid interventions.
It is expected that the rooftop photovoltaic (PV) systems can realize net-zero energy solar buildings (nZESBs), but it is not enough by itself. To realize 100% of nZESBs, the smart photovoltaic system blind (SPSB) was proposed to generate electricity in the PV system and to reduce indoor cooling demands through the shading effect in the blind system. Before its implementation, this study aims to investigate the impact of the proposed SPSB on nZESBs, which is conducted in three ways (i.e., technical, economic, and political analyses). The detailed results can be summarized as follows: (i) technical analysis: when applying the SPSBCIGS&2-axis (which represents the SPSB with the copper-indium-gallium-selenide (CIGS) PV panel and the two-axis tracking system), its energy self-sufficiency rate was determined to be 1.25-2.31 times superior to other alternatives; (ii) economic analysis: in terms of the NPV25 (net present value at year 25), SPSBCIGS&2-axis was determined to be 1.41-2.97 times superior to others; in terms of the SIR25 (savings-to-investment ratio at year 25), 1.14-1.26 times; and in terms of the break-even point, 1.4-3.0 years; and (iii) political analysis: the grid-connected utilization plan including solar renewable energy certificates (GC(incl.SREC) plan) was determined to improve the economic profitability of the proposed SPSB. (C) 2017 Elsevier Ltd. All rights reserved.
While previous work has focused on the positive impact of smiles on interpersonal perceptions, this research proposes and finds that smile intensity differentially affects two fundamental dimensions of social judgments-warmth and competence. A marketer displaying a broad smile, compared to a slight smile, is more likely to be perceived by consumers as warmer but less competent. Furthermore, the facilitative effect of smile intensity on warmth perceptions is more prominent among promotion-focused consumers and in low-risk consumption contexts, while the detrimental effect of smile intensity on competence perceptions is more likely to occur among prevention-focused consumers and in high-risk consumption situations. Field observations in a crowdfunding context further indicate that the effects of smile intensity on warmth and competence perceptions have downstream consequences on actual consumer behaviors.
Knowledge of molecular mechanism(s) implicated in smokeless tobacco (ST) associated oral carcinogenesis is meager. In an attempt to identify genes that are modulated by ST, we recently reported establishment of an oral epithelial cell culture. AMOL III from oral hyperplasia with hyperkeratosis of a khaini consumer. Herein we aimed to identify novel molecular targets of ST (khaini) in AMOL III cells using differential display. Fourteen novel differentially expressed genes (12 upregulated and 2 downregulated) were identified. These differentially expressed cDNAs were amplified. cloned. sequenced and confirmed by reverse northern blotting. Mainly these genes are components of transcriptional machinery. cell-cell adhesion. signaling, growth and transformation processes. The important novel molecular targets identified included activated leucocyte cell adhesion molecule (ALCANI). CDP-diacylglycerol-inositol 3-phosphatidyl transferase (phosphatidylinositol synthase). CDIPT an important enzyme in phosphatidyl inositol biosynthesis, ribosomal protein (RPS23), KIAA0121 and growth and transformation factor. E2IG5. Semi-quantitative RTPCR analysis of these five genes confirmed over-expression of these genes in oral pre-malignant lesions (OPLs) and oral squamous cell carcinomas (OSCCs) of ST consumers underscoring their biological relevance in ST-associated oral tumorigenesis. In depth studies are warranted to determine the functional significance of ALCAM and CDIPT in oral carcinogenesis. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Background: We have previously shown that genetically induced smooth muscle cell (SMC) cycle reentry in transgenic mouse models expressing the SV40 T antigen (TAg) resulted in adaptive arterial remodeling. The present investigation targeted the in vitro expression pattern of the collageneous matrix associated with TAg-induced SMC cycle modulation. Methods: SMC cultures were established from the transgenic model expressing temperature-sensitive TAg. This allowed inducible transgene expression at the permissive temperature of 33 degrees C compared with the restrictive temperature of 39.5 degrees C. To distinguish a transgene effect from a temperature effect, SMCs with constitutively expressed TAg were used as controls. Data were obtained using array technology, Northern blotting, reverse transcription polymerase chain reaction, and zymography. Results: TAg-induced SMC cycle reentry resulted in significant down-regulation of matrix metalloprotemase (MMP)-3, whereas NIMP-2, -9, and -11 were not influenced. In addition, SMC cycle reentry resulted in significantly increased RNA levels of procollagen alpha 2(IV), procollagen alpha 2(V), and procollagen alpha 1(XI), whereas procollagen alpha 1(III) and procollagen alpha 1(VIII) were down-regulated. Studies of the RNA expression levels of granulocyte-macrophage colony-stimulating factor revealed an up-regulation of this proinflammatory and matrix-modulating cytokine. Conclusions: This transgenic model provides evidence that TAg-induced cell cycle reentry is associated with a complex modulation of the collageneous matrix. Factors identified in this in vitro study reveal a comprehensive expression pattern of candidates, which might allow the vessel to undergo adaptive arterial remodeling under in vivo conditions. Our results will give rise to further investigations to elaborate on this hypothesis and to improve understanding of the role of such factors in vascular diseases. (c) 2008 Elsevier Inc. All rights reserved.
Up-regulation of the gap-junctional protein connexin43 (Cx43) in arterial smooth muscle cells (SMCs) features in response to injury and in atherosclerosis, in parallel with phenotypic transition to the synthetic state. TGF-beta 1 is known to have a role in SMC differentiation and extracellular matrix (ECM) synthesis, key characteristics of phenotypic state. Here, we set out to examine the effects of TGF-beta 1 on Cx43-gap junction expression in relation to SMC differentiation, ECM synthesis and growth. Cx43 expression was analysed by immunoconfocal microscopy and Western blotting in primary human aortic SMCs treated with TGF-beta 1 over a 48-h period, with assessment of gap-junctional communication by cell-to-cell transfer of microinjected ethidium bromide. In parallel, synthetic activity was analysed by Northern blotting for ECM components alpha-1(I) and alpha 1(III) procollagen transcripts, contractile differentiation was assessed by immunoconfocal microscopy and Western blotting of the markers smooth muscle a-actin, calponin and smooth muscle heavy chain isoform I (SM1), and growth was measured by BrdU incorporation. Our results demonstrate that TGF-beta 1 significantly up-regulates Cx43 expression and intercellular communication, in concert with increased expression of alpha-actin, calponin and SM1. Concomitant with contractile protein expression, ECM synthesis was increased rather than decreased, TGF-beta 1 inducing a significant up-regulation of both procollagen transcripts. These effects were independent of growth. We conclude that in human aortic SMCs, TGF-beta 1 treatment leads to up-regulation of Cx43-mediated gap-junctional communication and increased synthetic activity yet, somewhat paradoxically, also enhanced contractile differentiation. (c) 2006 Elsevier GmbH. All rights reserved.
Some animals can undergo a remarkable transition from active normal life to a dormant state called aestivation; entry into this hypometabolic state ensures that life continues even during long periods of environmental hardship. In this study, we aimed to identify those central nervous system (CNS) peptides that may regulate metabolic suppression leading to aestivation in land snails. Mass spectral-based neuropeptidome analysis of the CNS comparing active and aestivating states, revealed 19 differentially produced peptides; 2 were upregulated in active animals and 17 were upregulated in aestivated animals. Of those, the buccalin neuropeptide was further investigated since there is existing evidence in molluscs that buccalin modulates physiology by muscle contraction. The Theba pisana CNS contains two buccalin transcripts that encode precursor proteins that are capable of releasing numerous buccalin peptides. Of these, Tpi-buccalin-2 is most highly expressed within our CNS transcriptome derived from multiple metabolic states. No significant difference was observed at the level of gene expression levels for Tpi-buccalin-2 between active and aestivated animals, suggesting that regulation may reside at the level of post translational control of peptide abundance. Spatial gene and peptide expression analysis of aestivated snail CNS demonstrated that buccalin-2 has widespread distribution within regions that control several physiological roles. In conclusion, we provide the first detailed molecular analysis of the peptides and associated genes that are related to hypometabolism in a gastropod snail known to undergo extended periods of aestivation. (C) 2015 Elsevier Inc. All rights reserved.
beta-keratins of reptilian scales have been recently cloned and characterized in some lizards. Here we report for the first time the sequence of some beta-keratins from the snake Elaphe guttata. Five different cDNAs were obtained using 5'- and 3'-RACE analyses. Four sequences differ by only few nucleotides in the coding region, whereas the last cDNA shows, in this region, only 84% of identity. The gene corresponding to one of the cDNA sequences has a single intron present in the 5'-untranslated region. This genomic organization is similar to that of birds' beta-keratins. Cloning and Southern blotting analysis suggest that snake beta-keratins belong to a family of high-related genes as for geckos. PCR analysis suggests a head-to-tail orientation of genes in the same chromosome. In situ hybridization detected beta-keratin transcripts almost exclusively in differentiating oberhautchen and beta-cells of the snake epidermis in renewal phase. This is confirmed by Northern blotting that showed, in this phase, a high expression of two different transcripts whereas only the longer transcript is expressed at a much lower level in resting skin. The cDNA coding sequences encoded putative glycine-proline-serine rich proteins containing 137-139 amino acids, with apparent isoelectric point at 7.5 and 8.2. A central region, rich in proline, shows over 50% homology with avian scale, claw, and feather keratins. The prediction of secondary structure shows mainly a random coil conformation and few R-strand regions in the central region, likely involved in the formation of a fibrous framework of beta-keratins. This region was possibly present in basic reptiles that originated reptiles and birds. Developmental Dynamics 236:1939-1953, 2007. (c) 2007 Wiley-Liss, Inc.
The processes of yeast selection for using as wine fermentation starters have revealed a great phenotypic diversity both at interspecific and intraspecific level, which is explained by a corresponding genetic variation among different yeast isolates. Thus, the mechanisms involved in promoting these genetic changes are the main engine generating yeast biodiversity. Currently, an important task to understand biodiversity, population structure and evolutionary history of wine yeasts is the study of the molecular mechanisms involved in yeast adaptation to wine fermentation, and on remodeling the genomic features of wine yeast, unconsciously selected since the advent of winemaking. Moreover, the availability of rapid and simple molecular techniques that show genetic polymorphisms at species and strain levels have enabled the study of yeast diversity during wine fermentation. This review will summarize the mechanisms involved in generating genetic polymorphisms in yeasts, the molecular methods used to unveil genetic variation, and the utility of these polymorphisms to differentiate strains, populations, and species in order to infer the evolutionary history and the adaptive evolution of wine yeasts, and to identify their influence on their biotechnological and sensorial properties.
Background: Negative mental imagery is ubiquitous in cognitive models of social anxiety and in the social anxiety literature. Previous research has shown that it is causal of increased anxiety, lower social performance ratings and lower implicit self-esteem. Despite its prevalence, few studies have investigated this imagery directly. Aims: This study aimed to provide an in-depth analysis of the phenomenology of negative imagery experienced by socially anxious individuals, and to compare recurrent and intrusive images with images deliberately generated by participants during the study. Method: Thirty-eight undergraduate students screened to be above average in social anxiety scores completed a computerized imagery questionnaire adapted from previous qualitative work. Results: Thematic analyses revealed four major image themes for intrusive images and three for deliberately generated images including interacting with others and anxiety symptoms. Most intrusive images were based on negative episodic memories and were experienced at least fortnightly. Images were primarily visual, auditory and somatic but could involve any sensory modality. Depression anxiety stress scale (DASS-21) scores were higher in participants who experienced intrusive imagery and increased with the frequency of intrusions. Emotionality was generally higher in intrusive images than generated images. Conclusions: The phenomenology of negative imagery experienced by socially anxious individuals is idiosyncratic and may be inherently different from images generated for use in experimental research. Theoretical and clinical implications are discussed.
Little is known about the quality of socially anxious individuals' romantic relationships. In the present study, we examine associations between social anxiety and social support in such relationships. In Study 1, we collected self-report data on social anxiety symptoms and received, provided, and perceived social support from 343 undergraduates and their romantic partners. One year later couples were contacted to determine whether they were still in this relationship. Results indicated that men's social anxiety at Time 1 predicted higher rates of breakup at Time 2. Men's and women's perceived support, as well as men's provided support, were also significantly predictive of breakup. Social anxiety did not interact with any of the support variables to predict breakup. In Study 2, a subset of undergraduate couples with a partner high (n = 27) or low (n = 27) in social anxiety completed two 10-minute, lab-based, video-recorded social support tasks. Both partners rated their received or provided social support following the interaction, and trained observers also coded for support behaviors. Results showed that socially anxious individuals received less support from their partners during the interaction according to participant but not observer report. High and lower social anxiety couples did not differ in terms of the target's provision of support. Taken together, results suggest that social anxiety is associated with difficulties even in the context of established romantic relationships. Clinical implications are discussed.
Background and Objectives: This two-year follow-up study evaluated the long-term outcomes of two early interventions that aimed at reducing social and test anxiety in young adolescents at risk for developing social anxiety disorder. Methods: In this RCP, moderately socially anxious adolescents (N=240, mean age 13.6 years) were randomly assigned to a 10-week internet-based multifaceted cognitive bias modification training (CBM), a 10-week school-based cognitive behavioral group training (CBT), or a no-intervention control condition. Using multiple imputation, this study examined the changes in primary and secondary outcome measures from pretest to follow-up in a repeated measures design. Results: Primary outcome: Self-reported social and test anxiety generally decreased from pre-test to two-year follow-up, regardless of treatment condition. The percentage of adolescents who developed a social anxiety disorder was very low (6%) and similar across conditions. Secondary outcome: There were beneficial changes in self-esteem, self-reported prosocial behaviors, and fear of negative evaluation, but none of these were related to treatment condition. Automatic social-threat associations did not significantly change. The CBM intervention was effective in changing interpretative bias as indexed by the Recognition Task but this long-term effect did not transfer to the Adolescent Interpretation and Belief Questionnaire. Limitations: There was a substantial (50%) though seemingly non-selective attrition at follow-up. Conclusions: This RCT does not support the longer-term efficacy of school-based CBT or CBM as an early intervention for social and test anxiety. Rather, it emphasizes the positive 'natural' course of highly socially anxious adolescents over two years. (C) 2016 The Authors. Published by Elsevier Ltd.
Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate social learning and behavior, including conspecific recognition, social attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in social recognition, social attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of social behavioral diversity, with a particular focus on neural networks that modulate social learning, behavior, and salience of sociosensory stimuli during species-typical social contexts. Published by Elsevier Ltd.
Chronic social behavior problems after pediatric traumatic brain injury (TBI) significantly contribute to poor quality of life for survivors. Using a well-characterized mouse model of early childhood TBI, we have previously demonstrated that young brain-injured mice develop social deficits by adulthood. As biological sex may influence both normal and aberrant social development, we here evaluated potential sex differences in post-TBI psychosocial deficits by comparing the behavior of male and female mice at adulthood (8 weeks post-injury). Secondly, we hypothesized that pediatric TBI would influence neuronal morphology identified by Golgi-Cox staining in the hippocampus and prefrontal cortex, regions involved in social cognition and behavior, before the onset of social problems (3 weeks post-injury). Morphological analysis of pyramidal neurons in the ipsilateral prefrontal cortex and granule cells of the hippocampal dentate gyrus revealed a reduction in dendritic complexity after pediatric TBI. This was most apparent in TBI males, whereas neurons from females were less affected. At adulthood, consistent with previous studies, TBI males showed deficits in sociability and social recognition. TBI females also showed a reduction in sociability, but intact social recognition and increased sociosexual avoidance. Together, these findings indicate that sex is a determinant of regional neuroplasticity and social outcomes after pediatric TBI. Reduced neuronal complexity in the prefrontal cortex and hippocampus, several weeks after injury in male mice, appears to precede the subsequent emergence of social deficits. Sex-specific alterations in the social brain network are thus implicated as an underlying mechanism of social dysfunction after pediatric TBI. (C) 2016 Elsevier B.V. All rights reserved.
Children's early emerging intuitive theories are specialized for different conceptual domains. Recently attention has turned to children's concepts of social groups, finding that children believe that many social groups mark uniquely social information such as allegiances and obligations. But another critical component of intuitive theories, the causal beliefs that underlie category membership, has received less attention. We propose that children believe membership in these groups is constituted by mutual intentions: i.e., all group members (including the individual) intend for an individual to be a member and all group members (including the individual) have common knowledge of these intentions. Children in a broad age range (4-9) applied a mutual-intentional framework to newly encountered social groups early in development (Experiment 1, 2, 4). Further, they deploy this mutual-intentional framework selectively, withholding it from essentialized social categories such as gender (Experiment 3). Mutual intentionality appears to be a vital aspect of children's naive sociology. (C) 2017 Elsevier B.V. All rights reserved.
Contemporary China is experiencing deeper reform and social transformation. The newly born social media have participated in the historical process of China's reform and social change. Based on the existing literature of social media and internet public events, this article aims to study China's internet public events through the perspective of social transformation theory, especially theories of the civic society and public sphere. This study has used case study to explore the role that social media play in social change in China through in-depth analysis of 57 typical cases. We found that social media are not only an important information source and means for online civil mobilization, but also provide citizens an open and free space for discussion of internet public events. The impact of social media in promoting social change was reflected in the supervision of governmental, judiciary and other public power; maintenance of justice and protection of disadvantaged groups; attracting the government's attention, urging governmental information publicity and investigation of the events, and promoting social management innovation and institutional change. Social media are a helpful force in the construction of internet public sphere and civil society of contemporary China. Meanwhile, it is necessary to be cautious that social media is also likely to be a breeding ground for nationalist and populist discourses. (C) 2016 Elsevier Ltd. All rights reserved.
Sometimes our automatic evaluations do not correspond well with those we can reflect on and articulate. We present a novel approach to the assessment of automatic and reflective affective evaluations of exercising. Based on the assumptions of the associative-propositional processes in evaluation model, we measured participants' automatic evaluations of exercise and then shared this information with them, asked them to reflect on it and rate eventual discrepancy between their reflective evaluation and the assessment of their automatic evaluation. We found that mismatch between self-reported ideal exercise frequency and actual exercise frequency over the previous 14 weeks could be regressed on the discrepancy between a relatively negative automatic and a more positive reflective evaluation. This study illustrates the potential of a dual-process approach to the measurement of evaluative responses and suggests that mistrusting one's negative spontaneous reaction to exercise and asserting a very positive reflective evaluation instead leads to the adoption of inflated exercise goals.
Mimicry involves unconsciously imitating the actions of others and is a powerful and ubiquitous behavior in social interactions. There has been a long debate over whether mimicry is abnormal in people with autism spectrum conditions (ASC) and what the causes of any differences might be. Wang and Hamilton's (2012) social top-down response modulation (STORM) model proposed that people with ASC can and do mimic but, unlike neurotypical participants, fail to modulate their mimicry according to the social context. This study used an established mimicry paradigm to test this hypothesis. In neurotypical participants, direct gaze specifically enhanced congruent hand actions as previously found; in the ASC sample, direct gaze led to faster reaction times in both congruent and incongruent movements. This result shows that mimicry is intact in ASC, but is not socially modulated by gaze, as predicted by STORM.
A growing body of research suggests that social contextual factors such as desires and goals, affective states and stereotypes can shape early perceptual processes. We suggest that a generative Bayesian approach towards perception provides a powerful theoretical framework to accommodate how such high-level social factors can influence low-level perceptual processes in their earliest stages. We review experimental findings that show how social factors shape the perception and evaluation of people, behaviour, and socially relevant objects or information. Subsequently, we summarize the generative view of perception within the `Bayesian brain', and show how such a framework can account for the pervasive effects of top-down social knowledge on social cognition. Finally, we sketch the theoretical and experimental implications of social predictive perception, indicating new directions for research on the effects and neurocognitive underpinnings of social cognition.(C) 2016 Elsevier Inc. All rights reserved.
Eyes have been shown to play a key role during human social interactions. However, to date, no comprehensive cross-discipline model has provided a framework that can account for uniquely human responses to eye cues. In this review, I present a framework that brings together work on the phylogenetic, ontogenetic, and neural bases of perceiving and responding to eyes. Specifically, I argue for a two-process model: a first process that ensures privileged attention to information encoded in the eyes and is important for the detection of other minds and a second process that permits the decoding of information contained in the eyes concerning another person's emotional and mental states. To some degree, these processes are unique to humans, emerge during different times in infant development, can be mapped onto distinct but interconnected brain regions, and likely serve critical functions in facilitating cooperative interactions in humans. I also present evidence to show that oxytocin is a key modulator of sensitive responding to eye cues. Viewing eyes as windows into other minds can therefore be considered a hallmark feature of human social functioning deeply rooted in our biology.
Empathy is a complex construct, thought to contain multiple components. One popular measurement paradigm, the Interpersonal Reactivity Index (IRI), has been used extensively to measure empathic tendencies in schizophrenia research across four domains: empathic concern, perspective-taking, personal distress, and fantasy. However, no recent meta-analysis has been conducted for all four factors of this scale. The goal of this meta-analysis was to examine self-reported empathic tendencies for each factor of the IRI in people with schizophrenia as compared to healthy controls. A literature search revealed 32 eligible schizophrenia studies. The Hedges' g standardized difference effect size was calculated for each component using a random effects meta-analytic model. Compared to healthy controls, schizophrenia samples reported significantly reduced tendencies for empathic concern, perspective-taking, and fantasy, but significantly greater tendencies for personal distress. Duration of illness significantly moderated the results for perspective-taking such that those with a longer duration exhibited greater deficits; percent female significantly moderated the results for personal distress such that samples with more females exhibited reduced effect sizes. Future work is needed to examine the impact of heightened personal distress on the empathic tendencies and abilities of those with schizophrenia, including the possible role of emotion regulation.
Behavioral dysexecutive disorders are highly prevalent in patients with neurological diseases but cannot be explained by cognitive dysexecutive impairments. In fact, the underlying mechanisms are poorly understood. Given that socioemotional functioning underlies appropriate behavior, socioemotional impairments may contribute to the appearance of behavioral disorders. To investigate this issue, we performed a transnosological study.Seventy-five patients suffering from various neurological diseases (Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration, and stroke) were included in the study. The patients were comprehensively assessed in terms of cognitive and behavioral dysexecutive disorders and socioemotional processes (facial emotion recognition and theory of mind). As was seen for cognitive and behavioral dysexecutive impairments, the prevalence of socioemotional impairments varied according to the diagnosis. Stepwise logistic regressions showed that (i) only cognitive executive indices predicted hypoactivity with apathy/abulia, (ii) theory of mind impairments predicted hyperactivity-distractibility-impulsivity and stereotyped/perseverative behaviors, and (iii) impaired facial emotion recognition predicted social behavior disorders. Several dysexecutive behavioral disorders are associated with an underlying impairment in socioemotional processes but not with cognitive indices of executive functioning (except for apathy). These results strongly suggest that some dysexecutive behavioral disorders are the outward signs of an underlying impairment in socioemotional processes.
This study examined whether approach-avoidance related behaviour elicited by facial affect is moderated by the presence of an observer-irrelevant trigger that may influence the observer's attributions of the actor's emotion. Participants were shown happy, disgusted, and neutral facial expressions. Half of these were presented with a plausible trigger of the expression (a drink). Approach-avoidance related behaviour was indexed explicitly through a questionnaire (measuring intentions) and implicitly through a manikin version of the affective Simon task (measuring automatic behavioural tendencies). In the absence of an observer-irrelevant trigger, participants expressed the intention to avoid disgusted and approach happy facial expressions. Participants also showed a stronger approach tendency towards happy than towards disgusted facial expressions. The presence of the observer-irrelevant trigger had a moderating effect, decreasing the intention to approach happy and to avoid disgusted expressions. The trigger had no moderating effect on the approach-avoidance tendencies. Thus the influence of an observer-irrelevant trigger appears to reflect more of a controlled than automatic process.
Previous research suggests that the established link of vertical position and self-assignment of social power affects the processing of social exclusion. We hypothesized that verticality-induced self-assignment of social power moderates the evaluation of exclusion via a change in subjective expectancy of social participation. Following this idea, a superior position-associated with higher power-was supposed to increase the sensitivity for a transition to social exclusion. The transition was simulated in a virtual ball tossing game (cyberball): an inclusionary block was followed by partial exclusion of the participant. The participants' vertical position relative to the co-players was varied in three experimental groups (superior vs. even vs. inferior). From inclusion to partial exclusion, we observed an increase of an event-related brain potential related to the violation of subjective expectancy (P3), and participants reported a corresponding increase in threat to social needs and negative mood. For participants at inferior position exclusionary effects on both, P3 and need threat, were less pronounced as compared to participants at even or superior position. These results indicate that verticality impacts basic cognitive processes of subjective expectancy formation. An inferior position already provides a bias for the loss of social power, and the transition to social exclusion is less unexpected.
Research has tried to identify risk factors that increase the likelihood of difficulties with externalizing behavior. The relations between individual or environmental factors and externalizing behavior have been especially documented. Child-oriented and parent-oriented interventions have been designed in order to decrease externalizing behavior in preschoolers. To date, however, research has largely been compartmentalized. It is therefore not known whether child-oriented or parent-oriented intervention is more effective in reducing externalizing behavior. The aim of the current study was to answer this question by comparing two 8-week child with two 8-week parent-oriented group programs sharing a common experimental design. This was done in a pseudo-randomized trial conducted with 73 3-6-year-old children displaying clinically relevant levels of externalizing behavior who were assigned to one of the four interventions and 20 control participants who were allocated to a waiting list. The results indicate that the four programs focusing on a specific target variable, i.e., social cognition, inhibition, parental self-efficacy beliefs, or parental verbal responsiveness, are all effective in reducing externalizing behavior among preschoolers. Their effectiveness was moderated neither by their orientation toward the child or the parent nor by their content, suggesting that several effective solutions exist to improve behavioral adaptation in preschoolers. A second important highlight of this study is that, thanks to comparable effect sizes, brief focused programs appear to be a reasonable alternative to long multimodal programs, and may be more cost-effective for children and their families.
To manoeuvre in complex societies, it is beneficial to acquire knowledge about the social relationships existing among group mates, so as to better predict their behaviour. Although such knowledge has been firmly established in a variety of animal taxa, how animals acquire such knowledge, as well as its functional significance, remains poorly understood. In order to understand how primates acquire and use their social knowledge, we studied kin-biased redirected aggression in Japanese macaques (Macaca fuscata) relying on a large database of over 15 000 aggressive episodes. Confirming previous research, macaques redirected aggression preferentially to the kin of their aggressor. An analysis that controlled for the rate of affiliation between aggressors and targets of redirection showed that macaques identified the relatives of group mates on the basis of the frequency of their ongoing associations. By contrast, having observed group mates interact with their mother as infants did not increase the monkeys' success in correctly identifying kin relationships among third parties. Inter-individual variation in the successful identification of the kin of aggressors and in redirecting aggression accordingly translated into differences in the amount of aggression received, highlighting a selective advantage for those individuals that were better able to acquire and use social knowledge.
Social pain is often associated with social rejection and shares neural correlates with the bothersome aspect of physical pain, which may also indicate an overlap in function. Pain has been described as a motivational signal to respond to the source of the pain in an adaptive way, such as by altering behavior. We tested whether social pain causes similarly adaptive alterations in behavior. Participants played computerized ball-tossing tasks with putative players-one who passed to and one who excluded the participant from play-in both a social and nonsocial version. We assessed the behavioral consequences of social pain by comparing the number of throws to each stimulus (social rejector vs. nonsocial rejector) over the course of the task. Posttask questionnaires assessed subjective feelings of social pain. A decrease in throws to the rejecting stimulus was only observed in the social version, indicating that rejection that is social in nature leads to change in behavior. Moreover, participants reported more negative feelings toward the rejecting stimulus in the social than in the nonsocial version. These subjective feelings of social pain mediated the effect of version of the game (social vs. nonsocial) on changes in behavior, indicating that social pain from social rejection causes changes in behavior.
The American educational system currently yields disappointing levels of science, technology, engineering, and math (STEM) engagement and achievement among students. One way to remedy this may be to increase children's motivation in STEM from an early age. This study examined whether a social cue-being part of an experimental "minimal group"-increases STEM engagement in preschoolers (N = 141; 4.5-year-olds). Using a within-subjects design, participants were assigned to a group and an individual condition (counterbalanced for order) before they worked on a math task and a spatial task. Children persisted longer on, placed more pieces correctly, reported higher self-efficacy, and were more interested in the group STEM task than the individual STEM task. In addition, we conducted a continuously cumulating meta-analysis (CCMA) to combine the results of the current experiment with two previous experiments. These findings suggest that incorporating nonacademic social factors, such as group membership, into current STEM curricula could be an effective way to boost young children's STEM motivation.
Background and Objectives: Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. Methods:Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. Results: In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the multiple disconnection syndrome resulting from gray and white matters pathology might exceed the threshold for cerebral tolerance and can manifest as deficits in social cognition. Admitting the impact of the latter on patients' social functioning, a thorough screening for such deficits is crucial to improving patients' QoL.
A recently emerging view in music cognition holds that music is not only social and participatory in its production, but also in its perception, i.e. that music is in fact perceived as the sonic trace of social relations between a group of real or virtual agents. While this view appears compatible with a number of intriguing music cognitive phenomena, such as the links between beat entrainment and prosocial behaviour or between strong musical emotions and empathy, direct evidence is lacking that listeners are at all able to use the acoustic features of a musical interaction to infer the affiliatory or controlling nature of an underlying social intention. We created a novel experimental situation in which we asked expert music improvisers to communicate 5 types of non-musical social intentions, such as being domineering, disdainful or conciliatory, to one another solely using musical interaction. Using a combination of decoding studies, computational and psychoacoustical analyses, we show that both musically-trained and non musically-trained listeners can recognize relational intentions encoded in music, and that this social cognitive ability relies, to a sizeable extent, on the information processing of acoustic cues of temporal and harmonic coordination that are not present in any one of the musicians' channels, but emerge from the dynamics of their interaction. By manipulating these cues in two-channel audio recordings and testing their impact on the social judgements of non-musician observers, we finally establish a causal relationship between the affiliation dimension of social behaviour and musical harmonic coordination on the one hand, and between the control dimension and musical temporal coordination On the other hand. These results provide novel mechanistic insights not only into the social cognition of musical interactions, but also into that of non-verbal interactions as a whole. (C) 2017 The Authors. Published by Elsevier B.V.
Objective: There is considerable evidence that patients with schizophrenia have neurocognitive and social-cognitive deficits. It is unclear how such deficits in first-episode schizophrenia relate to current clinical symptoms. Method: Fifty-nine patients with first-episode schizophrenia (FES) were tested using the Danish version of NART (premorbid IQ), subtests from WAIS-III (current IQ), and global cognition using Brief Assessment of Cognition in Schizophrena (BACS), a neurocognitive test battery. Social perception was tested using film clips of everyday interactions (TASIT). Theory of mind (ToM) was tested using silent animations (Animated Triangles Task). The FES subjects had been experiencing psychotic symptoms for several years (mean duration 9.5 years 95% confidence interval (CI [7.6; 11.3]). The FES patients were divided into clinical subgroups based on their level of positive and negative symptoms (using SANS and SAPS). Healthy controls were matched to the patients. Results: High levels of negative symptoms were associated with low estimated functional IQ and poor neurocognition and social cognition. All SANS subscales, but Avolition-Apathy, had significant negative impact on social cognition. The effects of positive symptoms were complex. High levels of delusions were associated with higher premorbid IQ. In the presence of high levels of negative symptoms, high levels of positive symptoms were associated with the most comprehensive deficits in social perception, while, in the absence of negative symptoms, high levels of positive symptoms were not associated with such deficits. Conclusion: The results suggest that social-cognitive training will need to take account of the above mentioned effects of symptoms.
Impairment in daily functioning still represents a major treatment issue in schizophrenia and a more in-depth knowledge of underlying constructs is crucial for interventions to translate into better outcomes. This study aims to model factors influencing both functional capacity and real-life behaviour in a sample of outpatients with chronic schizophrenia, through a comprehensive assessment including evaluations of psychopathology, cognitive and social cognitive abilities, premorbid adjustment, family environment and early childhood experiences. No significant correlation was observed between functional capacity and real-life behaviour. Functional capacity was significantly predicted by IQ, while real-life behaviour was significantly predicted by empathy, affect recognition and symptoms. Functional capacity seems mainly related to neurocognition, whereas real-life behaviour appears more complex, requiring the integration of different factors including symptoms, with a major role of empathy. Results thus support a divergence between the two constructs of functioning and their underlying components and highlight the need to target both dimensions through individualized sequential rehabilitation programs in order to optimize functional outcome.
People use at least two strategies to solve the challenge of understanding another person's mind: inferring that person's perspective by reading his or her behavior (theorization) and getting that person's perspective by experiencing his or her situation (simulation). The five experiments reported here demonstrate a strong tendency for people to underestimate the value of simulation. Predictors estimated a stranger's emotional reactions toward 50 pictures. They could either infer the stranger's perspective by reading his or her facial expressions or simulate the stranger's perspective by watching the pictures he or she viewed. Predictors were substantially more accurate when they got perspective through simulation, but overestimated the accuracy they had achieved by inferring perspective. Predictors' miscalibrated confidence stemmed from overestimating the information revealed through facial expressions and underestimating the similarity in people's reactions to a given situation. People seem to underappreciate a useful strategy for understanding the minds of others, even after they gain firsthand experience with both strategies.
Although open-mindedness is generally valued, people are not equally open-minded in all situations. Open-mindedness is viewed as socially desirable when individuals encounter viewpoints that are compatible with conventional social norms. However, open-mindedness is viewed in less desirable terms when individuals encounter viewpoints that undermine these norms. The perceived desirability of open-mindedness is also influenced by the individual's personal attitudinal convictions. Individuals inflate' the normative appropriateness of open-mindedness when it serves to reinforce their convictions, but devalue the normative appropriateness of open-mindedness when it serves to contradict these convictions. Conversely, normative prohibition of closed-mindedness is exaggerated when a closed-minded orientation threatens the individual's personal attitudinal convictions, but is minimized (or reversed) when a closed-minded orientation reinforces these convictions. Paradoxically, the perceived appropriateness of open-mindedness is engendered (at least in part) by the motivation to confirm one's prior attitudinal convictions. Evidence of this attitude justification effect is obtained in two experiments.
Children's perceptions of social resource inequalities were investigated by measuring open-ended explanations for race-based disparities in access to societal resources. Fifth graders (N = 139, M = 11.14 years, SD = 0.61 years) viewed animated vignettes depicting hypothetical resource inequalities between institutions serving children of African-American and European-American background. Children frequently explained disparities in terms of institutions' differing financial resources, revealing awareness that economic inequalities often underlie groups' differential access to societal resources. Further, children attributed inequalities to differential treatment more often when they witnessed' African-Americans at a disadvantage than when they witnessed European Americans at a disadvantage, demonstrating awareness that racial minority groups are more likely to experience restricted access to resources. Finally, children who reasoned about differential treatment judged inequality, and actions that perpetuated inequality, more negatively than children who attributed inequalities to institutions' differing needs, revealing a link between awareness of discrimination and rejection of social inequalities. (C) 2016 Elsevier Inc. All rights reserved.
Social cognition is impaired in schizophrenia, is relatively independent of purely neurocognitive domains such as attention and executive functioning, and may be the strongest predictor of functional outcome in this disease. Within a motivated reasoning framework, we tested the hypothesis that the anti-inflammatory Th2-associated cytokines, IL-10 and MDC, would be correlated with behavioral measures of social cognitive threat-detection bias (self-referential gaze detection bias and theory of mind (ToM) bias) in delusional versus non-delusional patients. We administered to schizophrenia patients with delusions (n=21), non-delusional patients (n=39) and controls (n=20) a social cognitive task designed to be sensitive to psychosocial stress response (the Waiting Room Task) and collected plasma levels of inflammatory markers using a bead-based flow immunoassay. Results partially supported our hypothesis. The anti-inflammatory cytokine IL-10 was associated with self referential ToM bias in the delusional cohort as predicted, and not with non-delusional patients or healthy controls. This bias reflects a documented tendency of schizophrenia patients with delusions to excessively attribute hostile intentions to people in their environment. Since this cytokine correlated only with ToM bias and only in delusional patients, elevated levels of this cytokine in the blood may eventually serve as a useful biomarker distinguishing delusional patients from both non-delusional patients and healthy controls.
Rationale Dopamine (DA) plays a central role in reward processing. Accumulating evidence suggests that social interaction and social stimuli have rewarding properties that activate the DA reward circuits. However, few studies have attempted to investigate how DA is involved in the processing of social stimuli. Objectives In this study, we investigated the effects of pharmacological manipulations of DA D1 and D2 receptors on social vs. nonsocial visual attention preference in macaques. Methods Japanese macaques were subjected to behavioral tests in which visual attention toward social (monkey faces with and without affective expressions) and nonsocial stimuli was examined, with D1 and D2 antagonist administration. Results The macaques exhibited significantly longer durations of gazing toward the images with social cues than did those with nonsocial cues. Both D1 and D2 antagonist administration decreased duration of gazing toward the social images with and without affective valences. In addition, although D1 antagonist administration increased the duration of gazing toward the nonsocial images, D2 antagonism had no effect. Conclusions These results suggest that both D1 and D2 receptors may have roles in the processing of social signals but through separate mechanisms.
Social cognition is a topic of enormous interest and much research, but we are far from having an agreed taxonomy or factor structure of relevant processes. The aim of this review is to outline briefly what is known about the structure of social cognition and to suggest how further progress can be made to delineate the in(ter)dependence of core sociocognitive processes. We focus in particular on several processes that have been discussed and tested together in typical and atypical (notably autism spectrum disorder) groups: imitation, biological motion, empathy, and theory of mind. We consider the domain specificity/generality of core processes in social learning, reward, and attention, and we highlight the potential relevance of dual-process theories that distinguish systems for fast/automatic and slow/effortful processing. We conclude with methodological and conceptual suggestions for future progress in uncovering the structure of social cognition.
Background: This study examined whether acutely (aMDD) and remitted depressed patients (rMDD) show deficits in the two aspects of social cognition - facial emotion recognition (FER) and reasoning - when using ecologically valid material. Furthermore, we examined whether reduced facial mimicry mediates the association between depressive symptoms and FER, and whether FER deficits and reasoning deficits are associated. Method: In 42 aMDD, 43 rMDD, and 39 healthy controls (HC) FER was assessed using stimuli from the Amsterdam Dynamic Facial Expression Set, reasoning by the Movie for the Assessment of Social Cognition. Furthermore, the activity of Zygomaticus Major and Corrugator supercilii were recorded. Results: aMDD recognized happy faces less accurately, were less confident recognizing happiness and anger and found it more difficult to recognize happiness, anger and fear than HC. rMDD were less confident recognizing anger and found it more difficult to recognize happiness, anger and fear than HC. Reduced mimicry did not explain FER deficits. aMDD but not rMDD showed impaired reasoning. Limitations: The stimulus material was comparably easy to decode. Therefore, it is possible that the FER deficits of aMDD and rMDD patients are more pronounced than demonstrated in this study. Conclusions: aMDD show deficits in FER and reasoning, whereas rMDD only show mild impairments in the recognition of emotional expressions. There must be other processes - besides mimicry - that serve the accurate recognition of emotional facial expressions.
The purpose of this research was to investigate the relationship between temperament and social cognition, including theory of mind and emotion understanding, in 34 preschool-aged children (aged 3-4years). Theory of mind was measured with a belief-desire reasoning assessment, and emotion understanding was measured with an affective perspective-taking task. Child temperament was provided by online parent report. Consistent with previous research, theory of mind correlated with shy and socially observant temperament. In contrast, emotion understanding was associated with attention focusing and low intensity pleasure (enjoyment of low arousal activities). Both theory of mind and emotion understanding were positively related to inhibitory control and negatively related to activity level. In sum, theory of mind and emotion understanding, while both associated with executive functioning, correlate with distinct social preference temperament dimensions. Copyright (c) 2016 John Wiley & Sons, Ltd.
This paper argues that mind-reading hypotheses (MRHs), of any kind, are not needed to best describe or best explain basic acts of social cognition. It considers the two most popular MRHs: one-ToM and two-ToM theories. These MRHs face competition in the form of complementary behaviour reading hypotheses (CBRHs). Following Buckner (Mind Lang 29: 566-589, 2014), it is argued that the best strategy for putting CBRHs out of play is to appeal to theoretical considerations about the psychosemantics of basic acts of social cognition. In particular, need-based accounts that satisfy a teleological criterion have the ability to put CBRHs out of play. Yet, against this backdrop, a new competitor for MRHs is revealed: mind minding hypothesis (MMHs). MMHs are capable of explaining all the known facts about basic forms of social cognition and they also satisfy the teleological criterion. In conclusion, some objections concerning the theoretical tenability of MMHs are addressed and prospects for further research are canvassed.
Social cognitive deficits are common in neuropsychiatric disorders. Given the proximity of social cognition (SC) to everyday functioning, many intervention studies (including targeted, comprehensive, and broad-based approaches) have focussed on SC. The aim of this paper was to quantitatively meta-analyse the efficacy of SC interventions in adult neuropsychiatric patients. Databases Pubmed, PsycINFO, Web of Knowledge, and Embase were searched for controlled SC intervention studies published between 01-01-2003 and 01-01-2016. Forty-one studies, comprising 1,508 patients with schizophrenia, autism spectrum disorders, or acquired brain injury were included. Outcome measures evaluated emotion perception (EP), social perception (SP), Theory of Mind (ToM), and social functioning (SF). The meta-analyses showed that interventions were effective in improving SC (Cohen's d = .71). Interventions targeting one specific SC function were found to be most effective (d = .89), followed by broad-based interventions, targeting non-SC domains in addition to SC (d = .65), and comprehensive interventions, that target multiple SC processes (d = .61). Targeted interventions were especially effective in improving EP and ToM. Comprehensive interventions were able to ameliorate EP, ToM, and SF. Broad-based interventions were especially effective in improving SF, but also showed effects on EP and ToM.
Social disinhibition difficulties are common following traumatic brain injury (TBI). However, clinically sensitive tools to objectively assess the difficulties are lacking. This study aimed to pilot a new clinical measure of social disinhibition, the social disinhibition task (SDT). Whether social disinhibition is dependent on the type of social information judgements required and whether disinhibited responses can be adjusted with additional guidance were also examined. Participants were 31 adults (25 Male) with moderate-to-severe TBI and 22 adult (17 Male) healthy control participants. Participants viewed scenes of complex social situations and were asked to describe a character in them (Part A), describe a character while inhibiting inappropriate or negative responses (Part B), and describe a character while not only inhibiting negative responses, but also providing positive responses (Part C). One-half of the items contained a faux pas requiring participants to make inferences about a character'smental state. TBI and control participants responded similarly to Part A, although control participants responded less positively than TBI participants in the faux pas items. TBI participants were significantly impaired on Part B indicating they experienced difficulties in inhibiting automatic responding. TBI participants were however able to adjust their responding in Part C so that they respond similarly to the control participants. Between group differences were not detected in reaction time. Overall, the SDT appears to be suitable to detect social inhibition difficulties in clinical settings and provides a new direction for remediation of the difficulties in individuals with TBI.
Recent work has introduced social dynamic models of people's stress-related processes, some including amelioration of stress symptoms by support from others. The effects of support may be "direct", depending only on the level of support, or "buffering", depending on the product of the level of support and level of stress. We focus here on the nonlinear buffering term and use a model involving three variables (and 12 control parameters), including stress as perceived by the individual, physical and psychological symptoms, and currently active social support. This model is quantified by a set of three nonlinear differential equations governing its stationary-state stability, temporal evolution (sometimes oscillatory), and how each variable affects the others. Chaos may appear with periodic forcing of an environmental stress parameter. Here we explore this model carefully as the strength and amplitude of this forcing, and an important psychological parameter relating to self-kindling in the stress response, are varied. Three significant observations are made: 1. There exist many complex but orderly regions of periodicity and chaos, 2. there are nested regions of increasing number of peaks per cycle that may cascade to chaos, and 3. there are areas where more than one state, e.g., a period-2 oscillation and chaos, coexist for the same parameters; which one is reached depends on initial conditions. (C) 2017 Elsevier B.V. All rights reserved.
The anterior cingulate cortex (ACC) has been implicated in different aspects of cognition and decision making, including social cognition. Several studies suggest that this region is actually formed by sub-regions concerned with distinct cognitive functions. The ACC is usually divided in its rostro-caudal axis, with the caudal ACC playing a major role in processing own actions, and the rostral ACC being related to social cognition. Recently, it has been suggested that the ACC can also be functionally divided in its dorso-ventral axis into ACC gyrus (ACCg) and ACC sulcus (ACCs), with the ACCg having a central role in processing social information. In this context, we propose that the pregenual ACCg might be especially important for engaging in social interactions. We discuss previous findings that support this hypothesis and present evidence suggesting that the activity of pregenual ACCg neurons is modulated during spontaneous social interactions.
Single-issue protests and online mobilization have proliferated in the wake of social media. While significant ground has been covered regarding the changing possibilities for mobilization, the question of how specific circumstances condition the political impact of online mobilization and public protests has received much less attention. During the last couple of years, Greenlanders have increasingly employed Facebook to mobilize the populace and arrange public demonstrations with noteworthy results. Arguing that single-issue protests cannot be separated from the issues they are concerned with, the paper explores how a single and potential trivial political issue - a new parliament building - developed from a prestige project supported by a nearly unanimous Parliament into a public-contested issue and a failed political project. The paper invokes Actor-Network Theory to account for the trajectory of the issue and how it was translated along the way as actors built and broke alliances. The concepts of mobilizing structures, opportunity structures and framing processes are employed to shed light on the conditions of possibilities for the emergence, development and impact of the protest against the parliament building. Finally, the paper discusses social media's impact on the image of politically engaged Inuit and on the power relations between citizens and parliament in Greenland. This discussion is of paramount importance as Greenlanders are struggling with their colonial heritage while they are constructing Greenlandic democracy.
Social commerce, an emerging phenomenon rooted in social media and Web 2.0 technologies, has attracted the attention of many researchers. The number of publications on social commerce has grown exponentially in the past 10 years. Now, social commerce has become a significant emerging research area. In this paper, we first define the boundary of social commerce research and then attempt to review the extant literature in this area comprehensively and systematically. Based on the definition, this study surveyed 1369 peer-reviewed academic publications in the social media, Web 2.0, and other related areas. Following the survey, 418 of the publications were identified as social commerce research. Then, latent semantic analysis (LSA), a text mining approach, was applied to summarize the current state of social commerce research. LSA results show that there are three major research themes in the current social commerce research: organization, advertisement, and word-of-mouth. Each theme discusses topics such as innovation, user-generated content, and reputation, among others. In addition, we identify some interesting trends. The first main trend is that innovation, corporate reputation, and user-generated content remain the major research topics, although they are experiencing a slight decline. The second main trend is that online reviews, trust, and e-word-of-mouth are attracting more attention from researchers. (C) 2016 Elsevier Ltd. All rights reserved.
With the progressive role of computers and their users as actors in social networks, computations alike social network analysis (SNA) are gaining in attention. This work proposes an approach based on SNA, not alone on social networks as supported by existing approaches, to estimate the tourists' satisfaction with individual Points of Interest (POIs), and accordingly recommend those POIs or not to that tourist or its tour planning system. Moreover, instead of a common unimodal network, a bimodal tourist-reviewer network is modeled as suggested by the SNA literature given tourists and POI reviewers act as two distinct classes of entities with links between them representing their (dis)similarities. Both tourists and reviewers provide their personal attributes (like age), but reviewers then providing preferences for specific POIs, whereas tourists only preferences for certain types or categories of POIs (say archeology). Further, an algorithm for grouping into "islands" of most similar reviewers to a certain tourist given the strength of corresponding links in the bimodal network is developed. Additionally, a ranking algorithm based on in-degree or authority centrality is adopted to identify the highest ranked reviewers within the island and recommend their preferred POIs to a given tourist. If there are more than single POIs preferred per reviewer, and there remain more than requested POIs of the highly ranked reviewers to select among for recommendation, a similar centrality algorithm is applied over a reviewer-POI network with links representing a certain reviewer prefers that certain POI. The evaluation initially with an exemplary real-life experiment, and then extended to a massive online dataset from Foursquare, proves our approach as feasible in estimating the tourist's satisfaction with individual POIs. Moreover, it is already promising since incorporating location influence remains yet our future work and might further improve its performance.
Social networking sites (SNS) are a popular Internet-based technology that enable users to communicate and interact with each other. SNS have attracted a great deal of scholarly attention and have been used as an educational tool in recent years. However, there has been little research examining motivations and obstacles to teaching with SNS in higher education. Therefore, the purpose of this study is to investigate why faculty members in higher education prefer to use or not to use SNS for educational purposes. To this end, faculty members' current SNS usage, their purposes for using SNS, and the opinions of faculty members about their uses of SNS for education were investigated. A mixed method approach was utilized to collect data from a total of 658 faculty members from eight different state universities in Turkey. The findings show that nearly half of the faculty members who possessed an SNS account reported that they use SNS for educational purposes. Their greatest motivating factor to use SNS is that SNS provide a means for fast and effective communication. The main factor which impeded SNS usage by faculty members is their concerns about privacy. (C) 2017 Elsevier Ltd. All rights reserved.
The aim of this study was to examine differences in the neural processing of social information about kin and friends at different levels of closeness and social network level. Twenty-five female participants engaged in a cognitive social task involving different individuals in their social network while undergoing functional magnetic resonance imaging scanning to detect BOLD (Blood Oxygen Level Dependent) signals changes. Greater levels of activation occurred in several regions of the brain previously associated with social cognition when thinking about friends than when thinking about kin, including the posterior cingulate cortex (PCC) and the ventral medial prefrontal cortex (vMPFC). Linear parametric analyses across network layers further showed that, when it came to thinking about friends, activation increased in the vMPFC, lingual gyrus, and sensorimotor cortex as individuals thought about friends at closer layers of the network. These findings suggest that maintaining friendships may be more cognitively exacting than maintaining kin relationships.
Objective: To describe the reliability and validity of a new measure, the Soda! Skills Questionnaire for Traumatic Brain Injury (SSQ-TBI). Methods: Fifty-one adults with severe TBI completed the SSQ-TBI questionnaire. Scores were compared to informant- and self-report on questionnaires addressing frontal lobe mediated behaviour, as well as performance on an objective measure of social cognition and neuropsychological tasks, in order to provide evidence of concurrent, divergent and predictive validity. Results: Internal consistency was excellent at alpha = 0.90. Convergent validity was good, With informant ratings on the SSQ-TBI significantly correlated with Neuropsychiatric Inventory Disinhibition sub-scales (r = 0.50-63), the Current Behaviour Scale (r = 0.39-0.48) and Frontal Systems Behaviour Scale = 0.60-0:83). However, no relationship was seen with an objective measure of social skills or neuropsychological tasks of disinhibition. There was a significant relationship with real-world psychosocial outcomes on the Sydney Psythosocid Reintegration Scale-2 (r=-0.38-0.69) Conclusions: This study provides preliminary findings of good internal consistency and convergent and predictive validity of a social skills questionnaire adapted to be appropriate for individuals with TBI: Further assessment of psychometric, properties such as test-re-test reliability and factor structure is warranted.
In the last decade, jatropha-based bioenergy projects have gotten significant attention as a solution to various social, economic, and environmental problems. Jatropha's popularity stemmed out from different discourses, some real and some perceived, in scientific and non-scientific literature. These discourses positioned jatropha as a crop helpful in producing biodiesel and protecting sustainability by reducing greenhouse gas emissions compared to fossil fuels and increasing local, rural development by creating jobs. Consequently, many countries established national policies that incentivized the establishment of jatropha as a bioenergy feedstock crop. In this paper, we explore the case of jatropha bioenergy development in Yucatan, Mexico and argue that the popular discourse around jatropha as a sustainability and rural development tool is flawed. Analyzing our results from 70 semi-structured interviews with community members belonging to a region where plantation-scale jatropha projects were introduced, we found that these projects did not have many significant social sustainability benefits. We conclude from our case that by just adding bioenergy projects cannot help achieve social sustainability in rural areas alone. In ensuring social sustainability of bioenergy projects, future policymaking processes should have a more comprehensive understanding of the rural socioeconomic problems where such projects are promoted and use bioenergy projects as one of the many solutions to local problems rather than creating such policies based just on popular discourses.
A Summary: This study explores the courtroom interactions between judges, attorneys, and parents charged with child abuse or neglect. Drawing on ethnographic observations of court cases in a Family Court located in the northeastern United States, this study seeks to understand how judges encourage or inhibit parents' participation and the strategies and tactics used to influence parental behaviors and obtain cooperation with court orders. Findings: On one end of the spectrum are judges who engage little, or not at all with parents, preferring to speak only to the professional court actors. On the other end of the spectrum is a more participatory approach, with judges weaving parents into court room exchanges and engaging them in informational and decision-making dialogs. A similar divergence appears when soliciting cooperation from parents, with some judges relying on shaming rituals and others using a softer approach that incorporates praise and support. Applications: Strategic interventions are identified that will increase parents' cooperation and satisfaction with the Family Court system. These include vigorously engaging in both informational and decision-making dialogs with parents and using rituals of praise and support, rather than shaming.
A Summary: In social work practice, the role of substance use is often encountered in the context of other social problems such as child abuse and domestic violence. This article compares descriptions of important factors for initiating and maintaining positive changes among male and female clients treated for alcohol and/or drug problems. The results have a bearing both on substance use treatment and on other areas in social work practice where these problems are encountered. Studies highlighting gender perspective indicate differences regarding experience of alcohol and drug problems and treatment. An advantage of the study is the qualitative analysis of a rather comprehensive material (n=90) enabling more general conclusions than in previous research with a limited number of clients. Findings: Women more often than men stress poor mental health and their children as important for initiating change. When referring to partners, women report abusive rather than supportive partners while the opposite applies to men. For maintaining change, male clients more often stress changes in ways of thinking and feeling as important. Men also report becoming more sensitive while women get more active. This can be understood as transcending of gender with possibilities of a broader repertoire of how to act. Applications: A challenge for practical treatment work is to create possibilities for clients to broaden their repertoire of ways of living and thinking about themselves, expressed by women as the importance of taking space and speaking up and by the men of showing emotion and listening more.
The aim of this study was to assess the relationship between socially prescribed perfectionism (SPP) and aggressiveness according to their components: physiological-emotional( anger), motor (physical and verbal aggression), and cognitive (hostility). The sample included 776 children from the 3rd to 6th year of Primary School (M = 9.72 years; SD = 1.14). The Child and Adolescent Perfectionism Scale and the Aggression Questionnaire were used to assess, respectively, SPP and components of aggressive behaviour: Anger, Hostility, Physical and Verbal Aggression. The mean difference analysis showed that students with high levels of SPP scored significantly higher on all 4 sub-scales of Aggression Questionnaire, compared with their peers with lower levels of SPP. Moderate effect sizes were obtained for all cases, except for Hostility, where the magnitude of the differences was small. Logistic regression analysis revealed that the 4 dimensions of Aggression Questionnaire predicted significantly and positively high scores on SPP, with the OR ranging from 1.07 to 1.12. The results showed that there is a close relationship between the SPP and manifestations of aggression. (C) 2016 European Journal of Education and Psychology. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license
Background: Designing evidence-based interventions to address socioeconomic disparities in health and health behaviours requires a better understanding of the specific explanatory mechanisms. We aimed to investigate a comprehensive range of potential theoretical mediators of physical activity (PA) and screen time in different socioeconomic status (SES) groups: a high SES group of high school students, and a low SES group of vocational school students. The COM-B system, including the Theoretical Domains Framework (TDF), was used as a heuristic framework to synthesise different theoretical determinants in this exploratory study. Methods: Finnish vocational and high school students (N = 659) aged 16-19, responded to a survey assessing psychological, social and environmental determinants of activity (PA and screen time). These determinants are mappable into the COM-B domains: capability, opportunity and motivation. The outcome measures were validated self-report measures for PA and screen time. The statistical analyses included a bootstrapping-based mediation procedure. Results: Regarding PA, there were SES differences in all of the COM-B domains. For example, vocational school students reported using less self-monitoring of PA, weaker injunctive norms to engage in regular PA, and fewer intentions than high school students. Mediation analyses identified potential mediators of the SES-PA relationship in all of three domains: The most important candidates included self-monitoring (CI95 for b: 0.19-0.47), identity (0.04-0.25) and material resources available (0.01-0.16). However, SES was not related to most determinants of screentime, where there were mainly gender differences. Most determinants were similarly related with both behaviours in both SES groups, indicating no major moderation effect of SES on these relationships. Conclusions: This study revealed that already in the first years of educational differentiation, levels of key PA determinants differ, contributing to socioeconomic differences in PA. The analyses identified the strongest mediators of the SES-PA association, but additional investigation utilising longitudinal and experimental designs are needed. This study demonstrates the usefulness of combining constructs from various theoretical approaches to better understand the role of distinct mechanisms that underpin socioeconomic health behaviour disparities.
This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal-regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways-related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal-regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.
Aiming at designing biogas-to-electricity advanced systems, Solid Oxide Fuel Cells are promising candidates. They benefit from scalability on plant sizes that suit anaerobic digesters potentialities. For biogas-Solid Oxide Fuel Cells applications, the implementation of an external pre-reformer is usually considered. However, the possibility to perform direct fuel feeding to the Solid Oxide Fuel Cell offers new opportunities towards the realization of lean systems, which are competitive especially on small-scale installations (i.e. on-farm biogas-to-electricity conversion). In this frame, scientific literature is rather poor and, to cover this gap, system simulations are called for two reasons: first, to demonstrate the potential efficiency gain of new concepts; second, to provide a meaningful support for long-term experimental investigation on Solid Oxide Fuel Cells operated upon direct feeding of unreformed biogas. For that, the current study compares two system designs for biogas utilization into Solid Oxide Fuel Cells. The conventional one realizes biogas steam reforming prior the fuel cell, while the novel concept is based on direct feeding of partially upgraded biogas by means of carbon dioxide-separation membranes. As main outcome of the study, the system equipped with carbon dioxide-separation membranes achieves better perforinances than its conventional competitor does, scoring 51.1% energy efficiency and 523% exergy efficiency (compared to 37.2% and 38.6% respectively exhibited by the reformer-based system). Because of the lack a high endothermic process steps, the membrane-based system is also convenient whether heat recovery is required, producing a combined heat-and-power efficiency of 74.8% versus 47.0% obtained in the other system. Moreover, the results of a sensitivity analysis of the impact of membrane and reforming operating parameters on the overall system performances justify the convenience of adopting the solution of biogas direct feeding. Even in the hypothesis of a poorly performing membrane and an optimized reformer, the membrane-based system exhibits a gain in the system energy and combined heat-and-power efficiency of 25.2% and 34.9% respectively, with regard to the reforming based concept. The forcefulness of this result is reinforced by a preliminary evaluation of capital expenditures, which represents a further economic advantage beside the economic revenue coming from a higher energy conversion efficiency. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a fully digital-control soft start mechanism with coefficients Ki optimization for DC-DC power converters. During the soft start phase, a ladder reference voltage steps up gradually to make inductor current ramp up smoothly and overshoot voltage is minimized with the proposed coefficients Ki distribution. Simulation results show that massive inductor current can be well avoided during the soft start process with the proposed soft start mechanism, which only occupies a chip area of 300umx120um.
Rhizoctonia cerealis causes sharp eyespot in cereals and the pathogen survives as mycelia or sclerotia in soil. Real-time Polymerase Chain Reaction (qPCR) assays based on TaqMan chemistry are highly suitable for use on DNA extracted from soil. We report here the first qPCR assay for R. cerealis using TaqMan primers and a probe based on a unique Sequence Characterised Amplified Region (SCAR). The assay is highly specific and did not amplify DNA from a range of other binucleate Rhizoctonia species or isolates of anastomosis groups of Rhizoctonia solani. The high sensitivity of the assay was demonstrated in soils using a bulk DNA extraction method where 200 mu g sclerotia in 50 g of soil were detected. DNA of the pathogen could also be amplified from asymptomatic wheat plants. Using the assay on soil samples from fields under different crop rotations, R. cerealis was most frequently detected in soils where wheat was grown or soil under pasture. It was detected least frequently in fields where potatoes were grown. This study demonstrates that assays derived from SCAR sequences can produce specific and sensitive qPCR assays.
A microbial fuel cell (MFC) is a very promising way to remove organic pollutants. Hexachlorobenzene (HCB) is a widely used agricultural pesticide. In this study, single-chamber and membrane-less soil MFCs were constructed. The HCB was degraded to pentachlorobenzene (PeCB), tetrachlorobenzene (TeCB), and trichlorobenzene (TCB) in sequence by a reductive dechlorination process in soil MFCs. The influences of the external resistance, concentration of phosphate buffer, and electrode spacing in soil MFCs on the degradation rate and removal efficiency of HCB were analyzed. The results showed that the degradation rate and removal efficiency of HCB were increased when the external resistance decreased from 2000 to 20 (1, and also when the concentration of phosphate buffer increased. The anode area played a significant role in dechlorination of HCB. Altering the spacing of the reducing electrode resulted in a lower ohmic resistance in the soil MFCs. The ohmic resistance was negatively correlated with the removal efficiency and degradation rate (P < 0.05). In conclusion, HCB removal efficiency could be enhanced by soil MFCs, the performance of which was improved by a decrease in external resistance and internal resistance, and an increase in phosphate buffer concentration, rather than just by shortening the electrode spacing.
In recent years, the disposal of former industrial sites has widely become a key subject of interest in terms of remediation in order to promote their different use for the community. The use of biological processes, such as phytoremediation, has been worldwide discussed with varying success. In this study, we applied an Integrated Phytoremediation System (IPS), which represents a cost-effective system, environmentally friendly, socially accepted for the removal of the risks associated with the contamination of heavy metal (As, Cd, Pb and Zn) of unsaturated soils. The combination of suitable agronomic soil management and biostimulation of plant growth by inoculation of rhizosphere microbes allowed to increase biomass production of selected plant species (Acacia saligna and Eucalyptus camaldulensis) in very stressful conditions and, consequently, promote the phytoremediation of contaminants. The experimental study in situ revealed a significant positive aptitude of selected plant species to keep PTEs (Potential Toxic Elements) in their root system, with a restricted translocation to the aboveground parts. The "plant-fungi-bacteria" system in rhizosphere level showed, also, strong ability to remove the bioavailable fraction of contaminants with a considerable reduction of the risks associated to the contamination. This study reveals that the application of an Integrated Phytoremediation System (IPS) permits to reach the soil remediation in few years with economically, socially and environmentally sustainable costs. (C) 2016 Elsevier B.V. All rights reserved.
It is estimated that over a billion people are infected with soil-transmitted helminths (STHs) globally with majority occurring in tropical and subtropical regions of the world. The roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworms (Ancylostoma duodenale and Necator americanus) are the main species infecting people. These infections are mostly gained through exposure to faecally contaminated water, soil or contaminated food and with an increase in the risk of infections due to wastewater and sludge reuse in agriculture. Different methods have been developed for the detection and quantification of STHs eggs in environmental samples. However, there is a lack of a universally accepted technique which creates a challenge for comparative assessments of helminths egg concentrations both in different samples matrices as well as between locations. This review presents a comparison of reported methodologies for the detection of STHs eggs, an assessment of the relative performance of available detection methods and a discussion of new emerging techniques that could be applied for detection and quantification. It is based on a literature search using PubMed and Science Direct considering all geographical locations. Original research articles were selected based on their methodology and results sections. Methods reported in these articles were grouped into conventional, molecular and emerging techniques, the main steps in each method were then compared and discussed. The inclusion of a dissociation step aimed at detaching helminth eggs from particulate matter was found to improve the recovery of eggs. Additionally the selection and application of flotation solutions that take into account the relative densities of the eggs of different species of STHs also results in higher egg recovery. Generally the use of conventional methods was shown to be laborious and time consuming and prone to human error. The alternate use of nucleic acid-based techniques has improved the sensitivity of detection and made species specific identification possible. However, these nucleic acid based methods are expensive and less suitable in regions with limited resources and skill. The loop mediated isothermal amplification method shows promise for application in these settings due to its simplicity and use of basic equipment. In addition, the development of imaging soft-ware for the detection and quantification of STHs shows promise to further reduce human error associated with the analysis of environmental samples. It may be concluded that there is a need to comparatively assess the performance of different methods to determine their applicability in different settings as well as for use with different sample matrices (wastewater, sludge, compost, soil, vegetables etc.). (C) 2017 The Authors. Published by Elsevier B.V.
Abiotic stresses, especially salinity and drought, are major limiting factors for plant growth and crop productivity. In an attempt to develop salt and drought tolerant tomato, a DNA cassette containing tobacco osmotin gene driven by a cauliflower mosaic virus 35S promoter was transferred to tomato (Solanum lycopersicum) via Agrobacterium-mediated transformation. Putative T0 transgenic plants were screened by PCR analysis. The selected transformants were evaluated for salt and drought stress tolerance by physiological analysis at T1 and T2 generations. Integration of the osmotin gene in transgenic T1 plants was verified by Southern blot hybridization. Transgenic expression of the osmotin gene was verified by RT-PCR and northern blotting in T1 plants. T1 progenies from both transformed and untransformed plants were tested for salt and drought tolerance by subjecting them to different levels of NaCl stress and by withholding water supply, respectively. Results from different physiological tests demonstrated enhanced tolerance to salt and drought stresses in transgenic plants harboring the osmotin gene as compared to the wild-type plants. The transgenic lines showed significantly higher relative water content, chlorophyll content, proline content, and leaf expansion than the wild-type plants under stress conditions. The present investigation clearly shows that overexpression of osmotin gene enhances salt and drought stress tolerance in transgenic tomato plants.
Medical electronic implants can significantly improve people's health and quality of life. These implants are typically powered by batteries, which usually have a finite lifetime and therefore must be replaced periodically using surgical procedures. Recently, subdermal solar cells that can generate electricity by absorbing light transmitted through skin have been proposed as a sustainable electricity source to power medical electronic implants in bodies. However, the results to date have been obtained with animal models. To apply the technology to human beings, electrical performance should be characterized using human skin covering the subdermal solar cells. In this paper, we present electrical performance results (up to 9.05 mW/cm(2)) of the implantable solar cell array under 59 human skin samples isolated from 10 cadavers. The results indicate that the power densities depend on the thickness and tone of the human skin, e.g., higher power was generated under thinner and brighter skin. The generated power density is high enough to operate currently available medical electronic implants such as pacemakers that require tens of microwatt.
Solar energy is one of the most popular clean energy sources and is a promising alternative to fulfill the increasing energy demands of modern society. Solar cells have long been under intensive research attention for harvesting energy from sunlight with a high power-conversion efficiency and low cost. However, the power outputs of photovoltaic devices suffer from fluctuations due to the intermittent instinct of the solar radiation. Integrating solar cells and energy-storage devices as self-powering systems may solve this problem through the simultaneous storage of the electricity and manipulation of the energy output. This review summarizes the research progress in the integration of new-generation solar cells with supercapacitors, with emphasis on the structures, materials, performance, and new design features. The current challenges and future prospects are discussed with the aim of expanding research and development in this field.
Nanotechnology is a rapidly developing field with a wide range of potential applications. One such application is using nanoparticles to selectively absorb and transmit light. By controlling the material, size and shape of nanoparticles it is possible to achieve spectrally selective optical properties. This phenomena can be exploited in solar energy applications where selective absorption of the solar spectrum enables high efficient hybrid photovoltaic/thermal (PV/T) collectors. In this study, we suspend core-shell Ag-SiO2 nanoparticles in water to filter out the ideal spectrum for creating electricity from Si PV cells. A detailed optical and heat transfer model for this approach was developed and validated using the electric and thermal outputs from a prototype system operating in real outdoor conditions. The results of this experimental work indicates that 12% more value (weighted energy output) can be achieved from this PV/T prototype compared with a stand-alone PV system under the same illumination. Since the proposed system inherently decouples the thermal receiver from the PV cells, it is possible to extend this technology to industrial combined heat and power applications. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a power management system of a household photovoltaic-battery hybrid power system within demand side management under time of use electricity tariff. This system is easy to implement by employing cheap electrical switches, off-the-shelf chargers and inverters. Control system models combining both power dispatching level and home appliance scheduling level are proposed to minimize the residents` energy cost and energy consumption from the grid with the practical constraints strictly satisfied. In addition, the resident comfort inconvenience level is considered in the control system models. The trade-off among operating cost, energy consumption and inconvenience is considered and a multi-objective optimization problem is formulated. The optimal control strategies are derived by solving a mixed-integer nonlinear programming problem. Simulation results show that the energy cost and energy consumption from the grid can be largely reduced with the proposed strategies. These results are important for customers to dispel their major uncertainty in determining whether to newly install or update to such photovoltaic-battery hybrid power systems. (C) 2017 Elsevier Ltd. All rights reserved.
Home solar systems have the promise of bringing great welfare benefits to poor households without access to the electricity grid. We study the welfare impacts brought by the purchase of a popular home solar system in Uganda, d.light's D20g, and estimate impacts using prospective individual-level matching. We find substantial impacts on energy spending, with treatment households saving approximately 1.40 USD/week, which corresponds to 77 per cent of the comparison group's weekly energy expenditure. Assuming this savings stays constant, households will break even on their initial purchase after 3.14years, and accrue net energy savings of 134 USD over the 5-year expected lifetime of the D20g. We also find improved self-reported health and safety outcomes, as treatment households reported fewer lower incidence of coughing (9 percentage points). They also report a nearly complete elimination of fires and burns from lighting sources, compared to around 10 per cent of households reporting such incidents in the comparison group. We do not find impact on productive time use such as studying or working.
The annual consumption of petroleum products in India was about 221 million metric tons in 2015. Of this, 84% was imported. The Indian industrial sector accounts for about 16%-20% of the total fuel consumption for thermal energy for different heating applications in the temperature range of 50 degrees C-250 degrees C. Solar collectors can meet these temperature requirements and offer the possibility to mitigate the consumption of oil. This study highlights the fact that conversion efficiency from solar energy is much higher for process heating than for electricity generation and that process heating applications constitute a significant share of industrial energy consumption. In this paper, a methodology has been developed to estimate the potential for integration of solar collectors for process heating. The methodology employs process operating temperatures to select the type of solar collectors. The size of the solar field is estimated taking into account the thermal heat loads, working fluid and temperatures of these processes, the efficiency of the chosen solar collectors, location-based solar irradiance and capacity utilization of the solar collectors. The proposed methodology has been validated with a software tool called System Advisor Model (SAM). The techno-economic analysis will indicate the viability of solar systems for integration in industries. Therefore, the consociated parameters on economic (capital cost, fuel oil savings, monetary benefits), financial (Payback periods, Rates of Returns) and environmental (Carbon savings) are estimated. Further, the methodology has been applied to select Indian industries to verify its potential quantitatively. The industries selected include Textile, Pulp & Paper, Dairy, Leather and Automobile. Process-wise energy demands are considered while estimating the potential as the fuel requirement offset by solar energy in terms of absolute fuel oil savings, monetary benefits and carbon savings. The other economic and financial parameters mentioned above were estimated to verify the capability and present the market position of solar systems. Further, sensitivity analyses have been performed with respect to solar energy penetration and fuel oil prices to address the viability of integration of solar energy for process heating. (C) 2017 Published by Elsevier Ltd.
The present paper presents a system intended to be used in the development of photovoltaic inverters with maximum power point tracking capability. A simulation model was implemented in MATLAB/SIMULINK and an experimental model composed of a DSpace 1104 controller board, a Semikron inverter, a coupling transformer, an LC filter and two 75W solar panels was developed. The system facilitates the development and testing of digital control and MPPT algorithms for single-phase inverters connected to the utility grid.
Replacement of conventional energy sources with renewables such as solar panels and wind turbines requires adequate land. Impact assessments should be conducted to identify sites exhibiting least conflict with current and future land-uses and corresponding ecosystem services. We assessed the electricity potential and geographical distribution of wind turbines and solar panels for current land-use and under three Swiss land-change scenarios. The future scenario A2 with limited construction regulations, a liberalized market and more building surfaces increases the electricity potential of solar panels by 69% from 16.6 TWh (potential under current land-use and regulations) to a future 28.2 TWh. An increase of approximately 26% electricity potential from solar panels is expected for scenario B2 (regionalized economy) and the trend scenario. Wind-electricity potential could increase by 61% from 93 to 150 TWh under A2, and 29% under a B2 or trend scenario. The electricity potential for solar panels remains largely unaffected by conflicts with ecosystem services, but electricity production from wind could be reduced by as much as 98% due to conflicts with ecosystem services. Depending on the scenario used, low-conflict sites for solar panels and wind turbines could contribute between 85% (trend and B2 scenario) and >100% (A2 scenario) to the Swiss energy target of generating 25 TWh from new renewable energy sources by 2050. This includes expected technological developments. Positive impacts of sustainable energy production on regional economies are moderate and will not lead to strong changes in regional-economic development.
Economic dispatch is the optimal output for a number of electricity generating units, to meet the system load, at the lowest possible cost, subject to transmission and operational constraints. The different Economic Dispatch (ED) methods have been developed in order to deal with the challenge of continuous and sustainable power at an improved cost. The increase in cost depletion of non-renewable sources has forced us to use the renewable energy resource as an alternative energy source. For optimizing the Economic Dispatch problem, a new algorithm is proposed based on Combined Emission Economic Dispatch (CEED) for Photo Voltaic (PV) plants and thermal power generation units. In CEED approach for improvising the Economic Dispatch Euclidean Affine Flower Pollination Algorithm (eFPA) and Binary Flower Pollination Algorithm (BFPA) has been used for solving the optimization problem for twenty PV and five thermal generators are done with full solar radiations and with reduced solar radiation. Power demand data has been taken from India in the district of Tuticorin Thermal Power Station (TIPS). Simulation results are tested with IEEE 30 bus and IEEE 57 bus systems and the comparison has been made with existing algorithm to provide better results. (C) 2017 Elsevier Ltd. All rights reserved.
The solar photovoltaic (PV) system is known as one of the most outstanding new renewable energy systems for achieving the nearly zero energy building (nZEB). For the continuous deployment of the solar PV system in urban environments, it is crucial to estimate the rooftop solar PV potential. Urban areas, however, where high-rise buildings abound, are not always suitable for solar PV installation. Therefore, it is important to accurately estimate the available rooftop area considering the shadows from the surrounding buildings for reliable rooftop solar PV potential estimation. Therefore, this study proposed a method for estimating the rooftop solar PV potential by analyzing the available rooftop area through Hillshade analysis. Toward this end, the rooftop solar PV potential was estimated through the following hierarchical process: (i) calculation of the physical potential; (ii), calculation of the geographic potential; and (iii) calculation of the technical potential. For accurate estimation of the rooftop solar PV potential, the geographic potential (i.e., the available rooftop area) was explored in detail by analyzing the shadow based on the location of the sun through Hillshade analysis. By applying the proposed method to the Gangnam district in Seoul, South Korea, this study estimated the physical, geographic, and technical potentials on hourly, monthly, and annual bases. Overall, the physical, geographic, and technical potentials in the Gangnam district were found to be 9,287,982 MW h, 4,964,118 m(2), and 1,130,371 MW h, respectively. These rooftop solar PV potential results can be used in establishing solar policies by analyzing the different levels of the rooftop solar PV potential on hourly, monthly, and annual bases. (C) 2016 Elsevier Ltd. All rights reserved.
Solar PV and battery storage technologies are known to provide savings to customers in the form of reduced electricity charges. Currently, these savings are only determined for the volume component (kWh) and not the demand component (kW or kVA). As interest grows in commercial solar PV and battery storage installations, the need to predict demand charge reductions is great. The aim of this research is to determine, with accuracy and reliability, the ability of solar PV and battery storage technologies in reducing demand charges. Results have shown that when simulated against a commercial scale electricity consumption profile solar PV was able to reduce the maximum demand across five electricity networks in Australia by 0.05-1.51%. When coupled with a 12 kWh battery storage an additional 1.31-2.02% reduction was experienced. Battery utilisation strategy was shown to be critical in yielding greater demand reduction from the battery storage. Notably, it was shown that in the Ergon Energy electricity network, battery storage was able to supply demand at 34% lower cost ($/kW) than the network was able to. The results detail the first instance of demand reduction evaluation of solar PV coupled with battery storage, focusing on physical and financial outcomes in an Australian context. (C) 2017 Elsevier Ltd. All rights reserved.
Buildings need energy including heat and electricity, and both of them can be provided by the solar systems. Solar thermal and photovoltaic systems absorb the solar energy and can supply the heat and electricity for buildings, respectively. However, for the urban residential buildings, the limited available area makes installation of the solar thermal collectors and photovoltaic modules together impossible. A hybrid photovoltaic/thermal system can simultaneously generate heat and electricity, which is deemed to be quite suitable for the urban residential buildings application. And yet, for a rural house of China, the available area for installation of the solar collectors is large but daily domestic hot water demand of a rural family is generally not exceeded 300 L If only the hybrid photovoltaic/thermal collectors are installed on the whole available area, this will lead to an overproduction of the thermal energy, especially in summer. Moreover, buildings requiring for the heat and electricity are different in different regions and different seasons. In this paper, simulation models of the solar thermal, photovoltaic and hybrid photovoltaic/thermal systems are presented, and experiments are also performed to validate the simulation results. Using the validated models, performances of the three solar systems for residential applications were predicted. And energy comparison between the three solar systems used in Hongkong, Lhasa, Shanghai and Beijing of China, respectively, were also studied. Results show that, for the urban residential building with limited available installation space, a hybrid photovoltaic/thermal system may have the largest potential for reducing the energy consumption among the solar thermal, photovoltaic and hybrid photovoltaic/thermal systems. And for a rural house with large available area, system with photovoltaic and hybrid photovoltaic/thermal modules can obtained the most net annual electricity output, and the installation area of the hybrid photovoltaic/thermal collectors mainly depended on the hot water load of the building. (C) 2017 Elsevier Ltd. All rights reserved.
This paper aims to propose a methodology for optimization of solar chimney power plants taking into account the techno-economic parameters. The indicator used for optimization is the comparison between the actual achieved simple payback period for the design and the minimum possible (optimum) simple payback period as a reference. An optimization model was executed for different twelve designs in the range 5-200 MW to cover reinforced concrete chimney, sloped collector, and floating chimney. The height of the chimney was optimized and the associated collector area was calculated accordingly. Relationships between payback periods, electricity price, and the peak power capacity of each power plant were developed. The resulted payback periods for the floating Chimney power plants were the shortest compared to the other studied designs. For a solar chimney power plant with 100 MW at electricity price 0.10 USD/kWh, the simple payback period for the reference case was 4.29 years for floating chimney design compared to 23.47 and 16.88 years for reinforced concrete chimney and sloped collector design, respectively. After design optimization for 100 MW power plant of each of reinforced concrete, sloped collector, and floating chimney, a save of 19.63, 2.22, and 2.24 million USD, respectively from the initial cost of the reference case is achieved. Sensitivity analysis was conducted in this study to evaluate the impacts of varied running cost, solar radiation, and electricity price on the payback periods of solar chimney power plant. Floating chimney design is still performing after applying the highest ratio of annual running cost to the annual revenue. The sensitivity analysis showed that at the same solar radiation and electricity price, the simple payback period for 200 MW with sloped collector design would almost have the double simple payback period for 5 MW with floating chimney design. (C) 2017 Elsevier Ltd. All rights reserved.
The United States Geological Survey estimates that over four trillion barrels of crude oil are currently trapped within U.S. oil shale reserves. However, no cost-effective, environmentally sustainable method for oil production from oil shale currently exists. Given the continuing demand for low-cost fossil-fuel production, alternative methods for shale-oil extraction are needed. Geothermic Fuel Cells (TM) (GFC) harness the heat generated by high-temperature solid oxide fuel cells during electricity generation to process oil shale into "sweet" crude oil. In this paper, a thermo-electrochemical model is exercised to simulate the performance of a 4.5 kW(e) (gross) Geothermic Fuel Cell module for in situ oil-shale processing. The GFC analyzed in this work is a prototype which contains three 1.5 kW(e) solid oxide fuel cell (SOFC) stack-and-combustor assemblies packaged within a 0.3 m diameter, 1.8 m tall, stainless-steel housing. The high-temperature process heat produced by the SOFCs during electricity generation is used to retort oil shale within underground geological formations into high-value shale oil and natural gas. A steady-state system model is developed in Aspen Plus (TM) using user-defined subroutines to predict the stack electrochemical performance and the heat-rejection from the module. The model is validated against empirical data from independent single-stack performance testing and full GFC-module experiments. Following model validation, further simulations are performed for different values of current, fuel and air utilization to study their influence on system electrical and heating performance. The model is used to explore a wider range of operating conditions than can be experimentally tested, and provides insight into the competing physical processes at play during Geothermic Fuel Cell operation. Results show that the operating conditions can be tuned to generate desired heat-flux conditions as needed across applications. (C) 2017 Elsevier Ltd. All rights reserved.
In this study, a proton conducting solid oxide fuel cell (layered H+-SOFC) is prepared by introducing a La(2)NiO(4)perovskite oxide with a Ruddlesden-Popper structure as a catalyst layer onto a conventional Ni + BaZr(0.4)Ceo(0.4)Y(0.2)O(3-delta) (NiO + BZCY4) anode for in situ CO2 dry reforming of methane. The roles of the La2NiO4 catalyst layer on the reforming activity, coking tolerance, electrocatalytic activity and operational stability of the anodes are systematically studied. The La2NiO4 catalyst layer exhibits greater catalytic performance than the NiO + BZCY4 anode during the CO2 dry reforming of methane. An outstanding coking resistance capability is also demonstrated. The layered H+-SOFC consumes H-2 produced in situ at the anode and delivers a much higher power output than the conventional cell with the NiO + BZCY4 anode. The improved coking resistance of the layered H+-SOFC results in a steady output voltage of similar to 0.6 V under a constant current density of 200 mA cm(-2). In summary, the H+-SOFC with La2NiO4 perovskite oxide is a potential energy conversion device for CO2 conversion and utilization with cogeneration of electricity and syngas. (C) 2017 Elsevier B.V. All rights reserved.
Solvent excluded surface (SES) is one of the most popular surface definitions in biophysics and molecular biology. In addition to its usage in biomolecular visualization, it has been widely used in implicit solvent models, in which SES is usually immersed in a Cartesian mesh. Therefore, it is important to construct SESs in the Eulerian representation for biophysical modeling and computation. This work describes a software package called Eulerian solvent excluded surface (ESES) for the generation of accurate SESs in Cartesian grids. ESES offers the description of the solvent and solute domains by specifying all the intersection points between the SES and the Cartesian grid lines. Additionally, the interface normal at each intersection point is evaluated. Furthermore, for a given biomolecule, the ESES software not only provides the whole surface area, but also partitions the surface area according to atomic types. Homology theory is utilized to detect topological features, such as loops and cavities, on the complex formed by the SES. The sizes of loops and cavities are measured based on persistent homology with an evolutionary partial differential equation-based filtration. ESES is extensively validated by surface visualization, electrostatic solvation free energy computation, surface area and volume calculations, and loop and cavity detection and their size estimation. We used the Amber PBSA test set in our electrostatic solvation energy, area, and volume validations. Our results are either calibrated by analytical values or compared with those from the MSMS software. (C) 2017 Wiley Periodicals, Inc.
Somatic mutations in PIK3CA cause many overgrowth syndromes that have been recently coined the "PIK3CA-Related Overgrowth Spectrum." Here, we present seven molecularly confirmed patients with PIK3CA-Related Overgrowth Spectrum, including patients with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome, Klippel-Trenaunay syndrome, lymphatic malformation and two with atypical phenotypes that cannot be classified into existing disease categories. The literature on PIK3CA-Related Overgrowth Spectrum, suggests that PIK3CA c. 1258T>C; p.(Cys420Arg), c. 1624G>A; p.(Glu542Lys), c. 1633G>A; p.(Glu545Lys), c. 3140A>G; p.(His1047Arg), and c. 3140A>T; p.(His1047Leu) can be identified in approximately 90% of patients without brain overgrowth. Therefore, droplet digital polymerase chain reaction targeting these mutation hot-spots could be used as the first-tier genetic test on patients with PIK3CA-Related Overgrowth Spectrum who do not have signs of overgrowth in their central nervous system. (C) 2017 Wiley Periodicals, Inc.
Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity. To assess the expression of bone-related genes, treated cells were evaluated by real-time polymerase chain reaction. The MTT test demonstrated that SPRE had no toxic effects on the cell viability. Treating the cells with SPRE noticeably promoted ALP activity, mineralization, and mRNA expression of runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). Additionally, cells subjected to 0.1g/mL SPRE showed the highest osteogenic effects. According to high-performance liquid chromatography fingerprinting of SPRE, the osteoprotective effects of SPRE is probably due to presence of phytochemicals with estrogen-like activity in the extract. Thus, SPRE might be a suitable therapeutic agent for bone defects therapy in the future research. Copyright (c) 2017 John Wiley & Sons, Ltd.
As of 2012, liver cancer was the second leading cause of death worldwide, and hepatocellular carcinoma is the most common primary cancer of the liver. The identification of molecules that might be molecular markers or therapeutic targets is urgently needed to improve clinical management. Based on a microarray analysis performed in our laboratory, we selected six genes-namely, ANXA2, DYNLT1, PFKP, PLA2G7, KRT19, and SNX10-as candidates for validation as tumor markers of liver cancer in a rat model. Their patterns of overexpression in preneoplastic lesions and established tumors at 10 different time points between 24 h and 18 months were analyzed to identify putative tumor markers for further studies. We validated the microarray results by quantitative reverse transcription polymerase chain reaction, which revealed high transcriptional expression for five of the genes, consistent with their high protein expression during cancer progression reported in the literature. However, studies of the association of sorting nexin 10 with different types of cancer are limited, prompting further study. The characterization of sorting nexin 10 in preneoplastic lesions and established tumors revealed messenger RNA overexpression and a simultaneous decrease in sorting nexin 10 protein expression. A group of microRNAs related to sorting nexin 10 messenger RNA were selected based on a data analysis conducted using miRDB and microrna.org. An analysis of the expression of these microRNAs revealed an increase in the transcription of microRNA-30d whenever the sorting nexin 10 protein was downregulated. These results suggest that sorting nexin 10 is a potential liver cancer marker exhibiting characteristics of a putative suppressor protein that is likely regulated by microRNA-30d.
The history of the development of DNA blotting is described in this chapter. DNA blotting, involving the transfer of electrophoretically separated DNA fragments to a membrane support through capillary action, is also known as Southern blotting. This procedure enables the detection of a specific DNA sequence by hybridization with probes. The term Southern blotting led to a "geographic" naming tradition, with RNA blotting bearing the name Northern blotting and protein transfer to membranes becoming known as Western blotting.
Soybeans are part of the traditional food consumed in Asia countries. In this study, we investigated inhibitory effects of soybean oligosaccharides and water-soluble soybean fibre (Soyafibe) on putrefactive compounds from soy protein by gut microbiota in rats. Caecal microbial fermentation products and microbiota in rats fed 20% soy protein (SP-1) and whole soybean flour (SFL: protein content was 20%) diets were determined. The caecal environment in rats fed 20% soy protein without dietary fibre (SP-2) or with 2% Soyafibe (SFB) was also determined. Compared to SP-1 and SP-2 group, low indole content with high lactic acid was shown in SFL and SFB group, respectively. Using the 16S rRNA genes polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and pyrosequencing. Prevotella, Gram-negative anaerobic rods, were detected as dominant in both SFL and SFB groups. Our findings indicated that fermentable polysaccharides in soybeans have inhibitory effects on the formation of putrefactive compounds generated from soy protein by the microbiota. (C) 2017 Elsevier B.V. All rights reserved.
MicroRNA1511 (miR1511) is a small RNA with unknown function identified in several plants by deep sequencing. In this study, we showed that this small RNA is an authentic miRNA by analyzing the structure of the precursor stem-loop containing the newly identified miR1511* sequence. We confirmed this result by Northern blotting analysis. We used 5'RACE to identify one of the target genes (GmRPL4a) cleaved by both miR1511 and miR1511*. The site cleaved by miR1511* was located in the first exon of GmRPL4a, and the site cleaved by miR1511 was located in the second exon. The expression level of miR1511/1511* was higher in leaves than in roots and stems. In contrast, the lowest level of GmRPL4a expression was in the leaves and the highest in the root. These results indicate that an miRNA can co-regulate with an miRNA* to cleave the same target gene in plants, and that the level of GmRPL4a mRNA is regulated by miR1511/1511*.
A novel soybean-infecting sobemovirus termed Soybean yellow common mosaic virus (SYCMV) was characterized. The virus has a single, positive-strand RNA genome of 4152 nucleotides. The virus contains four putative open reading frames encoding P1 (78-566 nt), polyprotein ORF2a (524-2248 nt), polymerase domain ORF2b (1852-3417 nt), and CP (3227-4030 nt). The entire nucleotide sequence of SYCMV showed 31.2-71.3% nucleotide identity with the previously known eleven species of sobemovirus. In host range analysis of SYCMV, in which twenty one species and three different Nicotiana tabacum cultivars belonging to seven families were inoculated with the virus. SYCMV had a narrow host range, infecting only Glycine max and G. soja. Based on the obtained sequence, full-length clones of SYCMV were constructed. Symptoms produced by inoculation with clones were indistinguishable from those produced by inoculation with sap from symptomatic plants. Viral RNA accumulation of SYCMV was detected in the upper leaves by Northern blotting. This indicated that full-length clones of SYCMV were sufficient to produce disease symptoms. Genomic organization, the predicted amino acid sequence, and phylogenetic analyses with known sobemoviruses confirmed the assignment of SYCMV as a new member of the genus Sobemovirus. (C) 2011 Elsevier B.V. All rights reserved.
Problems aiming at finding budget constrained optimal upgrading schemes to improve network performance have received attention over the last two decades. In their general setting, these problems consist of designing a network and, simultaneously, allocating (limited) upgrading resources in order to enhance the performance of the designed network. In this paper we address two particular optimal upgrading network design problems; in both cases, the sought-after layout corresponds to a spanning tree of the input network and upgrading decisions are to be taken on nodes. We design Mixed Integer Programming-based algorithmic schemes to solve the considered problems: Lagrangian relaxation approaches and branch-and-cut algorithms. Along with the designed algorithms, different enhancements, including valid inequalities, primal heuristic and variable fixing procedures, are proposed. Using two set of instances, we experimentally compare the designed algorithms and explore the benefits of the devised enhancements. The results show that the proposed approaches are effective for solving to optimality most of the instances in the testbed, or manage to obtain solutions and bounds giving very small optimality gaps. Besides, the proposed enhancements turn out to be beneficial for improving the performance of the algorithms. (C) 2017 Elsevier Ltd. All rights reserved.
Little is known about consequences of Spartina alterniflora invasion on soil sulfate-reducing bacteria (SRB). This study compared the abundance, diversity, and community structure of SRB in S. alterniflora and in native plant communities along a successional gradient (bare mudflat, young/mature S. alterniflora, Suaeda salsa, and Phragmites australis) in coastal salt marshes of Eastern China. Quantitative polymerase chain reaction of dissimilatory sulfite reductase (dsrB) gene was applied to assess SRB abundance, and the diversity and composition of SRB was analyzed by 454 pyrosequencing of partial dsrB gene. We found that S. alterniflora had a significantly higher abundance and diversity of SRB than native plant species. For all plant covers, Desulfobacteraceae was the largest soil SRB group, with a relative abundance of 33.6%, followed by Desulfobulbaceae (29.2%). S. alterniflora showed a higher relative abundance of Desulfobacteraceae (42.5%) than native species (29.5%) did. Notably, S. alterniflora invasion decreased the relative abundance of a SRB branch clustering with the thermophilic Thermodesulfovibrio yellowstonii. In conclusion, S. alterniflora invasion of the eastern coast of China has greatly increased the abundance and diversity of SRB communities and altered their structure. This might further influence carbon mineralization and inhibit the production of methane in China's coastal marshes.
Spatial organization is an extensively studied field, in which most of the research has been on how the physical environment is perceived and conceived. There is a consensus that physical attributes such as environment geometry and landmarks are key factors in shaping spatial cognition. Nevertheless, the numerous studies of spatial behavior have usually been carried out on individuals, thereby overlooking the possible impact of the social environment. In the present study, rats were exposed to an unfamiliar open-field, first alone and then in tetrads of unfamiliar individuals, in order to monitor and analyze when and how their individual spatial behavior converged to a group spatial behavior. We found that the unfamiliar rats spent most of their time in companionship, first with preferred partners and ultimately as a quartet. Specifically, group formation was dynamic and gradual, with the rats first forming duos, then trios, and ultimately a quartet. Trios and quartets mostly huddled in the same specific corner that became a shared home base, from which they took solo or duo roundtrips to the arena. The present study unveils how, by means of gradual interactions among self, place, and conspecifics, four unfamiliar rats organized together their social spatial behavior.
Prior work shows that children selectively learn from credible speakers. Yet little is known how they treat information from non-credible speakers. This research examined to what extent and under what conditions children may or may not learn from problematic sources. In three studies, we found that children displayed trust toward previously inaccurate speakers. Children were equally likely to extend labels from previously accurate and inaccurate speakers to novel objects. Moreover, they expected third parties to share labels provided by previously inaccurate speakers. Only when there was clear evidence that the speakers' information was wrong (as in the case when speakers' perceptual access to the information was blocked), did young children reject the label. Together, the findings provide evidence that young children do not completely ignore the labels supplied by non-credible speakers unless there is strong reason to do so.
While an understanding of the structure and function of a generically described immune system is essential in contemporary biomedicine, it is clear that a one-size-fits-all approach applied across multiple species is fraught with contradictions and inconsistencies. Nevertheless, the breakthroughs achieved in immunology following the application of observations in murine systems to that of man have been pivotal in the advancement of biology and human medicine. However, as additional species have been used to further address biologic and safety assessment questions relative to the structure and function of the immune system, it has become clear that there are differences across species, gender, age and strain that must be considered. The meaningfulness of these differences must be determined on a case-by-case basis. This review article attempts to collect, consolidate and discuss some of these species differences thereby aiding in the accurate placement of new observations in a proper immunobiological and immunopathological perspective.
Urban vegetation is influenced by prior land use due to the dynamic nature of urban landscape. However, limited information is available on how strongly the land-use legacy impacts the diversity of urban vegetation, especially in areas of rapid urbanization. This study quantified the land-use legacy effect on taxonomic and functional diversity of woody plants in Haikou, China. We collected data on land use, percentages of woody vegetation cover, and abundance of woody plants from 461 randomly distributed sample plots. The influence of land-use legacy was examined by analyzing the land-use history of sample plots and taxonomic and functional alpha- and beta-diversity of woody plants. The relative importance of the land use and the percentage of woody vegetation cover on the diversity of woody plants were analyzed using the boosted regression tree model. The result showed that the land-use legacy effect caused significant divergence in taxonomic and functional diversity of woody plants and the effect was most obvious in sites where the lands were currently used as residential areas. Remnant trees, shrubs, and possibly shrubs growing from seed banks and roots contributed to this legacy effect. We also found that taxonomic and functional a-diversities of trees in a site were influenced by how frequent the land use of the place was changed and what type of land use that the place ended up with. Based on our findings, we recommend conservation programs in rapidly urbanizing regions give more attention to vegetation in residential areas and particularly species with low utilitarian value. (C) 2017 Elsevier B.V. All rights reserved.
Utilization of the spectrum simulation in many important fields widely, it has made the target spectral simulation technique to be an important development trends. With the rapid development of the application of the LED technology, the LED have the merits of long serving life, high lighting efficiency, rapid responding time, and high wide selection of light band. Consequently, taking the demands of designing for the target spectral scene reproduction systems into consideration, LED with variable light bands as the light source, and performs Gauss Curve calculation to fit spectra in scene via Matlab software, and therefore serving as the criteria to selection of LED. Meanwhile, the system of driving a light source applies high performance embedded MCU as the main data processor. The chip for LED is a specific driver chip which was made in TI Corporation. Through analyzing the data collected from the target spectra in scene, then the processor transfers the calculated results to the driver IC ( integrated circuit) of LED. The spectrum in scene is reproduced basing on the results. Moreover, this design method can also combine with spectrometer directly to realize the real-time capability of reproduction of the spectra in scene. It has a great potential application in the future.
Principles: B-domain deleted human coagulation factor VIII cDNA (BDD-hFVIIIcDNA) transgenic mice were produced by using sperm mediated gene transfer (SMGT). The transcription and expression of human FVIII in transgenic mice were also investigated. Methods: Sperm were isolated from caudae epididymides of male C57BL/6 mice and transfected with linearized RC/RSV-BDD-bFVIIIcDNA plasmid, and subsequently used to fertilize female mice via artificial insemination in vivo. After birth, F0 progeny were identified by PCR and Southern blotting for BDD-hFVIIIcDNA transgenic mice. F1 progeny were subsequently derived from a male transgenic F0 mouse and a normal C57BL/6 female mouse. The F1 progeny were then identified as BDD-hFVIIIcDNA transgenic mice by Southern blotting. The transcription and expression of BDDhFVIIIcDNA in transgenic mice were determined by northern blotting, western blotting and immunohistochemical staining. Blood was also collected from both F0 and F1 progeny to detect hFVTIT:Ag and anti-hFVIII inhibitors. Results: A total of 9 F0 and 8 F1 progeny were delivered, in which 3 F0 and 2 F1 progeny were identified to have BDD-hFVIIIcDNA. The transcription and expression of BDD-hFVIIIcDNA were found to exist in the liver and kidneys of all transgenic mice. HFVIII:Ag in plasma of the transgenic F0 progeny was 31.95 ng/ml, 23.52 ng/ml and 26.36 ng/ml respectively, whilst the F1 transgenic mice showed results of 18.82 ng/ml and 12.16 ng/ml. Anti-hFVIII inhibitors were negative in both F0 and F1 progeny. Conclusions: Human FVIII gene transgenic mice can be produced by the SMGT technique and express human FVIII protein in their bodies.
Objective: The properties of self-renewal and division in spermatogonial stem cells (SSCs) support spermatogenesis. There is a number of reported methods for in vitro SSC culture systems. The development of a culture system that effectively supports isolation and self-renewal of germline stem cells (GSCs) is of tremendous benefit for clinical trials, experimental research, and as potential treatment for male infertility. The current study aims to consider the cultivation and behavior of GSCs in a non-adherent culture system. Materials and Methods: In this experimental study, we cultured testicular cells from neonatal mice in agarose coated plates in the presence of Dulbecco's modified Eagle's medium (DMEM) medium (CTRL group), 10% fetal bovine serum (FBS)+DMEM (10% group), and growth factor (G group) that contained 2% FBS, glial cell-derived neurotrophic factor (GDNF), epidermal growth factor (EGF), and fibroblast growth factor (FGF). Mouse spermatogonial stem-like colonies were isolated approximately 3 weeks after digestion of the testis tissue. After passages 2-3, the identity of the mouse spermatogonial stem-like cells was confirmed by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry against the germ cell markers alpha 6, beta 1, c-Kit, Thy-1, c-Ret, Plzf, and Oct4. The statistical significance between mean values in different groups was determined by one-way analysis of variance (ANOVA). Results: We observed spermatogonial stem-like colonies in the G and 10% groups, but not the CTRL group. Immunocytochemistry, flow cytometry, and RT-PCR confirmed expressions of germ cell markers in these cells. In the spermatogonial stem-like cells, we observed a significant expression (P<0.05) of germ cell markers in the G and 10% groups versus the testis cells (T). Their proliferative and apoptotic activities were examined by Ki67 and PI/annexin V-FITC. Alkaline phosphatase assay showed that mouse spermatogonial stem-like colonies were partially positive. Conclusion: A non-adherent culture system could provide a favorable method for in vitro short-term culture of spermatogonial stem-like cell colonies.
Introduction. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid, derived from activated platelet, that is known to induce diverse cellular responses through at least five G-protein-coupled receptors on various cell types. Abnormal platelet and coagulation activation is often seen in patients with gastric cancer. However, neither the effects of this platelet-derived mediator S1P nor the distribution of S1P receptors on the gastric cancer cell are fully understood. The aim of this study was to examine the possible role of S1P and its receptors in the progression of gastric cancer. Materials and methods. We characterized the expression profiles of S1P receptors in nine human gastric cancer cell lines and evaluated the relationship between the responses to S1P and its receptor expression on cell migration by modified Boyden chamber and cell proliferation by MTS assay. Results. Northern blotting analysis has revealed that S1P2 was expressed in all gastric cancer cell lines to varying degrees, and S1P3 was expressed in four cell lines. S1P1 expression was weak, and no significant expression of either S1P4 or S1P5 was detected. The addition of S1P markedly stimulated the migration of MKN1 and HCG-27 that dominantly expressed S1P3, and the effect was potently inhibited by pertussis toxin or wortmannin. In contrast, S1P significantly inhibited the migration of AZ-521 that expressed S1P2 exclusively. This indicates that the balance between S1P2- and S1P3-mediated signals might be critical in determining the metastatic response of gastric cancer cells to S1P. S1P elicited weak but significant antiproliferative effects on all of the three cell lines, although the effects were not major. In these cells, S1P induced extracellular signal-regulated kinase (ERK) phosphorylation with transient Akt dephosphorylation that may cause the weak effects on proliferation. Conclusions. Our results suggest that the S1P receptor expression may critically determine the biological behavior of gastric cancers and thus therapeutic interventions directed at each S1P receptor might be clinically effective in preventing metastasis in gastric cancer. (c) 2006 Elsevier Inc. All rights reserved.
This paper presents the in vivo performances of a resource-optimized digital action potential (AP) detector featuring an adaptive threshold based on a new Sigma-delta control loop. The proposed AP detector is optimized for utilizing low hardware resources, which makes it suitable for real-time implementation on most common low-power microcontroller units (MCC). The adaptive threshold is calculated using a digital control loop based on a Sigma-delta modulator that precisely estimates the standard deviation of the neuronal signal amplitude. The detector was demonstrated using a common MCC from MSP430 family, incorporated into a small wireless platform for combined optogenetics and neural recording. The system has been fully characterized experimentally within in vivo experiments on a freely-moving transgenic mouse expressing ChannelRhodospin (Thyl::ChR2-YFP line4). The results demonstrate that the proposed AP detector can be used to achieve overall data reduction ratios above 11 when transmitting only the detected APs. A comparison of the obtained results with other thresholding approaches shows that the proposed detector provides similar performances to those significantly more resource demanding approaches.
Object. Because of toxicity at high concentrations, nitric oxide (NO) contributes to spinal cord injury (SCI) secondary lesions. At low concentrations NO modulates nuclear factor-kappa B (NF-kappa B) activation. The authors investigated the activity of neuronal and endothelial NO synthase (nNOS and eNOS) to determine correlations with NF-kappa B activation and inducible NOS (iNOS) expression soon after SCI. Methods. In 48 adult male Wistar rats clip-based (50 g/mm(2)/10 seconds) SCI was induced, and spinal cords were removed at different intervals for the following evaluations: 1) assaying specific activity of nNOS and eNOS; 2) electrophoresis mobility shift assay for activated NF-kappa B, 3) Northern blotting for iNOS; 4) immunohistochemistry for iNOS and NF-kappa B; and 5) immunofluorescence for iNOS and NF-kappa B. At 15 minutes postinjury, eNOS activity decreased significantly (p < 0.001). as did nNOS activity at 1 hour compared with these levels in control animals and rats killed at 15 and 30 minutes after SCI (p < 0.001). Basal NF-kappa B levels were variable in controls and at 15 and 30 minutes after injury. One hour postinjury, NF-kappa B activation was diffuse. Inducible NOS messenger RNA localized diffusely, peaking 6 hours after injury and remaining stable until 24 hours postinjury. Immunohistochemical analysis showed diffuse iNOS and NF-kappa B staining, especially in neurons inside and around the lesion. Immunofluorescence demonstrated that injured neurons were a source of NF-kappa B and iNOS soon after injury. Conclusions. Both nNOS and eNOS exhibited different regulation and roles soon after injury: nNOS correlated with NF-kappa B activation, whereas eNOS may have participated in vascular changes of the injured spinal cord. Neurons seemed to play a pivotal role in modulating and amplifying the inflammatory response in the injured spinal cord.
Spinal cord injury (SCI) is a devastating condition with few effective treatments. Resveratrol, a polyphenolic compound, has exhibited neuroprotective effects in many neurodegenerative diseases. However, the explicit effect and mechanism of resveratrol on SCI is still unclear. Adenosine 5' monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), the downstream protein, play key roles in metabolizing of energy, resisting of resistance, and cellular protein homeostasis. In this study, we determined the effects of resveratrol on SCI and their potential relationship with SIRT1/AMPK signaling pathway, autophagy and apoptosis. To determine the effect of resveratrol on SCI recovery, a spinal cord contusion model was employed. Rats received treatment with resveratrol or DMSO immediately following contusion. We determined that Basso, Beattie, and Bresnahan (BBB) scores were significantly higher for injured rats treated with resveratrol. Nissl and HE staining revealed that resveratrol treatment significantly reduced the loss of motor neurons and lesion size in the spinal cord of injured rats when compared to vehicle-treated animals. Spinal cord tissue was assessed by Western blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses 7 days after injury for changes in expression of SIRT1/AMPK signaling pathway, autophagy and apoptosis proteins. Expression of SIRT1, p-AMPK, Beclin-1, LC3-B, and Bcl-2 was elevated in resveratrol-treated animals, whereas expression of p62, Cleaved Caspase-3, Caspase-9, and Bcl-2 associated X protein (Bax) was inhibited. Immunofluorescence analysis of primary neurons treated with resveratrol alone or in combination with Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) revealed that treatment with the inhibitors blocks the increased LC3-B expression in cells and increases the portion of TUNEL-positive cells. Taken together, these results suggest that resveratrol exerts neuroprotective effects on SCI by regulating autophagy and apoptosis mediated by the SIRT1-AMPK signaling pathway. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Nonaccidental head injury, as seen in domestic child abuse cases, is often associated with spinal injury, and spinal subdural hematoma is the most frequent diagnosis. While spinal epidural hematomas are a rare occurrence, the incidence of spontaneous epidural hematomas occurring in nonaccidental head injury patients is even lower. Epidural hematomas often result in acute focal neurological deficits necessitating emergent neurosurgical intervention. In patients without focal neurological deficits, conservative management may allow for spontaneous resolution of the epidural hematoma. The authors present the case of a 2-year-old boy with a large spinal epidural hematoma resulting after an event of nonaccidental injury, specifically, domestic child abuse. This patient exhibited no focal neurological deficits and was managed conservatively without surgical clot evacuation. On a follow-up visit, repeat imaging studies demonstrated a stable resolution of spinal epidural hematoma, providing further support for the safety of conservative management in these patients. (C) 2016 S. Karger AG, Basel
Kiribati, a Pacific Island Country, is striving for high solar PV electricity into national grid in order to reduce its unsustainable dependence on imported fossil fuel. This, however, can pose technical challenges on the reliable operation of the small isolated system. In this work, a technical analysis was carried out to investigate the implications of the planned pipeline of grid connected PV systems on Kiribati's Tarawa power system. Variations in PV output and corresponding spinning reserve requirements to balance the short fall in the power output were analysed. The utility network was modelled using the PowerFactoty software. Steady state and dynamic analyses were then carried out for the simulated scenarios. There were no major concerns identified at times of high load with high PV output. For low system demand with high PV output, dispatch constraints were identified. The current grid system will sustain maximum PV capacity above a load of 3250 kW but will require curtailment below this load. Dynamic simulations showed that fast negative ramps in the PV output can lead to frequency instability during a time of low demand and maximum PV output. The system is stable with PV curtailed at 900 kW if low loads and maximum PV output conditions exist. (C) 2017 Elsevier Ltd. All rights reserved.
Suicide is an important public health problem for adolescents, and it is essential to increase our knowledge concerning the etiology of suicide among adolescent students. Therefore, this study was designed to examine the associations between hopelessness, depression, spirituality, and suicidal behavior, and to examine spirituality as a moderator between hopelessness, depression, and suicidal behavior among 1376 Malaysian adolescent students. The participants completed measures of depression, hopelessness, daily spiritual experience, and suicidal behavior. Structural equation modeling indicated that adolescent students high in hopelessness and depression, but also high in spirituality, had less suicidal behavior than others. These findings reinforce the importance of spirituality as a protective factor against hopelessness, depression, and suicidal behavior among Malaysian adolescent students.
Sucrose induces the expression of miR398 and the production of miR398 is controlled by SQUAMOSA promoter binding protein-like7 (SPL7) transcription factor under copper deficiency in Arabidopsis thaliana. Little else, however, is known about the sucrose-regulated copper homeostasis in Arabidopsis. Here, we employed the microarray technology to screen for sucrose-responsive microRNAs (miRNAs), and identified several candidates using northern blotting. In addition to miR398, miR408, miR319, and miR160 are also responsive to sucrose. Furthermore, the induction of miR398 and miR408 by sucrose depends on the presence of SPL7. MiR398 and miR408 induction by high sucrose was eliminated by high copper. Meanwhile, high sucrose treatment strongly suppressed copper accumulation. Knock-down of SPL7 dramatically reduced copper accumulation in plants under low sucrose, but this effect was corn promised in the presence of high levels of sucrose. Taken together, these results suggest a connection between sucrose signaling and copper accumulation in cells, and that sucrose-regulated copper accumulation is both SPL7-dependent and SPL7-independent in Arabidopsis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Research objectives: The European market for football club investors is undergoing a significant transformation, with German clubs opening up for strategic investors, French clubs being taken over by private majority investors, and English top-league clubs experiencing an influx of foreign investors. Economic and legal politics have played an important role in the deregulation of closed member associations.Research methods: This paper aims to summarize the history and market situation of the Big Five' European leagues, review available theory and empirical evidence on incorporations and public and private investors, and suggest research gaps that deserve further attention. The authors have also constructed a unique database covering all owners in the two premium divisions in England, France, Germany, and Italy for the period from 2003 to 2014.Results and findings: The available articles in the growing research field of football club investors cover various theoretical areas, such as the application of property rights theory to European football clubs. In addition, several empirical papers analyze the financial and sporting impact of domestic and foreign private investors and public listings. All these studies highlight the increasing importance of club ownership in the rat race of European football.Implications: Nevertheless, some research gaps remain to be studied at an appropriate depth. First, further empirical studies should analyze the impact of incorporations in German football and the entry of private majority investors in France. Furthermore, future research may address the paradox of de-listings in England and additional listings in continental Europe. Finally, this article identifies the impact of foreign investors and multi-ownership synergies as promising research fields. In this respect, the article provides some managerial implications for football club owners, managers, and regulators.
Use of strontium titanate (SrTiO3) as an anode in solid oxide fuel cells has attracted considerable research attention because of its excellent thermal stability. Mesoporous SrTiO3 increases the specific surface area for fuel cell reaction, which in turn increases the fuel-to-electricity conversion efficiency. Spray pyrolysis (SP) is advantageous because it entails short processing times and continuous production. In this study, we prepared mesoporous SrTiO3 particles through SP. Because surfactants, as pore forming agents, may aggregate and reduce the specific surface area of particles, the stable surfactant concentration range was investigated. In addition, the short calcination time of SP may cause incomplete decomposition and thus generate an unreacted phase; therefore, various calcination temperatures and an additional wash treatment were explored. Finally, SrTiO3 powder with the high specific surface area of 103 m(2)/g was obtained.
Rapid identification of commercially important squid species is essential to manage squid market and protect consumers' interests. In this study, two sets of loop-mediated isothermal amplification (LAMP)-based assays were developed for identification of jumbo flying squid (Dosidicus gigas). After analyzing the D. gigas mitochondrial genes reported in GenBank, the mitochondrial cytochrome c oxidase subunit I (COI) gene was selected for designing species-specific primers. When incubated at 65 A degrees C for 30 min, only D. gigas DNA can be detected by real-time fluorescence detection (RealAmp) or visual detection via SYBR GreenA (R) I staining (Visual-LAMP). The detection limits were 10 pg per reaction for purified D. gigas DNA, and 0.01 % w/w D. gigas in homogenized cephalopod mixtures. These methods can be applied to all kinds of processed squid and squid-containing products. They also have potential in on-site detection for the advantages of high specificity, high sensitivity, time saving, and ease in operation.
We describe a dc Superconducting Quantum Interference Device (SQUID) readout electronics in Flux Locked Loop (FLL) mode without integrator and with only one operational amplifier, which is called Single Chip Readout Electronics (SCRE). A weakly damped niobium-SQUID magnetometer with a large flux-to-voltage transfer coefficient of about. partial derivative V/partial derivative Phi approximate to 380 mu V/Phi(0) and SCRE results in a very simple SQUID system. We characterize the system and demonstrate its applicability to Magnetocardiography (MCG) and measurements using the Transient ElectroMagnetic (TEM) method. SCRE not only simplifies the readout scheme, but also improves the system stability, the bandwidth and the slew rate. The difference between SCRE and a conventional readout scheme (preamplifier + amplifier + integrator) is also discussed.
Small RNAs (sRNAs) are short (similar to 50-200 nucleotides) noncoding RNAs that regulate cellular activities across bacteria. Salmonella enterica starved of a carbon-energy (C) source experience a host of genetic and physiological changes broadly referred to as the starvation-stress response (SSR). In an attempt to identify novel sRNAs contributing to SSR control, we grew log-phase, 5-h C-starved and 24-h C-starved cultures of the virulent Salmonella enterica subspecies enterica serovar Typhimurium strain SL1344 and comprehensively sequenced their small RNA transcriptomes. Strikingly, after employing a novel strategy for sRNA discovery based on identifying dynamic transcripts arising from "gene-empty" regions, we identify 58 wholly undescribed Salmonella sRNA genes potentially regulating SSR averaging an similar to 1,000-fold change in expression between log-phase and C-starved cells. Importantly, the expressions of individual sRNA loci were confirmed by both comprehensive transcriptome analyses and northern blotting of select candidates. Of note, we find 43 candidate sRNAs share significant sequence identity to characterized sRNAs in other bacteria, and similar to 70% of our sRNAs likely assume characteristic sRNA structural conformations. In addition, we find 53 of our 58 candidate sRNAs either overlap neighboring mRNA loci or share significant sequence complementarity to mRNAs transcribed elsewhere in the SL1344 genome strongly suggesting they regulate the expression of transcripts via antisense base-pairing. Finally, in addition to this work resulting in the identification of 58 entirely novel Salmonella enterica genes likely participating in the SSR, we also find evidence suggesting that sRNAs are significantly more prevalent than currently appreciated and that Salmonella sRNAs may actually number in the thousands.
Bacterial regulatory small RNAs (sRNAs) play important roles in gene regulation and are frequently connected to the expression of virulence factors in diverse bacteria. Only a few sRNAs have been described for Pasteurellaceae pathogens and no in-depth analysis of sRNAs has been described for Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, responsible for considerable losses in the swine industry. To search for sRNAs in A. pleuropneumoniae, we developed a strategy for the computational analysis of the bacterial genome by using four algorithms with different approaches, followed by experimental validation. The coding strand and expression of 17 out of 23 RNA candidates were confirmed by Northern blotting, RT-PCR, and RNA sequencing. Among them, two are likely riboswitches, three are housekeeping regulatory RNAs, two are the widely studied GcvB and 6S sRNAs, and 10 are putative novel trans-acting sRNAs, never before described for any bacteria. The latter group has several potential mRNA targets, many of which are involved with virulence, stress resistance, or metabolism, and connect the sRNAs in a complex gene regulatory network. The sRNAs identified are well conserved among the Pasteurellaceae that are evolutionarily closer to A. pleuropneumoniae and/or share the same host. Our results show that the combination of newly developed computational programs can be successfully utilized for the discovery of novel sRNAs and indicate an intricate system of gene regulation through sRNAs in A. pleuropneumoniae and in other Pasteurellaceae, thus providing clues for novel aspects of virulence that will be explored in further studies.
Investigations of environmental microbial communities are crucial for the discovery of populations capable of degrading hazardous compounds and may lead to improved bioremediation strategies. The goal of this study was to identify microorganisms responsible for aerobic benzene degradation in coal tarcontaminated groundwater. Benzene degradation was monitored in laboratory incubations of well waters using gas chromatography mass spectrometry (GC-MS). Stable isotope probing (SIP) experiments using [C-13] benzene enabled us to obtain (13)Clabled community DNA. From this, 16S rRNA clone libraries identified Gammaproteobacteria and Betaproteobacteria as the active benzene-metabolizing microbial populations. Subsequent cultivation experiments yielded nine bacterial isolates that grew in the presence of benzene; five were confirmed in laboratory cultures to grow on benzene. The isolated benzene-degrading organisms were genotypically similar (>97% 16S rRNA gene nucleotide identities) to the organisms identified in SIP experiments. One isolate, Variovorax MAK3, was further investigated for the expression of a putative aromatic ring-hydroxylating dioxygenase (RHD) hypothesized to be involved in benzene degradation. Microcosm experiments using Variovorax MAK3 revealed a 10-fold increase in RHD (Vapar_5383) expression, establishing a link between this gene and benzene degradation. Furthermore, the addition of Variovorax MAK3 to microcosms prepared from site waters accelerated community benzene degradation and correspondingly increased RHD gene expression. In microcosms using uninoculated groundwater, quantitative (q) PCR assays (with 16S rRNA and RDH genes) showed that Variovorax was present and responsive to added benzene. These data demonstrate how the convergence of cultivation-dependent and -independent techniques can boost understandings of active populations and functional genes in complex benzene-degrading microbial communities. IMPORTANCE Benzene is a human carcinogen whose presence in contaminated groundwater drives environmental cleanup efforts. Although the aerobic biodegradation of benzene has long been established, knowledge of the identity of the microorganisms in complex naturally occurring microbial communities responsible for benzene biodegradation has evaded scientific inquiry for many decades. Here, we applied a molecular biology technique known as stable isotope probing (SIP) to the microbial communities residing in contaminated groundwater samples to identify the community members active in benzene biodegradation. We complemented this approach by isolating and growing in the laboratory a bacterium representative of the bacteria found using SIP. Further characterization of the isolated bacterium enabled us to track the expression of a key gene that attacks benzene both in pure cultures of the bacterium and in the naturally occurring groundwater microbial community. This work advances information regarding the documentation of microbial processes, especially the populations and genes that contribute to bioremediation.
This paper presents a new version of Wheelchair. q, a wheelchair with stair climbing ability. The wheelchair is able to climb single obstacles or staircases thanks to a hybrid wheel-leg locomotion unit with a triple-wheels cluster architecture. The new concept presented in this work represents an improvement respect to previous versions. Through a different arrangement of functional elements, the wheelchair performances in terms of stability and regularity during movement on stair ha ve been increased. In particular, attention has been paid to ensure a regular and comfortable motion for the user during stair climbing operation. For this reason, a cam mechanism has been introduced and designed with the aim to compensate the oscillation generated on the wheelchair frame by the locomotion unit rotation. A design methodology for the cam profile is presented. Moreover, a parametric analysis on the cam profile and on the mechanism dimensions has been conducted with the aim to find a cam profile with suitable dimensions and performances in terms of pressure angle and radius of curvature. (C) 2017 Elsevier Ltd. All rights reserved.
The main focus of this paper is to select an economically suitable sustainable standalone power supply system for a remote off-grid town in Western Australia. Existing power systems of such remote towns in Australia have adverse environmental impacts and contribute to global warming due to the utilization of fossil fuels, especially diesel and gas. The possible electricity supply systems for such towns can vary from a diesel/gas generator towards a hybrid system composed of a generator, Wind turbine, photovoltaic system, and battery energy storage. In order to limit the cost of the system and to propose the most economically feasible solution, various combinations of supply systems are considered. These systems are analyzed in this paper by the help of HOMER software to determine the optimal architecture and the control strategy of the supply system. This study has used real demand data of the town, as well as the prices of different electrical components in the Australian market. The scenario which yields the minimum cost of energy is defined and suggested. Also, a decision-making based technique is proposed to help the local electricity utility in finding the suitable solution in the case of budget limits on the investment and annual operation and maintenance. Another aim of this analysis is to investigate and illustrate the impact of a small annual load growth on the size of the selected components for the selected power system, as well as the total net present cost and the cost of electricity. A sensitivity analysis is also performed to analyze the impact of uncertainties of some of the parameters in the outcome of the study to obtain the optimized cost of the selected system. (C) 2017 Elsevier Ltd. All rights reserved.
Staphylococcus aureus is an important food-borne opportunistic pathogen that frequently causes severe blood and tissue infections or even fatal illnesses. Although S. aureus has been extensively studied in livestock and poultry foods in China, limited information has been reported in aquatic products. Accordingly, in this study, we aimed to characterize S. aureus in aquatic products purchased from retail markets in China. In total, 320 aquatic food samples were collected from 32 provincial capitals in China. The results showed that 119 samples (37.2%, 119/ 320) were positive for S. aureus by both qualitative and quantitative analyses. The contamination levels of 78.2% of samples ranged from 0.3 to 10 MPN/ g, and six samples exceeded 110 MPN/ g. A total of 119 S. aureus isolates from positive samples were selected to evaluate virulence factors, antibiotic resistance, and molecular characteristics. All S. aureus isolates were evaluated for the presence of 11 virulence genes by multiplex polymerase chain reaction, and a -hemolysin (hl a, 84.9%), fibronectin-binding protein A (fnbA, 79.0%), S. aureus enterotoxin E (see, 53.8%), and Panton-Valentine leucocidin (pvl, 50.4%) were identified as the major genes. These genes formed 56 different profiles, with the major profile identified as pvl-hl a -fnbA (28.6%). The antimicrobial susceptibility of all isolates was analyzed through the disk diffusion method, and the results showed high resistance to b -lactams, macrolides and tetracyclines, but susceptibility to linezolid and vancomycin. In addition, 26 sequence types (STs) were obtained via multilocus sequence typing, including seven novel STs, among which ST1 (20.2%), ST15 (18.5%), and ST188 (13.4%) were the most common STs. All the isolates were mecC negative, but nine isolates carrying mecA were evaluated by staphylococcal cassette chromosome mec (SCCmec) typing, all of which were SCCmecIII or SCCmecIV types. Isolates of SCCmecIII showed a high prevalence and were multidrug resistant. Our results showed that aquatic products could be a vehicle for transmission of virulence genes and multidrug-resistant S. aureus, representing a potential public health risk. The STs identified in this study indicated the genetic diversity of S. aureus, thereby providing important basic data for the dissemination of S. aureus in aquatic products.
Staphylococcus aureus is a gram-positive, coccus-shaped facultative anaerobe and a member of the Staphylococcaceae family. In recent years, alimentary toxicosis caused by S. aureus is a very serious problem worldwide, which constitutes a great threat to public health. In this review, we tried to summarize the conventional methods and newly developed rapid detection techniques of S. aureus (traditional detection method, biochemical detection, immunology method, molecular biology, and biosensor method) for their principles, advantages, disadvantages, and applications. Furthermore, the future perspectives of S. aureus detection methods were forecasted at last.
Objectives: This article describes the translation and evaluation of STAR-Community Consultants program (STAR-C), an evidence-based dementia caregiver training program, within the Oregon Department of Human Services. Method: Staff from two regional Area Agencies on Aging (AAAs) were trained to implement all aspects of STAR-C, including screening, recruitment of caregiver/care-receiver dyads, and treatment delivery. Mailed assessments of caregiver depression, burden, and care-receiver mood, behavior, and quality of life were collected at pre-treatment, post-treatment, and 6-month follow-up. Results: One hundred fifty-one dyads entered the program; 96 completed the 8-week intervention. Significant positive post-treatment effects were obtained for caregiver depression, burden, and reactivity to behavior problems, and care-receiver depression and quality of life. At 6-month follow-up, improvements in caregiver reactivity and care-receiver depression were maintained. Caregivers reported high levels of satisfaction with the program. Discussion: STAR-C was successfully and effectively implemented by participating AAAs. Recommendations for replication, including training, recruitment, and assessment procedures are provided.
Stabilizing alkenyl succinic anhydride (ASA) emulsions using fine particles instead of cationic starch have attracted much attention in recent years. Herein, starch nanocrystals (SNCs) made from maize starch by H2SO4 hydrolysis were used to co-stabilize ASA emulsions with fluorescent carbon dots (CDs) made hydrothermally from gelatin. The introduction of CDs can significantly enhance the stability and reduce the droplet size of SNC-stabilized ASA-in-water emulsions. Consequently, the sizing performance of the SNC-stabilized ASA emulsion is significantly improved by increasing the CD-to-SNC mass ratio. SNC and CD co-stabilized ASA emulsions show much better sizing performance than starch and CD co-stabilized ASA emulsions, achieving their best sizing performance at a CD-to-SNC mass ratio of 80%. Meanwhile, the morphology of SNC/starch and CD co-stabilized ASA emulsions can be traced under UV excitation. (C) 2017 Elsevier Ltd. All rights reserved.
The disorganization and reorganization of starch components considering systems with different levels of complexity is reviewed with particular attention on retrogradation. The approach consists of a gradual analysis of the architecture of starch granules, followed by a discussion of disorganization in excess water and high temperature and subsequent reorganization in model systems and cereal products. The primary progress, bottlenecks, and perspectives are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
The number of identified monogenic causes of childhood-onset autoimmunity due to nodal and extranodal lymphoproliferation has increased. These pathogenic genetic variants provide the potential for pathway-specific treatment. Novel variants also require pathway-specific verification. In this report, we describe a 14-year-old patient with a novel variant in STAT3. We report clinical and laboratory findings that support STAT3 p. G419R as a novel pathogenic STAT3 gain-of-function variant.
With the application of digital control, the problem of one-step-delay appears. It limits the achievable control bandwidth. Compared with one-step-delay, minimized delay can achieve superior performance. However, it leads to the low-frequency aliasing phenomenon because sampling is not happened in the middle of either the turn-on or the turn-off times of IGBT. To weaken the influence of aliasing and reduce the total harmonics distortion (THD) of output current, the strategy of reducing the inductor current feedback coefficient by adjusting non-dominant poles is proposed. Simulation and experimental results are provided to verify the feasibility and effectiveness of the scheme.
Ignition of a cloud of dry powder is a major concern in the field of industrial process safety. The different types of discharges are already defined (spark discharges, brush discharges, propagating discharges, cone discharges, corona discharges) such as their ignition properties in a gas or a dust atmosphere. For example, it is known that a classic brush discharge cannot ignite a cloud of dry flammable dust [6,13]. Glor and Schwenzfeuer performed direct ignition tests using brush discharges and defined that even if the energy released by this kind of discharge equaled the one of a spark, the power released by the brush discharge is too low to trigger an ignition. However, some doubts remained for super brush discharges. A brush discharge as a super brush discharge occurs between a charged insulating object and a conductive electrode. The main difference lies in the surface charge density reached on the insulator that is much higher for a super brush discharge than for a brush discharge. A high charge density can be reached for example using pipes of polyethylene individually charged by tribo-charging piled one above another. Such a configuration was evocated by Liittgens [12] and tested by Larsen [11] who performed direct ignition tests in oxygen enriched atmospheres. This study is relevant with the actual safety problems since pharmaceutical and chemical powders are well known to generate electrostatic charges during their transport or handling and since the same configuration of independent polyethylene fibers can be found in flexible bulk containers that are one of the most common solutions to package this kind of powder. This paper presents the experimental set-up and the results of direct ignition tests performed with a polyethylene wax whose MIE is lower than 1 mJ at ambient conditions. The electric field reached at 1 m and the charge transfer were also registered and are described. Finally, numerical simulations are carried out to define the original surface charge density in order to help to understand the phenomenology of this discharge and its frequency of occurrence in industry. (C) 2017 Elsevier B.V. All rights reserved.
In this work, a simplified method for the evaluation of equilibrium composition of plasmas consisted of monoatomic species is proposed. Multicomponent gas systems resulting from thermal ionization of spatially uniform mixtures are assumed enough rarefied to be treated as ideal gases even after multiple ionization steps. The method developed for the calculation of equilibrium composition of these mixtures makes use of the fundamental principles of statistical physics. Equilibrium concentrations of mixture components are determined by integration of distribution functions over the space of momentum and summation over electronic energy levels. These functions correspond to the entropy maximum. To determine unknown parameters, the systems of equations corresponding to the normalization conditions are derived. It is shown that the systems may be reduced to one algebraic equation if the equilibrium temperature is known. Numeral method to solve this equation is proposed. Special attention is given to the ionized mixtures, generated from the atoms of a single chemical species and the situations, when in the gas only the first-or the first- and second-order ionization are possible. (C) 2017 Elsevier B.V. All rights reserved.
In the steel industry, the iron making system deals with large quantities of materials and energy and so it can play a critical role in reducing emissions and production costs. More specifically, excess by-product gases should be used for electricity generation; otherwise, they lead to pollution. A life cycle analysis is performed to compare the environmental impact of an iron making system with a combined cycle power plant (CCPP), to a system producing the same amount of electricity in a coal power plant. The results for a Chinese steel plant show a 33% reduction in the energy conservation and emission reduction potential for the CCPP system, which is thus more environmentally friendly. A mathematical programming formulation is then proposed for optimal scheduling. It incorporates key technological constraints and is sensitive to hourly changing electricity prices. The outcome is a 19% increase in revenue from electricity sales compared to a schedule that does not dynamically adjust to the price profile. The results also show that emissions from by-product gases can be avoided completely. The paper ends with a sensitivity analysis to evaluate the impact of changes in product demand, gas storage and CCPP capacity, and emission cost.
Stem cell therapy is a promising approach to the treatment of ischemic heart disease via replenishing cell loss after myocardial infarction. Both preclinical studies and clinical trials have indicated that cardiac function improved consistently, but very modestly after cell-based therapy. This mainly attributed to low cell survival rate, engraftment and functional integration, which became the major challenges to regenerative medicine. In recent years, several new cell types have been developed to regenerate cardiomyocytes and novel delivery approaches helped to increase local cell retention. New strategies, such as cell pretreatment, gene-based therapy, tissue engineering, extracellular vesicles application and immunologic regulation, have surged and brought about improved cell survival and functional integration leading to better therapeutic effects after cell transplantation. In this review, we summarize these new strategies targeting at challenges of cardiac regenerative medicine and discuss recent evidences that may hint their effectiveness in the future clinical settings.
Surface topography of Titanium (Ti) dental implants strongly influences osseointegration. In the present work, we have analyzed the influence of two Ti implant surfaces characterized by similar microtopography but different nanotopography and chemistry on the osteoblastic phenotype of Dental Pulp Stem Cells (DPSCs). The effect on osteogenic differentiation, extracellular matrix (ECM) and cell adhesion molecules production have been evaluated by means of molecular biology analyses. The morphology of the cells grown onto these surfaces has been analyzed with SEM and immunofluorescence (IF), and the safety of the surfaces has been tested by using karyotype analysis, Ames test and hemocompatibility assay. Results showed that starting from 15 days of DPSCs culture, a substantial expression of osteoblast specific markers and a strong increase of cell adhesion molecules can be detected. In particular, when DPSCs are seeded on the Ti implants expression of microRNA (miRNA)-196a, which is involved in osteoblastic commitment of stem cells, and of Vascular Cell Adhesion Molecule 1 (VCAM1), a factor involved in angiogenesis, is strongly enhanced.
Scholars have argued that opposition to welfare is, in part, driven by stereotypes of African Americans. This argument assumes that when individuals think about welfare, they spontaneously think about Black recipients. We investigated people's mental representations of welfare recipients. In Studies 1 and 2, we used a perceptual task to visually estimate participants' mental representations of welfare recipients. Compared with the average non-welfare-recipient image, the average welfare-recipient image was perceived (by a separate sample) as more African American and more representative of stereotypes associated with welfare recipients and African Americans. In Study 3, participants were asked to determine whether they supported giving welfare benefits to the people pictured in the average welfare-recipient and non-welfare-recipient images generated in Study 2. Participants were less supportive of giving welfare benefits to the person shown in the welfare-recipient image than to the person shown in the non-welfare-recipient image. The results suggest that mental images of welfare recipients may bias attitudes toward welfare policies.
Stick balancing on the fingertip is a complex voluntary motor task that requires the stabilization of an unstable system. For seated expert stick balancers, the time delay is 0.23 s, the shortest stick that can be balanced for 240 s is 0.32 m and there is a approximate to 0.8 degrees dead zone for the estimation of the vertical displacement angle in the saggital plane. These observations motivate a switching-type, pendulum-cart model for balance control which uses an internal model to compensate for the time delay by predicting the sensory consequences of the stick's movements. Numerical simulations using the semi-discretization method suggest that the feedback gains are tuned near the edge of stability. For these choices of the feedback gains, the cost function which takes into account the position of the fingertip and the corrective forces is minimized. Thus, expert stick balancers optimize control with a combination of quick manoeuvrability and minimum energy expenditures.
The understanding of the influence of non-axisymmetric internal frames on the vibroa-coustic behavior of a stiffened cylindrical shell is of high interest for the naval or aeronautic industries. Several numerical studies have shown that the non-axisymmetric internal frame can increase the radiation efficiency significantly in the case of a mechanical point force. However, less attention has been paid to the experimental verification of this statement. That is why this paper proposes to compare the radiation efficiency estimated experimentally for a stiffened cylindrical shell with and without internal frames. The experimental process is based on scanning laser vibrometer measurements of the vibrations on the surface of the shell. A transform of the vibratory field in the wavenumber domain is then performed. It allows estimating the far-field radiated pressure with the stationary phase theorem. An increase of the radiation efficiency is observed in the low frequencies. Analysis of the velocity field in the physical and wavenumber spaces allows highlighting the coupling of the circumferential orders at the origin of the increase in the radiation efficiency. (C) 2017 Elsevier Ltd. All rights reserved.
In this paper, we consider the nested decomposition method in the context of multistage stochastic problems with scenario trees where we contribute with improvements in accelerating convergence to optimum. We first propose a hybrid protocol for transmitting cuts across nodes aiming at a trade-off between the inherent benefits and drawbacks of the single (aggregated) versus multi-cut (desegregated) versions. The idea we aim to explore is to reduce the size of the problem solved at each iteration by applying the aggregated version of the cuts on the furthest nodes of the tree. We then turn our attention towards the selection of first-stage solutions by employing sampling and simulation aiming to carefully choose those first-stage solution that are potentially capable to drastically decrease the gap between the upper and lower bound at each iteration. The problems on which the latter technique is applied present a special structure, according to which the first-stage variables are linked to all further stages. We test both accelerating techniques on a generic problem which displays a blend of two-stage and multistage structure and we report significant savings in terms of CPU time and number of iterations to convergence.
AIM: To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS: In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS: The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1). BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and -23 of Rb, 5' flanking region of IL-2 and clotting factor IX genes. CONCLUSION: GCRG123, an active member of the L1 family, was up-regulated in human gastric signet-ring cell carcinoma. (C) 2008 WJG. All rights reserved.
BACKGROUND & AIMS: Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. METHODS: We analyzed data from 1092 patients enrolled in a double-blind placebocontrolled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 x 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. RESULTS: Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P =.084), infection during treatment (P =.20), or infection after treatment (P =.27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [ OR], 1.27; 95% confidence interval [ CI], 1.27 - 2.92; P =.002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78 - 1.37; P =.80). However, a higher proportion (10%) of patients receiving prednisolone developed an infection after treatment than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07 - 2.69; P =-.024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41 - 4.30; P =.002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count (OR, 4.68; 95% CI, 1.80 - 12.17; P =.001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54 - 1.62; P =.82) or levels of bDNA (OR, 0.83; 95% CI, 0.39 - 1.75; P =.62). CONCLUSIONS: Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125.
Bulk strain solitons in solids attract considerable attention in applications due to their very small decay, permanent bell shape and the wave parameter dependence on waveguide elasticity and geometry. One of the reasons of an evident gap between theory and numerical simulation of strain solitons propagation in various waveguides and comparatively rare experimental verification of rigorous results lies in extensive variability of physical constants data available for polymers. We show how a dramatic improvement of experimental setup provides new opportunities in solitary wave observation and its parameters measurements. Digital holography based on high-speed registration cameras allowed us to refine the accuracy of measurements, and precise pulse synchronization provided direct measurements of bulk strain soliton velocity with proper accuracy. It confirms the fact that the soliton parameters depend rather on the waveguide geometry and material, not on an initial pulse, which power provides either a single soliton or a soliton train. (C) 2016 Elsevier B.V. All rights reserved.
In many proteins, especially allosteric proteins that communicate regulatory states from allosteric to active sites, structural deformations are functionally important. To understand these deformations, dynamical experiments are ideal but challenging. Using static structural information, although more limited than dynamical analysis, is much more accessible. Underused for protein analysis, strain is the natural quantity for studying local deformations. We calculate strain tensor fields for proteins deformed by ligands or thermal fluctuations using crystal and NMR structure ensembles. Strains-primarily shears-show deformations around binding sites. These deformations can be induced solely by ligand binding at distant allosteric sites. Shears reveal quasi-2D paths of mechanical coupling between allosteric and active sites that may constitute a widespread mechanism of allostery. We argue that strain-particularly shear-is the most appropriate quantity for analysis of local protein deformations. This analysis can reveal mechanical and biological properties of many proteins.
The paper analyses how the spatial vision of the Loop City for the Oresund Region has played an important persuasive role in legitimizing and mobilizing local and national political support for a light rail link along the outer ring road in the Greater Copenhagen Area. The paper discusses the persuasive power of spatial concepts and supportive storylines in bringing transport infrastructure projects onto the national policy agenda. In conclusion, the paper calls for critical attention to the rationalities underpinning practices of persuasive storytelling in contemporary strategic spatial planning.
Background. Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturally acquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant. Methods. Serum immunoglobulin G (IgG) titers to 28 pneumococcal protein antigens were measured among 242 individuals aged= 30 days after serum collection, and the antigen variant in each pneumococcal isolate was determined using genomic data. We assessed the association between preexisting variant-specific antibody titers and subsequent carriage of pneumococcus expressing a particular antigen variant. Results. Antibody titers often increased across pediatric groups before decreasing among adults. Individuals with low titers against group 3 pneumococcal surface protein C (PspC) variants were more likely to be colonized with pneumococci expressing those variants. For other antigens, variant-specific IgG titers do not predict colonization. Conclusion. We observed an inverse association between variant-specific antibody concentration and homologous pneumococcal colonization for only 1 protein. Further assessment of antibody repertoires may elucidate the nature of antipneumococcal antibody-mediated mucosal immunity while informing vaccine development.
The "Streptomyces genetics and secondary metabolism" laboratory course gives an introduction to the versatile soil dwelling Gram-positive bacteria Streptomyces and their secondary metabolism. The course combines genetic modification of Streptomyces; growing of the strain and protoplast preparation, plasmid isolation by alkaline lysis and phenol precipitation, digestions, and ligations prior to protoplast transformation, as well as investigating the secondary metabolites produced by the strains. Thus, the course is a combination of microbiology, molecular biology, and chemistry. After the course the students should understand the relationship between genes, proteins, and the produced metabolites. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
Primer extension with RNA from an RNase III null mutant of Streptomyces coelicolor M145 and a primer complementary to the polynucleotide phosphorylase gene revealed two major extension products. Two different extension products were observed using RNA from either wild type M145 or the null mutant with a primer complementary to rpsO. Mapping of the 5'-ends of these extension products to the rpsO-pnp intergenic region indicated that all four putative transcription start sites were preceded by possible promoter sequences. These putative promoters were synthesized by the PCR and cloned into pIPP2, a xylE-based streptomycete promoter probe vector. Transfer of the pIPP2 derivatives to S. coelicolor and catechol dioxygenase assays demonstrated that all four cloned fragments had promoter activity in vivo. The activities of the four promoters changed over the course of growth of S. coelicolor and studies in three sigma factor mutant strains demonstrated that three of the promoters were sigma(B) dependent. Northern blotting studies showed that the levels of the rpsO-pnp transcripts remained relatively constant over the course of growth of S. coelicolor M145, but that on a molar basis, the levels of the readthrough and pup transcripts were considerably lower than those of rpsO. PNPase is a cold shock protein in S. coelicolor and the activity of the rpsO-pnp promoters increased during cold shock at 10 degrees, resulting in a twofold increase in PNPase activity, compared with the activity at 30 degrees. (C) 2013 Elsevier B.V. All rights reserved.
In this study the stress protein response to unaccustomed maximal eccentric exercise in humans was investigated. Eleven healthy males performed 300 maximal eccentric actions with the quadriceps muscle. Biopsies from vastus lateralis were collected at 30 min and 4, 8, 24, 96, and 168 h after exercise. Cellular regulation and localization of heat shock protein (HSP) 27, (alpha B-crystallin, and HSP70 were analyzed by immunohistochemistry, ELISA technique, and Western blotting. Additionally, mRNA levels of HSP27, alpha B-crystallin, and HSP70 were quantified by Northern blotting. After exercise (30 min), 81 +/- 8% of the myofibers showed strong HSP27 staining (P < 0.01) that gradually decreased during the following week. alpha B-Crystallin mimicked the changes observed in HSP27. After exercise (30 min), the ELISA analysis showed a 49 +/- 13% reduction of the HSP27 level in the cytosolic fraction (P < 0.01), whereas Western blotting revealed a 15-fold increase of the HSP27 level in the myofibrillar fraction (P < 0.01). The cytosolic HSP70 level increased to 203 +/- 37% of the control level 24 h after exercise (P < 0.05). After 4 days, myofibrillar-bound HSP70 had increased similar to 10-fold (P < 0.01) and was accompanied by strong staining on cross sections. mRNA levels of HSP27 , alpha B-crystallin, and HSP70 were all elevated the first day after exercise (P < 0.01); HSP70 mRNA showed the largest increase (20-fold at 8 h). HSP27 and alpha B-crystallin seemed to respond immediately to maximal eccentric exercise by binding to cytoskeletal/myofibrillar proteins, probably to function as stabilizers of disrupted myofibrillar structures. Later, mRNA and total HSP protein levels, especially HSP70, increased, indicating that HSPs play a role in skeletal muscle recovery and remodeling/adaptation processes to high-force exercise.
Adolescent stress-related growth refers to enhancement in an adolescent's cognitive-affective or social resources as a result of experiencing stressors. We tested whether adolescents reporting high levels of stress-related growth showed superior adaptation outcomes on a day-to-day basis. Participants (n = 91; females = 46, age = 14) completed a questionnaire measure of stress-related growth and kept a diary of emotional and interpersonal functioning for 10 consecutive days. Individual differences in cognitive-affective stress-related growth moderated associations between daily stress levels and adaptive coping behaviors, whereas individual differences in social stress-related growth moderated associations between daily mother-child conflict and end-of-day negative affect. This study provides the first empirical demonstration of domain-specific forms of stress-related growth during adolescence.
In many digital control systems, it is required to perform computation in a strictly periodic fashion to provide high control performance. System designers need to assign time slots that are infinitely repeated given a strict period for each task such that the time slots of different tasks do not overlap. While previous work has studied how to decide if a system is schedulable with a certain time slot assignment, it is still an unexplored area of how to select time slots for strictly periodic tasks to make them schedulable. In this paper, we propose an efficient method to solve the above problem. Our method explores the relations among task periods to improve the possibility of finding feasible start time configurations. Finally, we conduct experiments with randomly generated workload to evaluate the performance of the proposed method. (C) 2016 Elsevier B.V. All rights reserved.
In September 2015, some 5000 women workers of the Kannan Devan Hills Plantation, a large tea estate in Munnar in Kerala, launched a spontaneous agitation demanding increased wages and bonuses. They staged a massive sit-in in Munnar town, bringing operations on the tea-estate to a halt. What was unique about this strike, which garnered considerable domestic media attention, was its non-violent nature and distancing from party-affiliated tea-plantation unions. In this paper, we use interview transcripts from a community radio program to analyze whether this strike can be seen as a precursor for a new unionism of the great mass of contractual, informal workers in India. We do so within the broader question of whether class identity is still relevant for informal labor in the global south. We conclude that a successful working class movement can only emerge when workers understand their roles in the long and convoluted chain of profits and are able to universalize their situations through concrete political action.
In this study, we report an unusual case of mutidimensional sensorimotor, cognitive, and socio-affective preservation in an adult with extensive, acquired bilateral brain damage. At age 43, patient CG sustained a cerebral hemorrhage and a few months later, she suffered a second (ischemic) stroke. As a result, she exhibited extensive damage of the right hemisphere (including frontal, temporal, parietal, and occipital regions), left Sylvian and striatal areas, bilateral portions of the insula and the amygdala, and the splenium. However, against all probability, she was unimpaired across a host of cognitive domains, including executive functions, attention, memory, language, sensory perception (e.g., taste recognition and intensity discrimination), emotional processing (e.g., experiencing of positive and negative emotions), and social cognition skills (prosody recognition, theory of mind, facial emotion recognition, and emotional evaluation). Her functional integrity was further confirmed through neurological examination and contextualized observation of her performance in real-life tasks. In sum, CG's case resists straightforward classifications, as the extent and distribution of her lesions would typically produce pervasive, multidimensional deficits. We discuss the rarity of this patient against the backdrop of other reports of atypical cognitive preservation, expound the limitations of several potential accounts, and highlight the challenges that the case poses for current theories of brain organization and resilience.
Background: Carbon monoxide has been regarded as a gaseous molecular messenger like nitric oxide. Purpose: To clarify the role of heme oxygenase-1 in the permanent cerebral ischemia at the protein and mRNA level. Methods: The expression of heme oxygenase-1 protein and messenger RNA was investigated at different time points following MCAO using immunohistochemistry, Western blotting, RT-PCR, and Northern blotting. Results: Increased HO 1 immunoreactivity was detected in hippocampal and cortical neurons after 1 hour of ischemia, and was also observed in astroglial cells. After 12 hours of ischemia, HO-1 was found in both neurons and glia in cerebral cortex and thalamus, and in striatal glia cells. Western blotting analysis show the expression of HO-1 protein in cortical neurons reached the peak after 12 hours of occlusion and decreased gradually, but was still detected at day 7 post-occlusion. The expression of messenger RNA was examined in the brains of rats subjected to permanent cerebral ischemia by semi-quantitative RT-PCR and Northern blotting. HO-1 mRNA transcription could be detected 1 hour after occlusion. After 1 to 6 hours of occlusion, the expression of HO-1 rose rapidly, reaching a peak at 12 hours post-occlusion, decreased gradually, and lasted until day 7 of occlusion. Although HO activity of cerebral tissue can be detected in both sham-operated group and operated groups, the HO activity in operated groups is much stronger than that in sham-operated group. Conclusions: The induction of HO-1 protein may protect cerebral tissues from ischemic damage.
Guided by indirect evidence, recent approaches propose a tripartite crosstalk among interoceptive signaling, emotional regulation, and low-level social cognition. Here we examined the neurocognitive convergence of such domains. First, we performed three meta-analyses of functional magnetic resonance imaging studies to identify which areas are consistently coactivated by these three systems. Multi-level Kernel Density Analysis (MKDA) revealed major overlaps in the right anterior insular and frontotemporal regions (viz., the orbitofrontal and inferior frontal gyri, the amygdala, and mid temporal lobe/subcortical structures). Second, we explored such domains in patients with fronto-insulo-temporal damage. Relative to controls, the patients showed behavioral impairments of interoception, emotional processing, and social cognition, with preservation of other cognitive functions. Convergent results from both studies offer direct support for a model of insular-frontotemporal regions integrating interoception, emotion, and social cognition. (C) 2016 Elsevier Ltd. All rights reserved.
Radiological features alone do not allow the discrimination between accidental paediatric long bone fractures or those sustained by child abuse. Therefore, there is a clinical need to elucidate the mechanisms behind each fracture to provide a forensic biomechanical tool for the vulnerable child. Four-point bending and torsional loading tests were conducted at more than one strain rate for the first time on immature bone, using a specimen-specific alignment system, to characterise structural behaviour at para-physiological strain rates. The bones behaved linearly to the point of fracture in all cases and transverse, oblique, and spiral fracture patterns were consistently reproduced. The results showed that there was a significant difference in bending stiffness between transverse and oblique fractures in four-point bending. For torsional loading, spiral fractures were produced in all cases with a significant difference in the energy and obliquity to fracture. Multiple or comminuted fractures were seen only in bones that failed at a higher stress or torque for both loading types. This demonstrates the differentiation of fracture patterns at different strain rates for the first time for immature bones, which may be used to match the case history given of a child and the fracture produced.
Recent biological studies draw attention to the question of variability between cells. We refer to the study of Kiviet et al. published in 2014 [15]. A cell in a controlled culture grows at a constant rate v >0, but this rate can differ from one individual to another. The biological question we address here states as follows. How does individual variability in the growth rate influence the growth speed of the population? The growth speed of the population is measured by the Malthus parameter we define thereafter, also called in the literature fitness. Even if the variability in the growth rate among cells is small, with a distribution of coefficient of variation around 10%, and even if its influence on the Malthus parameter would be still smaller, such an influence may become determinant since it characterises the exponential growth speed of the population.
It is well established that the maintenance of energy expenditure is linked to active hypothalamic neural mechanisms controlling adaptive stimuli such as food intake. Variations of glucose levels and hormonal (leptin plus orexin-A) parameters, which are involved with energy homeostasis during different behavioral states, have not yet been fully defined. In this first study, behavioral analyses of an unpredictable stress model dealing with the actions of a sub-chronic administration of orexin-A (ORX-A) and the anti-hunger neuropeptide, i.e., leptin (LEP) within the hypothalamic suprachiasmatic (SCH) nucleus, were conducted on the valuable hibernating rodent (hamster; Mesocricetus auratus) model noted for its distinct depression and anxiety states. Treatment with LEP accounted for a notable reduction (p < 0.01) of body weight in stressed hamsters that not only executed very evident (p < 0.001) movements to and from elevated plus maze (EPM) but also spent less time in the dark area of the light-dark box test (LDT). Conversely, ORX-A predominantly evoked anxiogenic effects that were inverted by LEP. Interestingly, the anti-hunger neuropeptide accounted for both down-regulated NPY1 transcripts in mostly lateral-posterior hypothalamic areas while up-regulated levels were detected in the parietal cerebral cortex, hippocampus, and amygdala, which largely behaved in an opposite manner to ORX-A-dependent effects. Overall, the present findings corroborate a predominating LEPergic effect of the SCH toward the reduction of hamster anxiety-like behaviors with respect to that of ORX-A signaling, which may constitute useful therapeutic targets for stress-related obesity states.
Composing queries is evidently a tedious task. This is particularly true of graph queries as they are typically complex and prone to errors, compounded by the fact that graph schemas can be missing or too loose to be helpful for query formulation. Despite the great success of query formulation aids, in particular, automatic query completion, graph query autocompletion has received much less research attention. In this paper, we propose a novel framework for subgraph query autocompletion (called AutoG). Given an initial query q and a user's preference as input, AutoG returns ranked query suggestions as output. Users may choose a query from and iteratively apply AutoG to compose their queries. The novelties of AutoG are as follows: First, we formalize query composition. Second, we propose to increment a query with the logical units called c-prime features that are (i) frequent subgraphs and (ii) constructed from smaller c-prime features in no more than c ways. Third, we propose algorithms to rank candidate suggestions. Fourth, we propose a novel index called feature Dag (FDag) to optimize the ranking. We study the query suggestion quality with simulations and real users and conduct an extensive performance evaluation. The results show that the query suggestions are useful (saved roughly 40% of users' mouse clicks), and AutoG returns suggestions shortly under a large variety of parameter settings.
Purpose Investigate the relative effect of response outcome expectancies, work conditions, and number of subjective health complaints (SHC) on anxiety and depression in Norwegian employees. Learned response outcome expectancies are important contributors to health. Individual differences in the expectancy to cope with workplace and general life demands may be important for how work conditions influence health. Method A survey was conducted among 1746 municipal employees (mean age 44.1, SD = 11.5, 81.5 % female), as part of a randomized controlled trial. This cross-sectional study used baseline data. Multiple logistic regression analysis was performed. Outcome variables were anxiety and depression; response outcome expectancies, work conditions, and number of SHC were independent variables. Results A high number of SHC was a significant factor in explaining anxiety (OR 1.26), depression (OR 1.22) and comorbid anxiety and depression (OR 1.31). A high degree of no and/or negative response outcome expectancies was a significant factor in explaining depression (OR 1.19) and comorbid anxiety and depression (OR 1.28). The variance accounted for in the full models was 14 % for anxiety, 23 % for depression, and 41 % for comorbid anxiety and depression. Conclusion A high number of SHC, and a high degree of no and/or negative response outcome expectancies were associated with anxiety and depression. The strongest association was found for number of SHC. However, previous studies indicate that it may not be possible to prevent the occurrence of SHC. We suggest that workplace interventions targeting anxiety and depression could focus on influencing and altering employees' response outcome expectancies.
Objectives: (i) To analyze if general cognitive performance, perceived health and depression are predictors of Subjective Memory Complaints (SMC) contrasting their effect sizes; (ii) to analyze the relationship between SMC and objective memory by comparing a test that measures memory in daily life and a classical test of associated pairs; (iii) to examine if different subgroups, formed according to the MFE score, might have different behaviors regarding the studied variables. Methods: Sample: 3921 community-dwelling people (mean age 70.41 +/- 4.70) without cognitive impairment. Consecutive non-probabilistic recruitment. Assessment: Mini Cognitive Exam (MCE), daily memory Rivermead Behavioural Memory Test (RBMT), Paired Associates Learning (PAL), Geriatric Depression Scale (GDS), Nottingham Health Profile (NHP). Dependent variable: Memory Failures Everyday Questionnaire (MFE). Results: Two different dimensions to explain SMC were found: One subjective (MFE, GDS, NHP) and other objective (RBMT, PAL, MCE), the first more strongly associated with SMC. SMC predictors were NHP, GDS, RBMT and PAL, in this order according to effect size. Considering MFE scores we subdivided the sample into three groups (low, medium, higher scores): low MFE group was associated with GDS; medium, with GDS, NPH and RBMT, and higher, with age as well. Effect size for every variable tended to grow as the MFE score was higher. Conclusion: SMC were associated with both health profile and depressive symptoms and, in a lesser degree, with memory and overall cognitive performance. In people with fewer SMC, these are only associated with depressive symptomatology. More SMC are associated with depression, poor health perception and lower memory. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Sublingual immunotherapy (SLIT) is a treatment for allergic respiratory diseases that has demonstrated efficacy and safety. Several formulations of SLIT are now available worldwide for treatment of allergic rhinitis (AR). Grass tablets containing 15 to 25 mu g of group 5 major allergen reduced combined AR symptoms and medication use by 23% to 41% in 3 treatment years and 2 follow-up years. Ragweed pollen tablets (12 mg of Ambrosia artemisiifolia 1) and liquid extracts (50 mg of Ambrosia artemisiifolia 1) reduced combined AR symptoms and medication use by 26% and 43%, respectively. House dust mite tablets containing 300 index of reactivity (16 mg of Dermatophagoides pteronyssinus 1 and 68 mg of Dermatophagoides farinae 1) reduced AR symptoms by 17.9% and 17.0% in 1 treatment year and 1 follow-up year, respectively. A different house dust mite tablet (12 standardized quality house dust mite) was able to reduce the risk of asthma exacerbation compared with placebo (hazard ratio, 0.69; 95% CI, 0.50-0.96). Most adverse events were local and mild to moderate in severity. For SLIT products reviewed herein, effective doses range from 1.12 to 84 mu g of major allergen(s). However, allergen content is not uniformly standardized, can be expressed in arbitrary or proprietary units (depending on the manufacturer), and assays for determination of allergen content are highly variable. Thus, results from one study of a given product cannot be extrapolated to other products. Despite these limitations, this Clinical Management Review aims to provide practitioners with relevant information on the dosing of selected SLIT formulations in the treatment of allergic respiratory disease. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:1-10)
Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:13-21)
Allergen immunotherapy is the only disease-modifying treatment for allergic diseases. Sublingual immunotherapy (SLIT) in liquid and tablet form has been used by clinicians in Europe for years, but has only recently gained popularity and approval in the United States. In 2014, the US Food and Drug Administration approved 3 SLIT tablets for the treatment of allergic rhinitis, with or without allergic conjunctivitis. Immunotherapy treatment strategies for the polysensitized patient vary between the United States and Europe. This variation hinges upon whether the polysensitized patient is truly polyallergic. Polysensitization is the positive response to 2 or more allergens on skin prick testing or in vitro specific-IgE testing. Polyallergy is the symptomatic clinical response to 2 or more allergens. In this review, we discuss the use of SLIT in the United States with a focus on treating the polyallergic patient with SLIT. (C) 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:41-5)
A recent upsurge of investment in photovoltaic (PV) industry in China has made outstanding contributions to the adjustment of energy structure. In order to further promote the investment and construction of PV projects, the state has published many fiscal subsidy policies. In addition to unified national subsidy standard, local standards have been developed according to local fiscal revenue. They either have greatly improved return on investment (ROI) or have no significant effect as a result of too many impact factors. This paper utilizes multi dimensional big dates of distributed PV projects to obtain the weight of factors influencing the ROI from the calculation equation of ROI, which is fitted with innovative big data mining method of LSSVM-PSO. Results show that construction cost, sunshine duration, retail electricity tariff and subsidy have the greatest impacts. This study provides decision makers with quantitative basis for more comprehensive understanding on economic aspect of the distributed PV projects. (C) 2017 Elsevier Ltd. All rights reserved.
Drawing attention to the governing role of capital accumulation and its interaction with the state, this study examines the dynamics of the new wave of suburbanization in China, which is characterized by the development of new towns. New towns essentially function as a spatial fix in China's contemporary accumulation regime. Rather than resulting from capital switching from the primary to the secondary circuits, new towns help to collect funds for the leverage of industrial capital and thus simultaneously sustain both circuits. Meanwhile, the development of new towns is also a process of territorial development, in which municipal governments expand the space of accumulation under strengthened fiscal and land controls and develop a metropolitan structure. Underlying the specific form and dynamics, however, is the worldwide trend of capital switching from declining manufacturing industries in developed countries to the new investment frontier in developing countries.
Background: Several studies have demonstrated that adjuvant therapies as exercise and breathing training are effective in improving cardiac autonomic control (CAC) in patients with affective spectrum disorders. However, the effects of Sudarshan Kriya Yoga (SKY) on autonomic function in this population is unknown. Our objective was to test the hypothesis that SKY training improves CAC and cardiorespiratory coupling in patients with anxiety and/or depression disorders. Methods: Forty-six patients with a diagnosis of anxiety and/or depression disorders (DSM-IV) were consecutively enrolled and divided in two groups: 1) conventional therapy (Control) and 2) conventional therapy associated with SKY (Treatment) for 15 days. Anxiety and depression levels were determined using quantitative questionnaires. For the assessment of CAC and cardiorespiratory coupling, cardiorespiratory traces were analyzed using monovariate and bivariate autoregressive spectral analysis, respectively. Results: After 15-days, we observed a reduction of anxiety and depression levels only in Treatment group. Moreover, sympathetic modulation and CAC were significantly lower while parasympathetic modulation and cardiorespiratory coupling were significantly higher in the Treatment compared to Control group. Conclusions: Intensive breathing training using SKY approach improves anxiety and/or depressive disorders as well as CAC and cardiorespiratory coupling. These finding suggest that the SKY training may be a useful non pharmacological intervention to improve symptoms and reduce cardiovascular risk in patients with anxiety/ depression disorders.
For the past decade, Thailand pursued a strategy of promoting biofuel crop production, including sugarcane, to meet the ever increasing energy demand and to increase the income of farmers. This study analyzed the influence of policy instruments implemented to promote the sugarcane cultivation, farm household socioeconomic levels, biophysical, and institutional factors driving the conversion of rice fields into sugarcane farms. Primary information was collected from 230 farm households through a structured questionnaire. Relevant policy documents published by the responsible government agencies were the main sources of secondary information collected for policy analysis. The analyses revealed that farmers in the study area converted 25-75% of their rice fields into sugarcane farms as a result of implementation of policy instruments that made sugarcane financially far more attractive than rice. The results of the regression analysis showed that eight variables were found significant and positively influenced the conversion of rice fields into sugarcane farms. These were access to extension services, information, sugarcane loading stations, and ground water for irrigation, and duration of experience in sugarcane farming as well as household head's age and education. Irrespective of landholding size, the majority of farmers were not concerned about food security. In view of the finding, if feasible, in the form of additional price supports and commercial cane sugar index-based pricing strategies to promote sugarcane production should benefit all concerned farmers. Likewise, attention should be paid to deliver essential extension and marketing services in an effective way, particularly to those farmers who are not receiving such services.
This study investigated whether personality traits, psychopathological characteristics, and sociodemographic factors in depressed patients differentiate patients with only suicidal thoughts from those who have attempted suicide. We investigated two groups of patients with an affective disorder: 198 patients with a suicide attempt within the last 3 months (sex ratio male to female, 1: 1.3; mean age male to female, 44.8/44.7 years) and 30 patients without a suicide attempt but with suicidal thoughts (sex ratio male to female, 1: 2; mean age male to female, 39.4/42.6 years) using a comprehensive measurement (Mini-International Neuropsychiatric Interview, Structured Clinical Interview for DSM-4 Axis II disorders, Hamilton Depression Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Hamilton Anxiety Scale, Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Beck-Hopelessness Scale, Scale for Suicide Ideation, Impulsivity Rating Scale, Barratt Impulsivity Scale, Inventory for the Assessment of Aggression Factors, State-Trait Anger Expression Inventory, Ways of Coping Checklist). Several differences distinguished the two groups, namely, in personality traits such as anxiety or coping strategies and sociodemographics (e.g., education level). Personality traits, psychopathological characteristics, and sociodemographic factors are useful tools for assessing suicidal risk. Our findings encourage us to suggest that clinicians pay particular attention to sociodemographic variables such as separation/divorce and a lower education level when conducting risk assessments on suicidal patients.
Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.
Victims of child abuse may be at increased risk of acting on suicide ideation, although this has not been empirically tested. We estimated the risk of suicide attempts associated with child abuse among individuals who reported suicide ideation. Secondary analysis of data from the population-based Canadian Community Health Survey Mental Health (n = 828). This population-based survey included various structured questionnaires, including the Composite International Diagnostic Interview to assess mental illness and suicidal thoughts and behaviours. Approximately 80 % of those who attempted suicide had a history of child abuse. Poor mental health, financial difficulties, poor coping skills, and reporting a suicide plan were also associated with an increased prevalence of attempting suicide; adjusted for these factors, child abuse was associated with a 1.77-fold increased prevalence (95 % CI 0.93, 3.36) of suicide attempts. Most individuals who attempt suicide experience child abuse, and worse health and social functioning. Adopting a life-course perspective to understand trajectories of suicide risk factors may inform prevention and treatment.
Background: All types of abuse and neglect have been associated with suicide attempts. However, the association between the level of each type of childhood trauma and suicidal behavior severity (including the progression from ideation to attempts), adjusting for their co-occurrence, is not yet clear. Methods: We used a cross-sectional web-based survey collected from the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP) to investigate the isolated effects of each type of childhood trauma on suicidal behavior severity. The sample consisted of 71,429 self-selected volunteers assessed with the Childhood Trauma Questionnaire (CTQ) and the following key question: "Have you ever thought about or attempted to kill yourself?'' (Suicidal Behavior Questionnaire, SBQ-17). Results: After adjusting for demographic variables, and childhood trauma subtypes, severe emotional abuse (EA) was associated with suicidal ideation and attempts, mainly for serious suicide attempts (OR, 22.71; 95% CI, 2.32-222.05). We found associations of smaller magnitude for severe emotional neglect (EN) with serious suicide attempts, and for severe physical neglect (PN) and sexual abuse (SA) with attempts without really meaning to die. No meaningful trend for physical abuse (PA) was found. Using as reference group ideators, EA was associated with serious suicide attempts, with a peak at the 95th percentile (OR, 4.39; 95% CI, 2.04-9.41). We found associations of smaller magnitude for PN and SA, and no meaningful trend for EN and PA. Conclusions: Suicidal behavior was strongly associated with emotional abuse in childhood, even when compared with ideators, suggesting that it is a relevant factor for the progression from ideation to attempts. (C) 2016 Elsevier Masson SAS. All rights reserved.
The objective of the present research was to examine the association between lifetime cannabis use disorder (CUD), current suicidal ideation, and lifetime history of suicide attempts in a large and diverse sample of Iraq/Afghanistan-era veterans (N = 3233) using a battery of well-validated instruments. As expected, CUD was associated with both current suicidal ideation (OR = 1.683, p = 0.008) and lifetime suicide attempts (OR = 2.306, p < 0.0001), even after accounting for the effects of sex, posttraumatic stress disorder, depression, alcohol use disorder, non-cannabis drug use disorder, history of childhood sexual abuse, and combat exposure. Thus, the findings from the present study suggest that CUD may be a unique predictor of suicide attempts among Iraq/Afghanistan-era veterans; however, a significant limitation of the present study was its cross-sectional design. Prospective research aimed at understanding the complex relationship between CUD, mental health problems, and suicidal behavior among veterans is clearly needed at the present time. Published by Elsevier Ltd.
This study investigated whether the use of thought control strategies specific to suicidal thoughts influenced suicide ideation and suicide risk in a sample of adult students (N = 135) who were selectively recruited after endorsing a history of suicide ideation on a pre-screen assessment. An adapted version of the Thought Control Questionnaire (TCQ; Wells & Davies, 1994) specific to controlling thoughts of suicide was employed to assess whether participants responded to thoughts of suicide with worry, self-punishment, reappraisal, concealment, and distraction. The suicide-specific thought control questionnaire demonstrated a reliable factor structure similar to the original measure. Results indicated that distraction from suicidal thoughts was negatively correlated with suicide ideation and risk, whereas self-punishment for having these thoughts and worrying about other thoughts were positively correlated with suicide ideation and suicide risk. Clinical implications and future research directions are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Brassica napus was grown under hydroponic conditions and responses to the removal of the external supply of sulfur (S) were analysed in roots and in leaves of different developmental age. The concentrations of sulfate and nitrate were greatest in the older leaves and least in younger leaves, whilst phosphate was greatest in roots and youngest leaves and least in old leaves. S-deprivation resulted in decreases in tissue sulfate concentrations at variable rates in the order: roots and young leaves >middle-aged leaves >oldest leaves. Phosphate concentrations were unaffected and nitrate concentrations were only depleted in the oldest leaves. Expression of representative members of the sulfate transporter gene family was assessed by Northern blotting in the respective tissues. Group 1 transporters (high affinity type) were induced in response to S-deprivation in all tissues except old leaves, where no expression was detected, and to the greatest extent in roots. Groups 2 and 5 (a Brassica Group 5 sulfate transporter is reported here, accession number: A]311389) transporters showed either no or only a small induction by S-deprivation. Group 4 transporters (localised in the tonoplast membrane and thought to be involved in vacuolar sulfate efflux) were induced by S-deprivation with a complex pattern: 4;1 was expressed in root and mature leaves, was strongly induced by sulfur-deprivation in roots, and was also induced in the middle-aged leaves alone; 4;2 was only expressed under S-deprivation in parallel with the observed pattern of tissue sulfate concentrations. Expression patterns indicated that both differences in intracellular sulfate pools and localised aspects of the signal transduction pathway link tissue sulfate-status and sulfur-nutrition regulated gene expression.
Biological denitrification typically requires the addition of a supplemental electron donor, which can add a significant operating expense to wastewater treatment facilities. Most common electron donors are organic, but reduced inorganic sulfur compounds (RISCs), such as sulfide (HS-) and elemental sulfur (S-0), may be more cost-effective. S-0 is an inexpensive and well characterized electron donor, but it provides slow denitrification rates due to its low solubility. A lesser-known RISC is sulfite (), which can be easily produced from S-0 by a simple combustion process. Unlike S-0, is highly soluble, and therefore may provide higher denitrification rates. However, very little is known about microbial denitrification with . Also, is a strong reductant that reacts abiotically with oxygen and has toxic effects on microorganisms. This paper reviews in the environment, chemistry, microbiology, toxicity, and its potential use for denitrification. Since is an intermediate in the sulfur oxidation pathway of most sulfur-oxidizing microorganisms, it is an energetic electron donor and it should select for a -oxidizing community. Our review of the literature, as well as our own lab experience, suggests that can effectively serve as an electron donor for denitrification. Further research is needed to determine the kinetics of -based denitrification, its toxic threshold for sulfur-oxidizing microorganisms, and its potential inhibition of sensitive species such as nitrifying microorganisms and potential formation of nitrous oxide. Its effect on sludge settling efficiency also should be explored.
The corrosion and odor caused by hydrogen sulfide formation are serious problems in sewer operations, and the cost to prevent these problems is high. Understanding the sulfur cycle mechanism and controlling the sulfur cycle in sediment biofilm are essential to solve these problems. In this review, the reaction mechanisms of the sulfur cycle in sediment biofilm in sewer systems revealed by using in situ microelectrode measurements and molecular biological technologies are summarized. The results indicated that the profile of the reaction process of the sulfur cycle in sediment biofilm was primarily affected by the substrate concentration change in the liquid phase and the various substrate penetrations in sediment biofilm. The biological community's distribution and shifting of sulfate reduction bacteria and sulfide oxidation bacteria across the sediment biofilm were in response to the substrate change of the microenvironment in sediment biofilm. The influence of flow fluctuation on the profile of the sulfur cycle in the sediment biofilm of field sewers, the advantageous biological techniques of pyrosequencing and metagenome analyses combined with novel in situ microelectrode measurements, and the new concept model-related control technology of the sulfur cycle in sediment biofilm should be promoted in future studies.
In grapevine, berry growth after veraison is paralleled by a notable intake of water and sugar. Our results show that in 'Sultanina', a seedless variety, this intake is significantly improved by gibberellic acid (GA(3)), which is normally sprayed to get a commercial berry size. As at this stage the pedicel xylem functionality is lost, it is presumed that water transport occurs via the phloem. This implies a possible role of water channels in cell membranes (aquaporins). Two complementary approaches were used to evaluate the effect of GA(3) on the expression of aquaporin genes. In the first one, PIP and TIP probes derived from 'Sultanina' cloned amplicons and ESTs were used for Northern blotting. Results from these experiments showed that there was not a uniform type of response, with some genes exhibiting a more intense expression at early developmental stages than at veraison, and others showing a lower expression difference. In second place, we confirmed a possible role for GA controlling PIP/TIP gene expression, but again, the results were quite diverse in terms of timing and level of response to the hormonal treatment. In spite of this diversity, a tendency to maintain a higher expression level during post-veraison in GA(3)-treated plants was observed. Microarray hybridizations showed a heterogeneous response to GA-treatment for different genes of the aquaporin family. However, these last experiments must be considered preliminary, both because of technical issues, mainly the requirement of a better reproducibility level, and because of pre-veraison being the developmental stage when one of the lowest levels of aquaporin genes expression was observed.
Impedance spectroscopy is a powerful tool to study the frequency behavior of supercapacitors, but it comes with pricy hardware and postprocessing routines. Here we present a non-impedance method to extract the fractional-order model parameters (R-s, C-alpha, alpha) of a supercapacitor-assumed to be equivalent to a series association of a resistance with a constant phase element-using the magnitude response of a measurement circuit consisting of a large bandwidth operational amplifier with negative feedback. The theory behind the measurement circuit, along with the extraction method of the model parameters, and validation within 1% error using simulated and experimental results from a commercial supercapacitor are presented and discussed.
A test campaign was launched to determine the mechanical properties of the High Luminosity-Large Hadron Collider (HL-LHC) 11 T Nb3Sn magnet components. The results can be used to accurately represent the mechanical properties in finite element models that predict the stress and strain distribution in these magnets. Particular attention is paid to anisotropic mechanical behavior of the different magnet materials. Static and dynamic test methods have been applied for determining elastic materials' behavior, and highly accurate Young's moduli are obtained with the nondestructive dynamic methods resonance and impulse excitation at ambient temperature and during in situ heat cycles.
We constructed a 36-channel magnetocardiography (MCG) system based on low-T-c direct current (DC) superconducting quantum interference device (SQUID) magnetometers operated inside a magnetically shielded room (MSR). Weakly damped SQUID magnetometers with large Steward-McCumber parameter beta(c) (beta(c) approximate to 5), which could directly connect to the operational amplifier without any additional feedback circuit, were used to simplify the readout electronics. With a flux-to-voltage transfer coefficient partial derivative V/partial derivative phi larger than 420 mu V/phi(0), the SQUID magnetometers had a white noise level of about 5.5 fT.Hz(-1/2) when operated in MSR. 36 sensing magnetometers and 15 reference magnetometers were employed to realize software gradiometer configurations. The coverage area of the 36 sensing magnetometers is 210 x 210 mm(2). MCG measurements with a high signal-to-noise ratio of 40 dB were done successfully using the developed system.
In spite of excellent properties of supercritical CO2 in enzyme catalyzed reactions, destabilizing effects of CO2 molecules on the enzyme structure limits the industrial applications of this green solvent in the field of biocatalysis. Here, based on the substantial role of charged surface residues such as lysines in enzyme inactivation, we introduced for the first time, Post Translational Modifications (PTMs), a famous concept in molecular biology, as a protein stabilization strategy in supercritical condition. Lysine groups were modified using PTM templates to find out more about the exact mechanism of enzyme inactivation in supercritical CO2 and to explore a new way for protein stabilization in this solvent. We used MD simulation as common tool for in situ examining enzyme structure in supercritical fluids, for the investigation of structural consequence of modifications. Different modifications including acetylation, methylation, phosphorylation, and carboxylation have been applied on the model enzyme. For comparison to CALB structure in supercritical CO2, the acetylated enzyme was also simulated in aqueous solvent at 300 and 353 K. Interestingly, acetylation of lysine residues prevents enzyme from denaturation at high temperatures in water, which is in agreement with experimental observation in aqueous solution. However, acetylation is not so useful for stabilization of enzyme in supercritical CO2. In contrast, methylation and carboxylation efficiently stabilize enzyme in supercritical CO2. Phosphate groups in phosphorylated lysines destabilize enzyme by formation of excess hydrogen bonds by inappropriate groups and perturb enzyme conformation. Moreover, it was found that modification of surface arginine residues was not so satisfactory in stabilization of the enzyme. This finding supports the mechanism of lipase inactivation through direct interaction of CO2 molecules on lysine residues and formation of carbamates. We think this new exploration can open new window for developing enzyme catalyzed mechanism of enzyme inactivation in scCO(2). (C) 2016 Elsevier B.V. All rights reserved.
Induction of metallothioneins (MTs) through the metal-activated transcription factor-1 (MTF-1) provides a model response for analyzing transcriptional gene regulation by heavy metals. Here, we report inhibition of protein synthesis by cycloheximide (CHX) increases induction of Mt1 by approximately five-fold, a phenomenon designated as "superinduction." Characterization of superinduction revealed it is time- and concentration-dependent of CHX, requires the presence of an MTF-1 activator, and occurs at a transcriptional level, suggesting a labile repressor in the control of Mt1 induction. Genetic analyses using Mtf1. null cells and a metal response element (MRE)-driven reporter construct showed that superinduction of Mt1 is mediated through MTF-1 and MRE-dependent transcription. Analyses of intracellular zinc content by inductively coupled plasma emission spectroscopy and fluorescence imaging demonstrated that treatment with CHX alone or CHX plus an inducer does not increase the total zinc accumulation or the concentration of free zinc in cells under the conditions in which superinduction occurs. Moreover, superinduction was observed in cells cultured in a zinc-depleted medium, suggesting that superinduction does not involve elevation of intracellular zinc concentration. Northern blotting showed that Cd, CHX, or Cd + CHX does not affect the expression of the mRNA of MTF-1. Immunoblotting using antibodies specific for MTF-1 demonstrated that Cd induces a down-regulation of the MTF-1 protein, whereas cotreatment with Cd and CHX blocked the Cd-induced degradation of MTF-1. The findings reveal a new mechanistic aspect of the superinduction of Mt1, in which a labile repressor negatively controls agonist-induced turnover of the MTF-1 protein. (c) 2006 Wiley Periodicals, Inc.
In this paper, we propose an efficient method for salient region detection. First, the image is decomposed by using superpixel segmentation which groups similar pixels and generates compact regions. Based upon the generated superpixels, similarity between the regions is calculated by benefiting from color, location, histogram, intensity, and area information of each region as well as community identification via complex networks theory in the over-segmented image. Then, contrast, distribution and complex networks based saliency maps are generated by using the mentioned features. These saliency maps are used to create a final saliency map. The applicability, effectiveness and consistency of the proposed approach are illustrated by conducting some experiments using publicly available datasets. The tests have been used to compare the proposed method with some state-of-the-art methods. The reported results cover qualitative and quantitative assessments which demonstrate that our approach outputs high quality saliency maps and mostly achieves the highest precision rate compared to the other methods.
We demonstrate that the notion of a family 'constitution' (self-enforcing, renegotiation-proof norm) requiring adults to provide attention for their elderly parents carries over from a world where identical individuals reproduce asexually, to one where individuals differentiated by sex and preferences marry, have children and bargain over the allocation of domestic resources. In this heterogenous world, couples are sorted by their preferences. If a couple's common preferences satisfy a certain condition, the couple have an interest in instilling those preferences into their children. Policies are generally nonneutral. In particular, wage redistribution may raise, and compulsory education will reduce, the share of the adult population that is governed by family constitutions, and thus the share of the elderly population who receive attention from their children.
Background: Suppressor of cytokine signaling (SOCS) 1 and 3 methylation have been associated with clinical features and outcomes of cancer patients. However, their roles in determining the treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) remain unknown. Results: We found that presence of SOCS3 methylation is significantly associated with the major clinical features of HCC patients, including tumor stage, lymph node and vascular invasion. Of note, we observed that the presence of SOCS3 methylation is closely related to TACE response. In prognosis analyses, HCC patients with SOCS3 methylation presence have a poorer prognosis indicated by lower 3-, and 5-year survival rates and shorter mean survival period, than those without. Multivariate COX analysis confirms the prognostic role of the presence of SOCS3 methylation in HCC patients receiving TACE treatment. Materials and Methods: A total of 246 HCC patients receiving TACE were enrolled in this study. Tumor samples was obtained from echo-guided fine needle aspiration and genomic DNA from tumor samples was purified. SOCS1 and SOCS3 methylation status were detected using methylation-specific polymerase chain reaction. The treatment responses to TACE of patients were evaluated after procedure and all patients were followed for prognosis analysis. Conclusions: This finding suggests that the presence of SOCS3 methylation is a marker to predict treatment response and prognosis in HCC patients receiving TACE therapy.
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine. (C) 2017 Elsevier Ltd. All rights reserved.
Recently, relationship between fracture surface roughness and material's strength has received too much attention in literature. In this paper, 2D image is used as a novel and economic tool to characterize the fracture surface roughness of steel fiber reinforced concrete (SFRC). The main purpose of this study was to investigate the effect of the steel fiber content, V-f, and the concrete design mix on the surface roughness. The direct tensile tests are carried out on dog-bone shape of SFRC's specimens with a constant size. The fracture surface of the specimens is photographed then fracture trajectory as a XY list of pixel numbers are extracted using image analysis (IA) techniques. The fractal dimensions are calculated based on the Box-counting algorithm via a computational code. Finally, to validate the results, they are applied into formulations of "Discrete fractal fracture mechanics" by Wnuk and Yavari published in 2008 [11]. Accordingly, an estimation for ratio of quantum fracture step to maximum void's size is given to describe the relationship between design strength f(d) and the fracture roughness. Also, steel fiber effect on formation of surface trajectory is discussed according to image analysis results. Correlation matrix of all significant parameters in this study is presented. It is concluded that 2D image analysis is a very economic and accessible method for surface roughness characterization. (C) 2017 Elsevier Ltd. All rights reserved.
Despite the significant attention gained by the three-dimensional (3D) printing technology in many research fields, it has not yet found application in tyre-road friction and pavement engineering. To better understand the impact of different roughness length scales on rubber friction, the feasibility of utilising 3D printing for replicating pavement texture and the strength of this technology in creating customised roughness patterns are investigated. An image-stitching algorithm was developed for a common portable optical profiler in order to obtain a large topography of an asphalt specimen for friction experiments. The printed topography showed a replication efficacy down to 0.5mm in wavelength. Printed samples with artificial surface patterns were then generated by random process theory and fractal modelling. Rubber sliding tests implied different frictional behaviour between the asphalt specimen and its printed replica, which was mainly attributed to severe wear of rubber on rougher asphalt specimen. For artificial geometries, friction increased as the Hurst exponent (H) increased. Results also suggested that reducing roll-off wavevector (q(0)), that is, increasing maximum aggregate size, reduces friction coefficient of a fractal surface.
The dynamics of child abuse have been recognised as a global emerging social issue which is highly associated with child humiliation. The Government of Pakistan has taken many initiatives for addressing issues regarding child abuse and neglect and has designed laws to protect children against exploitation, abuse and violence; however, most of them are not enforced at all or poorly implemented due to lack of proper definition of child abuse and related terms, and different ways of reporting child abuse cases. Most of the non-governmental organisations (NGOs) in Pakistan target extreme cases of child sexual abuse such as child rape or commercial sexual exploitation of children, but cases of physical and psychological abuse are under-reported by the NGOs most of the time. A proper surveillance system is therefore required to identify the hidden cases of all types of child abuse that can lead to effective policy formulation and implementation.
At present, survivin is one of the most cancer-specific proteins that has been identified. The present study aimed to investigate the antitumor effects of novel survivin small interfering RNA (siRNA) nanoliposomes targeting survivin in human hepatocellular carcinoma MHCC-97H cells and xenograft mouse models. Survivin-targeted siRNA nanoliposomes were prepared and transfected into MHCC-97H cells and MHCC-97H-bearing nude mice. Survivin expression was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell viability was analyzed using an MTT assay and apoptosis was evaluated using Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide staining. Tumor growth in MHCC-97H-bearing mice was monitored following treatment and tumor samples were obtained for survivin expression analysis using RT-qPCR, western blotting and immunohistochemistry staining. Survivin expression levels were significantly down-regulated by nanoliposome-mediated survivin siRNA delivery and this was associated with a significant inhibition of cell growth and an increase in the apoptosis of MHCC-97H cells. Downregulation of survivin expression using survivin siRNA nanoliposomes inhibited tumor growth in the MHCC-97H xenograft models without significant treatment-associated toxicity. Therefore, a cationic nanoliposome-based survivin siRNA delivery system was constructed and demonstrated to be efficient for survivin siRNA delivery in in vitro and in vivo studies. These results demonstrate that survivin downregulation was able to significantly attenuate cell proliferation and induce the apoptosis of MHCC-97H cells, as well as inhibit tumor cell growth in MHCC-97H xenograft models, indicating that survivin suppression using siRNA may contribute to the inhibition of tumor development by suppressing cell proliferation and promoting apoptosis.
Biogas has been earmarked as an efficient way to promote economic development and mitigate environmental emissions, and it requires a better accounting framework to evaluate its performance. In this study, we aim to develop an emergy-based accounting framework to assess and report the sustainability performance of biogas projects. First, the existing financial accounting and environmental accounting methodologies are combined to measure and report the economic events and environmental characteristics of a biogas project. Then, using the new metric of Emdollar value, the cost and revenue flows within the system boundary are unified and quantified by multiplying specific emergy transformity to reflect their embodiment and hierarchical characteristics. An integrated accounting framework covering economic aspects (economic profitability, economic efficiency, operation risk), environmental aspects (environmental resource utilization, load, emissions) and environmental-economic composited characteristics (emissions reduction efficiency, Emdollar intensity of emission reduction, emission intensity of profit) is set up accordingly. Results show that the biogas project has a positive net present value of 1.64E+04 Emdollars. The total cost can be returned after 5 years. The renewability ratio, environmental load ratio (ELR), and composite sustainability indicator (CSI) reflecting environmental load are 9%, 10.1, and 0.76, respectively. The proposed sustainability accounting framework may unveil the real environmental support and assess the ecological economic performance of a biogas project. (C) 2016 Elsevier Ltd. All rights reserved.
Ammonia is one of the most produced chemicals worldwide and is currently synthesized using nitrogen separated from air and hydrogen from natural gas reforming with consequent high consumption of fossil fuel and high emission of CO2. A renewable path for ammonia production is desirable considering the potential development of ammonia as energy carrier. This study reports design and analysis of an innovative system for the production of green ammonia using electricity from renewable energy sources. This concept couples Solid Oxide Electrolysis (SOE), for the production of hydrogen, with an improved Haber Bosch Reactor (HBR), for ammonia synthesis. An air separator is also introduced to supply pure nitrogen. SOE operates with extremely high efficiency recovering high temperature heat from the Haber-Bosch reactor. Aspen was used to develop a model to study the performance of the plant. Both the SOE and the HBR operate at 650 degrees C. Ammonia production with zero emission of CO2 can be obtained with a reduction of 40% of power input compared to equivalent plants. (C) 2016 Elsevier Ltd. All rights reserved.
Swine vesicular disease (SVD) was first observed in Italy in 1966, where it was clinically recognised as foot-and-mouth disease (FMD). SVD virus (SVDV) was subsequently isolated in an FMD vaccine trial in Hong Kong. At the beginning of the 1970s, it spread to several other European and Asian countries: Bulgaria, Austria, Italy, Great Britain, Poland, former Soviet Union (Ukraine), Romania, France, Germany, Belgium, Switzerland, the Netherlands and Japan, and lasted until the beginning of the 1980s. After that period, SVD outbreaks were sporadic. The disease was almost forgotten until it flamed up again in 1992 in the Netherlands. Once again it spread to several other European countries, such as Belgium, Spain, Portugal and Italy. Since 1995, SVD has been reported in Europe almost exclusively in Italy, except two isolated outbreaks in Portugal. Since the last two SVD outbreaks in 2014 in the Potenza province (Basilicata region), no new SVD outbreaks have been reported either in Italy or in any other European country. The clinical resemblance of SVD to FMD highlights the need for its reliable identification and discrimination. Differentiation from FMD, though not possible clinically, is feasible if appropriate diagnostic tests are applied. Improvements in diagnostic techniques are making differential diagnosis of vesicular disease increasingly affordable, feasible and easy, and nowadays, portable devices are capable of a rapid and accurate differentiation of SVDV from FMDV infections on site. As these tests become economical and as competent laboratory services become more and more accessible, the restrictions originally imposed on SVD because of its similarity to FMD will no longer be justified. This, together with the fact that in recent years SVD has been predominantly asymptomatic, makes it necessary to rethink the measures currently in place for the control and diagnosis of SVD. Therefore, by the decision of OIE, the SVD chapter was removed from the Terrestrial Code in January 2015. Consequently, the European Commission (EC) informed the Pirbright Institute that the EU Reference Laboratory for SVD would no longer receive financial support. Moreover, the EC position is that notification requirements have ceased in January 2015.
Transient gene expression in plant protoplasts is a powerful tool for analyzing gene function and for performing biotechnical manipulations. Here we-report the isolation of viable protoplastsfrom the fruit flesh of sweet cherry (Prunus avium L.) cv. Hong Deng and their polyethylene glycol (PEG)-mediated transient transfection using green fluorescent protein (GFP) as a marker gene. We investigated the main factors affecting the efficacy of protoplast isolation and transfection, including the composition of the enzymolysis solution, enzymolysis time, pH of the enzymolysis solution, PEG concentration, and transfection time. Protoplast isolation was optimal when the tissue was incubated in enzymolysis solution composed of 1.0% Cellulase R-10, 0.5% Pectolase Y-23, and 0.6 M mannitol (pH 5.8) for 18 h, resulting in a protoplast yield of 4.3 x 10(6) protoplasts/g fresh weight [FW] and viability of 84.1%. Protoplast transformation efficiency was measured by transient expression of the GFP reporter gene, and transformation efficiency was highest when protoplasts were incubated in transfection medium containing 40% PEG for 15 min. Collectively, this work describes an efficient protoplast isolation and protoplast transient expression system that can be used to facilitate molecular biology research in sweet cherry. (C) 2016 Elsevier B.V. All rights reserved.
Sweetpotatoes are important food crops with high starch and high carotene content. However, studies concerning the molecular biology of these crops are limited. In this paper, we selected two varieties of sweetpotato (Zhengshu 20 and Luoxushu 8) for transcriptome analysis. De novo RNA sequencing of these sweetpotatoes (tuberous roots, stems and leaves) under field conditions was performed using an Illumina Hiseq 2500 platform with PE125. Approximately 34.4 G nucleotide bases were sequenced. Following assembly, 176,167 transcripts and 109,401 unigenes were identified. 41,729 (Nr), 21,004 (Nt), 12,524 (KO), 29,444 (SwissProt), 30,212 (PFAM), 31,304 (GO), and 14,349 (KOG) unigenes were functionally annotated using different databases, and a total of 47,749 annotated sequences were identified. Simple sequence repeats (SSRs) analyses revealed 9549 SSR loci on the 8334 unigenes. The KEGG analysis uncovered 55 and 78 unigenes involved in the carotenoid and terpe-noid backbone biosynthesis pathways, respectively. Among these genes, 20 and 10 differentially expressed unigenes were observed in the Zhengshu 20 and Luoxushu 8, respectively. Eight differentially expressed unigenes were validated by qRT-PCR. Thus, we prepared and analyzed the transcriptome data of the two sweetpotato varieties, for which prior genomic information was limited. This new sequence information will improve the current knowledge in this important and healthy crop and provide valuable insight for further biological research. (C) 2017 SAAB. Published by Elsevier B.V. All rights reserved.
Objective: To examine the effects of feeding Bacillus subtilis C-3102 at the target inclusion rates of 0 colony forming units (CFU) per g, 500,000 CFU per g, and 1 million CFU per g on intestinal health in weaned pigs after challenge with porcine epidemic diarrhea virus (PEDV). Materials and methods: A two-by-three factorial design was conducted, composed of three experimental diets and PEDV or sham challenge. Sixty 14-day-old pigs, negative for PEDV by quantitative real-time reverse transcription polymerase chain reaction (PCR) and negative by PCR for porcine reproductive and respiratory syndrome virus, were randomly allocated into six treatment groups with 10 pigs per group. Pigs were housed in groups of five in solid-floor pens. Treatment diets were fed for a total of 23 days, including 19 days before and 4 days after PEDV challenge or sham challenge by oral gavage. Results: Pathological changes associated with PEDV were significantly less severe in challenged treatment groups that received B subtilis C-3102 than in the group that received no B subtilis treatment. There were no significant differences in small intestinal length, ratio of small intestinal weight to body weight, colon dry matter content, average daily gain, or fecal scoring between any of the six treatment groups.
A high-speed folded-cascode OP amplifier with a dynamic switching bias circuit, which enables low power consumption, high gain stably, and a relatively wide dynamic range in low power supply voltages, is proposed. Through simulations, it was shown that the OP amplifier is able to operate at a 10 MHz dynamic switching rate and a dissipated power of 71 % of that observed in continuous operation. It also showed an open loop gain of 51 dB and a 0.996 V output dynamic range which is wider than that in a telescopic OP amplifier. The 10 MHz high-speed switching operation, allowing processing video signals, was confirmed by applying to a switched capacitor non-inverting amplifier with a gain of below 2. The simulation results showed that the output inaccuracy for a switched capacitor amplifier with a gain of below 2 is below 1.5 %, which is practicable. This inaccuracy was caused by the static nonlinearity of the OP amplifier, determined on its limited open loop gain.
The operation principle of digital voltage-mode controlled buck converter with dual-edge modulation is analyzed in this paper. Based on the state equation of buck converter and six possible evolutions in one switching cycle, the discrete iterative-map model of digital voltage-mode controlled buck converter with dual-edge modulation is established. Ignoring the quantization error of analog-digital converter and on the basis of its discrete iterative-map model, the nonlinear dynamical behavior of digital voltage-mode controlled buck converter with dual-edge modulation is investigated in detail. Taking the input voltage and the load resistance as bifurcation parameters, the output voltage bifurcation diagram and the inductor current bifurcation diagram are plotted. Through analyzing the bifurcation diagrams, it is indicated that there are two kinds of similar but different Hopf bifurcation phenomena. By use of Poincare section, time-domain simulation waveforms and phase portraits, two different Hopf bifurcations and low-frequency oscillation phenomena are compared and studied. Observing the inductor current and capacitor voltage waveforms respectively, it is obviously found that their oscillation frequencies and amplitudes are different, the shapes of two Poincare sections and phase portraits are also different. In order to verify the correctness of the simulation and theoretical analysis, the eigenvalues of Jacobian matrix of the discrete iterative map model are introduced and solved in two kinds of stable evolutions. Through analyzing variation of eigenvalues of Jacobi matrix with input voltage, the existence and difference of two kinds of Hopf bifurcation phenomena are proved theoretically. Moreover, it is observed in this paper that the odd period-doubling bifurcation phenomenon exists in digital voltage-mode controlled buck converter with dual-edge modulation for the first time, where the operation state of the buck converter turns from period-one into period-three. Its authenticity is verified by using the time-domain simulation waveforms and phase portraits. In order to approach to the actual circuit, the equivalent series resistances of capacitor and inductor are considered. The actual circuit is simulated by using the software Psim. A comparison shows that there are little differences between the theoretical simulation and the actual circuit simulation. So the theoretical simulation can be used to analyze the performances of the actual circuit. The research results in this paper have guiding significance and practical value for designing the digital voltage-mode controlled buck converter with dual-edge modulation.
With the development of science and technology, the demand for high quality power supply electrical equipment increasing application of analog circuit Control Research and Application Development of power for many years already, but it still has many shortcomings. FPGA as a highly integrated, economical, high speed, low power consumption, it is easy to develop and maintain a significant advantage (upgrades) and the like. And faster, more integrated, more versatile, and other advantages, stand out from the MCU and DSP integrated circuits, etc., become the research and application in the field of power electronics control hot spots. Briefly introduces the basic theory of digital systems, we analyze the structure model of digital systems. There is an overview of the design method of digital control system, the completion of the selected device selection and related development environment and tools. This paper proposes all-digital power control scheme of special surface treatment, and the completion of the controller hardware and software design and implementation.
Most, if not all, animals engage in associations with bacterial symbionts. Understanding the mechanisms by which host immune systems and beneficial bacteria communicate is a fundamental question in the fields of immunology and symbiosis. The Hawaiian bobtail squid (Euprymna scolopes) engages in two known symbioses; a binary relationship with the light organ symbiont Vibrio fischeri, and a bacterial consortium within a specialized organ of the female reproductive system, the accessory nidamental gland (ANG). E. scolopes has a well-developed circulatory system that allows immune cells (hemocytes) to migrate into tissues, including the light organ and ANG. In the association with V. fischeri, hemocytes are thought to have a number of roles in the management of symbiosis, including the recognition of non-symbiotic bacteria and the contribution of chitin as a nutrient source for V. fischeri. Hemocytes are hypothesized to recognize bacteria through interactions between pattern recognition receptors and microbe-associated molecular patterns. Colonization by V. fischeri has been shown to affect the bacteria-binding behavior, gene expression, and proteome of hemocytes, indicating that the symbiont can modulate host immune function. In the ANG, hemocytes have also been observed interacting with the residing bacterial community. As a model host, E. scolopes offers a unique opportunity to study how the innate immune system interacts with both a binary and consortial symbiosis. This mini review will recapitulate what is known about the role of hemocytes in the light organ association and offer future directions for understanding how these immune cells interact with multiple types of symbioses.
The world runs on networks over which signals communicate sequences of symbols, e.g. numerals. Examining both engineered and natural communications networks reveals an unsuspected order that depends on contact with an unpredictable entity. This order has three roots. The first is a proof within quantum theory that no evidence can ever determine its explanation, so that an agent choosing an explanation must do so unpredictably. The second root is the showing that clocks that step computers do not "tell time" but serve as self-adjusting symbol-handling agents that regulate "logically synchronized" motion in response to unpredictable disturbances. Such a clock-agent has a certain independence as well as the capacity to communicate via unpredictable symbols with other clock-agents and to adjust its own tick rate in response to that communication. The third root is the noticing of unpredictable symbol exchange in natural systems, including the transmission of symbols found in molecular biology. We introduce a symbol-handling agent as a role played in some cases by a person, for example a physicist who chooses an explanation of given experimental outcomes, and in other cases by some other biological entity, and in still other cases by an inanimate device, such as a computer-based detector used in physical measurements. While we forbear to try to explain the propensity of agents at all levels from cells to civilizations to form and operate networks of logically synchronized symbol-handling agents, we point to this propensity as an overlooked cosmic order, an order structured by the unpredictability ensuing from the proof. Appreciating the cosmic order leads to a conception of agency that replaces volition by unpredictability and reconceives the notion of objectivity in a way that makes a place for agency in the world as described by physics. Some specific implications for physics are outlined. (C) 2016 Elsevier Inc. All rights reserved.
Background: Impeccable assessment of symptoms is central to palliative care (PC) practice. Objectives: The study objectives are (1) to test the validity of the Arabic Questionnaire for Symptom Assessment (AQSA) as a self-administered (SA) tool for assessing the severity of the listed symptoms among PC patients and (2) to test the validity of AQSA when completed by a proxy. Methods: The AQSA is a tool for assessing the severity of 11 symptoms in addition to the overall suffering experience on a 0 to 10 numeric scale. Symptom scores on the SA AQSA were compared to scores obtained through interviews with patients. The same procedure was repeated with patients' sitters to explore the validity of using the tool for symptom assessment by proxy. Results: The study involved 107 pairs (a patient and a sitter, each) with a mean age of 46.3 years (females 59.8%) for patients and 35.9 years (females 65.7%) for sitters. The correlation coefficient (r) for agreement between SA and interview-based (IB) scores for patients ranged from .65 (P < .0001) for drowsiness to .86 (P < .0001) for pain. The SA AQSA showed positive correlation between sitters' and patients' scores, with r ranging from .28 (P = .004) for depression to .62 (P .0001) for vomiting. Conclusions: The strong positive correlation between SA and IB AQSA indicates that the former is a valid tool. When the SA AQSA is used by proxy, it showed moderate to strong positive correlation with patients' actual scores for most of the symptoms.
Introduced the basic principle of synchronous rectification in low voltage high current fields. Using digital control's feature in switch power, a design scheme of SR digital Buck converter was put forward and analyzed the device choice. Designed all the circuit of the converter, designed and made a prototype. The experiment data were given including driving waveform and efficiency curve. One-cycle control strategy was made. To extend the using fields of the prototype, designed the intelligence communication interface. By means of experiment, the power supply has fast dynamic response and high precision and its efficiency can reach up to 95%.
In this paper, a novel adaptive synchronous rectification method for digitally controlled LLC converters is proposed. By sensing the synchronous rectifier (SR) body diode forward drop, both the SR turn-on and turn-off edges are optimized for efficiency. Negative current prevention is utilized to improve the system robustness and is enhanced by simple digital control capabilities. Compared with a conventional analog SR control approach, this method achieves higher system efficiency and flexibility. This control method has been implemented in a Texas Instruments digital power controller UCD3138A and a companion gate driver UCD7138 [1][2].
We investigated whether attachment quality is related to infant-mother dyadic patterns in monitoring animated social situations. Sixty 12-month-old infants and their mothers participated in an eye-tracking study in which they watched abstractly depicted distress interactions involving the separation of a baby and a parent character followed by reunion or further separation of the two characters. We measured infants' and their mothers' relative fixation duration to the two characters in the animations. We found that infant attachment disorganization moderated the correspondence between the monitoring patterns of infant-mother dyads during the final part of the animations resulting in reunion or separation. Organized infants and their mothers showed complementary monitoring patterns: the more the mothers focused their attention on the baby character, the more the infants focused their attention on the parent character, and vice versa. Disorganized infant-mother dyads showed the opposite pattern although the correlation was nonsignificant: mothers and their infants focused on the same character. The attachment-related differences in the nature of the synchrony in the attentional processes of infants and their mothers suggest that by 12months the dyads' representations of social situations reflect their shared social-emotional experiences.
This paper presents the synergistic effects in bipolar operational amplifier OP07. The radiation effects are studied by neutron beam, gamma ray, and mixed neutron/gamma ray environments. The characterateristics of the synergistic effects are studied through comparison of different experiment results. The results show that the bipolar operational amplifier OP07 exhibited significant synergistic effects in the mixed neutron and gamma irradiation. The bipolar transistor is identified as the most radiation sensitive unit of the operational amplifier. In this paper, a series of simulations are performed on bipolar transistors in different radiation environments. In the theoretical simulation, the geometric model and calculations based on the Medici toolkit are built to study the radiation effects in bipolar components. The effect of mixed neutron and gamma irradiation is simulated based on the understanding of the underlying mechanisms of radiation effects in bipolar transistors. The simulated results agree well with the experimental data. The results of the experiments and simulation indicate that the radiation effects in the bipolar devices subjected to mixed neutron and gamma environments is not a simple combination of total ionizing dose (TID) effects and displacement damage. The data suggests that the TID effect could enhance the displacement damage. The synergistic effect should not be neglected in complex radiation environments. (C) 2016 Published by Elsevier B.V.
Synthetic biology (or chemical biology) is a growing field to which the chemical synthesis of proteins, particularly enzymes, makes a fundamental contribution. However, the chemical synthesis of catalytically active proteins (enzymes) remains poorly documented because it is difficult to obtain enough material for biochemical experiments. We chose calstabin, a 107-amino-acid proline isomerase, as a model. We synthesized the enzyme using the native chemical ligation approach and obtained several tens of milligrams. The polypeptide was refolded properly, and we characterized its biophysical properties, measured its catalytic activity, and then crystallized it in order to obtain its tridimensional structure after X-ray diffraction. The refolded enzyme was compared to the recombinant, wild-type enzyme. In addition, as a first step of validating the whole process, we incorporated exotic amino acids into the N-terminus. Surprisingly, none of the changes altered the catalytic activities of the corresponding mutants. Using this body of techniques, avenues are now open to further obtain enzymes modified with exotic amino acids in a way that is only barely accessible by molecular biology, obtaining detailed information on the structure-function relationship of enzymes reachable by complete chemical synthesis.
The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. (C) 2016 Elsevier B.V. All rights reserved.
The focus of this work is to model the hydrodeoxygenation process to produce renewable jet fuel and co-products from low-input oilseeds, specifically camelina, carinata (non-edible oil) and used cooking oil (UCO), taking into account the fatty acid compositions by incorporating the stoichiometric hydrodeoxygenation reactions. This methodology provides insight into the effect of feedstock composition and hydrodeoxygenation reactions upon product yields, product distribution, hydrogen consumption and process utilities. The resulting product slates, hydrogen gas and utility demands are specific to each of the camelina, carinata and UCO feedstocks. The yield of kerosene-range alkanes ranged from 53 to 54% of the incoming oil, with 13-14% diesel range alkanes, 13-15% naphtha, and 7-9% liquefied petroleum gas, depending upon the fatty acid composition. The hydrogen consumption rate ranged from 26 to 30 kg per tonne of incoming oil, depending upon the degree of bond unsaturation. Thermal energy demand is 2.8 GJ/tonne oil when processing used cooking oil, versus 5.2 and 5.7 GJ/tonne of oil for carinata and camelina, respectively, owing to the additional energy required for oil extraction. Electricity demand was 73 kWh/tonne oil for UCO, versus 170 and 227 kWh/tonne oil for carinata and camelina. (C) 2017 Elsevier Ltd. All rights reserved.
Background: It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals. Methods: We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNa, IFN gamma, IL-1 beta, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy. Results: A total of 79 HIV-infected [ 44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS. Conclusion: PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals.
The use of a digital architecture in PWM controllers for point-of-load (POL) applications, together with system identification techniques, allows the development of fully automated routines for in-situ system performance optimization where controller parameters are specifically tailored to the application. In this context, this paper proposes a method for performing parametric system identification of digitally controlled power converters using a conventional analog frequency response analyzer (FRA). Nonlinearities intrinsic to the digital loop are taken into account, thus leading to accurate estimation of converter parameters. The proposed method has been verified on a digitally controlled POL with V-in=12V, V-out=1.2V, I-out=10A and f(sw)=400kHz for various bulk capacitor scenarios.
SETTING: Xpert (R) MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, C-T) correlates with the bacillary burden. OBJECTIVE: To investigate the association between Xpert C-T values and smear status through a systematic review and individual-level data meta-analysis. DESIGN: Studies on the association between C-T values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated. RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off C-T values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%C1 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples. CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off C-T values of 27.7 or 31.8 would not replace smear microscopy. How C-T values compare with smear microscopy in predicting infectiousness remains to be seen.
Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. Nolanguage or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.
Child abuse is a global problem, and parents with histories of childhood abuse are at increased risk of abusing their offspring. The objective of this systematic review is to provide a clear overview of the existing literature of randomized controlled trials evaluating the effectiveness of interventions to prevent child abuse. PubMed, PsychINFO, Web of Science, Sociological Abstracts, and CINAHL were systematically searched and expanded by hand search. This review includes all randomized controlled trials (RCTs) of interventions designed to prevent abuse among mothers identified as high-risk. Of the eight studies identified, only three found statistically significant reductions in abuse by any measure, and only two found reductions in incidents reported to child protective services. While much has been written about child abuse in high-risk families, few RCTs have been performed. Only home visitation has a significant evidence base for reducing child abuse, and the findings vary considerably. Also, data from low- and middle-income countries are limited. (C) 2017 The Authors. Published by Elsevier Ltd.
The design of "Lab on a Chip" microfluidic devices is, typically, preceded by a long and costly period of prototyping stages in which the system is gradually refined by an iterative process, involving the manufacturing of a physical prototype and the making of a lot of laboratory experiments. In this scenario, a virtual prototyping framework which allows the emulation of the behavior of the complete system is greatly welcome. This paper presents such a framework and details a virtual prototyping methodology able to soundly handle microfluidic behavior based on SystemC-AMS extensions. The use of these extensions will permit the communication of the developed microfluidic models with external digital or mixed signal devices. This allows the emulation of the whole Lab on a Chip system as it usually includes a digital control and a mixed-signal reading environment. Moreover, as SystemC-AMS is also being extended to cover other physical domains within the CATRENE CA701 project, interactions with these domains will be possible, for example, with electromechanical or optical parts, should they be part of the system. The presented extensions that can manage the modeling of a micro-fluidic system are detailed. Two approaches have been selected: to model the fluid analytically based on the Poiseuille flow theory and to model the fluid numerically following the SPH (Smoothed Particle Hydrodynamics) approach. Both modeling techniques are, by now, encapsulated under the TDF (Timed Data Flow) MoC (Model of Computation) of SystemC-AMS. (C) 2015 Elsevier B.V. All rights reserved.
This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported. (C) 2015 The Author. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license.
Digital Pulse Width Modulation (DPWM) is one of the most elementary parts in Digital Control Systems for the control of the power switch. Hence it has become an integral part of all System on Chips. It has also been broadly acknowledged as the control method in power converters. The principal focus of this paper is the design of FPGA based Digital controller for a DC-DC Buck convertor for SoC. The output voltage of a DC-DC convertor relies on the switching control circuit which is fundamentally an FPGA Digital controller-PWM. VHDL is employed for the coding of the Digital Controller, synthesis has been done using Xilinx XST 14.2, and Behavioral and Timing simulation has been handled by ModelSim. Also a power analysis using the XPower Analyzer is being carried out. After verification of the code, it will be downloaded onto a Spartan 3AN FPGA board.
Advancements in adoptive cell transfer therapy (ACT) has led to the use of T cells engineered with tumor specific T cell receptors, which after rapid expansion can be obtained in sufficient numbers for treating patients. However, due to massive proliferation these cells are close to replicative senescence, exhibit exhausted phenotype, and also display increased susceptibility to activation induced cell death. We have previously shown that tumor reactive T cells undergo caspase-independent cell death upon TCR restimulation with cognate antigen, which involves reactive oxygen species and c-jun N-terminal kinase. Herein, we show that a large fraction of the human melanoma epitope tyrosinase reactive TCR transduced T cells that exhibit effector memory (T-EM) phenotype and undergo programmed necrosis, or necroptosis, upon TCR restimulation. As compared to the T central memory (T-CM) subsets, the T-EM subset displayed an increased expression of genes involved in necroptotic cell death, and a necrotic phenotype upon TCR restimulation as confirmed by electron microscopy. Higher expression of receptor-interacting kinases (RIPK) that mediate necroptosis was also observed in the T-EM fraction. Further, the T-EM cells were rescued from undergoing necroptosis when pretreated with necroptotic inhibitor NecroX2 before TCR restimulation. Importantly, NecroX2 pretreated tumor reactive T cells also exhibited better tumor control and increased in vivo persistence when adoptively-transferred to treat subcutaneously established murine melanoma B16-F10. Thus, it is likely that the outcome of ACT could be vastly improved by interfering with the necroptotic cell death pathway in activated tumor reactive T cells used in immunotherapy.
Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Toll-inducing Toll-like receptor (TLR) agonists in vivo. In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection.
The immune response is determined by the speed of the T cell reaction to antigens assured by a state of readiness for proliferation and cytokine secretion. Proliferation, apoptosis and motion of many cell types are controlled by cytoplasmic proteases - mu- and m-calpain - and their inhibitor calpastatin, together forming the "calpain-calpastatin system" (CCS), assumed to modify their targets only upon activation-dependent cytoplasmic Ca2+ increase. Contrastingly to this notion, using quantitative real time PCR and semiquantitative flow cytometry respectively, we show here that the CCS genes are constitutively expressed, and that both calpains are constitutively active in resting, circulating human CD4(+) and CD8(+) lymphocytes. Furthermore, we demonstrate that calpain inhibition in the resting T cells prevents them from proliferation in vitro and greatly reduces secretion of multiple cytokines. The mechanistic reason for these effects of calpain inhibition on T cell functions might be the demonstrated significant reduction of the expression of active (phosphorylated) upstream signalling molecules, including the phospholipase C gamma, p56Lck and NF kappa B, in the inhibitor-treated cells. Thus, we propose that the constitutive, self-regulatory calpain-calpastatin system activity in resting human T cells is a necessary, controlling element of their readiness for complex and effective response to antigenic challenge.
Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.
Immunity represents an important defense mechanism against pathogens and is intimately linked to fitness. Previous studies have found significant interindividual variation of immune responses in wild populations and have emphasized the importance of ecological factors in explaining this variability. A deterioration of environmental conditions, such as agricultural intensification, can modify resource availability and, as a result, alter immune functions. The aim of this study was to investigate the effect of agricultural intensification on innate immune functions in breeding adult tree swallows (Tachycineta bicolor) over 6 yr. We investigated the relationship between agricultural intensification and bacteria-killing ability (BKA) against a strain of E. coli. We also assessed how the presence and the number of bacteria on the surface of eggshells changed with agricultural intensification. Contrary to our expectations, we found a positive relationship between agricultural intensification and BKA, where individuals had higher BKA in intensive compared to nonintensive farmlands. While this trend was observed through the 6-yr study, we also found a tendency for a reduction of BKA over time. We found no relationships between the presence or number of different types of eggshell bacteria and agricultural intensification or an association between BKA of females and eggshell bacteria of their clutch. Our results suggest that differences in immune function observed between intensive and nonintensive farmlands could reflect genetic differences among individuals and/or trade-offs with other traits expressed among habitats within our study system.
beta-Glucosidase is an essential part of cellulase enzyme system for efficient and complete hydrolysis of biomass. Psychrotolerant Pseudomonas lutea BG8 produced -glucosidase with lower temperature optima and hence can play important role in bringing down the energy requirement for bioethanol production. To enhance -glucosidase production, two statistical tools: Taguchi and Box-Behnken designs were applied to reveal the most influential factors and their respective concentration for maximum production of -glucosidase under submerged fermentation. The optimal medium composition for maximum -glucosidase production were 2.99% (w/v) bagasse, 0.33% (w/v) yeast extract, 0.38% (w/v) Triton X-100, 0.39% (w/v) NaNO3, and pH 8.0 at temperature 30 degrees C. Under optimized conditions, -glucosidase production increased up to 9.12-fold (17.52 +/- 0.24IU/g) in shake flask. Large-scale production in 7-L stirred tank bioreactor resulted in higher -glucosidase production (23.29 +/- 0.23IU/g) within 80H of incubation, which was 1.34-fold higher than shake flask studies. Commercial cellulase (Celluclast((R)) 1.5L) when supplemented with this crude -glucosidase resulted in improved sugar release (548.4 +/- 2.76mg/gds) from paddy straw at comparatively low temperature (40 degrees C) of saccharification. P. lutea BG8 therefore showed great potential for cold active -glucosidase production and can be used as accessory enzyme along with commercial cellulase to improve saccharification efficiency. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
In recent years, tannase has gained increasing interest mainly because of its potential applications. One of the most important functions of tannic acid (TA) hydrolase is the release of gallic acid (GA) from complex tannins. The aim of the study was to determine the dynamic changes in tannase activity depending on the carbon source in the culture medium. An extracellular and intracellular tannase activity analysis was carried out with the use of spectrophotometric analysis and confirmed by capillary electrophoresis in cultures of white-rot fungi: Phellinus pini, Fomes fomentarius, and Tyromyces pubescens. The inducible potential of TA and rapeseed meal on the activity of tannin acyl hydrolase was confirmed during 14 days of culturing. Different effects of the tested compounds on stimulation of tannase activity in selected fungal strains have been demonstrated. We concluded that rapeseed meal was the best inducer of tannase activity in the case of P. pini. However, the highest concentrations of GA were observed after stimulation by the TA in the cultures of F. fomentarius and T. pubescens. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Fundamental concepts in biochemistry important for drug design often lack connection to the macroscopic world and can be difficult for students to grasp, particularly those in introductory science courses at the high school and college level. Educational research has shown that multisensory teaching facilitates learning, but teaching at the high school and college level is almost exclusively limited to the visual and auditory senses. This approach neglects the lifetime of experience our students bring to the classroom in the form of taste perception and makes our teaching less supportive of those with sensory impairment. In this article, we outline a novel guided-inquiry activity that utilizes taste perception for a series of natural and artificial sweetener solutions to introduce the concepts of substrate affinity and selectivity in the context of drug design. The findings from this study demonstrate clear gains in student knowledge, as well as an increase in enthusiasm for the fields of biochemistry and drug design. (C) 2016 by The International Union of Biochemistry and Molecular Biology
We report a Danio rerio transposon named DrTRT, for D. rerio Transposon Related to Tc1. The complete sequence of the DrTRT transposon is 1,563 base pairs (bp) in length, and its transposase putatively encodes a 338-amino acid protein that harbors a DD37E motif in its catalytic domain. We present evidence based on searches of publicly available genomes that TRT elements commonly occur in vertebrates and protozoa. Phylogenetic and functional domain comparisons confirm that TRT constitutes a new subfamily within the Tc1 family. Hallmark features of having no premature termination codons within the transposase, the presence of all expected functional domains, and its occurrence in the bony fish transcriptome suggest that TRT might have current or recent activity in these species. Further analysis showed that the activity of TRT elements in these species might have arisen about between 4 and 19 Ma. Interestingly, our results also implied that the widespread distribution of TRT among fishes, frog, and snakes is the result of multiple independent HT events, probably from bony fishes to snakes or frog. Finally, the mechanisms underlying horizontal transfer of TRT elements are discussed.
T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways.
Although tea consumption has been reported to have various health benefits in humans, its association with health-related quality of life (HRQOL) has not been investigated directly. We aimed to examine the relationship between tea consumption and HRQOL among older Chinese adults. We analyzed community-based cross-sectional data of 5,557 older Chinese individuals aged 60 years or older who participated in the Weitang Geriatric Diseases study. Information on tea consumption and HRQOL assessed by the European Quality of Life-5 dimensions (EQ-5D) were collected by questionnaires. We estimated the relationship of tea consumption and the EQ-5D index score using linear regression models and the association between tea consumption and self-reported EQ-5D health problems using logistic regression models. The EQ-5D index score was higher for habitual tea drinkers than their counterparts. In multivariate linear analyses controlling for socio-demographic conditions, health conditions, and lifestyle habits, the differences in ED-5D index score between individuals with and without tea drinking habits was 0.012 (95% confidence interval, 0.006-0.017). In multivariate logistic analyses, habitual tea drinking was inversely associated with reporting of problems in EQ-5D dimensions mobility (odds ration [OR], 0.44; 95% CI: 0.23-0.84); pain/discomfort (OR, 0.74; 95% CI: 0.61-0.90); and anxiety/depression (OR, 0.60; 95% CI: 0.38-0.97). These associations were more evident for black or oolong tea than green tea. Habitual tea consumption was associated with better HRQOL in older adults.
This study aims to analyze the performance of conventional distribution network with covered cables called compact ones, with those with bare cables, which are still used in old distribution lines since they are cheaper than the covered ones. However, nowadays almost all the electricity companies started to study the feasibility of the installation of compact distribution lines because of its benefits regarding maintenance and reduction of outages. Therefore, this research aims to analyze the technical losses of compact distribution networks when compared to the conventional ones. For this purpose, electrical conductors were modelled using ATP software and the results were taken to MATLAB software to perform a three-phase power flow calculation by the Newton-Raphson method. Three different topologies of distribution networks have been tested: a real system composed by bare and covered cables, a conventional system with only bare cables and a compact one with only covered cables. The simulation results demonstrated that the efficiency of the second topology is better than the others.
Background: Gavi recommends solar refrigerators for vaccine storage in areas with less than eight hours of electricity per day, and WHO guidelines are more conservative. The question remains: Can solar refrigerators provide value where electrical outages are less frequent? Methods: Using a HERMES-generated computational model of the Mozambique routine immunization supply chain, we simulated the use of solar versus electric mains-powered refrigerators (hereafter referred to as "electric refrigerators") at different locations in the supply chain under various circumstances. Results: At their current price premium, the annual cost of each solar refrigerator is 132% more than each electric refrigerator at the district level and 241% more at health facilities. Solar refrigerators provided savings over electric refrigerators when one-day electrical outages occurred more than five times per year at either the district level or the health facilities, even when the electric refrigerator holdover time exceeded the duration of the outage. Two-day outages occurring more than three times per year at the district level or more than twice per year at the health facilities also caused solar refrigerators to be cost saving. Lowering the annual cost of a solar refrigerator to 75% more than an electric refrigerator allowed solar refrigerators to be cost saving at either level when one-day outages occurred more than once per year, or when two-day outages occurred more than once per year at the district level or even once per year at the health facilities. Conclusion: Our study supports WHO and Gavi guidelines. In fact, solar refrigerators may provide savings in total cost per dose administered over electrical refrigerators when electrical outages are less frequent. Our study identified the frequency and duration at which electrical outages need to occur for solar refrigerators to provide savings in total cost per dose administered over electric refrigerators at different solar refrigerator prices. (C) 2017 Published by Elsevier Ltd.
The last 20 years have seen an explosion in the availability, ownership and use of devices used to access the internet. There has been a simultaneous increase in the number of people viewing child abuse images. The ease of access to this material online has removed a key inhibitor for offenders. Technology has facilitated the distribution of child abuse images, but is also used to prevent and identify offending, as well as to manage offenders. There is a range of technological tools currently used in England and Wales to manage those offenders who have been convicted of accessing child abuse images and who are living in the community. Some are specific to the computer as the situation of the crime. This article analyses the evidence base for each. The article concludes that each tool has features which might contribute to the management of internet child sex offenders, but that none have yet been proven or disproven to be effective. Copyright (C) 2017 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Technology to help manage the risk posed by internet child sex offenders is developing and may offer promise. None of these technological tools have been proven or disproven to be effective management tools for internet child sex offenders. Offender managers in the police and probation services should be mindful of this and not be overly reliant on them. Robust evaluations of these types of technology for these offenders are needed.
In the design of nuclear power plants, various natural circulation passive cooling systems are considered to remove residual heat from the reactor core in the event of a power loss and maintain the plant's safety. These passive systems rely on gravity differences of fluids, resulting from density differentials, rather than using an external power-driven system. Unfortunately, a major drawback of such systems is their weak driving force, which can negatively impact safety. In such systems, there is a temperature difference between the heat source and the heat sink, which potentially offers a natural platform for thermoelectric generator (TEG) applications. While a previous study designed and analyzed a TEG-based passive core cooling system, this paper considers TEG applications in other passive cooling systems of nuclear power plants, after which the concept of a TEG-based passive cooling system is proposed. In such a system, electricity is produced using the system's temperature differences through the TEG, and this electricity is used to further enhance the cooling process.
Utility sector reform spread across the developing world in the 1980s and 1990s. In Egypt, as in many cases, the pace and nature of reform has been challenged by a state-owned national incumbent. However, in the Egyptian telecommunications sector, rapid growth in the cellular market has overtaken the archaic fixed-line system. Hence, the national monopoly provider, Telecom Egypt (TE), has been stripped of its market power as the market diversified. The implemented public sector reform and privatization placed efficiency pressures on TE resulting in improved outcomes for a range of stakeholders, consumers, workers, and the government, including reduced prices, increased access, and improved service quality. This experience offers lessons for policy makers and researchers about liberalization in the face of entrenched state interests. However, there are nuances in the findings relating to market type, that is, fixed-line versus cellular, residential versus non-residential, and national versus international. Despite attempted improvements, direct competition in its retail market has led to deterioration in TE's financial performance, although this has been partially offset by its monopoly supply of an essential input and a degree of protection provided by the regulator sympathetic to TE. The evidence from this case study supports the concept of a staggered introduction of competition. However, protecting inefficient market insiders, be it firms or workers, is always at the expense of potentially more efficient outsiders. (C) 2016 The Author. Published by Elsevier Ltd.
Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m(2), 12-24 h before surgery. Telomerase activity was evaluated in fresh tumor from surgery. Post-surgery and in the phase II study, patients received imetelstat IV (days 1 and 8 q21-days) at 285 mg/m(2). Imetelstat pharmacokinetic and pharmacodynamic studies were performed. Of two evaluable patients on the MB trial, intratumoral telomerase activity was inhibited by 95 % compared to baseline archival tissue in one patient and was inevaluable in one patient. Forty-two patients (40 evaluable for toxicity) were enrolled: 9 medulloblastomas, 18 HGG, 4 ependymomas, 9 diffuse intrinsic pontine gliomas. Most common grade 3/4 toxicities included thrombocytopenia (32.5 %), lymphopenia (17.5 %), neutropenia (12.5 %), ALT (7.5 %) and AST (5 %) elevation. Two patients died of intratumoral hemorrhage secondary to thrombocytopenia leading to premature study closure. No objective responses were observed. Telomerase inhibition was observed in peripheral blood mononuclear cells (PBMCs) for at least 8 days. Imetelstat demonstrated intratumoral and PBMC target inhibition; the regimen proved too toxic in children with recurrent CNS tumors.
Telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence. Most eukaryotic telomeres can be transcribed to generate a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous nuclear RNA and can be developmentally regulated. However, the precise function and regulation of TERRA in normal and cancer cell development remains poorly understood. Here, we show that TERRA accumulates in highly proliferating normal and cancer cells, and forms large nuclear foci, which are distinct from previously characterized markers of DNA damage or replication stress. Using a mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling, TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates could also be detected in highly proliferating zones of progenitor neurons. SHH could enhance TERRA expression in purified granule progenitor cells in vitro, suggesting that proliferation signals contribute to TERRA expression in responsive tissue. TERRA foci did not colocalize with gamma H2AX foci, promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue. We also provide evidence that TERRA is elevated in a variety of human cancers. These findings suggest that elevated TERRA levels reflect a novel early form of telomere regulation during replication stress and cancer cell evolution, and the TERRA RNA aggregates may form a novel nuclear body in highly proliferating mammalian cells.
Purpose Telomere length is a biomarker for aging. It is known that oxidative stress can accelerate telomere shortening, whereas antioxidants can delay their shortening. Carotenoids as antioxidants are favorably associated with health-and aging-related diseases caused by oxidative stress, but their association with telomere length is less certain. We investigated the association between blood carotenoid levels and leukocyte telomere length in a representative sample of US adults. Methods We analyzed 3660 participants aged 20 years and older in the 1999-2002 National Health and Nutrition Examination Survey. The levels of carotenoids-alphacarotene, beta-carotene (trans + cis), beta-cryptoxanthin, combined lutein/zeaxanthin, and trans-lycopene-were measured using high-performance liquid chromatography. The leukocyte telomere length (T/S ratio) was assayed using the quantitative polymerase chain reaction method. Results A doubling of blood alpha-carotene, beta-carotene (trans + cis), and beta-cryptoxanthin was associated with approximately 2 % longer telomeres. Compared with the lowest carotenoid quartile of alpha-carotene, beta-carotene (trans + cis), and beta-cryptoxanthin, telomere length for adults with the highest quartiles was significantly increased by 5-8 %. Conclusion We found that increasing levels of blood carotenoid were significantly associated with longer leukocyte telomeres in US adults. High intake of carotenoid-rich food may play a role in protecting telomeres and regulating telomere length.
Child temperament as well as parenting behaviors have been linked to adolescent depression. Beyond their main effects, the interplay between these factors is of interest. For example, in an interactive model, a differential susceptibility of temperamental variants to parenting has been suggested. However, so far, the differential susceptibility hypothesis has mostly been studied with a focus on externalizing disorders. On the other hand, parenting may shape the child's temperament and vice versa in a transactional process. In a prospective, longitudinal at-risk sample (163 boys, 176 girls), we assessed emotional (easy-difficult) and regulative (self-control) temperament at ages 4.5, and 8 years, respectively, as well as parenting quality at age 4.5 years using the HOME inventory. Hierarchical linear regression analysis was used to investigate the prediction of depressive symptoms at age 11, measured by the Child Depression Inventory, including interaction terms between the temperament variable and parenting. We additionally tested whether parenting was mediated by child temperament. As previously reported, both self-control and parenting were longitudinally associated with preadolescent depressive symptoms. There were no interactive effects between temperament and parenting. However, the effects of parenting were partly mediated by self-control. Our data do not support a differential susceptibility of temperamental variants in the development of preadolescent depression. However, our results are in line with the assumption that parenting may shape young children's temperament, with positive parenting in the early childhood fostering the development of regulative temperament.
The Evaluation technique for radiation degradation of temperature dependences of operational amplifier input bias currents was developed. The technique can improve the accuracy of prediction of radiation hardness of operational amplifiers in full operation temperature range.
Temperature is one of the basic biophysical quantity monitored for various biomedical systems. Moreover, the variation of temperature is also an important parameter which can be used for estimating other measurands, such as respiratory airflow. This paper proposes a simple operational amplifier-based astable multivibrator circuit for linearization of the characteristic of a negative temperature coefficient thermistor constituting one of the timing resistors. The circuit has been combined with a lookup table to get the unknown temperature value from multivibrator output. Moreover, the same system topology can be used as a linearizer for measurement of respiratory airflow. The performance of the composite system has been verified experimentally. A linearity of approximately +/- 0.75% has been achieved over 30 degrees C-110 degrees C in the case of temperature measurement and +/- 1.2% for airflow of 10-60 LPM. Better results can also be achieved with the introduction of interpolation algorithms, but at a higher computational and component cost. The compactness of the complete system makes it a good candidate for embedded sensing applications in biomedical systems, such as point-of-care monitoring or in sleep study.
Neural encoder is one of the key components in neuromorphic computing systems, whereby sensory information is transformed into spike coded trains. The design of temporal encoder has attracted a widespread attention in the field of neuromorphic computing in the past few years. The information in the temporal encoding scheme with inter-spike intervals can arise from correlations between spike times, which could not be incorporated in the traditional rate encoding scheme. In this paper, we propose a robust and energy efficient analog implementation of the spiking temporal encoder. We pattern the neural activities across multiple timescales and encode the sensory information using time dependent temporal scales. The concept of iteration structure is introduced to construct a neural encoder that greatly increases the information process ability of the proposed temporal encoder. Integrated with iteration technique and operational-amplifier- free design, the error rate of the output temporal codes is reduced to an extremely low level. A lower sampling rate accompanied by additional verification spikes is introduced in the schemes, which significantly reduces the power consumption of the encoding system. To the best of our knowledge, our proposed neuron circuit is the first analog hardware implementation of the neural encoder that could present the sensory data using inter-spike interval temporal encoding scheme. The simulation and measurement results show the proposed temporal encoder exhibits not only energy efficiency but also high accuracy.
Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence. Sites of stimulation and recording were systematically varied. Following recordings, slices were anatomically reconstructed using two-dimensional unitary slices as a reference for coronal and parasagittal planes. Local spatial patterns and spread of activity were assessed by incorporating the coordinates of electrical and optical recording sites into the respective unitary slice. A preferential directional spread of evoked electrical signals was observed from ventral to dorsal, rostra) to caudal and medial to lateral regions in the LA. No differences in spread of evoked activity were observed between spontaneously and non-spontaneously active LA slices, i.e. basic properties of evoked synaptic responses were similar in the two functional types of LA slices, including input output relationship, and paired-pulse depression. These results indicate a directed propagation of synaptic signals within the human LA in spontaneously active epileptic slices. We suggest that the lack of differences in local and in systemic information processing has to be found in confined epileptiform circuits within the amygdala likely involving well-known "epileptic neurons". (C) 2017 The Author(s). Published-by Elsevier Ltd on behalf of IBRO.
Social bonds are at the center of our daily living and are an essential determinant of our quality of life. In people with epilepsy, numerous factors can impede cognitive and affective functions necessary for smooth social interactions. Psychological and psychiatric complications are common in epilepsy and may hinder the processing of social information. In addition, neuropsychological deficits such as slowed processing speed, memory loss or attentional difficulties may interfere with enjoyable reciprocity of social interactions. We consider societal, psychological, and neuropsychological aspects of social life with particular emphasis on socio-cognitive functions in temporal lobe epilepsy. Deficits in emotion recognition and theory of mind, two main aspects of social cognition, are frequently observed in individuals with mesial temporal lobe epilepsy. Results from behavioural studies targeting these functions will be presented with a focus on their relevance for patients' daily life. Furthermore, we will broach the issue of pitfalls in current diagnostic tools and potential directions for future research. By giving a broad overview of individual and interpersonal determinants of social functioning in epilepsy, we hope to provide a basis for future research to establish social cognition as a key component in the comprehensive assessment and care of those with epilepsy. (C) 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
There is extensive evidence that perceived and internally planned actions have a common representational basis: action observation can induce an automatic tendency to imitate others. If perceived and executed action, however, are based on shared representations, the question arises how we can distinguish self-related and other-related representations. It has been suggested that the control of shared representations involves a neural network centered on the temporo-parietal junction (TPJ). However, the specific role of the TPJ in controlling shared representations is still not clear. In a conflict situation where participants have to execute action A while observing action B, the TPJ might either facilitate the relevant action A or inhibit the irrelevant action B (mirror response). In the present study, we used transcranial Direct Current Stimulation (tDCS) to condition neural activity in the right temporo-parietal junction (TPJ). We then analyzed the corticospinal output as indexed by motor-evoked potentials (MEPs) induced by single-pulse TMS (spTMS) of the left primary motor cortex (M1) during action observation in the context of a conflict task. Results showed that tDCS-mediated increased control did not entail the attenuation of the task-irrelevant response activation: the effect of motor mirroring was not suppressed or reduced. Rather, facilitating TPJ activity via anodal tDCS selectively enhanced the instructed motor plan (self-related representation). This outcome supports the idea that TPJ plays a critical role in detecting the mismatch between self-related and other-related representations and is at work to enhance task relevant representations.
Patients with masticatory muscle pain and migraine typically report that the intensity of pain fluctuates over time and is affected by weather changes. Weather variables, such as ambient temperature and humidity, may vary significantly depending on whether the individual is outdoor or indoor. It is, therefore, important to assess these variables at the individual level using portable monitors, during everyday life. This study aimed to determine and compare the temporal patterns of pain in individuals affected with facial and head pain and to investigate its relation with weather changes. Eleven patients (27374years) with chronic masticatory muscle pain (MP) and twenty (331 +/- 87years) with migraine headache (MH) were asked to report their current pain level on a visual analogue scale (VAS) every hour over fourteen consecutive days. The VAS scores were collected using portable data-loggers, which were also used to record temperature, atmospheric pressure and relative humidity. VAS scores varied markedly over time in both groups. Pain VAS scores fluctuate less in the MP group than in the MH group, but their mean, minimum and maximum values were higher than those of migraine patients (all P<005). Pain scores <2cm were more common in the MH than in the MP group (P<0001). Perceived intensity of pain was negatively associated with atmospheric pressure in the MP group and positively associated with temperature and atmospheric in the MH group. Our results reveal that patients with masticatory muscle pain and patients with migraine present typical temporal pain patterns that are influenced in a different way by weather changes.
Central to the basis of ecological immunology are the ideas of costs and trade-offs between immunity and life history traits. As a physical barrier, the insect cuticle provides a key resistance trait, and Tenebrio molitor shows phenotypic variation in cuticular colour that correlates with resistance to the ento-mopathogenic fungus Metarhizium anisopliae. Here we first examined whether there is a relationship between cuticular colour variation and two aspects of cuticular architecture that we hypothesised may influence resistance to fungal invasion through the cuticle: its thickness and its porosity. Second, we tested the hypothesis that tyrosine, a semi-essential amino acid required for immune defence and cuticular melanisation and sclerotisation, can act as a limiting resource by supplementing the larval diet and subsequently examining adult cuticular colouration and thickness. We found that stock beetles and beetles artificially selected for extremes of cuticular colour had thicker less porous cuticles when they were darker, and thinner more porous cuticles when they were lighter, showing that colour co-varies with two architectural cuticular features. Experimental supplementation of the larval diet with tyrosine led to the development of darker adult cuticle and affected thickness in a sex-specific manner. However, it did not affect two immune traits. The results of this study provide a mechanism for maintenance of cuticular colour variation in this species of beetle; darker cuticles are thicker, but their production is potentially limited by resource constraints and differential investments in resistance mechanisms between the sexes. (C) 2016 Elsevier Ltd. All rights reserved.
Invertebrate immune priming is a growing field in immunology. This phenomenon refers to the ability of invertebrates to generate a more vigorous immune response to a second encounter with a specific pathogen and can occur within and across generations. Although the precise mechanism has not been elucidated, it has been suggested that methylation of DNA is a cornerstone for this phenomenon. Here, using a novel method of analytical chemistry (a reversed-phase liquid chromatography procedure) and the beetle Tenebrio molitor as a model system, we did not find evidence to support this hypothesis taking into account the percentage of methylated cytosine entities in DNA (5mdC) within or across generations. However, we found a lower percentage of methylated cytosine entities in RNA (5mC) within but not across generations in immune priming experiments with adults against the bacteria Micrococcus lysodeikticus and larvae against the fungus Metarhizium anisopliae. To our knowledge, this is the first report suggesting a role of differential methylation on RNA during immune priming within generations.
Two tenuiviruses Rice stripe virus (RSV) and Rice grassy stunt virus (RGSV) were found to co-infect rice with the same reovirus Rice ragged stunt virus (RRSV). During the co-infection, both tenuiviruses recruited 10-21 nucleotides sized capped-RNA leaders from the RRSV. A total of 245 and 102 RRSV-RGSV and RRSV-RSV chimeric mRNA clones, respectively, were sequenced. An analysis of the sequences suggested a scenario consistent with previously reported data on related viruses, in which capped leader RNAs having a 3' end complementary to the viral template are preferred and upon base pairing the leaders prime processive transcription directly or after one to several cycles of priming and realignment (repetitive prime-and-realign). Interestingly, RSV appeared to have a higher tendency to use repetitive prime-and-realign than RGSV even with the same leader derived from the same RRSV RNA. Combining with relevant data reported previously, this points towards an intrinsic feature of RSV. (C) 2016 Elsevier Inc. All rights reserved.
Mountain pepper (Litseacubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs) involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE) using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF) served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR) results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil.
The study aimed to polish wastewater effluent from an activated treatment system for nitrogen removal by a packed bed bioreactor (PBR). The nitrogen removal via simultaneous partial nitrification, anammox and denitrification (SNAD) process was investigated with different hydraulic retention times (HRTs). The results show that both effluent ammonia-and nitrate-nitrogen concentrations approached to 0 mg/L at the HRT as low as 3 h. The total nitrogen removal efficiency decreased from an average of 84% at both 18- and 24-h HRTs to 38% at 3-h HRT. This low nitrogen removal efficiency was due to the presence of incomplete degradation of organic nitrogen at shorter HRTs. The analysis using quantitative real-time polymerase chain reaction resolves that the ratio of ammonia-oxidizing bacteria (AOB) to the domain Eubacteria changed limited in the range between 2.8 and 4.0% during the continuous operation. Meanwhile, the nitrite-oxidizing bacteria (NOB) increased from 0.0 to 2.9% when the HRT was gradually reduced to 3 h. The anammox bacteria accounting for 30.5% of microbial consortia dominated the AOB and the NOB at the 3-h HRT. In sum, inorganic form of nitrogen in a typical wastewater plant effluent could be efficiently polished via SNAD process in the PBR. (C) 2017 Elsevier Ltd. All rights reserved.
Background: A transposable element (TE) is a DNA fragment that can change its position within a genome. Transposable elements play important roles in maintaining the stability and diversity of organisms by transposition. Recent studies have shown that approximately half of the genes in Bombyx mori are TEs. Results: We systematically identified and analyzed the BmAGO2-associated TEs, which exceed 100 in the B. mori genome. Additionally, we also mapped the small RNAs associated with BmAGO2 in B. mori. The transposon Bm1645 is the most abundant TE associated with BmAGO2, and Bm1645-derived small RNAs represent a small RNA pool. We determined the expression patterns of several Bm1645-derived small RNAs by northern blotting, and the results showed there was differential expression of multiple small RNAs in normal and BmNPV-infected BmN cells and silkworms from various developmental stages. We confirmed that four TE-siRNAs could bind to BmAGO2 using EMSA and also validated the recognition sites of these four TE-siRNAs in Bm1645 by dual-luciferase reporter assays. Furthermore, qRT-PCR analysis revealed the overexpression of the four TE-siRNAs could downregulate the expression of Bm1645 in BmN cells, and the transcription of Bm1645 was upregulated by the downregulation of BmAGO2. Conclusions: Our results suggest Bm1645 functions as a source of small RNAs pool and this pool can produce many BmAGO2-associated small RNAs that regulate TE's expression.
Dr. Louis Dehner has contributed significantly to our understanding of testicular germ cell tumors in children. This review article considers the molecular biology, clinical attributes, pathologic findings, and prognosis of those lesions. Published by Elsevier Inc.
The aim of this study was to investigate the effects of tetrahydroberberine (THB) and tetrahydropalmatine (THP) on the expression of mouse liver cytochrome P450s, and evaluate their liver toxicity in mice. Real-time polymerase chain reaction (PCR) and western blot analyses were used to analyze the expression of major P450 isoforms. Liver toxicity was evaluated by measuring serum biochemical parameters and performing histopathological analysis. The real-time PCR results showed that THB induced Cyp1a2 (1.66 +/- 0.34 fold, P < 0.05), Cyp3a11 (1.57 +/- 0.24 fold, P < 0.05), and Cyp2e1 (1.75 +/- 0.97 fold, P < 0.05) mRNA expression, while THP inhibited Cyp1a2 (0.66 +/- 0.12 fold, P < 0.05) mRNA expression. The western blot results confirmed that the expression of CYP1A2, CYP3A, and CYP2E1 proteins in the mouse liver was induced by THB, whereas that of CYP1A2 was inhibited by THP. Toxicological studies showed that THB (40 mg/kg, oral gavage) increased mouse serum aspartate transaminase and total bilirubin, and liver malondialdehyde levels, and induced liver edema. No obvious changes in serum and liver tissue biochemical parameters were found and no significant pathological changes were detected in liver tissues after THP administration. Our results provide more information on the toxicity of THB and THP, and their related drug-drug interactions. (C) 2017 Elsevier B.V. All rights reserved.
About thirty years ago, studies on the RNA genome of Tobacco Etch Virus revealed the presence of an efficient and specific protease, called Tobacco Etch Virus protease (TEVp), that was part of the Nuclear Inclusion a (NIa) enzyme. TEVp is an efficient and specific protease of 27 kDa that has become a valuable biotechnological tool. Nowadays TEVp is a unique endopeptidase largely exploited in biotechnology from industrial applications to in vitro and in vivo cellular studies. A number of TEVp mutants with different rate of cleavage, stability and specificity have been reported. Similarly, a panel of different target cleavage sites, derived from the canonical ENLYFQ-G/S site, has been established. In this review we describe these aspects of TEVp and some of its multiple applications. A particular focus is on the use and molecular biology of TEVp in living cells and organisms. (C) 2016 Elsevier B.V. All rights reserved.
The study focuses on integration aids (i.e., signals) and their effect on how students process different types of graphical representations (representational pictures vs. organizational pictures vs. diagrams) in standardized multiple-choice items assessing science achievement. Based on text-picture integration theories each type of pictorial representation hold different cognitive requirements concerning integration processes of two representations. Further, depending on type of representation not every picture is needed to answer an item correctly. Students from fifth sixth grade (N = 60) work through 12 multiple choice items while their eye movements were recorded. Results showed that students achieved higher test scores when items were presented in an integrated format than in a non-integrated format, however, this was only true for diagrams. Eye movement data revealed that students looked longer on the graphical representations in items presented in the integrated format condition compared to the non-integrated format condition. Furthermore, relations between looking at the diagrams and achievement in the integrated format emerged. (C) 2017 The Authors. Published by Elsevier Ltd.
Building discriminative and robust texture representation to deal with the changes of texture appearance is a fundamental issue in texture classification. The Local Binary Pattern (LBP) and its variants gain a lot of attention during the past decade and achieve great success in texture description. However, the current existing LBP-based features which treat LBP as local differential or orientation gradient operator, exploited local orientation pattern or anisotropic structure information separately. In this paper, we investigate the theoretical scheme of local differential approximation on the polar coordinate system in order to build a new LBP-based descriptor which better takes into account both radial plus tangential components and derivative information. First, we present an operator called circumferential derivative (CD) based on the tangential information with different order of derivatives. Then, we present an operator called radial derivative (RD) based on the radial information with different order of derivatives. Both extract complementary information locally around a central pixel. A new descriptor, the local binary circumferential and radial derivative pattern (CRDP) is constructed to fuse both local circumferential and radial derivative features based on different orders as well as a global feature based on global difference (GD) of central pixel's intensity. Extensive experiments on Outex, CUReT, KTH-TIPS and KTH-TIPS2-a texture datasets indicate that the proposed CRDP descriptor is discriminative and robust. The results obtained by the proposed CRDP descriptor outperforms more than twenty recent LBP-based state-of-the-art methods, including the best reported results in the literature for aforementioned texture datasets to the best of our knowledge. (C) 2017 Elsevier Ltd. All rights reserved.
Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide. The PD-1/PD-L1 interaction plays important roles in cancer immunology, and expression of PD-L1 has been discovered in NSCLC tumor cells. Since follicular helper T (Tfh) cells have characteristic high PD-1 expression, we therefore investigated the inflammatory status of Tfh in NSCLC. CD4(+) CXCR5(+) T cell population was examined to define Tfh cells. Data showed that frequency of Tfh cells in peripheral blood was significantly lower in NSCLC patients than in healthy controls. In both primary and metastatic tumors, infiltration of Tfh cells was observed, suggesting that they participated in the antitumor immunity of NSCLC patients. Compared to other T cell subsets, the Tfh cells from the peripheral blood and the resected tumors of NSCLC patients presented elevated apoptosis and reduced proliferation capacity. The Tfh cells from NSCLC patients were also less effective at downregulating IgD and upregulating CD27 expression in naive B cells, and induced less IgM, IgG and IgA secretion, than those from healthy controls. We then found that the survival time from the date of surgery was positively correlated with the frequency of tumor-infiltrating Tfh cells in NSCLC subjects. Overall, the results from this study demonstrated that the Tfh cells were likely involved in the antitumor immunity and were associated with better clinical outcomes, but suffered strong immunosuppression in NSCLC. Enhancing the Tfh cell activity therefore represents a potential therapeutic strategy in NSCLC. (C) 2016 Elsevier B.V. All rights reserved.
Background/Aims: Connective tissue growth factor (CTGF/CCN2) has been implicated in the pathogenesis of hepatic fibrosis and suggested as a downstream mediator of the fibrogenic master cytokine TGF-beta. Methods: We investigated the effect of TGF-beta 1 on CTGF/CCN2 expression in cultured rat hepatic stellate cells and hepatocytes by means of Western and Northern blotting, immunocytochemistry, reporter gene analysis, and metabolic labelling. Results: We found that the expression of CTGF/CCN2 in hepatic stellate cells is (i) only marginally (if at all) stimulated by TGF-beta and by a constitutively active type I TGF-beta receptor, (ii) independent from Smad2/3 phosphorylation, (iii) not reduced by TGF-beta 1 antagonists or ALK5-receptor inhibitors and (iv) not upregulated during transdifferentiation to myofibroblasts in culture. However, expression and secretion of CTGF/CCN2 in cultured hepatocytes increased spontaneously during culture and was strongly stimulated by TGF-beta 1. In bile-duct ligated and CCl4-treated rat livers, a strong CTGF/ CCN2 expression in hepatocytes was noticed. Endothelin-1 stimulated CTGF/CCN2 expression in stellate cells but not in hepatocytes. Pathway specific signalling inhibitors point to the involvement of non-Smad signalling cascades but their contribution to CTGF/CCN2 regulation is different in both cell types. Conclusions: The results do not reveal a relevant interrelation between TGF-beta function and CTGF/CCN2 expression in hepatic stellate cells, which is in contrast to hepatocytes. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Background. We investigated the potential role of interleukin (IL)-17 family members (IL-17A to IL-17F) in the induction of inflammatory responses in human colonic subepithelial myofibroblasts (SEMFs). Methods. The expression of the inflammatory cytokines IL-6, IL-8, leukemia inhibitory factor (LIF), and matrix metalloproteinases (MMP)-1 and MMP-3 were evaluated by enzyme-linked immunosorbent assay and Northern blotting. Activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. Results. IL-17A and IL-17F significantly enhanced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. The effects of IL-17A were relatively stronger than those induced by IL-17F. The effects of IL-17B, IL-17C, IL-17D, and IL-17E were modest as compared with those induced by IL-17A and IL-17F. Both IL-17A and IL-17F augmented IL-1 beta-induced secretion of IL-6, IL-8, LIF, MMP-1, and MMP-3. A similar augmentation was also observed in tumor necrosis factor (TNF)-alpha-induced cytokine and MMP secretion. IL-17A and IL-17F rapidly induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, p38 MAPKs, and c-Jun-NH2-terminal kinase (JNK) as early as 15min after stimulation. Inhibitors for ERK (PD98059 and U0216) and p38 MAPK (SB203580) significantly reduced the IL-17F-induced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. Conclusions. Among IL-17 family members, IL-17A and IL-17F strongly stimulate human colonic SEMFs, inducing inflammatory responses.
Lung cancer is a leading cause of cancer-related deaths worldwide. Lung cancer risk factors, including smoking and exposure to environmental carcinogens, have been linked to chronic inflammation. An integral feature of inflammation is the activation, expansion and infiltration of diverse immune cell types, including CD4(+) T cells. Within this T cell subset are immunosuppressive regulatory T (Treg) cells and pro-inflammatory T helper 17 (Th17) cells that act in a fine balance to regulate appropriate adaptive immune responses. In the context of lung cancer, evidence suggests that Tregs promote metastasis and metastatic tumor foci development. Additionally, Th17 cells have been shown to be an integral component of the inflammatory milieu in the tumor microenvironment, and potentially involved in promoting distinct lung tumor phenotypes. Studies have shown that the composition of Tregs and Th17 cells are altered in the tumor microenvironment, and that these two CD4+ T cell subsets play active roles in promoting lung cancer progression and metastasis. We review current knowledge on the influence of Treg and Th17 cells on lung cancer tumorigenesis, progression, metastasis and prognosis. Furthermore, we discuss the potential biological and clinical implications of the balance among Treg/Th17 cells in the context of the lung tumor microenvironment and highlight the potential prognostic function and relationship to metastasis in lung cancer.
Glycated hemoglobin (Hb A(1c)) determination by multicapillary zone electrophoresis (MZE) can additionally be used to detect Hb A(2), Hb F and most common hemoglobin (Hb) variants. We assessed the effectiveness of this method for detecting -thalassemia (-thal), -thalassemia (-thal) and most common Hb variants. Moreover, Hb F/Hb A(2) is evaluated as an index for discriminating between - and -thal traits. The theoretical -thalassemia major (-TM) birth rate in our healthcare area is calculated and contrasted with real data. A MZE technique was used for Hb A(1c) measurements in 27,724 patients. Previous criteria for carrier detection were established and subsequently confirmed by molecular biology techniques. Positive predictive value (PPV) was 100.0%. The prevalence of -thal trait (including -thal) was 0.34%. The most prevalent mutations (estimated per 100,000 population) were HBB: c.118C>T (57.7%), HBB: c.93-21G>A (50.5%), HBB: c.92+1G>A (43.3%), HBB: c.92+6T>C (32.5%) and HBB: c.20delA (18.0%) for -thalassemias, and Hb S (HBB: c.20A>T) (32.5%) and Hb J-Baltimore (HBB:c.3880T>A) (28.9%) for Hb variants. We found a paradoxical result between the theoretical -TM birth rate and real data. We calculated an optimal Hb F/Hb A(2) index cutoff of 0.71 for discriminating between - and -thal traits. This method is highly cost-effective for detecting -thalassemias and common Hb variants. Prevalence results match previous data for the Spanish population. Heterogeneity of mutations in Spain has markedly increased as a consequence of migration. The Hb F/Hb A(2) index cutoff could be used to predict -thal trait.
With one operational amplifier (op-amp) in negative feedback, the traditional zero potential circuit could access one element in the two-dimensional (2-D) resistive sensor array with the shared row-column fashion but it suffered from the crosstalk problem for the non-scanned elements' bypass currents, which were injected into array's non-scanned electrodes from zero potential. Firstly, for suppressing the crosstalk problem, we designed a novel improved zero potential circuit with one more op-amp in negative feedback to sample the total bypass current and calculate the precision resistance of the element being tested (EBT) with it. The improved setting non-scanned-electrode zero potential circuit (S-NSE-ZPC) was given as an example for analyzing and verifying the performance of the improved zero potential circuit. Secondly, in the S-NSE-ZPC and the improved S-NSE-ZPC, the effects of different parameters of the resistive sensor arrays and their readout circuits on the EBT's measurement accuracy were simulated with the NI Multisim 12. Thirdly, part features of the improved circuit were verified with the experiments of a prototype circuit. Followed, the results were discussed and the conclusions were given. The experiment results show that the improved circuit, though it requires one more op-amp, one more resistor and one more sampling channel, can access the EBT in the 2-D resistive sensor array more accurately.
This study is carried out to examine whether the psychological capital with its conceptual analysis and sub-dimensions, hope, self-efficacy, durability and optimism existed in the Akhism Organization application which was founded in Kayseri in Anatolia about 810 years ago. The aim of this article is to emphasize the key importance of psyhological capital in creating organizational success and competitive advantage at present and draw attention to the similarities between the applications at the same time as the Akhism Organization regarding the development of psychological capital. In this context, this study includes some exminations concerning the possibility of Akhism Organization' being a source, a guide for the present businesses for the development and the share of psychological capital.
China's rapid economic growth causes a sharp increase in the demand for electricity. Electricity price in China is generally controlled at a low level by the government, leading to a substantial electricity subsidy. Electricity subsidy is the focus of energy price reform. It is also most closely linked with residential life and is a very sensitive issue to residents. This paper adopts the price-gap approach to estimate the scale of electricity subsidy and finds that in 2010, residential electricity subsidy in China amounted to 467.17 billion CNY (Chinese yuan), accounting for 1.17 % of GDP in that year. Subsequently, the paper estimates the impacts of residential electricity subsidy reform on the welfare of residents using the compensating variation (CV) measurement. The results show that if residential electricity price rises by 50, 100, 150, and 191 %, the CV should be 288.5, 394.2, 451.1, and 467.2 billion CNY, respectively. The residential electricity subsidy reform also has a moderating role in the rebound effect of electricity consumption. The direct rebound effect in China's residential electricity consumption is 20 %. Electricity subsidy reform will raise terminal electricity price and restrain residential electricity consumption. Therefore, electricity subsidy reform should be an effective measure to mitigate the rebound effect.
Background: An increasing need exists for suitable measures to evaluate treatment outcome in adolescents. YP-CORE is a pan-theoretical brief questionnaire developed for this purpose, but it lacks studies in different cultures or languages.Aims: To explore the acceptability, factor structure, reliability, validity, and sensitivity to change of the Finnish translation of YP-CORE.Methods: The study was conducted at the Department of Adolescent Psychiatry, Helsinki University Central Hospital. A Finnish translation was prepared by a team of professionals and adolescents. A clinical sample of 104 patients was asked to complete the form together with BDI-21 and BAI, and 92 of them filled the forms again after a 3-month treatment. Analysis included acceptability, confirmatory factor analysis, internal and test-re-test reliability, concurrent validity, influence of gender and age, and criteria for reliable change.Results: YP-CORE was well accepted, and the rate of missing values was low. Internal consistency (=0.83-.92) and test-re-test reliability were good (r=0.69), and the results of CFA supported a one-factor model. YP-CORE showed good concurrent validity against two widely used symptom-specific measures (r=0.62-0.87). Gender had a moderately strong effect on the scores (d=0.67), but the effect of age was not as evident. The measure was sensitive to change, showing a larger effect size (d=0.55) than in the BDI-21 and BAI (d=0.31-0.50).Conclusions: The results show that the translation of YP-CORE into Finnish has been successful, the YP-CORE has good psychometric properties, and the measure could be taken into wider use in clinical settings for outcome measurement in adolescents.
Background: Bovine theileriosis, caused by the haemoprotozoan Theileria orientalis, is an emerging disease in East Asia and Australasia. Previous studies have demonstrated transplacental transmission of various Theileria spp. but molecular confirmation of transplacental transmission of T. orientalis has never been confirmed in the field. In this study, cow-calf (< 48 h old) pairs were sampled across 3 herds; opportunistic samples from aborted foetuses or stillborn calves were also examined. Molecular (multiplex qPCR) and serological (ELISA) methods were used to determine infection prevalence and the presence of anti-Theileria antibodies in each herd. In addition, pregnant heifers and foetal calves were sampled at abattoir and tested for the presence of T. orientalis by qPCR. Results: The qPCR results indicated that, even though there was a high prevalence of T. orientalis infection in cows, the rate of transplacental transmission to their calves was low, with only one newborn calf from one herd and one foetus from the abattoir testing positive for T. orientalis DNA. Five aborted foetuses and stillborn calves, 3 of which were derived from a herd experiencing a high number of clinical theileriosis cases at the time of sampling, all tested negative for T. orientalis by qPCR. This suggests that in utero infection of calves with T. orientalis may not be a major driver of abortions during theileriosis outbreaks. Temporal monitoring of 20 calves born to T. orientalis-positive mothers indicated that T. orientalis was detectable in most calves between 10 and 27 days post-partum, consistent with prior field studies on adult cattle introduced to Theileria-affected herds. There was a positive correlation between the ELISA ratio of newborn calves and their mothers within 48 h of calving; however, maternal antibodies were only detectable in some calves and only for 4-4.5 weeks post-partum. All calves displayed high parasite loads peaking at 4-8 weeks post-partum, with only some calves subsequently mounting a detectable adaptive antibody response. Conclusions: These findings indicate transplacental transmission of T. orientalis appears to play only a minor role in persistence of T. orientalis infection in the field; however calves are highly susceptible to developing high level T. orientalis infections at 4-8 weeks of age regardless of whether maternal antibodies are present post-partum.
Whether theory of mind (ToM) is preserved in Alzheimer's disease (AD) remains a controversial subject. Recent studies have showed that performance on some ToM tests might be altered in AD, though to a lesser extent than in behavioural-variant Frontotemporal Dementia (bvFTD). It is however, unclear if this reflects a genuine impairment of ToM or a deficit secondary to the general cognitive decline observed in AD. Aiming to investigate the cognitive determinants of ToM performance in AD, a data-mining study was conducted in 29 AD patients then replicated in an independent age-matched group of 19 AD patients to perform an independent replication of the results. 44 bvFTD patients were included as a comparison group. All patients had an extensive neuropsychological examination. Hierarchical clustering analyses showed that ToM performance clustered with measures of executive functioning (EF) in AD. ToM performance was also specifically correlated with the executive component extracted from a principal component analysis. In a final step, automated linear modelling conducted to determine the predictors of ToM performance showed that 48.8% of ToM performance was significantly predicted by executive measures. Similar findings across analyses were observed in the independent group of AD patients, thereby replicating our results. Conversely, ToM impairments in bvFTD appeared independent of other cognitive impairments. These results suggest that difficulties of AD patients on ToM tests do not reflect a genuine ToM deficit, rather mediated by general (and particularly executive) cognitive decline. They also suggest that EF has a key role in mental state attribution, which support interacting models of ToM functioning. Finally, our study highlights the relevancy of data-mining statistical approaches in clinical and cognitive neurosciences. (C) 2016 Elsevier Ltd. All rights reserved.
Anger in the context of psychosis has a significant impact on treatment outcomes and serious implications for risk management. Understanding mechanisms underlying anger will improve interventions and inform strategies for prevention. This study is the first to examine the relationships between anger and key theoretical drivers across different phases of the psychosis continuum. A battery including measures of theory of mind, attachment, hostile attribution bias, paranoia and anger was administered to 174 participants (14 ultra-high risk, 20 first-episode, 20 established psychosis, 120 non-clinical participants). We tested the model that insecure attachment, paranoia, impaired theory of mind and hostile attribution bias would predict trait anger using multiple regression. Attachment avoidance, paranoia and hostile attribution bias were significantly associated with anger but attachment anxiety and theory of mind were not. Mediation analysis showed that paranoia partially mediated the relationship between avoidant attachment and anger but hostile attribution bias did not. Findings emphasise the importance of interventions targeting paranoia to reduce anger and the potential of preventive strategies focused on attachment relationships in early life or adulthood to reduce adult paranoia and anger.
The ability to attribute and represent others' mental states (e.g., beliefs; so-called "theory of mind") is essential for participation in human social interaction. Despite a considerable body of research using tasks in which protagonists in the participants' attentional focus held false or true beliefs, the question of automatic belief attribution to bystander agents has received little attention. In the current study, we presented adults and 6-year-olds (N = 92) with an implicit computer-based avoidance false-belief task in which participants were asked to place an object into one of three boxes. While doing so, we manipulated the beliefs of an irrelevant human-like or non-human-like bystander agent who was visible on the screen. Importantly, the bystander agent's beliefs were irrelevant for solving the task. Still, children's decision making was significantly influenced by the bystander agent's beliefs even if this was a non-human-like self-propelled object. Such an influence did not become obvious in adults' deliberate decisions but occurred only in their reaction times, which suggests that they also processed the bystander agent's beliefs but were able to suppress the influence of such beliefs on their behavior regulation. The results of a control study (N = 53) ruled out low-level explanations and confirmed that self-propelledness of agents is a necessary factor for belief attribution to occur. Thus, not only do humans spontaneously ascribe beliefs to self-propelled bystander agents, but those beliefs even influence meaningful decisions in children. (C) 2016 Elsevier Inc. All rights reserved.
Introduction: Being able to understand other people's emotions and intentions is crucial for social interactions and well-being. Deficits in theory of mind (ToM) functioning hamper this ability and have been observed in depression and other neuropsychiatric disorders. However, results of previous research in depression have been inconclusive, possibly due to the presence of comorbid disorders and the disregarding of other modulating factors. Methods: Thirty-eight patients with a major depressive disorder (MDD) and forty healthy matched controls were assessed with a ToM task using animated triangles. Results were correlated with attachment styles, empathy abilities and neurocognitive performance. Results: Our findings show that 1) healthy female controls performed significantly stronger on the ToM task than female MDD patients, 2) these performance differences were driven by attachment styles and 3) depression severity did not impact task performance. Limitations: The pharmacological treatment of the majority of patients might limit the generalizability of this study. Discussion: Results indicate a gender-specific impact of attachment styles on ToM performance. Future studies should investigate whether impairments in social cognitive tasks pose a risk factor for depression and/or interactional styles or vice versa. Moreover, with regard to remediation programs gender-specific needs should be taken into account.
Mentalizing or Theory of Mind (ToM), i.e., the ability to recognize what people think or feel, is a crucial component of human social intelligence. It has been recently proposed that ToM can be decomposed into automatic and controlled neurocognitive components, where only the latter engage executive functions (e.g., working memory, inhibitory control and task switching). Critical here is the notion that such dual processes are expected to follow different developmental dynamics. In this work, we provide novel experimental evidence for this notion. We report data gathered from about thirty thousand participants of a massive web poll of peoples cognitive skills, which included ToM and executive functions. We show that although the maturation of executive functions occurs in synchrony (around 20 years of age), this is not the case for different mentalizing competences, which either mature before (for elementary ToM constituents) or after (for higher-level ToM). In addition, we show that inter-individual differences in executive functions predict variability in higher-level ToM skills from the onset of adulthood onwards, i.e., after the complete maturation of executive functions. Taken together, these results indicate that the relative contribution of ToM's controlled component significantly changes with age. In particular, this implies that, over the lifespan, people may rely upon distinct cognitive architectures when reading others' minds. (C) 2016 Elsevier Ltd. All rights reserved.
Two studies examined the development of constructivist theory of mind (ToM) during late childhood and early adolescence. In Study 1, a new measure was developed to assess participants' understanding of the interpretive and constructive processes embedded in memory, comprehension, attention, comparison, planning, and inference. Using this measure, Study 2 tested a mediational model in which prosocial reasoning about conflict mediated the relation between constructivist ToM and behavior problems in high school. Results showed that the onset of constructivist ToM occurs between late childhood and early adolescence and that adolescents who have more advanced constructivist ToM have more prosocial reasoning about conflict, which in turn mediated the relation with fewer serious behavior problems in high school, after controlling for academic performance and sex. In both studies, girls showed more advanced constructivist ToM than boys in high school. (C) 2016 Elsevier Inc. All rights reserved.
Theory of Mind (ToM) is thought to play a key role in social information processing as it refers to the ability of individuals to represent the mental states of others (e.g., intentions, desires, beliefs). A provocative hypothesis has been put forward which espouses the existence of two ToM systems: one that is implicit and involves the automatic analysis of the belief states of others and another that is not automatic and is involved in explicitly reasoning about others' mental states. Recently, Phillips et al. (2015) have suggested that there is limited evidence for automatic ToM processing, after identifying a confound in a previous high-profile paper supporting the existence of this cognitive operation in infants and adults (Kovacs, Teglas, & Endress, 2010). Here, we take a broader view of the literature and find, contrary to the conclusions of Phillips et al., that there is a substantial body of literature which demonstrates that adult humans are able to engage in unconscious and unintentional, and thus automatic, analyses of others' mental states. However, whether this ability is best described under a one, two or multiple systems ToM account remains to be determined. (C) 2017 Elsevier B.V. All rights reserved.
Since the publication of Premack and Woodruff's classic paper introducing the notion of a 'theory of mind' (Premack and Woodruff in Behav Brain Sci 1(4):515-526, 1978), interdisciplinary research in social cognition has witnessed the development of theory-theory, simulation theory, hybrid approaches, and most recently interactionist and perceptual accounts of other minds. The challenges that these various approaches present for each other and for research in social cognition range from adequately defining central concepts to designing experimental paradigms for testing empirical hypotheses. But is there any approach that promises to dominate future interdisciplinary research in social cognition? Is social cognition witnessing a gradual paradigm shift where hitherto grounding notions such as theory of mind are no longer viewed as explanatorily necessary? Or have we simply lost our way in attempting to devise adequate experimental setups that could sway the debate in favour of one of the contending accounts? This special issue addresses these questions in an attempt to discover what the future holds for interdisciplinary research in social cognition.
Background: Individuals with autism spectrum disorder (ASD) experience marked challenges with social function by definition, but few modifiable predictors of social functioning in ASD have been identified in extant research. This study hypothesized that deficits in social cognition and motor function may help to explain poor social functioning in individuals with ASD. Method: Cross-sectional data from 108 individuals with ASD and without intellectual disability ages 9 through 27.5 were used to assess the relationship between social cognition and motor function, and social functioning. Results: Results of hierarchical multiple regression analyses revealed that greater social cognition, but not motor function, was significantly associated with better social functioning when controlling for sex, age, and intelligence quotient. Post-hoc analyses revealed that better performance on second-order false belief tasks was associated with higher levels of socially adaptive behavior and lower levels of social problems. Conclusions: Our findings support the development and testing of interventions that target social cognition in order to improve social functioning in individuals with ASD. Interventions that teach generalizable skills to help people with ASD better understand social situations and develop competency in advanced perspective taking have the potential to create more durable change because their effects can be applied to a wide and varied set of situations and not simply a prescribed set of rehearsed situations. (C) 2016 Published by Elsevier Ltd.
Kidd and Castano (in press) critique our failure to replicate Kidd and Castano (2013) on 3 grounds: failure to exclude people who did not read the texts, failure of random assignment, and failure to exclude people who did not take the Author Recognition Test (ART). This response addresses each of these critiques. Most importantly, we note that even when Kidd and Castano reanalyzed our data in the way that they argue is most appropriate, they still failed to replicate the pattern of results reported in their original study. We thus reaffirm that our replication of Kidd and Castano (2013) found no evidence that literary fiction uniquely and immediately improves theory of mind. Our objective remains not to prove that reading literary fiction does not benefit social cognition, but to call for in- depth research addressing the difficulties in measuring any potential effect and to note the need to temper claims accordingly. This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
We investigated theory of mind (ToM) deficits in Alzheimer's disease (AD) and its possible connection to autobiographical memory (ABM). Patients and matched controls were evaluated and compared using a video-based ToM test, an autobiographical fluency task, and a neuropsychological test battery. We found that ToM deficits were positively associated with semantic ABM in the clinical group, whereas a positive relationship appeared between ToM and episodic ABM in controls. We hypothesize that this reflects the course of the disease as well as that semantic ABM is used for ToM processing, being still accessible in AD. Furthermore, we assume that it is also less efficient, which in turn leads to a specific deficit profile of social cognition.
Two populations have been found to exhibit delays in theory of mind (ToM): deaf children of hearing parents and children with autism spectrum disorder (ASD). Deaf children exposed to sign from birth by their deaf parents, however, show no such delay, suggesting that early language exposure is key to ToM development. Sign languages also present frequent opportunities with visual perspective-taking (VPT), leading to the question of whether sign exposure could benefit children with ASD. We present the first study of children with ASD exposed to sign from birth by their deaf parents. Seventeen native-signing children with a confirmed ASD diagnosis and a chronological- and mental age-matched control group of 18 typically developing (TD) native-signing deaf children were tested on American Sign Language (ASL) comprehension, two minimally verbal social cognition tasks (ToM and VPT), and one spatial cognition task (mental rotation). The TD children outperformed the children with ASD on ASL comprehension (p<0.0001), ToM (p=0.02), and VPT (p<0.01), but not mental rotation (p=0.12). Language strongly correlated with ToM (p<0.01) and VPT (p<0.001), but not mental rotation (p=ns). Native exposure to sign is thus insufficient to overcome the language and social impairments implicated in ASD. Contrary to the hypothesis that sign could provide a scaffold for ToM skills, we find that signing children with ASD are unable to access language so as to gain any potential benefit sign might confer. Our results support a strong link between the development of social cognition and language, regardless of modality, for TD and ASD children. Autism Res2016, 9: 1304-1315. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Amyotrophic lateral sclerosis (ALS) is associated with executive dysfunction and behavioural impairment. Recent studies suggested that social cognitive deficits might also be a prominent feature of ALS. Current meta-analysis aimed to summarize available evidence for deficits in social cognition including theory of mind (ToM) and emotion recognition in ALS. In this meta-analysis of 15 studies, facial emotion recognition and ToM performances of 389 patients with ALS and 471 healthy controls were compared. ALS was associated with significant impairments with medium effect sizes in ToM (d = .65) and facial emotion recognition (d = .69). Among individual emotions recognition of disgust and surprise were particularly impaired. Deficits in perspective taking (d = .73) aspects of ToM (ToM-PT) was more pronounced in comparison to decoding (d = .28) aspects of ToM (ToM-decoding). The severity of social cognitive impairment was similar to level of executive dysfunction and there was a significant relationship between social cognition and executive dysfunction. Deficits in social cognition are part of the cognitive phenotype of ALS. (C) 2016 Elsevier Ltd. All rights reserved.
When do children acquire a propositional attitude folk psychology or theory of mind? The orthodox answer to this central question of developmental ToM research had long been that around age 4 children begin to apply "belief" and other propositional attitude concepts. This orthodoxy has recently come under serious attack, though, from two sides: Scoffers complain that it over-estimates children's early competence and claim that a proper understanding of propositional attitudes emerges only much later. Boosters criticize the orthodoxy for underestimating early competence and claim that even infants ascribe beliefs. In this paper, the orthodoxy is defended on empirical grounds against these two kinds of attacks. On the basis of new evidence, not only can the two attacks safely be countered, but the orthodox claim can actually be strengthened, corroborated and refined: what emerges around age 4 is an explicit, unified, flexibly conceptual capacity to ascribe propositional attitudes. This unified conceptual capacity contrasts with the less sophisticated, less unified implicit forms of tracking simpler mental states present in ontogeny long before. This refined version of the orthodoxy can thus most plausibly be spelled out in some form of 2-systems-account of theory of mind.
We present the ToMenovela, a stimulus set that has been developed to provide a set of normatively rated socio-emotional stimuli showing varying amount of characters in emotionally laden interactions for experimental investigations of (i) cognitive and (ii) affective Theory of Mind (ToM), (iii) emotional reactivity, and (iv) complex emotion judgment with respect to Ekman's basic emotions (happiness, anger, disgust, fear, sadness, surprise, Ekman and Friesen, 19(5). Stimuli were generated with focus on ecological validity and consist of 190 scenes depicting daily-life situations. Two or more of eight main characters with distinct biographies and personalities are depicted on each scene picture. To obtain an initial evaluation of the stimulus set and to pave the way for future studies in clinical populations, normative data on each stimulus of the set was obtained from a sample of 61 neurologically and psychiatrically healthy participants (31 female, 30 male; mean age 26.74 +/- 5.84), including a visual analog scale rating of Ekman's basic emotions (happiness, anger, disgust, fear, sadness, surprise) and free text descriptions of the content of each scene. The ToMenovela is being developed to provide standardized material of social scenes that are available to researchers in the study of social cognition. It should facilitate experimental control while keeping ecological validity high.
Background: The effects of therapeutic relationship (TR) in elder mental health are understudied. A greater understanding of TR in geriatric psychotherapy is particularly needed for treating late-life depression with executive dysfunction, which predicts poor response to antidepressant medication and presents unique clinical challenges. Methods: Participants were older patients (N = 220) with major depression and executive dysfunction who received 12 weeks of problem-solving therapy or supportive therapy in a randomized control trial. Multilevel growth curve modeling and latent change scores were used to analyze TR dimensions of Understanding and Accepting at the patient level (individual patient ratings, N = 194) and therapist level (ratings of each therapist averaged across participants, N = 10). Results: TR predicted reduction of depression in both treatment groups, while treatment x TR interactions were not significant. Patients treated by therapists with higher average Understanding (patient and therapist level) and Accepting (therapist level) ratings had greater decreases in depression. The patient level x therapist level interaction for Understanding approached statistical significance (p=.065), suggesting a synergistic effect on treatment outcome. Together, Understanding and Accepting predicted 21% of variance in depression level changes. Limitations: TR was not assessed throughout the course of treatment (only after the first therapy session and at post-treatment) and did not include ratings from an objective evaluator. Conclusions: Assessment of patient's experience of the TR and of therapist ability to foster Understanding and Accepting can play a significant role in the delivery of geriatric psychosocial interventions.
Cooking oils are an integral part of a human diet as they are used in almost all types of culinary practices. They serve as sources of lipids with a significant nutritive value and health benefits which can be attributed to their fatty acid compositions and biological antioxidants. However, cooking oils are usually subjected to thermal oxidation which occurs when fresh cooking oil is heated at high temperatures during various food preparations. Repeated use of cooking oils in the commercial food industry is also common to maximize profit. Thermal oxidation of edible oils had since attracted great attention of nutritionist and researchers given the deteriorative effect such as generation of very cytotoxic compounds, loss of carotenoid, phenolics and vitamins thus reducing the overall antioxidant properties of the oils. Furthermore, several in vivo studies had suggested that consumption of thermally-oxidized cooking oils might not be healthy as it might negatively influence the lipid profile (increased low density lipoprotein (LDL), decreased high density lipoprotein (HDL) and elevated cholesterol level), haematological system (alteration in concentration of heamoglobin (Hb), packed cell volume (PCV), white blood cell (WBC) count, neutrophil and lymphocyte counts), kidney function, and induce lipid peroxidation and oxidative stress which have been associated with the pathogenesis of various degenerative diseases. Therefore, thermal oxidation seems not to provide any health benefit, as it deteriorates cooking oils and the consumption of the oils may predispose consumers to various disease conditions that may ensue from free radical generation, thereby having deleterious effect on human health.
The reported digital thermionic emission current controllers use floating voltage sources which produce noise current and consequently decrease the quality of an electron beam. The implementation of digital control in an electron source biasing system without floating sources gives the average value of the electron emission current standard deviation of 0.015%. The described controller has been developed in order to investigate the properties of new hot-emitters.
Cyclic stability is a key factor in the design of thermochemical heat storage systems. Because carbon dioxide (CO2) may react with heat storage materials and lead to a decrease in energy storage efficiency, the effect of CO2 on Ca(OH)(2)/CaO and Mg(OH)(2)/MgO systems is investigated in this study. The experimental results show that CO2 reacts with CaO in the water vapor that appears during the heat release process. Therefore, in the design of Ca(OH)(2)/CaO systems, CO2 should be cleared from the system. The results from Mg(OH)(2)/MgO systems show that CO2 only slightly reacts with MgO and Mg(OH)(2) during heat storage and release processes. This study indicates that carbonic acid (H2CO3) could easily react with CaO/Ca(OH)(2) to form CaCO3 during heat release processes. Generally, the remaining CO2 reduces the reversibility of Ca(OH)(2)/CaO systems but has only a slight influence on Mg(OH)(2)/MgO systems. In addition, the experimental results show that carbonate shell does not exist in rehydration for both of the CaO/MgO samples, but the influence of CO2 on the entire process increases after each cycle. (C) 2017 Elsevier Ltd. All rights reserved.
In past centuries, men have mainly looked to increase their production of energy in order to develop their industry, means of transport and quality of life. Since the recent energy crisis, researchers and industrials have looked mainly to manage energy in a better way, especially by increasing energy system efficiency. This context explains the growing interest for thermoelectric generators. Today, thermoelectric generators allow lost thermal energy to be recovered, energy to be produced in extreme environments, electric power to be generated in remote areas and microsensors to be powered. Direct solar thermal energy can also be used to produce electricity. This review begins with the basic principles of thermoelectricity and a presentation of existing and future materials. Design and optimization of generators are addressed. Finally in this paper, we developed an exhaustive presentation of thermoelectric generation applications covering electricity generation in extreme environments, waste heat recovery in transport and industry, domestic production in developing and developed countries, micro-generation for sensors and microelectronics and solar thermoelectric generators. Many recent applications are presented, as well as the future applications which are currently being studied in research laboratories or in industry. The main purpose of this paper is to clearly demonstrate that, almost anywhere in industry or in domestic uses, it is worth checking whether a TEG can be added whenever heat is moving from a hot source to a cold source. (C) 2017 Elsevier Ltd. All rights reserved.
Micro/small-scale thermoelectric generation modules are able to produce continuous, noise-free and reliable electricity power using low temperature differences that widely exist in nature or industry. These advantages bring them great application prospects in the fields of remote monitoring, microelectronics/micro-electromechanical systems (MEMS), medical apparatus and smart management system, which often require a power source free of maintenance and vibration. In this work, a prototypical thermoelectric module (12 mm x 12 mm x 0.8 mm) with 15 pairs of micro-scale thermoelectric legs (0.2 mm in width and 0.6 mm in height for each leg) is fabricated using a low-cost mechanical machining process. In this process, cutting and polishing are the main methods for the preparation of thermoelectric pairs from commercial polycrystalline materials and for the fabrication of electrode patterns. The as-fabricated module is tested for its power generation properties with the hot side heated by an electrical heater and the cold side by cold air. With the heater temperature of 375 K, the thermoelectric potential is about 9.1 mV, the short circuit current is about 14.5 mA, and the maximum output power is about 32.8 mu W. The finite element method is applied to analyze the heat transfer of the module during our test. The temperature difference and heat flux are simulated, according to which the output powers at different temperatures are calculated, and the result is relatively consistent compared to the test results.
This study explores a method of generating electricity while recovering waste heat through the integration of heat pipes and thermoelectric generators (i.e. HPTEG system). The simultaneous waste heat recovery and power generation processes are achieved without the use of any moving parts. The HPTEG system consists of bismuth telluride thermoelectric generators (TEG), which are sandwiched between two finned pipes to achieve a temperature gradient across the TEG for electricity generation. A counter-flow heat exchanger was built using two separate air ducts. The air ducts were thermally coupled using the HPTEG modules. The evaporator section of the heat pipe absorbed the waste heat in a hot air duct. The heat was then transferred across the TEG surfaces. The condenser section of the HPTEG collected the excess heat from the TEG cold side before releasing it to the cold air duct. A 2-kW electrical heater was installed in the hot air duct to simulate the exhaust gas. An air blower was installed at the inlet of each duct to direct the flow of air into the ducts. A theoretical model was developed for predicting the performance of the HPTEG system using the effectiveness-number of transfer units method. The developed model was able to predict the thermal and electrical output of the HPTEG, along with the rate of heat transfer. The results showed that by increasing the cold air velocity, the effectiveness of the heat exchanger was able to be increased from approximately 52% to 58%. As a consequence of the improved heat transfer, maximum power output of 4.3 W was obtained.
Thermoelectric materials, which can convert waste heat into electricity, have received increasing research interest in recent years. This paper describes the recent progress in thermoelectric nanocomposites based on solution-synthesized nanoheterostructures. We start our discussion with the strategies of improving the power factor of a given material by using nanoheterostructures. Then we discuss the methods of decreasing thermal conductivity. Finally, we highlight a way of decoupling power factor and thermal conductivity, namely, incorporating phase-transition materials into a nanowire heterostructure. We have explored the lead telluride-copper telluride thermoelectric nanowire heterostructure in this work. Future possible ways to improve the figure of merit are discussed at the end of this paper.
Thiazolidinediones improve insulin resistance and endothelial dysfunction. However, the mechanisms underlying the vasoprotective effects of thiazolidinediones remain to be fully elucidated. The present study aimed to examine the molecular mechanism for the anti-vasoconstrictive effects of rosiglitazone in response to endothelin (ET) 1. Mouse aortas were treated with rosiglitazone for 24 hours, and ET-1-induced vasoconstriction was assessed by wire myography. The results showed that rosiglitazone attenuated ET-1-induced contraction in mouse aortas; this effect was abolished by ET-B receptor (ET(B)R) antagonist, NO synthase inhibitor, and by the removal of endothelium. By using Northern blotting, real-time RT-PCR, Western blotting, and immunohistochemical techniques, we found that rosiglitazone upregulated expression of ET(B)R at both mRNA and protein levels in mouse aortas and human vascular endothelial cells. The induction of ET(B)R was prevented by peroxisome proliferator-activated receptor-gamma antagonism. Luciferase reporter assay showed that rosiglitazone enhanced ETBR gene promoter activity. Furthermore, chromatin immunoprecipitation assays demonstrated that peroxisome proliferator-activated receptor-gamma can directly bind to ET(B)R gene promoter. Furthermore, in vivo treatment with rosiglitazone also attenuated the ET-1-induced vasoconstrictions and increased the ET(B)R expression in mouse aortas and mesenteric arteries. In conclusion, these results demonstrate that rosiglitazone attenuated ET-1-induced vasoconstriction through the upregulation of endothelial ET(B)R, which is a peroxisome proliferator-activated receptor-gamma direct target. (Hypertension. 2010; 56: 129-135.)
Organic and inorganic thin film transistors (TFTs) are fabricated, simulated, and tested for circuit applications. The devices are based on polycrystalline cadmium sulfide (CdS) and pentacene thin films. Both devices are simulated and analyzed using two-dimensional finite element simulation methodology. For CdS, grain boundary and uniform trap distribution approaches are implemented. It is assumed that traps due to grain boundaries are uniformly distributed throughout the film. For pentacene a Poole-Frenkel mobility model is employed. After matching device simulation with experimental data, the SPICE model parameters are extracted for circuit simulation. The devices are tested for both analog and digital circuits. operational amplifier (OPAMP) and inverter circuits are tested. Two OPAMP topologies are compared and the results are discussed. One of the topologies is based on all n-type transistors using CdS TFT and the other topology is the two-stage Miller compensated CMOS design based on CdS and pentacene TFTs. The operational amplifiers have an open-loop voltage gain of 25.9 dB and 29.7 dB respectively. The performance of the CMOS design is found to be limited by performance of pentacene transistor. (C) 2016 Elsevier B.V. All rights reserved.
A new sandwich structure which core is made of thin-walled semi-ellipsoidal shell is designed, column cell sandwich composite was prepared by pre-panel preparation process. A series of quasi-static axial compression experiments were carried out on 2 x 2 thin-walled semi-ellipsoidal shell, the compression deformation and yield behavior of thin wall semi-ellipsoidal shells with different materials, diameters and wall thicknesses were studied by means of ANSYS/LS-DYNA finite element simulation and experiment. Then, the effect of filling mode of epoxy resin on the mechanical properties of Column-cell sandwich composites was studied. The results show that the deformation process of the thin spherical shell can be divided into local flattening, axisymmetric depression, non-axisymmetric depression and compaction stage. As the wall thickness increases, the deformation"mode changes from the polygon to the ring and the deformation process become three stages; small diameter requires larger force under the conditions of the same compression displacement, as the diameter increases, the critical displacement of flipping and asymmetric buckling increases; Epoxy filled in the spherical shell of the sample specific compression performance is better than filled in the outer shell and better than unfilled with epoxy resin. (C) 2017 Elsevier B.V. All rights reserved.
In this study, we prepared a multi-functional thin-film thermoelectric device for small-scale energy harvesting and self-powered light sensing. A comprehensive optimization was conducted in terms of thermoelectric material, device, and system integration. The thermoelectric thin films in the device were prepared using the sputtering method together with a post-annealing process. A Fresnel lens was incorporated into the thin-film thermoelectric device for energy concentration. In addition, a simulation procedure was used to facilitate the optimization of the heat sink, which can provide fast heat dissipation and mechanical support for the thin-film thermoelectric device. The electricity generation and light sensing performance was then characterized under solar irradiation, followed by a feasibility study for sensor application. The results indicate that our thin-film thermoelectric device exhibits high voltage output and greatly enhanced responsivity. This work presents a significant progress toward an integrated design of an applicable and multifunctional thin-film thermoelectric sensor for detecting sunlight intensity.
Third-party punishment (TPP) for norm violations is an essential deterrent in large-scale human societies, and builds on two essential cognitive functions: evaluating legal responsibility and determining appropriate punishment. Despite converging evidence that TPP is mediated by a specific set of brain regions, little is known about their effective connectivity (direction and strength of connections). Applying parametric event-related functional MRI in conjunction with multivariate Granger causality analysis, we asked healthy participants to estimate how much punishment a hypothetical perpetrator deserves for intentionally committing criminal offenses varying in levels of harm. Our results confirmed that TPP legal decisions are based on two domain-general networks: the mentalizing network for evaluating legal responsibility and the central-executive network for determining appropriate punishment. Further, temporal pole (TP) and dorsomedial prefrontal cortex (PFC) emerged as hubs of the mentalizing network, uniquely generating converging output connections to ventromedial PFC, temporo-parietal junction, and posterior cingulate. In particular, dorsomedial PFC received inputs only from TP and both its activation and its connectivity to dorsolateral PFC correlated with degree of punishment. This supports the hypothesis that dorsomedial PFC acts as the driver of the TPP activation pattern, leading to the decision on the appropriate punishment. In conclusion, these results advance our understanding of the organizational elements of the TPP brain networks and provide better insights into the mental states of judges and jurors tasked with blaming and punishing legal wrongs.
This paper presents the three stage CMOS operational amplifier (op amp) with class A output stage designed in SilTerra's 130 nm CMOS technology. The designed three stage op amp employed an indirect feedback compensation technique produces an open loop gain (AOL), for both schematic and layout are 102 dB and 117 dB respectively. the op amp produces 40.5 MHz gain-bandwidth product (GBW), 90 degrees phase margin(PM) and 54.6 V/mu s slew rate (SR) for 5 pF load. Furthermore, the op amp has capability to drive the 15 pF load, produces 25.5 MHz GBW and 45 degrees PM. The circuit was operated at the single supply voltage of 2.5 V with power consumption of 0.977 mW and the layout area was 0.0022 mm(2).
Due to the potential applications of the chaotic system, in the recent years, the research of the new type of chaotic systems and their chaotic circuits is a research hot spot. However, there are obvious differences between real characteristics and simulation results of the devices such as operational amplifier. In this paper, the simplified method of circuit improvement is proposed, which achieves the same results between Multisim software simulation and actual circuit implementation. Meanwhile feedback synchronization method is applied to complete the actual circuit of the synchronization control. Compared with the original circuit, the proposed method of circuit improvement makes minor changes from the simulation circuits and is easy to be implemented, which can be applied for other chaotic systems.
Due to the potential applications of the chaotic system, in recent years, the research of a new type of chaotic system and chaotic circuit is a hot spot. However, there are obvious differences between real characteristics and simulation results of the devices, such as the operational amplifier. In this paper, the simplified method of the circuit improvement is proposed, which achieves the same results between Multisim software simulation and actual circuit implementation. Meanwhile, impulsive synchronization method is applied to complete the synchronization control of the chaotic system. Compared with the original circuit, the proposed method of circuit improvement makes minor changes from the simulation circuit and is easy to be implemented, which can be applied for other chaotic systems.
This paper presents a three-dimensional (3-D) space vector pulse width modulation (SVPWM) technique via a 4 x 4 orthonormal transformation matrix that has been used as a new approach in controlling a three-phase four-leg voltage source inverter (VSI). A fully optimal digital control scheme for the closed-loop regulation of the three-phase four-leg VSI has been used to synthesize a sinusoidal waveform with the help of the proposed method. Discrete-time modelling of each phase has been obtained independently in abc reference frame, and its optimal controller has been designed using a predefined performance index. A DSP-based controlled three-phase four-leg prototype VSI has been designed to verify the proposed discrete time modelling and the control scheme. The simulations and the real-time experiments show that satisfactory results have been obtained for the modelling of the three-phase four-leg VSI in abc reference frame and the 3-D SVPWM technique via 4 x 4 orthonormal transformation matrix at 20 kHz switching frequency.
The principle of a diode neutral point clamped three-phase three-level inverter with neutral line was analyzed, and the mathematical model of the main circuit is established on the basis of the operation principle. The oversample and multi-time calculation control strategy was proposed to reduce the typical delay in digital control and improve the system calculation accuracy, lower the inverter output voltage THD. In order to further improve the inverter output voltage waveform, the logic external execution was also proposed. The proposed control method was verified on a 20kVA inverter controlled by microchip processor IC30F5015 DSP. The experiment results indicated that the THD of the inverter output voltage is decreased considerably.
A novel frequency compensation technique, named Regular Miller plus Reversed Indirect Compensation (RMRIC), is presented in this paper for fast-settling three-stage amplifiers. The RMRIC topology includes, on the one hand, a Miller capacitor combined with one nulling resistor connected between the first stage and the third stage, and on the other hand, an indirect compensation capacitor in series with a resistor added between the first and the second stage, which improves remarkably the performance such as gain-bandwidth product (GBW) and sensitivity of the proposed amplifier. Detailed design considerations are carried out to demonstrate the stability of the compensation technique. Circuit simulation results show the amplifier driving a 2-pF load capacitance achieves a 9.25-GHz GBW dissipating only 16.5 mW with a 1.2 V supply voltage using a TSMC 65 nm CMOS technology, which shows a significant improvement in figure of merits. The implemented amplifier reaches a settling time of 3.35 ns with 0.006 % accuracy.
An analysis is reported here for three-time level integration methods following the global spectral analysis (GSA) described in High Accuracy Computing Methods, T.K. Sengupta, Cambridge Univ. Press, USA. The focus is on the second order Adams-Bashforth (AB2) and the extrapolation in time (EXT2) methods. Careful distinction is made for the first time step at t = 0 by either Euler forward or four-stage, fourth order Runge-Kutta (RK4) time schemes. The latter is used to solve a benchmark aeroacoustic problem. Several one-dimensional wave propagation models are analyzed: pure advection and advection-diffUsion equations. Various spatial discretizations are discussed, including Fourier spectral method. Attention is paid to the presence of physical and numerical modes as noted in the quadratic equation obtained from the difference equation for the model 1D convection equation. It is shown that AB2 method is less stable and accurate than EXT2 method, with respect to numerical dissipation and dispersion. This is true for the methods, in which the physical mode dominates over the numerical mode. Presented analysis provides useful guide to analyze any three-time level methods. (C) 2017 Elsevier Inc. All rights reserved.
Thymic atrophy occurs during infection being associated with apoptosis of double positive (DP) and premature exit of DP and double negative (DN) thymocytes. We observed for the first time that a significant bone marrow aplasia and a decrease in common lymphoid progenitors (CLPs) preceded thymic alterations in mice infected with Trypanosoma cruzi. In addition, depletion of the DN2 stage was previous to the DN1, indicating an alteration in the differentiation from DN1 to DN2 thymocytes. Interestingly, infected mice deficient in IL-6 expression showed higher numbers of DP and CD4(+) thymocytes than wild type infected mice, while presenting similar percentages of DN1 thymocytes. Moreover, the drop in late differentiation stages of DN thymocytes was partially abrogated in comparison with wild type littermates. Thus, our results suggest that thymic atrophy involves a drop in CLPs production in bone marrow and IL-6-dependent and independent mechanisms that inhibits the differentiation of DN thymocytes.
Survivin and its splice variants DEx3 and 2B are involved in pathogenesis of numerous types of cancer. Proliferating cell nuclear antigen (PCNA) level correlates with cellular proliferation. The present study aimed to analyze the potential utility of survivin and its splice variants DEx3 and 2B as biomarkers for thyroid cancer. PCNA, survivin and its splice variants DEx3 and 2B expressions were analyzed in 22 tissue samples (15 thyroid cancers and 7 benign lesions) by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry (IHC). There was significantly higher staining for survivin (P=0.019), survivin DEx3 (P=0.001), survivin 2B (P=0.0149) and PCNA (P=0.0237) in thyroid malignant tumors when compared with benign lesions. The receiver operating characteristics curve analysis has shown that the cut-off points of survivin IHC expression >2 [sensitivity 46.7%; specificity 100%; area under curve (AUC) 0.810; P=0.0005] and survivin DEx3 IHC expression >0 (sensitivity 86.7%; specificity 100%; AUC 0.933; P1 (sensitivity 93.3%; specificity 71.4%; AUC 0.790; P=0.0243) and survivin 2B >2 (sensitivity 46.7%; specificity 100%; AUC 0.824; P=0.0002) were the best predictors of thyroid cancer. In conclusion, the present study exhibited that survivin DEx3 expression has high specificity and sensitivity for discrimination between benign thyroid lesions and cancers. Survivin DEx3 may be considered a biological marker of thyroid malignancy and therefore applied in clinical practice.
Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF(V600E) is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF(V600E) and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated.
Thyroid hormones (THs) are crucial for normal vertebrate development and are the one obligate morphogen that drives amphibian metamorphosis. However, contrary to other metamorphosing vertebrates, lampreys exhibit a sharp drop in serum TH early in metamorphosis, and anti-thyroid agents such as potassium perchlorate (KClO4) induce metamorphosis. The type 2 deiodinase (D2) enzyme is a key regulator of TH availability during amphibian metamorphosis. We set out to determine how D2 may be involved in the regulation of lamprey metamorphosis and thyroid homeostasis. We cloned a 1.8 Kb Petromyzon marinus D2 cDNA that includes the entire protein coding region and a selenocysteine (Sec) codon. Northern blotting indicated that the lamprey D2 mRNA is the longest reported to date (>9 Kb). Using real-time PCR, we showed that intestinal and hepatic D2 mRNA levels were elevated prior to and during the early stages of metamorphosis and then declined dramatically to low levels that were sustained for the remainder of metamorphosis. These data are consistent with previously reported changes in serum TH levels and deiodinase activity. Treatment of larvae with either TH or KClO4 significantly affected D2 mRNA levels in the intestine and liver. These D2 mRNA levels during metamorphosis and in response to thyroid challenges suggest that D2 may function in the regulation of TH levels during lamprey metamorphosis and the maintenance of TH homeostasis. (C) 2013 Elsevier Inc. All rights reserved.
Most patients with thyroid cancer will evolve very well with current therapies. However, 10-30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical management of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular variant of papillary thyroid carcinomas, 11 poorly differentiated thyroid carcinomas and 42 follicular thyroid carcinomas. Patients were treated according to current guidelines and followed-up for 1-150 months. Additionally, we studied 96 samples of non-malignant tissues. We investigated the expression of IL-10 in tumor cells by semiquantitative and quantitative methods. Malignant tissues presented higher positivity (0.773 +/- 0.140) than non-malignant samples (0.623 +/- 0.190; p < 0.001). Tumors with extrathyroidal invasion at diagnosis presented higher levels of positivity for IL-10 (0.802 +/- 0.125) than tumors without extrathyroidal invasion (0.731 +/- 0.147; p = 0.004). We observed a positive correlation between tumor size and IL-10 positivity (correlation coefficient = 0.407; p < 0.001). Patients with IL-10 positivity above the median presented lower relapse-free survival rate compared to those patients whose tumors presented IL-10 positivity below the median. We suggest that a simple IL-10 IHC analysis could help selecting patients who would benefit from a more intensive approach.
A 2x2 pixel array for Sub-THz detection in which each pixel can be separately addressed has been integrated in a low-cost 0.18 mu m CMOS technology. Each pixel comprises of an NMOS incoherent power detection circuit and a high gain operational amplifier. Efficiency of self-mixing is analyzed and improved for FET detector and the operational amplifier. Sequential pulse generator is used in the design of row and column signal producing circuit in pixel array. The measured peak responsivity is 3.3 kV/W at 90 GHz, 4.3 kV/W at 155 GHz. For comparison, the pixel without load resistor is also characterized. The measured results show that the pixel with load resistor can efficiently increase the pixel output.
Background: There has been an emergence and expansion of tick-borne diseases in Europe, Asia and North America in recent years, including Lyme disease, tick-borne encephalitis and human anaplasmosis. The primary vectors implicated are hard ticks of the genus Ixodes. Although much is known about the host response to these bacterial and viral pathogens, there is limited knowledge of the cellular responses to infection within the tick vector. The bacterium Anaplasma phagocytophilum is able to bypass apoptotic processes in ticks, enabling infection to proceed. However, the tick cellular responses to infection with the flaviviruses tick-borne encephalitis virus (TBEV) and louping ill virus (LIV), which cause tick-borne encephalitis and louping ill respectively, are less clear. Results: Infection and transcriptional analysis of the Ixodes ricinus tick cell line IRE/CTVM20 with the viruses LIV and TBEV, and the bacterium A. phagocytophilum, identified activation of common and distinct cellular pathways. In particular, commonly-upregulated genes included those that modulate apoptotic pathways, putative anti-pathogen genes, and genes that influence the tick innate immune response, including selective activation of toll genes. Conclusion: These data provide an insight into potential key genes involved in the tick cellular response to viral or bacterial infection, which may promote cell survival and host resistance.
Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.
The Pacific coast tick, Dermacentor occidentalis Marx, is found throughout California and can harbor agents that cause human diseases such as anaplasmosis, ehrlichiosis, tularemia, Rocky Mountain spotted fever and rickettsiosis 364D. Previous studies have demonstrated that nonpathogenic endosymbiotic bacteria can interfere with Rickettsia co-infections in other tick species. We hypothesized that within D. occidentalis ticks, interference may exist between different nonpathogenic endosymbiotic or nonendosymbiotic bacteria and Spotted Fever group Rickettsia (SFGR). Using PCR amplification and sequencing of the romp A gene and intergenic region we identified a cohort of SFGR-infected and non-infected D. occidentalis ticks collected from San Diego County. We then amplified a partial segment of the 16S rRNA gene and used next-generation sequencing to elucidate the microbiomes and levels of co-infection in the ticks. The SFGR R. philipii str. 364D and R. rhipicephali were detected in 2.3% and 8.2% of ticks, respectively, via romp. A sequencing. Interestingly, next generation sequencing revealed an inverse relationship between the number of Francisella- like endosymbiont (FLE) 16S rRNA sequences and Rickettsia 16S rRNA sequences within individual ticks that is consistent with partial interference between FLE and SFGR infecting ticks. After excluding the Rickettsia and FLE endosymbionts from the analysis,there was a small but significant difference in microbial community diversity and a pattern of geographic isolation by distance between collection locales. In addition, male ticks had a greater diversity of bacteria than female ticks and ticks that weren't infected with SFGR had similar microbiomes to canine skin microbiomes. Although experimental studies are required for confirmation, our findings are consistent with the hypothesis that FLEs and, to a lesser extent, other bacteria, interfere with the ability of D. occidentalis to be infected with certain SFGR. The results also raise interesting possibilities about the effects of putative vertebrate hosts on the tick microbiome.
Groups of a typical operational amplifier-mu A741 were irradiated in a cobalt unit, each group accumulating a different total ionizing dose (TID). The results showed that the TID caused power consumption current and slew rate (SR) to degenerate in ultra-linearity, owing to a severe reduction in the current gain of the internal LPNP transistors. Pulsed X-ray irradiation experiments were carried out on the mu A741 groups with different values, and the results revealed that the impact on the response to the pulsed X-ray irradiation was greater when the devices absorbed more TID. The mechanism for this is explained on the basis of the circuit construction of the mu A741; the sensitive parameters of the circuit were obtained via simulation on SPICE. The simulation results additionally showed that if the sensitive parameters were optimized, the duration of interruption caused by the pulsed X-ray irradiation would be reduced significantly. In addition, several proposals are provided for hardening the devices.
Laboratory testing of tidal turbine models is an essential tool to investigate hydrodynamic interactions between turbines and the flow. Such tests can be used to calibrate numerical models and to estimate rotor loading and wake development to inform the design of full scale machines and array layout. The details of the design and manufacturing techniques used to develop a highly instrumented turbine model are presented. The model has a 1.2 m diameter, three bladed horizontal axis rotor and is bottom mounted. Particular attention is given to the instrumentation which can measure streamwise root bending moment for each blade and torque and thrust for the overall rotor. The model is mainly designed to investigate blade and shaft loads due to both turbulence and waves. Initial results from tests in a 2 m deep by 4 m wide flume are also presented. (C) 2017 The Authors. Published by Elsevier Ltd.
This article aims at introducing the first steps of development and validation of a CFD tool dedicated to realistic tidal turbine farm modelling. The fluid solver is presented in details, together with the actuator disc model used to represent tidal turbines. A particular attention is paid to the spatial scheme in order to limit the numerical diffusion in the wakes. Comparisons with experimental results from Mycek et al. [1] on a horizontal axis tidal turbine (HATT) are presented and discussed. For the different cases, averaged axial velocities and averaged turbulence intensity rates are compared from 1.2 to 10 tidal turbine diameters behind the device. The properties of this tool are discussed in terms of accuracy, CPU costs and applicability to industrial purpose. (C) 2017 Elsevier Ltd. All rights reserved.
The time delay caused by the calculation time is unavoidable for the implementation of digital controller and also degrades the control performance. In order to cope with the time delay for the control of single-phase uninterruptible power supply (UPS), this paper proposes the time delay compensator based on the Smith-predictor for both voltage and current controller and also evaluates the usefulness of the compensator by analytic analysis and experimental results. Theoretically the compensator alleviates the effect of time delay for both voltage and current controller, but the compensation for the fast current control is usually sufficient from the practical point of view. The experimental results are presented to show the validity of the proposed design and analysis of the time delay compensator for single-phase UPS.
This paper analyzes first the stability of single-loop digital voltage control scheme for the LC-filtered voltage source inverters. It turns out that the phase lag, caused by the time delay of digital control system and by the use of integral controller, can stabilize the voltage loop without damping of LC-filter resonance. The stability regions are then identified with alternative voltage controller synthesized. For further widening the stability region, an active damping approach is proposed and co-designed with the voltage controller in the discrete z-domain. Simulations and experimental results of both 50-Hz and 400-Hz systems validate the theoretical analyses and the performance of the approach.
Perceptual systems must rapidly generate accurate representations of the world from sensory inputs that are corrupted by internal and external noise. We can typically obtain more veridical representations by integrating information from multiple channels, but this integration can lead to biases when inputs are, in fact, not from the same source. Although a considerable amount is known about how different sources of information are combined to influence what we perceive, it is not known whether temporal features are combined. It is vital to address this question given the divergent predictions made by different models of cue combination and time perception concerning the plausibility of cross-modal temporal integration, and the implications that such integration would have for research programs in action control and social cognition. Here we present four experiments investigating the influence of movement duration on the perceived duration of an auditory tone. Participants either explicitly (Experiments 1-2) or implicitly (Experiments 3-4) produced hand movements of shorter or longer durations, while judging the duration of a concurrently presented tone (500-950 ms in duration). Across all experiments, judgments of tone duration were attracted toward the duration of executed movements (i.e., tones were perceived to be longer when executing a movement of longer duration). Our results demonstrate that temporal information associated with movement biases perceived auditory duration, placing important constraints on theories modeling cue integration for state estimation, as well as models of time perception, action control and social cognition.
In deregulated electricity markets the independent system operator (ISO) oversees the power system and manages the supply and demand balancing process. In a typical day the ISO announces the electricity demand forecast for the next day and gives participants an option to prepare offers to meet the demand. In order to have a reliable power system and successful market operation, it is crucial to estimate the electricity demand accurately. In this paper, we develop an hourly demand forecasting method on annual, weekly and daily horizons, using a linear model that takes into account the harmonics of these variations and the modulation of diurnal periodic variations by seasonal variations. The electricity demand exhibits cyclic behavior with different seasonal characteristics. Our model is based solely on sinusoidal variations and predicts hourly variations, without using any climatic or econometric information. The method is applied to the Turkish power market on data for the period 2012-2014 and predicts the demand over daily and weekly horizons within a 3% error margin in the Mean Absolute Percentage Error (MAPE) norm. We also discuss the week day/weekend/holiday consumption profiles to infer the proportion of industrial and domestic electricity consumption. (C) 2017 Elsevier Ltd. All rights reserved.
This study examines the statistical process control chart used to detect a parameter shift with Poisson integer-valued GARCH (INGARCH) models and zero-inflated Poisson INGARCH models. INGARCH models have a conditional mean structure similar to GARCH models and are well known to be appropriate to analyzing count data that feature overdispersion. Special attention is paid in this study to conditional and general likelihood ratio-based (CLR and GLR) CUSUM charts and the score function-based CUSUM (SFCUSUM) chart. The performance of each of the proposed methods is evaluated through a simulation study, by calculating their average run length. Our findings show that the proposed methods perform adequately, and that the CLR chart outperforms the GLR chart when there is an increased shift of parameters. Moreover, the use of the SFCUSUM chart in particular is found to lead to a lower false alarm rate than the use of the CLR chart.
Over the past years, many representations for time series were proposed with the main purpose of dimensionality reduction and as a support for various algorithms in the domain of time series data processing. However, most of the transformation algorithms are not directly applicable on streams of data but only on static collections of the data as they are iterative in their nature. In this work we propose a symbolic representation of time series along with a method for transformation of time series data into the proposed representation. As one of the basic requirements for applicable representation is the distance measure which would accurately reflect the true shape of the data, we propose a distance measure operating on the proposed representation and lower bounding the Euclidean distance on the original data. We evaluate properties of the proposed representation and the distance measure on the UCR collection of datasets. As we focus on stream data processing, we evaluate the properties and limitations of the proposed representation on very long time series from the domain of electricity consumption monitoring, simulating the processing of potentially unbound data stream. (C) 2016 Elsevier Inc. All rights reserved.
In this paper, we analyse the local stability of a gene-regulatory network and immunotherapy for cancer modelled as nonlinear time-delay systems. A numerically generated kernel, using the sum-of-squares decomposition of multivariate polynomials, is used in the construction of an appropriate Lyapunov-Krasovskii functional for stability analysis of the networks around an equilibrium point. This analysis translates to verifying equivalent LMI conditions. A delay-independent asymptotic stability of a second-order model of a gene regulatory network, taking into consideration multiple commensurate delays, is established. In the case of cancer immunotherapy, a predator-prey type model is adopted to describe the dynamics with cancer cells and immune cells contributing to the predator-prey population, respectively. A delay-dependent asymptotic stability of the cancer-free equilibrium point is proved. Apart from the system and control point of view, in the case of gene-regulatory networks such stability analysis of dynamics aids mimicking gene networks synthetically using integrated circuits like neurochips learnt from biological neural networks, and in the case of cancer immunotherapy it helps determine the long-term outcome of therapy and thus aids oncologists in deciding upon the right approach.
This paper presents the control method of an LCL filter implemented for a three-phase, voltage-source, grid-connected inverter for not only offering better attenuation of switching harmonics but also for highly damping the resonance. A discrete-time deadbeat current controller with tuned state-feedback gains is proposed to realize the time optimum responses with high control accuracy. In addition, the influences of different grid inductances and switching frequencies of the three-level T-type inverter on the controller gains are discussed. The analytical design of the three dimensional deadbeat controller dealing with the instantaneous space vectors is examined under varying grid inductance. The effectiveness of the optimum feedback gains on the control performance is validated experimentally. The deadbeat controller can provide the fastest response and damp the resonance of the LCL filter at relatively low switching frequency in comparison with the filter size.
This paper explores the large-signal and small-signal dynamics of a series-capacitor (SC) buck-type converter and introduces an optimal closed-loop control scheme to accommodate both the steady-state and transient modes. As opposed to a conventional buck converter, where time-optimal control is realized by a single on-off cycle, in the SC-buck topology there is a need to distribute the switching phases to satisfy the charge-balance of the flying capacitor. The new control method hybrids a voltage-mode small-signal controller for steady-state operation and a non-linear, state-plane based transient-mode control scheme for load transients. A detailed principle of operation of the SC-buck converter is provided and explained through an average behavioral model and state-plane analysis. The operation of the controller is experimentally verified on a 12W 12V-to-1.5V converter, demonstrating voltage-mode control operation as well as time-optimal response for load transients.
There is a growing consensus that a fuller understanding of social cognition depends on more systematic studies of real-time social interaction. Such studies require methods that can deal with the complex dynamics taking place at multiple interdependent temporal and spatial scales, spanning sub-personal, personal, and dyadic levels of analysis. We demonstrate the value of adopting an extended multi-scale approach by re-analyzing movement time-series generated in a study of embodied dyadic interaction in a minimal virtual reality environment (a perceptual crossing experiment). Reduced movement variability revealed an interdependence between social awareness and social coordination that cannot be accounted for by either subjective or objective factors alone: it picks out interactions in which subjective and objective conditions are convergent (i.e., elevated coordination is perceived as clearly social, and impaired coordination is perceived as socially ambiguous). This finding is consistent with the claim that interpersonal interaction can be partially constitutive of direct social perception. Clustering statistics (Allan Factor) of salient events revealed fractal scaling. Complexity matching defined as the similarity between these scaling laws was significantly more pronounced in pairs of participants as compared to surrogate dyads. This further highlights the multi-scale and distributed character of social interaction and extends previous complexity matching results from dyadic conversation to non-verbal social interaction dynamics. Trials with successful joint interaction were also associated with an increase in local coordination. Consequently, a local coordination pattern emerges on the background of complex dyadic interactions in the PCE task and makes joint successful performance possible.
Variations of the examination timetabling problem have been investigated by the research community for more than two decades. The common characteristic between all problems is the fact that the definitions and datasets used all originate from actual educational institutions, particularly universities, including specific examination criteria and the students involved. Although much has been achieved and published on the state-of-the-art problem modelling and optimisation, a lack of attention has been focussed on the students involved in the process. This work presents and utilises the results of an extensive survey seeking student preferences with regard to their individual examination timetables, with the aim of producing solutions which satisfy these preferences while still also satisfying all existing benchmark considerations. The study reveals one of the main concerns relates to fairness within the student's cohort; i.e. a student considers fairness with respect to the examination timetables of their immediate peers, as highly important. Considerations such as providing an equitable distribution of preparation time between all student cohort examinations, not just a majority, are used to form a measure of fairness. In order to satisfy this requirement, we propose an extension to the state-of-the-art examination timetabling problem models widely used in the scientific literature. Fairness is introduced as a new objective in addition to the standard objectives, creating a multi-objective problem. Several real-world examination data models are extended and the benchmarks for each are used in experimentation to determine the effectiveness of a multi-stage multi-objective approach based on weighted Tchebyceff scalarisation in improving fairness along with the other objectives. The results show that the proposed model and methods allow for the production of high quality timetable solutions while also providing a trade-off between the standard soft constraints and a desired fairness for each student. (C) 2017 Elsevier B.V. All rights reserved.
The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.
Anatase TiO2 crystal facets are garnering increasing attention due to their unique surface property. However, no specific linear relationship had been derived between the facet exposed on TiO2 and the surface adsorption capacity as well as photocatalytic performance. This study systematically explored the facet effects on antimony (Sb) adsorption and photocatalytic oxidation using high-index {201) and low-index {101), {001), and {100) TiO2. The results suggest that high-index {201) TiO2 exhibits the best Sb(III) adsorption and photocatalytic activity compared to the low-index TiO2. Both the Sb(III) adsorption density and the amount of "OH and O-2(.)-generated in solution were correlated to the magnitude of surface energy on TiO2 facets. Photocatalytically generated 'OH and (T)-were responsible for Sb(III) photooxidation as evidenced by radical-trapping experiments. The great contribution of 'OH was observed only on {2011 not on low-index TiO2. This phenomenon was found to be attributable to the high surface energy on {201), which enables the generation of a large amount of photogeneration 'OH to compensate for the fast rate of (OH)-O-. dissipation. Therefore, the predominant participation of 'OH in Sb(III) photooxidation was only possible on high-index {201) TiO2, which resulted in an enhanced photocatalytic rate. On the other hand, %-dominated the Sb(III) photocatalytic oxidation on low-index TiO2. The intrinsic facet-dependent adsorption and photocatalytic mechanism obtained from this study would be useful for developing TiO(2)based environmental technologies. (C) 2017 Elsevier Inc. All rights reserved.
Light-driven synthetic micro-/nanomotors have attracted considerable attention in recent years due to their unique performances and potential applications. We herein demonstrate the dye-enhanced self-electrophoretic propulsion of light-driven TiO2-Au Janus micromotors in aqueous dye solutions. Compared to the velocities of these micromotors in pure water, 1.7, 1.5, and 1.4 times accelerated motions were observed for them in aqueous solutions of methyl blue (10(-5) g L-1), cresol red (10(-4) g L-1), and methyl orange (10(-4) g L-1), respectively. We determined that the micromotor speed changes depending on the type of dyes, due to variations in their photodegradation rates. In addition, following the deposition of a paramagnetic Ni layer between the Au and TiO2 layers, the micromotor can be precisely navigated under an external magnetic field. Such magnetic micromotors not only facilitate the recycling of micromotors, but also allow reusability in the context of dye detection and degradation. In general, such photocatalytic micro-/nanomotors provide considerable potential for the rapid detection and "on-thefly'' degradation of dye pollutants in aqueous environments.
Aim: The aim of this study was to evaluate proliferation and chondrogenic differentiation of human bone-marrow mesenchymal stromal cells (hBMSCs) cultured on collagen biomaterials. Materials and Methods: hBMSCs were seeded on five different collagen (Col) sponges: C1C2 (types I and II Col), C1C2HS (types I and II Col plus heparan sulphate (HS)), C1C2CHS (types I and II Col plus chondroitin sulphate (CHS)), C1-OLH3 (type I Col plus low molecular weight heparin) and C1CHS (type I Col plus CHS). The resulting constructs were analyzed by histological and immunohistochemical staining, molecular biology and electron microscopy. Col released into culture media was measured by a dye-binding method. Results: hBMSCs on biomaterials C1C2, C1C2HS and C1C2CHS had more capacity to attach, proliferate and synthesize Col II and proteoglycans in the extracellular matrix (ECM) than on C1-OLH3 and C1CHS. The presence of aggrecan was detected only at the gene level. Total Col liberated by the cells in the supernatants in all scaffold cultures was detected. The level of Col I in the ECM was lower in C1-OLH3 and that of Col II was highest in C1C2 and C1C2HS. Electron microscopy showed differently shaped cells, from rounded to flattened, in all constructs. Col fibers in bundles were observed in C1C2CHS by transmission electron microscopy. Conclusions: The results show that Col I and Col II (C1C2, C1C2HS and C1C2CHS) biomaterials allowed cell proliferation and chondrogenic-like differentiation of hBMSCs at an early stage. Constructs cultured on C1C2HS and C1C2CHS showed better cartilage-like phenotype than the other ones.
In this paper a low power and low output ripple regulator is designed with teaching-learning-based optimization (TLBO) for radio frequency identification applications. In order to decrease the power consumption the voltage of regulator sub-blocks is supplied from elementary stages. In the proposed operational amplifier employed to the regulator, adaptive biasing is used and bandgap reference of the regulator is totally designed by MOSFET. To optimize the proposed regulator after modeling the regulator with the help of neural network, TLBO algorithm is used. The outputs of TLBO are output voltage, ripple value and power consumption. By using this algorithm the output voltage is 0.8 V with 2.78 mV ripple and power consumption. Also the quiescent current of this design is decreased to 290 nA. The chip area of the layout design in Cadence software is about . The operation frequency of this circuit is 960 MHz and the simulation is done in CMOS technology.
Background: High mobility group box-1 (HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 participates in the pathogenesis of autoimmune thyroiditis, and whether glycyrrhizin (GL), a direct inhibitor of HMGB1, attenuates the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis. Methods: A total of 80 male NOD. H-2(h4) mice were randomly divided into a control or iodine supplement (NaI) group at four weeks of age, and the control group was fed with regular water, whereas the NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD. H-2(h4) mice were also randomized into three groups (eight mice per group) as follows: control, NaI, and GL treatment after iodine supplementation (NaI + GL). The NOD.H-2 (h4) mice were fed with 0.005% sodium iodide water for eight weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of GL for four weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological studies. The serum levels of HMGB1, tumor necrosis factor alpha, interleukin (IL)-6, IL-1 beta, and thyroglobulin antibody titers were measured using an enzyme-linked immunosorbent assay. HMGB1 expression was measured by immunohistochemical staining and real-time polymerase chain reaction. TLR2, HMGB1, MyD88, and nuclear transcription factor kappa B were measured by Western blot. Results: The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in the NaI group than it was in the control group. Serum levels of thyroglobulin antibodies, HMGB1, tumor necrosis factor alpha, IL-6, and IL-1 beta were significantly increased in the NaI group, but they were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor jB in the thyroid gland and attenuated the severity of thyroiditis. Conclusion: HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD. H-2(h4) mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.
BACKGROUND: Polybutylene succinate (PBSu) and PBSu/beta-tricalcium phosphate (TCP) composites are biocompatible and good candidates as bone graft materials. However, little is known about the responses of T lymphocytes to these biomaterials, which play an important role in the success of bone grafting. METHODS: Activated T lymphocytes were cultured onto 32 mm diameter films (PBSu/TCP films), that had previously been placed in 6-well culture plates, for 8, 24 and 72 hours. A plastic-well culture plate was used as a control surface. The effects of PBSu-based biomaterials on T lymphocytes were examined by the using flow cytometry and reversetranscription polymerase chain reaction. RESULTLTS: These biomaterials were non-toxic to T lymphocytes, allowing their normal DNA synthesis and activation. All materials induced only transient activation of T lymphocytes, which existed no longer than 72 hours. Proportions of four main CD4/CD8 T lymphocyte subpopulations were not affected by these biomaterials. Moreover, PBSu and PBSu/TCP significantly suppressed the expression of IL-1 beta and IL-6 genes by 15-35% and 21-26%, respectively. In contrast, a PBSu/TCP composite (at PBSu: TCP= 60: 40) significantly stimulated the expression of IL-10 and IL-13 genes by 17% and 19%, respectively. CONCLUSIONS: PBSu and PBSu/TCP composites were non-toxic to T lymphocytes and did not induce unfavorable responses of T lymphocytes. The tested biomaterials down-regulated key proinflammatory cytokine genes and up-regulated anti-inflammatory cytokine genes in T lymphocytes. These suggest that the biomaterials studied are good candidates as bone graft materials.
PURPOSE. Trabecular meshwork (TM) cell volume is a determinant of aqueous humor outflow resistance, and thereby IOP. Regulation of TM cell volume depends on chloride ion (Cl-) release through swelling-activated channels (I-Cl,I-Swell), whose pore is formed by LRRC8 proteins. Chloride ion release through swelling-activated channels has been reported to be regulated by calcium-activated anoctamins, but this finding is controversial. Particularly uncertain has been the effect of anoctamin Ano6, reported as a Ca2+-activated Cl- (CaCC) or cation channel in other cells. The current study tested whether anoctamin activity modifies volume regulation of primary TM cell cultures and cell lines. METHODS. Gene expression was studied with quantitative PCR, supplemented by reverse-transcriptase PCR andWestern immunoblots. Currents were measured by ruptured whole-cell patch clamping and volume by electronic cell sizing. RESULTS. Primary TM cell cultures and the TM5 and GTM3 cell lines expressed Ano6 3 to 4 orders of magnitude higher than the other anoctamin CaCCs (Ano1 and Ano2). Ionomycin increased cell Ca2+ and activated macroscopic currents conforming to CaCCs in other cells, but displayed significantly more positive mean reversal potentials (+5 to +12 mV) than those displayed by I-Cl,I-Swell (-14 to -21 mV) in the same cells. Nonselective CaCC inhibitors (tannic acid>CaCC(inh-)A01) and transient Ano6 knockdown strongly inhibited ionomycin-activated currents, I-Cl,I-Swell and the regulatory volume response to hyposmotic swelling. CONCLUSIONS. Ionomycin activates CaCCs associated with net cation movement in TM cells. These currents, I-Cl,I-Swell, and cell volume are regulated by Ano6. The findings suggest a novel clinically-relevant approach for altering cell volume, and thereby outflow resistance, by targeting Ano6.
The tumor necrosis factor (TNF) receptors and their corresponding cytokine ligands have been implicated in many aspects of the biology of immune functions. TNF receptors have key roles during various stages of T cell homeostasis. Many of them can co-stimulate lymphocyte proliferation and cytokine production. Additionally, several TNF cytokines can regulate T cell differentiation, including promoting Th1, Th2, Th17, and more recently the newly described Th9 subset. Four TNF family cytokines have been identified as regulators for IL-9 production by T cells. OX40L, TL1A, and GITRL can promote Th9 formation but can also divert iTreg into Th9, while 4-1BBL seems to inhibit IL-9 production from iTreg and has not been studied for its ability to promote Th9 generation. Regulation of IL-9 production by TNF family cytokines has repercussions in vivo, including enhancement of anti-tumor immunity and immunopathology in allergic lung and ocular inflammation. Regulating T cell production of IL-9 through blockade or agonism of TNF family cytokine receptors may be a therapeutic strategy for autoimmune and allergic diseases and in tumor.
Posttranscriptional gene silencing, also known as RNA interference, involves degradation of homologous mRNA sequences in organisms. In plants, posttranscriptional gene silencing is part of a defense mechanism against virus infection, and double-stranded RNA is the pivotal factor that induces gene silencing. In this paper, we got seven hairpin RNAs (hpRNAs) constructs against different hot-spot sequences of Tobacco mosaic virus (TMV) or Potato virus Y (PVY) genome. After expression in Escherichia coli HT115, we extracted the seven hpRNAs for the test in tobacco against TMV or PVY infection. The data suggest that different hpRNAs against different hot-spot sequences of TMV or PVY genome had different ability to protect tobacco plants from viral infection. The resistance to TMV conferred by the hpRNA against the TMV movement protein was stronger than other TMV hpRNAs; the resistance to PVY conferred by the hpRNA against the PVY nuclear inclusion b was better than that induced by any other PVY hpRNAs. Northern blotting of siRNA showed that the resistance was indeed an RNA-mediated virus resistance.
We have examined whether toll-like receptor (TLR)2-mediated stimulation by macrophage-activating lipopeptide-2 (MALP-2), originally purified from Mycoplasma fermentans, induces cyclooxygenase (COX)-2 and prostaglandin (PG)E-2 in human placental trophoblast cells. The signaling mechanism by which MALP-2 exerts its effect has also been examined. Human placental trophoblast cells isolated from term placenta were used. TLR expression in trophoblast cells was confirmed by multiplex PCR and immunocytochemistry, and examined whether MALP-2 induces COX-2 and PGE(2) by Northern blotting, RT-PCR, Western blotting and ELISA, respectively. The activation of NF-kappa B and MAP kinases (ERK1/2 and p38) was examined by Western blotting. The effects of inhibitors of NF-kappa B, MEK1/2 and p38 on MALP-2-induced PGE, production were also evaluated. TLR2, TLR6 and TLR4 were expressed in human placental trophoblast cells. MALP-2 significantly induced COX-2 expression and enhanced PGE(2) production in a dose-dependent manner. MALP-2 induced the activation of NF-kappa B, ERK1/2 and p38 MAPK. Inhibitors of NF-kappa B, MEK1/2 and p38 blocked MALP-2-inducible PGE(2) production. TLR2-mediated stimulation by MALP-2 induces COX-2 and PGE(2) in human placental trophoblast cells via NF-kappa B and MAP kinases pathways. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
A full-length cDNA, named LeEIN2 was cloned from tomato (Lycopersicon esculentum) by RT-PCR and RACE. Then the genomic DNA sequence of Le EIN2 was isolated by LA (Long and Accurate) PCR and Inverse PCR. This DNA sequence was 6838 bp including six introns. The Le EIN2 cDNA was 4343 bp and contained a 3951 bp open reading frame, encoding a 142.63 kDa protein of 1316 amino acids. Comparison of this protein sequence with that of Arabidopsis and Petunia showed that the amino acid homology was 66 and 90%, respectively. Northern blotting analysis indicated that the expression level of the LeEIN2 in young leaves was higher than in mature leaves and senescent leaves. During the development of fruits, the expression of the Le EIN2 was detected before mature green stage and got up to maximum at mature green and breaker stages, then reduced rapidly after breaker stage. The expression level of LeEIN2 in wild type tomato fruit at mature green stage did not distinctively change when treated with exogenous ethylene.
The objective of this study was to determine the heterosis, inbreeding depression and genetics for yield, quality and resistance to early blight in tomato. Consequently, twenty inter-specific crosses of tomato were developed by crossing five susceptible cultivars and four wild resistant accessions and tested in field and glasshouse conditions for early blight (EB) resistance. Biochemical responses were also critically studied both in parents and hybrids. All the crosses showed moderately susceptible reaction except five crosses of EC-520061 (Solarium habrochaites). Biochemically the wild parents exhibited better results over susceptible parents but their hybrids showed moderate reaction for early blight resistance. High level of phenol was found both in resistant parents and hybrids. Among the 20 crosses, those made by EC-520061 and H-88-78-1 manifested resistance capacity, low heterosis and high inbreeding depression for EB disease. For yield associated traits most of the crosses expressed high heterosis and low inbreeding depression which indicated better yield capacity. The crosses made by EC-520061 (S. habrochaites) segregated in 3:1 (resistant:susceptible) Mendelian ratio and indicated monogenic dominant and additive gene effects. Remaining crosses showed 1:2:1 (resistant:intermediate:susceptible) genetic ratio and indicated heterozygous nature of crosses mediated by multiple genes or QTLs. This fact can be utilized in future tomato breeding program for developing resistant varieties against EB disease. (C) 2017 Published by Elsevier B.V.
We hypothesized that epithelial cells of the remnant small intestine display "colonic" phenotype after total proctocolectomy. The aims of the present study were to identify preferentially expressed molecules in the colon or in the small intestine and to evaluate mRNA levels of those in the ileal pouch. Differential gene expression was investigated between the small intestine and the colon by using cDNA microarray and was confirmed by Northern blotting. Expression of three colonic mRNAs (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2, deleted malignant brain tumors 1, carcinoembryonic antigen-related cell adhesion molecule 1) and one "small intestinal" (microsomal triglyceride transfer protein) mRNA were compared between the control and the ileal pouch mucosae by quantitative reverse transcriptase-polymerase chain reaction. Seventy-four clones were differentially expressed with more than a threefold difference. Differential expression was confirmed in all mRNAs examined, including 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 and microsomal triglyceride transfer protein. The mucosal expression of carcinoembryonic antigen-related cell adhesion molecule 1 mRNA in the ileal pouch was enhanced in humans. The remnant ileum develops some, but not all, colonic phenotype after total proctocolectomy. Comparative study of epithelial gene expression between the small intestine and the colon enables us to analyze mechanisms of intestinal adaptation after total proctocolectomy.
Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-I mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy.
Objective: To explore the subjective quality of life (QoL) in children with Tourette Syndrome (TS) in China to provide a basis for more effective interference. Method: A total of 107 patients and 107 controls were enrolled. Subjective QoL was investigated by Inventory of Subjective Life Quality, Family Environment Scale of Chinese Version, and the Yale Global Tic Severity Scale, and a case-control study was performed. Results: The total score of subjective QoL and family life, school life, peer relationship, cognitive component, environment, self-awareness, cognitive component and depression experience in the TS were lower than control. Patients with co-morbid exhibited significantly lower scores within the subjective QoL family life, peer relationship, school life, self-awareness, and cognitive affective domains. Conclusion: The subjective QoL is impaired and it is important to control clinical symptoms and improve family environment for the improvement of the subjective QoL in TS.
Background: Peptide and protein toxins are essential tools to dissect and probe the biology of their target receptors. Venoms target vital physiological processes to evoke pain. Snake venoms contain various factors with the ability to evoke, enhance and sustain pain sensation. While a number of venom-derived toxins were shown to directly target TRPV1 channels expressed on somatosensory nerve terminals to evoke pain response, such toxins were yet to be identified in snake venoms. Methods: We screened Echis coloratus saw-scaled viper venom's protein fractions isolated by reversed phase HPLC for their ability to activate TRPV1 channels. To this end, we employed heterologous systems to analyze TRPV1 and NGF pathways by imaging and electrophysiology, combined with molecular biology, biochemical, and pharmacological tools. Results: We identified TRPV1 activating proteins in the venom of Echis coloratus that produce a channel-dependent increase in intracellular calcium and outwardly rectifying currents in neurons and heterologous systems. Interestingly, channel activation was not mediated by any of its known toxin binding sites. Moreover, although NGF neurotropic activity was detected in this venom, TRPV1 activation was independent of NGF receptors. Conclusions: Echis coloratus venom contains proteins with the ability to directly activate TRPV1. This activity is independent of the NGF pathway and is not mediated by known TRPV1 toxins' binding sites. General significance: Our results could facilitate the discovery of new toxins targeting TRPV1 to enhance current understanding of this receptor activation mechanism. Furthermore, the findings of this study provide insight into the mechanism through which snakes' venom elicit pain. (C) 2017 Elsevier B.V. All rights reserved.
Toxocariasis is an important, neglected zoonosis caused mainly by Toxocara canis. Although our knowledge of helminth molecular biology is improving through completed draft genome projects, there is limited detailed information on the molecular biology of Toxocara species. Here, transcriptomic sequencing of male and female adult T. canis and comparative analyses were conducted. For each sex, two-thirds (66-67%) of quality-filtered reads mapped to the gene set of T. canis, and at least five reads mapped to each of 16,196 (87.1%) of all 18,596 genes, and 321 genes were specifically transcribed in female and 1467 in male T. canis. Genes differentially transcribed between the two sexes were identified, enriched biological processes and pathways linked to these genes established, and molecules associated with reproduction and development predicted. In addition, small RNA pathways involved in reproduction were characterized, but there was no evidence for piwi RNA pathways in adult T. canis. The results of this transcriptomic study should provide a useful basis to support investigations of the reproductive biology of T. canis and related nematodes(2) (C) 2016 Elsevier B.V. All rights reserved.
Toxoplasma gondii iswidely distributed in humans and other animals including birds throughout theworld. However, little is known of themolecular epidemiology and genotypes of T. gondii infecting quails in China. Therefore, the present study was conducted to characterize T. gondii genotypes in common quails in China. During December 2014 to October 2015, a total of 390 muscle tissue samples of common quails were collected and the T. gondii B1 gene was amplified using a nested PCR, and the positive samples were genotyped at 11 genetic markers (SAG1, 5'-and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Twenty-five of the 390 common quails (6.41%) were tested positive by nested PCR. Three DNA samples from the 25 positive samples were typed completely and were identified as ToxoDB Genotype # 9 (http://toxodb. org/toxo/). The results of the present study indicated that T. gondii infection in common quails was common in China, which provided the information of T. gondii genetic diversity in this host species. This is the first genetic characterization of T. gondii isolates from quails in China, which is useful for monitoring and controlling the T. gondii infection in quails, other animals and humans. (C) 2016 Published by Elsevier B. V.
The comparison of the sensitivities of two molecular assays designed to target the multi-copy sequences of the Toxoplasma gondii genomic B1 region and 529 bp-RE respectively, in detecting T gondii in swine muscle was assessed. Diaphragm pillars were obtained from 498 slaughtered pigs managed in intensive farms in Central Italy. Genomic DNA was extracted from the tissues and T. gondii-B1 and 529 bp-RE sequences were amplified by specific PCR protocols. Toxoplasma gondii DNA was detected in 165 samples (33.13%). There was a good correlation (kappa = 0.77) between the results obtained targeting the two different genetic markers, however the 529 bp RE-PCR assay overall detected a significantly higher (P < 0.05) number of T. gondii-positive samples (150 samples) than the B1-PCR protocol (134). Our results show that: i) standardized B1 and 529 bp-RE PCRs applied to muscle tissues can detect a high rate of T gondii-infection; ii) a multi-target PCR approach is recommended for the accurate diagnosis of infection in swine and can also be used in food testing. (C) 2016 Elsevier Ltd. All rights reserved.
Background: Primary infection with Toxoplasma gondii during pregnancy may pose a threat to the fetus. Women infected prior to conception are unlikely to transmit the parasite to the fetus. If maternal serology indicates a possible primary infection, amniocentesis for toxoplasma PCR analysis is performed and antiparasitic treatment given. However, discriminating between primary and latent infection is challenging and unnecessary amniocenteses may occur. Procedure-related fetal loss after amniocentesis is of concern. The aim of the present study was to determine whether amniocentesis is performed on the correct patients and whether the procedure is safe for this indication. Methods: Retrospective study analysing data from all singleton pregnancies (n = 346) at Oslo University Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma infection during 1993-2013. Maternal, neonatal and infant data were obtained from clinical hospital records, laboratory records and pregnancy charts. All serum samples were analysed at the Norwegian Institute of Public Health or at the Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses were performed at Oslo University Hospital by experienced personnel. Time of maternal infection was evaluated retrospectively based on serology results. Results: 50% (173) of the women were infected before pregnancy, 23% (80) possibly in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring were infected with toxoplasma, one of them with negative PCR in the amniotic fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs) (Q(1) = 15, Q(3) = 22), with median sample volume 4 ml (Q(1) = 3, Q(3) = 7). Two miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One of these had severe fetal toxoplasma infection. Conclusions: Half of our study population were infected before pregnancy. In order to reduce the unnecessary amniocenteses we advise confirmatory serology 3 weeks after a suspect result and suggest that the serology is interpreted by dedicated multidisciplinary staff. Amniocentesis is safe and useful as a diagnostic procedure in diagnosing congenital toxoplasma infection when performed after 15 GW.
CASE HISTORY: A 1-year-old female New Zealand sea lion (Phocarctos hookeri) was intermittently observed in the Otago region of New Zealand over an 11-month period, always dragging her hind flippers. In December 2012 the sea lion was found dead, after a period of several days being observed to be harassed by male sea lions.PATHOLOGICAL FINDINGS: At gross postmortem examination the sea lion was in moderate body condition with signs of recent bite wounds and bruising. The lungs were dark and poorly inflated. Histological findings included meningoencephalomyelitis, radiculomyelitis of the cauda equina, myocarditis and myositis. Toxoplasmosis gondii organisms were detected histologically and following immunohistochemistry in the brain, spinal cord, spinal nerves and pelvic muscles.MOLECULAR BIOLOGY: Nested PCR analysis and sequencing confirmed the presence of T. gondii DNA in uterine and lung tissue. A variant type II T. gondii genotype was identified using multilocus PCR-restriction fragment length polymorphism analysis.DIAGNOSIS: Systemic toxoplasmosis.CLINICAL RELEVANCE: Infection with T. gondii involving the spinal cord and nerves was the likely cause of the paresis observed in this sea lion before death. Ultimately, death was attributed to crushing and asphyxiation by a male sea lion, presumably predisposed by impaired mobility. Diagnosis of toxoplasmosis in a New Zealand sea lion highlights the possibility that this disease could play a role in morbidity and mortality in this endangered species, particularly in the recently established mainland populations that are close to feline sources of T. gondii oocysts.
Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c.541C >T, R181C (rs587782596), in two women from unrelated Arab families. The two probands were diagnosed with breast cancer at a young age (27 and 34 years) and had significant family history spanning a wide range of tumors (breast cancer (BC), papillary thyroid cancer, glioblastoma multiform (GBM), colon cancer and leukemia). The R181C variant is expected to disrupt p53 at the ASPP2 binding domain but not the DNA binding domain and is defined by Clinvar as likely pathogenic and in HGMD as disease mutation. We further tested 85 unrelated Arab cancer patients and father of a BC carrier patient for TP53 c.541C >T using a real time polymerase chain reaction (RT-PCR) approach and identified four additional carriers, two with BC one with lung cancer, and the father of a BC carrier patient, diagnosed with GBM. Another carrier suffering from BC was identified using a Myriad panel, suggesting a recurrent mutation in this population with a frequency of 5/42 (11.9%) of our selected BC patients. We suggest testing Arab women with a breast cancer at a young age, Arab patients with multiple malignancies, or with suggestive family history for TP53 c.541C >T.
This paper draws attention to a fundamental problem for a version of the tracing strategy defended by a number of theorists in the current literature (Rosen in Philos Perspect 18(1):295-313, 2004; Fischer and Tognazzini in NoA >>s, 43(3):531-556, 2009). I argue that versions of the tracing strategy that require reasonable foreseeability (rather than actual foresight) are in tension with the view that blameless ignorance excuses. A stronger version of the tracing strategy (i.e., one that requires actual foresight) is consistent with the view that blameless ignorance excuses and is therefore preferable for those tracing theorists who wish to continue maintaining that it does.
This paper proposes a novel compressive sensing based perceptual hashing algorithm for visual tracking. A tracking object is represented by dimensionality reduced feature projected from perceptual hashing feature through a sparse measurement matrix. Besides, an updating weight map is assigned for each object and the weight map is updated according to the accumulation of foreground block and the distance between the foreground block and the center of the weight map. Based oh above object representation and its weight map, our tracker searches the local region with the maximum similarity in coarse-to-fine way. In addition, we introduce a visual attention knowledge that the object, namely foreground, should be always located in the center of the weight map, to handle the model drift problem. Extensive experiments demonstrate that the proposed tracking method outperforms state-of-the-art methods in challenging scenarios and our tracker is especially insensitive to the location of the initial box. (C) 2017 Elsevier B.V. All rights reserved.
Despite the gradual adoption of technology in the rail industry, such as automatic warning systems (AWS), train driving still remains a relatively complex form of human performance. In this paper we examine the key contextual and psychological factors that influence train driving performance and driving-related incidents. We argue that goal conflicts such as on time running and safe train management can contribute to poor driving performance and increased risk of incidents for disinhibited drivers. By drawing on a well-established model of disinhibition, namely, the response modulation model of Patterson and Newman (1993), we explain how impulsive behavior and negative emotions can arise in individuals with high threat sensitivity and low working memory when facing approach-avoidance conflict (a form of goal conflict). Disinhibited train drivers, we propose, have difficulty switching attention between competing tasks, which contributes to poor driving performance and increased risk of incidents. We also present the results from an experimental study involving 56 experienced train drivers that provides evidence in support of this proposition. Finally, we believe that the methods and measures used in this study could eventually improve the way train drivers are selected and trained. (C) 2017 Elsevier Ltd. All rights reserved.
This multi-study analysis (6 fMRI studies; 142 participants) explores the functional activation and connectivity of the cerebellum with the cerebrum during repeated behavioral information uptake informing about personality traits of different persons. The results suggest that trait repetition recruits activity in areas belonging to the mentalizing and executive control networks in the cerebrum, and the executive control areas in the cerebellum. Cerebral activation was observed in the executive control network including the posterior medial frontal cortex (pmFC), the bilateral prefrontal cortex (PFC) and bilateral inferior parietal cortex (IPC), in the mentalizing network including the bilateral middle temporal cortex (MTC) extending to the right superior temporal cortex (STC), as well as in the visual network including the left cuneus (Cun) and the left inferior occipital cortex. Moreover, cerebellar activation was found bilaterally in lobules VI and VII belonging to the executive control network. Importantly, significant patterns of functional connectivity were found linking these cerebellar executive areas with cerebral executive areas in the medial pmFC, the left PFC and the left IPC, and mentalizing areas in the left MTC. In addition, connectivity was found between the cerebral areas in the left hemisphere involved in the executive and mentalizing networks, as well as with their homolog areas in the right hemisphere. The discussion centers on the role of these cerebello-cerebral connections in matching internal predictions generated by the cerebellum with external information from the cerebrum, presumably involving the sequencing of behaviors. (C) 2016 Elsevier Inc. All rights reserved.
In this paper, a single-stage multi-path operational transconductance amplifier (OTA) with fast-settling response for high performance applications is designed. The produced amplifier uses current-shunt technique, double recycling structure, cross-coupled positive feedback configuration and all idle devices in the signal path to enhance transconductance of the conventional folded cascode (FC) amplifier. These transconductance boosting techniques lead to higher DC gain, gain bandwidth (GBW), slew rate and lower settling time compared to the previous FC structures while phase margin is degraded. Simulation results are presented using 90nm CMOS technology which show 1,800% increment in GBW and a 33.2 dB DC gain improvement in the approximately same power consumption compared to the conventional FC amplifier.
Type II restriction-modification (R-M) systems are composed of linked restriction endonuclease and modification methyltransferase genes and serve as barriers to horizontal gene transfer even though they are mobile in themselves. Their products kill host bacterial cells that have lost the R-M genes, a process that helps to maintain the frequency of the R-M systems in the viable cell population. Their establishment and maintenance in a bacterial host are expected to involve fine regulation of their gene expression. In the present study, we analyzed transcription of the modification gene and its regulation within the EcoRIR-M system. Northern blotting revealed that the downstream ecoRIM gene is transcribed as a monocistronic mRNA and as part of a larger bicistronic mRNA together with the upstream ecoRIR gene. Primer extension, RNase protection, and mutational analysis using lacZ gene fusions identified two overlapping promoters for ecoRIM gene transcription within the ecoRIR gene. Further mutational analysis revealed that two upstream AT-rich elements within the ecoRIR gene, "AATAAA" and "ATTATAAATATA," function as negative regulators of these promoters. Simultaneous substitution of these two elements resulted in a fourfold increase in beta-galactosidase activity and a five-fold increase in transcript levels as measured by RNase protection assay. RNA measurements of the ecoRIM transcript suggested that these elements decreased ecoRIM expression by interfering with transcription initiation of the ecoRIM promoters. Possible roles for these ecoRIM promoters and their negative regulators in the EcoRIR-M system are discussed. (c) 2007 Elsevier B.V. All rights reserved.
Despite recent advances in improving titers for therapeutic proteins such as antibodies to the 10 g/L scale, these high yields can only be achieved in select mammalian hosts. Regardless of the host or product, strong promoters are required to obtain high levels of transgene expression. However, the promoters employed to drive this expression are rather limited in variety and are usually either viral-derived or screened empirically during vector design. To begin to move away from viral parts, we employed a more systematic approach to identify and design new synthetic promoters using endogenous elements. To do so, we established a workflow to design these elements by (1) analyzing the transcriptomics profile of a specific cell line under a desired, representative cell culture condition, (2) identifying key genetic motifs using bioinformatics that can be used to rationally construct synthetic promoters, (3) building synthetic promoters using conventional DNA synthesis and molecular biology techniques, and (4) evaluating the performance of these synthetic promoters using model proteins. The resulting promoters perform comparably to the hCMV IE promoter variants tested, but with endogenous components. During this design-build-test cycle we also investigated the underlying design rules for transcription factor binding site arrangement in synthetic promoters. Overall, this approach of using an "omics-guided" workflow for designing synthetic promoters facilitates the construction of high expression vectors for immediate use in current production hosts.
Social cognitive skills are indispensable for successful communication with others. Substantial research has determined deficits in these abilities in patients with mental disorders. In neurobiological development and continuing into adulthood, cross-cultural differences in social cognition have been demonstrated. Moreover, symptomatic patterns in mental disorders may vary according to the cultural background of an individual. Cross-cultural studies can thus help in understanding underlying (biological) mechanisms and factors that influence behavior in health and disease. In addition, studies that apply novel paradigms assessing the impact of culture on cognition may benefit and advance neuroscience research. In this review, the authors give an overview of cross-cultural research in the field of social cognition in health and in mental disorders and provide an outlook on future research directions, taking a neuroscience perspective.
The Control Systems course is taught in educational electric engineering programs all over the world. The method used for teaching this course is mainly by mathematical representation and software simulation of systems' behavior. In this work the author presents a different approach, which is based on making hands-on experimental applications. The solution presented in this article is based on decomposing and re-arranging the transfer function representation of a dynamic system in order to implement it using electronic circuits. Combining the presented method with a popular simulation software leads to the implementation of practical and effective laboratory classes for this course.
The rapidly growing list of small RNA species generated by next-generation sequencing technologies has accelerated the development of new bioinformatics tools for their detection. Small RNAs generated from tRNAs, transfer RNA-derived fragments (tRFs), represent a novel challenge in accurately identifying and distinguishing them from random degradation products of tRNAs. Here, we describe a bioinformatics approach to detect tRFs in next-generation sequencing libraries. We also present a biochemical purification protocol for enriching 5' tRFs and separating them from miRNAs. And finally, we suggest reliable methods for detecting and quantifying tRFs.
Objective: Root resorption is a complication of orthodontic treatment and till date, there is a dearth of information regarding this issue. The aim of this study was to determine whether the expression of transforming growth factor-beta 1 (TGF-beta 1, an inflammatory cytokine) is related to orthodontic force. Moreover, if associated, the expression level may be helpful in differential diagnosis, control and ultimate treatment of the disease. Materials and Methods: In this experimental study, a total of 24 eight-week-old male Wistar rats were selected randomly. On day 0, an orthodontic appliance, which consisted of a closed coil spring, was ligated to the upper right first molar and incisor. The upper left first molar in these animals was not placed under orthodontic force, thus serving as the control group. On day 21, after anesthesia, the animals were sacrificed. The rats were then divided into two equal groups where the first group was subjected to histological evaluation and the second group to reverse transcriptase-polymerase chain reaction (RT-PCR). Orthodontic tooth movement was measured in both groups to determine the influence of the applied force. Results: Statistical analysis of data showed a significant root resorption between the experimental group and control group (P<0.05), however, there was no significant difference in the expression level of the inflammatory cytokine, TGF-beta 1. Conclusion: Based on the findings of this study, we suggest that there is a direct relationship between orthodontic force and orthodontic induced inflammatory root resorption. In addition, no relationship is likely to exist between root resorption and TGF-beta 1 expression in the resorptive lacunae.
This review paper discusses the perspective of complex biological systems as applied to inheritance and ontogeny, focusing on the continuity of genetic, epigenetic (transgenerational) and microbiotic inheritance. The informational processuality within this continuity can be used as to exemplify the insufficiency of hierarchical concepts in grasping the complex and integrated nature of biological processes. The argument follows Bruni and Giorgi (Progress in Biophysics and Molecular Biology 119, 481-92, 2015) in emphasizing that while structures and substrates are organized hierarchically, communicational processes are organized heterarchically. The essay also argues the insufficiency of a single, basic, i.e. genetic level of description, which is the prevalent idea of twentieth century biology, to explain all phenotypic variation. I argue that inheritance and development cannot be fully explained by some sub- or super-ordination and that such descriptions are merely heuristic tools that do not reflect the nature of such processes.
The ability of TRAM for detecting parametric faults in a second-order filter selected as a case of study is studied in this work. Particularly, we adopt a low-pass Sallen-Key filter synthesized on a 500nm CMOS technology. We perform the design using diffused resistors, poly-poly capacitors and a full-custom operational amplifier. For fault injection and simulation, we adopt a previously reported fault model. Different combinations of test parameters are evaluated in this paper with the aim of determining the tradeoff between fault coverage and complexity of the test. Our results show that the simultaneous monitoring of peak time and overshoot gives reasonable fault coverage. The monitoring of other test parameters causes (in some cases) an improvement that should be considered as marginal.
This paper discusses the high-bandwidth trans-impedance amplifier combined with data acquisition system with high sampling rate for building nanopore system detection platform. The measured currents vary from 1 pA to nanoamperes and the output voltage is processed by computer. The amplifier must be constructed in multi stages and the key point for designing this amplifier is the low noise technique, especially for the head stage. For application of the nanopore system in single molecule detection, this amplifier can achieve the bandwidth of 1 MHz and detection sensitivity of 1 nA. We chose AD811 and AD8615 as the main operational amplifier chips for the trans-impedance amplifier and also designed a three level enlarged circuit using trans-impedance amplification principle for the AD8615 preamplifier circuit. We also selected high-precision metal foil resistors with high stability as feedback resistor so that the entire amplifier noise was as low as possible. The second and third enlarged circuit with the AD811, for continuous voltage amplification, improving of input impedance and lowering of output impedance for the object, was achieved by circuit designing and making of the trans-impedance amplifier, to improve the loading capacity. The characteristics for this trans-impedance amplifier include; low cost and excellent performance, which provide broader prospects for weak signal detection in biomedical research.
Equivalent input current noise and bandwidth are the most relevant parameters qualifying a low-noise transimpedance amplifier. In the conventional topology consisting of an operational amplifier in a shunt-shunt configuration, the equivalent input noise decreases as the feedback resistor (R-F), which also sets the gain, increases. Unfortunately, as R-F increases above a few M Omega as it is required for obtaining high sensitivity, the bandwidth of the system is set by the parasitic capacitance of R-F and reduces as R-F increases. In this paper, we propose a new topology that allows overcoming this limitation by employing a large-bandwidth voltage amplifier together with a proper modified feedback network for compensating the effect of the parasitic capacitance of the feedback resistance. We experimentally demonstrate, on a prototype circuit, that the proposed approach allows to obtain a bandwidth in excess of 100kHz and an equivalent input noise of about 4fA/root Hz, corresponding to the current noise of the 1G Omega resistor that is part of the feedback network. The new approach allows obtaining larger bandwidth with respect to those obtained in previously proposed configurations with comparable background noise. Copyright (c) 2014 John Wiley & Sons, Ltd.
Recently, two-dimensional (2D) layered materials have drawn much attention due to their unique atomic and electronic properties. Among 2D layered materials, transition metal dichalcogenides (TMDs) display metallic or semiconducting properties depending on the structural phase. In particular, MoS2, which is one such TMD, has the most stable structure in the trigonal prismatic phase with a sizable band gap of about 1.8 eV. To utilize this semiconducting property and take advantage of the nature of metal-MoS2 contacts, many efforts have been made to employ MoS2 in electronic devices such as field-effect transistors. Despite various studies of metal-MoS2 contacts, however, understanding of the contact behavior between ferromagnetic metals and MoS2 is insufficient. Additionally, we need to understand the contact nature between metals and various TMDs for various applications. Here, we report on ferromagnetic contacts between Ni(1 1 1) and MoX2 (X = S, Se, or Te) with first-principles calculations. In particular, we study the different electronic and spin properties at Ni-MoX2 interfaces, depending on the type of chalcogen atoms. Our calculations show that the Fermi level is not simply aligned by the work function difference between Ni(1 1 1) and MoX2, representing the Fermi-level pinning occurring at metal-semiconductor interfaces, and that Schottky barrier types are varied depending on MoX2. Interestingly, spin splitting occurs at the conduction band offset or valence band offset, depending on the X type in the MoX2, and a spin magnetic moment is induced on MoX2 by Ni(1 1 1) due to the ferromagnetic nature of Ni.
Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP). The TSTP is an intensive 2- to 3-day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):13-24, 2017.
Cardiac allograft vasculopathy (CAV) is a transplant pathology, limiting graft survival after heart transplantation. CAV arteries are surrounded by ectopic lymphoid structures (ELS) containing B cells and plasma cells. The aim of this study was to characterize the antigenic targets of antibodies produced in ELS. Coronary arteries and surrounding epicardial tissue from 56 transplant recipients were collected during autopsy. Immunofluorescence was used to identify antibody-producing plasma cells. Immunoglobulin levels in tissue lysates were measured by enzyme-linked immunosorbent assay and analyzed for donor-specific HLA antibodies by Luminex assay. Cytokine and receptor expression levels were quantified using quantitative polymerase chain reaction. Plasma cells in ELS were polyclonal and produced IgG and/or IgM antibodies. In epicardial tissue, IgG (p < 0.05) and IgM levels were higher in transplant patients with larger ELS than smaller ELS. In 4 of 21 (19%) patients with ELS, donor-specific HLA type II antibodies were detected locally. Cytokine and receptor expression (CXCR3, interferon and TGF-) was higher in large ELS in the epicardial tissue than in other vessel wall layers, suggesting active recruitment and proliferation of T and B lymphocytes. ELS exhibited active plasma cells producing locally manufactured antibodies that, in some cases, were directed against the donor HLA, potentially mediating rejection with major consequences for the graft. Ectopic lymphoid structures surrounding coronary arteries with allograft vasculopathy contain high levels of antibodies directed, in part, toward donor HLA class II.
In spite of reduction of rejection rates and improvement in short-term survival post-kidney transplantation, modest progress has occurred in long-term graft attrition over the years. Timely identification of molecular events that precede clinical and histopathological changes might help in early intervention and thereby increase the graft half-life. Evolution of omics tools has enabled systemic investigation of the influence of the whole genome, epigenome, transcriptome, proteome and microbiome on transplant function and survival. In this omics era, systemic approaches, in-depth clinical phenotyping and use of strict validation methods are the key for further understanding the complex mechanisms associated with graft function. Systems biology is an interdisciplinary holistic approach that focuses on complex and dynamic interactions within biological systems. The complexity of the human kidney transplant is unlikely to be captured by a reductionist approach. It appears essential to integrate multi-omics data that can elucidate the multidimensional and multilayered regulation of the underlying heterogeneous and complex kidney transplant model. Herein, we discuss studies that focus on genetic biomarkers, emerging technologies and systems biology approaches, which should increase the ability to discover biomarkers, understand mechanisms and stratify patients and responses post-kidney transplantation. This review focuses on the importance of a multi-omics integration approach and its advantages over the reductionist and one-dimensional omics approaches for better mechanistic understanding and diagnosis of kidney graft outcomes.
Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100-fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung. Investigation of the viral microbiome of donor organs and recipient allografts early after lung transplantation reveals that Torque teno viruses are markedly elevated in donor lungs prior to organ recovery, and perioperative viral dynamics differ in transplant recipients who experience primary graft dysfunction.
The membrane (M) protein is the most abundant component of the porcine transmissible gastroenteritis virus (TGEV) particle. To exploit the possibility of using RNA interference (RNAi) as a strategy against TGEV infection, three plasmids (pRNAT-1, pRNAT-2, and pRNAT-3) expressing short hairpin RNAs were designed to target three different coding regions of the M gene of TGEV. The plasmids were constructed and transiently transfected into a porcine kidney cells, PK-15, to determine whether these constructs inhibited TGEV production. The analysis of cytopathic effects demonstrated that pRNAT-2 and pRNAT-3 could protect PK-15 cells against pathological changes specifically and efficiently. Additionally, indirect immunofluorescence and 50% tissue culture infectious dose (TCID50) assays showed that pRNAT-2 and pRNAT-3 inhibited the multiplication of the virus at the protein level effectively. Quantitative real-time PCR further confirmed that the amounts of viral RNAs in cell cultures pre-transfected with the three plasmids were reduced by 13, 68, and 70%, respectively. This is the first report showing that RNAi targeting of the M gene. Our results could promote studies of the specific function of viral genes associated with TGEV infection and might provide a theoretical basis for potential therapeutic applications.
The transmission network switching is proposed in the literature as a way to improve social welfare in liberalized power markets. (7) Moreover, exercise of market power by strategic generating companies (Gencos) causes some extra cost in electricity market which can be alleviated by implementing appropriate switching policies. This paper contributes td the existing literature by developing a mathematical model that explores, from an economic perspective, the transmission network switching in the context of market power. The strategic Gecnos are modelled based on the Cournot game. The Nash equilibrium of the game between Gencos is formulated as an equilibrium problem with equilibrium constraint (EPEC). The EPEC problem is transformed to a mixed-integer linear feasibility problem. To handle the multiple Nash-equilibria situations, the solution concept of the extremal-Nash equilibrium (ENE) is introduced. A mixed-integer linear program (MILP) is derived for finding ENE. The transmission switching decisions are modelled as binary variables controlled by the system operator (TSO). The TSO minimizes the system dispatch cost calculated at ENE and network reconfiguration cost. The TSO minimizes the cost using its transmission switching decisions. The problem faced by the TSO is a mixed-integer bilevel linear program (MIBLP) with binary variables in both upper and lower levels. The upper level models the TSO's action and the lower level the oligopolistic Gencos (competing in Cournot game). A (parallel) branch and-bound technique is used to solve the developed MIBLP model. An illustrative 3-bus example system and the IEEE-RTS96 are modelled and carefully studied. (8)The numerical results demonstrate that: 1 - the (parallel) branch-and-bound technique can effectively solve the developed MIBLP, 2 - using the developed model, the system operator can change topology of the network by switching the lines in order to reduce the adverse effect of the strategic behaviour of Gecnos. (C) 2017 Elsevier B.V. All rights reserved.
The increasing interest in thin flexible and bendable devices has led to a strong demand for mechanically robust and electrically reliable transparent electrodes. Indium doped Tin Oxide (ITO) and Aluminium doped Zinc Oxide (AZO) are among the most employed transparent conductive oxides (TCO) and their reliability on flexible substrates have thus received a great attention. However, a high flexibility is usually achieved at very low thickness, which, unfortunately, compromises the electrical conductivity. Here we report the effects of mechanical bending cycles on the electrical and optical properties of ultra thin AZO/Ag/AZO multilayers (45 nm/10 nm/45 nm) and, for comparison, of AZO and ITO single layers whose thickness was, in both cases, 100 nm and 700 nm, deposited at room-temperature on flexible polyethylene naphthalate (PEN) plastic substrates. The electrical stability of the films after several cycles of bending were evaluated by monitoring the relative variation of the electrical resistance with respect to the as prepared sample; the structural damage induced by bending was detected by Scanning Electron Microscopy (SEM). We observed an excellent electrical stability and high flexibility in the AZO/Ag/AZO sample even after 100 cycles, whereas for the single AZO and ITO films the resistivity rapidly increases. The experimental results and numerical simulations provide clear evidences of the key role played by the ductile Ag interlayer that provides improved robustness under mechanical strain.
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells. Their suppression was also mostly reversed when effector T cells lacked Fas receptor. Indeed, these FasL+Tregs induced T cell apoptosis in vitro in a Fas/FasL-dependent manner. However, their suppression of T cell proliferation in vitro was dependent on IL-10, but not FasL expression. Furthermore, adoptive transfer of CD8+CD122+PD-1+ Tregs significantly extended allograft survival even in wild-type mice if Tregs lacked Fas receptor or if recipients received recombinant IL-15, as these two measures synergistically expanded adoptively-transferred Tregs in recipients. Thus, this study may have important implications for Treg therapies in clinical transplantation.
Transportation biofuel production efficiencies and cruising ranges provided by one hectare of land are studied from a life cycle perspective in the boreal climate zone. Efficient biofuel production is essential in terms of sustainability - especially land use, biodiversity and GHG emissions. Grass methane produced by anaerobic digestion and synthetic natural gas (SNG) produced from willows by gasification provide the longest cruising ranges. However, electricity production by solar panels for electric vehicles is a significantly more efficient option than biofuels. Grass methane, straw ethanol and SNG require less primary energy per produced fuel energy than other options. Increasing biofuel production for passenger cars from cultivated biomass in the boreal climate zone should be very carefully considered because electricity for transportation is significantly more efficient. (C) 2017 Elsevier Ltd. All rights reserved.
We isolated and cloned full-length cDNAs of transthyretin (TTR) from 2 genera of lamprey, Petromyzon marinus and Lampetra appendix. These sequences represent the first report of TTR sequences in vertebrates basal to teleost fishes. The deduced amino acid sequence of lamprey TTR cDNAs showed 36-47% identity with those from other vertebrates; secondary structure predictions and homology-based modeling were both consistent with TTRs from other vertebrates, and these cDNAs lacked the signatures found in TTR-like sequences of non-vertebrates. Of evolutionary interest is the observation that the N-termini of the lamprey TTR subunits are nine amino acids longer than those of eutherian TTRs and four to six amino acids longer than those from all other vertebrates. Sequencing of intron I confirmed that this longer N-terminal region is a result of the position of the intron 1/exon 2 splice site, further supporting previous studies. TTR mRNA was detected in a variety of larval lamprey tissues, with the highest levels found in the liver. TTR mRNA was also readily detected by Northern blotting, in the livers of animals at all phases of the lifecycle and was significantly elevated during metamorphosis. The upregulation of lamprey TTR gene expression during a major developmental event is consistent with observations in other vertebrates. In all other vertebrates studied to date, the transient upregulation of TTR gene expression or some other thyroid hormone distributor protein coincides with, and is thought to facilitate, the surge in serum thyroid hormone concentrations required for normal development. However, in lampreys, the upregulation of TTR gene expression occurs when serum thyroid hormone concentrations are at their lowest. (c) 2006 Elsevier Inc. All rights reserved.
The authors describe a rapid and sensitive magnetic relaxation switch (MRSw) aptasensor for the determination of the food-borne pathogen Pseudomonas aeruginosa. An aptamer against P. aeruginosa is covalently bound to superparamagnetic iron oxide nanoparticles. On incubation with P. aeruginosa bacteria, they will be captured by the aptamer, and this affects the formation of SPIO aggregates. The resulting strong increase in the spin-spin relaxation time (T-2) is utilized as the analytical information to quantify the bacteria. Under optimized conditions, the assay has a linear range that extends from 100 cfuai...mL(-1) to 10(6) cfuai...mL(-1), and a detection limit of 50 cfuai...mL(-1) (at an S/N ratio of 3). The method was applied to the detection of P. aeruginosa in (spiked) real food and drinking water samples and was validated by the established plate counting method. This aptasensor is considered to represent a promising platform for the determination of P. aeruginosa. Conceivably, the method may be extended to other food-borne bacteria or biomolecules for which respective aptamers are available.
Background: Trauma and depression have each been associated with neurocognitive alterations, but their combined effect on neurocognition is unclear. We investigated the separate and interactive associations of trauma and depression on neurocognition in a sample of ethnically diverse urban dwellers, and explored the impact of age on these effects. Methods: 284 adults aged 30-89 were divided into groups based on their current depression and trauma history. Individuals meeting DSM-IV criteria for depression were considered Depressed (D+) and individuals rated through diagnostic interview as having trauma history were considered positive for Trauma (T+). Resulting Ns were 73 D+T+, 56 D+T-, 68 D-T+, and 87 D-T-. A principal component analysis of neuropsychological scores resulted in a 3-factor solution representing verbal learning/memory/recognition (VERBAL-LMR), visual learning/memory/recognition, and speeded attention/cognitive flexibility accounting for 70.21% of the variance. Results: Multivariable linear regressions adjusting for age revealed that Trauma, regardless of Depression, is associated with worse VERBAL-LMR performance. This Trauma association was driven by verbal list and prose passages learning and memory, but not recognition memory. Age-stratified (= 60 years) regressions revealed the Trauma association was only significant for older adults. No main or interactive effects for Depression were observed. Conclusions: Trauma, regardless of Depression, is associated with worse verbal learning and memory, but not recognition performance. These results suggest that trauma exposure may negatively impact neurocognition. Clinicians working with adults in urban settings should query for trauma in addition to depression when considering subjective and objective measures of neurocognitive functioning, particularly in older adults. (C) 2017 Elsevier Ltd. All rights reserved.
Purpose Traumatic injury is a leading cause of work disability. Receiving compensation post-injury has been consistently found to be associated with poorer return to work. This study investigated whether the relationship between receiving compensation and return to work was associated with elevated symptoms of psychological distress (i.e., anxiety, depression, and posttraumatic stress disorder) and perceived injustice. Methods Injured persons, who were employed at the time of injury (n = 364), were recruited from the Victorian State Trauma Registry, and Victorian Orthopaedic Trauma Outcomes Registry. Participants completed the Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist, Injustice Experience Questionnaire, and appraisals of pain and work status 12-months following traumatic injury. Results Greater financial worry and indicators of actual/perceived injustice (e.g., consulting a lawyer, attributing fault to another, perceived injustice, sustaining compensable injury), trauma severity (e.g., days in hospital and intensive care, discharge to rehabilitation), and distress symptoms (i.e., anxiety, depression, PTSD) led to a twofold to sevenfold increase in the risk of failing to return to work. Anxiety, post-traumatic stress and perceived injustice were elevated following compensable injury compared with non-compensable injury. Perceived injustice uniquely mediated the association between compensation and return to work after adjusting for age at injury, trauma severity (length of hospital, admission to intensive, and discharge location) and pain severity. Conclusions Given that perceived injustice is associated with poor return to work after compensable injury, we recommend greater attention be given to appropriately addressing psychological distress and perceived injustice in injured workers to facilitate a smoother transition of return to work.
Traumatic brain injury (TBI) affects an ever-growing population of all ages with long-term consequences on health and cognition. Many of the issues that TBI patients face are thought to be mediated by the immune system. Primary brain damage that occurs at the time of injury can be exacerbated and prolonged for months or even years by chronic inflammatory processes, which can ultimately lead to secondary cell death, neurodegeneration, and long-lasting neurological impairment. Researchers have turned to rodent models of TBI in order to understand how inflammatory cells and immunological signaling regulate the post-injury response and recovery mechanisms. In addition, the development of numerous methods to manipulate genes involved in inflammation has recently expanded the possibilities of investigating the immune response in TBI models. As results from these studies accumulate, scientists have started to link cells and signaling pathways to pro-and anti-inflammatory processes that may contribute beneficial or detrimental effects to the injured brain. Moreover, emerging data suggest that targeting aspects of the immune response may offer promising strategies to treat TBI. This review will cover insights gained from studies that approach TBI research from an immunological perspective and will summarize our current understanding of the involvement of specific immune cell types and cytokines in TBI pathogenesis.
Objectives: This study examined the current assessment practices of clinicians working with people with social cognition impairment following traumatic brain injury. Method: Two hundred and sixty clinicians completed an on-line survey that was disseminated through professional brain injury organisations. Of respondents around 90% were allied health clinicians, with the remainder comprising medical, nursing and academia. Main outcomes: The four areas of social cognition that were routinely assessed across the disciplines were insight, disinhibition, anger and social adjustment. The least routinely assessed areas were theory of mind and alexithymia. The test suggested most likely to identify social cognition impairments was The Awareness of Social Inference Test, although only 8% of clinicians responded to this question. Clinicians preferred informal assessment methods over standardised assessment methods for identifying social cognition rehabilitation goals. Higher levels of education were associated with greater use of standardised assessment modalities. Whilst there was paucity of responses overall, TBI Express was most commonly used for social cognition rehabilitation. Conclusions: Considering the high prevalence of social cognition impairments in this population, formal assessment is extremely limited. The under-utilisation of assessment tools is problematic for the assessment and rehabilitation initiatives offered to people with TBI. These results have implications for the training of clinicians working in brain injury rehabilitation.
The present research examined how particular types of combat exposure may be associated not only with increased mental health symptoms but also with perceived benefits that are associated with decreased mental health symptoms. Using a longitudinal sample of military personnel who had returned from combat in Iraq or Afghanistan, active combat experiences (such as shooting or directing fire at the enemy) were related to higher levels of perceived benefits following the deployment, whereas passive experiences (such as being the recipient of an attack or witnessing destruction) were not. Perceived benefits 3 months postdeployment were associated with lower posttraumatic stress disorder (PTSD) symptoms 3 months later. A mediational analysis revealed that although active combat experiences were associated with greater PTSD symptoms, a portion of this relationship was reduced as a result of the association between active combat experiences and benefit finding. Discussion focuses on additional research needed on the role of benefit finding in postcombat adjustment, and how employees may derive benefits from their work that predict future mental health symptoms.
Background: While short-term psychodynamic psychotherapies have been shown effective for major depression, it is unclear if this could be a treatment of choice for depressed patients, many of whom have chronic and complex health issues, who have not sufficiently responded to treatment. Method: This superiority trial used a single blind randomised parallel group design to test the efficacy of time-limited Intensive Short-Term Dynamic Psychotherapy (ISTDP) for treatment resistant depression (TRD). Patients referred to secondary care community mental health teams (CMHT) who met DSM-IV criteria for major depressive episode, had received antidepressant treatment weeks, and had Hamilton Depression Rating Scale (HAM-D) scores of were recruited. The effects of 20 sessions of ISTDP were judged through comparison against secondary care CMHT treatment as usual (TAU). The primary outcome was HAM-D scores at 6 months. Secondary outcomes included the Patient Health Questionnaire (PHQ-9) self-report measures for depression and dichotomous measures of both remission (defined as HAM-D score <= 7) and partial remission (defined as HAM-D score <= 12). Results: Sixty patients were randomised to 2 groups (ISTDP = 30 and TAU = 30), with data collected at baseline, 3, and 6 months. Multi-level linear regression modelling showed that change over time on both depression scales was significantly greater in the ISTDP group in comparison to TAU. Statistically significant between-group treatment differences, in the moderate to large range, favouring ISTDP, were observed on both the observer rated (Cohen's d=0.75) and self-report measures (Cohen's d=0.85) of depression. Relative to TAU, patients in the ISTDP group were significantly more likely after 6 months to achieve complete remission (36.0% vs. 3.7%) and partial remission (48.0% vs. 18.5%). Limitations: It is unclear if the results are generalizable to other providers, geographical locations and cultures. Conclusions: Time-limited ISTDP appears an effective treatment option for TRD, showing large advantages over routine treatment delivered by secondary care services.
Trees Outside Forests (TOF) represent a source of lignocellulosic biomass that has received increasing attention in the recent years. While some studies have already investigated the potential of TOF in Germany, a spatial explicit analysis, specifically for Baden-Wuerttemberg, is still lacking. We used a unique wall-to-wall airborne Light Detection and Ranging (LiDAR) dataset combined with OpenStreetMap (OSM) data to map and classify TOF of the federal state of Baden-Wuerttemberg (similar to 35.000 km(2)) in south-western Germany. Furthermore, from annual biomass potentials of TOF areas collected from available literature, we calculated the mean annual biomass supply for all TOF areas in Baden-Wuerttemberg. This combination of remote sensing-based classification and available literature resulted in a mean annual biomass supply between similar to 490,000-730,000 t from TOF in Baden-Wuerttemberg. The classification congruence on three reference sites was very high (similar to 99%) using a simple filter technique applied to the LiDAR data and masking man-made objects using OSM data. In contrast, the available literature revealed a high variability of biomass potentials, supporting the demand for an inventory system. Still, the results demonstrate the applicability of LiDAR based vegetation mapping and the value of OSM data in Baden-Wuerttemberg to detect man-made objects. (C) 2017 Elsevier B.V. All rights reserved.
The oriental leafworm moth, Spodoptera litura, is a major agricultural pest in southeast Asia and nearby Pacific regions. Two distinct trehalases have been identified in insects: soluble trehalase (Treh1) and membrane-bound trehalase (Treh2), although there is currently no information on these genes in S. litura. To characterize the distribution and function of treh, cDNAs of Treh proteins were cloned from S. litura. SpoliTreh1 cDNA has an open reading frame of 1758 nucleotides, which encodes a protein of 585 amino acids, with a predicted mass of approximately 67.07 kDa and an isoelectric point of 4.86. SpoliTreh2 cDNA has an open reading frame of 2325 nucleotides, encoding a protein of 645 amino acids, a mass of approximately 73.62 kDa, and an isoelectric point of 5.90. Northern blotting analysis revealed that SpoliTreh1 transcripts are in the midgut, fat body, tracheae, and epidermis, but not in the brain and Malpighian tubules of S. litura larvae, whereas SpoliTreh2 transcripts were found in all 6 tissues. SpoliTreh1 transcripts were highly expressed in the fat body the pre-pupal stage, and SpoliTreh2 transcripts were highly expressed in the fat body of 3-day-old larvae of the 6th instar and during the 1st 6 days of the pupal stage, except the 2nd day. Both SpoliTreh1 and SpoliTreh2 were highly expressed in third-instar larvae.
Pile foundations are usually used when heavy superstructural loads have to be transmitted through weaker subsoil. Piles are also subjected to significant amounts of lateral loads and overturning moments besides axial loads. Lateral loads are in the order of 10-15% of the vertical loads in the case of onshore structures, whereas in the case of coastal and offshore structures, these lateral loads can exceed 30% of the vertical loads. Therefore, proper attention has to be given in designing such pile structures under lateral loads. In recent years, many investigations have addressed the externally bonded fiber-reinforced polymer composites for strengthening of concrete structures. This paper presents an experimental study on glass and carbon fiber-reinforced polymers (GFRP and CFRP) strengthened reinforced concrete (RC) piles subjected to cyclic lateral loads. The effects of GFRP and CFRP strengthening on RC piles were studied. The load deflection, stiffness degradation, and energy dissipation of piles are also presented. (C) 2017 American Society of Civil Engineers.
Social knowledge beyond one's direct relationships is a key in successfully manoeuvring the social world. Individuals gather information on the quality of social relationships between their group companions, which has been termed triadic awareness. Evidence of the use of triadic awareness in natural contexts is limited mainly to conflict management. Here we investigated triadic awareness in wild Barbary macaques (Macaca sylvanus) in the context of bridging interactions defined as male-infant-male interactions whereby a male (initiator, holder) presents an infant to another male (receiver, non-holder) in order to initiate an affiliative interaction with that male. Analyses based on 1263 h of focal observations on ten infants of one wild social group in Morocco supported the hypothesis that males use their knowledge of the relationship between infants and other adult males when choosing a male as a partner for bridging interactions. Specifically, (i) the number of bridging interactions among holder-infant-receiver triads was positively affected by the strength of the infant-receiver relationship and (ii) when two males were available as bridging partners, a male was more likely to be chosen as the receiver the stronger his social relationship with the infant relative to the other available male. This demonstrates that non-human primates establish triadic awareness of temporary infant-male relationships and use it in a naturally occurring affiliative context. Our results contribute to the discussion about the mechanism underlying the acquisition of triadic awareness and the benefits of its usage, and lend support to hypotheses linking social complexity to the evolution of complex cognition.
Little is known about how the virulence of a human pathogen varies in the environment it shares with its vector. This study focused on whether the virulence of Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae), the causal agent of Chagas' disease, is related to altitude. Accordingly, Triatoma dimidiata (Hemiptera: Reduviidae) specimens were collected at three different altitudes (300, 700 and 1400 m a. s. l.) in Chiapas, Mexico. The parasite was then isolated to infect uninfected T. dimidiata from the same altitudes, as well as female CD-1 mice. The response variables were phenoloxidase (PO) activity, a key insect immune response, parasitaemia in mice, and amastigote numbers in the heart, oesophagus, gastrocnemius and brain of the rodents. The highest levels of PO activity, parasitaemia and amastigotes were found for Tryp. cruzi isolates sourced from 700 m a. s. l., particularly in the mouse brain. A polymerase chain reaction-based analysis indicated that all Tryp. cruzi isolates belonged to a Tryp. cruzi I lineage. Thus, Tryp. cruzi from 700 m a. s. l. may be more dangerous than sources at other altitudes. At this altitude, T. dimidiata is more common, apparently because the conditions are more beneficial to its development. Control strategies should focus activity at altitudes around 700 m a. s. l., at least in relation to the region of the present study sites.
A novel magnetic force driven noncontact electromagnetic-triboelectric hybrid nanogenerator for scavenging biomechanical energy to sustainably power portable electrics is presented. Based on the effective conjunction of electromagnetic induction and triboelectrification, the hybrid nanogenerator with a small dimension consists of an electromagnetic generator (EMG) with a peak output power of 3.4 mW under a load resistance of 200 Omega and a triboelectric nanogenerator (TENG) with a peak output power of 0.23 mW under a load resistance of 25 M Omega. For TENG, the electrospun Fe3O4 nanoparticles embedded PVDF fibers membrane is employed as triboelectric layer. A magnet is utilized as the trigger to non-contactly drive contact-separation mode TENG due to the magnetic responsiveness of triboelectric materials, and the EMG can be drived by coupling magnet with copper coils simultaneously. The hybrid nanogenerator exhibits a good stability for the output performance and charging performance, so it can be utilized to charge energy storage devices and sustainably power some portable electronics. This work demonstrates a novel prototype of hybrid nanogenerators toward harvesting human biomechanical energy and its potential applications in building up self-powered systems.
As a green and eco-friendly technology, triboelectric nano generator (TENG) can harvest energy from human motion to generate electricity, so TENGs have been widely applied in wearable electronic devices to replace traditional batteries. However, the surface of these TENGs is easily contaminated and breeds bacteria, which is a threat to human health. Here, we report an antibacterial composite film -based triboelectric nanogenerator (ACF-TENG) that uses Ag-exchanged zeolite (Ag-zeolite) and polypropylene (PP) composite film as the triboelectric layer. Adding a small amount of Ag-zeolite with excellent antibacterial properties can increase the dielectric permittivity and improve the surface charge density of composite films, which enhances the output performance of the ACF-TENG. The open -circuit voltage (V-OC), shortcircuit current (I-SC), and transferred charge (Q(Tr)) of the ACF-TENG are about 193.3, 225.4, and 233.3% of those of a pure PP film -based TENG, respectively. Because of the silver in the Ag-zeolite, the ACF-TENG can effectively kill Escherichia coli and fungi. When used in insoles, the ACF-TENG can resist the athlete's foot fungus effectively and work as a power source to light up light -emitting diodes and charge capacitors. The ACF-TENG has wide application prospects in self powered medical and healthcare electronics.
Soil salinity is a serious problem worldwide that reduces agricultural productivity. Trichoderma longibrachiatum T6 (T6) has been shown to promote wheat growth and induce plant resistance to parasitic nematodes, but whether the plant-growth-promoting fungi T6 can enhance plant tolerance to salt stress is unknown. Here, we determined the effect of plant-growth-promoting fungi T6 on wheat seedlings growth and development under salt stress, and investigated the role of T6 in inducing the resistance to NaCl stress at physiological, biochemical, and molecular levels. Wheat seedlings were inoculated with the strain of T6 and then compared with non-inoculated controls. Shoot height, root length, and shoot and root weights were measured on 15 days old wheat seedlings grown either under 150 mM NaCl or in a controlled setting without any NaCl. A number of colonies were re-isolated from the roots of wheat seedlings under salt stress. The relative water content in the leaves and roots, chlorophyll content, and root activity were significantly increased, and the accumulation of proline content in leaves was markedly accelerated with the plant growth parameters, but the content of leaf malondialdehyde under saline condition was significantly decreased. The antioxidant enzymes-superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in wheat seedlings were increased by 29, 39, and 19%, respectively, with the application of the strain of T6 under salt stress; the relative expression of SOD, POD, and CAT genes in these wheat seedlings were significantly up-regulated. Our results indicated that the strain of T6 ameliorated the adverse effects significantly, protecting the seedlings from salt stress during their growth period. The possible mechanisms by which T6 suppresses the negative effect of NaCl stress on wheat seedling growth may be due to the improvement of the antioxidative defense system and gene expression in the stressed wheat plants.
Background: The industrial workhorse fungus, Trichoderma reesei, is typically exploited for its ability to produce cellulase enzymes, whereas use of this fungus for over-expression of other proteins (homologous and heterologous) is still very limited. Identifying transformants expressing target protein is a tedious task due to low transformation efficiency, combined with highly variable expression levels between transformants. Routine methods for identification include PCR-based analysis, western blotting, or crude activity screening, all of which are time-consuming techniques. To simplify this screening, we have adapted the 2A peptide system from the foot-and-mouth disease virus (FMDV) to T. reesei to express a readily screenable marker protein that is co-translated with a target protein. The 2A peptide sequence allows multiple independent genes to be transcribed as a single mRNA. Upon translation, the 2A peptide sequence causes a "ribosomal skip" generating two (or more) independent gene products. When the 2A peptide is translated, the "skip" occurs between its two C-terminal amino acids (glycine and proline), resulting in the addition of extra amino acids on the C terminus of the upstream protein and a single proline addition to the N terminus of the downstream protein. To test this approach, we have cloned two heterologous proteins on either side of a modified 2A peptide, a secreted cellobiohydrolase enzyme (Cel7A from Penicillium funiculosum) as our target protein, and an intracellular enhanced green fluorescent protein (eGFP) as our marker protein. Using straightforward monitoring of eGFP expression, we have shown that we can efficiently monitor the expression of the target Cel7A protein. Results: Co-expression of Cel7A and eGFP via the FMDV 2A peptide sequence resulted in successful expression of both test proteins in T. reesei. Separation of these two polypeptides via the modified 2A peptide was similar to 100% efficient. The Cel7A was efficiently secreted, whereas the eGFP remained intracellular. Both proteins were expressed when cloned in either order, i. e., Cel7A-2A-eGFP (C2G) or eGFP-2A-Cel7A (G2C); however, eGFP expression and/or functionality were dependent upon the order of transcription. Specifically, expression of Cel7A was linked to eGFP expression in the C2G orientation, whereas expression of Cel7A could not be reliably correlated to eGFP fluorescence in the G2C construct. Whereas eGFP stability and/or fluorescence were affected by gene order, Cel7A was expressed, secreted, and exhibited the expected functionality in both the G2C and C2G orientations. Conclusions: We have successfully demonstrated that two structurally unrelated proteins can be expressed in T. reesei using the FMDV 2A peptide approach; however, the order of the genes can be important. The addition of a single proline to the N terminus of eGFP in the C2G orientation did not appear to affect fluorescence, which correlated well with Cel7A expression. The addition of 21 amino acids to the C terminus of eGFP in the G2C orientation, however, appeared to severely reduce fluorescence and/or stability, which could not be linked with Cel7A expression. The molecular biology tool that we have implemented in this study will provide an efficient strategy to test the expression of heterologous proteins in T. reesei, while also providing a novel platform for developing this fungus as an efficient multi-protein-expressing host using a single polycistronic gene expression cassette. An additional advantage of this system is that the co-expressed proteins can be theoretically produced at equimolar ratios, as ( A) they all originate from a single transcript and ( B) unlike internal ribosome entry site ( IRES)-mediated polycistronic expression, each cistron should be translated equimolarly as there is no ribosomal dissociation or reloading between cistrons.
Acriflavin (3,6-acridinediamine) and other acridine derivatives act in both prokaryotic and eukaryotic cells at the level of DNA-coiling enzymes (topoisomerases) causing the stabilization of the enzyme-DNA cleavable complex. In order to better understand the mode of action of acriflavin, Differential Display RT-PCR was used to isolate transcripts specifically over-expressed during exposure of Trichophyton rubrum mycelia to this drug. Five transcripts, whose differential expressions were confirmed by Northern blotting, revealed genes not previously described in this dermatophyte. Functional grouping identified putative enzymes possibly involved in the mitochondrial respiratory electron-transport chain and in iron transport. These results may be relevant to our understanding of the molecular events involved in the stress response of T. rubrum to acriflavin.
Diversity in the macrophage models currently employed in immunology studies may lead to opposed results and interpretations. In this study, we aimed to analyze the suitability of J774 macrophage-like cells as a model for the interaction between the dermatophyte Trichophyton rubrum and macrophages. J774 cells were competent in fungal phagocytosis, but succumbed to hyphal growth. Nevertheless, they could also secrete IL-1 beta in response to the dermatophyte. On the opposite direction, inflammatory, thioglycollate-induced peritoneal macrophages did not succumb to fungal growth and showed no significant IL-1 beta production. The proteomic profiling of these cells uncovered vimentin and plastin-2 as proteins whose abundance was altered by the fungal interaction. Our study indicates that this cell line could be an interesting tool in the investigation of T. rubrum infection biology.
Trichosanthin (TCS) exhibits an anti-cancer effect on various human cancer cells. However, the mechanism of anti-cancer effect at the molecular level remains to be elucidated. In this study, the underlying anti-cancer mechanism of TCS in human ovarian cancer cells (OVCAR-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting. We major focus on the potential roles of apoptosis and autophagy in TCS inhibition of human ovarian cancer cells. The results demonstrated TCS inhibits human ovarian cancer cells growth due to apoptosis and autophagy. TCS triggers autophagy firstly, which was confirmed by an increased ATG5 expression and promoted LC3 cleavage, and subsequent apoptotic cell death. The apoptotic cell death induced by TCS was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor 3-MA, which functions at the early stage of autophagy, significantly reduced TCS-induced cell death and caspase-3 activity in human ovarian cancer cells. We also demonstrated that inhibition of apoptosis had no effect on TCS-induced autophagy in OVCAR-3 cells. In conclusion, we found that a common pathway between autophagy and apoptosis exists in TCS-induced cell death in human ovarian cancer cells, which might shed light on drug therapy.
It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 +/- 2 degrees C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X(3) receptor-immunoreactive (P2X(3)R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X(3)R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X(3)R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X(3)R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.
Here we present the technical and economical performances of a small scale trigeneration power plant based on solid oxide fuel cells and designed for a small residential cluster (i.e. 10 apartments). The energy system features a natural gas solid oxide fuel cell, a boiler, a refrigerator, and a thermal storage system. We compare different power plant configurations varying the size of the fuel cell and the refrigeration technology to satisfy the chilling demand (i.e. absorption or mechanical chiller). Given that the ability to meet the power demand is crucial in this kind of applications, the plant performances are assessed following an optimal control strategy, as a function of different energy demand profiles and electricity prices, and of rated and part load efficiencies of each energy converter. The optimization of the energy system operating strategy is performed through a graph theory-based methodology. Results are provided in terms of electrical and thermal efficiency, operating strategy, as well as economic saving, primary energy consumption reduction, and pay back period, considering different capital costs of the fuel cell. (C) 2016 Elsevier Ltd. All rights reserved.
We aimed to study the anti-tumor effects of triptolide on osteosarcoma and the related molecular mechanisms. The cell viability, apoptosis portion, tumor size, tumor weight, and invasion of osteosarcoma cells were determined. The relative level of microRNA-181 in osteosarcoma tissues and the adjacent tissues was determined by quantitative real-time reverse transcription polymerase chain reaction. The target gene of microRNA-181a was determined and verified by luciferase report assay. At last, osteosarcoma cells were treated with triptolide and triptolide + microRNA-181a mimics to verify the relationship between triptolide and microRNA-181a. Triptolide inhibited the cell viability, promoted the apoptosis, decreased the tumor size and weight, and reduced the invasion of osteosarcoma cells. The level of microRNA-181a in osteosarcoma cells decreased significantly after treating with triptolide, and the relative level of microRNA-181a in osteosarcoma tissues was markedly higher than that in the adjacent tissues. PTEN was reported and verified the direct target gene of microRNA-181a. The overexpression of microRNA-181a decreased the inhibition of triptolide on osteosarcoma proliferation and promotion on osteosarcoma apoptosis. In conclusion, triptolide inhibited cell growth and invasion of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.
The prevalence of the use of herbal medicines is on the rise across the world, especially amongst pregnant women. A fact that draws attention is that many species commonly used by pregnant women, including the Tropaeolum majus L. (Tropaeolaceae), also present inhibitory activity on the angiotensin-converting enzyme (ACE). Herein, we have investigated the effects of T. majus extract (HETM) on fetal development, evaluating its relationship with possible ACE inhibitory activity. Pregnant Wistar rats were treated with different HETM doses (3, 30 and 300 mg/kg/day) from gestational days 8-20. Rats were sacrificed on the day 20 of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights, maternal ACE activity and aldosterone levels, live fetuses mean; dead fetuses percentage, fetus weight, and fetal malformation. All pregnant rats treated with high HETM doses showed significant reduction in plasma ACE activity accompanied by a decrease in serum aldosterone levels. Moreover, significant changes in fetal development were observed, including growth retardation and renal damage after 20 days of gestation. Thus, data presented demonstrate the significant effects of the use of HETM on fetal development during pregnancy.
Trust in reciprocity (TR) is defined as the risky decision to invest valued resources in another party with the hope of mutual benefit. Several fMRI studies have investigated the neural correlates of TR in one-shot and multiround versions of the investment game (IG). However, an overall characterization of the underlying neural networks remains elusive. Here, a coordinate-based meta- analysis was employed (activation likelihood estimation method, 30 articles) to investigate consistent brain activations in each of the IG stages (i.e., the trust, reciprocity and feedback stage). Results showed consistent activations in the anterior insula (AI) during trust decisions in the one-shot IG and decisions to reciprocate in the multiround IG, likely related to representations of aversive feelings. Moreover, decisions to reciprocate also consistently engaged the intraparietal sulcus, probably involved in evaluations of the reciprocity options. On the contrary, trust decisions in the multiround IG consistently activated the ventral striatum, likely associated with reward prediction error signals. Finally, the dorsal striatum was found consistently recruited during the feedback stage of the multiround IG, likely related to reinforcement learning. In conclusion, our results indicate different neural networks underlying trust, reciprocity, and feedback learning. These findings suggest that although decisions to trust and reciprocate may elicit aversive feelings likely evoked by the uncertainty about the decision outcomes and the pressing requirements of social standards, multiple interactions allow people to build interpersonal trust for cooperation via a learning mechanism by which they arguably learn to distinguish trustworthy from untrustworthy partners. (C) 2016 Wiley Periodicals, Inc.
Differential gene expression in three pairs of Trypanosoma cruzi populations or clones susceptible or resistant to benznidazole (BZ) was investigated by differential display (DD) and representation of differential expression (RDE). GenBank searches of 14 genes selected by DD showed that four sequences corresponded to different hypothetical proteins and the others were very similar to T. cruzi genes encoding mucin (TcMUC), dihydrolipoamide dehydrogenase (TcLipDH), the hexose transporter (TcHT), or a ribosomal protein. Sequence analysis was performed on 34 clones obtained by RDE; approximately half of these clones encoded 14 different hypothetical proteins and the other half encoded proteins involved with stress response, antioxidant defence, metabolism, transporter proteins, surface proteins, ribosomal proteins and others. The mRNA levels of eight T. cruzi genes obtained by RDE and Do were analysed by northern blotting to confirm the differential expression of these sequences. For six of the eight genes, TcLipDH, TcHT, TcFeSOD-A (iron superoxide dismutase-A), TcHSP70, TcHSP100 (heat shock protein) and Tc52 (thiol-transferase), mRNA levels in the drug-resistant T. cruzi population were at least twice those in the susceptible population. Further analysis of TcHSP70 showed that although the levels of TcHSP70 mRNA were four-fold higher in T. cruzi BZ-resistant population, no corresponding increase was observed in the levels of TcHSP70 protein expression. The results suggest that TcHSP70 is not directly associated with the T. cruzi drug resistance phenotype. (C) 2008 Elsevier B.V. All rights reserved.
Tuberculosis is a public health problem. In recent years, there is a change in the epidemiological profile of tuberculosis. The diagnosis of tuberculosis is based on clinical and radiological arguments but confirmation is bacteriological and/or histological. Culture remains the gold standard. Technological progress especially in molecular biology provides the clinician now new means of tuberculosis diagnostics. (C) 2016 Elsevier Masson SAS. All rights reserved.
Background: The year 2015 marked the end of United Nations Millennium Development Goals which was aimed at halting and reversing worldwide tuberculosis (TB). The emergence of drug resistance is a major challenge for worldwide TB control. The aim of this study was to give a bibliometric overview of publications on multi-, extensively, and totally drug-resistant TB. Methods: Scopus database was used to retrieve articles on multidrug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis for the study period (2006-2015). The number of publications, top productive countries and institutions, citation analysis, co-authorships, international collaboration, active authors, and active journals were retrieved and analyzed. Results: A total of 2260 journal articles were retrieved. The mean +/- SD citations per article was 7.04 +/- 16.0. The h-index of retrieved data was 76. The number of publications showed a three - fold increase over the study period compared with less than two - fold increase in tuberculosis research during the same study period. Stratified by number of publications, the United States of America ranked first while Switzerland ranked first in productivity per 100 million people, and South Africa ranked first in productivity stratified per one trillion Gross Domestic Product. Three of the High Burden Countries (HBC) MDR-TB (India, China, and South Africa) were present in top productive countries. High percentage of international collaboration was seen among most HBC MDR-TB. Except for Plos One journal, most active journals in publishing articles on MDR, XDR, TDR-TB were in infection - related fields and in general medicine. Top 20 cited articles were published in prestigious journal such as Lancet and New England Journal of Medicine. The themes in top 20 cited articles were diverse, ranging from molecular biology, diagnostic tools, co-infection with HIV, and results of new anti-TB drugs. Conclusion: Publications on MDR, XDR and TDR - TB are increasing in the past decade. International collaboration was common. Many low resourced African and Asian countries will benefit from research leading to new diagnostic and screening technology of TB. The exchange of expertise, ideas and technology is of paramount importance in this field.
At a global level, with the increase in healthcare costs, there is a need to assess the economic impact of the incorporation of new technologies in different health disorders in different countries. There is scarce information regarding costs incurred with the use of current or new diagnostic tests for tuberculosis or from the vantage point of their incorporation within the healthcare systems of high-burden countries. The present study aimed to assess the mean cost and the activity based cost of the laboratory diagnosis for tuberculosis by means of conventional techniques and from the Detect TB (R) LabTest molecular test kit in a general high-complexity hospital of the public health system in Brazil. Cost analysis was performed by means of primary data, collected in the Mycobacteria and Molecular Biology Laboratory in 2013. The mean cost and activity based cost were, respectively, U$10.06/U$5.61 for centrifuged bacilloscopy by Ziehl Neelsen (ZN) and Auramine (AU); U$7.42/U$4.15 for direct bacilloscopy by ZN; U$27.38/U$16.50 for culture in a Loweinstein-Jensen solid medium; and U$115.74/U$73.46 for the Detect TB (R) LabTest Kit. The calculation of the ABC should be used in making decisions by administrators to be the best method of assessing the costs of conventional techniques and molecular method for providing the real value of the tests. So it is need to calculate the ABC, and not of the mean cost, in various scenarios before incorporating new technologies in health institutions.
Introduction: Tuberculosis (TB) is a leading killer worldwide. End TB strategy aims at ending the TB epidemic by 2030. Early, accurate, and affordable diagnosis represents a cornerstone to achieve this goal. Innovative strategies for TB diagnostics have been introduced. However, the ideal assay is yet unavailable and conventional methods remain necessary for diagnosis. Unique properties of nanoparticles (NPs) have allowed their utilization in TB detection via targeting disease biomarkers.Area covered: Until now, around thirty-five TB NP-based assays have been partially or fully characterized. Accuracy, low-cost, and short time-to-result represent the common properties of proposed platforms. TB nanodiagnostics now encompass almost all clinical aspects of the disease including active TB, non-tuberculous mycobacteria, rifampicin resistant TB, TB/HIV co-infection, latent TB, and extra-pulmonary TB. This review summarizes state-of-the-art knowledge of TB nanodiagnostics for the last 10years. Special consideration is given for fabrication concepts, detection strategies, and clinical performance using various clinical specimens. The potential of TB nanodiagnostics to fulfill the need for ideal MTB testing is assessed.Expert commentary: TB nanodiagnostics show promise to be ideal detection tools that can meet the rigorous demands to end the TB epidemic by 2030.
Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.
Tuberculosis (TB) is still a serious public health problem in various countries. One of the long-elusive but critical questions about TB is what the risk factors are and how they contribute for its seasonality. An ecologic study was conducted to examine the association between the variation of outdoor PM2.5 concentration and the TB seasonality based on the monthly TB notification and PM2.5 concentration data of Hong Kong and Beijing. Both descriptive analysis and Poisson regression analysis suggested that the outdoor PM2.5 concentration could be a potential risk factor for the seasonality of TB disease. The significant relationship between the number of TB cases and PM2.5 concentration was not changed when regression models were adjusted by sunshine duration, a potential confounder. The regression analysis showed that a 10 mu g/m(3) increase in PM2.5 concentrations during winter is significantly associated with a 3% (i.e. 18 and 14 cases for Beijing and Hong Kong, respectively) increase in the number of TB cases notified during the coming spring or summer for both Beijing and Hong Kong. Three potential mechanisms were proposed to explain the significant relationship: (1) increased PM2.5 exposure increases host's susceptibility to TB disease by impairing or modifying the immunology of the human respiratory system; (2) increased indoor activities during high outdoor PM2.5 episodes leads to an increase in human contact and thus the risk of TB transmission; (3) the seasonal change of PM2.5 concentration is correlated with the variation of other potential risk factors of TB seasonality. Preliminary evidence from the analysis of this work favors the first mechanism about the PM2.5 exposure-induced immunity impairment. This work adds new horizons to the explanation of the TB seasonality and improves our understanding of the potential mechanisms affecting TB incidence, which benefits the prevention and control of TB disease. (C) 2016 Elsevier Ltd. All rights reserved.
Tuberculosis is one of the main etiologies to evoke in the context of lymphocyte pleurisy. However, diagnosis is difficult and is based on mycobac-teriology that is not enough sensitive and time-consuming, or on histology that requires invasive biopsy gesture. This literature review, carried out from Med-line, summarizes the main meta-analyzes, reviews, and originator publications in English on biomarkers, classic and more innovative, studied for the diagnosis of tuberculous pleurisy. Among the immuno-biochemical markers, interferon- gamma (IFN-gamma), isoenzyme of adenosine deaminase 2 (ADA2) and total adenosine deaminase (ADA) seem the most relevant with respective sensitivities of 89% (87-91), 97.2% (95 to 98.7) and 92% (90-93) and specificities of 97% (96-98), 94.2% (91.8 to 96) and 90% (89-91). About molecular biology, PCR Xpert MTB/RIF has a sensitivity of 46.4% (26.3 to 67.8), which is much higher than the direct examination, while providing rapid diagnostic confirmation, with a specificity of 99.1% (95.2 to 99.8), and a resistance to rifampicin screening. The release assay of interferon-gamma (IGRA) is less effective with a sensitivity of 75% (69-81) and a specificity of 82% (75-88) in blood and a sensitivity of 80% (74-86%) and a specificity of 72% (64-80) in pleural fluid. Other biomarkers (including several cytokines) might have an interest but are still under evaluation. These innovative methods, particularly the determination of ADA and the use of PCR Xpert MTB/RIF should find their place in the diagnostic algorithm of TB pleurisy.
Tuberous sclerosis complex (TSC) is a rare multi-system disorder, primary manifestations of which are benign tumors and lesions in various organs of the body, including the brain. TSC patients often suffer from epilepsy, mental retardation, and autism spectrum disorder (ASD). Therefore, TSC serves as a model of epilepsy, ASD, and tumorigenesis. TSC is caused by the lack of functional Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of mammalian Target of Rapamycin Complex 1 (mTORC1). mTORC1 is a kinase controlling most of anabolic processes in eukaryotic cells. Consequently, mTORC1 inhibitors, such as rapamycin, serve as experimental or already approved drugs for several TSC symptoms. However, rapalogs, although quite effective, need to be administered chronically and likely for a lifetime, since therapy discontinuation results in tumor regrowth and epilepsy recurrence. Recent studies revealed that metabolism and excitability (in the case of neurons) of cells lacking Tsc1-Tsc2 complex are changed, and these features may potentially be used to treat some of TSC symptoms. In this review, we first provide basic facts about TSC and its molecular background, to next discuss the newest findings in TSC cell biology that can be used to improve existing therapies of TSC and other diseases linked to mTORC1 hyperactivation. (C) 2016 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 68(12): 955-962, 2016
Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume through the application of energy or chemicals. Methods such as radiotherapy, chemical and biological ablation, photodynamic therapy, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and electric-based ablation have been developed for focal malignancies. In recent years a large volume of data emerged on the effect of in situ tumor destruction (ablation) on inflammatory and immune components resulting in systemic anti-tumor reactions. It is evident that in situ tumor ablation can involve tumor antigen release, cross presentation and the release of DAMPS and make the tumor its own cellular vaccine. Tumor tissue destruction by in situ ablation may stimulate antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) attracted to this microenvironment, will undergo maturation after internalizing cellular debris containing tumor antigens and will be exposed to damage associated molecular pattern (DAMP). Mature DCs can mediate antigen-specific cellular immunity via presentation of processed antigens to T cells. The immunomodulatory properties, exhibited by in situ ablation could portend a future collaboration with immunotherapeutic measures. In this review are summarized and discuss the preclinical and clinical studies pertinent to the phenomena of stimulation of specific anti-tumor immunity by various ablation modalities and the immunology related measures used to boost this response.
The fractional cell kill is a mathematical expression describing the rate at which a certain population of cells is reduced to a fraction of itself. In order to investigate the fractional cell kill that governs the rate at which a solid tumor is lysed by a cell population of cytotoxic CD8(+) T cells (CTLs), we present several in silico simulations and mathematical analyses. When the CTLs eradicate efficiently the tumor cells, the models predict a correlation between the morphology of the tumors and the rate at which they are lysed. However, when the effectiveness of the immune cells is decreased, the mathematical function fails to reproduce the process of lysis. This limit is thoroughly discussed and a new fractional cell kill is proposed. (C) 2016 Elsevier B.V. All rights reserved.
Correlative studies from checkpoint inhibitor trials have indicated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplantation method to reconstitute the human tumor immune microenvironment in vivo. We were able to genetically mark the engrafted CD34+ bone marrow cells as well as the tumor cells, and follow the endogenous leukocytic infiltration into the autologous tumor. To investigate human tumor intrinsic factors that can potentially regulate the immune cells in our system, we silenced STAT3 signaling in the tumor compartment. As expected, STAT3 signaling suppression in the tumor compartment in these autologously reconstituted humanized mice showed increased tumor infiltrating lymphocytes and reduction of arginase-1 in the stroma, which were associated with slower tumor growth rate. We also used this novel system to characterize human myeloid suppressor cells as well as to screen novel agents that can alter endogenous leukocytic infiltration into the tumor. Taken together, we present a valuable method to study individualized human tumor microenvironments in vivo without confounding allogeneic responses.
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8), a transcription factor nuclear factor kappa B-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P = .001), advanced TNM stage (P < .001), high histologic grade (P < .001), molecular subtype (P < .001), and postoperative recurrence (P < .001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P = .008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P = .041 and P = .020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC. (C) 2017 Elsevier Inc. All rights reserved.
The complete nucleotide sequence of polyprotein gene 1 and the assembled full-length genome sequence are presented for turkey coronavirus (TCoV) isolates 540 and ATCC. The TCoV polyprotein gene encoded two open reading frames (ORFs), which are translated into two products, pp1a and pp1ab, the latter being produced via - 1 frameshift translation. TCoV polyprotein pp1a and pp1ab were predicted to be processed to 15 non-structure proteins (nsp2-nsp16), with nsp1 missing. ClustalW analysis revealed 88.99% identity and 96.99% similarity for pp1ab between TCoV and avian infectious bronchitis virus (IBV) at the amino acid level. The whole genome consists of 27,749 nucleotides for 540 and 27,816 nucleotides for ATCC, excluding the poly(A) tail. A total of 13 ORFs were predicted for TCoV. Five subgenomic RNAs were detected from ATCC-infected turkey small intestines by Northern blotting. The whole genome sequence had 86.9% identity between TCoV and IBV, supporting that TCoV is a group 3 coronavirus. (c) 2008 Elsevier B.V. All rights reserved.
The operational amplifier (OP-AMP) is a really significant and a widely used building block in analog and mixed signal circuit design. Since the performance of OP-AMP in an integrated circuit affects the overall performance of the system, therefore, the power consumption of OP-AMP needs to be reduced. The designs of low-power circuits require the reduction in the internal power supply voltage and minimum interconnection of parasitic elements. Considering the requirements of low-power low-voltage and high efficient circuit, an ultra-low-power low-voltage two stage CMOS OP-AMP with very high open-loop gain (DC gain) and high Unity-Gain Bandwidth (UGB) is proposed here to achieve accuracy and fast settling requirements giving 0.7 V power supply. In this work, high open-loop gain with fast settling time is attained through Cascode technique while the Unity-Gain Bandwidth is enhanced with the help of gain-stage in Miller capacitor feedback path. The proposed OP-AMP provides an open-loop gain of 92 dB, Unity-Gain Bandwidth of 230 MHz, having power consumption of only 20.6 mu W. All the simulations have been performed using Cadence in 45 nm technology.
Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman's or Pearson's rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation (P<0.01) with leukocyte telomere length. Waist circumference and systolic blood pressure were negatively related (P=0.03) with leukocyte telomere length in men. Oral glucose tolerance test result-based glycemic categories did not show differences between mean leukocyte telomere length in categories of normal fasting plasma glucose and 2-h post-load plasma glucose (NGT, n=33); diabetes mellitus (DM), n=18 and impaired fasting glucose/tolerance (IFG/IGT, n=31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups (P=0.027; 0.029 and 0.049, respectively) was revealed; the association between leukocyte telomere length and fasting plasma glucose was confirmed in DM group only (P=0.009). Increase of 2-h post-load plasma glucose (but not fasting plasma glucose) level improves the chances of revealing short telomeres: OR 1.52 (95% CI 1.04-2.22), P=0.03. After the adjustment for age, gender, waist circumference, systolic blood pressure, and fasting plasma glucose, these phenomena remain significant. We conclude that 2-h post-load plasma glucose but not fasting plasma glucose is inversely associated with leukocyte telomere length. Impact statement Contradictory epidemiologic data have been obtained about the link between the leucocyte telomere length (LTL) and diabetes. Type 2 diabetes (T2D) is likely to be pathophysiologically heterogeneous, but comparison of the association of LTL separately with fasting plasma glucose (FPG) and 2-h post-load plasma glucose (2hPG) levels has not been done before. Thus, the study of LTL changes associated with different types of hyperglycaemia, that largely determine the heterogenity of T2D is important. In a population-based study of rural Ukrainians, we were the first to demonstrate that the increase of 2hPG (but not FPG) level increases the chances of revealing short telomeres. The obtained data can help to clarify the relationship between the LTL shortening and different conditions of the insulin resistance (mainly liver resistance in high FPG and mostly muscle and adipose tissue resistance in high 2hPG).
This paper presents a proposed new approach for complex control combining several simpler individual fuzzy controllers. This method is particularly useful when the case of study is a multivariable control system. The proposed method has a hierarchical architecture with 2 levels (individual fuzzy systems and a superior control to adjust the global result). The behavior of the proposed method is illustrated with a problem of flight control that requires several individual controllers. In addition a statistical comparison is performed using the t student test, where the proposed control strategy is compared against a simple fuzzy control approach. Finally, an optimization method is also applied to achieve an optimal design of the fuzzy systems. (C) 2015 Elsevier Inc. All rights reserved.
Background: Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures. Methodology/Principal findings: Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had >= 1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had >= 1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia. Conclusions/Significance: Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association.
The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology. As a result, several classes of TAM inhibitors that include small molecule tyrosine kinase inhibitors, monoclonal antibodies, decoy receptors, as well as novel strategies to target TAM ligands are being developed. This paper will review the biology of TAM receptors and their ligands with a focus on cancer, as well as evidence-based data for the continued pursuit of TAM/Gas6 inhibitors in clinical practice.
The deterioration of the U.S. highway system has received significant attention from scholars, industry practitioners, and policymakers over the last several decades. This growing interest has encouraged the production of multiple reports highlighting the challenges of enhancing system conditions in the long term. Because government agencies do not have sufficient resources to take care of roads in a timely manner, deterioration worsens, and available funds are primarily used for previously deferred maintenance and rehabilitation activities. The current work seeks to gain insight into the dynamics of capital investments and maintenance expenditures in U.S. road infrastructure. Based on a system dynamics model, the authors argue that the highway system is stuck in a capability trap (failure to achieve sustained improvements) because authorities tend to promote short-term reactive efforts over long-term proactive actions. The study contributes to the existing literature by highlighting the feedback mechanisms that connect maintenance and rehabilitation expenditures with aging and deterioration processes. Building on a counterfactual analysis between 1994 and 2010, the research reveals that incentivizing preventive practices not only enhances system conditions but also reduces major rehabilitation expenses and, in the long term, frees up resources for capacity expansion. Conclusions point to the difficulties associated with escaping the trap and the impacts of implementing reactive and proactive policies throughout the highway system. (C) 2017 American Society of Civil Engineers.
Background: Small nucleolar RNAs are a highly conserved group of small RNAs found in eukaryotic cells. Genes encoding these RNAs are diversely located throughout the genome. They are functionally conserved, performing post transcriptional modification (methylation and pseudouridylation) of rRNA and other nuclear RNAs. They belong to two major categories: the C/D box and H/ACA box containing snoRNAs. U3 snoRNA is an exceptional member of C/D box snoRNAs and is involved in early processing of pre-rRNA. An antisense sequence is present in each snoRNA which guides the modification or processing of target RNA. However, some snoRNAs lack this sequence and often they are called orphan snoRNAs. Results: We have searched snoRNAs of Entamoeba histolytica from the genome sequence using computational programmes (snoscan and snoSeeker) and we obtained 99 snoRNAs (C/D and H/ACA box snoRNAs) along with 5 copies of Eh_U3 snoRNAs. These are located diversely in the genome, mostly in intergenic regions, while some are found in ORFs of protein coding genes, intron and UTRs. The computationally predicted snoRNAs were validated by RT-PCR and northern blotting. The expected sizes were in agreement with the observed sizes for all C/D box snoRNAs tested, while for some of the H/ACA box there was indication of processing to generate shorter products. Conclusion: Our results showed the presence of snoRNAs in E. histolytica, an early branching eukaryote, and the structural features of E. histolytica snoRNAs were well conserved when compared with yeast and human snoRNAs. This study will help in understanding the evolution of these conserved RNAs in diverse phylogenetic groups.
Aims: Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Methods: Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. Results: E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p < 0.05). Ectopic E2-EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p < 0.01). The 5-year survival rate of glioma patients with high E2-EPF levels was shorter than in patients with low expression (p < 0.05). Furthermore, the 5-year survival rate of patients with ectopic E2-EPF was significantly shorter than patients with only nuclear E2-EPF (p < 0.01). Conclusions: These results suggest that higher E2-EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma.
Recently, ubiquitous manufacturing has attracted wide attention in both academia and industry. To create a successful ubiquitous manufacturing system, an efficient material handling system is essential. In accordance with this reason, mobile robots have been used for transporting materials. This paper aims at developing a methodology for scheduling the material supply for a single mobile robot in a ubiquitous manufacturing environment. In this type of environment, the processing rate of the materials along with supply quantity corresponds to the cycle of material supply. The carrying capacity of the robots are limited and thus the problem of determining the material supply quantity and material supply schedule without lack of materials for production or service processes becomes complicated. In this work, a nonlinear program is formulated to schedule the supply of material and determine the required material quantity. A heuristic algorithm based on genetic algorithm is developed to solve the problem. From the numerical experiments conducted in this study, it is observed that the proposed algorithm shows good performance and can also be implemented to solve large scale problems. (C) 2016 Elsevier Ltd. All rights reserved.
This work proposes a Digitally Enhanced Low-Drop Out Voltage Regulator (DE-LDO) for Ultra High Radio Frequency IDentification (UHF RFID) passive tags. The DE-LDO design approach is based on the Finite State Machine (FSM) nature of the tag Digital Control. Injecting part of the FSM unconsumed current into LDO loop to enhance transient response, a more flat output voltage is obtained. Chip measurements shows that DE-LDO consumes a quiescent current of 600 nA at 1.6V, delivering an output current and voltage of 8 mu A and 1.2V; a 69.76% Power Efficiency (PE) is observed. Circuit design and fabrication were performed using 0.50 mu m CMOS technology.
The present study aimed to investigate the regulatory effect of probiotics on the expression of Toll-like receptors (TLRs) in an ulcerative colitis (UC) rat model, and to determine the role of probiotics in the underlying mechanisms through which UC develops and progresses in rat models. Rats were randomly allocated to one of the four following groups: i) The healthy control, ii) the model, iii) the Golden bifid treatment group, and iv) the TLR4 monoclonal antibody (TLR4mAb) intervention group. The UC rat model was established using 2,4,6-trinitro-benzene sulfonic acid. The general status and histological changes of rats were scored using the disease activity index and the histopathological scoring method, respectively. In these rats, the expression of TLR4 and TLR2 was measured using reverse transcription-quantitative polymerase chain reaction. The expression of TLR4 and TLR2 in the model group was significantly higher than that in the healthy control group. However, when compared with the model rats, those that received either Golden bifid treatment or TLR4mAb intervention exhibited significantly decreased mRNA expression levels of TLR4 and TLR2 (P < 0.05). The development of UC is characterized by an abnormal immune response in the intestines. Probiotics alleviated inflammatory reactions in rats with UC. The underlying mechanism of UC may be associated with the expression of TLRs and the subsequent release of inflammatory cytokines.
Transmission towers play an important role in transmitting electricity in a power grid safely and reliably. In traditional design practice, the second-order P-Delta (frame side sway) and P-delta (member curvature) effects and joint effects such as load eccentricities, slippage effects, and semirigid connection are commonly ignored in analysis. Great discrepancy is frequently noted between full-scale tower tests and numerical simulations using first-order linear analysis. In this paper, second-order direct analysis is used and slippage of bolted joints as well as semirigid connection behavior are taken into account. Member initial bowing and frame out-of-plumbness imperfections are considered in the present study, which is verified by full-scale test on an ultrahigh-voltage (UHV) lattice transmission tower. The technique of semirigid design and simulation of joint stiffness for load eccentricity by simple modeling for transmission towers meeting the requirements for direct analysis with verification by a full-scale test is unavailable in literature and proposed in this paper. Furthermore, the influences of joint slippage on the deflection and load behavior of the studied towers are quantified and reported. (C) 2017 American Society of Civil Engineers.
This paper presents sub-threshold, bulk-driven two-stage cascode compensated operational transconductor, which drive load up to 60 pF. The input core in the first stage uses a bulk-driven source-degenerated, gate-regenerated class AB flipped voltage follower (FVF), which ensures rail-to-rail linear input signal drive capability in its unity gain configuration. The self-cascode load of input stage followed by a common source (CS) second stage having simple current source load, have enhanced overall gain around 100 dB. at 1 mHz. Instead of Miller compensation, cascode compensation has been implemented by using two capacitors (C-c/2) each of value 4 pF in this OTA. It has increased its phase margin and gain bandwidth as compared to Miller compensation, under identical load and total compensation capacitors. It ensured better rail-to-rail linearity (THD < -44 dB) at 200 Hz frequency consuming around 74 nW power from +/- 250 mV dual power supply. Another three-stage OTA is also proposed, which includes one additional CS class AB buffer at the output of OTA1, to drive R-C shunt load. This buffered OTA is additionally nested Miller compensated using capacitor (C-NMC) of 0.2 pF. This buffering enhances slew rate and gain bandwidth (GBW) by two-times as compared to un-buffered structure at the cost of power. The Cadence VIRTUOSO environment using UMC 0.18 mu m CMOS process technology has been used to simulate the proposed circuits. (C) 2016 Elsevier Ltd. All rights reserved.
A switched-current (SI) based beamformer, suitable for low-power and low-area applications, is presented. The most important feature of the proposed beamformer is that the current consumption does not increase linearly with memory size. This is achieved by employing external capacitors for memory storage unlike a conventional SI memory. This is a fully differential design implemented using delay and sum approach. An Analog RAM (ARAM) has been used to implement the delay and each memory cell in the ARAM has been implemented using an SI circuits. There are 16 memory cells in each ARAM consuming 35.15 mu A/cell. The signal-to-noise ratio (SNR) of 63 dB is measured after summation of 16 channels. The total current consumption of beamformer including the bias, and digital control is 9 mA and area is 1.27 mm(2). (C) 2015 Elsevier Ltd. All rights reserved.
Background: Arabidopsis thaliana is widely used as model organism in plant biology. Although not of agronomic significance, it offers important advantages for basic research in genetics and molecular biology including the availability of a large number of mutants and genetically modified lines. However, Arabidopsis seed longevity is limited and seeds stored for more than 10 years usually show a very low capacity for germination. Results: The influence of ultrasonic stimulation was investigated on the germination of A. thaliana L. seeds. All experiments have been performed using a frequency of 45 kHz at constant temperature ( 24 degrees C). No germination rate differences were observed when using freshly collected seeds. However, using artificially deteriorated seeds, our results show that short ultrasonic stimulation (<1 min) significantly increased germination. Ultrasonic stimulation application of 30 s is the optimal treatment. A significant increase in the germination rate was also verified in naturally aged seeds after ultrasonic stimulation. Scanning electron microscopy observations showed an increase in the presence of pores in the seed coat after sonication that may be the cause, at least in part, of the increase in germination. The ultrasound treated seeds developed normally to mature fertile plants. Conclusions: Ultrasound technology can be used to enhance the germination process of old Arabidopsis seeds without negatively affecting seedling development. This effect seems to be, at least in part, due to the opening of pores in the seed coat. The use of ultrasonic stimulation in Arabidopsis seeds may contribute to the recovering of long time stored lines.
The epigenetics and molecular biology of human embryonic stem cells (hES cells) have received much more attention than their architecture. We present a more complete look at hES cells by electron microscopy, with a special emphasis on the architecture of the nucleus. We propose that there is an ultrastructural signature of pluripotent human cells. hES cell nuclei lack heterochromatin, including the peripheral heterochromatin, that is common in most somatic cell types. The absence of peripheral heterochromatin may be related to the absence of lamins A and C, proteins important for linking chromatin to the nuclear lamina and envelope. Lamins A and C expression and the development of peripheral heterochromatin were early steps in the development of embryoid bodies. While hES cell nuclei had abundant nuclear pores, they also had an abundance of nuclear pores in the cytoplasm in the form of annulate lamellae. These were not a residue of annulate lamellae from germ cells or the early embryos from which hES cells were derived. Subnuclear structures including nucleoli, interchromatin granule clusters, and Cajal bodies were observed in the nuclear interior. The architectural organization of human ES cell nuclei has important implications for cell structure-gene expression relationships and for the maintenance of pluripotency. (C) 2016 Wiley Periodicals, Inc.
Introduction. Dermatitis bullosa pratensis (phytophotodermatitis) is an acute phototoxic reaction caused by photosensitizing substances present in different kinds of plants, activated by ultraviolet radiation exposure. An acute phototoxic reaction manifests as erythema, vesicles and even blisters with morphology of burns. Objective. We present a case report of phytophotodermatitis due to Heracleum sosnowskyi. Heracleum sosnowskyi was discovered in 1772 and described as a separate species in botanical literature in 1944 by I. P. Man-denova. Case report. In our case, skin lesions coexisted with erythema multiforme. Implemented therapy - corticosteroids, antihistamines and topical medications - was successful. After clinical resolution post-inflammatory hyperpigmentations were observed. Conclusions. Appropriate diagnosis of phytophototoxic reaction may constitute a challenge in everyday practice.
An extract of ulvan obtained from the green alga Ulva clathrata was lyophilized and confirmed by Fourier transform infrared spectrometry (FTIR) and H-1-nuclear magnetic resonance (NMR). The percentage of sulfate groups calculated by elemental quantitative analysis in the lyophilized ulvan was twice (8 %) than that of dry algae (4 %). The dietary effect of ulvan on hematology, immunology, and growth was evaluated in tilapia (Oreochromis niloticus). The fish (25 +/- 3 g) were fed a commercial diet (negative control group), and the diet was supplemented with three levels of ulvan (0.1, 0.5, and 1 % kg(-1) feed). Additionally, a positive control with yeast (Saccharomyces cerevisiae, 2 % kg(-1) feed) was included. During a trial period of 90 days (60 days of treatment + 30 days of suspended treatment), hematocrit (Ht), hemoglobin (Hb), red blood cell (RBC) count, white blood cell (WBC) count, total serum protein (TP), albumin (Al), globulin (Gb), and phagocytic activity (Pa) were measured. After 15 days of treatment until the 60th day, the Pa was increased (P < 0.001) in fish with diets containing 0.1, 0.5, and 1 % ulvan. An increase (P < 0.001) in the WBC count was observed at day 30 in fish with diets containing 0.1, 0.5, and 1 % ulvan; which maintained for 15 days in 0.5 and 1 % ulvan after their dietary suspension. There was no significant difference (P < 0.05) in growth performance among fish for any of the diets tested. This is the first report of an increment in the immune response by a dietary supplementation with ulvan from U. clathrata in the Nile tilapia. These results demonstrate the potential activity of ulvan on at least two mechanisms of the immune response in tilapia and the time over which the activity is sustained in the organism after suspension of supplementation.
The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4(+) CD25(+) CD127(low/-Tregs) in resting CD4(+) T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (-beta 1, and interleukin-10, along with a reduced interferon-gamma. production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4(+) CD25(-)T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC- primed (naive) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4(+) CD25(-)Teffs was observed in UC-MSC-primed Tregs from MS patients and naive Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach.
For more than 40 years, the uncanny valley model has captivated researchers from various fields of expertise. Still, explanations as to why slightly imperfect human-like characters can evoke feelings of eeriness remain the subject of controversy. Many experiments exploring the phenomenon have emphasized specific visual factors in connection to evolutionary psychological theories or an underlying categorization conflict. More recently, studies have also shifted away focus from the appearance of human-like entities, instead exploring their mental capabilities as basis for observers' discomfort. In order to advance this perspective, we introduced 92 participants to a virtual reality (VR) chat program and presented them with two digital characters engaged in an emotional and empathic dialogue. Using the same prerecorded 3D scene, we manipulated the perceived control type of the depicted characters (human controlled avatars vs. computer-controlled agents), as well as their alleged level of autonomy (scripted vs. self-directed actions). Statistical analyses revealed that participants experienced significantly stronger eeriness if they perceived the empathic characters to be autonomous artificial intelligences. As human likeness and attractiveness ratings did not result in significant group differences, we present our results as evidence for an "uncanny valley of mind" that relies on the attribution of emotions and social cognition to non-human entities. A possible relationship to the philosophy of anthropocentrism and its "threat to human distinctiveness" concept is discussed. (C) 2016 Elsevier B.V. All rights reserved.
This paper describes the introduction of synchrotron-based macromolecular crystallography (MX) into an undergraduate laboratory class. An introductory 2 week experimental module on MX, consisting of four laboratory sessions and two classroom lectures, was incorporated into a senior-level biochemistry class focused on a survey of biochemical techniques, including the experimental characterization of proteins. Students purified recombinant protein samples, set up crystallization plates and flash-cooled crystals for shipping to a synchrotron. Students then collected X-ray diffraction data sets from their crystals via the remote interface of the Molecular Biology Consortium beamline (4.2.2) at the Advanced Light Source in Berkeley, CA, USA. Processed diffraction data sets were transferred back to the laboratory and used in conjunction with partial protein models provided to the students for refinement and model building. The laboratory component was supplemented by up to 2 h of lectures by faculty with expertise in MX. This module can be easily adapted for implementation into other similar undergraduate classes, assuming the availability of local crystallographic expertise and access to remote data collection at a synchrotron source.
Participating in undergraduate research can be a pivotal experience for students in life science disciplines. Development of critical thinking skills, in addition to conveying scientific ideas in oral and written formats, is essential to ensuring that students develop a greater understanding of basic scientific knowledge and the research process. Modernizing the current life sciences research environment to accommodate the growing demand by students for experiential learning is needed. By developing and implementing a structured, theory-based approach to undergraduate research in the life sciences, specifically biochemistry, it has been successfully shown that more students can be provided with a high-quality, high-impact research experience. The structure of this approach allowed students to develop novel, independent projects in a computational molecular modeling lab. Students engaged in an experience in which career goals, problem-solving skills, time management skills, and independence in a research lab were developed. After experiencing this approach to undergraduate research, students reported feeling challenged to think critically and prepared for future career paths. The approach allowed for a progressive learning environment where more undergraduate students could participate in publishable research. Future areas for development include implementation in a bench-top lab and extension to disciplines beyond biochemistry. In this study, it has been shown that utilizing the structured approach to undergraduate research could allow for more students to experience undergraduate research and develop into more confident, independent life scientists well prepared for graduate schools and professional research environments. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
This paper (re) tells the story of a sports coach who was accused of emotional abuse of a child athlete and, following an investigation by his club, cleared of the allegation. Accounts of such allegations are rare and no research to date has explored coaches' lived experiences of this. Such stories are 'dangerous' and remain largely unrecognised and undebated as they represent a challenge to the meta-narrative of child protection. Using the stance of a 'storyteller', the coach-participant's story is presented as a monologue crafted using his words and embellished with literary techniques. The story is purposefully largely left open for interpretation in an attempt to encourage readers to engage cognitively and emotionally with it. Telling such a 'dangerous' story aims to add to the narrative repertoires available to those working in this field and expand understandings of child protection in sport.
Background: Early adversity is a known risk factor for unipolar depression. We examined the impact of 9 types of early adversity on risk for moderate to severe unipolar depression in adolescence or adulthood, and evaluated whether these effects were moderated by gender and adversity timing. Methods: We conducted a prospective, population-based cohort study using Danish national registers. The sample included all individuals born in Denmark between 1980 and 1998 (N=978,647). Exposure to early adversity was assessed from ages 0-15. Types of adversity included parental illness, incarceration, death, disability, and psychiatric diagnosis; family disruption; out-of-home care; and childhood abuse. Individuals were followed from age 15 until first in- or outpatient depression diagnosis (ICD-10 codes F32, F33) in a psychiatric hospital, death, emigration, or December 31st, 2013, whichever came first. Hazard ratios (HRs) were calculated using Cox regressions. Results: All adversities were significantly associated with increased risk for moderate to severe adolescent/adult depression (HR range: 1.30-2.72), although the effects were attenuated after mutual adjustment (adjusted HR range: 1.06-1.70). None of the effects were moderated by gender. The effect of family disruption was strongest between ages 0-4 (HR=1.66, 95% CI=1.61-1.71), while the effect of out-of-home care was strongest between ages 10-14 (HR=2.45, 95% CI=2.28-2.64). Limitations: Untreated and primary-care treated depression were not measured. Conclusions: Our results support past findings that multiple types of early adversity increase risk for moderate to severe unipolar depression in adolescence and adulthood. Certain adversities may be more harmful if they occur during specific developmental time periods.
Objective: Structural and functional brain alterations in major depression disorder (MDD) are well studied in cross-sectional designs, but little is known about the causality between onset and course of depression on the one hand, and neurobiological changes over time on the other. To explore the direction of causality, longitudinal studies with a long time window (preferably years) are needed, but only few have been undertaken so far. This article reviews all prospective neuroimaging studies in MDD patients currently available and provides a critical discussion of methodological challenges involved in the investigation of the causal relationship between brain alterations and the course of MDD. Method: We conducted a systematic review of studies published before September 2015, to identify structural magnetic resonance imaging (MRI) studies that assess the relation between neuronal alterations and MDD in longitudinal (1year) designs. Results: Only 15 studies meeting minimal standards were identified. An analysis of these longitudinal data showed a large heterogeneity between studies regarding design, samples, imaging methods, spatial restrictions and, consequently, results. There was a strong relationship between brain-volume outcomes and the current mood state, whereas longitudinal studies failed to clarify the influence of pre-existing brain changes on depressive outcome. Conclusion: So far, available longitudinal studies cannot resolve the causality between the course of depression and neurobiological changes over time. Future studies should combine high methodological standards with large sample sizes. Cooperation in multi-center studies is indispensable to attain sufficient sample sizes, and should allow careful assessment of possible confounders.
This article explores the difference in the time series property of economic output for the Great China Economic Area (GCEA) (Mainland China, Hong Kong and Taiwan). Using the powerful Kim and Perron (2009) unit root test and real GDPs over the period 1992-2014 as the study sample, results indicate the presence of a break for all economies that corresponds to the Asian financial crisis. Additionally, allowing for a break leads to the rejection of the unit root hypothesis for Taiwan only. Important implications are provided. First, considering the presence of a break in testing for nonstationarity is important or false conclusions can be drawn. Second, given the stationarity of GDP found for Taiwan only, investors should look beyond any local economic shocks and focus more on world economy development when investing in Taiwan. By contrast, investors in Mainland China and Hong Kong should pay attention to any shock because it is likely to be persistent. Third, relevant authorities should recognize that any government policy intended to promote long-run economic growth may be ineffective in Taiwan whereas it can be more effective in Mainland China and Hong Kong.
A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home (students as samplers) were employed as teaching material in three different courses of Genetics during the academic year 2014-2015: Experimental Methods in Food Production (MBTA) (Master level), and Applied Molecular Biology (BMA) and Conservation Genetics and Breeding (COMGE) (Bachelor/Degree level). Molecular genetics based on PCR amplification of DNA markers was employed for species identification of 22 seafood products in COMGE and MBTA, and for detection of genetically modified (GM) maize from nine products in BMA. In total six seafood products incorrectly labeled (27%), and two undeclared GM maize (22%) were found. A postLaboratory survey was applied for assessing the efficacy of the approach for improving motivation in the Laboratory Practices of Genetics. Results confirmed that students that worked on their own samples from local markets were significantly more motivated and better evaluated their Genetic laboratory practices than control students (chi(2) = 12.11 p=0.033). Our results suggest that citizen science approaches could not be only useful for improving teaching of Genetics in universities but also to incorporate students and citizens as active agents in food control. (C) 2016 by The International Union of Biochemistry and Molecular Biology.
This paper presents a model for the evaluation of the void ratio dependency of water retention curve (WRC) in deformable porous media. Models currently available in the literature for this purpose are primarily empirical in nature and rely on extensive laboratory testing for parameter identification. The approach proposed requires no additional parameters and enables quantification of the dependency of WRC on void ratio solely based on the form of WRC at the reference void ratio. Particular attention is given to the effect of hydraulic hysteresis on the evolution process, an aspect rarely addressed in the literature. Incremental expressions are presented for the evolution of main drying, main wetting, and scanning curves due to loading and change in the hydraulic path from scanning to main wetting/drying and vice versa. Validity of the model is demonstrated using experimental data for a range of compacted and reconstituted soils subjected to various hydro-mechanical paths. Good agreement is obtained between model predictions and experimental data in all the cases considered. (C) 2017 American Society of Civil Engineers.
Unsteady friction and its modeling have been widely studied in transient pipe flows for its influences and modification effect on pressure waves. Such a feature is of great importance particularly in pipe systems where the extreme pressure values are due to the overlapping of pressure waves generated in different sections. This paper investigates the relevance of unsteady friction term by considering different models available in the literature. In particular, attention is focused on the following two commonly used one-dimensional (1D) models: the weighting function-based (WFB) model and the instantaneous acceleration-based (IAB) model. The investigation is executed using laboratory experiments and field tests as well as 1D/2D numerical simulations in simple pipeline systems. Realistic ranges of both initial (pretransient) conditions and geometrical characteristics are considered. The data collected in experimental tests are first used to calibrate the unsteady friction models under investigation. The validated models are then applied to identify their respective domains of applicability and the limitations. The differences between models and data are measured using the local transient analysis (LTA) norm and the integral total energy (ITE) norm along the pipeline, and the reasons for such discrepancies are explored in the paper. The practical implications of the use and improvements of different unsteady friction models for transient pipe flow simulations are discussed in the paper. (C) 2017 American Society of Civil Engineers.
In recent years, Upconversion (UC) material has attracted much attention because of its fantastic energy transfer capability of converting the low-energy photons into high-energy photons via anti-Stokes process. Among UC materials, the visible-to-UV UC materials exhibit remarkable potential in laser conversion, photo-catalysis, the sterilization as well as antibiosis in biological areas because of their capability of converting the visible radiation into ultraviolet emission. Considering the interesting UC process and large potential application of the visible-to-UV UC materials, it is necessary to overview its intrinsic UC mechanism, material structure, as well as material synthesis techniques for the development of UC material. This work focus on the visible-to-UV UC materials and review its current research situation, the challenges in its research field, as well as analyzing and comparing recent investigations to provide valuable evaluation for such materials both from theoretical and commercial perspective. The most effective UC matrix and luminescent centers in recent works were summarized and the intrinsic mechanisms of visible-to-UV UC were introduced. The material design strategies and techniques for the synthesis of visible-to-UV UC phosphors were focused. The advantages and the limitations of visible-to-UV UC material are discussed in detail, and a reasonable expectation for the emerging trends of such potential material is provided. (C) 2017 Elsevier B.V. All rights reserved.
Background: Upstream open reading frames (uORFs) are commonly found in the 5'-untranslated region (UTR) of many genes and function in translational control. However, little is known about the existence of the proteins encoded by uORFs, and the role of the proteins except translational control. There was no report about uORFs of the McKusick-Kaufman syndrome (MKKS) gene that causes a genetic disorder. Methods: Northern blotting, 3'-RACE, and bioinformatics were used for determining the length of transcripts and their 3' ends. Luciferase assay and in vitro translation were used for evaluation of translational regulatory activity of uORFs. Immunoblotting and immunocytochemical analyses were used for detection of uORF-derived protein products and their subcellular localization. Results: The MKKS gene generates two types of transcripts: a canonical long transcript that encodes both uORFs and MKKS, and a short transcript that encodes only uORFs by using alternative polyadenylation sites at the 5'-UTR. The simultaneous disruption of the uORF initiation codons increased the translation of the downstream ORF. Furthermore, both protein products from the two longest uORFs were detected in the mitochondrial membrane fraction of HeLa cells. Database searches indicated that such uORFs with active alternative polyadenylation sites at the 5'-UTR are atypical but surely exist in human transcripts. Conclusions: Multiple uORFs at the 5'-UTR of the MKKS long transcript function as translational repressor for MKKS. Two uORFs are translated in vivo and imported onto the mitochondrial membrane. General significance: Our findings provide unique insights into production of uORF-derived peptides and functions of uORFs. (C) 2012 Elsevier By. All rights reserved.
Although place-related identity is receiving increasing attention within the environmental psychology field, little attention has been paid to deepen on place identity at the local level and better understand the social nature of urban identity. Focusing on the case of Zaragoza (the fifth largest city in Spain), this work aims to contribute to previous literature by understanding how shared city meanings and sociodemographic characteristics influence urban identity formation, proposing a standard measure of urban identity as a social identity formed by three-dimensions (cognitive, affective and evaluative), and testing the influence of urban identity on citizens' behaviors. Results show that: (1) city social representations participate in the formation process of the three dimensions of urban identity, (2) the operationalization of urban identity as a second-order construct is validated, and (3) urban identity influences citizens behavioral support to local initiatives via personal and social norms. (C) 2017 Elsevier Ltd. All rights reserved.
China's rapid urbanization has generated substantial attention throughout the world. There are various studies that assess China's urbanization process but without consistent conclusions. This paper attempts to evaluate China's urbanization level based both on global urban development experience and on urbanization theories; in addition, it adopts the quadrant plots method to assess China's regional urbanization level. The results of this study show that China's urbanization rate is proceeding at a normal level that is consistent with Northam Curve Growth Theory, the Lewis's Migration Theory, Chenery's Theory of Normal Growth, and also with China's economic development stage. However, certain problems and challenges remain to be examined, such as the low-level coordination between China's urbanization and nonagricultural employment and the narrow difference between urbanization rate and industrialization level. In general, most of the eastern provinces show a high coordination between urbanization and economic development, whereas all the provinces with low coordination, both low urbanization rate and economic development levels, are located in central and western China. These results not only advance the previous literature but also deserve particular attention from Chinese policymakers. Local governments should pay close attention to the urbanization quality, the urban planning support systems, and the upgrading of industry structure while not focusing too much on the urbanization quantity. (C) 2016 American Society of Civil Engineers.
Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement. To outline potential strategies to overcome tumor immune resistance, herein, we summarize current models of tumor immunology with a specific focus on bladder cancer. Recognition of tumor-specific antigens through cross presentation, T-cell priming and activation, and trafficking of immune cells to the tumor microenvironment are some of the critical steps we now understand to be necessary for an effective antitumor immune response. Many of the involved steps are important targets for therapeutic interventions. As new immunotherapies are developed, predictive biomarkers would also be important to select patients most likely to respond and to better understand tumor biology. Several potential biomarkers are reviewed including PD-L1 expression, identification of T-cell-inflamed/non T-cell-inflamed tumors based on immune gene expression, intrinsic molecular subtyping based on luminalThasal or the cancer genome atlas (TCGA) groups, T-cell receptor sequencing, and somatic mutational density. Even within the past few years, our current knowledge of immune biology has exploded, and we are highly optimistic about the future of UBC therapy that will be available to patients. (C) 2016 Elsevier Inc. All rights reserved.
Tremendous advances in our understanding of the tumor immunology and molecular biology of urothelial carcinoma (UC) have led to the recent approval of immunotherapy as a novel option for patients with UC with advanced disease. Despite the promising data of novel immune checkpoint inhibitors, only a small subset of patients with UC achieves durable remissions. Because an optimal antitumor response requires coordination of multiple immune, tumor, and microenvironment effector cells, novel approaches targeting distinct mechanisms of action likely in combination are needed. In addition, discovery of reliable immune biomarkers, understanding of mechanisms of resistance, and novel clinical trial designs are warranted for maximum benefit of UC immunotherapy. (C) 2016 Elsevier Inc. All rights reserved.
Electricity power is a basic industrial component which plays an important role in the economy of a nation. In this paper, the correlations evolution of electricity prices among 50 states and the District of Columbia are studied based on random matrix theory (RMT) Four regime shifts are identified from January 1990 to August 2014 in the U.S. residential, commercial and industrial electricity markets. Then, the genetic algorithm (GA) is applied to analyze the clusters of evolution. The results show that, the correlations of electricity prices increased continually in the three departments. However, it decreased in 2012 which further confirms its sensitivity to fuel market. Besides, four regime shifts exist in the three departments though the different times of occurrence caused by price level. And, the fluctuation of community evolution is consistent with four regime shifts. The final part is a summary of the research analyzed and results. (C) 2016 Elsevier Ltd. All rights reserved.
Light has a profound impact on the human body. Visually, light determines what aspects of our surroundings we can perceive and interpret. Non-visually, light contributes to regulating our physiology and psychology. Light is thus an unusual medium that can work both in and out of our conscious attention, and with new lighting technology this aspect is falling within our control. Computer controllable solid-state lighting has advanced such that they are now a commonplace technology in the world around us. While many of the characteristics of light-emitting diode (LED) lighting must fulfill the same requirements as lighting in the past, the ability to readily integrate LED technology into digital control systems presents exciting new opportunities that were not possible with other artificial light sources; for example, the potential to integrate the small form factor of an LED into the very fabric of a material or control them remotely over the Internet are aspects that set this technology apart from what has gone before. This unprecedented flexibility presents the opportunity for new functionality and novel interactive solutions for and with light. In this chapter, we present three categories of interactive lighting with many concrete examples: interacting with light at the center of our attention, interacting with light outside our attentional field, and interacting with light in the periphery of our attention. We conclude by considering the factors that make lighting a special medium for peripheral interaction and the role peripheral interaction can play in exposing the many new degrees of freedom ubiquitous digital lighting presents.
Uveal melanoma (UM) is the most common intraocular malignancy and arises from melanocytes in the iris, ciliary body, or choroid. Early diagnosis and local treatment is crucial, as survival correlates with primary tumor size. However, approximately 50% of patients will develop metastatic disease with 6-12 months' survival from metastatic diagnosis. Genomic analyses have led to the development of gene-expression profiles that effectively predict metastatic progression; unfortunately, no adjuvant therapy has been shown to prolong survival to date. New insights into the molecular biology of UM have found frequent activating mutations in genes encoding for the G-protein a-subunit, GNAQ and GNA11, and improved understanding of the downstream signaling pathways MAPK, PI3K/Akt, and Hippo have afforded an array of new targets for treatment of this disease. Studies are under way with rationally developed regimens targeting these pathways, and novel agents are under development. We review the diagnosis, management, and surveillance of primary UM and the adjuvant therapy trials under way.
Ocular toxoplasmosis, a chorioretinal infection with Toxoplasma gondii, is the most common etiology of posterior uveitis in many countries. Accurate diagnosis depends heavily on the characteristic clinical features of this disease, but atypical presentations, especially in immunocompromised patients, may create diagnostic challenges and lead to misdiagnosis and inappropriate treatment. Molecular biology techniques to diagnose ocular toxoplasmosis have been available for many years and are now accessible as standard laboratory tests in many countries. Aqueous humor or vitreous evaluation to detect parasite DNA by polymerase chain reaction or specific antibody may provide definitive evidence for rapid diagnosis. Oral pyrimethamine and sulfadiazine plus systemic corticosteroids are an effective therapy for ocular toxoplasmosis. Recent data supports the use of other treatment approaches, including intravitreal antibiotics. The aim of the present review is to discuss briefly the new diagnostic tools and treatment options for ocular toxoplasmosis. (C) 2016 S. Karger AG, Basel
Biomaterial vaccines offer new capabilities that can be exploited for both infectious disease and cancer. We recently developed a novel vaccine platform based on self-assembly of immune signals into immune polyelectrolyte multilayers (iPEMs). These iPEM vaccines are electrostatically assembled from peptide antigens and nucleic acid-based toll-like receptor agonists (TLRas) that serve as molecular adjuvants. Gold nanoparticles (AuNPs) coated with iPEMs stimulate effector cytokine secretion in vitro and expand antigen-specific T cells in mice. Here we investigated how the dose, injection route, and choice of molecular adjuvant impacts the ability of iPEMs to generate T cell immunity and anti-tumor response in mice. Three injection routesintradermal, subcutaneous, and intramuscularand three iPEM dosing levels were employed. Intradermal injection induced the most potent antigen-specific T cell responses and, for all routes, the level of response was dose-dependent. We further discovered that these vaccines generate durable memory, indicated by potent, antigen-specific CD8(+) T cell recall responses in mice challenged with vaccine 49 days after a prime-boost immunization regimen. In a common exogenous antigen melanoma model, iPEM vaccines slowed or stopped tumor growth more effectively than equivalent ad-mixed formulations. Further, iPEMs containing CpGa TLR9awere more potent compared with iPEMs containing polyIC, a TLR3a. These findings demonstrate the ability of iPEMs to enhance response to several different classes of vaccine cargos, supporting iPEMs as a simple vaccine platform that mimics attractive features of other nanoparticles using immune signals that can be self-assembled or coated on substrates. Biotechnol. Bioeng. 2017;114: 423-431. (c) 2016 Wiley Periodicals, Inc.
In this study, synthetic vaccine nanoparticles (SVNPs) that efficiently targeted lymph nodes, where immune responses against foreign antigens are primed, were developed to enhance antitumor immunity. The size (20-70 nm) and surface character (amination) of poly(gamma-glutamic acid)-based SVNPs were selected for effective loading and delivery (i.e., migration and retention) of model tumor antigen (OVA) and toll-like receptor 3 agonist (poly (I:C)) to immune cells in lymph nodes. Antigen-presenting cells treated with SVNP-OVA and SVNP-IC showed higher uptake of OVA and poly (I: C) and higher secretion of inflammatory cytokines (TNF-alpha, IL-6) and type I interferon (IFN-alpha, IFN-beta) than those treated with OVA and poly (I: C) alone. In vivo analysis revealed higher levels of activation markers, inflammatory cytokines, and type I IFNs in the lymph nodes of mice immunized with SVNP-IC compared to those of mice in other groups. SVNP-IC-treated mice showed significantly greater in vivo natural killer cell expansion/activation (NK1.1(+) cells) and CD8(+) T cell response (CD8(+) INF-gamma(+) cells) in innate and adaptive immunity, respectively. Both preventive and therapeutic vaccination of EG7-OVA tumor-bearing mice using the simultaneous injection of both SVNP-OVA and SVNP-IC induced higher antitumor immunity and inhibited tumor growth. (C) 2017 Elsevier Ltd. All rights reserved.
The development of prophylactic vaccines remains largely empirical in nature and rarely have general rules been applied in the strategic decision and the formulation of a viral vaccine. Currently, there are a total of 15 virus agents from 12 unique virus families with vaccines licensed by the U.S. Food and Drug Administration. Extensive structural information on these viral particles and potential mechanisms of protection are available for the majority of these virus pathogens and their respective vaccines. Here I review the quantitative features of these viral surface antigens in relation to the molecular mechanisms of B-cell activation and point out a potential correlation between the density of immunogenic proteins displayed on the surface of the vaccine antigen carrier and the success of a vaccine. These features help us understand the humoral immunity induced by viral vaccines on a quantitative ground and re-emphasize the importance of antigen density on the activation of the immune system. Although the detailed mechanisms behind this phenomenon remain to be explored, it implies that both the size of antigen carriers and the density of immunogenic proteins displayed on these carriers are important parameters that may need to be optimized for the formulation of a vaccine. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Past research finds that people behave as though the particular qualities of specific, strongly valenced individuals "rub off" on objects. People thus value a sweater worn by George Clooney but are disgusted by one worn by Hitler. We hypothesized that social traces of generic humans can also adhere to objects, increasing their value. Experiments 1 and 2 found that simply marking that consumer products (mugs, giftwrap) were made by generic strangers (e.g., "by people using machines" vs. "by machines run by people") increased their perceived value. Experiment 3 demonstrated that this effect was mediated by thoughts about attention the object received from other people, which, in turn, led people to see the object as possessing more positive social qualities (e.g., friendly), increasing valuation. The results suggest that generic humans are perceived positively, possessing warm social qualities, and these can "rub off" and adhere to everyday objects increasing their value.
A new large dynamic-range variable gain amplifier (VGA) with improved dB linearity is presented. The traditional cascade VGA has the disadvantages of gain mismatch between sub-stages and difficulty of employing mismatch cancelation or suppression algorithms. In this paper, switch arrays were used to make the sub-stages or called gain cells in the coarse-tuning stage (CTS) work independently and therefore prevent the integral operation of the gain errors. Then, a second-order mismatch-shaping DEM was applied conveniently to the CTS and shown to be a useful design technique in improving the dB-linearity performance. The cascade VGA and its second-order mismatch-shaping DEM had been integrated in a 2.4-GHz receiver chip which was fabricated in a 0.18-mu m CMOS technology with a supply voltage of 1.8V. Measurement results showed that the gain errors were significantly reduced with second-order mismatch-shaping DEM with respect to the traditionally thermometric decoding over a temperature range of [-40, 80] degrees C. Copyright (c) 2015 John Wiley & Sons, Ltd.
Wheel-torque control bandwidth in vehicle dynamics model is crucial in evaluating optimal tracking ability of tire slip and in analysis of control system stability. Electric drives' control dynamics are influenced by timing of digital control events, e.g. by sampling instant of motor currents. Reflecting this timing in drive analytical models is therefore important for analysis of vehicle traction systems. The paper considers five various transfer-function models including issues of digital control events timing. The aim of the paper is to compare the accuracy of the models in representing dynamics of a Permanent Magnet Synchronous Motor (PMSM) drive. Bode characteristics of the analytical models are compared to these of a reference model. The comparison is made for three commonly used cases of PMSM current sampling. Applicability of presented models has been discussed and frameworks to use specific models have been indicated.
In this paper the space variable-order fractional Schrodinger equation (VOFSE) is studied numerically, where the variable-order fractional derivative is described here in the sense of the quantum Riesz-Feller definition. The proposed numerical method is the weighted average non-standard finite difference method (WANSFDM). Special attention is given to study the stability analysis and the convergence of the proposed method. Finally, two numerical examples are provided to show that this method is reliable and computationally efficient.
A woman presented with at least four manifestations of varicella-zoster virus (VZV) infection, including central nervous system vasculitis, during her first 2 years of HIV infection. We evaluated her CD4 T cell responses to VZV given the infrequency with which multiple recurrences of VZV occurred, especially following immune reconstitution on antiretroviral therapy.
Ageing is characterized by a decline in all systemic functions. A greater susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells. They play an important role in neo-angiogenesis and endothelial repair. Vascular ageing is associated with changes in the structure and functions of vessels' wall. There are many possible causes of this damage. For sure, inflammation and oxidative stress play a fundamental role in the pathogenesis of endothelial dysfunction, commonly attributed to a reduced availability of nitric oxide. Inflammageing, the chronic low-grade inflammation that characterizes elderly people, aggravates vascular pathology and provokes atherosclerosis, the major cardiovascular disease. Nutraceutical and molecular biology represent new insights in this field. In fact, the first could represent a possible treatment in the prevention or delay of vascular ageing; the second could offer new possible targets for potential therapeutic interventions. In this review, we pay attention on the causes of vascular ageing and on the effects of nutraceuticals on it. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Background: Modifiable cardiovascular risk factors elevate risk of subsequent depression in older adults, but the effect of their onset before or after age 65 on incident depression is unclear. Methods: Participants were 1190 male medical students without a diagnosis of depression, who matriculated in 1948-1964 and followed through 2011. Cox proportional hazards models were used to assess associations of vascular risk-factor burden, diabetes, hypertension, hyperlipidemia, smoking status, and overweight/obese status with onset of incident depression. Adjustment covariates were race, enrollment wave, baseline age, physical activity, and heavy alcohol use. Results: The analysis included 44,175 person-years of follow-up. Among participants depression-free until age 65, vascular risk-factor burden after age 65 (Hazard Ratio, [HR]: 2.13, 95% Confidence Interval, [CI]: 1.17, 3.90) was associated with incident depression risk after age 65. The magnitude of vascular risk-factor burden after age 65 on depression risk after age 65 is comparable to the effect of 8.2 additional years of age. Diabetes (HR: 2.79, 95% CI: 1.25, 6.26), hypertension (HR: 2.72, 95% CI: 1.52, 4.88), and hyperlipidemia (HR: 1.88, 95% CI: 1.05, 3.35) before age 65 were associated with incident depression risk after age 65. Men diagnosed with diabetes after age 65 had 2.87 times the risk of incident depression after age 65 (95% CI: 1.24, 6.62). Limitations: Our findings are restricted to male former medical students, which may affect study generalizability. Conclusions: Results support the vascular depression hypothesis. Depression screening in older adults with vascular risk-factor burden may provide an avenue for prevention of late-onset depression.
Vacuolar H+-ATPase (V-ATPase), an electrogenic proton pump, is highly expressed in Plasmodium falciparum, the human malaria parasite. Although V-ATPase-driven proton transport is involved in various physiological processes in the parasite, the overall features of the V-ATPase of P falciparum, including the gene organization and biogenesis, are far less known. Here, we report cDNA cloning of proteolipid subunit c of P falciparum, the smallest and most highly hydrophobic subunit of V-ATPase. RT-PCR analysis as well as Northern blotting indicated expression of the proteolipid gene in the parasite cells. cDNA, which encodes a complete reading frame comprising 165 amino acids, was obtained, and its deduced amino acid sequence exhibits 52 and 57% similarity to the yeast and human counterparts, respectively. Southern blot analysis suggested the presence of a single copy of the proteolipid gene, with 5 exons and 4 introns. Upon transfection of the cDNA into a yeast null mutant, the cells became able to grow at neutral pH, accompanied by vesicular accumulation of quinacrine. In contrast, a mutated proteolipid with replacement of glutamate residue 138 with glutamine did not lead to recovery of the growth ability or vesicular accumulation of quinacrine. These results indicated that the cDNA actually encodes the proteolipid of P falciparum and that the proteolipid is functional in yeast. (c) 2005 Elsevier B.V. All rights reserved.
The widely-distributed North American species Peromyscus leucopus and P. maniculatus of cricetine rodents are, between them, important natural reservoirs for several zoonotic diseases of humans: Lyme disease, human granulocytic anaplasmosis, babesiosis, erhlichiosis, hard tickborne relapsing fever, Powassan virus encephalitis, hantavirus pulmonary syndrome, and plague. While these infections are frequently disabling and sometimes fatal for humans, the peromyscines display little pathology and apparently suffer few consequences, even when prevalence of persistent infection in a population is high. While these Peromyscus spp. are unable to clear some of the infections, they appear to have partial resistance, which limits the burden of the pathogen. In addition, they display traits of infection tolerance, which reduces the damage of the infection. Research on these complementary resistance and tolerance phenomena in Peromyscus has relevance both for disease control measures targeting natural reservoirs and for understanding the mechanisms of the comparatively greater sickness of many humans with these and other infections. (C) 2016 Elsevier Ltd. All rights reserved.
Intranasal infection with vaccine strain of Venezuelan equine encephalitis virus (TC83) caused persistent viral infection in the brains of mice without functional a beta T-cells (a beta-TCR -/-). Remarkably, viral kinetics, host response gene transcripts and symptomatic disease are similar between a beta-TCR -/- and wild-type C57BL/6 (WT) mice during acute phase of infection [0-13 days post-infection (dpi)]. While WT mice clear infectious virus in the brain by 13 dpi, a beta-TCR -/- maintain infectious virus in the brain to 92 dpi. Persistent brain infection in a beta-TCR -/- correlated with inflammatory infiltrates and elevated cytokine protein levels in the brain at later time points. Persistent brain infection of a beta-TCR -/- mice provides a novel model to study prolonged alphaviral infection as well as the effects and biomarkers of long-term viral inflammation in the brain.
The potential for electric vehicles to obtain income from energy supplied to a commercial building together with revenue accruing from specific ancillary service markets in the UK is evaluated in this work. A hybrid time-series/probabilistic simulation environment using real-world data is described, which is applied in the analysis of electricity trading with vehicle-to-grid to vehicles, buildings and markets. Key parameters are found to be the electric vehicle electricity sale price, battery degradation cost and infrastructure costs. Three vehicle-to-grid scenarios are evaluated using pool vehicle trip data, market pricing index data and half-hourly electricity demand for a commercial building. Results show that provision of energy to the wholesale electricity market with additional income from the capacity market results in the greatest projected return on investment, producing an individual vehicle net present value of similar to 8400 pound. This is over 10 years for a vehicle supplying energy three times per week to the half-hour day ahead market and includes the cost of installing the vehicle-to-grid infrastructure. The analysis also shows that net income generation is strongly dependent upon battery degradation costs associated with vehicle-to-grid cycling. (C) 2017 Elsevier Ltd. All rights reserved.
Venous malformations (VMs) are characterized by ectatic and tortuous venous channels with decreased perivascular cell coverage. Recent studies have discovered that miR-145 plays a critical role in amounts of vascular diseases through regulating the differentiation and phenotype of vascular smooth muscle cells (VSMCs). However, the potential roles of miR-145 in VMs remain unknown. In this study, 21 samples of VMs without treatment history, and 10 samples of healthy donor skin, were collected to evaluate the expression level of TGF-beta, miR-145, and alpha-SMA by immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction (PCR). Subsequently, their correlations were analyzed using the Spearman rank correlation testin vitro studies were performed using human umbilical vein endothelial cells (HUVECs). The results showed that miR-145 was significantly downregulated in VMs compared with normal skin tissues, accompanied by a synchronously decreased TGF-beta expression level and perivascular alpha-SMA(+) cell coverage. Correlation analysis revealed that miR145 expression was positively correlated with TGF-beta expression and perivascular alpha-SMA+ cell coverage in VMs. In addition, TGF-beta, miR-145, and alpha-SMA were concurrently increased in the tissues of VMs treated with bleomycin A5. More importantly, in vitro studies revealed that both recombinant human TGF-beta and bleomycin A5 could significantly upregulate TGF-beta and miR-145 expression in HUVECs with the similar increasing tendency. In summary, our present study unmasked the downregulation of miR-145 in VMs, possibly induced by TGF-beta depression and closely correlated with disorganized vessels. Moreover, miR-145 may be involved in the sclerotherapy of VMs and possess the target potential. (C) 2017 Elsevier B.V. All rights reserved.
Let ohm subset of R-2 be an open domain with fractal boundary partial derivative ohm. We define a proper, convex and lower semicontinuous functional on the space X-2(ohm,partial derivative ohm) := L-2(ohm, dx) x L-2(partial derivative ohm, d mu), and we characterize its subdifferential, which gives rise to nonlocal Venttsel' boundary conditions. Then we consider the associated nonlinear semigroup T-p generated by the opposite of the subdifferential, and we prove that the corresponding abstract Cauchy problem is uniquely solvable. We prove that the (unique) strong solution solves a quasi-linear parabolic Venttsel' problem with a nonlocal term on the boundary partial derivative ohm of ohm. Moreover, we study the properties of the nonlinear semigroup T-p and we prove that it is order-preserving, Markovian and ultracontractive. At the end, we turn our attention to the elliptic Venttsel' problem, and we show existence, uniqueness and global boundedness of weak solutions. (C) 2016 Elsevier Ltd. All rights reserved.
Objective: Very preterm (VP) children are at risk for social difficulties, including autism spectrum disorder (ASD). This study used eye tracking to determine viewing behaviors that may reflect these difficulties. Design: The gaze patterns of 47 VP (mean gestational age: 28 weeks, mean birth weight: 948 g, and mean chronological age: 49 months) were assessed while viewing dynamic social scenes and compared with those of 25 typically developing (TD) and 25 children with ASD. The temporo-spatial gaze patterns were summarized on a two-dimensional plane using multidimensional scaling (MDS) and the median of the TD children was used to characterize the gazes of the VP children. Time spent viewing the face was also compared. Results: The VP children formed two clusters: one had a mean MDS distance comparable to that of TD group (n = 32; VP small), and the other had a larger mean distance comparable to that of ASD group (n = 15; VP -large). The VP -large were similar to the ASD group by spending significantly less time viewing the face. Their performance was comparable to the TD during the initial 1 s, but they could not remain focused on the face thereafter. Conclusions: The VP children were objectively classified into two groups based on gaze behaviors. One group was comparable to TD children, whereas the other had difficulty maintaining attention and exhibited atypical viewing behaviors similar to those of the ASD group. Our method may be useful in identifying VP children at higher risk for experiencing social difficulties. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Introduction: Compared to the general population, veterans of the wars in Afghanistan and Iraq (OEF/OIF) are more likely to engage in hazardous alcohol use and meet criteria for mental health disorders including Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder. Less is known how distinct profiles of alcohol use behavior relate to mental health symptoms. Method: The current study examined the extent that indicators of alcohol use (i.e., drinks per week, peak blood alcohol concentration, and alcohol-related problems) are categorized into different alcohol risk profiles utilizing a person-centered approach. We also examined how mental health symptoms (i.e., PTSD, depression, and anxiety-related symptoms) were associated with the alcohol risk profiles. Participants were 252 Veterans who reported consuming alcohol within the past month. Results: Latent profile analysis indicated a four-class solution yielded the best-fitting model, and profiles were named based on their respective levels and patterns of alcohol use. Mental health symptoms were significantly different among the four profiles. Profiles of veterans who endorsed more alcohol-related problems (i.e., the "Severe alcohol behavior" and "Steady drinkers with functional impairment") also reported comorbid clinical symptoms of PTSD, depression, and anxiety. The "Binge drinkers with no functional impairment" and "Mild alcohol behavior" profiles reported the lowest levels of mental health symptoms. Discussion: Findings highlight the unique relationship between distinct alcohol risk profiles and mental health outcomes. Targeted interventions and treatment options based on unique alcohol risk profiles may be helpful in tailoring prevention and intervention efforts in detecting co-occurring mental health symptoms among OEF/OIF veterans. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Suicide rates are higher in veterans compared to the general population, perhaps due to trauma exposure. Previous literature highlights depressive symptoms and anger as contributors to suicide risk. PTSD symptoms may indirectly affect suicide risk by increasing the severity of such cognitive-emotional factors. Method: A sample of community dwelling veterans (N=545) completed online surveys, including the PTSD Checklist-Military Version, Suicidal Behaviors Questionnaire-Revised, Multidimensional Health ProfilePsychosocial Functioning, and Differential Emotions Scale -Iv. Bivariate and serial mediation analyses were conducted to test for direct and indirect effects of PTSD symptoms on suicide risk. Results: In bivariate analyses, PTSD symptoms, depression, anger, and internal hostility were positively related to suicide risk. In serial mediation analyses, there was a significant total effect of PTSD symptoms on suicide risk in both models. PTSD symptoms were also indirectly related to suicidal behavior via depression and internal hostility, and via internal hostility alone. Anger was not a significant mediator. Limitation: Our cross-sectional sample was predominantly White and male; prospective studies with diverse veterans are needed. Discussion: Our findings may have implications for veteran suicide prevention. The effects of PTSD and depression on anger, particularly internal hostility, are related to suicide risk, suggesting a potential mechanism of action for the PTSD-suicide linkage. A multi-faceted therapeutic approach, targeting depression and internal hostility, via cognitive-behavioral techniques such as behavioral activation and cognitive restructuring, may reduce suicide risk in veterans who have experienced trauma.
The role of the veterinary forensic pathologist in the investigation of animal abuse or neglect can go beyond documenting the condition of animals presented as evidence. Although animal cruelty is a moral concern and a crime in itself, law enforcement response to such crimes is often enhanced by the recognition that crimes against animals can be both indicators of other ongoing crimes against people and predictors of the potential for interpersonal violence. An understanding of common motives underlying animal cruelty can aid the pathologist in asking appropriate questions. The authors review the forms of pathology evidence commonly seen in various presentations of animal cruelty. Understanding these forms of evidence can help the pathologist describe findings that can be significant for assessing the potential risks the alleged perpetrator may pose to other animals and humans.
Design of variable-gain amplifier (VGA), based on fully differential operational amplifier is presented. The proposed VGA topology was verified through simulations and analysis of main circuit parameters. The VGA is designed in 0.35 mu m CMOS technology using Cadence environment and BSIM3 family of models. Designed circuit works with the power supply of 3.3 V. The simulation results show that gain bandwidth (GBW) of about 12 MHz (for capacitive load of 1 pF) and the total harmonic distortion of less than 1% for input amplitude 100 mV were achieved. Implemented feedback circuit is stable according to phase margin of 68.15 degrees.
This study examined whether victimization is associated with negatively distorted social cognition (bias), or with a specific increased sensitivity to social negative cues, by assessing the perception of social exclusion and the consequences for psychological wellbeing (moods and fundamental needs). Both self-reported and peer-reported victimization of 564 participants (M-age = 9.9 years, SD = 1.04; 49.1% girls) were measured, and social exclusion was manipulated through inclusion versus exclusion in a virtual ball tossing game (Cyberball). Children's perceptions and psychological well-being were in general more negative after exclusion than after inclusion. Moreover, self-reported but not peer-reported victimi zation was associated with the perception of being excluded more and receiving the ball less, as well as more negative moods and less fulfillment of fundamental needs, regardless of being excluded or included during the Cyberball game. In contrast, peer-reported victimization was associated with more negative mood and lower need fulfillment in the exclusion condition only. Together, these results suggest that children who themselves indicate being victimized have negatively distorted social cognition, whereas children who are being victimized according to their peers experience increased sensitivity to negative social situations. The results stress the importance of distinguishing between self-reported and peer-reported victimization and have implications for interventions aimed at victimized children's social cognition. (C) 2016 Elsevier Inc. All rights reserved.
The use of violent video games has been often linked to increase of aggressive behavior. According to the General Aggression Model, one of the central mechanisms for this aggressiveness inducing impact is an emotional desensitization process resulting from long lasting repeated violent game playing. This desensitization should evidence itself in a lack of empathy. Recent research has focused primarily on acute, short term impact of violent media use but only little is known about long term effects. In this study 15 excessive users of violent games and control subjects matched for age and education viewed pictures depicting emotional and neutral situations with and without social interaction while fMRI activations were obtained. While the typical pattern of activations for empathy and theory of mind networks was seen, both groups showed no differences in brain responses. We interpret our results as evidence against the desensitization hypothesis and suggest that the impact of violent media on emotional processing may be rather acute and short-lived.
Energy recovery from waste is one of the strategies that can assist the expansion of renewable energy in Brazil. Among the various types of waste, vinasse, which is a residue that contains a high organic load, originates from the sugarcane industry, which is a very important industry for the Brazilian economy. Due to high levels of sugarcane harvesting in the country and the production of large amounts of ethanol, vinasse is, produced at high levels in Brazil. In this context, this paper presents an energy analysis of the avoided carbon dioxide emissions and economic viability associated with the combustion of biogas produced by the anaerobic digestion of the vinasse that results from the use of sugar cane planted in Brazil. Based on the literature review, data related to the process of biogas production from anaerobic digestion of the vinasse were collected and used for the calculation of the energy potential associated. The results show that to achieve economic viability for the use of this waste for energy, the following plantation areas would be required, considering their processed sugarcane equivalents: 14,580 ha (if considering the processing of sugarcane in attached plants), and 6000 ha (if considering the processing of sugarcane in autonomous plants). The total energy potential of this use may reach 3.26 TWh(e)/y, which represents 0.52% of all domestic energy consumption in 2014. The potential to avoid emissions from the same use could reach 1.9 Mt CO2/y, which is approximately 2.1% of the emissions for the whole industry in Brazil in 2014. These results demonstrate the environmental and energy benefits that can be obtained via power generation from biogas produced by the anaerobic digestion of vinasse and highlight the need to include the use of such residue for energy in expansion plans for the Brazilian energy matrix. (C) 2017 Elsevier Ltd. All rights reserved.
OBJECTIVE: The objective of this study is to analyze the association between intimate partner violence against women and maternal educational practice directed to children at the beginning of formal education. METHODS: This is a cross-sectional study, carried out between 2013 and 2014, with 631 mother/child pairs, registered in the Family Health Strategy of the Health District II of the city of Recife, State of Pernambuco, Brazil. It integrates a prospective cohort study designed to investigate the consequences of exposure to intimate partner violence in relation to the child who was born between 2005 and 2006. The maternal educational practice has been assessed by the Parent-Child Conflict Tactics Scale and the intimate partner violence by a questionnaire adapted from the Multi-Country Study on Women's Health and Domestic Violence of the World Health Organization. Intimate partner violence referred to the last 12 months and was defined by specific acts of psychological, physical, and sexual violence inflicted to women by the partner. The crude and adjusted prevalence ratios were estimated for the association studied, using log-binomial regression. RESULTS: The prevalence of intimate partner violence was 24.4%, and violent maternal educational practice was 93.8%. The use of non-violent discipline was mentioned by 97.6% of the women, coexisting with violent strategies of discipline. Children whose mothers reported intimate partner violence presented a higher chance of suffering psychological aggression (PR = 2.2; 95% CI 1.0-4.7). CONCLUSIONS: The violence suffered by the mother interferes in the parental education. The findings show high prevalence of violent maternal educational practice, pointing to the need for interventions that minimize the damage of violence in women and children.
Background Physical, emotional and sexual abuse of children is a major problem in South Africa, with severe negative outcomes for survivors. To date, no known studies have used data directly obtained from community-based samples of children to investigate prevalence, incidence, locations and perpetrators of child abuse victimisation. This study aims to investigate prevalence and incidence, perpetrators, and locations of child abuse victimisation in South Africa using a multicommunity sample. Methods 3515 children aged 10-17years (56.6% female) were interviewed from all households in randomly selected census enumeration areas in two South African provinces. Child self-report questionnaires were completed at baseline and at 1-year follow-up (96.7% retention). Results Prevalence was 56.3% for lifetime physical abuse (18.2% past-year incidence), 35.5% for lifetime emotional abuse (12.1% incidence) and 9% for lifetime sexual abuse (5.3% incidence). 68.9% of children reported any type of lifetime victimisation and 27.1% reported lifetime multiple abuse victimisation. Main perpetrators of abuse were reported: for physical abuse, primary caregivers and teachers; for emotional abuse, primary caregivers and relatives; and for sexual abuse, girlfriend/boyfriends or other peers. Conclusions This is the first study assessing current self-reported child abuse through a large, community-based sample in South Africa. Findings of high rates of physical, emotional and sexual abuse demonstrate the need for targeted and effective interventions to prevent incidence and re-victimisation.
Accurate definitions of phenomena are essential to any scientific enterprise. A definition of violence should be fully capable of accounting for the exclusion of behaviors such as accidents and self-defense, and the inclusion of behaviors such as child abuse, sexual offenses, and manslaughter. Violence research has produced numerous and sometimes conflicting definitions of violence that can be organized into 4 general camps: the exemplars approach, the social psychology approach, the public health approach, and the animal research approach. Each approach has strengths and limitations, but to fully distinguish violence from other behaviors requires incorporating elements from all of them. A comprehensive definition of violence includes 4 essential elements: behavior that is (a) intentional, (b) unwanted, (c) nonessential, and (d) harmful. More sophisticated recognition of some elements is needed. For example, shortened telomeres-a known consequence of child abuse-is a far more serious harm than a scratch or bruise that will fully heal in a few days. Many problems in the field are due at least in part to insufficient attention to definitions, such as minimization of sexual violence, bullying, and other behaviors that do not map onto prototypical exemplars. More precise definitions of violence can improve surveillance, promote more accurate identification of causes and consequences, enhance evaluation of treatment outcomes, and guide development of prevention programs, among other benefits.
Objectives Inappropriate discipline such as harsh physical punishment is a social determinant of health. The objective was to determine if a brief parent training intervention that teaches discipline strategies is culturally sensitive. Methods English or Spanish-speaking parents of 1-5 year old children viewed a multimedia program that teaches appropriate discipline strategies. The intervention, Play Nicely, was viewed in the exam room before the physician's visit. Parents viewed 4 of 20 discipline strategies of their choosing; the average viewing time was 7 min. Results Of 204 parents eligible to participate, 197 (96 %) completed the study; 41 % were Black, 31 % were White, and 21 % were Hispanic. At least 80 % of parents from each racial/ethnic group reported that the program built their confidence to care for their child, addressed their family needs, explained things in a way they could understand, respected their family values, and was sensitive to their personal beliefs. Overall, 80 % of parents reported that the program answered individual questions. One parent (0.5 %) reported that the program did not respect her family values. Conclusions for Practice Discipline education can be integrated into the pediatric primary care clinic in a way that is family-centered and culturally sensitive for the majority of parents. The results have implications for the development and implementation of population-based parenting programs and the primary prevention of child abuse and violence.
Violence is increasing worldwide mainly among the most socially vulnerable groups such as women, elderly people, children and adolescents. In addition to the justice sector, many other areas and workers are involved and they are becoming even more important for addressing violence. One such area is the health sector. This article aims to identify the creative potential of videos that aim to tackle issues involving domestic violence against children which are categorized based on generation (age) and gender. A search was conducted between 2013 and 2014 on official sites and video channels of institutions that deal with child-related topics. We used the webQDA software to conduct our analysis and for reference purposes we used "Generation" and "Gender" as categories. We collected 40 video campaigns, of which ten were analyzed qualitatively. Upon analyzing complete scenes and parts of scenes we were able to see both inter/intra -generational and inter/intra-gender violence and its consequences for children. The videos allowed for critical reflections to be made on the educational processes and training used to combat violence against children in the context of "Generations" and "Genders".
Objectives: Besides group A streptococcus (GAS), microbial causes of pharyngitis in children are not well known. We aimed to document the viral and bacterial aetiology of pharyngitis and to assess the pathogenic role of viruses by determining the myxovirus resistance protein A (MxA) in the blood as a marker of interferon response. Methods: In this prospective observational study, throat swabs and blood samples were collected from children (age 1-16 years) presenting to the emergency department with febrile pharyngitis. Microbial cause was sought by bacterial culture, polymerase chain reaction, and serology. Blood MxA level was determined. Results: A potential pathogen was detected in 88% of 83 patients: GAS alone in 10%, GAS and viruses in 13%, group C or G streptococci alone in 2% and together with viruses in 3%, and viruses alone in 59% of cases. Enteroviruses, rhinoviruses, and adenoviruses were the most frequently detected viruses. Blood MxA levels were higher in children with viral (880 [245-1250] mu g/L; median [IQR]) or concomitant GAS-viral (340 [150-710] mu g/L) than in those with sole GAS (105 [80-160] mu g/L) infections. Conclusions: Detection of respiratory viruses simultaneously with elevated blood MxA levels supports the causative role of viruses in the majority of children with pharyngitis. (C) 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments.
Cell-to-cell trafficking through different cellular layers is a key process for various RNAs including those of plant viruses and viroids, but the regulatory mechanisms involved are still not fully elucidated and good model systems are important. Here, we analyse the function of a simple RNA motif (termed 'loop19') in potato spindle tuber viroid (PSTVd) which is required for trafficking in Nicotiana benthamiana leaves. Northern blotting, reverse transcriptase PCR (RT-PCR) and in situ hybridization analyses demonstrated that unlike wild-type PSTVd, which was present in the nuclei in all cell types, the trafficking-defective loop19 mutants were visible only in the nuclei of upper epidermal and palisade mesophyll cells, which shows that PSTVd loop19 plays a role in mediating RNA trafficking from palisade to spongy mesophyll cells in N. benthamiana leaves. Our findings and approaches have broad implications for studying the RNA motifs mediating trafficking of RNAs across specific cellular boundaries in other biological systems.
New hepatitis B virus (HBV) therapies are expected to have breakthrough benefit for patients. HBV functional cure is sustained hepatitis B surface antigen loss and anti-HBs gain, with normalization of serum aminotransferases off therapy. Virologic or complete cure additionally includes loss of HBV covalently closed circular DNA. Currently available endpoints of therapy are inadequate to evaluate the efficacy of many of the new therapeutics. Therefore, either new ways of using the existing virologic endpoints and laboratory values or entirely new biomarkers are needed. In this review, we discuss the currently used endpoints, potential new endpoints, as well as what new markers are needed to assess the ability of HBV therapeutics to achieve functional and virologic cure in various phases of HBV infection. In addition, we discuss how patient selection from differing phases of HBV impacts the choice of HBV drug(s) needed to achieve cure.
Human Immunodeficiency Virus (HIV) infection of humans represents a complex biological system and a great challenge to public health. Novel approaches for the analysis and prediction of the infection dynamics based on a multi-scale integration of virus ontogeny and immune reactions are needed to deal with the systems' complexity. The aim of our study is: (1) to formulate a multi-scale mathematical model of HIV infection; (2) to implement the model computationally following a hybrid approach; and (3) to calibrate the model by estimating the parameter values enabling one to reproduce the standard observed dynamics of HIV infection in blood during the acute phase of primary infection. The modeling approach integrates the processes of infection spread and immune responses in Lymph Nodes (LN) to that observed in blood. The spatio-temporal population dynamics of T lymphocytes in LN in response to HIV infection is governed by equations linking an intracellular regulation of the lymphocyte fate by intercellular cytokine fields. We describe the balance of proliferation, differentiation and death at a single cell level as a consequence of gene activation via multiple signaling pathways activated by IL-2, IFNa and FasL. Distinct activation thresholds are used in the model to relate different modes of cellular responses to the hierarchy of the relative levels of the cytokines. We specify a reference set of model parameter values for the fundamental processes in lymph nodes that ensures a reasonable agreement with viral load and CD4(+) T cell dynamics in blood.
Capripoxviruses, comprising sheep pox virus, goat pox virus and lumpy skin disease virus cause serious diseases of domesticated ruminants, notifiable to The World Organization for Animal Health. This report describes the evaluation of a mobile diagnostic system (Enigma Field Laboratory) that performs automated sequential steps for nucleic acid extraction and real-time PCR to detect capripoxvirus DNA within laboratory and endemic field settings. To prepare stable reagents that could be deployed into field settings, lyophilized reagents were used that employed an established diagnostic PCR assay. These stabilized reagents demonstrated an analytical sensitivity that was equivalent, or greater than the established laboratory-based PCR test which utilizes wet reagents, and the limit of detection for the complete assay pipeline was approximately one log(10) more sensitive than the laboratory-based PCR assay. Concordant results were generated when the mobile PCR system was compared to the laboratory-based PCR using samples collected from Africa, Asia and Europe (n=10) and experimental studies (n=9) representing clinical cases of sheep pox, goat pox and lumpy skin disease. Furthermore, this mobile assay reported positive results insitu using specimens that were collected from a dairy cow in Morogoro, Tanzania, which was exhibiting clinical signs of lumpy skin disease. These data support the use of mobile PCR systems for the rapid and sensitive detection of capripoxvirus DNA in endemic field settings.
The availability of some sorts of biological samples which require noninvasive collection methods has led to an even greater interest in applying molecular biology on visceral leishmaniasis (VL) diagnosis, since these samples increase the safety and comfort of both patients and health professionals. In this context, this work aimed to evaluate the suitability of the urine as a specimen for Leishmania infantum kinetoplast DNA detection by real-time quantitative PCR (qPCR). Subsequent to the reproducibility analysis, the detection limit of the qPCR assay was set at 5 fg (similar to 0.025 parasites) per mu L. of urine. From the comparative analysis performed with a set of diagnostic criteria (serological and molecular reference tests), concordance value of 96.08% was obtained (VL-suspected and HIV/AIDS patients, n = 51) (P>0.05). Kappa coefficient (95% CI) indicated a good agreement between the test and the set of diagnostic criteria (k = 0.778 +/- 0.151). The detection of Leishmania DNA in urine by qPCR was possible in untreated individuals, and in those with or without suggestive renal impairment. Fast depletion of the parasite's DNA in urine after treatment (from one dose of meglumine antimoniate) was suggested by negative qPCR results, thus indicating it as a potential alternative specimen to follow up the efficacy of therapeutic approaches. Even when evaluated in a clinically heterogeneous set of patients, the urine showed good prospect as sample for VL diagnosis by qPCR, also indicating a good negative predictive value for untreated suspected patients. (C) 2016 Elsevier B.V. All rights reserved.
Humans typically exhibit a tendency to follow the gaze of conspecifics, a social attention behaviour known as gaze cueing. Here, we addressed whether episodically learned social knowledge about the behaviours performed by the individual bearing the gaze can influence this phenomenon. In a learning phase, different faces were systematically associated with either positive or negative behaviours. The same faces were then used as stimuli in a gaze-cueing task. The results showed that faces associated with antisocial norm-violating behaviours triggered stronger gaze-cueing effects as compared to faces associated with sociable behaviours. Importantly, this was especially evident for participants who perceived the presented normviolating behaviours as far more negative as compared to positive behaviours. These findings suggest that reflexive attentional responses can be affected by our appraisal of the valence of the behaviours of individuals around us.
This paper presents a novel fixation prediction and saliency modeling framework based on inter-image similarities and ensemble of Extreme Learning Machines (ELM). The proposed framework is inspired by two observations, (1) the contextual information of a scene along with low-level visual cues modulates attention, (2) the influence of scene memorability on eye movement patterns caused by the resemblance of a scene to a former visual experience. Motivated by such observations, we develop a framework that estimates the saliency of a given image using an ensemble of extreme learners, each trained on an image similar to the input image. That is, after retrieving a set of similar images for a given image, a saliency predictor is learnt from each of the images in the retrieved image set using an ELM, resulting in an ensemble. The saliency of the given image is then measured in terms of the mean of predicted saliency value by the ensemble's members. (C) 2017 Elsevier B.V. All rights reserved.
Secure parent-child attachment may help children to overcome the challenges of growing up with a visual or visual-and-intellectual impairment. A large literature exists that provides a blueprint for interventions that promote parental sensitivity and secure attachment. The Video-feedback Intervention to promote Positive Parenting (VIPP) is based on that blueprint. While it has been adapted to several specific at risk populations, children with visual impairment may require additional adjustments. This study aimed to identify the themes that should be addressed in adapting VIPP and similar interventions. A Delphi-consultation was conducted with 13 professionals in the field of visual impairment to select the themes for relationship-focused intervention. These themes informed a systematic literature search. Interaction, intersubjectivity, joint attention, exploration, play and specific behavior were the themes mentioned in the Delphi-group. Paired with visual impairment or vision disorders, infants or young children (and their parents) the search yielded 74 articles, making the six themes for intervention adaptation more specific and concrete. The rich literature on six visual impairment specific themes was dominated by the themes interaction, intersubjectivity, and joint attention. These themes need to be addressed in adapting intervention programs developed for other populations, such as VIPP which currently focuses on higher order constructs of sensitivity and attachment.
Introduction: An impairment of visually perceiving backward masked stimuli is commonly observed in patients with schizophrenia, yet it is unclear whether this impairment is the result of a deficiency in first or higher order processing and for which subtypes of schizophrenia it is present. Methods: Here, we compare identification (first order) and metacognitive (higher order) performance in a visual masking paradigm between a highly homogenous group of young firstepisode patients diagnosed with paranoid schizophrenia (N = 11) to that of carefully matched healthy controls (N = 13). Results: We find no difference across groups in first-order performance, but find a difference in metacognitive performance, particularly for stimuli with relatively high visibility. Conclusions: These results indicate that the masking deficit is present in first-episode patients with paranoid schizophrenia, but that it is primarily an impairment of metacognition.
The present study examines 536 Indian publications on "Vitamin D Deficiency" as covered in Scopus database during 2006-15, experiencing an annual average growth rate of 37.08%, citation impact per paper of 8.30 and international collaborative publication share of 15.30%. The global publications share on "Vitamin D Deficiency" came from several countries, of which the top 10 most productive countries accounted for 73.67% share of global publications and 99.22% share of global citations during 2006-15. A large number of Indian organizations and authors participated in Indian research on "Vitamin D Deficiency" during 2006-15, of which the top 15 organizations and 15 authors contributed 47.57% and 33.02% publications share and 71.45% and 69.59% citation share respectively of the Indian output and citations. Medicine, among subjects, contributed the largest publications share of 88.62%, followed biochemistry, genetics & molecular biology (22.01%), pharmacology, toxicology & pharmaceutics (6.53%), nursing (6.34%) neurosciences (2.80%), agricultural & biological science (2.05%) and immunology & microbiology (1.68%) during 2006-15. Of the total Indian publications, 530 appeared in several journals, of which the top 15 journals contributed 31.72% share of the India's output. The top 13 highly cited papers registered 50 to 479 citations, and together contributed 1535 citations, leading to the average citation per paper of 118.08. Concludes that there is an urgent need to frame a national policy in this area, undertake more R&D and recognize vitamin D deficiency as a public health problem and allocate more healthcare funds in this area.
Vitamin D is a molecule that is actively involved in multiple metabolic pathways. It is mostly known for its implications related to calcium metabolism. It has also been determined that it actively participates in the cardiovascular system, influencing blood pressure, coronary artery disease and other vascular diseases, such as heart failure and atrial fibrillation. Furthermore, it has been established that this vitamin is extensively involved in the regulation of both the renin angiotensin aldosterone system and the immune system. In this review, we present the different vitamin D metabolic pathways associated with the cardiovascular pathophysiology, and we include studies in animal and human models, as well as some of the controversies found in the literature. This review also incorporates an overview of the implications in the molecular biology and public health fields.
The first full-length mRNA for vitellogenin (Vg) from ticks was sequenced. This also represents the first complete sequence of Vg from the Chelicerata and of a heme binding Vg. The Vg cDNA from the American dog tick, Dermacentor variabilis was 5744 nt in length (GenBank Accession number AY885250), which coded for a protein of 1843 aa with a calculated molecular weight of 208 kD. This protein had an 18 aa signal sequence, a single RXXR cleavage signal that would generate two subunits (49.5 and 157 K in molecular weight) and lipoprotein N-terminal and carboxy von Willebrand factor type D domains. Tryptic digest MS analysis of vitellin protein confirmed the function of the cDNA as the tick yolk protein. Apparently, vitellin in D. variabilis is oligomeric (possibly dimeric) and is comprised of a mixture of the uncleaved monomer and subunits that were predicted from the single RXXR cleavage signal. The highly conserved GL/ICG motif close to the C-terminus in insect Vg genes was different in the tick Vg message, i.e., GLCS. This variant was also present in a partial sequence of Vg from Boophilus microplus. Phylogenic analysis showed that the full length Vg cDNA from D. variabilis and the partial cDNA from B. microplus were distinct from insects and Crustacea. The Vg message was not found in whole body RNA from unfed or fed males or in unfed and partially fed (virgin) females as determined by Northern blotting. The message was found in replete (mated) pre-ovipositional females, increased to higher levels in ovipositing females and was absent after egg laying was complete. The endocrine regulation of the Vg mRNA is discussed. The tissue sources of the Vg message are both the gut and fat body. Tryptic digest MS fingerprinting suggests that a second Vg mRNA might be present in the American dog tick, which needs further study. (c) 2007 Elsevier Ltd. All rights reserved.
This paper examines the closed-loop characteristics of the basic Current-Feedback Operational Amplifier (CFOA), and in particular, the dynamic response. Additionally, it also examines the design and advantages of the CFOA regarding its ability to provide a significantly constant closed-loop bandwidth for closed-loop voltage gain. Secondly, the almost limitless slew-rate provided by the class AB input stage that makes it superior to the voltage-mode operational amplifier (VOA) counterpart. Additionally, this paper also concerns the definitions and measurements of the terminal parameters of the CFOA, regarded as a black box'. It does not deal with the way that these parameters are related to the properties of the active passive and active components of a particular circuit configuration. Simulation is used in terminal parameter determination: this brings with it the facility of using test conditions that would not normally prevail in a laboratory test on silicon implementations of the CFOAs. Thus, we can apply 1mA and 1mV test signals from, respectively, infinite and zero source impedances that range in frequency from d.c to some tens of GHz. Also, we assume the existence of resistors with identical Ohmic value and very high value ideal capacitors. Where appropriate, practical test methods are referred to physical laboratory prototypes.
The largest volcanic constructs on Earth are the seismically imaged seaward dipping reflector (SDR) units found offshore of many rifted continental margins, including most that border the Atlantic Ocean. Whether their formation requires large magnitude (i.e. 10 s of km) of normal fault slip or results from the deflection of the lithosphere by the weight of volcanic flows is controversial. Though there is evidence for faulting associated with some SDRs, this paper considers the range of structures that can be produced by magmatic and volcanic loading alone. To do this an idealized mechanical model for the construction of rift-related volcanic flow structures is developed. Dikes open as plates move away from the center of a model rift and volcanic flows fill the depression produced by the load caused by dike solidification. The thin elastic plate flexure approximation allows a closed form description of the shape of both the contacts between flows and between the flows and underlying dikes. The model depends on two independent parameters: the flexure parameter, alpha, and the maximum isostatically supported extrusive layer thickness, w(0). For reasonable values of these parameters the model reproduces the observed down dip thickening of flows and the range of reflector dip angles. A numerical scheme using the analytic results allows simulation of the effect of temporal changes in the locus of magmatic spreading as well as changes in the amount of volcanic infill. Either jumps in the location of the center of diking or periods with no volcanism result in separate units or "packages" of model SDRs, in which the flow-dike contact dips landward, consistent with observations previously attributed only to listric normal fault offset. When jumps in the spreading center are small (i.e. less than a) they result in thicker, narrower volcanic units on one side of a rift compared to those on the other side. This is similar to the asymmetric distributions of volcanic packages seen across some conjugate margins. (C) 2017 Elsevier B.V. All rights reserved.
Volcanosedimentary boron deposits are formed in specific volcano and lake facies deposition environment in Neogene period, and the characteristic of the boron bearing stratum is the containing boron lacustrine sedimentary rocks and tuff and andesite volcanic rocks interbedded cyclically and composed binary sedimentary structure. As the borate mineral deposition occurred in the late deposition period, usually associated with tuff and clay and limestone, so the formed boron deposits had the characteristics of low density, low electrical resistivity. According to the characteristic of the boron deposits, we employ comprehensive geophysical technology in the exploration. We firstly conducted the 1 : 50000 high-precision gravity survey in the Xiongba area, Tibet, and obtain the Bouguer gravity anomalies. Through the processing and analysis of the gravity data, we got access to the fault structures development and gravity anomaly changes in the study area, deduced the spatial variation characteristics of underground lithology and delineated the favorable mining area of volcanosedimentary boron deposits; based on that, the 1 :5000 audio magnetotelluric sounding is carried out on the favorable area and the electrical structure characteristics of the underground strata in the study area are obtained. Combining the seismic-electric fitting of the electrical data, the joint inversion of gravity and electricity data and the geological data in the study area, we further analyzed stratum structure, fracture system and the distribution of sedimentary rocks and their relation to the volcanosedimentary boron deposits. Then we predicted the distribution of the volcanosedimentary boron deposits, the drilling test results are basically consistent with the predicted results.
To improve the constant output voltage accuracy of primary-side controlled flyback converter, this study described a digital control scheme based on accurate sampling and cable voltage drop compensation. The voltage drops of output diode and the cable were analysed first, they were two most important factors that influence the accuracy of output voltage. Then, an accurate sampling method that can eliminate the voltage drop of the output diode was proposed. With output current estimating and digital resistance capacitance (RC) filter, the compensation of cable voltage drop was also designed. Finally, the software simulation and prototype test results verified the proposed scheme, and the constant voltage accuracy of the prototype achieved -0.6 approximate to +0.6%.
BiCMOS bandgap reference (BGR) has advantage over MOS based BGR in terms of its accuracy at its reference output and very less temperature coefficient (TC). This paper presents bandgap reference circuit with folded cascode operational amplifier (op-amp) in order to improve the stability of final V-REF output. The temperature stability of output can be improved by using trimming circuit in voltage mode architecture of bandgap reference operating with less power consumption. Using only first order temperature compensation technique, the proposed circuit gives output voltage of 1.181V with 0 degrees C to 100 degrees C temperature variations that corresponds to TC of 19ppm/ degrees C. The output reference voltage exhibits line variations of 2.4mV/V with supply range of 1.62V to 1.98V at typical process corner. A single stage folded cascode op-amp that is included in the proposed bandgap improves the stability of output voltage in closed loop, power supply rejection ratio (PSRR) of BGR and input common mode range. The proposed circuit includes start-up circuit to avoid start-up problem because of closed loop, the reference current for op-amp is generated from BGR current mirror and impact of its TC on final V-REF is negligible. The simulation results shows that PSRR of proposed BGR is -43db from dc to 30KHz frequency, Phase margin (PM) is 70 degrees, input offset of op-amp is 1.96 mu V and closed loop gain of op-amp in BGR is 118dB. The total current for overall BGR is 12 mu A and total power consumption is 18.4 mu W. The proposed bandgap reference is simulated using Mentor-Graphics Pyxis tool, Eldo-Spice simulator in 130nm CMOS technology. The proposed BGR output is used in low-drop-out (LDO) regulator circuit that is operating at 3.3V supply and gives regulated output of 1.8V.
This paper describes a novel operational amplifier (OPA) voltage controlled oscillator (VCO) circuit which can be used in frequency range exceeding unity gain bandwidth. The VCO topology is based on the operational-amplifier- negative-inductance converter. The oscillator architecture, mathematical modeling, simulation and measurement results are presented. The designed VCO uses an ultra low noise wideband OPA LMH6624, covers frequency band between 786.3 MHz and 1.0 GHz and exhibits a maximum in-band phase noise of - 141.3 dBc/Hz at 1 MHz offset from carrier frequency. Power consumption of the VCO core is 57 mW from a +/- 2.5 V power supply. The simulation results are verified by implementing the oscillator that generates a low-noise signal.
This study presents a K-band differential voltage-controlled oscillator (VCO) with robust start-up. A hybrid technique that combines open-loop digitally controlled tail current with switchable auxiliary cross-coupled pairs (ACCPs) is proposed to ensure robust start-up for wideband operation. Compared with prior closed-loop current controlling method, the proposed technique does not suffer from phase-noise degradation. Furthermore, by evenly distributing the ACCPs, transistors with smaller size are allowed to achieve the same start-up condition, which leads to frequency boost and phase-noise improvement. Implemented in 0.18 m complementary metal-oxide-semiconductor technology, the VCO achieves a wide-frequency tuning range of 21.4-26.29 GHz (20.5%) and a low phase noise of -108.8 dBc/Hz at 1 MHz offset from 25.8 GHz carrier frequency. At 1.1 V power supply, the power consumption of the core circuit is 7.9-11.4 mW across the entire output frequency range.
This paper proposes a method that analog multiplier and current feedback operational amplifier have been used to form second-order voltage-controlled multifunctional filter. The designed circuit has been achieved theoretical analysis, PSPICE simulation and actual measurement. It can simultaneously realize low-pass, high pass and band pass filter function. Results show that the pass band can be adjusted with the frequency range of the input signal, and can be used in the field of frequency characteristic analysis, harmonic analysis, frequency measurement, signal detection. Furthermore, it shows more importance in theoretical significance and application prospects.
A simple voltage-to-frequency converter (VFC) with modulated duty cycles is proposed. The proposed VFC is composed of an operational amplifier, a voltage-to-current circuit, a charge and discharge circuit, a comparator, and a Schmitt trigger. The 50% duty cycle signal is always obtained at the output of the Schmitt trigger and multiple duty cycles can be obtained at the output of the comparator by simply adjusting an external voltage level. Due to its simplicity, the proposed VFC circuit can be easily combined with other circuitry to extend its practical application. The errors caused by the circuit non-idealities are investigated to quantify the trade-offs between performance and cost. The proposed VFC, which features modulated duty cycles, is realized in a standard 0.18-m 1P6M complementary metal-oxide-semiconductor (CMOS) technology, and an active area of 210mx190m is occupied. Experimental results show that the proposed converter is useful for output frequency ranges from 315kHz to 2.53MHz with an input voltage range of 0.2-1.6V and a power consumption of 0.8mW.
In this study, trends in synonymous codons usage of Volvariella volvecea have been first examined by analysis of complete coding sequences and gene chip data. The results showed that GC content at three codon positions are obviously different and there were several factors shaping the codon usage of V. volvacea genes, including base composition. The comparison of codon usage among four edible fungi such as V. volvacea, Agaricus bisporus, Coprinopsis cinerea, and Pleurotus ostreatus indicated that the similar codon usage pattern was used among V. volvacea, A. bisporus and P. ostreatus, but there was significantly different codon usage pattern of C. cinerea. Two arrays of optimal codons were determined by effective number of codons (ENC) values and gene chip database separately, resulting that most of the ENC-predicted optimal codons were included in the array of gene chip resulted optimal codons. This study can provide useful information for codon usage pattern analysis and gene transformation of V. volvacea. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
A means to digitally generate a partially coherent beam with orbital angular momentum is presented. Our approach is based on encoding the randomness of broadband light passing through a spiral phase plate in a spatial light modulator. We illustrate the technique by generating partially coherent beams with orbital angular momentum content and different coherence lengths, with no moving optical elements. We study the cross correlation spectra which yields to good agreement with theory.
Conventional shaping mehod of tire curing depends on bladder with high elasticity and low rigidity to determine tire cavity profile, it is inevitably difficult to aquire high uniform mass distribution,which leads to low product manufacturing precision and low dynamic balance of tire.Meanwhile conventional tire curing process has defects of low heat transfer efficiency and geat useless consumption which adopts steam or water to heat green tire,especially tire cavity indirectly obtains themal energy from bladder with very low thermal conductivity.A new generation of tire energy saving curing and precision manufacturing technology is expected.Authors of this paper developed a kind of curing technology of direct pressure shaping with inner mould for tire and complete plants that an controlled telescopic metal mould with high rigidity and high heat conductivity replaces bladder and electromagnetic induction heating is applid to curing process which thoroughly abandons conventional heating mediums,further more intelligent and digital control of curing procedure is realized,which provide a new approach for curing saving and precision manufacturing of high-performance tire.Product trial-manufacture is carrid out on 255/30R22 tire and experimental results show that uniformity and dynamic balance of tire respectively increases 33% and 51%,utility cost saves 64% in curing process.
Recent advances in our understanding of the molecular biology of vulvar squamous cell carcinoma (VSCC) provide insight into the future management of VSCC with molecular targeted therapies and offer an opportunity to improve the treatment of this forgotten women's cancer.The incidence of vulvar squamous cell carcinoma (VSCC) has been on the rise since the 1990s. There has been no new treatment for advanced and recurrent disease in decades, with most women succumbing to the disease. Despite two distinct etiologies of VSCC, human papillomavirus (HPV)-associated and HPV-independent disease, there is no difference in therapeutic options. A literature review was carried out by searching EMBASE and Medline databases between January 1990 and March 2016 by pairing the keywords of vulvar carcinoma, vulva cancer, vulvar and vulva with molecular markers involved in the cell cycle, apoptosis and angiogenesis. Molecular targets of prognostic significance were identified and targeted agents of therapeutic relevance to both HPV-independent and HPV-associated VSCC were then reviewed. Recent advances in our understanding of the molecular biology of VSCC provide insight into the future management of VSCC with molecular targeted therapies. Aberrant cell cycle activity is common in both HPV-associated and HPV-independent VSCC and is characterized by overexpression of p53, Rb and cyclin D1, supporting targeting of these protein products and their downstream pathways. Extracellular regulators of cellular activity, such as EGFR, as well as inhibitors of angiogenesis are being clinically evaluated in VSCC. HPV-independent VSCC is characterized by actionable mutations, including PI3K, CDKN2A and PTEN. In HPV-associated disease, therapeutic vaccines targeting the E6 and E7 HPV oncogenes and immune-based therapies are under investigation. There has been a paucity of clinical trials in recent years in this neglected women's cancer. Directed therapy against cell cycle regulatory molecules and extracellular proteins and the inhibition of angiogenesis are of broad therapeutic relevance in VSCC. Therapeutic strategies that target actionable mutations should be explored. In HPV-associated VSCC, novel treatments that exploit the virology of HPV and/or enhance the host immune response merit further study.
The Roadmap to a Resource Efficient Europe aims that by 2020, waste will be managed as a resource. Thus materials that have the ability for the reuse of several types of wastes, such as alkali-activated cement-based binders (AACBs), will merit special attention. Some wastes like fly ash deserve special attention because they are generated in high amounts and have a very low reuse rate. This paper reports experimental results regarding the influence of the mix design of fly ash and waste glass AACB mortars containing two different biopolymers (carrageenan and xanthan) on their short-term mechanical performance. Microstructure and cost analysis are also included. The results show that a mixture of 80% fly ash, 10% waste glass, and 10% calcium hydroxide activated with an alkaline activator has the highest compressive strength. The results also show that the mortars with minor biopolymer carrageenan content are associated with a relevant increase in compressive strength and that the use of 0.1% of carrageenan leads to optimum compressive strength in most mixtures. The use of xanthan shows no beneficial effects on the compressive strength of AACB mortars. Several mixtures with xanthan even show a reduction in the compressive strength.
Previous studies on waste incineration as part of the energy system show that waste management and energy supply are highly dependent on each other, and that the preconditions for the energy system setup affects the avoided emissions and thereby even sometimes the total outcome of an environmental assessment. However, it has not been previously shown explicitly which key parameters are most crucial, how much each parameter affects results and conclusions and how different aspects depend on each other. The interconnection between waste incineration and the energy system is elaborated by testing parameters potentially crucial to the result: design of the incineration plant, avoided energy generation, degree of efficiency, electricity efficiency in combined heat and power plants (CHP), avoided fuel, emission level of the avoided electricity generation and avoided waste management. CO2 emissions have been calculated for incineration of 1 kWh mixed combustible waste. The results indicate that one of the most important factors is the electricity efficiency in CHP plants in combination with the emission level of the avoided electricity generation. A novel aspect of this study is the plant by plant comparison showing how different electricity efficiencies associated with different types of fuels and plants influence results. Since waste incineration typically have lower power to fuel ratios, this has implications for further analyses of waste incineration compared to other waste management practises and heat and power production technologies. New incineration capacity should substitute mixed landfill disposal and recovered energy should replace energy from inefficient high polluting plants. Electricity generation must not be lost, as it has to be compensated for by electricity production affecting the overall results.
In Central and Eastern Europe huge wastewater treatment (WWT) developments have been carried out in the last 25 years. These include the building and upgrading of wastewater treatment plants (WWTPs), especially extending their lifetimes through nutrient removal and digester gas production. In Hungary, for example, in 1990, 42% of households were connected to a WWT, and this number had increased to 75% by 2015, an increase of 33%. Currently, medium-sized WWTPs with a capacity of up to around 120,000 population equivalent (PE) are facing further development needs, especially in their technical and energy-efficiency aspects. This paper presents the results of a comprehensive investigation program that included 21 WWTPs with capacities ranging from 10,000 to 120,000 PE. The investigations included an evaluation of all important parameters, such as inflowing wastewater (WW) characteristics, mechanical and biological WWT, and effluent wastewater quality and removal efficiency. These were investigated with reference to their electrical energy consumption. The extension of these WWTPs with anaerobic sludge digestion has led to the possibility of producing electricity from digester gas. This prospect is currently of great interest for medium-sized WWTPs and so was also investigated. The results are also compared to international data, standards, and guidelines obtained for this research. As a basis for a development strategy, the main bottleneck areas of design and operation are considered, and further upgrading requirements are explored. (C) 2017 American Society of Civil Engineers.
Special attention is required to the removal of nitrogen and phosphorous in treated wastewaters. Although, there are a wide range of techniques commercially available for nutrient up-take, these processes entail high investment and operational costs. In the other hand, microalgae growth can simultaneously remove inorganic constituents of wastewater and produce energy rich biomass. Among all the cultivation technologies, High Rate Algae Ponds (HRAPs), are accepted as the most appropriate system. However, the optimization of the operation that maximizes the productivity, nutrient removal and lipid content in the biomass generated has not been established. In this study, the effect of two levels of depth and the addition of CO2 were evaluated. Batch essays were used for the calculation of the kinetic parameters of microbial growth that determine the optimum conditions for continuous operation. Nutrient removal and lipid content of the biomass generated were analyzed. The best conditions were found at depth of 03 m with CO2 addition (biomass productivity of 26.2 g TSSm-2 d(-1) and a lipid productivity of 6.0 g lipids m(-2) d(-1)) in continuous mode. The concentration of nutrients was in all cases below discharge limits established by the most restrictive regulation for wastewater discharge. (C) 2017 Elsevier B.V. All rights reserved.
A greater than twofold diversity in the expression level of aquaporin 5 (AQP5) has been observed in the membrane fraction of the submandibular gland (SMG) in Sprague-Dawley rats (Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C, Akamatsu T, Kanamori N, and Hosoi K. Pflugers Arch 445: 405-412, 2002). In the present study, breeding between brother and sister rats was repeated within high AQP5 producers and low ones to obtain inbred offspring. High- and low-producer rats from 3rd to 18th generations were used for experiments. By Western blotting, levels of AQP5 proteins in the parotid and lacrimal glands, and lungs were all low in low producers, whereas they were all high in high producers, implying genetic variations of the gene for this water channel. Despite this implication, AQP5 mRNA levels were almost the same between the two groups by Northern blotting, suggesting the irrelevance of transcriptional regulation for this diversity. AQP5 cDNAs from the SMGs of the two groups were sequenced. The nucleotide sequence of AQP5 cDNA from low producers indicated the existence of a point mutation at nt 308 (G308A), leading to a replacement of (103)Gly with (103)Asp in the third transmembrane domain, but no alteration was detected in the Kozak area. The existence of such a mutation was confirmed by the assessment of genomic DNA also. This mutation may have resulted in an abnormal membrane insertion or ineffective trafficking of AQP5, since the rats having this mutation showed extremely low membrane expression of AQP5 in the SMG acinar cells and decreased water secretion from their salivary glands.
No specific pathognomonic tissue changes establish death from water intoxication, which makes a postmortem diagnosis of water intoxication difficult. We report an autopsy case of fatal water intoxication in which the postmortem computed tomography (PMCT) examination showed findings suggestive of antemortem excessive water drinking, such as diluted intestinal contents and hemodilution. A 52-year-old man who had schizophrenia was found dead in his house. He frequently complained of polydipsia, and drank a large amount of water and vomited before his death. PMCT findings showed distention of the duodenum with low radiodensity content (7 HU). In addition, the right atrium showed a low radiodensity content (46 HU). Autopsy results showed moderate congestion in all the organs, a large amount of light-brownish liquid in the duodenum and upper jejunum, and aspiration pneumonia. Electrolyte concentrations of sodium in the vitreous humor of the right and left eyes were 105 and 107 mEq/L, respectively, and neither drugs nor alcohol was detected in the blood. On the basis of the autopsy and biochemical findings, we determined water intoxication as the cause of death. An evaluation of PMCT findings of cases of various causes of death indicated that the radiodensities of the right atrium and duodenal content in our case were lower than those of the cases of various causes of death, except for fresh water drowning. The present case showed that PMCT provides supplementary findings regarding antemortem excessive water drinking. In addition, PMCT may provide findings to consider death from water intoxication before autopsy.
Nowadays, water and energy consumption is intensifying every year in most of the countries. This perpetual increase will not be supportable in the long run, making urgently to manage these resources on a sustainable way. Domestic consumptions of water and electric energy usually are related and it's important to study that relation, identifying opportunities for use efficient improvement. In fact, without an understanding of water-energy relations, there are water efficiency measures that may lead to unintentional costs in the energy efficiency field. In order to take full advantage of combined effect between water and energy water management methodologies, it is necessary to collect data to ensure that the efforts are directed through the most effective paths. This paper presents a study based in the characterization, measurement and analysis of water and electricity consumption in a single family house (2 months period) in order to find an interdependent relationship between consumptions at the end user level. The study was carried out on about 200 baths, divided in four different scenarios where the influence of two variables was tested: the flow reducer valve and the bath temperature. Data showed that the presence of flow reducer valve decreased electric energy consumption and water consumption, but increased the bath duration. Setting a lower temperature in water-heater, decreased electric consumption, water consumption and bath duration. Analysing the influence of the flow reducer valve and 60 degrees C temperature simultaneously, it was concluded that it had a significant influence on electric energy consumption and on the baths duration but had no influence on water consumption. (C) 2017 The Author(s). Published by Elsevier B.V.
The present paper is principally concerned with the disclosure of historical cultural potential of waterfront areas in modern architectural & landscape planning. Moreover, the attitude to water bodies of landscape has changed in recent years: not only as objects of nature, but also as an integral part of the spiritual heritage of the nation. The historic cultural field of actions is a significant part of general, complex program for "ecoresponsible" design of urban waterfront territories along with other blocks, such as engineering & hydro-technological measures; functional planning actions; landscape spatial composition; informative steps and digital control. The author's algorithm of historical cultural potential's disclosure of waterfront territories is shown in the paper. Today such territories need the efficient ecologically responsible architectural-landscape organization due to necessary protection of the environment from one side and accelerated urbanization process from the other with necessary creating comfortable living conditions in the general trend of climate change and the highly rapid development of smart technologies in modern world.
The Overtopping BReakwater for Energy Conversion (OBREC) is an overtopping type wave energy converter, totally embedded into traditional rubble mound breakwaters. The device consists of a reinforced concrete front reservoir designed with the aim of capturing the wave overtopping in order to produce electricity. The energy is extracted through low head turbines, using the difference between the water levels in the reservoir and the sea water level. This paper investigates the nature and magnitude of wave loadings exerting on various parts of the structure. The results improve the overall knowledge on the device behavior, completing the highlights from the complementary test campaign carried out in the same wave flume in 2012 (Vicinanza et al., 2014). The formulas provided have been used to design the first OBREC prototype breakwater in operation since January 2016 at Naples Harbour (Italy).
In this paper, a novel Current-Mode (CM) square/triangular wave oscillator, based on second generation current conveyor (CCII), operating as resistance/capacitance to time conversion is described. The proposed oscillator, which consists of two CCII as an active element, three grounded resistances and one capacitance found to be an effective alternate of voltage mode based interfaces for wide range capacitive and resistive sensors. The interface circuit was implemented with commercially available current feedback operational amplifier AD844 from Analog Devices and passive components. Experimental results confirmed the theoretical expectations, showing good linearity in wide oscillation frequency/period range, which can be independently adjusted through resistive or capacitive external passive components. Experimental measurement was also conducted on a fabricated capacitive humidity sensor to verify the real time application of the proposed interface circuit. The interface circuit has shown a good accuracy and linearity for wide variation in capacitance of humidity sensor.
Wavelength stabilization for a pulsed laser presents more challenges than that of continuous wave laser. We have developed a simple and efficient long-term wavelength drifts compensation technique for tunable pulsed dye lasers (PDL) applied in sodium detection lidar system. Wavelength calibration and locking are implemented by using optogalvanic (OG) spectroscopy in a Na hollow cathode lamp (HCL) in conjunction with a digital control software. Optimization of OG signals for better laser wavelength discrimination and feedback control is performed. Test results indicate that locking the multimode broadband PDL to the Na atomic transition corresponding to 589.158 nm is well achieved although the temperature in the laboratory is unstable. Through active compensation, the maximum wavelength drift is reduced from over 5 pm to 0.42 pm in 10 h and the maximum wavelength drift rate of the PDL is improved from 3.3 pm/h to 0.3 pm/h It has been used to efficient sodium resonance fluorescence lidar detection. This technique is economical and easy to implement, and it provides flexible wavelength control and allows generalization for some other applications which require the wavelength of tunable pulsed lasers to be fixed at an atomic resonance transition references. (C) 2015 Elsevier B.V. All rights reserved,
Soil varies from location to location as a result of complex combinations of soil forming factors and processes operating at different scales and intensities. The scale-dependent variability in soil properties causes challenges for the characterization and mapping of soils. With the advent of technologies, proximal sensors such as gamma radiometrics can characterize soil spatial variability and the digital mapping of soil properties. In this study we aim to characterize scale-dependent variability of proximal gamma radiometrics and its complex relationship with soil properties at different scales using wavelet transform and wavelet coherency. We measured gamma radio metrics (gamma-ray potassium (K-40), uranium (U-238), thorium (Th-232) and Total Count (gamma-TC)) using a hand-held device in the field every 25 m along a 3.0 km transect. At each point we measured elevation (m) and land use and collected soil samples to determine key soil properties (electrical conductivity EC1:5, pH (CaCl2), soil organic carbon (SOC), cation exchange capacity (CEC), exchangeable potassium (exch. K), and Colwell P). Wavelet spectra identified significant (P < 0.05) variations at different scales and locations for both gamma-ray and soil properties. There were significant localized variations with changes in elevation and land use also important. In most cases a 'global' Pearson correlation between the gamma-ray and soil properties was not significant. In contrast, wavelet coherency provided a more powerful scale-and location-specific relationship between gamma-ray, elevation and land use with selected soil properties. For example, a strong correlation (18% of the area was significant) was detected between land use and soil EC1:5 at all scales (800 m) there was significant positive correlations between gamma-TC and SOC (36% by area). At medium scales (similar to 400 m) there was significant and positive correlations between K-40 and CEC (23% by area), but only along the first half of the transect which was underlain with Bushy Creek Granodiorite. These findings provide an improved understanding of the spatial variability of gamma-ray-soil relationships. The approach used shows the scope and significant potential to use wavelet analysis of gamma-soil property relationships that are scale-specific and would be useful for digital soil mapping. Moreover, scale-specific spatial information of soil properties aids understanding of soil formation processes and it illustrates an approach to improve future soil sampling strategies. (C) 2017 Elsevier B.V. All rights reserved.
Waxy starches consist almost exclusively of amylopectin and don't contain amylose molecules. Despite extensive knowledge - and certain applications - of waxy maize starch in former times, the production and use of other high amylopectin starches is now increasing. This review deals with the physical processing of these starches (via gelatinization, gelation, extrusion, annealing, and heat moisture treatment) and with chemical and biochemical modification (e.g. acetylation, debranching of amylopectin, hydrolysis). Great attention is paid to the digestibility of the products and the formation of nanoparticles. Both usual and new food and non-food uses of rice, maize, wheat, barley and potato waxy starches are referred to. (C) 2017 Elsevier Ltd. All rights reserved.
This paper introduces a kind of receiver that can receive signal which weak to UV level. First, the common mode rejection for the input differential signal is necessary, and a low noise amplifier followed by. Then we should let the signal go through a Programmable filter whose center frequency, Q are all selected via pin- strapped inputs. In order to get the appropriate amplitude of the signal, an automatic gain control amplifier is needed. Last, before the signal sampled by the A/D converters, an active filter and an operational amplifier is followed by the AGC amplifier. Through the actual test, the low frequency signal receiver with high sensitivity introduced in this paper has the characteristics of high sensitivity and stability, so it can be applied in some engineering.
Current European policies define targets for future direct emissions of new car sales that foster a fast transition to electric drivetrain technologies. However, these targets do not consider the emissions produced in electricity generation and material production, and therefore fail to incentivise car manufacturers to consider the benefits of vehicle weight reduction. In this paper, we examine the potential benefits of limiting the average weight and altering the material composition of new cars in terms of global greenhouse gas emissions produced during the use phase, electricity generation and material production. We anticipate the emissions savings for the future car fleet in Great Britain until 2050 for various alternative futures, using a dynamic material flow analysis of ferrous metals and aluminium, and considering an evolving demand for car use. The results suggest that fostering vehicle weight reduction could produce greater cumulative emissions savings by 2050 than those obtained by incentivising a fast transition to electric drivetrains, unless there is an extreme decarbonization of the electricity grid. Savings promoted by weight reduction are immediate and do not depend on the pace of decarbonization of the electricity grid. Weight reduction may produce the greatest savings when mild steel in the car body is replaced with high-strength steel. This article is part of the themed issue 'Material demand reduction'.
This study presents the effects of various mineral admixtures such as silica fume, fly ash, ground granulated blast furnace slag (GGBFS), and metakaolin and steel fiber on the rheology, strength, and chloride ion penetration resistance characteristics wet-mix shotcrete (WMS) mixtures made with crushed aggregates. The mixtures tested in this study are mostly ternary mixtures blended with silica fume. Potential implications of measured rheological properties in relation to pumping and shooting performance of WMS mixtures were also analyzed. The results have shown that silica fume may be an effective admixture benefiting both pumpability and shootability of WMS. Fly ash was found to adversely affect the pumpability of WMS mixtures by markedly increasing the torque viscosity. GGBFS had non-significant effects on both pumpability and shootability, whereas it strongly improved the chloride ion penetration resistance and strength of WMS. It was also identified that no more than 5% metakaolin by mass of cement is necessary to enhance the pumpability, shootability, and chloride penetration resistance of WMS. Despite many expected advantages of using steel fibers in WMS, special attention should be paid to prevent excessive degradation of pumpability and chloride ion penetration resistance when a high dosage (>50 kg/m(3)) of steel fibers is used. (C) 2017 Elsevier Ltd. All rights reserved.
Wharton's jelly mesenchymal stem cells (WJMSCs) are being increasingly recognized for their ectodermal differentiation potential. Previously, we demonstrated that when WJMSC were seeded onto an acellular matrix material derived from Wharton's jelly and cultured in osteogenic induction media, generated CK19 positive cells and hair-like structures indicative of ectodermal differentiation of WJMSCs. In this manuscript, we examine the underlying mechanism behind this observation using a variety of microscopy and molecular biology techniques such as western blotting and qPCR. We demonstrate that these hair-like structures are associated with live cells that are positive for epithelial and mesenchymal markers such as cytokeratin-19 and alpha-smooth muscle actin, respectively. We also show that up regulation of beta-catenin and noggin, along with the expression of TGF-beta and SMAD and inhibition of BMP4 could be the mechanism behind this ectodermal differentiation and hair-like structure formation. (C) 2016 Elsevier Inc. All rights reserved.
Drought is considered one of the major constraints of plant growth and productivity worldwide. Plants respond to drought through different mechanisms including physiological, biochemical, and gene expression modulation. Studying these mechanisms will provide better understanding of drought response mechanisms and will help breeders in developing new cultivars. In this study, growth, biochemical, and molecular responses of four wheat (Triticum durum Desf.) landraces to drought stress (300 mM mannitol) were investigated at the seedling stage. Reverse transcription-polymerase chain reaction was used to assess gene expression level for a drought stress responsive gene (DHN15.1). Germination percentage, shoot length, root length, and root number for all T. durum landraces were decreased significantly under drought stress. However, drought stress caused an increase in proline content, lipid peroxidation level, and DHN15.1 transcript level. According to the studied traits, the Karak landrace showed long shoots (48% relative to its control), the longest roots (45% relative to its control) and the highest proline content (483% relative to its control). The results indicate that from the landraces studied, Karak may be selected as the most tolerant wheat landrace and may help in wheat breeding programs for adaptation to drought-prone environments.
MicroRNAs (miRNAs) play critical roles in post-transcriptional gene regulation and act as important endogenous regulators to various stressors. Ultraviolet-B (UV-B) radiation is a major factor influencing crop growth and development. In this study, we isolated a novel wheat miRNA, named Tae-miR6000, and confirmed its expression diversity after UV-B treatments. Additionally, using the Northern blotting technique, we found that six miRNAs were highly responsive to UV-B stress in wheat. Of these six miRNAs, miR159, miR167a, and miR171 were significantly upregulated, and the remaining three miRNAs were downregulated, at different time points after UV-B treatment. This result indicates that miRNAs may be involved in the regulation of targets after induction by UV-B stress. Furthermore, promoter analysis of the UV-B-responsive miRNA genes revealed some light-relevant cis-elements, such as the I-box and G-box. Taken together, the results of this study suggest that wheat miRNAs play important roles in the response to UV-B stress.
Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections.
Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body. To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats. Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting. Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression. The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.
The Italian white certificate scheme is the main national policy instrument to incentivise energy efficiency of the industrial sector, with savings from white certificates amounting to 2% of Italy's 2012 primary energy consumption. The mechanism sets binding energy-saving targets on electricity and gas distributors with at least 50,000 clients and includes a voluntary opt-in model for participation from other parties. This paper investigates and assesses the elements of the scheme that help overcome several barriers to deliver industrial energy efficiency. Results from a survey conducted among leading experts indicate that the Italian system provides a strong financial incentive to energy efficiency investments, covering a significant share of investment costs and thus reducing payback time. Moreover, the scheme fosters the development of energy service companies (ESCOs), which are key to developing, installing and arranging finance for projects on the ground. In conjunction with other policies, the mechanism also raises awareness of energy efficiency investment opportunities, thus helping overcome the market failure of insufficient information. Core challenges remain, including tackling regulatory uncertainty and improving access to finance.
White spot syndrome virus (WSSV) is the most severe viral pathogen to the crustacean aquaculture industry worldwide. Recently, serious WSSV outbreaks caused catastrophic losses in the Chinese mitten crab, Eriocheir sinensis in Jiangsu Province, Eastern China. However, to date, little is known about its infection mechanism in the new natural host. This study aimed to reveal the temporal and spatial dynamics of WSSV in E. sinensis. The slow viral growth in the early stage of infection was the light infection stage (from 0 to 24hpi), and the exponential growth stage that followed was the logarithmic phase (from 24 to 72hpi). The viral growth curve ended with the plateau phase (from 72 to 144hpi) which demonstrated a consistent high level of viral load and accompanied heavy crab mortality. The viral load increased as time progressed with similar growth curves, however, at different degrees. The viral copy numbers of tissues at different time intervals, analysed using one-way analysis of variance (anova), showed significant differences between tissues at all time points (P<0.05). Infection was detectable as early as 6hpi in all the tissues screened. The severity of infection was found to be maximum in gill and pleopods, which could be recommended for diagnostic testing. This study might provide important data to analyse theoretically the interaction between WSSV and the host.
This paper discusses the concepts and current trends in the structure of wholesale electricity markets and additionally reviews the structure of some electricity markets in the world. It also reviews the experience around the system operation and market operation, as well as how the main processes are handled in European and American markets. This review shows that there are various designs to which these markets are converging depending on your needs and structures. Some trends turn around the presence of TSO, ISO and market operator (OM); as well as the operation of derivatives markets.
We present for the first time analytic solutions for the nonlinear dynamics of a Wien bridge oscillator stabilised by three common methods: an incandescent lamp, signal diodes, and the field effect transistor. The results can be used to optimise oscillator design, and agree well with measurements. The effect of operational amplifier marginal nonlinearity on oscillator performance at high frequencies is clarified. The oscillator circuits and their analysis can be used to demonstrate nonlinear dynamics in the undergraduate laboratory.
The study regards attitudes of Russian immigrants in Israel toward wife abuse and corporal punishment. The sample consisted of 1,028 participants, based on a multistage cluster sampling. The study used a questionnaire related to immigration, acculturation, and attitudinal issues. The findings indicate a dual-causal model, in which corporal punishment attitudes contribute to wife abuse attitudes and vice versa. However, the effect of attitudes supporting corporal punishment was stronger than the effect of wife abuse attitudes, indicating that the attitudinal system as a precursor of violent behavior is already merging the two types of violence.
A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mammalians including humans living in their natural habitat are continuously facing pathogen encounters throughout their life. The influences of environmental conditions on the signatures of the immune system and on experimental outcomes are yet not well defined. Thus, the transferability of results obtained in current experimental systems to the physiological human situation has always been a matter of debate. Studies elucidating the diversity of wild immunology imprintings in detail and comparing it with those of clean lab mice are sparse. Here, we applied multidimensional mass cytometry to dissect phenotypic and functional differences between distinct groups of laboratory and pet shop mice as a source for wild mice. For this purpose, we developed a 31-antibody panel for murine leukocyte subsets identification and a 35-antibody panel assessing various cytokines. Established murine leukocyte populations were easily identified and diverse immune signatures indicative of numerous pathogen encounters were classified particularly in pet shop mice and to a lesser extent in quarantine and non-SPF mice as compared to SPF mice. In addition, unsupervised analysis identified distinct clusters that associated strongly with the degree of pathogenic priming, including increased frequencies of activated NK cells and antigen-experienced B- and T-cell subsets. Our study unravels the complexity of immune signatures altered under physiological pathogen challenges and highlights the importance of carefully adapting laboratory settings for immunological studies in mice, including drug and therapy testing. (c) 2016 International Society for Advancement of Cytometry
The relationship between sustainability and tourists is complex. There has been little increase in the number of studies published over recent years focusing on the concept of 'pro-sustainable' tourists, or the tourist's willingness to pay (WTP) for sustainability, making it increasingly difficult to identify key explanatory factors that determine tourists' WTP for sustainable destinations. To provide a richer understanding of tourists' heterogeneous preferences for sustainable destinations, this study allows us to determine current tourists' attitude toward sustainability and to identify explanatory variables that influence their WTP to enjoy a more sustainable destination. This study surveyed tourists on the Western Costa del Sol (Spain), a mature sun and sand destination that is currently restructuring and facing several developmental challenges associated with sustainability.
The assessment of the economic potential of wind electricity is of critical importance for wind power development in China. Based on the wind resource data between 1995 and 2014 and geological assumptions, this paper calculates economic potential of China's onshore wind electricity. Furthermore, it builds an econometric model to update the net-present-value model, based on a survey sample of various wind farms. Results show that the economic potential of China's onshore wind electricity is 8.13 PWh per year with a feed-in-tariff price at 0.60 yuan (about 9.6 U.S. cents) per kilowatt-hour. (C) 2016 Elsevier B.V. All rights reserved.
Using data from two measurement networks, we analyse the following aspects of wind speeds over Switzerland to assess the possibility of high wind power penetration: spatial correlation, persistent low wind power conditions and the diurnal and seasonal wind speed patterns. We show that correlation amongst speeds as a function of distance is significantly lower compared to values found in literature. This can be attributed to the complex terrain of the Alps, which has a profound influence on meteorological parameters. Secondly, using extreme value analysis we calculate return levels for low wind power periods. Large differences are found, with return levels ranging from 29 to 1017 h of no power production for a return period of 10 years. No clear spatial pattern was found that can account for these values. However, the length of no-production periods decreases with increasing elevation. Next, we investigate diurnal and seasonal wind speed patterns and show how the different patterns and their intra-annual variation can be explained by local topography. We also find that with increasing elevation mean wind speeds and power production increase, even when accounting for lower air density. Wind speeds are on average higher in winter, and at elevation the relative increase in winter compared to summer is higher. Notable exceptions are explained from topography and carry implications for wind power development. In view of Switzerland's electricity shortage in winter, these findings make a strong claim for wind power development, especially at higher elevations. (C) 2017 Elsevier Ltd. All rights reserved.
The main source of electricity in Brazil is from hydro, which has about 65.2% share of the country's electric energy matrix. However, over the last decade the wind energy increased from 19 MW to 2.2 GW. Since wind is an intermittent energy source, heavily determined by the weather and climatic conditions, and important effects on wind power generation can be expected in the mid and long term, in particular related to the impacts of extreme winds. The IPCC AR5 (Intergovernmental Panel on Climate Change) indicates changes in wind speed at the surface in some regions of the world, and increased wind strength in mid-latitude regions. This study scrutinizes future scenarios of extreme winds in Brazil by applying trend analysis techniques on a 50-year historical series of observational wind speed and meteorological parameters at 10 m height in Brazil. Embracing techniques of cluster analysis it was possible to characterize six main regions with macro climatic similarities. To assess the goodness fit distribution, we designate two stations per homogenous region, taking as criteria the stations with better performance in the qualification process to determine the wind distribution pattern in each region applying the Kolmogorov-Smirnov test (KS) and the lowest standard error (SE). After evaluating the frequency distribution of wind speed, the best fit result for the frequency distribution of maximum wind speed is the Gumbel model. The analysis of climatic trends performed by Mann-Kendall test revealed that in minimum wind speed series is not conclusive because it shows disparate results between homogeneous regions. On the other hand, the analysis of climatic trends of maximum wind speed presents 100% positive trends in Group#1, an equal number of stations with not significant trends and positive trends for Group#2, 36.8% more stations with positive trends than negative trends for Group#3 and 20% of stations with more negative trends than stations with positive trends for Group#4. This way, based in these results, is possible assert that there are an increase in the maximum extreme wind in Brazil, mainly in mid-latitudes. (C) 2016 Published by Elsevier Ltd.
Wind energy has become one of the most cost-effective renewable sources nowadays. However, the stochastic nature associated with wind-energy production represents a great challenge for power-system operations. Therefore, probabilistic techniques are necessary to evaluate the performance of power systems with substantial amounts of wind generation. This paper presents a probabilistic based bi-level optimization approach for evaluating the impact of wind farm location and control strategy on the penetration level of wind farms and electricity market prices. The bi-level optimization model is formulated as mathematical program with equilibrium constraints (MPEC) and solved by means of the NLPEC solver in the General Algebraic Modeling System (GAMS) environment. Several cases studies are presented in this paper to determine to the optimal wind generation penetration and market prices with different locations and control strategies for wind farms. Moreover, some scenarios are discussed in regards to the practical allocation of wind farms. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
This article investigates the risk of cost overruns and underruns occurring in the construction of 51 onshore and offshore wind farms commissioned between 2000 and 2015 in 13 countries. In total, these projects required about $39 billion in investment and reached about 11 GW of installed capacity. We use this original dataset to test six hypotheses about construction cost overruns related to (i) technological learning, (ii) fiscal control, (iii) economies of scale, (iv) configuration, (v) regulation and markets and (vi) manufacturing experience. We find that across the entire dataset, the mean cost escalation per project is 6.5% or about $63 million per windfarm, although 20 projects within the sample (39%) did not exhibit cost overruns. The majority of onshore wind farms exhibit cost underruns while for offshore wind farms the results have a larger spread. Interestingly, no significant relationship exists between the size (in total MW or per individual turbine capacity) of a windfarm and the severity of a cost overrun. Nonetheless, there is an indication that the risk increases for larger wind farms at greater distances offshore using new types of turbines and foundations. Overall, the mean cost escalation for onshore projects is 1.7% and 9.6% for offshore projects, amounts much lower than those for other energy infrastructure. Copyright (c) 2016 John Wiley & Sons, Ltd.
The wind farm layout optimization problem has received considerable attention over the past two decades. The objective of this problem is to determine the wind farm layout that maximizes the annual energy generated. The majority of studies that have solved this problem simulated the velocity deficit using the Jensen wake model. However, this model is not in agreement with field measurements and computational fluid dynamics simulations. In this study, an approach to solve the wind farm layout optimization problem based on a Gaussian wake model is proposed. The Gaussian wake model uses an exponential function to evaluate the velocity deficit, in contrast to the Jensen wake model that assumes a uniform velocity profile inside the wake. The proposed approach minimizes the annual cost of energy of a wind farm using a genetic algorithm. The application of the proposed approach yields higher annual generation and a lower computational time for all wind scenarios under study. Under a more complex wind scenario, the improvement was relatively small. This suggests that the use of a more robust wake model in the WFLO problem, does not lead to greater efficiency in real wind cases. (C) 2017 Elsevier Ltd. All rights reserved.
To study climate-related aspects of power system operation with large volumes of wind generation, data with sufficiently wide temporal and spatial scope are required. The relative youth of the Wind industry means that long-term data from real systems are not available. Here, a detailed aggregated Wind power generation model is developed for the Republic of Ireland using MERRA reanalysis wind speed data and verified against measured wind production data for the period 2001-2014. The model is most successful in representing aggregate power output in the middle years of this period, after the total installed capacity had reached around 500 MW. Variability on scales of greater than 6 h is captured Well by the model; one additional higher resolution wind dataset was found to improve the representation of higher frequency variability. Finally, the model is used to hindcast hypothetical aggregate wind production over the 34-year period 1980-2013, based on existing installed wind capacity. A relationship is found between several of the production characteristics, including capacity factor, ramping and persistence, and two large-scale atmospheric patterns the North Atlantic Oscillation and the East Atlantic Pattern. (C) 2017 Elsevier Ltd. All rights reserved.
This work presents a techno-financial evaluation of two Chilean locations with promising wind potential: Laguna Verde placed in the central region of the country, and Porvenir in the southern region. A small scale wind farm was studied, considering a nominal electrical production capacity of 90 kW. This facility is comprised of three wind turbine models, all available in the national market. Currently, the tariff method used in Chile is the net billing scheme, where the energy bought and sold to the grid has different prices. The study is based on 300 hypothetical residential households. The software tool used to perform the assessment was the Hybrid Optimization of Multiple Energy Resources (HOMER). For all the scenarios the results showed a Net Present Cost (NPC), instead of a financial profit from the proposed projects. A sensitivity analysis was also carried out. From the group of variables studied, the NPC exhibited itself as more sensitive to the price of buying energy from the grid and to the annual average wind speed. Finally, a few government policies and their applications are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
PMSG wind turbine system configured with three-level neutral-point-clamped (3L-NPC) back-to-back power converter and direct-drive train has good properties and is a nice solution for high power wind energy applications. Direct model predictive control has emerged as a viable alternative for power electronics and electrical drives. This work presents a direct model predictive current control (DMPCC) solution for both the grid and generator side control of grid-connected 3L-NPC back-to-back power converters in PMSG wind turbine systems. The presented DMPCC is realized all in alpha beta frame and evaluated all with experimental results on a fully FPGA based platform. Experimental results confirm both its effectiveness and its better steady state control performances in comparison with the conventional switching table based DTC-DPC technique.
Pitch control comprises a significant proportion of current wind turbine load-control approaches. Collective pitching is used in restricting the overall power generation at high winds, whereas individual pitching has the added advantage of mitigating cyclic loads that are detrimental in fatigue damage of the turbines. Currently, there are many studies on conventional pitching control that account for long-term variations in wind speeds and associated high loads, but a smaller number of studies in short-term pitch action. The present study focuses on the use of rapid pitch control for handling short-term variations in wind conditions and load fluctuations within one cycle of rotation, with special attention to the prognosis of the aeroelastic response of the rotor. We use a numerical model capable of handling the complexities of the multi-physics dynamics of a wind turbine rotor. Based on a nonlinear adaptive ODE algorithm, it provides a natural way to integrate the various multi-physics aspects of wind turbine dynamics, including the control system and the coupled response of the aerodynamics and the structural deformations of the rotor. Results are presented for the case study of the NREL-5MW Reference Wind Turbine, and their significance for wind-turbine rotors in general is discussed. (C) 2017 Elsevier Ltd. All rights reserved.
The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent depression though face, predictive and construct validities of the model to depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (similar to 30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.
The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20mel and the expression of tumor-suppressor genes in acute leukemia (AL) to better understand the pathogenesis of leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls; pyrophosphate sequencing was performed to detect the methylation status of the Wnt5a promoter; and western blotting was performed to detect the overall expression levels of Wnt5a protein and histone H4K20mel in patients with acute myeloid leukemia (AML) and in normal controls. The relationship between Wnt5a protein expression and histone H4K20mel was analyzed. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was performed to investigate the recruitment of H4K20mel and SET8 to the Wnt5a promoter and coding regions. Our results demonstrated that the expression levels of Wnt antagonists were generally low in AML, but showed differential expression in acute lymphocytic leukemia (ALL). In most cases of AML, methylation of the Wnt5a promoter was observed and Wnt5a protein expression was low. In some cases of AML, the overall level of H4K20mel protein was higher than that in normal controls. In addition, Wnt5a expression was positively correlated with H4K20mel expression and was unrelated to the methylation status of its promoter. Moreover, H4K20mel and SET8 were enriched in the Wnt5a promoter region and coding region. By contrast, Wnt5a expression was unrelated to H4K20mel expression in normal controls. Moreover, we observed that the methylation of Wnt antagonists was often found in patients with AL, particularly those with AML, whereas the extent of methylation was variable in ALL patients. Wnt5a expression was positively correlated with the enrichment of H4K20mel and SET8 at the Wnt5a promoter and coding regions. H4K20mel increased Wnt5a expression by promoting transcription initiation and elongation.
The rarely reported red pigmented dinoflagellate, Woloszynskia pascheri, is described from frozen surface waters in Ontario, Canada. New information based on light microscopy (LM) is provided on cell organelles (dinokaryon, chromosomes, pigment droplets and ectoplasmic vesicular layer), the thin-walled ice-bound pellicle cysts and thick-walled summer resting cysts. An earlier published suggestion that W. pascheri has morphology similar to that of Gymnodinium cryophilum (Wedemayer, Wilcox et Graham) G. Hansen et Moestrup is refuted. The process of red ice formation depends on a number of weather-related and other environmental factors. The most important of these being a mid-winter thaw that creates pathways (cracks and melted areas of ice) for passage of swimming cells from the water underlying the ice to water on the surface of the ice. In thin-walled ice-bound pellicle cysts, W. pascheri remained viable at ambient air temperatures lower than -20A degrees C for several days and suggests a unique biochemical physiology that needs research. A summary of the historical classification of this species reveals a tumultuous past and the continuing assignment of this species within the genus Woloszynskia appears doubtful, given the rapidly improving state of knowledge about the fine structure and molecular biology of many other similar species.
Worry is a common phenotype in both psychiatric patients and the normal population. Worry can be seen as a covert behavior with primary function to avoid aversive emotional experiences. Our research group has developed a treatment protocol based on an operant model of worry, where we use exposure -based strategies to extinguish the catastrophic worry thoughts. The aim of this study was to test this treatment delivered via the Internet in a large-scale randomized controlled trial. We randomized 140 high-worriers [PSWQ]) to either Internet-based extinction therapy (IbET) or to a waiting-list condition (WL). Results showed that IbET was superior to WL with an overall large between-group effect size of d 1.39 (95% confidence interval [1.04,1.73]) on the PSWQ. In the IbET group, 58% were classified as responders. The corresponding figure for WL participants was 7%. IbET was also superior to the WL on secondary outcome measures of anxiety, depression, meta-cognitions, cognitive avoidance, and quality of life. Overall treatment results were maintained for the IbET group at 4- and 12-month follow-up. The results from this trial are encouraging as they indicate that worry can be targeted with an accessible and novel intervention for worry. Replication trials with active control group are needed.
Background: Wound healing is often impaired in diabetic animals and humans. Matrix metalloproteases act as proinflammatory agents in physiological wound healing pathways by stimulating cytokines including the interleukins, IL6, IL1A and IL1B, and the tumor necrosis factor and transforming growth factor beta1. Botanicals are traditionally used to assist healing of different types of wounds, because they produce fewer side effects. Our specific aim here was to develop a plant-based recipe supporting effective wound healing in diabetic animals. Methods: Plant materials from Adiantum capillus-veneris, Commiphora molmol, Aloe Vera, and henna were collected for this study, and oven-dried at 60 degrees C. The dried leaves and resins were then crumbled into a powder and mixed in equal parts with Vaseline as a preservative. This mixture was used as an ointment on wounds induced in 60 diabetic and non-diabetic rats that were divided into 6 subgroups receiving agent or control treatments. Necrotic tissue surrounding the wound was periodically removed during wound healing. RNA was extracted from the healing region of the wound at days 7, 14 and 21 for cDNA synthesis to monitor changes in Tgfb1, Mmp3, Mmp9, Il6 and Tnf alpha expression using real-time PCR. Results: The expression of the Mmp3, the Tnf alpha, and the Tgfb1 genes from wound tissue were significantly different (p0.05) of the Mmp9 gene expression in diabetic and non-diabetic rats treated only with Vaseline after 7, 14, and 21 days. But, the expression of the Mmp9 gene decreased significantly (p < 0.05) in diabetic rats after 14 days in comparison to non-diabetic rats, when the herbal mixture was added to Vaseline. Conclusions: Our study presents an herbal treatment that alters the gene expression signature at wounds induced in the rat model for type I diabetes in a manner consistent with accelerated healing, and demonstrates that this herbal treatment might be effective to treat wounds in diabetic patients.
Fault detection in induction machines is commonly realized through motor current signature analysis. In case of Wound-Rotor Induction Machine rotor faults, the amplitude of the inverse sequence harmonic component -sf of the rotor current space-vector is monitored in order to sense its variation. However, motor current signature analysis is limited by some drawbacks. In fact, under transient operating conditions an efficient Fast Fourier Transform cannot be made, since slip or frequency vary, and so the amplitude of the harmonic component -sf. In this paper, a new technique based on the Square Current Space-vector Signature Analysis (SCSSA) is proposed for rotor fault detection in Wound-Rotor Induction Machines operating under time-varying conditions. The performance of the proposed approach is confirmed by simulation and experimental results. The proposed technique can be easily embedded in the digital control system for modern wind power plants.
We conducted two separate, exploratory studies to evaluate the differences between the supervision of wraparound (in-home) and outpatient (office) child treatment interventions. Study one (n = 96) examined the structure and norms of supervision between groups as well as rates of general disclosure to direct supervisors. Study two (n = 116) specifically examined the frequency of child abuse and neglect encountered in each intervention setting, and the level of disclosure in supervision of these mandatory reporting events. Findings from the first study suggest that wraparound clinicians received significantly less individual supervision and colleague consultation than their office-based counterparts. Additionally, wraparound clinicians were significantly more likely to withhold information about client cases from their direct supervisors. In the second study, wraparound clinicians endorsed significant increases for observed child abuse, observed child neglect, and verbally reported child neglect compared to their office-based counterparts. In regards to mandatory reporting issues with children, wraparound clinicians were found to be significantly less likely to disclose issues pertaining to child neglect to their direct supervisors than office-based clinicians. Our studies show preliminary evidence for a needed increase of individual supervision in wraparound practice, in addition to a greater focus on clinician disclosures related to incidents of child abuse and neglect.
The X chromosome has played a critical role in the development of sexually selected characteristics for over 300 million years, and during that time it has accumulated a disproportionate number of genes concerned with mental functions. There are relatively specific effects of X-linked genes on social cognition, language, emotional regulation, visuospatial, and numerical skills. Many human X-linked genes outside the X-Y pairing pseudoautosomal regions escape X-inactivation. Dosage differences in the expression of such genes (which constitute at least 15% of the total) are likely to play an important role in male-female neural differentiation, and in cognitive deficits and behavioral characteristics, particularly in the realm of social communication, that are associated with sex chromosome aneuploidies. (C) 2016 Wiley Periodicals, Inc.
The rapid development of energy, electricity, and transportation industries has created a market for steel pipes; however, buried steel pipelines near high-voltage transmission lines and electrified railways often experience alternating current (AC) corrosion at the damaged coating of pipelines; such phenomenon is mostly due to the resistance between the capacitance and inductance coupling, especially for long-distance pipelines in parallel operation. AC corrosion can cause pipeline corrosion perforation and stress corrosion cracking (SCC) in some cases, which has been a vital threat to the pipeline safety. In this work, the influence of AC on corrosion behavior of X80 pipeline steel was investigated in NS4 near-neutral solution by data acquisition technique, electrochemical test, immersion tests and surface analysis techniques. Results show that with the increasing of AC density, corrosion morphology changed from uniform corrosion to localized corrosion with many pits. Under the full AC interference, X80 steel occurred cathodic and anodic polarization which resulted in iron dissolution and hydrogen precipitation. The negative half wave AC would lead to hydrogen evolution and hydrogen induced anodic dissolution, the pits in X80 steel surface present sharp. However, under disturbance of positive half-wave AC, only anodic dissolution occurred and the pitting appeared spill shape and smoothly. Under various AC waveform interference, the corrosion products of X80 steel surface were different. Under full AC wave and positive half-wave interference, the corrosion products were loose, had have no alpha-FeOOH and occurred cracks; however, under negative half-wave AC interference, the corrosion products were denser and contained alpha-FeOOH which has protective effect on substrates.
Model animals are crucial to biomedical research. Among the commonly used model animals, the amphibian, Xenopus, has had tremendous impact because of its unique experimental advantages, cost effectiveness, and close evolutionary relationship with mammals as a tetrapod. Over the past 50years, the use of Xenopus has made possible many fundamental contributions to biomedicine, and it is a cornerstone of research in cell biology, developmental biology, evolutionary biology, immunology, molecular biology, neurobiology, and physiology. The prospects for Xenopus as an experimental system are excellent: Xenopus is uniquely well-suited for many contemporary approaches used to study fundamental biological and disease mechanisms. Moreover, recent advances in high throughput DNA sequencing, genome editing, proteomics, and pharmacological screening are easily applicable in Xenopus, enabling rapid functional genomics and human disease modeling at a systems level.
Xyloglucan endotransglycosylase (XET) catalyses the transglycosylation of xyloglucan, the major hemicellulose polymer, which has been thought to mediate the cross-linking of cellulose microfibrils in cellular walls and proposed to be involved in the control of cell wall relaxation. To understand the relationship between litchi fruit cracking and gene expression patterns, three XET genes from litchi fruit were identified and then examined for their expression profiles in pericarp and aril tissues at different development stages, using a cracking-resistant cultivar, 'Huaizhi', and a cracking-susceptible cultivar, 'Nuomici'. Three full-length cDNAs of 1267, 1095 and 1156 bp encoding XETs, named LcXET1, LcXET2 and LcXET3, respectively, were isolated from expanding fruit using RT-PCR and RACE-PCR (rapid amplification of cDNA ends) methods. Northern blotting analysis showed that LcXET1 mRNA accumulation occurred much earlier in aril tissues at 59 days after anthesis (DAA) than in pericarp tissues at 73 DAA in 'Nuomici'. However, it appeared at almost the same time (66 DAA) in pericarp and aril tissues in 'Huaizhi'. which suggested that differential accumulation of LcXET1 in pericarp and aril tissues in 'Nuomici' and 'Huaizhi' was closely associated with fruit cracking. LcXET2 mRNA accumulation could be detected in pericarp and aril tissues throughout fruit development but exhibited a differential accumulation pattern between pericarp and aril tissues. In the aril of 'Nuomici', intensive signal bands were detectable at 59-73 DAA in rapidly expanding fruits of 'Nuomici' but only weak bands could be found in the pericarp tissues. In contrast, moderate signal bands were detectable both in pericarp and aril tissues of 'Huaizhi' fruits. Furthermore, LeXET3 showed constitutive expression in both pericarp and aril tissues of developing 'Nuomici' and 'Huaizhi' litchi fruit. In addition, differential expression patterns of three XETs genes were observed in different tissues of litchi, with only LcXET1 being fruit-specific. To further address the role of LcXET in fruit cracking, alpha-naphthalene acetic acid (NAA) was used to treat 'Nuomoci' to reduce fruit cracking. Enhanced LcXET1 mRNA accumulation appeared in pericarp while LcXET2 and LeXET3 mRNTA accumulation enhanced in aril tissues in the NAA-treated fruits. Thus, LcXET1 is more likely to play a role in reducing litchi fruit cracking than LcXET2 and LcXET3. (c) 2006 Elsevier Masson SAS. All rights reserved.
Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies. Recent reports have shown molecular alterations in the gene encoding XPO1 and showed a mutation hotspot (E571K) in the following two hematological malignancies with similar phenotypes and natural histories: primary mediastinal diffuse large B cell lymphoma and classical Hodgkin's lymphoma. Emerging evidence suggests that the mutant XPO1 E571K plays a role in carcinogenesis, and this variant is quantifiable in tumor and plasma cell-free DNA of patients using highly sensitive molecular biology techniques, such as digital PCR and next-generation sequencing. Therefore, it was proposed that the XPO1 E571K variant may serve as a minimal residual disease tool in this setting. To clarify and summarize the recent findings on the role of XPO1 in B cell hematological malignancies, we conducted a literature search to present the major publications establishing the landscape of XPO1 molecular alterations, their impact on the XPO1 protein, their interest as biomarkers, and investigations into the development of new XPO1-targeted therapies in B cell hematological malignancies.
A 1.8V, 932 nA, rail-to-rail CMOS operational amplifier operating in the weak inversion regime in order to amplify the output signal of an air pressure sensor is presented. The two main parts of the ASIC are the beta-multiplier current source and the two stage amplifier. The layout has been drawn considering the matching techniques and the chip was fabricated and further characterized and measured.
Background: Sex chromosome aneuploidies occur in approximately one in 420 live births. The most frequent abnormalities are 45, X (Turner syndrome), 47, XXX (triple X), 47, XXY (Klinefelter syndrome), and 47, XYY. The prevalence of males with more than one extra sex chromosome (e.g. 48, XXYY or 48, XXXY) is less common. However, the literature provides little information about the cognitive and behavioural phenotype and the natural history of the disease. We report the clinical, neurocognitive, social cognitive and psychiatric characterization of a patient with 49, XYYYY syndrome. Case presentation: The patient presented with a complex phenotype including a particular cognitive profile with intellectual deficiency and autism spectrum disorder (ASD) with limited interests. Moreover, social anxiety disorder with selective mutism and separation anxiety disorder were observed (DSM-5 criteria, MINI Assessment). Conclusion: It is now admitted that 49, XYYYY has unique medical, neurodevelopmental and behavioural characteristics. Interestingly, ASD is more common in groups with Y chromosome aneuploidy. This clinical report suggests that understanding the cognitive and social functioning of these patients may provide new insights into possible therapeutic strategies, as cognitive remediation or social cognitive training.
Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic quality control mechanism which triggers decay of mRNAs harboring premature translation termination codons. In this chapter, I describe methods for monitoring the influence of NMD on mRNA abundance and decay rates in Saccharomyces cerevisiae. The descriptions include detailed methods for growing yeast cells, total RNA isolation, and Northern blotting. Although the chapter focuses on NMD, the methods can be easily adapted to assess the effect of other mRNA decay pathways.
Young adult (YA) cancer survivors report substantial distress, social isolation, and body image concerns that can impede successful reintegration into life years after treatment completion. Mindful Self-Compassion (MSC) interventions focus on developing mindfulness and self-compassion for managing distress, hardships, and perceived personal inadequacies. An MSC intervention would be beneficial in supporting YA survivors' management of psychosocial challenges that arise in survivorship; however, a telehealth intervention modality is essential for reaching this geographically dispersed population. We conducted a single-arm feasibility study of an MSC 8-week videoconference intervention for nationally recruited YA survivors (ages 18-29). The MSC intervention was group-based, 90-minute videoconference sessions, held weekly over 8 weeks, with audio-supplemented home practice. Feasibility and acceptability were assessed via attendance rate and an intervention satisfaction scale. Baseline to post-intervention changes in psychosocial outcomes (body image, anxiety, depression, social isolation, posttraumatic growth, resilience, self-compassion, mindfulness) were assessed using paired t tests and Cohen's d effect sizes. Thirty-four participants were consented and 25 attended a videoconference group. Feasibility was established with 84% attending at least six of the eight sessions, and intervention acceptability was high (M = 4.36, SD = 0.40, score range = 1-5). All psychosocial outcomes, except for resilience, demonstrated significant changes (p0.5). YA survivors are interested in receiving an MSC videoconference intervention. Feasibility, acceptance, and potential psychosocial benefits of the intervention were demonstrated. Findings can be applied toward the design of an efficacy randomized controlled trial to improve quality of life for YA survivors in transition after cancer treatment.
Although young adult women consume the majority of their total daily energy intake from home food sources, the decision-making processes that shape their home food environments have received limited attention. Further, how decision-making may be affected by the transformative experience of motherhood is unknown. In this study, we explore the factors that influence two key decision-making processes food choices while grocery shopping and the use of non-home food sources-and whether there are differences by motherhood status. In-depth interviews were conducted with 40 women, aged 20-29, living in southwest Georgia. Thematic analysis was used to analyze qualitative data stratified by whether or not children were present in the home. Decision-making was affected by numerous factors, Which differed across groups. In regard to grocery shopping, women with children more frequently discussed the influence of nutrition and the preferences of children, while women without children more frequently discussed the influence of taste and the preferences of other household members. Cost, convenience, weight control, and pre-planning meals emerged as salient in both groups. In regard to the use of non-home food sources, convenience and taste were discussed by both groups, while social factors were only discussed by women without children. The cost of eating out was the only reason cited for eating inside the home, and this factor only emerged among women with children. Motherhood may be an important contributor to the decision-making processes that shape young adult women's home food environments. Interventions may find success in framing messaging to emphasize factors identified as motivating healthy decisions, such as protecting the health of children, and practical strategies may be adapted from those already in use, such as pre-planning and budgeting for healthy meals. (C) 2017 Elsevier Ltd. All rights reserved.
YY1 is a multifunctional transcription factor that activates or represses gene transcription depending on interactions with other regulatory proteins that include coactivator YY1AP. Here, we describe the cloning of a novel homolog of YY1AP, referred to as YARP, from the human neuroblastoma cell line SK-N-SH. The cloned cDNA encoded a 2240 amino acid protein that contained a domain which was 97% homologous to an entire YY1AP sequence of 739 amino acids. Two splice variants, YARP2 and YARP3, were also cloned. Northern blotting demonstrated the YARP mRNA (similar to 10kb), which was increased 1.7-fold after dibutyryl cAMP-induced neural differentiation of the cells. Presence of YARP mRNA was also confirmed in human tissues such as the heart, brain and placenta. Bioinformatic analysis predicted various functional motifs in the YARP structure, including nuclear localization signals and domains associated with protein-protein interactions (PAH2), DNA-binding (SANT), and chromatin assembly (nucleoplasmin-like), outside the YY1AP-homology domain. Thus, we propose that YARP is multifunctional and plays not only a role analogous to YY1AP, but also its own specific roles in DNA-utilizing processes such as transcription.
This study aimed to evaluate the protein metabolism effect of Zanthoxylum alkylamides and to explore the potential mechanism in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were orally treated with 2, 4 and 8 mg per kg bw of alkylamides daily for 28 days. Alkylamides decreased the relative weight of the liver and food intake, significantly increased the relative skeletal muscle weight and significantly decreased the blood urea nitrogen levels. Insulin, insulin-like growth factor 1, total protein (TP) and albumin (ALB), globular proteins and ALB proteins/globulin protein levels in serum significantly increased. TP, RNA content and RNA/DNA ratio significantly increased in the skeletal muscle of diabetic rats. Real-time quantitative polymerase chain reaction results indicated that alkylamides significantly increased the mRNA expression of insulin receptor (InR), IGF1 and insulin-like growth factor 1 receptor (IGF1R) in the liver and skeletal muscle. Moreover, the mRNA and protein expression levels of PI3K, PKB and mTOR significantly increased, whereas those of atrogin-1, muscle ring finger 1 and FOXO in the skeletal muscle significantly decreased. Alkylamides may advance protein synthesis by the PI3K/PKB/mTOR signalling pathway and attenuate the catabolism of protein through the ubiquitin-proteasome pathway. Therefore, it was possible that alkylamides ameliorate protein metabolism disorders in diabetic rats by activating the mTOR pathway.
Zika virus is a mosquito-borne flavivirus that causes clinical symptoms similar to those observed in dengue and chikungunya virus infections. The Korea Centers for Disease Control and Prevention initiated laboratory testing using a real-time reverse transcription-polymerase chain reaction in January 2016. More than 1,000 suspected cases of infection were tested and nine were confirmed as imported cases of Zika virus infection from January to July 2016. The travel destinations of the infected individuals were Brazil, Philippines, Viet Nam, Guatemala, Puerto Rico, and the Dominican Republic. Phylogenetic analysis based on the partial envelope gene indicated that the viruses belonged to the Asian genotype circulating in South America. We further investigated the duration for which the viral RNA and virus-specific antibodies were detectable after the symptom onset. After the day of symptom onset, Zika virus was detectable until 6 days in serum, 14 days in urine and saliva, and 58 days in semen. Immunoglobulin M against Zika virus was detected as early as 2 days after the symptom onset and was maintained at these levels until 41 days, whereas Immunoglobulin G was detectable from 8 days after the symptom onset and was maintained until 52 days. These findings would help diagnostic laboratories improve their testing programs for Zika virus infection.
Distribution of Zika virus has spread throughout the world. WHO has announced that Zika virus disease is a global health problem. As a tropical country, Indonesia has the potential to spread Zika virus. This letter is to report that there was a single case of zika in Jambi province published by the Eijkman Institute for Molecular Biology. This case was analyzed with the temperature in the scene, which is considered as an appropriate factor to development of Zika virus.
The gene product of the zinc finger CCCH-type containing 15 (ZC3H15) gene, an immediate early erythropoietin response gene (synonymous: LEREPO4), was further characterized. ZC3H15 was expressed ubiquitously in all human tissues tested by northern blotting and showed mainly a diffuse cytoplasmic distribution by immune fluorescence microscopy and western blotting of subcellular protein fractions. The expression of ZC3H15 was downregulated effectively in HeLa cells to 5.13% of the control by transfection of specific small interfering RNA (siRNA). Subsequent Affymetrix microarray analysis revealed 202 differentially expressed genes including 114 induced (>= 3-fold) genes and 88 suppressed (<= 0.3-fold) genes. The gene ontology (GO) categories containing an over-representation of differentially expressed genes comprised cell growth, transcription, cell adhesion, regulation of NF-kappa B, regulation of MAPK, cell cycle arrest and immune response. ZC3H15 interacted with the signaling adapter protein tumor necrosis factor receptor associated factor 2 (TRAF-2) as shown by co-immunoprecipitation. ZC3H15 expression was found to be significantly increased in acute myeloid leukemia (AML) samples compared to MDS, CML, ALL and normal bone marrow samples using the Leukemia Gene Atlas (LGA) database. Based on these data, it is hypothesized that ZC3H15 may interact with TRAF-2 functionally within the NF-kappa B pathway, and may be explored as a potential target in AML.
The intercalation of L-phenylalanate (LP) into the interlayer gallery of zinc layered hydroxide (ZLH) has been successfully executed using a simple direct reaction method. The synthesised intercalation compound, zinc layered hydroxide-L-phenylalanate (ZLH-LP), was characterised using PXRD, FTIR, CHNS, ICP-OES, TGA/DTG, FESEM and TEM. The PXRD patterns of the intercalation compound demonstrate an intense and symmetrical peak, indicating a well-ordered crystalline layered structure. The appearance of an intercalation peak at a low angle of 20 with a basal spacing of 16.3 A, signifies the successful intercalation of the L-phenylalanate anion into the interlayer gallery of the host. The intercalation is also validated by FTIR spectroscopy and CHNS elemental analysis. Thermogravimetric analysis confirms that the ZLH-LP intercalation compound has higher thermal stability than the pristine L-phenylalanine. The observed percentage of L-phenylalanate accumulated release varies in each release media, with 84.5%, 79.8%, 63.8% and 61.8% release in phosphate buffer saline (PBS) solution at pH 4.8, deionised water, PBS solution at pH 7.4 and NaCI solution, respectively. The release behaviour of LP from its intercalation compounds in deionised water and PBS solution at pH 4.8 follows pseudo second order, whereas in NaCl solution and PBS solution at pH 7.4, it follows the parabolic diffusion model. This study shows that the synthesised ZLH-LP intercalation compound can be used for the formation of a new generation of materials for targeted drug release with controlled release properties.
There is current interest in harnessing the combined anticancer and immunological effect of nano particles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (K-b = 1.6-2.8 g(-1) L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-gamma. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma.
Aim: The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor, and it could inhibit HBV RNA synthesis in vitro experiments. However, the role of ZAP against HBV in vivo environment is unclear. This study aimed to investigate whether ZAP could act against HBV transcription and replication in ZAP tansgenic mouse model. Methods: HBV-replication-competent plasmid pHBV4.1 was transferred to ZAP transgenic ICR mouse via the tail vein using a hydrodynamic in vivo transfection procedure, and ICR mouse were used as controls. HBV RNA and HBV DNA replication intermediates in the liver were respectively analyzed by Northern blotting and Southern blotting. The expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue was detected by immunohistochemical staining. Results: As compared to ICR control mouse, the levels of 3.5 kb mRNA in ZAP transgenic mouse were decreased by 8.4%; while the level of HBV DNA replication intermediates was decreased by 82%. In addition, the expression of HBsAg and HBcAg in ZAP transgenic mouse liver were both significantly less than that of ICR control mouse. Conclusions: Our findings suggest that ZAP could inhibit HBV replication in vivo in mice, which offers a new target for anti-HBV drug development.
The present article reviews the biotechnological research in Zingiber montanum (Koenig) Link ex A. Dietr. (cassumunar ginger). Studies on biotechnological interventions in this plant were focused mainly on the application of tissue culture techniques. Recently, attentions are being drawn towards the genomic studies which mostly aimed at establishing the genetic relationship of different gene pools. The present review summarizes the various aspects of tissue culture protocol for in vitro micropropagation, in vitro microrhizome induction, in vitro conservation technology and molecular biology studies of this medicinal plant. This review will help in further research of this plant in areas related to tissue culture for propagation and increased production of important secondary metabolites, phylogenetic analysis and genetic engineering. Moreover, it will offer an insight into crop improvement and breeding programs of this important underutilized medicinal plant for improved yield and quality of secondary metabolites.
This paper focuses on a new kind of artificial neural networks - the Z-transform artificial neural networks (ZTANNs). It is proposed to use the Z-transform instead of ordinary weights and a linear activation function of an artificial neuron. This extension allows to use artificial neural networks in new areas. The ordinary description of artificial neural networks is a special case of the description proposed in this paper. It also contains a description of the use of the ZTANN for automatic identification of objects in digital control system. (C) 2015 Elsevier B.V. All rights reserved.